Datasets:

turingmachine

/

hupd-npe-balanced-same-year-same-class-subset

like 0

ACCEPTED

Imidazo [2,1-b]-1,3,4-thiadiazole suflonamides

This invention relates to compounds of Formula (I) and the use of compounds of Formula (I) as neuroprotective agents in the treatment of neuronal disorders of the central and peripheral nervous systems.

1-12. (Cancelled) 13. An imidazo[2,1-b]-1,3,4-thiadiazole sulfonamide compound according to Formula I: or a pharmaceutically acceptable salt thereof, wherein: R1 and R2 are individually selected from the group consisting of H and C(1-6)-alkyl; R5 is selected from the group consisting of H, halogen, substituted and unsubstituted C(1-4)-alkyl, substituted and unsubstituted aryl, and substituted and unsubstituted heteroaryl; and R6 is selected from the group consisting of fluoro C(1-6)-alkyl, substituted and unsubstituted C(6-16)-aryl, substituted and unsubstituted heteroaryl, substituted and unsubstituted biphenyl, substituted and unsubstituted diphenyl ether, substituted and unsubstituted coumarinyl, and adamantyl; wherein the substituents are selected from the group consisting of: a) halogen, nitro, cyano, substituted and unsubstituted C(1-8)-alkyl, fluoroalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, acyl, substituted and unsubstituted C(1-8)-alkylcarbonyl, substituted and unsubstituted arylcarbonyl, substituted and unsubstituted heteroarylcarbonyl, azide, B(OH)2, and adamantyl; b) SO2NR16R17 wherein R16 and R17 are independently selected from the group consisting of hydrogen, substituted and unsubstituted C(1-8)-alkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heteroaralkyl, substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, and wherein R16 and R17 are joined to form a substituted or unsubstituted alkyl or substituted or unsubstituted heteroalkyl ring system; c) SO2R18 wherein n=0, 1 or 2, and wherein R18 is selected from the group consisting of C(1-8)-alkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heteroaralkyl, substituted and unsubstituted aryl, and substituted and unsubstituted heteroaryl; d) OR19 wherein R19 is defined as substituted or unsubstituted alkyl, substituted and unsubstituted hydroxyl C(1-4)-alkyl, azidoalkyl, fluoroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted and unsubstituted C(1-8)-alkylcarbonyl, substituted and unsubstituted arylcarbonyl, substituted and unsubstituted heteroarylcarbonyl, C(1-8)-alkylaminocarbonyl, and substituted and unsubstituted arylaminocarbonyl; e) NR14R15 wherein R14 and R15 are independently defined as hydrogen, substituted or unsubstituted acyl, substituted and unsubstituted aryl or heteroarylcarbonyl, substituted or unsubstituted C(1-8)-alkyl, or where R14 and R15 are joined to form a substituted or unsubstituted alkyl or substituted or unsubstituted heteroalkyl ring system; f) CO2R20 wherein R20 is defined as H, C(1-8)-alkyl, substituted C(1-8)-alkyl, aralkyl, substituted aralkyl, aryl, substituted aryl, heteroaryl, or substituted heteroaryl; and g) CONR21R22, wherein R21 and R22 are independently selected from the group consisting of C(1-8)-alkyl, aralkyl, and aryl; and wherein adjacent carbons in ring systems of the aryl or heteroaryl R5 substituents or adjacent carbons in ring systems of the aryl, heteroaryl, biphenyl, diphenyl ether, or coumarinyl R6 substituents may together be substituted by a fused cycloalkyl or heterocycloalkyl ring, which cycloalkyl or heterocycloalkyl ring may be further substituted by one or more an alkyl groups, or two alkyl groups joined to form a ring; with the proviso that the following compounds are excluded: 1-6, 10-19, 22, 37, 38, 45, 47, 48, 60, 65, 66, 69, 70, 72, 105-107, 109, 112-114, 124-129, 132, 133, 153, imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide; 5-phenylimidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide; 6-(1,1-dimethylethyl)-imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide; 6-(2-furanyl)-imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide; 5-bromo-6-(2-furanyl)-imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide, 2-(aminosulfonyl)-6-(4-chlorophenyl)imidazo[2,1-b]-1,3,4-thiadiazol-5-yl alkyl ester; 6-(3-(aminosulfonyl)phenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide; 2-(aminosulfonyl)-6-phenylimidazo[2,1-b]-1,3,4-thiadiazole-5-carboxylic acid ethyl ester; 6-[(4-oxo-3(4H)-quinazolinyl)methylimidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide; 6-[4-(acyloxy)phenyl]imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide; 6-[4-[(methylsulfonyl)amino]phenylimidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide; acetamide, N-[4-[2-(aminosulfonyl)imidazolo[2,1-b]-1,3,4-thiadiazol-6-yl]phenyl-; 6-[3-[(methylsulfonyl)amino]phenylimidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide; 6-(4-hydroxy-3-methoxyphenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide; 6-(5-(4-nitrophenyl)-2-furanyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide; 5-bromo-6-(5-(4-nitrophenyl)-2-furanyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide; 6-(4-hydroxy-3-methylphenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide; and 5-bromo-6-(2-oxo-2H-1-benzopyran-3-yl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide. 14. The imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide compound of claim 13, or a pharmaceutically acceptable salt thereof, wherein: R1 and R2 are individually selected from the group consisting of H and C(1-6)-alkyl; R5 is selected from the group consisting of H, halogen, substituted and unsubstituted C(1-4)-alkyl, substituted and unsubstituted aryl, and substituted and unsubstituted heteroaryl; R6 is represented by: wherein: X is represented by a bond, O, or S(O)n, wherein n=0, 1, or 2, and is attached to ring A at the 2, 3, or 4 position; R23 on ring A may be chosen from the group consisting of halogen and alkoxy, and may represent up to 4 substitutions; and R24 through R28 of ring B may be independently selected from the group consisting of H, halogen, C(1-8)-alkyl, lower flouroalkyl, lower alkoxy, or any two adjacent R groups may be combined to form members of a fused aryl, substituted aryl, heteroaryl, or substituted heteroaryl, ring system. 15. The imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide compound of claim 13, or a pharmaceutically acceptable salt thereof, wherein: R1 and R2 are individually selected from the group consisting of H and C(1-6)-alkyl; R5 is selected from the group consisting of H, halogen, substituted and unsubstituted C(1-4)-alkyl, substituted and unsubstituted aryl, and substituted and unsubstituted heteroaryl; R6 is selected from the group consisting of: wherein X is represented by a bond, O or S(O)n, wherein n=0, 1, or 2; R23 on ring A may be chosen from the group consisting of H, halogen, alkoxy and may represent up to 4 substitutions; the heteroaryl ring systems of ring A and B contain at least one heteroatom and may be additionally substituted or nonsubstituted; and R24 through R28 of ring B may be independently selected from the group consisting of H, halogen, C(1-8)-alkyl, lower flouroalkyl, lower alkoxy, or any two adjacent R groups may be combined to form members of a fused aryl, substituted aryl, heteroaryl, or substituted heteroaryl, ring system. 16. The imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide compound of claim 13, or pharmaceutically acceptable salt thereof, wherein: R1 and R2 are individually selected from the group consisting of H and C(1-6)-alkyl; R5 is selected from the group consisting of H, halogen, substituted and unsubstituted C(1-4)-alkyl, substituted and unsubstituted aryl, and substituted and unsubstituted heteroaryl; R6 is represented by: wherein n represents 0 or 1; wherein the ring system containing X7-X11 represents a 5 or 6 membered (n=0 or 1, respectively) aromatic or heteroaromatic ring system, in which each of X7-X11 are independently chosen from the group consisting of C, N, S, and O; wherein each of X7-X11, when independently representing C, have a respective R7-R11 group selected from the group consisting of: a) H, halogen, nitro, cyano, substituted and unsubstituted C(1-8)-alkyl, fluoroalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, acyl, substituted and unsubstituted C(1-8)-alkylcarbonyl, substituted and unsubstituted arylcarbonyl, substituted and unsubstituted heteroarylcarbonyl, azide, B(OH)2, and adamantyl; b) SO2NR16R17 wherein R16 and R17 are independently selected from the group consisting of hydrogen, substituted and unsubstituted C(1-8)-alkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heteroaralkyl, substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, and wherein R16 and R17 are joined to form a substituted or unsubstituted alkyl or substituted or unsubstituted heteroalkyl ring system; c) SOnR18 wherein n=0, 1 or 2, and wherein R18 is selected from the group consisting of C(1-8)-alkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heteroaralkyl, substituted and unsubstituted aryl, and substituted and unsubstituted heteroaryl; d) OR19 wherein R19 is defined as substituted or unsubstituted alkyl, substituted and unsubstituted hydroxyl C(1-4)-alkyl, azidoalkyl, fluoroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted and unsubstituted C(1-8)-alkylcarbonyl, substituted and unsubstituted arylcarbonyl, substituted and unsubstituted heteroarylcarbonyl, C(1-8)-alkylaminocarbonyl, and substituted and unsubstituted arylaminocarbonyl; e) NR14R15 wherein R14 and R15 are independently defined as hydrogen, substituted or unsubstituted acyl, substituted and unsubstituted aryl or heteroarylcarbonyl, substituted or unsubstituted C(1-8)-alkyl, or where R14 and R15 are joined to form a substituted or unsubstituted alkyl or substituted or unsubstituted heteroalkyl ring system; f) CO2R20 wherein R20 is defined as H, C(1-8)-alkyl, substituted C(1-8)-alkyl, aralkyl, substituted aralkyl, aryl, substituted aryl, heteroaryl, or substituted heteroaryl; and g) CONR21R22, wherein R21 and R22 are independently selected from the group consisting of C(1-8)-alkyl, aralkyl, and aryl; and wherein each of X7-X11, when independently representing N, is (i) attached to adjacent atoms by one single and one double bond, and the respective R7-R11 represents a lone pair, or (ii) attached to adjacent atoms by two single bonds, and the respective R7-R11 is selected from the groups consisting of H, lower alkyl, substituted lower alkyl, aralkyl, substituted aralkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, SO2R18, and COR18, wherein R18 is defined as in c); wherein, when n=0, R7 and R8, or R8 and R10 may be combined to form a fused 5, 6, or 7 membered alkyl, substituted alkyl, heteroalkyl, substituted heteroalkyl, heteroaralkyl, substituted heteroaralkyl, aryl, substituted aryl, heteroaryl, or heteroaryl ring system; wherein when n=1 and X9 represents C, R7 and R8, or R8 and R9 may be combined to form a fused 5, 6, or 7 membered alkyl, substituted alkyl, heteroalkyl, substituted heteroalkyl, aryl, substituted aryl, or heteroaryl ring system; wherein each of X7-X11, when independently representing S or O, has a respective R7-R11 representing a lone pair; and wherein, as a member of a heteroaryl ring system, the C1 carbon of R6, as labeled above, is attached to X7 by a single bond and to X11 by a double bond, or C1 is attached to X7 by a double bond and to X11 by a single bond. 17. The imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide of claim 13, or a pharmaceutically acceptable salt thereof, wherein: R1 and R2 are individually selected from the group consisting of H and C(1-6)-alkyl; R5 is selected from the group consisting of H, halogen, substituted and unsubstituted C(1-4)-alkyl, substituted and unsubstituted aryl, and substituted and unsubstituted heteroaryl; and R6 is a phenyl substituted by NR14R15, wherein R14 and R15 are each independently a substituted or unsubstituted C(1-8)-alkyl or are joined to form a substituted or unsubstituted heteroalkyl ring system. 18. An imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide compound or a pharmaceutically acceptable salt thereof, wherein the compounds is selected from the group consisting of compounds 7, 8, 9, 20, 21, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 39, 40, 41, 42, 43, 44, 46, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 61, 62, 63, 64, 67, 68, 71, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 108, 110, 111, 115, 116, 117, 118, 119, 120, 121, 122, 123, 130, 131, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, and 152. 19. A method for the prevention or treatment of neuropathies, polyneuropathies, and neurodegenerative conditions of the central and peripheral nervous systems, said neuropathies, polyneuropathies, and neurodegenerative conditions resulting from axonal and/or neuronal cell body damage, and/or from the loss of axonal growth and repair, in a subject, comprising administering to the subject a therapeutically effective amount of an imidazo[2,1-b]-1,3,4-thiadiazole sulfonamide compound according to Formula I: or a pharmaceutically acceptable salt thereof, for neuroprotection for the prevention or treatment of neuropathies, polyneuropathies, and neurodegenerative conditions of the central and peripheral nervous systems, said neuropathies, polyneuropathies, and neurodegenerative conditions resulting from axonal and/or neuronal cell body damage, and/or from the loss of axonal growth and repair, wherein: R1 and R2 are individually selected from the group consisting of H and C(1-6)-alkyl; R5 is selected from the group consisting of H, halogen, substituted and unsubstituted C(1-4)-alkyl, substituted and unsubstituted aryl, and substituted and unsubstituted heteroaryl; and R6 is selected from the group consisting of fluoro C(1-6)-alkyl, substituted and unsubstituted C(6-16)-aryl, substituted and unsubstituted heteroaryl, substituted and unsubstituted biphenyl, substituted and unsubstituted diphenyl ether, substituted and unsubstituted coumarinyl, and adamantyl; wherein the substituents are selected from the group consisting of: a) halogen, nitro, cyano, substituted and unsubstituted C(1-8)-alkyl, fluoroalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, acyl, substituted and unsubstituted C(1-8)-alkylcarbonyl, substituted and unsubstituted arylcarbonyl, substituted and unsubstituted heteroarylcarbonyl, azide, B(OH)2, and adamantyl; b) SO2NR16R17 wherein R16 and R17 are independently selected from the group consisting of hydrogen, substituted and unsubstituted C(1-8)-alkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heteroaralkyl, substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, and wherein R16 and R17 are joined to form a substituted or unsubstituted alkyl or substituted or unsubstituted heteroalkyl ring system; c) SOnR18 wherein n=0, 1 or 2, and wherein R18 is selected from the group consisting of C(1-8)-alkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heteroaralkyl, substituted and unsubstituted aryl, and substituted and unsubstituted heteroaryl; d) OR19 wherein R19 is defined as substituted or unsubstituted alkyl, substituted and unsubstituted hydroxyl C(1-4)alkyl, azidoalkyl, fluoroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted and unsubstituted C(1-8)-alkylcarbonyl, substituted and unsubstituted arylcarbonyl, substituted and unsubstituted heteroarylcarbonyl, C(1-8)-alkylaminocarbonyl, and substituted and unsubstituted arylaminocarbonyl; and e) NR14R15 wherein R14 and R15 are independently defined as hydrogen, substituted or unsubstituted acyl, substituted and unsubstituted aryl or heteroarylcarbonyl, substituted or unsubstituted C(1-8)alkyl, or where R14 and R15 are joined to form a substituted or unsubstituted alkyl or substituted or unsubstituted heteroalkyl ring system; and wherein adjacent carbons in ring systems of the aryl or heteroaryl R5 substituents or adjacent carbons in ring systems of the aryl, heteroaryl, biphenyl, diphenyl ether, or coumarinyl R6 substituents may together be substituted by a fused cycloalkyl or heterocycloalkyl ring, which cycloalkyl or heterocycloalkyl ring may be further substituted by one or more an alkyl groups, or two alkyl groups joined to form a ring. 20. A method for the prevention or treatment of neuropathies, polyneuropathies, and neurodegenerative conditions of the central and peripheral nervous systems, said neuropathies, polyneuropathies, and neurodegenerative conditions resulting from axonal and/or neuronal cell body damage, and/or from the loss of axonal growth and repair, in a subject, comprising administering to the subject a therapeutically effective amount of a compound of claim 13. 21. A method for the prevention or treatment of a neurodegenerative condition of the central nervous system, in a subject, comprising administering to the subject a therapeutically effective amount of a compound of claim 13. 22. The method according to claim 21, wherein the neurodegenerative condition of the central nervous system is cerebral ischemia, encephalopathy, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, or hepatic encephalopathy. 23. A method according to claim 19, for the prevention or treatment of a neurodegenerative condition of the peripheral nervous system. 24. A method according to claim 23, wherein the neurodegenerative condition of the peripheral nervous system is acute idiopathic neuropathy, HIV neuropathy, neurilemma, or neurofibroma. 25. A method according to claim 19, for the prevention or treatment of axonal and/or neuronal cell body damage resulting from a neurodegenerative condition of the eye. 26. A method according to claim 19, for the prevention and/or treatment of damage resulting from axonal and/or neuronal cell body damage. 27. A method according to claim 19, for induction or stablization of axonal growth and/or repair, to prevent or treat neurodegenerative conditions of both the central and peripheral nervous systems. 28. A method according to claim 19, for the prevention or treatment of a neurodegenerative condition of the central nervous system resulting from chemotherapeutic agents. 29. A method according to claim 19, for the prevention or treatment of a neurodegenerative condition of the peripheral nervous system resulting from chemotherapeutic agents. 30. A method according to claim 19, for the prevention or treatment of motor neuropathies. 31. A method according to claim 19, for the prevention or treatment of diabetic, sensory, autonomic, or motor neuropathy or polyneuropathies. 32. A method according to claim 19, for altering signal transduction. 33. A method according to claim 19, wherein the compound is used in combination with other compounds known in the art. 34. A pharmaceutical composition for the treatment of neuropathies, polyneuropathies, and neurodegenerative conditions of the central and peripheral nervous systems, said neuropathies, polyneuropathies, and neurodegenerative conditions resulting from axonal and/or neuronal cell body damage, and/or from the loss of axonal growth and repair, comprising a pharmaceutically effective amount of a compound according to claim 13, in admixture with a pharmaceutically acceptable carrier. 35. A kit containing the composition of claim 34, together with instructions for its use for the treatment of neuropathies, polyneuropathies, and neurodegenerative conditions of the central and peripheral nervous systems, said neuropathies, polyneuropathies, and neurodegenerative conditions resulting from axonal and/or neuronal cell body damage, and/or from the loss of axonal growth and repair.

FIELD OF THE INVENTION This invention relates to sulfonamide compounds useful in the prevention of neuronal cell loss or in the treatment of nerve cell or axonal degradation. BACKGROUND OF THE INVENTION Various neurotrophins characterized by Neuronal Growth Factor (NGF), brain derived growth factor (BDNF), neurotrophin-3 (NT-3), and others (NT-4, CNTF, GDNF, IGF-1), have been identified as key survival factors for neurons. NGF plays a critical role in the development and maintenance of cholinergic forebrain neurons of the CNS and neurons of the peripheral nervous system (PNS); neurons of the PNS are characterized as small fiber sensory neurons associated with pain and temperature sensation, in addition to neurons of the sympathetic ganglia and dorsal root ganglia (SCGs and DRGs, respectively). BDNF plays a role in motor neuron survival. Both BDNF and NT-3 are expressed in the CNS and serve similar purposes in multiple subsets of cortical and hyppocampal neurons; neurons of the CNS are characterized by those found in the brain, spinal chord, and eye. The removal of these, and related trophic factors from in vitro cellular media results in the degradation of the axonal processes, leading to apoptosis of cultured neurons. Localized tissue loss of NGF, or reduced axonal retrograde transport of NGF to the cell body, have been causally implicated in the development of peripheral neuropathies and neuropathic pain regularly observed in diabetes and HIV patients. Several double blind Phase II clinical trials have found that the systemic administration of recombinant human NGF (rhNGF) (U.S. Pat. No. 5,604,202) displayed beneficial effects on neuropathic pain, physiology, and cognition related to these diseases (Apfel, S. C. et. al. JAMA, 248(17), 2215-2221; Apfel, S. C. Neurology 51, 695-702, 1998; McAurthur, J. C. et al. Neurology 54, 1080-1088, 2000). Side effects related to rhNGF treatment included injection site pain, hyperalgesia, and other pain related symptoms. Despite these symptoms, a large number of patients continued rhNGF treatment after unblinding. Various chemotherapeutic drugs such as Taxol™, cisplatin, vinblastine, and vincristine, cause dose dependent peripheral neuropathies, characterized by peripheral pain and loss of function. In many cases these neuropathies effectively limit the amount, and duration, of chemotherapy given to, patients. For example, upwards of 50% of patients receiving Taxol™ chemotherapy experience severe, and cumulative, peripheral neuropathies. The progression of the neuropathy necessitates the use of a dosing regime which is characterized by three cycles of fourteen days of Taxol™ treatment, followed by 14 days of recovery. Regression of the neuropathy is often observed between treatment cycles and following the final treatment. The degree and duration of recovery varies largely between patients. In addition to peripheral neuropathies, cisplatin treatment invariably results in some form of auditory loss, especially in children, due to neuronal damage in the inner ear, with minimal recovery of the neurons after completion of treatment. SUMMARY OF THE INVENTION The invention relates to imidazo[2,1-b]thiadiazole sulfones, which are useful in the treatment of neurodegenerative diseases of the CNS and/or PNS, for the inhibition of various serine-threonine protein kinases, phosphatases, CA, for inhibiting the degradation, dysfunction, or loss of neurons of the CNS and/or PNS, or enhancing the phenotype of neuronal cell types and preserving the axonal function of neuronal and synaptic processes of the CNS and/or of the PNS. Also included are selected methods for the preparation of these compounds. The imidazo[2,1-b]-1,3,4-thiadiazole sulfonamide derivatives and precursors of the present invention include compounds of the Formula I: or pharmaceutically acceptable salts thereof wherein: R1 and R2 are individually selected from the group consisting of H, lower alkyl, substituted lower alkyl, and fluoroalkyl; R5 is selected from the group consisting of H, halogen, cyano, azide, thiocyanate, formyl, lower alkyl, substituted lower alkyl, fluoroalkyl, aralkyl, substituted aralkyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl; R6 is selected from the group consisting of H, lower alkyl, substituted lower alkyl, fluoroalkyl, substituted fluoroalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, adamantly, coumarinyl, and substituted coumarinyl; or R6 is represented by W: wherein: n represents 0 or 1; the ring system containing X7-X11 represents a 5 or 6 membered aromatic or heteroaromatic ring system, in which X7-X11 are independently selected from the group consisting of C, N, S, and O; when any one of X7-X11 independently represents C, a respective R7-R11 is independently selected from the group consisting of: a) H, halogen, nitro, cyano, lower alkyl, substituted lower alkyl, fluoroalkyl, aralkyl, substituted aralkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyl, lower alkylcarbonyl, substituted lower alkylcarbonyl, arylcarbonyl, substituted arylcarbonyl, heteroarylcarbonyl, or substituted heteroarylcarbonyl; b) SO2NR16R17 wherein R16 and R17 are independently selected from the group consisting of lower alkyl, substituted lower alkyl, aralkyl, substituted aralkyl, heteroaralkyl, substituted heteroaralkyl aryl, substituted aryl, heteroaryl, and substituted heteroaryl, or wherein R16 and R17 are joined to form an alkyl, substituted alkyl, heteroalkyl, or substituted heteroalkyl ring system; c) SOnR18 wherein n=0, 1 or 2, and wherein R18 is selected from the group consisting of lower alkyl, substituted lower alkyl, aralkyl, substituted aralkyl, heteroaralkyl, substituted heteroaralkyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl; d) XR19 wherein X is defined as S or O, and R19 is defined as alkyl, substituted alkyl, fluoroalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyl, lower alkylcarbonyl, substituted lower alkylcarbonyl, arylcarbonyl, substituted arylcarbonyl, heteroarylcarbonyl, substituted heteroarylcarbonyl, lower alkylaminocarbonyl, arylaminocarbonyl, or substituted arylaminocarbonyl; e) NR14R15 wherein R14 and R15 are defined as lower alkyl joined to form an alkyl, substituted alkyl, heteroalkyl, or substituted heteroalkyl ring system; and f) CO2R20 wherein R20 is defined as H, lower alkyl, substituted lower alkyl, aralkyl, substituted aralkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, or NR21R22, wherein R21 and R22 are independently selected from the group consisting of lower alkyl, aralkyl, aryl; wherein when any one of X7-X11 represents N, that nitrogen is attached to the adjacent atoms by either one single and one double bond (as in pyridinyl systems), or by two single bonds (as in indolyl or imidazolyl systems); wherein when any one of X7-X11 represents N, and that nitrogen is attached to the adjacent atoms by one single and one double bond, the respective R7-R11 represents a lone pair; when any one of X1-X5 represents N, and that nitrogen is attached to the adjacent atoms by two single bonds (as in indolyl or imidazolyl systems), the respective R7-R11 is selected from the group consisting of H, lower alkyl, substituted lower alkyl, aralkyl, substituted aralkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, SO2R18, wherein R18 is defined as in c), COR18, wherein R18 is defined as in c); when n=0, R7 and R8, or R8 and R9 are combined to form a fused 5, 6, or 7 membered alkyl, substituted alkyl, heteroalky, substituted heteroalkyl, heteroaralkyl, substituted heteroaralkyl, aryl, substituted aryl, heteroaryl, or heteroaryl ring system; when n=1 and X9 represents C, R7 and R8, or R8 and R10 are combined to form a fused 5, 6, or 7 membered alkyl, substituted alkyl, heteroalky, substituted heteroalkyl, aryl, substituted aryl, or heteroaryl ring system; and any one of R7-R11 represents a lone pair when the respective X7-X11 represents S or O; with the proviso that compounds 1, 4, 10, 14, 20, 60, 72, 105, 109, 111, 114, 124, 126, 127, 133, and 153 are excluded. The invention relates to sulfonamide compounds of Formula I and the use of compounds of Formula I (including those noted within the proviso excluding the actual compounds themselves) for the prevention of neuronal cell loss or the treatment of nerve cell or axonal degradation, in either the central or peripheral nervous systems (CNS and PNS, respectively). The invention is useful in prevention or treatment of conditions leading to or resulting from such diseases as Alzheimer's, Huntington's, Parkinson's, muscular dystrophy, diabetes, HIV, from ischemic insults such as stroke in the brain (CNS), retinal ganglion loss following acute ocular stroke or hypertension as in glaucoma, and from infection by viruses such as Hepatitis C and Herpes Simplex. Further, the invention provides compounds for use in treatment of neuropathies resulting from chemotherapeutic agents used in the treatment of HIV and proliferative disease such as cancer, for the treatment of inflammatory diseases. In order to identify compounds which mimic the positive effects of NGF on peripheral neurons, but which lack the inherent difficulties associated with the use of recombinant human proteins and the rhNGF related hyperalgesia, we have developed several in vitro screens using a variety of neurotoxic insults. PNS neurons such as the superior cervical ganglion (SCG) and dorsal root ganglion (DRG) undergo apoptosis when subjected to NGF withdrawal. Treatment with chemotherapeutic agents such as Taxol™, cisplatin, vinblastine, vincristine, and anti-viral agents such as D4T, also induce neuronal apoptosis. Similarly, neurons of the CNS, such as cortical neurons, are sensitive to various neurotoxic agents such as β-amyloid, NMDA, osmotic shock, Taxol™ and cisplatin. Additionally, retinal ganglion neurons subjected to hypoxia undergo apoptosis. Compounds which protect neurons from neurotoxic insults such as those mentioned above will be useful in the treatment of the peripheral neuropathies observed in diseases such as diabetes and HIV. Compounds which protect neurons from chemotherapeutic toxicity, if given concurrently with, or following, chemotherapeutic treatment will allow for the use of increasing concentrations of chemotherapeutics and/or extend the duration of chemotherapy treatments. Alternatively, enhanced recovery will be observed if such compounds are given during the recovery stages, and post treatment. These compounds will also be useful in the treatment of neurodegenerative diseases of the CNS, such as AD, PD, HD, stroke, MS, macular degeneration, glaucoma, optical stroke and retinal degeneration, and the like. We have shown that compounds of Formula I protect SCG neurons from several neurotoxic insults, including NGF withdrawal and treatment with chemotherapeutics such as Taxol™, cisplatin, and vincristine. Compounds of Formula I also protect cortical motor neurons from malonate induced death. When such agents are administered to mice treated with Taxol™, either during or after a two week dosing period, marked improvements are observed in the animal's general health, weight gain, and gait, as compared to animals treated with Taxol™ alone. Additionally, compounds of Formula I aid in the regeneration of neurons damaged as a result of sciatic nerve crush. Selected examples from Formula I have been previously described. Their uses include anti-bacterial agents (Gadad, A. K. Eur J. Med. Chem., 35(9), 853-857, 2000), anti-proliferative agents (Gadad, A. K. India. Arzneim.-Forsch., 49(10), 858-863, 1999), and as carbonic anhydrase (CA) inhibitors (Barnish, I. T., et. al. J. Med. Chem., 23(2), 117-121, 1980; Barnish, I. T. et. al GB 1464259, abandoned; Supuran, C, T. Met.-Based Drugs 2(6), 331-336, 1995—Co(II), Cu (II), Zn(II) complexes of compound 1). Barnish et al. demonstrated that certain compounds reduced the number and intensity of electroshock induced seizures in rats. This anti-seizure activity was linked to increased cerebral blood flow, attributed to the ability of these compounds to inhibit CA. No direct evidence of neuronal protection as a result of these compounds has been previously demonstrated in vitro or in vivo (ie. histology, neuronal cell count, etc.). We have found that various aryl sulfonamide CA inhibitors do not protect SCG neurons from apoptosis. These finding indicate that the neuroprotection mediated by compounds represented by Formula I is independent of their CA activity. Additionally, we have prepared several synthetic derivatives of represented by Formula I which display reduced CA inhibition inhibit CA, while retaining their neuroprotective capabilities. The invention relates to synthetic routes for preparation of compounds represented by Formula I, and methods for the functionalization of compounds represented by Formula I. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 illustrates the protection of SCG neurons from Taxol™ induced killing provided by Compound 1 (AEG 3482). FIG. 2 illustrates the protection of cortical motor neurons from malonate killing in the presence of compound 91. 350 uM slices of P1 rat motor cortex were treated with malonate and incubated in media for 14 days, before malonate and drug were added. Part (a) shows control motor neurons, and illustrates large diamond-shaped neurons; part (b) shows malonate treatment alone, which results in killing with a complete loss of neurons; and part (c) shows 90% rescue of cortical motor neurons in the presence of compound 91 (1 uM) and malonate. FIG. 3 illustrates the co-treatment of HA460 and OV2008 cancer cell line with Taxol™ and Compound 1. HA460 and OV2008 cells were treated with Taxol™ and/or Taxol™ +compound 1. FIG. 4 illustrates weight loss induced by Taxol™ in Spraugue Dawley rats treated with 50% HPDC vehicle (veh/veh), compound 1 dissolved in 50% HPDC at 1, 5, or 10 mg/kg (veh/1, veh/5, veh/10, respectively), or Taxol™ (9 mg/kg)+compound 1 dissolved in 50% HPDC at 1, 5, and 10 mg/kg (Tax/1, Tax/5, Tax/10) according to the dosing regime described in Example 123. FIG. 5 illustrates that gait disturbance in rats induced by Taxol™ was reduced with compound 1. FIG. 6 illustrates that compound 1 caused a reversal in H/M wave disturbance induced by Taxol™, as indicated by H-reflex amplitude. FIG. 7 illustrates sciatic nerve recovery after crush injury, as measured by inner toe spread in male Spraugue Dawley rats treated with either vehicle control; compound 1 or compound 76. FIG. 8 illustrates the effect of intravitreal compound 1, followed by subsequent daily injetions on protection of DRGs after ocular stroke. Compound 1, given post stroke, protects the DRG population allowing for normal conductance. FIG. 9 illustrate the neuroprotection of cortical neurons provided by Compound 76 from amyloid beta 25-35 toxicity. Top (a) shows control untreated cultures display low level annexin V staining; middle (b) shows 48 hour treatment with amyloid beta peptide results in the appearance of apoptotic cells; and bottom (c) illustrates co-treatment with 10 uM Compound 76 prevents the occurrence of annex in V stained cells. DETAILED DESCRIPTION The compounds represented by Formula (I) may be referred to herein interchangeably as as Compound (1). Compounds referred to herein by number (such as compound 1 or compound 76) refer to the compounds outlined as Examples 1 to 152. In the definitions of the groups of Formula I, lower alkyl means a straight-chain or branched alkyl group having 1 to 8 carbon atoms, such as methyl, ethyl, propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, pentyl, iso-amyl, neopentyl, 1-ethylpropyl, hexyl, and octyl. The lower alkyl moiety of lower alkoxy, lower alkylsulfonyl, lower alkoxylcarbonyl, lower alkylaminocarbonyl has the same meaning as lower alkyl defined above. The acyl moiety of the acyl and the acyloxy group means a straight-chain or branched alkanoyl group having 1 to 6 carbon atoms, such as formyl, acetyl, propanoyl, butyryl, valeryl, pivaloyl and hexanoyl, and arylcarbonyl group described below, or a heteroarylcarbonyl group described below. The aryl moiety of the aryl, the arylcarbonyl and arylaminocarbonyl groups means a group having 6 to 16 carbon atoms such as phenyl, biphenyl, naphthyl, or pyrenyl. The heteroaryl moiety of the heteroaryl and the heteroarylcarbonyl groups contain at least one hetero atom from O, N, and S, such as pyridyl, pyrimidyl, pyrroleyl, furyl, benzofuryl, thienyl, benzothienyl, imidazolyl, triazolyl, quinolyl, iso-quinolyl, benzoimidazolyl, thiazolyl, benzothiazolyl, oxazolyl, and indolyl. The aralkyl moiety of the aralkyl and the aralkyloxy groups having 7 to 15 carbon atoms, such as benzyl, phenethyl, benzhydryl, and naphthylmethyl. The heteroaralkyl moiety of the heteroaralkyl and the heteroaralkyloxy groups having 7 to 15 carbon such as pyridylmethyl, quinolinylmethyl, and iso-quinolinylmethyl. The substituted lower alkyl group has 1 to 3 independently-substitutuents, such as hydroxyl, lower alkyloxy, carboxyl, lower alkylcarbonyl, nitro, amino, mono- or di-lower alkylamino, dioxolane, dioxane, dithiolane, and dithione. The lower alkyl moiety of the substituted lower alkyl, and the lower alkyl moeity of the lower alkoxy, the lower alkoxycarbonyl, and the mono- and di-lower alkylamino in the substituents of the substituted lower alkyl group have the same meaning as lower alkyl defined above. The substituted aryl, the substituted heteroaryl, the substituted aralkyl, and the substituted heteroaralkyl groups each has 1 to 5 independently-selected substituents, such as lower alkyl, hydroxy, lower alkoxy, carboxy, lower alkoxycarbonyl, nitro, amino, mono or di-lower alkylamino, azido, and halogen. The lower alkyl moiety of the lower alkyl, the lower alkoxy, the lower alkylamino, and the mono- and di-lower alkylamino groups amoung the susbtituents has the same meaning as lower alkyl defined above. The heterocyclic group formed with a nitrogen atom includes rings such as pyrrolyl, piperidinyl, piperidino, morpholinyl, morpholino, thiomorpholino, N-methylpiperazinyl, indolyl, and isoindolyl. The cycloalkyl moeity means a cycloalkyl group of the indicated number of carbon atoms, containing one or more rings anywhere in the structure, such as cycloalkyl groups include cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, 2-norbornyl, 1-adamantyl and the like. The fluoroalkyl moiety means a lower fluoroalkyl group in which one or more hydrogens of the corresponding lower alkyl group, as defined above, is replaced by a fluorine atom, such as CH2F, CHF2, CF3, CH2CF3, and CH2CH2CF3. Some of the compounds described herein contain one or more chiral centres and may thus give rise to diastereomers and optical isomers. The present invention is meant to comprehend such possible diastereomers as well as their racemic, resolved and enantiomerically pure forms, and pharmaceutically acceptable salts thereof. The term “subject” or “patient” as used herein may refer to mammals including humans, primates, horses, cows, pigs, sheep, goats, dogs, cats and rodents. The pharmaceutical compositions of the invention are administered to subjects in effective amounts. An effective amount means that amount necessary to delay the onset of, inhibit the progression of, halt altogether the onset or progression of or diagnose the particular condition or symptoms of the particular condition being treated. In general, an effective amount for treating a neurological disorder is that amount necessary to affect any symptom or indicator of the condition In general, an effective amount for treating neuropathies and neuropathic pain will be that amount necessary to favorably affect mammalian cancer cell proliferation in situ. When administered to a subject, effective amounts will depend, of course, on the particular condition being treated; the severity of the condition; individual patient parameters including age, physical condition, size and weight; concurrent treatment; frequency of treatment; and the mode of administration. These factors are well known to those of ordinary skill in the art and can be addressed with no more than routine experimentation. It is preferred generally that a maximum dose be used, that is, the highest safe dose according to sound medical judgment. A variety of administration routes are available. The particular mode selected will depend, of course, upon the particular condition being treated, the particular drug selected, the severity of the condition being treated and the dosage required for therapeutic efficacy. The methods of this invention, generally speaking, may be practiced using any mode of administration that is medically acceptable, meaning any mode that produces effective levels of the active compounds without causing clinically unacceptable adverse effects. Such modes of administration include oral, rectal, sublingual, topical, nasal, transdermal, intradermal or parenteral routes. The term “parenteral” includes subcutaneous, intravenous, intramuscular, or infusion. Oral routes are preferred. Dosage may be adjusted appropriately to achieve desired drug levels, locally or systemically. Generally, daily oral doses of active compounds will be from about 0.01 mg/kg per day to 1000 mg/kg per day. It is expected that IV doses in the range of about 1 to 1000 mg/m2 per day will be effective. In the event that the response in a subject is insufficient at such doses, even higher doses (or effective higher doses by a different, more localized delivery route) may be employed to the extent that patient tolerance permits. The compositions may conveniently be presented in unit dosage form and may be prepared by any of the methods well known in the art of pharmacy. All methods include the step of bringing the conjugates of the invention into association with a carrier that constitutes one or more accessory ingredients. In general, the compositions are prepared by uniformly and intimately bringing the compounds into association with a liquid carrier, a finely divided solid carrier, or both, and then, if necessary, shaping the product. Compositions suitable for oral administration may be presented as discrete units such as capsules, cachets, tablets, or lozenges, each containing a predetermined amount of the active compound. Other compositions include suspensions in aqueous liquors or non-aqueous liquids such as a syrup, an elixir, or an emulsion. Other delivery systems can include time-release, delayed release or sustained release delivery systems. Such systems can avoid repeated administrations of the active compounds of the invention, increasing convenience to the subject and the physician. Many types of release delivery systems are available and known to those of ordinary skill in the art. They include polymer based systems such as polylactic and polyglycolic acid, polyanhydrides and polycaprolactone; nonpolymer systems that are lipids including sterols such as cholesterol, cholesterol esters and fatty acids or neutral fats such as mono-, di and triglycerides; hydrogel release systems; silastic systems; peptide based systems; wax coatings, compressed tablets using conventional binders and excipients, partially fused implants and the like. In addition, a pump-based hardware delivery system can be used, some of which are adapted for implantation. A long-term sustained release implant also may be used. “Long-term” release, as used herein, means that the implant is constructed and arranged to deliver therapeutic levels of the active ingredient for at least 30 days, and preferably 60 days. Long-term sustained release implants are well known to those of ordinary skill in the art and include some of the release systems described above. Such implants can be particularly useful in treating solid tumors by placing the implant near or directly within the tumor, thereby affecting localized, high-doses of the compounds of the invention. When administered, the Formulations of the invention are applied in pharmaceutically acceptable compositions. Such preparations may routinely contain salts, buffering agents, preservatives, compatible carriers, and optionally other therapeutic ingredients. When used in medicine the salts should be pharmaceutically acceptable, but non-pharmaceutically acceptable salts may conveniently be used to prepare pharmaceutically acceptable salts thereof and are not excluded from the scope of the invention. Such salts include, but are not limited to, those prepared from the following acids: hydrochloric, hydrobromic, sulphuric, nitric, phosphoric, maleic, acetic, salicylic, p-toluenesulfonic, tartaric, citric, methane sulfonic, formic, malonic, succinic, naphthalene-2-sulfonic, benzene sulfonic, and the like. Also, pharmaceutically acceptable salts can be prepared as alkaline metal or alkaline earth salts, such as sodium, potassium or calcium salts. Suitable buffering agents include: phosphate buffers, acetic acid and a salt (1-2% W/V); citric acid and a salt (1-3% W/V); and phosphoric acid and a salt (0.8-2% W/V), as well as others known in the art. Suitable preservatives include benzalkonium chloride (0.003-0.03% W/V); chlorobutanol (0.3-0.9% W/V); parabens (0.01-0.25% W/V) and thimerosal (0.004-0.02% W/V), as well as others known in the art. Suitable carriers are pharmaceutically acceptable carriers. The term pharmaceutically acceptable carrier means one or more compatible solid or liquid filler, dilutants or encapsulating substances that are suitable for administration to a human or other animal. The term “carrier” denotes an organic or inorganic ingredient, natural or synthetic, with which the active ingredient is combined to facilitate the application. The components of the pharmaceutical compositions are capable of being commingled with the molecules of the present invention, and with each other, in a manner such that there is no interaction which would substantially impair the desired pharmaceutical efficacy. Carrier Formulations suitable for oral, subcutaneous, intravenous, and intramuscular administration etc., are those which are known in the art. The compounds of the invention may be delivered with other therapeutic agents. The invention additionally includes co-administration of compound I of the invention with other compounds known to be useful in treating neurodegenerative diseases, typified by but not limited to, acetylcholinesterase inhibitors for treating AD, such as tacrine, doneprizil, and rivastigmin, and L-dopa for treating PD, and ACE inhibitors and insulin for the treatment of diabetes. In the case of peripheral neuropathy induced by a toxic agent, compound I would be delivered separately before, simultaneously with (ie. in the form of anti-cancer coctails, see below), or after exposure to the toxic agent. Preferably, compound I and the chemotherapeutic agent are each administered at effective time intervals, during an overlapping period of treatment in order to prevent or restore at least a portion of the neurological function destroyed by the neurotoxic or chemotherapeutic agent. The chemotherapeutic can be any chemotherapeutic agent that causes neurotoxicity, such as dideoxyinosine, deoxy cytizine, D4T, cisplatin, etoposide, vincristine, epithilone or its derivatives, or Taxol™/Taxoter™ and derivatives thereof, which are representative of the classes of agents induce neuropathies. By “toxic agent” or “neurotixic agent” is meant a substance that through its chemical action injures, impairs, or inhibits the activity of a component of the nervous system. The list of neurotoxic agents that cause neuropathies is lengthy (see a list of candidate agents provided in Table 1). Such neurotoxic agents include, but are not limited to, neoplastic agents such as vincristine, vinblastine, cisplatin, Taxol™, or dideoxy-compounds, eg., dideoxyinosine; alcohol; metals; industrial toxins involved in occupational or environmental exposure; contaminants in food or medicinals; or over-doses of vitamines or therapeutic drugs, eg. Antibiotics such as penicillin or chloramphenicol, or mega-doses of vitamins A, D, or B6. TABLE 1 Neurotoxic Agents AGENT ACTIVITY acetazolimide diuretic acrylamide flocculant, grouting agent adriamycin antineoplastic alcohol (ie. ethanol) solvent, recreational drug almitine respiratory stimulant amiodarone antiarrthymic amphotericin antimicrobial arsenic herbicide, insecticide aurothioglucose antirheumatic barbiturates anticonvulsive, sedative buckthorn toxic berry carbamates insecticide carbon disulfide industrial applications chloramphenicol antibacterial chloroquine antimalarial chlorestyramine antihyperlipoproteinemic cisplatin antineoplastic clioquinol amebicide, antibacterial colestipol antihyperlipoproteinemic colchicine gout suppressant colistin antimicrobial cycloserine antibacterial cytarabine antineoplastic dapsone dermatological including leprosy dideoxycytidine anatineoplastic dideoxyinosine antineoplastic dideoxythymidine antiviral disulfiram antialcohol doxorubicin antineoplastic ethambutol antibacterial ethionamide antibacterial glutethimide sedative, hypnotic gold antirheumatic hexacarbons solvents hormonal contraceptives hexamethylolmelamine fireprooing, crease proofing hydralazine antihypertensive hydroxychloroquine antirheumatic imipramine antidepressant indomethacin anti-inflammatory inorganic lead toxic metal in paint, etc. iso-niazid antituberculousis lithium antidepressant methylmercury industrial waste metformin antidiabetic methylhydrazine synthetic intermediate metronidazole antiprotozoal misonidazole radiosensitizer nitrofurantoin urinary antiseptic nitrogen mustard antineoplastic, nerve gas nitous oxide anesthetic organophosphates insecticides ospolot anticonvulsant penicillin antibacterial perhexiline antiarrhythmic perhexiline maleate antiarrythmic phenytoin anticonvulsant platnim drug component primidone anticonvulsant procarbazine antineoplastic pyridoxine vitamin B6 sodium cyanate antisickling streptomycin antimicrobial sulphonamides antimicrobial suramin anteneoplastic tamoxifen antineoplastic Taxol ™ antineoplastic thalidomide antileprous thallium rat poison triamterene diuretic trimethyltin toxic metal L-trypophan health food additive vincristine antineoplastic vinblastine antineoplastic vindesine antineoplastic vitamine A or D mega doses Several neurotoxic agents and protocols may be used to induce apoptosis in SCG neurons. Several of these insults include the withdrawal of trophic support (for example NGF), treatment with neurotoxic chemotherapeutics such as Taxol™, cisplatin, vincristine, or vinblastine, and treatment with neurotoxic anti-virals such as D4T. Selected compounds represented by Formula I have been found to inhibit apoptosis induced by the above insults. Neurotrophins are critical to the growth, development, and survival of small fiber neurons of the PNS. SCG neurons are neurons of the PNS that undergo apoptosis upon NGF withdrawal. In a typical experiment SCG neurons are cultured in the presence of NGF, which induces survival and neurite out-growth. After 5 days the NGF is removed by either the addition of anti-NGF polyclonal antibody (Sigma) or by repeated washings (4 times) with NGF free media, resulting in the apoptosis of up to 90% of the neurons after 48 hours, as measured by MTS staining. The addition of selected compounds of Formula I to the final cellular media provides upwards of 100% protection, at drug concentrations ranging from 3 to 50 μM (see Example 154). Taxol™ is regularly used in breast cancer chemotherapy. In cancer cells Taxol™ binds to the cyto-skeletal protein tubulin, thereby inhibiting normal microtubular assembly and inducing cellular apoptosis. Despite its potency as an anti-tumour agent, Taxol™ is also toxic to neurons, inducing dose limiting peripheral neuropathies. The addition of Taxol™ (100 ng/mL) to cultured SCG neurons induces the degradation or loss of upwards of 80% of the neurons. The addition of selected compounds of Formula I to the cellular media, concurrently with Taxol™, protects upwards of 100% of the neurons, at drug concentrations ranging from 3 to 50 μM (see Example 155 and FIG. 1). The mechanism of Cisplatin's anti-cancer action is not fully understood, but is believed to involve DNA binding and cleavage. Cisplatin is highly toxic to neurons. The addition of cisplatin (3 μg/mL) to cultured SCG neurons induces apoptosis of upwards of 80% of the neurons. The addition of selected compounds of Formula I to the cellular media, concurrently with cisplatin, protects upwards of 100% of the neurons, at drug concentrations ranging from 1 to 50 μM (see Example 156). Similarly, vincristine and vinblastine are commonly used anti-tumour agents whose mode of action involve tubulin binding. As above, the addition of vincristine (100 ng/mL) to cultured SCG neurons induces apoptosis of upwards of 80% of the neurons. The addition of selected compounds of Formula I to the cellular media, concurrently with vincristine, protects upwards of 100% of the neurons, at drug concentrations ranging from 1 to 50 μM (see Example 157). Various neurodegenerative diseases are related to the cellular or functional loss of motor neurons of the CNS and PNS. ALS is a characterized by motor neuron loss as a result of mitochondrial dysfunction, which can be mimicked in culture by the addition of malonate to organotypic brain slices. P1 rat motor cortex brain slices were cultured for 2 weeks prior to drug and malonate addition. After an additional two weeks the slices were fixed and stained with SMI-32 antibody which selectively stains motor neurons found in layer V of the cortex. Compound 91 protected upwards of 80% of these labeled motor neurons at a drug concentration of 1 μM (Example 158). Taken together, compound of Formula I display remarkable neuroprotective capabilities, against a wide range of insults in both the CNS and the PNS. One of the intended uses of these agent is in the conjugation with chemotherapeutic agents. If compounds represented by Formula I were to protect cancer cells from the same chemotherapeutic agents, it would have limited value. Two pieces of evidence suggest these compounds do not protect cancer cells from chemotherapeutics. Selected compounds represented by Formula I have previously been shown to be anit-proliferative (Gadad, A. K. India. Arzneim.-Forsch., 49(10), 858-863, 1999), suggesting these compounds will be beneficial when used in conjunction with other chemotherapeutic agents. Additionally, we have shown that compound 1 displays no protection when human ovarian carcinoma cells (OV2008) and human lung carcinoma cells (HA460) were treated with Taxol™ and/or cisplatin (see Example 159 and FIG. 3). Compound 1 and several of its derivatives have been reported to be potent inhibitors of carbonic anhydrase (CA) (Barnish, I. T., et. al. J. Med. Chem., 23(2), 117-121, 1980). CA plays an important role in maintaining both intra- and extra-cellular pH levels. In an effort to determine whether the neuroprotective profile of compound 1 was due to CA inhibition, a number of well-known, cell permeable, aryl sulfonamide CA inhibitors were evaluated against the Taxol™ killing of SCGs. Dorzolamide, (Ponticello, G. S., et. al J. Med. Chem., 1987, 30, 591) aminobenzolamide N-acetylaminobenzolamide, acetazolamide, and methazolamide (see Marten, T. H. J. Glaucoma, 1995, 4, 49) all failed to significantly inhibit Taxol™ induced killing of SCGs at concentrations as high as 50 μM. Additionally, the ability of compounds represented by Formula I to inhibit CAII varied greatly depending upon the substitution patterns found on the sulfonamide or the C6 position (see Example 163). For example, compound 139 is the N-methyl derivative of compound 1, compound 139, displays a 100 fold decrease in CAII activity (CAII(50) 11.2 μM and 250 nM, respectively) while retaining a similar IC(50) against Taxol (7 μM each). Similarly, compound 77 is a poor CAII inhibitor (IC(50) 6.3 μM), but displays a more potent against Taxol killing of SCGs (IC (50) 2 μM). Based on these results it is clear that although compounds of Formula I are known CA inhibitors, the primary mechanism by which it is protecting neurons appears to be independent of CA inhibition. Adenovirus overexpression of Erk1 and Erk2, two members of the MAP kinase family of signaling proteins, have been shown to stimulate neuronal out-growth and the formation of new synaptic connections in primary neurons of the PNS and CNS. Additionally, the Erks protect cultured neurons from a number of insults including neurotrophin withdrawal (Bonni, A., et al., Science, 1999, 286, 1358-1362). A dramatic increase in Erk activity was observed in both PC12 cells and in primary cultures of sympathetic neurons when treated with compound 1. The activity of Akt, however, remained unchanged when both PC12 cells and SCGs were treated with compound 1. Akt is activated by NGF and has been demonstrated to be neuroprotective in both PNS and CNS neurons. Compound 1, therefore, protects neurons by activating a subset of NGF-stimulated signaling pathways. Taxol™ commonly causes dose dependent peripheral neuropathies during cancer treatment. When treated with Taxol™ (9 mg/kg in Cremophor EL and ethanol) twice weekly for 3 weeks, Sprague Dawley rats displayed acute symptoms of chemotoxicity, characterized by reduced appetite, weight loss, gait disturbance (a general marker of Taxol™ induced peripheral neuropathy), and general poor health (see Example 123). For example, over a thirteen day period control animals gained an average of 50 g, whereas the Taxol™ treated animals displayed no weight gain (see FIG. 2). All of the Taxol™ treated animals developed peripheral neuropathies, characterized by ‘tip toe walking’. The extent of this neuropathy was analyzed by quantifying the refracted light captured by a video camera as the animals walked over a glass plate. This data was analyzed by Northern Eclipse software. The Taxol™ treated animals displayed a 46% reduction in foot-pad contact with the glass plate, as compared to control animals (see Example 160). When compound 1 (5 mg/kg) was given with Taxol™ (9 mg/kg) on a bi-weekly schedule, the animals displayed greatly improved health. This was characterized by normal weight gain, as compared to control (FIG. 2), and a reduction in the severity of the peripheral neuropathies; a 23% loss in foot pad contact was observed, as compared to a 46% loss in the animals treated with Taxol™ alone (see Example 160 and FIGS. 4, 5 and 6). No acute signs of toxicity were observed in animals in acute toxicity studies with compound 1 alone (1, 5, and 10 mg/kg for 3 weeks). The sciatic nerve crush model is a representative model of axonal repair and regeneration. The sciatic nerve is physically crushed with forceps at the mid-thigh; only the right leg is injured, the left leg serving as a control. The axons die from the crush point to their point of innervation. Functional loss of the axons is rapidly observed as the animals drag their right leg and the toes of the right leg no longer spread. Recovery is observed in approximately 28 days as the animals regain use of their right leg. More quantitative measurements of recovery include toe spread measurements between the digits 1 and 5 and digits 2 and 4, gait analysis and electrical conductivity from the toes to the injury site (see Example 161). Rats were subjected to the crush injury and treated with either vehicle control or compounds 1, 76 or 111 (1 and 10 mg/kg). Functional recovery was measured as above and improved recovery was observed when the animals were treated with compound. For example, increase toe spread was observed for those animal treated with compound (see FIG. 7). Various diseases which result in loss of vision are related to increased inter-ocular pressure and ocular stroke or ischemia. Loss of the dorsal root ganglion (DRGs) occur during ischemic insult and in diseases such as diabetes and glaucoma. A model of inter-ocular ischemia involves an invasive increase in ocular pressure which results in the collapse of the central retinal artery. Retinal ischemia is confirmed by whitening of the iris and loss of red reflex. The inter-ocular pressure is normalized after 30 minutes. This procedure is performed on the right eye and the left eye serves as a control. Compound was given either by intra-vitrial injection or via SC injections at 10 mg/kg (see Example 162). The health of the DRG neurons was assessed by means of histological staining of retinal slices and electro-retinogram (ERG) recordings. Histology of the control animals showed almost complete loss of the DRG layer, where as animals treated with compound 1 showed healthy DRG layers. Similarly, significant improvements were observed in the ERG for those animals treated with compound verses vehicle control animals (see FIG. 8). This protection was observed for both the animals which received intra-vitrial injections and those that were treated systemically (SC). Alzheimer's disease is one of the biggest unmet medical needs in neurology. One of the main areas of AD research has been deposition and neurotoxicity of amyloid beta peptide fragments. Amyloid peptides are potently toxic to cortical neurons and protection of the cortical neurons would be a very desirable therapeutic target. We establish mixed neuronal/glial cortical cultures from postnatal rat pups. Amyloid beta peptides are potently toxic to neurons in these cultures. Exposure to 10 uM 25-35 amyloid beta increased the number of apoptotic cells compared to control. AEG33764 prevented the appearance of annexin V positive cells indicating that it protected in vitro against the amyloid beta peptide. For any of the compounds having the structure of Formula I which bear similarity to those known in the art, the use of these compounds for treatment and/or prevention of neurological disorders, cancer, inflammation, or symptoms related thereto are encompassed by the invention. Examples of Formula I are provided below in Table 2. These compounds are referred to throughout the disclosure as their corresponding example number. TABLE 2 Compounds Example STRUCTURE 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 Synthetic Procedures 2-Amino-5-thiadiazole sulfonamide, intermediate E1, was prepared by the acid hydrolysis of acetazolamide (Aldrich). Selected 2-bromoaryl ketones were purchased from either Aldrich Chemical Co. or from Maybridge Inc. Various acetophenones were readily prepared by the following protocols. A selection of 4-phenoxyacetophenones were prepared under standard Ullmann condensation conditions by heating 4-fluoroacetophenone with the appropriate phenol and K2CO3 in DMF or DMAc. Selected 4′-arylacetophenones were prepared by Suzuki coupling of either 3′- or 4′-haloacetophenone with an arylboronic acid, or 4-acetylbenzeneboronic acid with an arylbromide, using an appropriate palladium catalyst, base, and solvent system. These products may be obtained using alternative coupling partners; ie. Suzuki coupling between aryl bromides and aetophenone boronic acids, the use of flouroboranate salts, the use of Stille couplings between aryl bromides and arylstannanes, etc. Various acetophenones were α-brominated using bromine or pyridinium tribromide in an appropriate solvent system. The imidazo[2,1-b]-1,3,4-thiadiazole sulfonamides were prepared according to literature procedures. For example, compound 1 was prepared in good yield by refluxing intermediate A1, with an 2-bromoacetophenone, intermediate B1, in either alcohol or 1,4-dioxane, for 48 hours. Compound 1 was either mono- or dialkylated by the treatment of compound 1 with the appropriate alcohol (1 or 2 equiv), triphenyphosphine, and DIAD or polymer supported DIAD to yield compounds such as 137 and 138. Alternatively, N-alkylation may be accomplished using MeI and NaF/alumina ( ) as base, for the conversion of 1 to 137. Selective mono alklylation may be accomplished by alkylation of the N-acyl derivatives of 1, followed by alkylation using Mitsunobu conditions, as above, followed by de-acylation with PrNH2, to provide the mono N-methyl derivative 137. This last series of reactions also works with solid supported chemistry. Compound 1 was readily functionalized at the imidazole methine position by treatment with NaOCl or Br2, to provide compounds 123 and 124, respectively. Demethylation of intermediate D with BBr3 provides the phenolic compound 145. Acylation of compound 145 with benzoyl chloride provides compound 146. In several cases the requisite 2-bromoacetophenones were commercially available. In other cases they were prepared by the treatment of an appropriately substituted acetophenone with bromine, in an appropriate solvent, as exemplified below. Acylation of 4-aminoacetophenone was followed by bromination in MeOH to provide intermediate A69. Condensation of intermediate A69 with intermediate E1, yielded the desired compound 69. Treatment of compound 69 with methanolic HCl provided compound 70. Several α-bromoketones were prepared by bromination of the appropriate enol silyl ether. Therefore, deprotonation of either 4′-piperidenylaceophenone (A67) or 4′-morpholinoacetophenone (A68) with LiHMDS, silation with TMSCl, and quenching with N-bromosuccinamide, yielding the desired α-bromoketone intermediates B67 and A68, respectively, as shown below. Condensation of A67 and A68 with E1, provided compounds 67 and 68, respectively. Treatment of selected aryl ketones with bromine or pyridinium perbromide also provided the desired 2-bromoacetophenones, which were again condensed with 2-amino-1,3,4-thiadiazole-5-sulfonamide to provide the desired 6-aryl-imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamides, as shown below for compound 58. Compound 114 was prepared using the following strategy. 2′,3′,4′,5′, 6′-Pentafluoroacetophenone, A6, was treated with sodium azide, followed by bromide, to provide 2-bromo-4′-azido-2′,3′,5′,6′-tetrafluoroacetophenone, A151 (Keana, J. F. W.; Cai, S. X. J. Org. Chem., 1990, 55, 3640). Condensation of A151 with E1 to provided compound 151. Selected Compound Synthesis General Preparative Methods Commercially available acetophenones, 2-haloacetophenones (Intermediates A and B, respectively), phenols (Intermediate C), and benzeneboronic acids (Intermediate D) were purchased from either Aldrich Chemical Company, Lancaster, Maybridge Inc, or Fisher Scientific. The remainder of starting materials were obtained from Aldrich Chemical Company. 2-Amino-5-thiadiazole sulfonamide, intermediate E1, was prepared by the acid hydrolysis of acetazolamide (Aldrich). Method A: Bromination of Acetophenones with Bromine The appropriate acetophenone (Intermediate A) was dissolved in diethyl ether, methylene chloride, or chloroform, and cooled to 0° C. Bromine (1.1 equiv) was dissolved in either methylenechloride or diethyl ether and added to the solution of acetophenone via a dropping funnel. After the addition of bromine was complete 2 drops of acetic acid were added and the solution was warmed to room temperature. Solvent was removed under reduced pressure to provide crude 2-bromoacetophenone (Intermediate B) which was generally used without further purification. Method B: Bromination of Acetophenones with Pyridinium Tribromide The appropriate acetophenone (Intermediate A) was dissolved in acetic acid and treated with pyridinium tribromide (1.1 equiv). The solution was stirred until all solid had reacted, the solvent was removed under reduced pressure and the residue was extracted with an appropriate solvent, washing with water. The organic layer was dried over anhydrous magnesium sulphate, filtered, and the solvent removed under reduced pressure to provide the title compounds, which was generally used without further purification. Method C: Condensation of 2-bromoacetophenone with 2-amino-1,3,4-thiadiazole-5-sulfonamide The appropriate 2-rromoacetophenone and 2-amino-1,3,4-thiadiazole-5-sulfonamide (1.0 equiv) were refluxed in 1,4-dioxane or an appropriate alcohol for 12-60 hrs. The resulting solution was cooled on ice and the resulting precipitate was collected by filtration to provide compound 1 as a white crystalline solid. If no solid was observed the solvent was removed under reduced pressure and the title compounds were purified by silica gel chromatography, trituration, or recrystallization from an appropriate solvent. EXAMPLE 1 6-Phenylimidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Bromoacetophenone (4.00 g, 20.0 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (3.60 g, 20.0 mmol) were refluxed in ethanol (150 mL) for 60 hrs. The resulting solution was cooled on ice and the resulting precipitate was collected by filtration to provide compound 1 as a white crystalline solid (2.50 g, 44%). 1H NMR (200 MHz, DMSO-d6) δ 8.89 (s, 1H), 8.72 (br s, 2H), 7.90 (d, 2H), 7.43 (t, 2H), 7.32 (t, 1H). EXAMPLE 2 6-(2-Fluorophenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 2 was prepared by the bromination of 2′-fluoroacetophenone with bromine, according to Method A, followed by condensation with 2-amino-1,3,4-thiadiazole-5-sulfonamide hydrochloride, according to Method C, to provide a white solid. 1H NMR (200 MHz, DMSO-d6) δ 8.75 (br s, 2H), 8.6 (d, 1H, j=3.6 Hz), 8.1 (m, 1H), 7.3 (m, 3H). EXAMPLE 3 6-(3-Fluorophenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 3 was prepared by the bromination of 3′-fluoroacetophenone with bromine, according to Method A, followed by condensation with 2-amino-1,3,4-thiadiazole-5-sulfonamide hydrochloride, according to Method C, to provide a white solid. 1H NMR (200 MHz, DMSO-d6) δ 8.95 (s, 1H), 8.74 (s, 1H), 7.73 (m, 2H), 7.5 (m, 1H), 7.1 (m, 1H). EXAMPLE 4 6-(4-Fluorophenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Bromo-4′-fluoroacetophenone (1.08 g, 5.0 mmol) 2-amino-1,3,4-thiadiazole-5-sulfonamide hydrochloride (900 mg, 5.0 mmol) were refluxed in ethanol (25 mL) for 48 hrs. The resulting solution was cooled on ice and the resulting precipitate was collected by filtration to provide compound 19 as a white crystalline solid (17 mg). 1H NMR (200 MHz, DMSO-d6) δ 8.87 (s, 1H), 8.74 (br s, 2H), 7.40 (m, 2H), 7.28 (m, 2H). EXAMPLE 5 6-(3,4-Difluorophenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Chloro-3′,4′-difluoroacetophenone (190 mg, 1.0 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (150 mg, 1.0 mmol), and CETAB (437 mg, 1.20 mmol) were refluxed in dioxane (5 mL) for 48 hrs. The solvent was removed under reduced pressure and the resulting solid was purified by silica gel chromatography, eluting with 1:1 hexane/ethyl acetate, to provide compound 20 (173 mg, 57%) as a white crystalline solid. 1H NMR (200 MHz, acetone-d6) δ 8.41 (d, 1H), 8.26 (m, 1H), 7.92 (br s, 2H), 7.24-7.08 (m, 2H). EXAMPLE 6 6-(2,3,4,5,6-Pentafluorophenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Bromo-1-(pentafluorophenyl)ethan-1-one (2.89 g, 10.0 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (1.80 g, 10.0 mmol) were refluxed in ethanol (20 mL) for 60 hrs. Solvent was evaporated and the crude solid was purified by flash chromatography using 20:80:0.1 ethyl acetate:hexanes:acetic acid to provide compound 115 as white needles (125 mg, 3.4%). 1H NMR (200 MHz, DMSO-d6) δ 8.82 (s, 1H), 8.78 (s, 2H). EXAMPLE 7 6-(4-Ethylthio-2,3,5,6-tetrafluorophenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2′,3′,4′,5′,6′-Pentafluoroacetophenone (2.5 mmol) was heated with ethanethiol (2.5 mmol) in THF (5 mL). Solvent was removed underreduced pressure to provide the desired compounds as a white solid. Pyridinium tribromide (920 mg, 2.5 mmol)) was added and the mixture stirred for 16 hours. Solvent was removed under reduced pressure and 2-amino-1,3,4-thiadiazole-5-sulfonamide (450 mg, 2.5 mmol) was added and solution was refluxed for 48 hours. The solution was cooled to room temperature and filtered to provide compound 7 as a white solid (173 mg, 17%). 1H NMR (200 MHz, DMSO-d6) δ 8.82 (s, 1H), 8.79 (br s, 2H), 3.00 (quart, J=8.2 Hz, 2H), 1.98 (t, J=8.2 Hz, 3H). EXAMPLE 8 6-(4-Benzylthio-2,3,5,6-tetrafluorophenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 8 was prepared according to the procedure described for compound 7, using benzylmercaptan in the place of ethanethiol, to provide compound 8 as a white solid (204 mg, 16%). 1H NMR (200 MHz, DMSO-d6) δ 8.83 (s, 1H), 8.79 (br s, 2H), 7.23 (s, 5H), 4.21 (s, 2H). EXAMPLE 9 6-(4-Morpholino-2,3,5,6-tetrafluorophenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 6 (100 mg) was dissolved in 1 ml of DMSO and 1 ml of morpholine was added, the solution was heated to 90° C. for 2 hrs. The solution was allowed to cool down to room temperature and ethyl acetate was added. The solution was washed twice with water and once with brine. The organic layer was separated dried over magnesium sulfate and evaporated under reduced pressure. The residue was purified by silica gel chromatography using a 20% to 50% ethyl acetate in hexanes gradient to give a white solid (30 mg). 1H NMR (200 MHz, CDCl3) δ 8.05 (s, 1H), 3.76 (m, 4H), 3.27 (m 4H). EXAMPLE 10 6-(4-Chlorophenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 21 was obtained from Talon. EXAMPLE 11 6-(3,4-Dichlorophenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Bromo-3′,4′-dichloroacetophenone (267 mg, 1.0 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide hydrochloride (180 mg, 1.00 mmol) were refluxed in ethanol (20 mL) for 48 hrs. The resulting solution was cooled on ice and the resulting precipitate was collected by filtration to provide compound 11 as a white crystalline solid (91 mg, 26%). 1H NMR (200 MHz, DMSO-d6) δ 9.01 (s, 1H), 8.74 (s, 2H), 8.13 (d, 1H), 7.89 (dd, 1H), 7.70 (d, 1H). EXAMPLE 12 6-(2,3,4-trichlorophenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 12 was prepared by bromination of 2′,3′,4′-trichloroacetophenone with bromine according to Method A, and condensation of the corresponding 2-bromoacetophenone with 2-amino-1,3,4-thiadiazole-5-sulfonamide, according to Method C, to yield compound 12 as a white solid (22% yield). 1H NMR (200 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.74 (br s, 2H), 8.07 (d, J=8.5 Hz, 2H), 7.74 (d, J=8.5 Hz, 2H). EXAMPLE 13 6-(3-bromophenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 13 was prepared by bromination of 3′-bromoacetophenone with bromine according to Method A, and condensation of the corresponding 2-bromoacetophenone with 2-amino-1,3,4-thiadiazole-5-sulfonamide, according to Method C, to yield compound 13 as a white solid. 1H NMR (200 MHz, DMSO-d6) δ 8.94 (d, J=1.3 Hz, 1H), 8.74 (br s, 2H), 8.08 (d, J=1.1 Hz, 1H), 7.90 (dd, J=1.4, 7.7 Hz, 1H), 7.48 (d, J=7.7 Hz, 1H), 7.38 (t, J=8.6 Hz, 1H). EXAMPLE 14 6-(4-Bromophenyl)-imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Bromo-4′-bromoacetophenone (2.78 g, 10.0 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (1.80 g, 12.0 mmol) were refluxed in 1,4-dioxane (25 mL) for 16 hrs. The resulting solution was cooled on ice and the resulting precipitate was collected by filtration to provide compound 24 as a white crystalline solid (3.60 g). 1H NMR (200 MHz, DMSO-d6) δ 8.92 (s, 1H), 8.75 (br s, 2H), 7.85 (d, 2H), 7.62 (d, 2H). EXAMPLE 15 6-(2-Methoxyphenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Bromo-2′-methoxyacetophenone (916 mg, 4.0 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (720 mg, 4.0 mmol) were refluxed in ethanol (20 mL) for 48 hrs. The resulting solution was cooled on ice and the resulting precipitate was collected by filtration to provide compound 40 as a white crystalline solid. 1H NMR (200 MHz, DMSO-d6) δ 9.68 (br s, 1H), 8.78 (br s, 2H), 8.12 (d, 1H), 7.34 (t, 1H), 7.11 (d, 1H), 7.05 (t, 1H), 3.96 (s, 3H). EXAMPLE 16 6-(3-Methoxyphenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Bromo-3′-methoxyacetophenone (1.00 g, 4.37 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (786 mg, 4.37 mmol) were refluxed in 1,4-dioxane (25 mL) for 48 hrs. The resulting solution was cooled on ice and the resulting precipitate was collected by filtration to provide compound 41 as a white crystalline solid (375 mg, 28%). 1H NMR (200 MHz, DMSO-d6) δ 8.89 (s, 1H), 8.73 (br s, 2H), 7.46 (s, 2H), 7.33 (t, J=8.1 Hz, 1H), 6.88 (d, J=7.3 Hz, 1H), 3.80 (s, 3H). 13C NMR (50 MHz, DMSO-d6) δ 164.3, 159.8, 146.7, 145.2, 134.8, 130.0, 117.4, 113.7, 111.4, 110.3, 55.1. EXAMPLE 17 6-(4-Methoxyphenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Bromo-4′-methoxyacetophenone (2.29 g, 10.0 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (1.80 g, 12.0 mmol) were refluxed in 1,4-dioxane (25 mL) for 24 hrs. The resulting solution was cooled on ice and the resulting precipitate was collected by filtration to provide compound 42 as a white crystalline solid (2.65 g, 86%). 1H NMR (200 MHz, DMSO-d6) δ 8.83 (s, 1H), 8.00 (d, 2H), 7.13 (d, 2H), 3.88 (s, 3H). EXAMPLE 18 6-(2,5-Dimethoxyphenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Bromo-2′,5′-dimethoxyacetophenone (261 mg, 1.00 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (180 mg, 1.20 mmol) were refluxed in 1,4-dioxane (7 mL) for 48 hrs. The resulting solution was cooled on ice and the resulting precipitate was collected by filtration to provide compound 44 as a white crystalline solid (15.5 mg, 5%). 1H NMR (200 MHz, DMSO-d6) δ 8.72 (br s, 2H), 8.60 (s, 1H), 7.70 (d, 1H), 7.04 (d, 1H), 6.87 (dd, 1H), 3.89 (s, 3H), 3.74 (s, 3H). EXAMPLE 19 6-(2,4-Dimethoxyphenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Bromo-2′,4′-dimethoxyacetophenone (259 mg, 1 mmol) and 2-amino-1,3,4-thiadiazole-2-sulfonamide (180 mg, 1 mmol) were refluxed in ethanol for 5 days. After cooling the resulting precipitate was filtered and washed with methanol, providing 43 (56 mg) as a beige powder. 1H NMR (200 MHz, DMSO-d6) δ 8.69 (br s, 2H), 8.47 (s, 1H), 8.06 (d, J=8.8 Hz, 1H), 6.66 (s, 1H), 6.62 (d, J=2.4 Hz, 1H), 3.93 (s, 3H), 3.80 (s, 3H). EXAMPLE 20 6-(1,3-Benzodioxol-5-yl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 1-(1,3-benzodioxol-5-yl)-2-bromoethan-1-one (100 mg, 0.41 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (74 mg, 0.41 mmol) were refluxed in ethanol (5 mL) for 30 hrs. The resulting solution was cooled on ice and the resulting precipitate was collected by filtration to provide compound 95 as a pale yellow powder (40 mg, 44%). 1H NMR (200 MHz, DMSO-d6) δ 8.75 (s, 1H), 8.69 (s, 2H), 7.43 (m, 2H), 6.97 (d, J=8.6 Hz, 1H), 6.04 (s, 2H). EXAMPLE 21 6-(3,4-dihydro-2H-1,5-benzodioxepin-7-yl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Bromo-1-(3,4-dihydro-2H-1,5-benzodioxepin-7-yl)ethan-1-one (542 mg, 2 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (360 mg, 2 mmol) were refluxed in ethanol (10 ml) for 60 hours. The resulting mixture was cooled on ice and the resulting precipitate collected by suction filtration, giving 96 (310 mg) as a yellow powder. 1H NMR (200 MHz, DMSO-d6) δ 8.79 (s, 1H), 8.71 (br s, 2H), 7.49 (s, 1H), 7.45 (d, J=7.9 Hz, 1H), 7.00 (d, J=7.9 Hz, 1H), 4.2-4.0 (m, 4H), 2.10 (t, J=4.9 Hz, 2H). 13C NMR (50 MHz, DMSO-d6) δ 163.9, 151.4, 151.0, 146.2, 145.1, 128.9, 122.0, 120.1, 118.2, 110.7, 70.6, 31.5. EXAMPLE 22 6-(3,4-Dihydroxyphenyl-imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Chloro-3′,4′-dihydroxyacetophenone (186 mg, 1.0 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (150 mg, 1.0 mmol), and CETAB (10 mg) were refluxed in dioxane (5 mL) for 48 hrs. The solvent was removed under reduced pressure and the resulting solid was purified by silica gel chromatography, eluting with 1:1 hexane/ethyl acetate, to provide compound 48 (11 mg, 4%) as a white crystalline solid. 1H NMR (200 MHz, acetone-d6) δ 8.38 (s, 1H), 8.10 (br s, 2H), 7.84 (br s, 2H), 7.44 (d, 1H), 7.39 (dd, 1H), 6.88 (d, 1H). EXAMPLE 23 Compound 23 was prepared by the bromination of 2′-fluoroacetophenone with bromine, according to Method A, followed by condensation with 2-amino-1,3,4-thiadiazole-5-sulfonamide hydrochloride, according to Method C, to provide a white solid. 1H NMR (200 MHz, DMSO-d6) δ 8.75 (br s, 2H), 8.6 (d, 1H, j=3.6 Hz), 8.1 (m, 1H), 7.3 (m, 3H). EXAMPLE 24 6-(3-trifloromethoxyphenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 24 was prepared by bromination of 3′-trifluoromethoxyacetophenone with bromine according to Method A, and condensation of the corresponding 2-bromoacetophenone with 2-amino-1,3,4-thiadiazole-5-sulfonamide, according to Method C, to yield compound 24 as a white solid (22% yield). 1H NMR (200 MHz, DMSO-d6) δ 9.01 (s, 1H), 8.74 (br s, 2H), 7.92 (d, J=7.6 Hz, 1H), 7.91 (s, 1H), 7.57 (t, J=7.6 Hz, 1H), 7.30 (d, J=7.6 Hz, 1H). EXAMPLE 25 6-(4-trifloromethoxyphenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 25 was prepared by bromination of 4′-trifluoromethoxyacetophenone with bromine according to Method A, and condensation of the corresponding 2-bromoacetophenone with 2-amino-1,3,4-thiadiazole-5-sulfonamide, according to Method C, to yield compound 25 as a white solid (22% yield). 1H NMR (200 MHz, DMSO-d6) δ 8.93 (s, 1H), 8.73 (s, 2H), 8.00 (d, J=8.8 Hz, 2H), 7.43 (d, J=8.4 Hz, 2H). EXAMPLE 26 Compound 26 was prepared in a manner similar to compound 31. 1H NMR (200 MHz, DMSO-d6) δ=3.71 (t, 2H, J=4.6 Hz), 4.00 (t, 2H, J=4.9 Hz), 6.99 (d, 2H, J=8.3 Hz), 7.81 (d, 2H, J=8.2 Hz), 8.67 (s, 2H), 8.73 (s, 1H). EXAMPLE 27 Step 1: Compound 26 (472 mg, 1.39 mmol), di-tert-butyldicarbonate (383 μL, 1.67 mmol), triethylamine (194 μL, 1.39 mmol), DMAP (20 mg, 0.16 mmol) were added to DMF (5 mL) and stirred at RT under N2 for 45 min. The volatiles were removed under reduced pressure and the contents washed with H2O and EtOAc. The organic layer was collected, dried over MgSO4. 1H NMR (200 MHz, CDCl3) δ 1.23 (s, 9H), 3.73 (t, 2H, J=5.4 Hz), 4.00 (t, 2H, J=5.6 Hz), 7.02 (d, 2H, J=8.8 Hz), 7.82 (d, 2H, J=8.4 Hz), 8.69 (s, 1H). Step 2: The material from step 1 (627 mg, 1.39 mmol), acetic anhydride (158 μL, 1.67 mmol), triethlyamine (233 μL, 1.67 mmol), DMAP (21 mg, 0.17 mmol) were added to DMF (5 mL) and stirred under N2 for 3 h. The volatiles were removed under reduced pressure and the contents washed with H2O and EtOAc. The organic layer was collected, dried over MgSO4. 1H NMR (200 MHz, CDCl3) δ 1.20 (s, 9H), 2.08 (s, 3H), 4.09 (b, 2H), 4.40 (b, 2H), 6.90 (d, 2H, J=8.8 Hz), 7.62 (d, 2H, J=8.4 Hz). Step 3: The material from Step 3 was dissolved in 10 mL TFA/CH2Cl2 (1:1) and stirred for 30 min at RT. The volatiles were removed under reduced pressure and the contents washed with NaHCO3 (aq) and EtOAc. The organic layer was collected, dried over MgSO4. The product was recrytallized from ethanol. 1H NMR (200 MHz, DMSO-d6) δ 2.03 (s, 3H), 4.20 (b, 2H), 4.31 (b, 2H), 7.02 (d, 2H, J=8.8 Hz), 7.82 (d, 2H, J=8.4 Hz), 8.69 (s, 2H), 8.76 (s, 1H). EXAMPLE 28 Step 1: 2-Bromoethanol, K2CO3 and 4-hydroxy acetophenone were refluxed together in MeOH. The solvent was removed under reduced pressure and the residue treated to standard ethyl acetate/water work-up to provide a white semi-sold. 1H NMR (200 MHz, CDCl3) δ 2.55 (s, 3H), 3.65 (t, 2H, J=6.1 Hz), 4.35, t, 2H, J=6.4 Hz), 6.94 (d, 2H, J=9.5 Hz), 7.93 (d, 2H, J=8.8 Hz). Step 2: The material from Step 1 (50 mg, 0.216 mmol), NaN3 (20 mg, 0.307 mmol) were dissolved in acetone (5 mL) and H2O (0.5 mL) and heated to reflux with stirring for 16 h. Solvent was removed and the desired compounds was obtained in quantitative yield. 1H NMR (200 MHz, CDCl3) δ 2.55 (s, 3H), 3.63 (t, 2H, J=4.6 Hz), 4.21 (t, 2H, J=5.19 Hz), 6.95 (d, 2H, J=8.85 Hz), 7.94 (d, 2H, J=8.9 Hz). Step 3: The material from Step 2 was brominated according to Method A and purified on silica gel (4:1, CH2Cl2:Hexanes) to give 2-Bromo-4′-(2-azidoethoxy)acetophenone. 1H NMR (200 MHz, CDCl3) δ 3.63 (t, 2H, J=4.9 Hz), 4.21 (t, 2H, J=5.2 Hz), 4.40 (s, 2H), 6.95 (d, 2H, J=9.2 Hz), 7.94 (d, 2H, J=8.6 Hz). Step 4: 2-Bromo-4′-(2-azidoethoxy)acetophenone was condensed with 1,3,4-thiadiazole-2-sulfonamide according to Method C yielding an off yellow solid. 1H NMR (200 MHz, DMSO-d6) δ 3.65 (t, 2H, J=4.0 Hz), 4.20 (t, 2H, J=4.3 Hz), 7.02 (d, 2H, J=8.2 Hz), 7.83 (d, 2H, J=8.2 Hz), 8.71 (s, 2H), 8.76 (s, 1H). EXAMPLE 29 Step 1: 3-Bromo-1,1,1-trifluoropropane, K2CO3 and 4′-hyrdoxyacetophenone were refluxed together in MeOH for 16 hours. Volatiles were removed under reduced pressure and the residue subjected to standard ethyl acetate/water work-up. 1H NMR (200 MHz, CDCl3) δ 2.48-2.70 (m, 5H), 4.19 (t, 2H, J=6.4 Hz), 6.87 (d, 2H, J=8.8 Hz), 7.87 (d, 2H, 9.2 Hz). Step 2: 4′-(3,3,3-trifluoropropoxy)acetophenone was brominated according to Method A. 1H NMR (200 MHz, CDCl3) δ 2.48-2.70 (m, 2H), 4.27 (t, 2H, J=6.4 Hz), 4.40 (2, 2H) 6.96 (d, 2H, J=8.8 Hz), 7.98 (d, 2H, 9.2 Hz). Step 3: 2-Bromo-4′-(3,3,3-trifluoropropoxy)acetophenone was condensed with 1,3,4-thiadiazole-2-sulfonamide according to Method C, yielding an off yellow solid. 1H NMR (200 MHz, DMSO-d6) δ 2.65-2.85 (m, 2H), 4.23 (t, 2H, J=6.2 Hz), 7.02 (d, 2H, J=8.6 Hz), 7.83 (d, 2H, J=8.6 Hz), 8.71 (s, 2H), 8.76 (s, 1H). EXAMPLE 30 Step 1:1-Bromo-2-(2-methoxyethoxy)ethane, K2CO3 and 4′-hyrdoxyacetophenone were refluxed together in MeOH for 16 hours. Volatiles were removed under reduced pressure and the residue subjected to standard ethyl acetate/water work-up. 1H NMR (200 MHz, CDCl3) δ 2.55(s, 3H) 3.39 (s, 3H), 3.56 (t, 2H, J=4.0 Hz), 3.71 (t, 2H, J=4.6 Hz), 3.88 (t, 2H, 4.3 Hz), 4.21 (t, 2H, J=4.9 Hz), 6.94 (d, 2H, J=8.8. Hz), 7.92 (d, 2H, J=8.2 Hz). Step 2: The material from Step 1 was brominated according to Method A. 1H NMR (200 MHz, CDCl3) δ 3.40 (s, 3H), 3.56 (t, 2H, J=4.0 Hz), 3.71 (t, 2H, J=4.6 Hz), 3.88 (t, 2H, 4.3 Hz), 4.21 (t, 2H, J=4.9 Hz), 4.40 (s, 2H), 6.94 (d, 2H, J=8.8. Hz), 7.92 (d, 2H, J=8.2 Hz). Step 3: The Material from Step 2 was condensed with 2-amino-1,3,4-thiadiazole-2-sulfonamide according to Method C to provide a yellow solid. 1H NMR (200 MHz, DMSO-d6) δ 3.23 (s, 3H), 3.47 (b, 2H), 3.57 (b, 2H), 3.73 (b, 2H), 4.11 (b, 2H), 7.00 (d, 2H, J=8.2 Hz), 7.81 (d, 2H, J=8.6 Hz), 8.70 (s, 2H), 8.74 (s, 1H). EXAMPLE 31 Step 1: 4-Hydroxyacetophenone (500 mg, 3.67 mmol), K2CO3 (510 mg, 3.69 mmol) and benzyl-2-bromoethyl ether (580 μL, 3.67 mmol) were suspended in ethanol (25 mL). The mixture was heated to reflux with stirring for 21 h. The volatiles were removed under reduced pressure and the contents washed with H2O and EtOAc. The organic layer was collected, dried over MgSO4 and purified on silica gel (1:3 EtOAc/Hexanes) yielding 4′-(2-Benzyloxyethoxy)acetophenone as a white crystalline solid (600 mg, 61%). 1H NMR (200 MHz, CDCl3) δ 2.55 (s, 3H), 3.85 (t, 2H, J=4.9 Hz), 4.21 (t, 2H, J=4.9 Hz), 4.64 (s, 2H), 6.95 (d, 2H, J=8.9 Hz), 7.35 (b, 5H), 7.93 (d, 2H, J=8.8 Hz). Step 2: 4-(2-Benzyloxyethoxy)acetophenone (447 mg, 1.65 mmol) was brominated using Method A to yield a yellow oil (51% conversion). 1H NMR (200 MHz, CDCl3) δ 3.85 (t, 2H, J=4.9 Hz), 4.21 (t, 2H, J=4.9 Hz), 4.64 (s, 2H), 4.80 (s, 2H), 6.95 (d, 2H, J=8.9 Hz), 7.35 (b, 5H), 7.93 (d, 2H, J=8.8 Hz). Step 3: 6-(4′-(2-Benzyloxyethoxy)phenyl)-imidazo[2,1-b]-1,3,4-thidiazole-2 sulfonamide The crude material from Step 2 (299 mg, 0.86 mmol) was condensed with 2-amino-1,3,4-thiadiazole-2-sulfonamide using Method C in 2-propanol, yielding a yellow solid (140 mg, 38%). 1H NMR (200 MHz, DMSO-d6) δ 3.77 (b, 2H), 4.18 (b, 2H), 4.55 (s, 2H), 7.01 (d, 2H, J=8.5 Hz), 7.33 (b, 5H) 7.81 (d, 2H, J=8.5 Hz), 8.69 (s, 2H), 8.74 (s, 1H). EXAMPLE 32 Step: 4-Hydroxyacetophenone (500 mg, 3.67 mmol), K2CO3 (510 mg, 3.69 mmol) and benzyl-3-bromopropyl ether (547 μL, 3.67 mmol) were suspended in ethanol (25 mL). The mixture was heated to reflux with stirring for 21 h. The volatiles were removed under reduced pressure and the contents washed with H2O and EtOAc. The organic layer was collected, dried over MgSO4 and purified on silica gel (1:3 EtOAc/Hex) yielding 4′-(2-Benzyloxyethoxy)acetophenone as a white crystalline solid (737 mg, 71%). 1H NMR (200 MHz, CDCl3) δ 2.08-2.14 (m, 2H), 2.56 (s, 3H), 3.67 (t, 2H, J=6.1 Hz), 4.16 (t, 2H, J=6.1 Hz), 4.53 (s, 2H), 6.92 (d, 2H, J=8.5 Hz), 7.31 (s, 5H), 7.93 (d, 2H, J=8.9 Hz). Step 2: 4′-(3-Benzyloxy)propoxyacetophenone (447 mg, 1.65 mmol) was brominated using Method A to provide a yellow oil (82% conversion). 1H NMR (200 MHz, CDCl3) δ 2.08-2.14 (m, 2H), 3.67 (t, 2H, J=6.1 Hz), 4.16 (t, 2H, J=6.1 Hz), 4.40 (s, 2H), 4.53 (s, 2H), 6.92 (d, 2H, J=8.5 Hz), 7.93 (d, 2H, J=8.9 Hz). Step 3: The crude material from step 3 (671 mg, 1.85 mmol) was condensed with 2-amino-1,3,4-thiadiazole-2-sulfonamide using Method C (2-propanol) provided a yellow solid (85 mg, 10%). 1H NMR (200 MHz, DMSO-d6) δ 1.96-2.06 (m, 2H), 3.58 (t, 2H, J=6.4 Hz), 4.08 (t, 2H, J=5.8 Hz), 4.47 (s, 2H), 6.98 (d, 2H, J=8.5 Hz), 7.30 (s, 2H), 7.80 (d, 2H, J=8.5 Hz), 8.69 (s, 2H), 8.73 (s, 1H). EXAMPLE 33 6-(4-(2-Morpholinoethoxy)phenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Bis(methanesulfonic Acid) 6-(4-(2-Morpholinoethoxy)phenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide was prepared according to Method C. 1H NMR (200 MHz, DMSO-d6) δ 8.70 (s, 1H), 7.82 (8.2 Hz, 2H), 7.05 (d, J=8.2 Hz, 2H), 4.34 (m, 4H), 3.81 (m, 4H), 3.48 (m, 2H), 3.26 (m, 2H). 6-(4-(2-Morpholinoethoxy)phenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide (100 mg) was suspended in MeOH (2 mL) and treated with methanesulfonic acid (100 uL). Diethyl ether (10 mL) was added and the resulting solid was filtered and washed with diethyl ether to provide compound 33. 1H NMR (200 MHz, D2O) δ 8.09, 7.53 (d, J=6.7 Hz, 2H), 6.97 (d, J=6.7 Hz, 2H), 4.43 (s, 2H), 4.20 (m, 2H), 3.96 (br t, 2H), 3.70 (m, 4H), 3.35 (m, 2H), 2.80 (br s, 4H). EXAMPLE 34 Compound 34 was prepared in a manner similar to that described for compound 32. 1H NMR (200 MHz, DMSO-d6) δ 3.71 (t, 2H, J=4.9 Hz), 3.82 (s, 2H), 3.98 (t, 2H, J=4.6 Hz), 7.01 (d, 1H, J=8.2 Hz), 7.40-7.48 (m, 3H), 8.71 (s, 2H), 8.79 (s, 1H). EXAMPLE 35 Compound 35 was prepared in a manner similar to compound 32. 1H NMR (200 MHz, DMSO-d6) δ 8.78 (s, 1H), 8.67 (s, 2H), 7.48 (s, 1H), 7.40 (d, J=8.6 Hz, 1H), 7.34 (s, 5H), 7.02 (d, J=8.6 Hz, 1H), 4.56 (s, 2H), 4.14 (br s, 2H), 3.83 (s, 3H), 3.77 (br s, 2H). EXAMPLE 36 Compound 36 was prepared in a manner similar to compound 32. 1H NMR (200 MHz, DMSO-d6) δ 8.78 (s, 1H), 8.70 (s, 2H), 7.47 (s, 1H), 7.42 (d, J=8.2 Hz, 1H), 7.30 (s, 5H), 7.01 (d, J=8.2 Hz, 1H), 4.47 (s, 2H), 4.06 (t, J=6.1 Hz, 2H), 3.80 (s, 3H), 3.59 (t, J=6.3 Hz, 2H), 1.99 (t, J=6.1 Hz, 2H). EXAMPLE 37 6-(3-Nitrophenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Bromo-3′-nitroacetophenone (224 mg, 1.0 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (180 mg, 1.20 mmol) were refluxed in 1,4-dioxane (7 mL) for 48 hrs. The resulting solution was cooled on ice and the resulting precipitate was collected by filtration to provide compound 37 as a yellow crystalline solid (54 mg, 15%). 1H NMR (200 MHz, DMSO-d6) δ 9.12 (s, 1H), 8.75 (br s, 2H), 8.70 (t, 1H), 8.31 (d, 1H), 8.14 (d, 1H), 7.72 (t, 1H). EXAMPLE 38 6-(3-nitro-4-chlorophenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 38 was prepared by bromination of 3-nitro-4-chloroacetophenone with bromine according to Method A, and condensation of the corresponding 2-bromoacetophenone with 2-amino-1,3,4-thiadiazole-5-sulfonamide, according to Method C, to yield compound 38 as a white solid (22% yield). 1H NMR (200 MHz, DMSO-d6) δ 9.09 (s, 1H), 8.77 (s, 2H), 8.53 (s, 1H), 8.18 (d, J=6.9 Hz, 2H), 7.86 (d, J=8.5 Hz, 2H). EXAMPLE 39 Step 1: 4-Acetylbenzoic acid (1.00 g, 6.09 mmol) was suspended in methanol (10 mL). Hydrochloric acid (500 μL) was added. The reaction mixture was refluxed overnight. The resulting suspension was cooled to −10° C., filtered and the solid washed with cold methanol (3×2 mL) to provide methyl 4-acetylbenzoate as a white solid (799 mg, 74%). 1H NMR (200 MHz, CDCl3) δ 8.12 (d, J=8.9 Hz, 2H), 8.01 (d, J=8.9 Hz, 2H), 3.95 (s, 3H), 2.65 (s, 3H). Step 2 Methyl 4-acetylbenzoate (200 mg, 1.12 mmol) was suspended in chloroform (5 mL) and treated with pyridinium tribromide (359 mg, 1.12 mmol). The reaction mixture was stirred overnight. One half equivalent of pyridinium tribromide (179 mg, 0.56 mmol) was added to the reaction mixture and stirred for two days. The solvent was removed under reduced pressure. Standard aqueous/ethyl acetate workup provided a brown solid, which was identified as a 8:12:3 mixture of starting material, methyl 4-(2-bromoacetyl)benzoate and methyl 4-(2,2-dibromoacetyl)benzoate compound. 1H NMR (200 MHz, DMSO-d6) δ 8.08 (d, J=6.7 Hz, 4H), 4.98 (s, 2H), 3.87 (s, 3H). Step 3 Methyl 4-(2-bromoacetyl)benzoate (100 mg, 0.39 mmol) and 5-amino-1,3,4-thiadiazole-2-sulfonamide (70 mg, 0.39 mmol) were refluxed together in methanol (10 mL) for 48 hours. The resulting suspension was cooled to −10° C., filtered and the solid washed with cold methanol (3×2 mL) to provide compound 39 as a white solid (12.9 mg, 9.35%). 1H NMR (200 MHz, DMSO-d6) δ 9.03 (s, 1H), 8.70 (br s, 2H), 8.03 (s, 4H), 3.85 (s, 3H). EXAMPLE 40 6-(4-carboxyphenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Step 1: 4-Acetylbenzoic acid (186 mg, 1.14 mmol) was dissolved in warm acetic acid (5 mL) and treated with bromine (58 mL, 1.14 mmol). The solution was stirred overnight before being cooled on ice. The resulting solid was filtered, washed with 1:1 methanol/water (3×10 mL) and dried in vacuo to provide 4-(2-bromoacetyl)benzoic acid as a white solid (102 mg). 1H NMR (200 MHz, DMSO-d6) δ 8.07 (s, 4H), 4.98 (s, 2H). Step 2: 4-(2-bromoacetyl)benzoic acid (102 mg) and 5-amino-1,3,4-thiadiazole-2-sulfonamide (75 mg, 0.42 mmol) were refluxed together in methanol (20 mL) for 48 hours. The resulting suspension was cooled to −10° C., filtered and the solid washed with cold methanol (3×5 mL) to provide compound 40 as a white crystalline solid (16 mg). 1H NMR (200 MHz, DMSO-d6) δ 9.02 (s, 1H), 8.00 (s, 4H). EXAMPLE 41 6-(3-cyanophenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 3-(2-bromoacetyl)benzonitrile (100 mg, 0.45 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (80 mg, 0.45 mmol) were refluxed in ethanol (10 mL) for 60 hrs. The resulting solution was cooled on ice and the resulting precipitate was collected by filtration to provide compound 98 as a white crystalline solid (78 mg, 57%). 1H NMR (200 MHz, DMSO-d6) δ 9.03 (s, 1H), 8.76 (s, 2H), 8.32 (s, 1H), 8.23 (d, J=7.6 Hz, 1H), 7.71 (m, 2H); 13C NMR (50 MHz, DMSO) δ 164.9, 145.8, 144.6, 134.6, 131.3, 130.2, 129.4, 128.3, 118.7, 112.4, 112.1. EXAMPLE 42 6-(4-cyanophenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 4-(2-bromoacetyl)benzonitrile (448 mg, 2 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (360 mg, 2 mmol) were refluxed in ethanol for 60 hours. The resulting mixture was cooled on ice and the precipitate collected by suction filtration to provide 42 (300 mg) as a white powder. 1H NMR (200 MHz, DMSO-d6) δ 9.07 (s, 1H), 8.77 (br s, 2H), 8.09 (d, 2H), 7.90 (d, 2H). EXAMPLE 43 6-(4-(methylsulfonyl)phenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Bromo-1-[4-(methylsulfonyl)phenyl]ethan-1-one (100 mg, 0.36 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (65 mg, 0.36 mmol) were refluxed in ethanol (5 mL) for 60 hrs. The resulting solution was cooled on ice and the resulting precipitate was collected by filtration to provide compound 43 as a white powder (55 mg, 43%). 1H NMR (200 MHz, DMSO-d6) δ 9.08 (s, 1H), 8.76 (s, 2H), 8.15 (d, J=8.1 Hz, 2H), 7.96 (d, J=8.1 Hz, 2H), 3.23 (s, 3H). EXAMPLE 44 6-(4-(phenylmethylsulfonyl)phenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 44 was prepared by bromination of 4′-(phenylmethylsulfonyl)acetophenone with bromine according to Method A, and condensation of the corresponding 2-bromoacetophenone with 2-amino-1,3,4-thiadiazole-5-sulfonamide, according to Method C, to yield compound 44 as a white solid. 1H NMR (200 MHz, DMSO-d6) δ 9.06 (s, 1H), 8.74 (s, 2H), 8.02 (m, 6H), 7.65 (m, 3H). EXAMPLE 45 Compound 44 was prepared by according to Methods A and C, to yield compound 45 as a white solid. 1H NMR (200 MHz, DMSO-d6) δ 9.08 (s, 1H), 8.65 (s, 2H), 8.08 (d, J=8.0 Hz, 2H), 7.85 (d, J=8.0 Hz, 2H), 3.18 (quart, J=7.6 Hz, 2H), 1.05 (t, J=7.6 Hz, 3H). EXAMPLE 46 6-(4-Pentylphenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Bromo-1-(4-pentylphenyl)ethan-1-one (269 mg, 1.0 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (180 mg, 1.0 mmol) were refluxed in ethanol (10 mL) for 48 hrs. The resulting solution was cooled on ice and the resulting precipitate was collected by filtration to provide compound 46 as a white powder (180 mg, 51%). 1H NMR (200 MHz, DMSO-d6) δ 8.81 (s, 1H), 8.71 (s, 2H), 8.79 (d, J=8.2 Hz, 2H), 7.24 (d, J=8.2 Hz, 2H), 2.54 (t, J=7.0 Hz, 2H), 1.57 (quintet, J=7.6 Hz, 2H), 1.27 (m, 4H), 0.85 (t, J=6.7 Hz, 3H); 13C NMR (50 MHz, DMSO): δ 164.0, 147.1, 145.3, 142.5, 130.9, 128.9, 125.2, 110.7, 34.9, 30.9, 30.6, 22.0, 14.0. EXAMPLE 47 6-(4-Methylphenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Bromo-1-(4-methylphenyl)ethan-lone (213 mg, 1 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (148 mg, 1 mmol) were refluxed in ethanol (10 mL) for 60 hours. Solvent was removed under reduced pressure. The suspension was cooled to −4° C., filtered and washed with cold methanol (3×5 mL), to provide compound 47 (118 mg, 42%) as a white powder. 1H NMR (200 MHz, DMSO-d6) δ 8.80 (s, 1H), 8.71 (s, 2H), 7.78 (d, 2H), 7.23 (d, 2H), 2.31 (s, 3H). EXAMPLE 48 6-(2,4-dimethylphenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Bromo-1-(2,4-dimethylphenyl)ethan-1-one (227 mg, 1 mmol) and 2-amino-1,3,4-thiadiazole-2-sulfonamide (180 mg, 1 mmol) were refluxed in ethanol for 5 days. The volatiles were removed in vacuo. The residue was purified by column chromatography on silica using 30% ethyl acetate/1% acetic acid in hexane as eluant. Recrystallization from dichloromethane gave 48 (30 mg) as a white powder. 1H NMR (200 MHz, DMSO-d6) δ 8.71 (br s, 2H), 8.52 (s, 1H), 7.70 (d, J=7.6 Hz, 1H), 7.10 (s, 1H), 7.06 (s, 1H), 2.46(s, 3H), 2.29 (s, 3H). EXAMPLE 49 6-(4-(phenylmethylsulfonyl)phenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 44 was prepared by bromination of 4′-tert-butylacetophenone with bromine according to Method A, and condensation of the corresponding 2-bromoacetophenone with 2-amino-1,3,4-thiadiazole-5-sulfonamide, according to Method C, to yield compound 49 as a white solid. 1H NMR (200 MHz, DMSO-d6) δ 8.81 (s, 1H), 8.70 (s, 2H), 7.81 (d, J=7.9 Hz, 2H), 7.44 (d, J=8.2 Hz, 2H), 1.29 (s, 9H). EXAMPLE 50 Compound 50 was prepared according to Method A and Method C, to yield compound 50 as a white solid. 1H NMR (200 MHz, DMSO-d6) δ 8.72 (br s, 2H), 8.54 (s, 1H), 7.80 (s, 1H), 7.18 (s, 1H), 3.05 (t, 2H), 1.95 (t, 2H), 1.15 (s, 9H). EXAMPLE 51 MS (m/z) M+=249.10. EXAMPLE 52 6-(4-(Trifluoromethyl)phenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Bromo-1-[4-(trifluoromethyl)phenyl]ethan-1-one (534 mg, 2.0 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (360 mg, 2.0 mmol) were refluxed in ethanol (10 mL) for 60 hrs. The resulting solution was cooled on ice and the resulting precipitate was collected by filtration to provide compound 52 as a white powder (270 mg, 39%). 1H NMR (200 MHz, DMSO-d6) δ 9.05 (s, 1H), 8.74 (s, 2H), 8.10 (d, J=8.0 Hz, 2H), 7.80 (d, J=8.0 Hz, 2H). EXAMPLE 53 6-(5-chloro-2-trifluoromethylphenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 51 was prepared by bromination of 5′-chloro-4′-trifluoromethylacetophenone with bromine according to Method A, and condensation of the corresponding 2-bromoacetophenone with 2-amino-1,3,4-thiadiazole-5-sulfonamide, according to Method C, to yield compound 52 as a white solid. 1H NMR (200 MHz, DMSO-d6) δ 9.04 (s, 1H), 8.78 (s, 2H), 8.47 (s, 1H), 7.82 (d, J=8.6 Hz, 1H), 7.72 (d, J=8.6 Hz, 1H). EXAMPLE 54 6-(3,5-di(trifluoromethyl)phenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Bromo-1-[3,5-di(trifluoromethyl)phenyl]ethan-1-one (670 mg, 2.0 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (360 mg, 2.0 mmol) were refluxed in ethanol (10 mL) for 60 hrs. The resulting solution was cooled on ice and the resulting precipitate was collected by filtration to provide compound 54 as a white powder (292 mg, 70%). 1H NMR (200 MHz, DMSO-d6) δ 9.26 (s, 1H), 8.77 (s, 2H), 8.54 (s, 2H), 8.04 (s, 1H). EXAMPLE 55 6-(3,4-Di-tert-butyl-4-hydroxyphenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Bromo-1-(3,4-di-tert-butyl-4-hydroxyphenyl)ethan-1-one (327 mg, 1 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (148 mg, 1 mmol) were refluxed in ethanol (10 mL) for 60 hours. Solvent was removed under reduced pressure. The resulting solid was suspended in methanol (5 mL) and stirred for 30 minutes prior to suction filtration, washing twice for cold methanol (2 mL), to provide compound 55 (93 mg, 24%) as a white powder. 1H NMR (200 MHz, DMSO-d6) δ 8.72 (s, 1H), 8.68 (s, 2H), 7.63 (s, 2H), 1.41 (s, 9H). EXAMPLE 56 6-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Bromo-1-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)ethan-1-one (250 mg, 0.81 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (146 mg, 0.81 mmol) were refluxed in ethanol (10 mL) for 60 hours. Solvent was evaporated under reduced pressure and the resulting solid suspended in ethanol (3 ml). The precipitate was collected by suction filtration and washed with ethanol to provide compound 56 (45 mg) as an off white solid. 1H NMR (200 MHz, DMSO-d6) δ 8.8 (s, 1H), 8.6 (br s, 2H), 7.8 (br s, 1H), 7.6 (dd, 1H), 7.3 (d, 1H), 1.6 (s, 4H), 1.3 (s, 6H), 1.2 (s, 6H). EXAMPLE 57 1H NMR (200 MHz, DMSO-d6) δ 8.73 (s, 2H), 8.48 (s, 1H), 7.75 (s, 1H), 7.18 (s, 1H), 5.42 (br s, 4H), 2.21 (s, 3H), 1.63 (s, 3H), 1.23 (s, 9H). EXAMPLE 58 6-(4-(S-1-acetamidoethyl)phenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Bromo-4′-(S-1-acetamidoethyl)acetophenone (426 mg, 1.5 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (222 mg, 1.5 mmol) were refluxed in ethanol (10 mL) for 60 hours. The resulting solution was cooled to −4° C. for 2 hours and the resulting solid was filtered, washing twice for cold methanol (2 mL), to provide compound 57 (172 mg, 34%) as white crystals. 1H NMR (200 MHz, DMSO-d6) δ 8.82 (s, 1H), 8.70 (s, 2H), 8.28 (d, 1H), 7.83 (d, 2H), 7.34 (d, 2H), 4.91 (dt, 1H), 1.83 (s, 3H), 1.33 (d, 3H). EXAMPLE 59 6-(4-(Trifluoromethyl)phenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Bromo-1-[4-(trifluoromethyl)phenyl]ethan-1-one (534 mg, 2.0 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (360 mg, 2.0 mmol) were refluxed in ethanol (10 mL) for 60 hrs. The resulting solution was cooled on ice and the resulting precipitate was collected by filtration to provide compound 59 as a white powder (270 mg, 39%). 1H NMR (200 MHz, DMSO-d6) δ 9.05 (s, 1H), 8.74 (s, 2H), 8.10 (d, J=8.0 Hz, 2H), 7.80 (d, J=8.0 Hz, 2H). EXAMPLE 60 6-(1-adamantyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 1-(1-Adamantyl)-2-bromoethan-1-one (514 mg, 2.0 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (360 mg, 2.0 mmol) were refluxed in ethanol (10 mL) for 60 hrs. The resulting solution was cooled on ice and the resulting precipitate was collected by filtration to provide compound 60 as a white powder (120 mg, 18%). 1H NMR (200 MHz, DMSO-d6) δ 8.64 (s, 2H), 8.03 (s, 1H), 2.03 (m, 3H), 1.90 (m, 6H), 1.72 (m, 6H). EXAMPLE 61 6-(2-Naphthyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 61 was prepared by bromination of 1-acetylnapthylene with bromine according to Method A, followed by condensation of the corresponding bromide with 2-amino-1,3,4-thiadiazole-5-sulfonamide, according to Metod C, to yield an off white solid. 1H NMR (200 MHz, DMSO-d6) δ 9.25 (br s, 2H), 8.79 (s, 1H), 8.77 (s, 1H), 8.63 (dd, 1H), 7.97 (m, 2H), 7.78 (dd, J=1.2, 7.0 Hz, 1H), 7.61-7.49 (m, 3H). EXAMPLE 62 6-(2-Naphthyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Bromonaphthone (2.50 g, 10.0 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (1.80 g, 1.2 mmol) were refluxed in 1,4-dioxane (20 mL) for 96 hrs. The resulting solution was cooled on ice and the resulting precipitate was collected by filtration to provide compound 62 as a tan crystalline solid (2.36 g, 38%) in two crops. 1H NMR (200 MHz, DMSO-d6) δ 8.99 (s, 1H), 8.74 (br s, 2H), 8.42 (s, 1H), 8.05 (d, 1H), 7.96-7.89 (m, 2H), 7.51 (m, 2H). EXAMPLE 63 6-(2-(6-methoxy-7-bromonaphthyl))imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Step 1: 2-Acetyl-6-methoxyacetophenone (1.00 g, 5.0 mmol) was dissolved in methanol (5 mL) and was treated with bromine (500 μL, 10.0 mmol). The reaction was stirred at room temperature for 2 hours before the volatiles were removed in vacuo to provide a 95:5 mixture of 2,7′-dibromo-6′-methoxylnaphone and 2-acetyl-6-methoxyacetophenone. This crude mixture was advanced to the next step without further purification. 1H NMR (200 MHz, DMSO-d6) δ 8.75 (s, 1H), 8.20 (d, 1H), 8.10 (d, 1H), 8.07 (dd, 1H), 7.64 (d, 1H), 5.01 (s, 2H), 4.03 (s, 3H). Step 2: To the crude mixture obtained above was added 5-amino-1,3,4-thiadiazole-2-sulfonamide (740 mg, 5.0 mmol) and methanol (20 mL). The resulting suspension was refluxed for 48 hours, cooled on ice and the solid filtered off, to provide compound 63 as a white solid (230 mg). 1H NMR (200 MHz, DMSO-d6) δ 8.95 (s, 1H), 8.76 (d, 1H), 8.44 (s, 1H), 8.11 (s, 2H), 8.02 (d, 1H), 7.52 (d, 1H), 3.99 (s, 3H). EXAMPLE 64 6-pyrenylimidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 1-(Bromoacetyl)-pyrene (646 mg, 2 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (360 mg, 2 mmol) were refluxed in ethanol (20 ml) for 60 hrs. Solvent was removed under reduced pressure. The resulting solid was purified by silica gel chromatography, eluting with solvent gradient of 30-100% ethyl acetate/hexane, to afford compound 64 as a brownish orange solid (4.5 mg). 1H NMR (200 MHz, DMSO-d6) δ 9.0 (s, 1H), 8.8 (s, 2H), 8.50-8.00 (m, 9H). EXAMPLE 65 5-Methyl-6-phenyl-imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Bromopropiophenone (1.07 mg, 5.00 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide hydrochloride (900 mg, 5.0 mmol) were refluxed in ethanol (25 mL) for 48 hrs. The resulting solution was cooled on ice and the resulting precipitate was collected by filtration to provide compound 65 as a white crystalline solid (100 mg). 1H NMR (200 MHz, DMSO-d6) δ 8.75 (br s, 3H), 7.75 (d, 2H), 7.45 (t, 2H), 7.30 (t, 1H), 2.65 (s, 3H). EXAMPLE 66 5,6-Diphenyl-imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Desyl bromide (550 mg, 2 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (360 mg, 2 mmol) were refluxed in ethanol (20 ml) for 60 hrs. Solvent was removed under reduced pressure. Purification by silica gel chromatography, eluting with 30:0.1:70 ethyl acetate/acetic acid/hexane, and recrystallization from dichloromethane gave compound 66 as a white crystalline solid (175 mg). 1H NMR (200 MHz, DMSO-d6) δ 8.8-8.6 (s, 2H), 7.7-7.4 (m, 7H), 7.4-7.2 (m, 3H). EXAMPLE 67 6-(4-Piperidinophenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Step 1: 4′-Piperidinoacetophenone (203 mg, 1.00 mmol) was dissolved in THF (5 mL) and treated with lithium bis(trimethylsilyl)amide (1.10 mL, 11.0M in THF, 1.10 mmol). The solution was stirred for 30 minutes prior to the addition of chlorotrimethylsilane (140 μL, 1.10 mmol). After stirring for an additional 30 minutes N-bromosuccinamide (300 mg, 1.73 mmol) was added and the mixture was refluxed from 4 hours. Standard aqueous/ethyl acetate workup provided a yellow solid which was further purified by silica gel chromatography, eluting with 3:1 hexane/ethyl acetate, to provide 2-bromo-4′-piperidinoacetophenone as an off white solid (209 mg, 74%). 1H NMR (200 MHz, CDCl3) δ 8.75 (d, 2H), 6.84 (d, 2H), 4.61 (s, 2H), 3.40 (m, 4H), 1.68 (m, 6H). Step 2: 2-Bromo-4′-piperidinoacetophenone (209 mg, 0.74 mol) and 5-amino-1,3,4-thiadiazole-2-sulfonamide (220 mg, 1.48 mmol) were suspended in 1,4-dioxane (10 mL) and refluxed for 48 hours. The solvent was removed under reduced pressure and the residue was purified by silica gel chromatography, eluting with 1:1 hexane/ethyl acetate, to provide compound 67 as a yellow solid (8.0 mg, 2.7%). 1H NMR (200 MHz, DMSO-d6) δ 8.68 (s, 3H), 7.75 (d, 2H), 6.98 (d, 2H), 3.23 (m, 4H), 1.57 (m, 6H). EXAMPLE 68 6-(4-Morpholinophenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Step 1: 4′-Morpholinoacetophenone (218 mg, 1.0 mmol) was dissolved in THF (5 mL) and treated with lithium bis(trimethylsilyl)amide (1.1 mL, 1.0M in THF, 1.1 mmol). The solution was stirred for 30 minutes prior to the addition of chlorotrimethylsilane (140 μL, 1.1 mmol). After stirring for an additional 30 minutes N-bromosuccinamide (300 mg, 1.73 mmol) was added and the mixture was refluxed from 4 hours. Standard aqueous/ethyl acetate workup provided a yellow solid, which was identified as a 3:1 mixture of 2-bromo-4′-morpholinoacetophenone and starting material. 1H NMR (200 MHz, CDCl3) δ 7.86 (d, 2H), 6.84 (d, 2H), 4.62 (s, 2H), 3.84 (t, 4H), 3.32 (t, 4H). Step 2: The crude 2-Bromo-4′-morpholinoacetophenone from above and 5-amino-1,3,4-thiadiazole-2-sulfonamide (100 mg, 0.66 mmol) were suspended in 1,4-dioxane (10 mL) and refluxed for 48 hours. The solvent was removed under reduced pressure and the residue was purified by silica gel chromatography, eluting with 1:1 hexane/ethyl acetate, to provide compound 68 as a yellow solid (23 mg). 1H NMR (200 MHz, DMSO-d6) δ 8.67 (s, 3H), 7.74 (d, 2H), 6.99 (d, 2H), 3.75 (t, 4H), 3.13 (t, 4H). EXAMPLE 69 6-(4-Benzoylamidophenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Step 1: 4-Aminoacetophenone (1.35 g, 10.0 mmol) was dissolved in dichloromethane (10 mL) and treated with benzoyl chloride (1.74 mL, 15.0 mmol). The mixture was stirred for 16 hours at which time a white precipitate had formed. The solid was removed by filtration, washing with dichloromethane (3×20 mL) to provide 4-acetamidoacetophenone as a white sold (2.74 g). 1H NMR (200 MHz, DMSO-d6) δ 10.53 (s, 1H), 7.92 (s, 7H), 7.54 (m, 3H), 2.50 (s, 3H). Step 2: 4-Benzoylamidoacetophenone (2.55 g) was dissolved in acetic acid (25 mL) and was treated with pyridinium tribromine (3.00 g, 8.0 mmol). The reaction was stirred at room temperature for 24 hours before the volatiles were removed in vacuo to provide 2-bromo-4′-benzoylamidoacetophenone. This crude mixture was advanced to the next step without further purification. 1H NMR (200 MHz, DMSO-d6) δ 10.61 (s, 1H), 8.96 (d, 2H), 8.61 (t, 1H), 8.15-8.00 (m, 7H), 4.86 (s, 2H). Step 3: To the crude mixture obtained above was added 5-amino-1,3,4-thiadiazole-2-sulfonamide (1.50 mg, 10.0 mmol) and methanol (20 mL). The resulting suspension was refluxed for 48 hours. The solvent was removed under reduced pressure and the residue was triturated from acetone to provide compound 69 as a yellow solid (120 mg). 1H NMR (200 MHz, DMSO-d6) δ 10.35 (s, 1H), 8.82 (s, 1H), 8.70 (br s, 2H), 7.92 (d, 2H), 7.82 (s, 5H), 7.54 (d, 2H). EXAMPLE 70 6-(4-Aminophenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 66 (60 mg) was suspended in methanol (10 mL) and treated with 6N HCl (1 mL). The suspension was refluxed for 16 hours until all solids had dissolved. The solvent was removed under reduced pressure and the residue was suspended in water (10 mL), neutralized with saturated aqueous NaHCO3. The resulting precipitate was extracted with ethyl acetate to provide compound 70 as a yellow solid (15 mg). 1H NMR (200 MHz, DMSO-d6) δ 8.65 (br s, 2H), 8.53 (s, 1H), 7.58 (d, 2H), 6.58 (d, 2H), 5.32 (br s, 2H). EXAMPLE 71 Compound 77 was prepared by the bromination of 4-acetylphenylboronic acid according to Method A to yield the desired α-bromoacetophenone, which was condensed with 2-amino-1,3,4-thiadiazole-5-sulfonamide according to Method C, to yield compound 71 as a white solid. 1H NMR (200 MHz, DMSO-d6) δ 8.89 (s, 1H), 8.73 (s, 2H), 8.05 (br s, 2H), 7.86 (s, 4H). EXAMPLE 72 6-(Biphenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Bromo-4′-phenylacetophenone (1.38 g, 5.0 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide hydrochloride (0.90 g, 5.0 mmol) were refluxed in ethanol (20 mL) for 60 hrs. The resulting solution was cooled on ice and the resulting precipitate was collected by filtration to provide compound 72 as a white solid (0.75 g, 45%). 1H NMR (200 MHz, DMSO-d6) δ 8.95 (s, 1H), 8.74 (s, 2H), 8.00 (d, J=8.6 Hz, 2H), 7.74 (m, 4H), 7.44 (m, 3H). EXAMPLE 73 6-(4-(2,3,4,5,6-tetrafluorophenyl)phenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Step 1: 4′-Bromoacetopherione and 2,3,4,5,6-tetrafluorobenzene boronic (5.0 mmol) acid, K2CO3 (10 mmol), and PdCl2(PPh)2 (0.1 equiv) were refluxed in toluene for 16 hours. The solvent was removed under reduced pressure and the residue was purified by silica gel chromatography, eluting with 4:1 hexane/ethyl acetate, to provide 4′-(2,3,4,5,6-tetrafluorophenylacetophenone as a white solid. Step 2: 4′-(2,3,4,5,6-Tetrafluorophenylacetophenone was dissolved in diethyl ether and treated with bromine (5 mmol). Solvent was removed under reduced pressure to provide 2-bromo-4′-(2,3,4,5,6-tetrafluorophenylacetophenone, which was used without further purification. Step 3: 2-bromo-4′-(2,3,4,5,6-tetrafluorophenylacetophenone and 2-amino-1,3,4-thiadiazole-5-sulfonamide hydrochloride (0.90 g, 5.0 mmol) were refluxed in ethanol (20 mL) for 60 hrs. The resulting solution was cooled on ice and the resulting precipitate was collected by filtration to provide compound 72 as a white solid (0.75 g, 45%). 1H NMR (200 MHz, DMSO-d6) δ 8.99 (s, 1H), 8.74 (s, 2H), 8.05 (d, J=8.6 Hz, 2H), 7.57 (d, J=8.6 Hz, 2H). EXAMPLE 74 6-(4-(hydroxymethylphenyl)phenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 74 was prepared in a manner similar to compound 73. 1H N (200 MHz, DMSO-d6) δ 8.93 (s, 1H), 8.73 (s, 2H), 7.98 (d, J=8.2 Hz, 2H), 7.73 (d, J=8.2 Hz, 2H), 7.67 (d, J=8.2 Hz, 2H), 7.39 (d, J=8.2 Hz, 2H), 4.53 (s, 2H). EXAMPLE 75 6-(4-(2-methoxyphenyl)phenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 75 was prepared in a manner similar to compound 73. 1H NMR (200 MHz, DMSO-d6) δ 8.89 (s, 1H), 8.73 (s, 2H), 7.92 (d, J=8.3 Hz, 2H), 7.53 (d, J=8.3 Hz, 2H), 7.31 (m, 2H), 7.10 (d, J=8.5 Hz, 1H), 7.02 (t, J=7.3 Hz, 1H), 3.76 (s, 3H). EXAMPLE 76 6-(4-(3-methoxyphenyl)phenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 76 was prepared in a manner similar to compound 73. 1H NMR (200 MHz, DMSO-d6) δ 8.94 (s, 1H), 8.73 (s, 2H), 7.97 (d, J=8.2 Hz, 2H), 7.74 (d, J=8.3 Hz, 2H), 7.34 (t, J=7.3 Hz, 1H), 7.26 (d, J=7.3 Hz, 1H), 7.23 (s, 1H), 6.92 (d, J=7.3 Hz, 1H), 3.81 (s, 3H). EXAMPLE 77 6-(4-(4-trifluoromethylphenyl)phenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 77 was prepared in a manner similar to compound 73. 1H NMR (200 MHz, DMSO-d6) δ 8.91 (s, 1H), 8.73 (s, 2H), 7.96 (d, J=8.6 Hz, 2H), 7.70 (d, J=8.8 Hz, 2H), 7.66 (d, J=8.6 Hz, 2H), 7.02 (d, J=8.8 HZ, 2H), 3.80 (s, 3H). EXAMPLE 78 6-(4-(3-trifluoromethoxyphenyl)phenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 78 was prepared in a manner similar to compound 73. 1H NMR (200 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.75 (s, 2H), 8.01 (d, J=8.0 Hz, 2H), 7.79 (m, 3H), 7.69 (s, 1H), 7.59 (t, J=8.1 Hz, 1H), 7.35 (d, J=7.9 Hz, 1H). EXAMPLE 79 6-(4-(hydroxymethylphenyl)phenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 79 was prepared in a manner similar to compound 73. MS (m/z) M+1=401. EXAMPLE 80 6-(4-(2-trifluoromethylphenyl)phenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 80 was prepared in a manner similar to compound 73. 1H NMR (200 MHz, DMSO-d6) δ 8.93 (s, 1H), 8.71 (s, 2H), 7.95 (d, 2H), 7.77 (d, 2H), 7.66 (t, 1H), 7.60 (t, 1H), 7.35 (m, 2H). EXAMPLE 81 6-(4-(3-trifluoromethylphenyl)phenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 81 was prepared in a manner similar to compound 73. 1H NMR (200 MHz, DMSO-d6) δ 8.98 (s, 1H), 8.74 (s, 2H), 8.02 (m, 4H), 7.84 (d, J=8.2 Hz, 2H), 7.70 (m, 2H). EXAMPLE 82 6-(4-(4-trifluoromethylphenyl)phenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 82 was prepared in a manner similar to compound 73. 1H NMR (200 MHz, DMSO-d6) δ 8.97 (s, 1H), 8.73 (s, 2H), 8.05-7.80 (m, 8H). EXAMPLE 83 6-(4-(3,5-ditrifluoromethylphenyl)phenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 83 was prepared in a manner similar to compound 73. 1H NMR (200 MHz, DMSO-d6) δ 9.02 (s, 1H), 8.75 (s, 2H), 8.38 (s, 2H), 8.01 (m, 5H). EXAMPLE 84 6-(thiophen-2-yl-phenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 85 was prepared in a manner similar to compound 73. 1H NMR (200 MHz, DMSO-d6) δ 8.92 (s, 1H), 8.70 (s, 2H), 7.94 (d, J=8.2 Hz, 2H), 7.73 (d, J=8.2 Hz, 2H), 7.56 (m, 2H), 7.15 (m, 1H). EXAMPLE 85 6-(thiophen-3-yl-phenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 86 was prepared in a manner similar to compound 73. 1H NMR (200 MHz, DMSO-d6) δ 8.79 (s, 1H), 8.72 (s, 2H), 7.88 (d, J=8.2 Hz, 2H), 7.16 (t, J=8.2 Hz, 1H), 7.03 (d, J=8.2 Hz, 2H), 6.49 (d, J=8.2 Hz, 1H), 6.38 (s, 1H), 6.27 (d, J=7.3 Hz, 1H), 2.86 (s, 6H). EXAMPLE 86 6-(thiophen-3-yl-phenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 86 was prepared in a manner similar to compound 73. 1H NMR (200 MHz, DMSO-d6) δ 8.98 (s, 1H), 8.72 (s, 2H), 8.14 (s, 1H), 7.84 (d, J=7.3 Hz, 1H), 7.67 (d, J=8.5 HZ, 2H), 7.54 (m, 2H), 7.05 (d, J=8.9 Hz, 2H), 2.80 (s, 3H). EXAMPLE 87 6-(4-phenoxyphenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Step 1: 4-Phenoxyacetopheneone was prepared by refluxing 4-fluoroaceotone and phenol in DMAc for 16 hours. The solvent was removed under reduced pressure and the reside subjected to standard ethyl acetate/water work-up and the resulting material purified by silica gel chromatography. Step 2: 4-Phenoxyacetophenone was brominated with bromine according to Method A to provide the desired α-bromoacetophenone, which was condensed with 2-amino-13,4,-thiadiazole-5-sulfonamide according to method C, to provide compound 87 as an off white, solid. 1H NMR (200 MHz, DMSO-d6) δ 8.82 (s, 1H), 8.71 (s, 2H), 7.90 (d, J=7.9 Hz, 2H), 7.40 (t, J=7.3 Hz, 2H), 7.07 (t, J=7.3 Hz, 1H), 7.08-7.03 (m, 6H). EXAMPLE 88 6-(4-chlorophenoxyphenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 88 was prepared in a manner similar to compound 87. 1H NMR (200 MHz, DMSO-d6) δ 8.81 (s, 1H), 8.72 (s, 2H), 7.89 (d, J=8.5 Hz, 2H), 7.23 (m, 2H), 7.11-7.01 (m, 4H). EXAMPLE 89 6-(4-(3,4-difluorophenoxy)phenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 89 was prepared in a manner similar to that described for compound 87. MS (m/z) M+1=409. EXAMPLE 90 6-(4-(4-azaphenoxy)phenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 90 was prepared in a manner similar to that described for compound 87. 1H NMR (200 MHz, DMSO-d6) δ 9.02, 8.76 (s, 2H), 8.41 (d, J=8.6 Hz, 2H), 8.10 (d, J=8.6 Hz, 2H), 7.71 (d, J=8.6 Hz, 2H), 7.01 (d, J=8.6 Hz, 2H). EXAMPLE 91 6-(4-chlorophenoxyphenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 91 was prepared in a manner similar to compound 87. 1H NMR (200 MHz, DMSO-d6) δ 8.84 (s, 1H), 8.72 (s, 2H), 7.92 (d, J=8.5 Hz, 2H), 7.44 (d, J=8.5 Hz, 2H), 7.08 (m, 4H). EXAMPLE 92 6-(3,4-dichlorophenoxyphenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 92 was prepared in a manner similar to compound 87. 1H NMR (200 MHz, DMSO-d6) δ 8.86 (s, 1H), 8.72 (s, 2H), 7.94 (d, J=8.5 Hz, 2H), 7.63 (d, J=8.9 Hz, 1H), 7.34 (d, J=2.7 Hz, 1H), 7.16 (d, J=8.9 Hz, 2H), 7.04 (dd, J=8.9 Hz, 2J=2.8 Hz, 1H). EXAMPLE 93 6-(2-bromophenoxyphenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 93 was prepared in a manner similar to compound 87. 1H NMR (200 MHz, DMSO-d6) δ 8.82 (s, 1H), 8.72 (s, 2H), 7.90 (d, J=8.2 Hz, 2H), 7.74 (d, J=7.9 Hz, 1H), 7.37 (t, J=7.5 Hz, 1H), 7.15 (t, J=8.4 Hz, 2H), 7.00 (d, J=8.5 Hz, 2H). EXAMPLE 94 6-(3-bromophenoxyphenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 93 was prepared in a manner similar to compound 87. MS (m/z) M+1=452, M+2=454. EXAMPLE 95 6-(4-bromophenoxyphenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 95 was prepared in a manner similar to compound 87. 1H NMR (200 MHz, DMSO-d6) δ 6.98-7.19 (m, 4H), 7.55 (d, 2H, J=8.5 Hz), 7.92 (d, 2H, J=8.5 Hz), 8.71 (s, 2H), 8.84 (s, 1H). EXAMPLE 96 6-(3-dimethylaminophenoxyphenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 96 was prepared in a manner similar to compound 87. 1H NMR (200 MHz, DMSO-d6) δ 8.79 (s, 1H), 8.72 (s, 2H), 7.88 (d, J=8.2 Hz, 2H), 7.16 (t, J=8.2 Hz, 1H), 7.03 (d, J=8.2 Hz, 2H), 6.49 (d, J=8.2 Hz, 1H), 6.38 (s, 1H), 6.27 (d, J=7.3 Hz, 1H), 2.86 (s, 6H). EXAMPLE 97 6-(4-(4-iso-propylphenoxy)phenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 97 was prepared in a manner similar to compound 87. 1H NMR (200 MHz, DMSO-d6) δ 8.81 (s, 1H), 8.72 (s, 2H), 7.89 (d, J=8.9 Hz, 2H), 7.26 (d, J=8.5 Hz, 2H), 7.03 (d, J=8.9 Hz, 2H), 6.97 (d, J=8.5 Hz, 2H), 2.88 (septet, J=6.9 Hz, 1H), 1.19 (d, J=6.7 Hz, 6H). EXAMPLE 98 6-(4-(4-azaphenoxy)phenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 98 was prepared in a manner similar to that described for compound 87. 1H NMR (200 MHz, DMSO-d6) δ 8.79 (s, 1H), 8.71 (s, 2H), 7.84 (d, J=8.8 Hz, 2H), 7.06-6.94 (m, 4H), 3.74 (s, 3H). EXAMPLE 99 6-(4-(4-nitrophenoxy)phenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 99 was prepared in a manner similar to compound 87. 1H NMR (200 MHz, DMSO-d6) δ 8.91 (s, 1H), 8.73 (s, 2H), 8.25 (d, J=8.9 Hz, 2H), 8.00 (d, J=8.2 Hz, 2H), 7.27 (d, J=8.5 Hz, 2H), 7.18 (d, J=8.9 Hz, 2H). EXAMPLE 100 6-(3-bromophenoxyphenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 100 was prepared in a manner similar to compound 87. MS (m/z) M+1=409. EXAMPLE 101 Step 1: 4-Hydroxyacetophenone (5.00 g, 36.7 mmol) was dissolved in THF (100 mL) and cooled on ice. Sodium bis(trimethylsilyl)amide (40.5 mL, 1.0M in THF, 40.5 mmol) was added and the solution was warmed to room temperature. After stirring for 2 hours the solution was cooled on ice and ethyl bromoacetate (6.14 mL, 55.1 mmol) was added; The solution was stirred over night. Standard aqueous workup provided the desired ester as a clear oil, which was dissolved in 3:2:1 THF/methanol/1.0M NaOH (36 mL). After stirring over night the solution was diluted with diethyl ether and water. The aqueous layer was separated, washed with diethyl ether, and acidified. The resulting solid was extracted with ethyl acetate to provide 2-(4-acetylphenoxy)acetic acid as a white solid (2.91 g). Step 2: 2-(4-acetylphenoxy)acetic acid (2.81 g, 14.5 mmol) was dissolved in acetic acid (100 mL) and treated with bromine (740 μL, 14.5 mmol) and stirred 48 hours. Bromine (370 mL, 7.25 mmol) was added and solution was stirred for an additional 16 hours. Volatiles were removed under reduced pressure to provide a brown solid which was titurated with diethyl ether to provide 2-(4-(2-bromoacetyl)phenoxy)acetic acid (1.82 g) as a light brown solid. Step 3: 2-(4-(2-Bromoacetyl)phenoxy)acetic acid (1.00 g, 3.66 mmol) and 5-amino-1,3,4-thiadiazole-2-sulfonamide (659 mg, 3.66 mmol) were refluxed together in methanol (20 mL) for 48 hours. The resulting suspension was cooled to −10° C., filtered and the solid washed with cold methanol (3×5 mL) to provide compound 101 as a white crystalline solid (578 mg, 44%). 1H NMR (200 MHz, DMSO-d6) δ 8.69 (s, 1H), 7.65 (d, 2H), 7.02 (d, 2H), 4.83 (s, 2H), 3.70 (s, 3H), 2.64 (s, 3H). EXAMPLE 102 Compound 101 (50 mg, 0.14 mmol) was dissolved in 3:2:1 THF/methanol/1M NaOH (9 mL) and stirred over night. The resulting solution was diluted with ethyl acetate and water. The aqueous layer was washed with ethyl acetate and acidified to yield a white suspension. The suspension was extracted with ethyl acetate, the organic layer was dried over anhydrous MgSO4, filtered, and the solvent removed under reduced pressure to provide compound 102 as a white solid (10.2 mg). 1H NMR (200 MHz, DMSO-d6) δ 8.74 (s, 1H), 7.80 (d, J=8.8 Hz, 2H), 6.96 (d, J=8.8 Hz, 2H), 4.66 (s, 2H). EXAMPLE 103 4-(2-Bromopropionyl)phenylacetic acid (256 mg, 1.0 mmol) and 5-amino-1,3,4-thiadiazole-2-sulfonamide (185 mg, 1.22 mmol) were refluxed together in methanol (20 mL) for 48 hours. The resulting suspension was cooled to −10° C., filtered and the solid washed with cold methanol (3×5 mL) to provide compound 103 as a white crystalline solid (22 mg, 7%). 1H NMR (200 MHz, DMSO-d6) δ 8.69 (s, 1H), 7.65 (d, 2H), 7.02 (d, 2H), 4.83 (s, 2H), 3.70 (s, 3H), 2.64 (s, 3H). EXAMPLE 104 6-(3-chloro-4-methylphenyl)-5-methylimidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Bromo-1-(3-chloro-4-methylphenyl)propan-1-one (262 mg, 1.0 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (180 mg, 1.0 mmol) were refluxed in ethanol (10 mL) for 5 days. The resulting solution was concentrated and the crude material was purified by column chromatography on silica gel, eluting with 25:75 ethyl acetate/hexanes to provide compound 104 as a yellow powder (38 mg, 11%). 1H NMR (200 MHz, DMSO-d6) δ 8.72 (s, 2H), 7.74 (m, 1H), 7.59 (m, 1H), 7.48 (m, 1H), 2.68 (s, 3H), 2.39 (s, 3H). EXAMPLE 105 6-(2-Pyridyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-(2-bromoacetyl)pyridine (2.5 g, 12.4 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (2.2 g, 12.4 mmol) were refluxed in methanol (75 mL) for 48 hrs. After evaporation of methanol 1M sodium hydroxide (25 mL) was added and the resulting solution was washed with ether (3×20 mL). The aqueous layer was acidified to a pH of 7 with 1M hydrochloric acid and extracted with ethyl acetate (3×25 mL). The solid obtained from the organic layers was recrystallized in acetone to provide compound 105 as a light brown powder (84 mg, 2.4%). 1H NMR (200 MHz, DMSO-d6) δ 8.82 (s, 1H), 8.74 (br s, 2H), 8.58 (d, J=5.5 Hz, 1H), 7.92 (m, 2H), 7.33 (m, 1H). EXAMPLE 106 6-(2-Pyridyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide HCl Compound 105 (25 mg) was dissolved in methanol and HCl gas was bubbled through for 30 seconds. Volatiles were removed under reduced pressure to provide a white solid (99%). 1H NMR (200 MHz, D2O-d6) δ 8.86 (s, 1H), 8.57 (d, J=5.8 Hz, 1H), 8.50 (t, J=7.5 Hz, 1H), 8.27 (d, J=8.2 Hz, 1H), 7.80 (t, J=6.7 Hz, 1H). EXAMPLE 107 6-(4-Pyridyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Bromo-1-(4-pyridinyl)-1-ethanone hydrobromide (100 mg, 0.356 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (64 mg, 0.356 mmol) were refluxed in 1,4-dioxane (5 mL) for 48 hours. The resulting solid was isolated by filtration and recrystallized from methanol to provide compounds 80 as a brown solid (129 mg, 42% yield). 1H NMR (200 MHz, DMSO-d6) δ 9.52 (s, 1H), 8.90 (d, 2H), 8.84 (s, 2H), 8.39 (d, 2H). EXAMPLE 108 6-(2-Pyrimidenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Step 1: Acetylpyrazine (244 mg, 2.0 mmol) was suspended in glacial acetic acid (10 mL) and treated with pyridinium tribromide (640 mg, 2.0 mmol). The reaction mixture was stirred overnight. The solvent was removed under reduced pressure and the residue was purified by silica gel chromatography, eluting with 1:1 hexane/ethyl acetate, to provide 2-(2-bromoacetyl)pyrazine as a brown solid (154 mg, 38%). 1H NMR (200 MHz, DMSO-d6) δ 9.16 (d, J=1.5 Hz, 1H), 8.94 (d, J=2.4 Hz, 1H), 8.82 (dd, J=1.5, 2.4 Hz, 1H), 4.99 (s, 2H). Step 2 2-(2-Bromoacetyl)pyrazine (154 mg, 0.764 mmol) and 5-amino-1,3,4-thiadiazole-2-sulfonamide (138 mg, 0.764 mmol) were refluxed together in methanol (10 mL) for 48 hours. The resulting suspension was cooled to −10° C., filtered and the solid washed with cold methanol (3×2 mL) to provide compound 108 as a brown solid (6.6 mg, 3.1%). 1H NMR (200 MHz, DMSO-d6) δ 9.19 (s, 1H), 8.98 (s, 1H), 8.78 (s, 2H), 8.65 (d, J=1.5 Hz, 1H), 8.59 (d, J=2.7 Hz, 1H). EXAMPLE 109 6-(coumaran-2-yl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-(2-Bromoacetyl)coumaran (mg, 1.0 mmol) and 5-amino-1,3,4-thiadiazole-2-sulfonamide (180 mg, 1.0 mmol) were refluxed together in methanol (10 mL) for 72 hours. The resulting suspension was cooled to −10° C., filtered and the solid washed with cold methanol (3×2 mL) to provide compound 92 as a white solid (15.6 mg, 5.4%). 1H NMR (200 MHz, DMSO-d6) δ 8.79 (s, 1H), 8.65 (br s, 1H), 8.61 (s, 1H), 7.81 (d, J=7.6 Hz, 1H), 7.58 (m, 1H), 7.38 (m, 2H). 13C NMR (50 MHz, DMSO-d6) δ 164.7, 158.5, 152.5, 139.9, 137.5, 131.9, 128.9, 124.8, 119.8, 119.1, 116.0, 114.6, 96.7. EXAMPLE 110 6-(Chloroacetyl)-2-H-1,4-benzoxazin-3(4H)-one (248 mg, 1.1 mmol), n-Bu4NI (405 mg, 1.1 mmol) and 5-amino-1,3,4-thiadiazole-2-sulfonamide (148 mg, 1.0 mmol) were refluxed together in methanol (12 mL) for 4 days. The resulting precipitate was isolated by filtration, washing with cold methanol, to provide compounds 110 as a white solid (58 mg). 1H NMR (200 MHz, DMSO-d6) δ 10.84 (s, 1H), 8.79 (s, 3H), 7.48 (s, 1H), 7.42 (d, 2H), 7.00 (d, 2H), 4.58 (s, 2H). EXAMPLE 111 6-(Benzo[b]furan-2-yl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 1-(1-benzofuran-2-yl)-2-bromoethan-1-one (100 mg, 0.41 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (74 mg, 0.41 mmol) were refluxed in ethanol (5 mL) for 30 hrs. The resulting solution was cooled on ice and the resulting precipitate was collected by filtration to provide compound 111 as an off white powder (47 mg, 33%). 1H NMR (200 MHz, DMSO-d6) δ 8.86 (s, 1H), 8.77 (br s, 2H), 7.65 (m, 2H), 7.29 (m, 3H). EXAMPLE 112 6-(2-Thiophenyl)-imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Acetylthiophene (252 mg, 2.0 mmol) was dissolved in acetic acid (5 mL) and treated with bromine (100 μL, 2.0 mmol). The solution was stirred overnight before the volatiles were removed under reduced pressure to provide a white solid, which contained a 3:1 mixture of (2-bromoacetyl)thiophene and starting material. This crude mixture was refluxed in methanol (10 mL) with 5-amino-1,3,4-thiadiazole-2-sulfonamide (300 mg, 2.0 mmol) for 5 days. The resulting solid was filtered, washing with methanol (3×5 mL) to provide compounds 112 as a light pink solid (60.5 mg). 1H NMR (200 MHz, DMSO-d6) δ 8.70 (s, 1H), 7.48 (m, 2H), 7.11 (t, 1H). EXAMPLE 113 6-(5-Phenylthiophen-2-yl)-imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Bromo-1-(5-phenyl-2-thienyl)-1-ethanone (100 mg, 0.36 mmol) and 2-amino-1,3,4-thiadiazole-2-sulfonamide were refluxed in ethanol for 120 hours. The volatiles were removed in vacuo. The residue was purified by column chromatography on silica gel using 20% ethyl acetate/1% acetic acid in hexane followed by 30% ethyl acetate/1% acetic acid in hexane as eluant. Triturating with diethyl ether provided compound 113 (7 mg) as an orange solid. 1H NMR (200 MHz, DMSO-d6) δ 8.82 (s, 1H), 8.70 (br s, 2H), 7.70-7.20 (m, 7H). EXAMPLE 114 5-Bromo-6-(5-Nitro-2-thiophenyl)-imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Hydrobromide EXAMPLE 115 6-(3-Methylbenzo[b]thiophen-2-yl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Bromo-1-(3-methylbenzo[b]thiophen-2-yl)ethan-1-one (125 mg, 0.5 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (74 mg, 0.5 mmol) were refluxed in ethanol (10 mL) for 72 hrs. The resulting solution was cooled on ice and the resulting precipitate was collected by filtration to provide compound 115 as a white crystalline solid (63 mg, 39%). 1H NMR (200 MHz, DMSO-d6) δ 8.80 (s, 1H), 8.78 (s, 2H), 8.94 (dd, 1H), 8.83 (dd, 1H), 7.42 (dt, 1H), 7.37 (dt, 1H), 2.58 (s, 3H). EXAMPLE 116 6-(Benzo[b]thiophen-3-yl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 1-Benzo[b]thiophen-3-yl-2-bromoethan-1-one (125 mg, 0.5 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (74 mg, 0.5 mmol) were refluxed in ethanol (10 mL) for 72 hrs. The resulting solution was cooled on ice and the resulting precipitate was collected by filtration to provide compound 116 as a white crystalline solid (63 mg, 39%). 1H NMR (200 MHz, DMSO-d6) δ 8.91 (s, 1H), 8.74 (br s, 2H), 8.52 (d, 1H), 8.13 (s, 1H), 8.05 (d, 1H), 7.50-7.42 (m, 2H). EXAMPLE 117 6-(4-Phenylisoxazol-3-yl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Prepared according to Method C. 1H NMR (200 MHz, DMSO-d6) δ 9.03 (s, 1H), 8.79 (s, 2H), 7.95 (m, 3H), 7.53 (m, 2H), 7.36 (s, 3H). EXAMPLE 118 6-(5-Methyl-3-phenylisoxazol-4-yl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Bromo-1-(5-methyl-3-phenylisoxazol-4-yl)ethan-1-one (100 mg, 0.36 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (65 mg, 0.36 mmol) were refluxed in ethanol (5 mL) for 60 hrs. Solvent was evaporated and the crude solid was purified by flash chromatography using 35:65 ethyl acetate:hexanes to provide compound 118 as a yellowish powder (64 mg, 50%). 1H NMR (200 MHz, DMSO-d6) δ 8.73 (br s, 2H), 8.25 (s, 1H), 7.58 (m, 2H), 7.45 (m, 3H), 2.56 (s, 3H). EXAMPLE 119 6-(Ethyl isoxazol-5-yl-3-carboxylate)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Ethyl 5-(2-bromoacetyl)isoxazole-3-carboxylate (100 mg, 0.38 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (70 mg, 0.38 mmol) were refluxed in ethanol (5 mL) for 60 hrs. The resulting solution was cooled on ice and the resulting precipitate was collected by filtration to provide compound 229-053 as an orange powder (21 mg, 16%). 1H NMR (200 MHz, DMSO-d6) δ 9.14 (s, 1H), 8.82 (s, 2H), 7.16 (s, 1H), 4.39 (q, J=7.0 Hz, 2H), 1.34 (t, J=7.1 Hz, 3H). EXAMPLE 120 6-(5-methyl-1-phenyl-1H-pyrazol-4-yl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Bromo-1-(5-methyl-1-phenyl-1H-pyrazol-4-yl)ethan-1-one (100 mg, 0.36 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (65 mg, 0.36 mmol) were refluxed in ethanol (5 mL) for 45 hrs. Solvent was evaporated and the solid was recrystallized from ethanol to provide compound 120 as a beige powder (30 mg, 28%). 1H NMR (200 MHz, DMSO-d6) δ 8.71 (s, 2H), 8.55 (s, 1H), 7.98 (s, 1H), 7.52 (m, 5H), 2.56 (s, 3H). EXAMPLE 121 6-(Thiaxol-2-yl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Step 1 2-Acetylthiazole (400 μL, 3.86 mmol) was suspended in chloroform (10 mL) and treated with pyridinium tribromide (1.23 g, 3.86 mmol). The reaction mixture was stirred for two days. The solvent was removed under reduced pressure. Standard aqueous/ethyl acetate workup provided a dark orange solid, which was identified as a 8:1 mixture of 2-(2-bromoacetyl)thiazole and starting material. 1H NMR (200 MHz, DMSO-d6) δ 8.30 (d, J=2.1 Hz, 1H), 8.18 (d, J=2.1 Hz, 1H), 4.93 (s, 2H). Step 2 2-(2-Bromoacetyl)thiazole (206 mg, 1.0 mmol) and 5-amino-1,3,4-thiadiazole-2-sulfonamide (180 mg, 1.0 mmol) were refluxed together in methanol (10 mL) for 72 hours. The resulting suspension was cooled to −10° C., filtered and the solid washed with cold methanol (3×2 mL) to provide compound 121 as a white solid (15.6 mg, 5.4%). 1H NMR (200 MHz, DMSO-d6) δ 8.90 (s, 1H), 8.74 (br s, 2H), 7.90 (d, J=3.1 Hz, 1H), 7.75 (d, J=3.3 Hz, 1H). EXAMPLE 122 6-(2,4-Thiaxol-5-yl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compoudn 122 was prepared according to the method described for compound 103 to provide compound 122 as an off white solid. 1H NMR (200 MHz, DMSO-d6) δ 8.74 (s, 2H), 8.65 (s, 1H), 2.63 (s, 3H), 2.47 (s, 3H). EXAMPLE 123 5-Chloro-6-phenyl-imidazo[2,1-b]-1,3,4-thiadiazole-sulfonamide Compound 1 (250 mg, 0.891 mmol) was dissolved in 10:1 THF/water (22 mL) and treated with 40% sodium hypochlorite (1 mL). The solution was stirred for 3 hours before the volatiles were removed under reduced pressure to provide a light yellow solid (310 mg, 98%). 1H NMR (200 MHz, DMSO-d6) δ 7.96 (m, 2H), 7.43 (t, 2H), 7.39 (t, 1H). EXAMPLE 124 5-Bromo-6-phenyl-imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Hydrobromide Compound 1 (5.00 g, 17.8 mmol) in AcOH (200 mL) was treated with bromine (0.96 mL, 18.7 mmol). The solution was stirred overnight and the formation of a white precipitate was observed. The solvent was evaporated and the solid was suspended in MeOH (50 mL). That suspension was put in the fridge for one hour and filtered to provide compound 12 as a white powder (4.8 g, 76% after 3rd crop). 1H NMR (200 MHz, DMSO): δ 8.82 (s, 2H), 7.98 (d, J=8.2 Hz, 2H), 7.46 (m, 3H). EXAMPLE 125 5-Bromo-6-(2-pyridyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Hydrobromide Compound 105 (50 mg, 0.18 mmol) was suspended in acetic acid (5 mL) and treated with bromine (10 μL, 0.20 mmol). After stirring overnight the volatiles were removed under reduced pressure and the solid was dried under vacuum to provide compound 125 as a yellow solid (54 mg, 84%). 1H NMR (200 MHz, DMSO-d6) δ 8.84 (s, 2H), 8.67 (d, J=4.6 Hz, 1H), 8.02 (m, 2H), 7.43 (m, 1H); 13C NMR (50 MHz, DMSO) δ 166.9, 147.1, 146.0, 142.6, 137.9, 124.8, 122.4, 98.7. EXAMPLE 126 5-Bromo-6-(4-nitrophenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Hydrobromide EXAMPLE 127 5-Bromo-6-(4-chlorophenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Hydrobromide EXAMPLE 128 5-Bromo-6-(4-bromophenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Hydrobromide Compound 14 (100 mg, 0.278 mmol) was suspended in acetic acid (5 mL) and treated with neat bromine (16 μL, 0.306 mmol). The reaction mixture was stirred overnight and volatiles were removed under reduced pressure to provide compounds 128 as a light orange solid (143 mg, 99%). 1H NMR (200 MHz, DMSO-d6) δ 8.82 (s, 2H), 7.92 (d, 2H), 7.68 (d, 2H). EXAMPLE 129 5-Bromo-6-(2-bromo3-methoxyphenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Hydrobromide Prepared according to the method described for compound 128. EXAMPLE 130 5-Bromo-6-(2-naphthyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Hydrobromide Compound 62 (192 mg, 0.582 mmol) was suspended in acetic acid (10 mL) and treated with neat bromine (31 μL, 0.612 mmol). After stirring overnight the volatiles were removed under reduced pressure, to provide compound 130 as a tan solid (279 mg, 93%). 1H NMR (200 MHz, DMSO-d6) δ 8.83 (br s, 2H), 8.42 (s, 1H), 8.04 (d, 1H), 7.98-7.80 (m, 3H), 7.48 (m, 2H). EXAMPLE 131 5-Chloro-6-(biphenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Hydrobromide Compound 131 was prepared according to the method described for compound 123 to provide a white solid. EXAMPLE 132 5-Bromo-6-(biphenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Hydrobromide Compound 72 (1.00 g, 2.80 mmol) was suspended in AcOH (20 mL) and treated with bromine (172 μL, 3.4 mmol). The solution was stirred overnight and the formation of a white precipitate was observed. The solvent was evaporated and the solid was dissolved in 10 mL MeOH. That suspension was put in the fridge for one hour to increase precipitation. Successive precipitations and filtrations provided compound 132 as a yellow powder (1.10 g, 79%). 1H NMR (200 MHz, DMSO) δ 8.82 (s, 1H), 8.11 (d, J=8.5 Hz, 2H), 7.82 (d, J=8.6 Hz, 2H), 7.74 (d, J=8.5 Hz, 2H), 7.45 (m, 3H). EXAMPLE 133 5-Bromo-6-(5-nitrothiophen-2-yl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Hydrobromide EXAMPLE 134 5-Bromo-6-trifluoromethylimidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 74 (430 mg, 1.59 mmol) was suspended in acetic acid (10 mL) and treated with bromine (244 μL, 4.76 mmol). After stirring stirring overnight the volatiles were removed under reduced pressure to provide a 1:1 mixture of compounds 74 and 75. The above process was repeated to provide compound 134 as a white solid (477 mg). 1H NMR (200 MHz, DMSO-d6) δ 8.89 (s, 2H). EXAMPLE 135 5-Thiophenyl-6-(2-naphthyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 130 (100 mg, 0.204 mmol) and mercaptobenzene (28 uL, 0.269 mmol) were combined in THF (10 mL) and refluxed for 16 hours, followed by 72 hours at room temperature. Volatiles were removed under reduced pressure and the resulting residue was triturated with diethyl ether to provide compound 135 as a yellow solid (62 mg, 69% yield). 1H NMR (200 MHz, DMSO-d6) δ 8.82 (br s, 2H), 8.58 (s, 1H), 8.19 (d, 1H), 7.92 (d, 1H), 7.83 (m, 2H), 7.53 (m, 2H), 7.38-7.12 (m, 5H). EXAMPLE 136 5-(S-(2-Thio-5-amino-1,3,4-thiadiazolyl)-6-(2-naphthyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Compound 130 (102 mg, 0.208 mmol) and 5-amino-1,3,4-thiadiazole-2-thiol (37 mg, 0.275 mmol) were combined in a 2:1 mixture of ethyl acetate/methanol (15 mL) and refluxed for 16 hours, followed by 72 hours at room temperature. Volatiles were removed under reduced pressure and the resulting residue was recrystallized from methanol to provide compound 136 as a yellow solid (32 mg, 34% yield). 1H NMR (200 MHz, DMSO-d6) δ 8.86 (br s, 2H), 8.66 (s, 1H), 8.28 (d, 1H), 8.02 (d, 1H), 7.98 (m, 2H), 7.57 (m, 2H), 7.36 (br s, 2H). EXAMPLE 137 6-Phenyl-imidazo[2,1-b]-1,3,4-thiadiazole-2-N-methylsulfonamide Compound 1 (110 mg, 0.50 mmol), methanol (30 mg, 0.5 mmol), and triphenylphosphine (130 mg, 0.5 mmol) were combined in THF (5 mL). This solution was added to a reaction vessel containing polymer supported DIAD (500 mg, 0.50 mmol). After being shaken overnight, the solid resin was removed by filtration and the filtrate was concentrated under reduced pressure. The resulting semi-solid was purified by silica gel chromatography, eluting with 10% ethyl acetate/hexane, to provide compound 137 as a white solid. 1H NMR (200 MHz, acetone-d6) δ 8.58 (s, 1H), 7.98 (d, 2H), 7.42 (t, 2H), 7.31 (t, 1H), 2.93 (s, 3H). EXAMPLE 138 6-(2,3,4,5,6-pentafluorophenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-N-methylsulfonamide MS (m/z) M+1=385. EXAMPLE 139 6-Phenyl-imidazo[2,1-b]-1,3,4-thiadiazole-2-N,N-dimethylsulfonamide Compound 1 (140 mg, 0.5 mmol), methanol (64 mg, 2.0 mmol), and triphenylphosphine (525 mg, 2.0 mmol) were combined in THF (2 mL) and treated with DIAD (200 μL, 2.0 mmol). The resulting solution was stirred over night. The resulting solid was filtered and washed with THF (2×3 mL) to provide compound 4 as a white crystalline solid. 1H NMR (200 MHz, DMSO-d6) δ 8.92 (s, 1H), 8.91 (d, 2H), 7.44 (t, 2H), 7.34 (t, 1H), 2.93 (s, 6H). EXAMPLE 140 6-(2,3,4,5,6-pentafluorophenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-N,N-dimethylsulfonamide Compound 140 was prepred in a manner similar to compound 138. 1H NMR (200 MHz, DMSO-d6) δ 8.86 (t, 1H), 2.95 (s, 6H). EXAMPLE 141 6-(3-Methoxyphenyl-imidazo[2,1-b]-1,3,4-thiadiazole-2-N,N-diethylsulfonamide Compound 16 (50 mg, 0.162 mmol), ethanol (28 μL, 0.486 mmol), and triphenylphosphine (127 mg, 0.86 mmol) were combined in THF (10 mL) and treated with DIAD (96 μL, 0.468 mmol). The resulting solution was stirred over night. Solvent was removed under reduced pressure and the resulting semi-solid was triturated with diethyl ether to provide compound 141 as a white crystalline solid (19.6 mg, 33%). 1H NMR (200 MHz, CDCl3) δ 8.06 (s, 1H), 7.38 (d, 2H), 7.35 (t, 1H), 6.88 (d, 1H), 3.88 (s, 3H), 3.45 (q, 4H), 1.35 (t, 6H). EXAMPLE 142 6-(3-Methoxyphenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-N,N-dibutylsulfonamide Compound 16 (50 mg, 0.162 mmol), butanol (44 μL, 0.486 mmol), and triphenylphosphine (127 mg, 0.486 mmol) were combined in THF (10 mL) and treated with DIAD (96 μL, 0.486 mmol). The resulting solution was stirred over night. The solvent was removed under reduced pressure and the resulting semi-solid was purified by silica gel chromatography, eluting with 10% ethyl acetate/hexane, to provide compound 142 as a light yellow solid (49 mg, 72%). 1H NMR (200 MHz, CDCl3) δ 8.08 (s, 1H), 7.38 (d, 2H), 7.35 (t, 1H), 3.89 (s, 3H), 3.34 (t, 4H), 1.67 (m, 4H), 1.36 (m, 3H), 0.93 (t, 6H). EXAMPLE 143 6-(4-Bromophenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-N,N-dimethylsulfonamide Compound 143 was prepared from compound 14 according to the method described for compound 142. EXAMPLE 144 6-(4-Bromophenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-N,N-dimethylsulfonamide Hydrobromide 6-(4-Bromophenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-N,N-dimethylsulfonamide (100 mg, 0.258 mmol) was suspended in acetic acid (5 mL) and treated with neat bromine (18 μL, 0.315 mmol). The reaction mixture was stirred overnight and volatiles were removed under reduced pressure to provide compounds 144 as a light orange solid (140 mg, 99%). 1H NMR (200 MHz, DMSO-d6) δ 7.84 (d, 2H), 7.63 (d, 2H), 2.93 (s, 6H). EXAMPLE 145 6-(3-Hydroxyphenyl-imidazo[2,1-b]-1,3,4-thiadiazole-2-N,N-dimethylsulfonamide Step 1: Compound 16 (212 mg, 0.851 mmol), methanol (103 μL. 2.55 mmol), and triphenylphosphine (669 mg, 2.55 mmol) were combined in THF (10 mL) and treated with DIAD (502 uL, 2.55 mmol). The resulting solution was stirred over night. Solvent was removed under reduced pressure and the resulting semi-solid was triturated with methanol to provide white crystalline solid (244 mg, 85%). 1H NMR (200 MHz, DMSO-d6) δ 8.12 (s, 1H), 7.40 (dd, 1H), 7.38 (d, 1H), 7.33 (t, 1H), 6.88 (ddd, 1H), 3.87 (s, 3H), 3.02 (s, 6H). Step 2: The above compound (420 mg, 1.24 mmol) was suspended in methylenechloride (10 mL) and treated with a BBr3 (6.20 mL, 1.0M in CH2Cl2, 6.20 mmol). The reaction mixture was stirred overnight before being quenched with water (1 mL), followed by saturated NaHCO3 (10 mL). The resulting mixture was diluted with ethyl acetate (20 mL) and subjected to standard workup. The organic layer provided a off yellow solid which was further purified by recrystallization from methanol to provide compounds 49 was a gray solid (14 mg, 32%). 1H NMR (200 MHz, DMSO-d6) δ 9.50 (br s, 1H), 8.83 (s, 1H), 7.30 (m, 2H), 7.25 (t, 1H), 6.71 (dd, 1H), 2.93 (s, 6H). EXAMPLE 146 6-(3-Benzoyloxyphenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-N,N-dimethylsulfonamide Compound 145 (20 mg, 0.062 mmol) was dissolved in THF (2 mL) and treated with triethylamine (10 mL, 0.068 mmol) followed by benzoyl chloride (9 mL, 0.068 mmol). The reaction mixture was stirred for 4 hours before a second equiv of triethylamine and benzoyl chloride were added. Standard aqueous workup and purification by silica gel chromatography, eluting with 30% ethyl acetate/hexane, provided compound 146 as a white solid (16 mg, 62%). 1H NMR (200 MHz, CDCl3) δ 8.22 (m, 2H), 8.12 (s, 1H), 7.77-7.60 (m, 3H), 7.58-7.44 (m, 3H), 7.22 (m, 1H). EXAMPLE 147 6-(2-Naphthyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-N,N-dimethylsulfonamide Compound 62 (330 mg, 1.0 mmol), methanol (180 μL, 4.40 mmol), and triphenylphosphine (1.15 g, 4.40 mmol) were combined in THF (10 mL) and treated with DIAD (1.90 mL, 4.40 mmol). The resulting solution was stirred over night. The solvent was removed under reduced pressure and the resulting semi-solid was triturated with diethyl ether, to provide compound 147 as a white crystalline solid (268 mg, 75%). 1H NMR (200 MHz, DMSO-d6) δ 9.02 (s, 1H), 8.45 (s, 1H), 8.07-7.83 (m, 3H), 7.56 (m, 2H), 2.91 (s, 6H). EXAMPLE 148 6-Phenyl-imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Sodium Salt Compound 1 (200 mg, 0.71 mmol) was added to a solution of sodium hydroxide (28 mg, 0.71 mmol) in 4:1 MeOH/H2O (5 mL). The solution was stirred overnight at room temperature before the solvent was removed under reduced pressure to provide compound 2 as a white solid (235 mg, 99%). 1H NMR (200 MHz, DMSO-d6) δ 8.59 (s, 1H), 7.85 (d, J=8.2 Hz, 2H), 7.32 (m, 3H). EXAMPLE 149 6-Phenyl-imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Sodium Salt Compound 149 was prepared according to the method described for compound 148; white solid (96%). 1H NMR (200 MHz, DMSO-d6) δ 8.65 (s, 1H), 7.93 (d, J=8.8 Hz, 2H), 7.70 (d, J=8.8 Hz, 2H), 7.36 (m, 2H), 7.24 (s, 1H), 6.90 (d, J=6.4 Hz, 1H), 3.81 (s, 3H). EXAMPLE 150 6-Phenyl-imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide Sodium Salt Compound 150 was prepared according to the method described for compound 148; white solid (96%). 1H NMR (200 MHz, DMSO-d6) δ 8.71 (s, 1H), 7.98 (m, 4H), 7.79 (d, J=8.2 Hz, 2H), 7.69 (m, 2H). EXAMPLE 151 6-(4-Azido-2,3,5,6-tetraflourophenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Bromo-4′-azido-2′,3′,5′,6′-tetrafluoroacetophenone (Keana, J. F. W.; Cai, S. X. J. Org. Chem., 1990, 55, 3640) (353 mg, 1 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (148 mg, 1 mmol) were refluxed in ethanol (10 mL) for 60 hours. The resulting solid was filtered, washing twice for cold methanol (2 mL), to provide compound 114 (102 mg, 25%) as a white powder. 1H NMR (200 MHz, DMSO-d6) δ 8.81 (t, J=2.0 Hz, 1H), 8.79 (br s, 2H). EXAMPLE 152 6-(4-azido-2,3,5,6-pentafluorophenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-N,N-dimethylsulfonamide Compound 152 was prepred in a manner similar to compound 138. 1H NMR (200 MHz, DMSO-d6) δ 8.22 (t, 1H), 3.07 (s, 6H). EXAMPLE 153 6-(4-Nitrophenyl)imidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamide 2-Bromo-4′-nitroacetophenone (2.44 g, 10.0 mmol) and 2-amino-1,3,4-thiadiazole-5-sulfonamide (1.50 g, 10.0 mmol) were refluxed in 1,4-dioxane (20 mL) for 48 hrs. The resulting solution was cooled on ice and the resulting precipitate was collected by filtration to provide compound 153 as a white crystalline solid (2.40 g, 67%). 1H NMR (200 MHz, DMSO-d6) δ 9.18 (s, 1H), 8.69 (br s, 1H), 8.35 (d, 2H), 8.16 (d, 2H). EXAMPLE 154 Protection of SCG Neurons from Anti-NGF Killing SCG neurons were isolated from day 1 neonatal Sprague Dawley rats, plated at a cell density of 5,000 cells/well, and incubated in Biowhittaker Utraculture containing 1% Penstrep, 1% L-glutamine, 0.7% ARAC, 3% rat serum, and NGF (50 ng/mL, Calomone Labs), at 37° C., under a 5% CO2 atmosphere. After 4 days the cells were treated with anti-NGF antibody (Sigma). At this time compound was added and the cells were maintained serum and NGF free for 48 hours, at which time viability was assessed using Alamar Blue (Medicorp) staining. Table 3a summarizes selected IC(50) values from compounds tested using this protocol. TABLE 3a Rescue from anti-NGF killing of SCG neurons Compound IC(50) (uM)* 1 22 2 20 3 10 9 8 21 22 23 25 26 23 34 >30 35 >30 36 17 72 17 74 20 75 10 76 5 79 7 81 5 82 25 84 >30 85 >30 86 17 87 10 88 10 89 10 91 7 92 7 93 7 94 10 95 7 96 20 97 7 98 17 99 7 106 7 111 7 148 22 149 7 150 7 *+/−1 uM EXAMPLE 155 In Vitro Protection of SCG Neurons from Taxol Killing SCG neurons were isolated from day 1 neonatal Sprague Dawley rats, plated at a cell density of 10,000 cells/well, and incubated in Biowhittaker Utraculture containing 1% Penstrep, 1% L-glutamine, 0.7% ARAC, 3% rat serum, and NGF (50 ng/mL, Calomone Labs) at 37° C., under a 5% CO2 atmosphere. After 5 days the cells were treated with compound and Taxol™ (50 ng/mL). Viability was assessed 48 hours later using MTS (Promega) staining. Table 3b summarizes selected IC(50) values from compounds tested using this protocol. TABLE 3b Rescue from anti-NGF killing of SCG neurons Compounds IC(50) (uM)* 1 7 4 5 5 5 6 3 7 4 8 5 11 3 12 5 13 7 14 5 15 10 16 5 17 3 18 20 19 15 20 15 21 7 22 25 24 7 25 5 26 7 30 10 31 10 32 10 37 10 38 3 40 23 41 3 42 3 46 7 47 6 48 5 49 5 50 7 51 5 52 3 53 5 54 10 55 15 56 3 57 6 58 30 59 10 60 25 61 10 62 15 63 7 64 10 65 15 66 20 67 10 68 7 70 22 71 >30 72 10 73 2 74 7 75 5 76 2 77 2 81 3 82 2 87 5 95 3 99 2 101 >30 102 >30 103 >30 104 7 105 7 107 20 108 5 109 7 110 >30 111 2 112 5 113 7 114 7 115 7 116 7 117 3 118 17 120 7 121 2 122 8 123 >30 124 3 125 3 128 2 129 7 130 2 131 3 132 1 134 1 135 7 136 5 137 10 138 2 139 10 140 5 141 >30 142 >30 143 10 144 15 145 20 146 20 147 17 148 7 151 2 152 2 153 5 FIG. 1 illustrates the protection provided by compound 1 (referred to here as AEG3482) against Taxol™ induced killing. P1 Sprague Dawley rat SCG neurons were cultured and incubated with NGF (50 ng/mL) for 5 days. Addition of Taxol™ (50 ng/mL) resulted in a 72% loss in viability as measured by MTS staining. Co-treatment with compound 1 resulted in 100% protection at 10 uM, with an IC50 of 7 uM. EXAMPLE 156 In Vitro Protection of SCG Neurons from Cisplatin Killing SCG neurons were isolated from day 1 neonatal Sprague Dawley rats, plated at a cell density of 10,000 cells/well, and incubated in Biowhittaker Utraculture containing 1% Penstrep, 1% L-glutamine, 0.7% ARAC, 3% rat serum, and NGF (50 ng/mL, Calomone Labs) at 37° C., under a 5% CO2 atmosphere. After 5 days the cells were treated with compound and cisplatin (3 μg/mL). Viability was assessed 48 hours later using MTS (Promega) staining. TABLE 4 Protection of SCG neurons against cisplatin killing Entry Compound IC50 (±1 μM) 1 1 5 EXAMPLE 157 In Vitro Protection of SCG Neurons from Vincristine Killing SCG neurons were isolated from day 1 neonatal Sprague Dawley rats, plated at a cell density of 10,000 cells/well, and incubated in Biowhittaker Utraculture containing 1% Penstrep, 1% L-glutamine, 0.7% ARAC, 3% rat serum, and NGF (50 ng/mL, Calomone Labs) at 37° C., under a 5% CO2 atmosphere. After 5 days the cells were treated with compound and vincristine (50 ng/mL). Viability was assessed 48 hours later using MTS (Promega) staining. TABLE 5 Protection of SCG neurons against Vincristine killing Entry Compound IC50 (±1 μM) 1 1 10 EXAMPLE 158 Protection of Motor Neurons in Layer V of the Motor Cortex 350 uM slices of P1 rat motor cortex were obtained using a McIlwain tissue chopper (Mickle Laboratory Engineering Co., England). Slices were cultured in 50% Neurobasal, 25% HBSS, 25% Horse serum, 1% penicillin/streptomycin, 2 mM glutamine, 6.4 mg/mL glucose for 2 weeks. Neuronal death was initated by addition of 5 mM malonate. Test compounds were added coincident with malonate and slices were cultured for an additional two weeks. Slices were fixed in 4% paraformaldehyde and stained with SMI-32 antibody (Sternberger monoclonals, Maryland). Large SMI positive cells with apical dendrites residing in layer V of the the cortex were identified as motor neurons and counted. Malonate treatment greatly reduced the SMI-positive motor neuron count. FIG. 2 illustrates the protection of cortical motor neurons from malonate killing. Slices of P1 rat motor cortex (350 uM) were treated with malonate and incubated in media for 14 days, before malonate and drug were added. Part (a) shows control motor neuons. Large sized diamond-shaped neurons are visible; part (b) shows malonate treatment alone, which results in killing with a complete loss of neurons; and part (c) shows 90% rescue of cortical motor neurons in the presence of compound 91 (1 uM) and malonate. In Part C, large diamond-shaped neurons are again visible. EXAMPLE 159 Co-Treatment of HA460 and OV2008 Cell Line with Taxol™ and Compound 1 HA460 and OV2008 cells were plated and incubated for 48 hours. Compound 1 and/or compound 1 and Taxol™ were added. Viability was determined after 24 hours, staining with MTT (Promega). FIG. 3 illustrates the co-treatment of H460 and OV 2008 cell lines with Taxol™ and compound 1. HA460 lung carcinoma and OV2008 ovarian carcinoma cells were treated with Taxol™ (50 nM) and/or Taxol™ (50 nM)+compound 1 (noted as AEG 03482) at levels of 5, 10, and 20 uM. Compound 1 did not protect HA460 or OV2008 cells from Taxol™ induced apoptosis. EXAMPLE 160 Protection of Sprague Dawley Rats from Taxol™ Induced Neuropathies Adult Sprague Dawley rats were treated with Taxol™ (IP, 9 mg/kg in Cremophor EL and ethanol) twice weekly for 3 weeks (J. Neuro-Oncology (1999) 41: 107-116). Compound was administered 1 hour prior to Taxol™ treatment (IP, 1, 5 and 10 mg/kg in hydroxypropyl-β-cyclodextrin). Taxol™ treated control animals were treated with saline solution at the same time of Compound treated animals. Non-treated control animals were treated with saline solution as above. Weight gain was measured every second day, starting at Day 1. Gait analysis was measured by quantifying the refracted light captured by a video camera as the animals walked over a glass plate, 2 days after the final Taxol™ treatment (Physiology and Behavior (1994), 55(4): 723-726; Med. Sci. Res. (1988) 16: 901-902). This data was analyzed by Northern Eclipse software. H/M wave recovery was analyzed using standard procedures 2 days after the final Taxol™ treatment (Muscle Nerve (1998) 21: 1405-1413; Annals of Neurology (1998) 43 (1): 46-55). FIG. 4 shows weight loss induced by Taxol™. Male Spraugue Dawley rats were treated with 50% HPDC vehicle (veh/veh), compound 1 dissolved in 50% HPDC at 1, 5, or 10 mg/kg (veh/1, veh/5, veh/10, respectively), or Taxol™ (9 mg/kg)+compound 1 dissolved in 50% HPDC at 1, 5, and 10 mg/kg (Tax/1, Tax/5, Tax/10) according to the dosing regime described in Example 123. Weight measurements were made ever other day. FIG. 5 shows gait disturbance induced by Taxol™ with compound 1. Two days after the completion of drug treatments animal walking gait was analyzed according to a) total imprint area, and b) total number of contact points. Compound 1 prevented Taxol™ induced gait disturbance. FIG. 6 illustrates the effect of Compound 1 on H-reflex amplitude, a measurement of H/M wave disturbance induced by Taxol™. Two days after the completion of drug treatments, the dorsal root ganlia and attached nerves were dissected bilaterally from L4 and L5 and their H/M wave conductance measured. Compound 1 caused a reversal in H/M wave disturbance induced by Taxol™. EXAMPLE 161 Sciatic Nerve Crush Injury Model Male Sprague Dawley rats were anaesthetized (halothane and buprenorphine) and the right hind leg was blunt dissected to expose the sciatic nerve at mid-thigh. The nerve was crushed twice for a total of 30 seconds using No.7 Dumont jeweller's forceps. The incision is sutured and the animals are allowed to recover for 28 days. Functional recovery was measured by gait, nerve conductance and toe spread measurements between digits land 5 and digits 2 and 4. FIG. 7 illustrates sciatic nerve recovery after crush injury, as indicated by inner toe spread. Male Spraugue Dawley rats were subjected to sciatic nerve crush and treated with either vehicle control, compound 1 or compound 76 (noted as AEG 33764). Compounds 1 and 76 induced increased recovery in toe spread area. EXAMPLE 162 Optical Stroke Model The right eye of each rat was dilated fully using 1% tropacamide and 2.% pheylephrine hydrochloride (Alcon Canada). A single drop of 0.5% proparacaine (Alcon) was used as a topical anesthetic. The anterior chamber of the right eye was cannulated with a 30-gauge needle connected to a saline reservoir and a manometer to monitor intraocular pressure. Intraocular pressure was raised to 110 mm Hg by raising the saline reservoir for 60 minutes. This increase in pressure collapses the central retinal artery. Retinal ischemia was confirmed by whitening of the iris and loss of red reflex. After 60 minutes of ischemia, the intraocular pressure was normalized and the needle withdrawn. A 33-blunt needle (Hamilton) was inserted through the corneal puncture, maneuvered around the lens displacing it medially, and advanced into the intravitrial space. A 2 mL volume of drug or vehicle (50% HPCD) was injected into the vitreous of the eye. The needle was withdrawn and maxitrol (Alcon) was applied to the cornea to prevent infection. Alternatively, drug was given subcutaneously before or after the insult, for a period of up to 14 days. Optical function after 24 hrs, 28 hrs and 7 days was assessed using ERG measurements and histological staining of the DRG layer. FIG. 8 shows protection of DRGs by compound 1 after ocular stroke. Ocular stroke was induced in the right eye of rats resulting in almost complete loss of the DRG population, as seen here by a loss in reactivity of the optic fiber to stimulation. Compound 1 was delivered intravitreally followed by subsequent daily injections for 1 week post-ischemia (post stroke). Compound 1, given post stroke, protects the DRG population allowing for normal conductance. EXAMPLE 163 CA II Inhibition CA II inhabition was measured using the protocol described by Pocker, Y.' Stone, J. Biochemistry 1967, 6, 668. The IC (50)s if selected compound represented by Formula I are listed in Table 6. TABLE 6 CA II inhibition by compounds represented by formula I Compounds IC(50) (uM) 1 0.250 4 0.217 5 0.192 6 0.164 7 0.581 8 1.47 11 1.80 12 1.59 13 4.05 14 0.198 15 0.152 16 0.150 17 0.179 18 0.337 19 0.373 20 0.404 21 5.32 22 0.153 24 0.613 25 0.302 37 0.199 38 0.577 39 0.154 40 1.52 41 0.346 42 0.272 43 0.886 44 0.619 45 0.166 46 0.601 47 0.361 48 0.288 49 0.466 50 0.938 72 1.61 72 2.19 74 1.68 75 0.441 76 0.526 81 1.58 82 5.43 87 0.128 99 0.914 105 0.150 111 53.2 137 2.06 139 11.3 142 60.3 EXAMPLE 164 Neuroprotection of Cortical Neurons in the Presence of B-Amyloid Primary neuronal/glial cortical cultures were established from postnatal day 1 Sprague Dawley rats. Cerbral cortices were isolated and dissociated with 0.25% trypsin for 20 minutes at 37 degrees. The tissue was then triturated in PBS containing 0.1% bovine serum albumin and 0.2 mg/ml DNAse. Cells were plated in poly D-lysine coated 96 well plates at a density of 1e6 cells per mL. Cultures were maintained at 37 degrees in 5% CO2/95% air for 2 weeks in Neurobasal (Gibco) supplemented with B27, glutamine, and penicillin/streptomycin. 5 ng/mL AraC was added after 48 hours. After 2 weeks cells were exposed to 10 uM 25-35 amyloid beta peptide with and without 10 uM AEG33764. After 2 days of treatment apoptotic cells were detected with Cy3-conjugated annexin V (Sigma). FIG. 9 shows the protection of provided by Compound 76 from amyloid beta 25-35 toxicity. Mixed neuronal/cortical cultures were obtained from P1 rat cortex. After 2 weeks in vitro cells were exposed to 10 uM 25-35 amyloid beta peptide. Top (a) shows control untreated cultures display low level annexin V staining. Middle (b) shows 48 hour treatment with amyloid beta peptide results in the appearance of apoptotic cells which stain with annexin V on the cell periphery. Bottom (c) illustrates co-treatment with 10 uM Compound 76 prevents the occurrence of annex in V stained cells.

<SOH> BACKGROUND OF THE INVENTION <EOH>Various neurotrophins characterized by Neuronal Growth Factor (NGF), brain derived growth factor (BDNF), neurotrophin-3 (NT-3), and others (NT-4, CNTF, GDNF, IGF-1), have been identified as key survival factors for neurons. NGF plays a critical role in the development and maintenance of cholinergic forebrain neurons of the CNS and neurons of the peripheral nervous system (PNS); neurons of the PNS are characterized as small fiber sensory neurons associated with pain and temperature sensation, in addition to neurons of the sympathetic ganglia and dorsal root ganglia (SCGs and DRGs, respectively). BDNF plays a role in motor neuron survival. Both BDNF and NT-3 are expressed in the CNS and serve similar purposes in multiple subsets of cortical and hyppocampal neurons; neurons of the CNS are characterized by those found in the brain, spinal chord, and eye. The removal of these, and related trophic factors from in vitro cellular media results in the degradation of the axonal processes, leading to apoptosis of cultured neurons. Localized tissue loss of NGF, or reduced axonal retrograde transport of NGF to the cell body, have been causally implicated in the development of peripheral neuropathies and neuropathic pain regularly observed in diabetes and HIV patients. Several double blind Phase II clinical trials have found that the systemic administration of recombinant human NGF (rhNGF) (U.S. Pat. No. 5,604,202) displayed beneficial effects on neuropathic pain, physiology, and cognition related to these diseases (Apfel, S. C. et. al. JAMA, 248(17), 2215-2221; Apfel, S. C. Neurology 51, 695-702, 1998; McAurthur, J. C. et al. Neurology 54, 1080-1088, 2000). Side effects related to rhNGF treatment included injection site pain, hyperalgesia, and other pain related symptoms. Despite these symptoms, a large number of patients continued rhNGF treatment after unblinding. Various chemotherapeutic drugs such as Taxol™, cisplatin, vinblastine, and vincristine, cause dose dependent peripheral neuropathies, characterized by peripheral pain and loss of function. In many cases these neuropathies effectively limit the amount, and duration, of chemotherapy given to, patients. For example, upwards of 50% of patients receiving Taxol™ chemotherapy experience severe, and cumulative, peripheral neuropathies. The progression of the neuropathy necessitates the use of a dosing regime which is characterized by three cycles of fourteen days of Taxol™ treatment, followed by 14 days of recovery. Regression of the neuropathy is often observed between treatment cycles and following the final treatment. The degree and duration of recovery varies largely between patients. In addition to peripheral neuropathies, cisplatin treatment invariably results in some form of auditory loss, especially in children, due to neuronal damage in the inner ear, with minimal recovery of the neurons after completion of treatment.

<SOH> SUMMARY OF THE INVENTION <EOH>The invention relates to imidazo[2,1-b]thiadiazole sulfones, which are useful in the treatment of neurodegenerative diseases of the CNS and/or PNS, for the inhibition of various serine-threonine protein kinases, phosphatases, CA, for inhibiting the degradation, dysfunction, or loss of neurons of the CNS and/or PNS, or enhancing the phenotype of neuronal cell types and preserving the axonal function of neuronal and synaptic processes of the CNS and/or of the PNS. Also included are selected methods for the preparation of these compounds. The imidazo[2,1-b]-1,3,4-thiadiazole sulfonamide derivatives and precursors of the present invention include compounds of the Formula I: or pharmaceutically acceptable salts thereof wherein: R 1 and R 2 are individually selected from the group consisting of H, lower alkyl, substituted lower alkyl, and fluoroalkyl; R 5 is selected from the group consisting of H, halogen, cyano, azide, thiocyanate, formyl, lower alkyl, substituted lower alkyl, fluoroalkyl, aralkyl, substituted aralkyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl; R 6 is selected from the group consisting of H, lower alkyl, substituted lower alkyl, fluoroalkyl, substituted fluoroalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, adamantly, coumarinyl, and substituted coumarinyl; or R 6 is represented by W: wherein: n represents 0 or 1; the ring system containing X 7 -X 11 represents a 5 or 6 membered aromatic or heteroaromatic ring system, in which X 7 -X 11 are independently selected from the group consisting of C, N, S, and O; when any one of X 7 -X 11 independently represents C, a respective R 7 -R 11 is independently selected from the group consisting of: a) H, halogen, nitro, cyano, lower alkyl, substituted lower alkyl, fluoroalkyl, aralkyl, substituted aralkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyl, lower alkylcarbonyl, substituted lower alkylcarbonyl, arylcarbonyl, substituted arylcarbonyl, heteroarylcarbonyl, or substituted heteroarylcarbonyl; b) SO 2 NR 16 R 17 wherein R 16 and R 17 are independently selected from the group consisting of lower alkyl, substituted lower alkyl, aralkyl, substituted aralkyl, heteroaralkyl, substituted heteroaralkyl aryl, substituted aryl, heteroaryl, and substituted heteroaryl, or wherein R 16 and R 17 are joined to form an alkyl, substituted alkyl, heteroalkyl, or substituted heteroalkyl ring system; c) SO n R 18 wherein n=0, 1 or 2, and wherein R 18 is selected from the group consisting of lower alkyl, substituted lower alkyl, aralkyl, substituted aralkyl, heteroaralkyl, substituted heteroaralkyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl; d) XR 19 wherein X is defined as S or O, and R 19 is defined as alkyl, substituted alkyl, fluoroalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyl, lower alkylcarbonyl, substituted lower alkylcarbonyl, arylcarbonyl, substituted arylcarbonyl, heteroarylcarbonyl, substituted heteroarylcarbonyl, lower alkylaminocarbonyl, arylaminocarbonyl, or substituted arylaminocarbonyl; e) NR 14 R 15 wherein R 14 and R 15 are defined as lower alkyl joined to form an alkyl, substituted alkyl, heteroalkyl, or substituted heteroalkyl ring system; and f) CO 2 R 20 wherein R 20 is defined as H, lower alkyl, substituted lower alkyl, aralkyl, substituted aralkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, or NR 21 R 22 , wherein R 21 and R 22 are independently selected from the group consisting of lower alkyl, aralkyl, aryl; wherein when any one of X 7 -X 11 represents N, that nitrogen is attached to the adjacent atoms by either one single and one double bond (as in pyridinyl systems), or by two single bonds (as in indolyl or imidazolyl systems); wherein when any one of X 7 -X 11 represents N, and that nitrogen is attached to the adjacent atoms by one single and one double bond, the respective R 7 -R 11 represents a lone pair; when any one of X 1 -X 5 represents N, and that nitrogen is attached to the adjacent atoms by two single bonds (as in indolyl or imidazolyl systems), the respective R 7 -R 11 is selected from the group consisting of H, lower alkyl, substituted lower alkyl, aralkyl, substituted aralkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, SO 2 R 18 , wherein R 18 is defined as in c), COR 18 , wherein R 18 is defined as in c); when n=0, R 7 and R 8 , or R 8 and R 9 are combined to form a fused 5, 6, or 7 membered alkyl, substituted alkyl, heteroalky, substituted heteroalkyl, heteroaralkyl, substituted heteroaralkyl, aryl, substituted aryl, heteroaryl, or heteroaryl ring system; when n=1 and X 9 represents C, R 7 and R 8 , or R 8 and R 10 are combined to form a fused 5, 6, or 7 membered alkyl, substituted alkyl, heteroalky, substituted heteroalkyl, aryl, substituted aryl, or heteroaryl ring system; and any one of R 7 -R 11 represents a lone pair when the respective X 7 -X 11 represents S or O; with the proviso that compounds 1, 4, 10, 14, 20, 60, 72, 105, 109, 111, 114, 124, 126, 127, 133, and 153 are excluded. The invention relates to sulfonamide compounds of Formula I and the use of compounds of Formula I (including those noted within the proviso excluding the actual compounds themselves) for the prevention of neuronal cell loss or the treatment of nerve cell or axonal degradation, in either the central or peripheral nervous systems (CNS and PNS, respectively). The invention is useful in prevention or treatment of conditions leading to or resulting from such diseases as Alzheimer's, Huntington's, Parkinson's, muscular dystrophy, diabetes, HIV, from ischemic insults such as stroke in the brain (CNS), retinal ganglion loss following acute ocular stroke or hypertension as in glaucoma, and from infection by viruses such as Hepatitis C and Herpes Simplex. Further, the invention provides compounds for use in treatment of neuropathies resulting from chemotherapeutic agents used in the treatment of HIV and proliferative disease such as cancer, for the treatment of inflammatory diseases. In order to identify compounds which mimic the positive effects of NGF on peripheral neurons, but which lack the inherent difficulties associated with the use of recombinant human proteins and the rhNGF related hyperalgesia, we have developed several in vitro screens using a variety of neurotoxic insults. PNS neurons such as the superior cervical ganglion (SCG) and dorsal root ganglion (DRG) undergo apoptosis when subjected to NGF withdrawal. Treatment with chemotherapeutic agents such as Taxol™, cisplatin, vinblastine, vincristine, and anti-viral agents such as D4T, also induce neuronal apoptosis. Similarly, neurons of the CNS, such as cortical neurons, are sensitive to various neurotoxic agents such as β-amyloid, NMDA, osmotic shock, Taxol™ and cisplatin. Additionally, retinal ganglion neurons subjected to hypoxia undergo apoptosis. Compounds which protect neurons from neurotoxic insults such as those mentioned above will be useful in the treatment of the peripheral neuropathies observed in diseases such as diabetes and HIV. Compounds which protect neurons from chemotherapeutic toxicity, if given concurrently with, or following, chemotherapeutic treatment will allow for the use of increasing concentrations of chemotherapeutics and/or extend the duration of chemotherapy treatments. Alternatively, enhanced recovery will be observed if such compounds are given during the recovery stages, and post treatment. These compounds will also be useful in the treatment of neurodegenerative diseases of the CNS, such as AD, PD, HD, stroke, MS, macular degeneration, glaucoma, optical stroke and retinal degeneration, and the like. We have shown that compounds of Formula I protect SCG neurons from several neurotoxic insults, including NGF withdrawal and treatment with chemotherapeutics such as Taxol™, cisplatin, and vincristine. Compounds of Formula I also protect cortical motor neurons from malonate induced death. When such agents are administered to mice treated with Taxol™, either during or after a two week dosing period, marked improvements are observed in the animal's general health, weight gain, and gait, as compared to animals treated with Taxol™ alone. Additionally, compounds of Formula I aid in the regeneration of neurons damaged as a result of sciatic nerve crush. Selected examples from Formula I have been previously described. Their uses include anti-bacterial agents (Gadad, A. K. Eur J. Med. Chem., 35(9), 853-857, 2000), anti-proliferative agents (Gadad, A. K. India. Arzneim .- Forsch., 49(10), 858-863, 1999), and as carbonic anhydrase (CA) inhibitors (Barnish, I. T., et. al. J. Med. Chem., 23(2), 117-121, 1980; Barnish, I. T. et. al GB 1464259, abandoned; Supuran, C, T. Met .- Based Drugs 2(6), 331-336, 1995—Co(II), Cu (II), Zn(II) complexes of compound 1). Barnish et al. demonstrated that certain compounds reduced the number and intensity of electroshock induced seizures in rats. This anti-seizure activity was linked to increased cerebral blood flow, attributed to the ability of these compounds to inhibit CA. No direct evidence of neuronal protection as a result of these compounds has been previously demonstrated in vitro or in vivo (ie. histology, neuronal cell count, etc.). We have found that various aryl sulfonamide CA inhibitors do not protect SCG neurons from apoptosis. These finding indicate that the neuroprotection mediated by compounds represented by Formula I is independent of their CA activity. Additionally, we have prepared several synthetic derivatives of represented by Formula I which display reduced CA inhibition inhibit CA, while retaining their neuroprotective capabilities. The invention relates to synthetic routes for preparation of compounds represented by Formula I, and methods for the functionalization of compounds represented by Formula I.

20040614

20070612

20050331

98265.0

TRAN, SUSAN T

IMIDAZO [2,1-B]-1,3,4-THIADIAZOLE SULFONAMIDES

UNDISCOUNTED

ACCEPTED

ACCEPTED

Method of and apparatus for testing a server

A method for testing a server. A component (2) captures a session consisting of requests of and responses from a server (3). The captured session is stored as script files (4, 5). A GUI component (6) facilitates the identification of variable data (30) within the script files. Variable data is data which may vary from session to session. The identification process generates a database (14) with field headers (18) corresponding to the types of data identified (15). A component populates the database (13). A driver component (9) uses the script files (11, 12) and the database (13) to test the server (3) by running multiple threads (10) each directing their own session with the server. Where data within the script files has been identified as variable data (13) the thread may substitute data from the database (13). A server testing apparatus and software for implementing the method is also disclosed.

1. A method of testing a server, the method including the steps of: capturing script files resulting from the interaction between a server and another device; utilising a Graphical User Interface (GUI) to identify variable data within the script files; forming A database of substitute values for the variable data; and testing the server by using one or more separate threads each selecting data from the database in substitution for the variable data. 2. A method as claimed in claim 1 wherein the other device is a user device. 3. A method as claimed in claim 1 wherein the server is a web server. 4. A method as claimed in claim 1 wherein the user interaction with the server occurs via a browser. 5. A method as claimed in claim 1 wherein a proxy is used to capture the interaction with the server. 6. A method as claimed in claim 1 wherein the variable data is user identification data. 7. A method as claimed in claim 1 wherein the variable data is product information data. 8. A method as claimed in claim 1 wherein the variable data is user option data. 9. A method as claimed in claims 1 wherein variable data is identified within the GUI by highlighting data. 10. A method as claimed in claim 1 wherein variable data is identified within the GUI by using a mouse device. 11. A method as claimed in claim 1 wherein the GUI assists identification by using pattern matching to automatically identify as variable data that data which is similar to data already identified as variable data by the user. 12. A method as claimed in any claim 1 wherein the GUI is used to identify data as validation data within the script files and the threads used to test the server use the identified validation data to verify server responses. 13. A method as claimed in claim 1 wherein the database is formed from a delimited file in turn generated from data identified in the GUI. 14. A method as claimed in claim 1 wherein the database is formed from a Comma-Separated Variables (CSV) header file in turn generated from data identified in the GUI. 15. A method as claimed in claim 13 wherein the database is populated using a database program. 16. A method as claimed in claim 13 wherein the database is populated using a spreadsheet program. 17. A method as claimed in claim 13 wherein the database is populated automatically. 18. A method as claimed in claim 1 further including setting thread options to specify the number of threads to execute when testing the server. 19. A method as claimed in claim 1 further including setting thread options to specify the number of threads to execute simultaneously. 20. A method as claimed in claim 19 wherein the number of threads executed simultaneously is increased from zero to the number specified. 21. A method as claimed in claim 1 further including setting thread options to specify delays affecting the execution of a thread. 22. A method as claimed in claim 1 further including setting environment options identifying which files to use as the variable data files and fabricated data files 23. A method as claimed in any one of the preceding claims further including setting the duration of the test. 24. Apparatus programmed and configured to perform the method of claim 1 on a server. 25. A server testing apparatus including: means for capturing script files resulting from interaction between a server and another device; a Graphical User Interface (GUI) responsive to a user input device for identifying data within the script files; means for forming a database of substitute values for the variable data; and means for generating one or more separate threads to test a server based upon the captured script files in which data from the database is substituted for the variable data. 26. A server testing apparatus as claimed in claim 25 including a proxy device for capturing script files resulting from interaction between a server and another device. 27. A server testing apparatus as claimed in claim 25 wherein the user input device is a mouse device. 28. A server testing apparatus as claimed in claim 25 including a means for assisting the identification of variable data by using pattern matching to identify as variable data data similar to variable data identified by the user. 29. A server testing apparatus claimed in claim 25 including a means for populating a database. 30. A set of instructions and data coded signals which operate as software for effecting the method of claim 1 when executing on a computer system. 31. Storage media containing software as claimed in claim 30.

FIELD OF INVENTION The present invention relates to a method of testing a server. More particularly, but not exclusively, the present invention relates to a method of load testing a web server. BACKGROUND TO THE INVENTION Standard approaches to testing web servers involve creating scripts using a programming language and using a driver program to run these scripts to test a server. A disadvantage to this approach is that the individuals who are testing the web server must be competent in using a programming language. Another approach involves the capture of traffic between a user and the server. This captured script can be then used to load test the web server by running multiple simultaneous instances using a driver program. Programs that implement this approach include LoadRunner and Astra SiteTest. This approach has a number of disadvantages. Firstly it can be difficult to thoroughly test a server as the script when used by multiple instances is unchanged, therefore only one type of user is tested. Secondly, a problem arises if the server to be tested requires unique data, for example unique simultaneous users. The only way for this approach to overcome the difficulty is by capturing multiple user sessions and having each instance use the script from a different session. This can be time-consuming for the user. SUMMARY OF THE INVENTION It is an object of the invention to provide a simple method of testing a web server which thoroughly tests the server without requiring users to have advanced programming ability, or to at least provide the public with a useful choice. According to the invention there is provided a method of testing a server, the method including the steps of: capturing script files resulting from the interaction between a server and another device; utilising a Graphical User Interface (GUI) to identify variable data within the script files; forming a database of substitute values for the variable data; and testing the server by using one or more separate threads each selecting data from the database in substitution for the variable data. There is further provided software for effecting the method. There is still further provided a server testing apparatus, the apparatus including: means for capturing script files resulting from interaction between a server and another device; a Graphical User Interface (GUI) responsive to a user input device for identifying data within the script files; means for forming a database of substitute values for the variable data; and means for generating one or more separate threads to test a server based upon the captured script files in which data from the database is substituted for the variable data. BRIEF DESCRIPTION OF THE DRAWINGS A preferred embodiment of the invention will now be described, by way of example only, with reference to the accompanying drawings in which: FIG. 1 illustrates the capture of data and how the data is used to later test the server. FIG. 2 illustrates how variable data is identified within the GUI and converted into a variable data file and a fabricated data file. FIG. 3 illustrates how the method may be deployed on computer hardware. FIG. 4 illustrates how the method may be deployed on a single personal computer with a processor and memory. DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS Referring to FIGS. 1 and 2, a user operates a browser 1 to interact with the web server 3. The data generated by the user's requests is captured by a proxy 2 and recorded in an input script file 4. The data generated by the web server's response is captured by the proxy into an output script file 5. The user then utilises a Graphical User Interface (GUI) 6 to identify data 7 within the input script file that may change between user sessions (variable data), this data may include user names, user passwords, and URLs. The GUI assists the user in this process by searching the input script file for all occurrences of data identified by the user as variable data and marking this data as variable data. The result of the identification of variable data 29 is stored in a variable data file 11. The user may also utilise the GUI 6 to identify data 8 within the output script file that can be used to validate the server's response. The result of the identification of validation data 30 is stored in validation data file 12. The identification of variable data may be used to generate a Comma-Separated Variables (CSV) header file 14 with field headers 35 corresponding to the types of variable data identified 33. The CSV header file may be edited by the user using MICROSOFT EXCEL 97™15, or any other spreadsheet program, database program, etc., to fabricate different variable data 34. This file is stored as the fabricated data file 13. A driver program 9 is provided which runs a thread 10 which uses the variable data file 11 to make requests of the server. Where the data within the variable data file is identified as variable data 31 the thread may select data from the fabricated data file 13. Data may be selected from the fabricated data file sequentially. Data returned by the server is verified by the thread using data identified as validation data 32 within the validation data file 12. The driver program may run any number of threads each using different data in place of variable data and each independently verifying server responses. The threads may run simultaneously or in succession, or some may run simultaneously and some may run in succession. The driver program provides the ability to specify different options, including thread options, such as the number of threads, the number of simultaneous threads, time delays within thread execution to simulate actual user behaviour; environment options, such as identifying which variable data file or fabricated data file to use; and other options, such as specifying the overall duration of the test. An option may be provided to increase the number of simultaneous threads from zero to a specified number over the course of the test. While the invention describes the server as a web server and the software used to interact with the server as a browser, it will appreciated by those skilled in the art that any server may be tested in this way and any program could be used in place of the browser. Although the invention has been described with the user generating the fabricated data file from the CSV header file with a spreadsheet program it will be appreciated that any other method of generating the fabricated data file may be used, including computer generation. For example, a software module may generate the fabricated data file by creating random data, by extracting data from another database, or by selecting data from multiple lists and compiling them, randomly or in a defined pattern, into a composite. Although the invention has been described with the data selected from the fabricated data file sequentially it will be appreciated that any other method of selecting the data may be used. For example, a deterministic random selection process or a hash function may be used. FIG. 3 shows a possible server testing apparatus connected to a web server. The browser may be MICROSOFT INTERNET EXPLORER™ running under a MICROSOFT WINDOWS 2000™ environment on a workstation such as a IBM INTELLISTATION Z PRO™ 16. The web server may be running under a MICROSOFT NT™ environment on an IBM XSERIES 250 server device 17. The proxy program may be running under a MICROSOFT WINDOWS 2000™ environment on a computing device such as an IBM INTELLISTATION Z PRO™ 18. The script files may be stored on a storage device such as an IBM XSERIES 200VL™ 19 file server. The GUI may be running under a MICROSOFT WINDOWS 2000™ environment on a workstation such as an IBM INTELLISTATION Z PRO™ 20. The variable data file and the validation data file may be stored on a storage device such as an IBM XSERIES 200VL™ 21 file server. The CSV header file may be stored on a storage device such as an IBM XSERIES 200VL™ 22 file server. The CSV header file may be edited by MICROSOFT EXCEL 97™ running under a MICROSOFT WINDOWS 2000™ environment on a workstation such as an IBM INTELLISTATION Z PRO™ 23. The fabricated data file may be stored on a storage device such as an IBM XSERIES 200VL™ 24 file server. The driver program may be running under a MICROSOFT WINDOWS 2000™ environment on a workstation such as an IBM INTELLISTATION Z PRO™ 25. The workstations, the server device, and the file servers may be connected to one another via a communications systems such as a Local Area Network (LAN) utilising coaxial cables. Although this invention has been described with some of the script, variable data, validation data, CSV header and fabricated data files stored on separate file servers it will be appreciated that the files may be stored on a single file server or on internal hard disk drives or in any other storage arrangement. FIG. 4 shows an implementation utilising a single PC connected to a server. The browser, the proxy, the GUI, MICROSOFT EXCEL 97™, and the driver program may be running under a MICROSOFT WINDOWS 2000™ environment on a single workstation such as an IBM INTELLISTATION Z PRO™ 26. The workstation may be connected to the web server 27 via a communications system such as a Local Area Network (LAN) utilising coaxial cables. The script files, the variable data file, the validation data file, the CSV header file, and the fabricated data file may be stored on a hard disk drive such as an IBM DESKSTAR 120GXP™ 28 within the workstation. Although this invention has been described with the method deployed on a number of workstations, file servers, and a server; and with the method deployed on a single workstation and a server; it will be appreciated that the method may be deployed in other arrangements. For example, the browser and proxy may be deployed on a single workstation and the GUI, MICROSOFT EXCEL 97™, and driver program may be deployed on a second single workstation. Although this invention has been described by way of example it is to be appreciated that improvements and/or modifications may be made thereto without departing from the scope or spirit of the present invention.

<SOH> BACKGROUND TO THE INVENTION <EOH>Standard approaches to testing web servers involve creating scripts using a programming language and using a driver program to run these scripts to test a server. A disadvantage to this approach is that the individuals who are testing the web server must be competent in using a programming language. Another approach involves the capture of traffic between a user and the server. This captured script can be then used to load test the web server by running multiple simultaneous instances using a driver program. Programs that implement this approach include LoadRunner and Astra SiteTest. This approach has a number of disadvantages. Firstly it can be difficult to thoroughly test a server as the script when used by multiple instances is unchanged, therefore only one type of user is tested. Secondly, a problem arises if the server to be tested requires unique data, for example unique simultaneous users. The only way for this approach to overcome the difficulty is by capturing multiple user sessions and having each instance use the script from a different session. This can be time-consuming for the user.

<SOH> SUMMARY OF THE INVENTION <EOH>It is an object of the invention to provide a simple method of testing a web server which thoroughly tests the server without requiring users to have advanced programming ability, or to at least provide the public with a useful choice. According to the invention there is provided a method of testing a server, the method including the steps of: capturing script files resulting from the interaction between a server and another device; utilising a Graphical User Interface (GUI) to identify variable data within the script files; forming a database of substitute values for the variable data; and testing the server by using one or more separate threads each selecting data from the database in substitution for the variable data. There is further provided software for effecting the method. There is still further provided a server testing apparatus, the apparatus including: means for capturing script files resulting from interaction between a server and another device; a Graphical User Interface (GUI) responsive to a user input device for identifying data within the script files; means for forming a database of substitute values for the variable data; and means for generating one or more separate threads to test a server based upon the captured script files in which data from the database is substituted for the variable data.

20040614

20071016

20050414

75546.0

IQBAL, NADEEM

METHOD OF AND APPARATUS FOR TESTING A SERVER

UNDISCOUNTED

ACCEPTED

ACCEPTED

Devices and method for the production of sheet material

The invention relates to sheet material having an electrical circuit and to apparatuses and methods for processing said sheet material. The present invention describes sheet material having an electrical circuit as well as apparatuses and methods for processing same, which reduce the effort required for processing the sheet material and/or facilitate processing and/or improve it and/or make it more reliable. For this purpose, the sheet material has at least one electrical circuit, with energy and/or data being transmitted from the apparatus to the electrical circuit and/or from the electrical circuit to the apparatus and at least part of the transmitted data being used for processing.

1. An apparatus for processing sheet material, in particular banknotes, that has at least one electrical circuit, characterized by a checking device for the transfer of energy and/or data to the electrical circuit of the sheet material and/or for the reception of energy and/or data from the electrical circuit of the sheet material, with at least part of the transferred energy and/or data being used for the processing. 2. An apparatus according to claim 1, characterized in that the checking device is designed to record and/or determine and/or check one or more properties, such as the authenticity and/or the denomination and/or the aggregate value and/or the serial number and/or other individual data and/or the life history of the sheet material from the transferred data. 3. An apparatus according to at least one of the prior claims, characterized in that the checking device is equipped with the following transfer methods either alone or in combination: A contact-type coupling, a noncontacting coupling, an inductive coupling, a capacitive coupling, a galvanic coupling via contacts, a coupling by means of an electrical field, a coupling by a magnetic field, an optical coupling by electromagnetic waves, a coupling by deformation, such as piezoelectric elements, a coupling by electromechanical elements, a coupling by sound and/or a coupling by heat. 4. An apparatus according to at least one of the prior claims, characterized in that the checking device has at least one coupling unit, such as an electrode to the capacitive coupling, a magnet for producing a magnetic field, a coil for inductive coupling, a light source for optical coupling, in particular for illuminating a photo cell and/or a photodiode of the sheets, and/or a sound source, in particular an ultrasonic source, in order to irradiate an electric element of the sheet material that reacts to sound, such as a piezoelectrical element, with the coupling unit preferentially being provided in a base surface on which the sheets are provided stacked for a measurement and/or integrated in another component of the processing apparatus, such as a singler and/or a transport path and/or a sensor path and/or a stacker and/or a temporary memory and/or a deposit means. 5. An apparatus according to at least one of the prior claims, characterized in that a plurality of different transfer methods is available to the checking device in each case for the reception of energy and/or data of the sheet circuit and/or for the transfer of energy and/or data to the sheet circuit. 6. An apparatus according to at least one of the prior claims, characterized in that selection of one or more of the different transfer methods is dependent on a control signal that is preferentially transferred to the circuit of the sheet material from the processing apparatus or to the processing apparatus of the circuit from the sheet material. 7. An apparatus according to at least one of the prior claims, characterized in that the checking device for the reception of energy and/or data of the sheet circuit has a receiving unit that can use the same and/or another transfer method such as for the transfer of energy and/or data to the sheet circuit. 8. An apparatus according to at least one of the prior claims, characterized in that the checking device for the reception of energy and/or data from the sheet circuit has a receiving unit that is situated in the same and/or another processing section of the processing apparatus as a transmitting unit for the transfer of energy and/or data to the sheet circuit. 9. An apparatus according to at least one of the prior claims, characterized in that the checking device for the reception of energy from the sheet circuit and/or for the transfer of energy to the sheet circuit can use the same and/or another transfer method as for the reception of data from the sheet circuit and/or for the transfer of data to the sheet circuit. 10. An apparatus according to at least one of the prior claims, characterized in that the checking device for the reception of energy and/or data from the sheet circuit can use an optical coupling and that it can use an inductive and/or capacitive coupling for the transfer of energy and/or data to the sheet circuit. 11. An apparatus according to at least one of the prior claims, characterized in that the checking device can measure the properties of a plurality of sheets with a stationary stack of sheets and/or with a moving stack of sheets and/or the properties of individual sheets with stationary and/or moving individual sheets. 12. An apparatus according to at least one of the prior claims, characterized in that the sheets of the sheet material can be transported and/or processed, in particular tested, both individually and in a stack in the apparatus. 13. An apparatus according to at least one of the prior claims, characterized in that the checking device can successively measure the properties of individual sheets and/or simultaneously measure the properties of several sheets, in particular all sheets. 14. An apparatus according to at least one of the prior claims, characterized in that the checking device can address, e.g. activate, several circuits of different sheets simultaneously and/or in serial succession, and/or that several circuits of different banknotes that are addressed can simultaneously and/or in serial succession send response signals back to the processing apparatus. 15. An apparatus according to at least one of the prior claims, characterized in that the checking device can not activate a circuit of one of the sheets until a circuit of another of the sheets to be processed has already sent out a response signal. 16. An apparatus according to at least one of the prior claims, characterized in that, in particular when an optical and/or inductive coupling is used to transfer energy and/or data to the sheet circuit, the position of the coupling field of the processing apparatus is moved, in particular in the stacking direction of the stack being checked so that the different sheets in a stack can be addressed successively. 17. An apparatus according to at least one of the prior claims, characterized in that, in particular when an inductive coupling is used to transfer energy and/or data from the processing apparatus to the sheet circuit, the strength of the coupling field of the processing apparatus can be increased selectively during the checking operation so that the different sheets in a stack can be addressed successively. 18. An apparatus according to at least one of the prior claims, characterized in that the transfer of data can be effected via single-stage and/or multi-stage modulation of the transferred signal, in particular when optical coupling is used, and/or via load modulation, e.g. of the transferring energy, and/or via changing coefficients of optical transmission, reflection and/or absorption. 19. An apparatus according to at least one of the prior claims, characterized in that when optical coupling is used, the spectral composition and/or time behavior, in particular the duration, level, intervals and/or sequence of pulse of the light signals emitted by or, as the case may be, received from the sheet material depends on the data to be transferred. 20. An apparatus according to at least one of the prior claims, characterized by a light source to irradiate an individual photodiode of a sheet or several photodiodes of several sheets of a stack. 21. An apparatus according to at least one of the prior claims, characterized in that the checking device can initially determine individual data, such as a serial number of one or more sheets, such as via the reception of data from the sheet circuits, in order to then be able to selectively address individual sheet circuits or a subset of all of the sheet circuits in a further step. 22. An apparatus according to at least one of the prior claims, characterized in that the checking device can transfer data on the life history of the sheets to the sheets. 23. An apparatus according to at least one of the prior claims, characterized in that the checking device can transfer an authentication signal to the sheet circuit to obtain authorization for carrying out certain processing operations such as reading and/or modifying the contents of a memory of the circuit. 24. An apparatus according to at least one of the prior claims, characterized by a singler for separating sheet material, which can remove one sheet at a time from a stack of sheet material, with the checking device designed such that the transfer of energy and/or data between the circuit situated on a sheet that is to be pulled off and the device takes place before and/or as the sheet is being pulled from the stack. 25. An apparatus according to at least one of the prior claims, characterized in that means for securing transfer of the data, such as encryption or a digital signature of the transferred data are provided. 26. An apparatus according to at least one of the prior claims, characterized in that the checking device can communicate with the circuit of the sheet material via both or only one of the two frequencies when sheet material with several coupling elements of different coupling frequencies is used. 27. An apparatus according to at least one of the prior claims, characterized in that the checking device can only communicate with the circuit of the sheet material via the other frequency if and only if a communication at one of the two coupling frequencies of the coupling elements fails. 28. An apparatus according to at least one of the prior claims, characterized in that the checking device can alter the circuit at a certain point in time following application to or, as the case may be, incorporation in the sheet material such that the writing of data is prevented in all or part of the memory areas of the circuit. 29. An apparatus according to at least one of the prior claims, characterized in that the checking device can deactivate the circuit of a checked sheet and/or at least interrupt one of possibly several connecting lines that are connected with the circuit during or after a checking operation, preferentially dependent on the result of the check. 30. An apparatus according to at least one of the prior claims, characterized in that the checking device can irradiate an oscillating circuit of the sheet material with an alternating field and that signals produced by the oscillating circuit and received by the checking device can be evaluated so as to check the sheet material, for e.g. authenticity. 31. An apparatus according to at least one of the prior claims, characterized in that the checking device can check the presence and/or the form and/or a surface structure, e.g. a surface pattern, and/or the position and/or the distribution with several circuits in or, as the case may be, on the sheet material as an authenticity feature. 32. An apparatus according to at least one of the prior claims, characterized in that the checking device can measure and evaluate the temperature, such as the heat distribution of the sheet material, or another quantity derived from same, when the sheet material is checked. 33. An apparatus according to at least one of the prior claims, characterized in that, in order to examine the contents of a container, the checking device can compare data about the contents of the container, which are stored in a memory of the container, with data about the contents of the container, which are stored in a memory of the sheet material circuit of at least one of or all of the sheets in the container. 34. An apparatus according to at least one of the prior claims, characterized in that, in a processing operation, the checking device can transmit data to a container, which are intended for writing into the sheets in the container, so that these data will be stored temporarily in a memory of the container in order to write the data to the corresponding memory of at least one of the sheets only at a later point in time after completion of the processing operation, e.g. during removal of the sheets contained therein. 35. An apparatus according to at least one of the prior claims, characterized in that a circuit can be applied to or, as the case may be, incorporated into a band already during production of the band or only during or after a banding operation during which a stack of sheets is provided with a band. 36. An apparatus according to at least one of the prior claims, characterized in that the checking device has a device for generating an alternating magnetic field that can penetrate a stack of banknotes to be checked, preferentially in the stacking direction and/or perpendicular to the stacking direction. 37. An apparatus according to at least one of the prior claims, characterized in that the frequency of an alternating magnetic field generated by the device corresponds to a mechanical resonance frequency of a magnetostrictive element of the sheet material or to a mechanical resonance frequency of a compound material of the sheet material with the magnetostrictive element. 38. An apparatus according to at least one of the prior claims, characterized in that the checking device can perform an anticollision detection procedure in the processing apparatus and/or in the sheet material circuit during a checking operation. 39. An apparatus according to at least one of the prior claims, characterized in that the apparatus further has a pressing device, which can compress the sheets for a stack measurement and/or the apparatus further has an aligning device, which can align the sheets such that they are flush with reference to one or two edges disposed perpendicularly to one another. 40. An apparatus according to at least one of the prior claims, characterized in that the checking device has a sonic sensor for detecting sound waves that are radiated from a sonic source connected with the sheet material circuit, such as a reciprocal piezoelectric element of the sheet material. 41. An apparatus according to at least one of the prior claims, characterized in that there is/are one or more keys and/or sets of keys, which can be used alternatively, for encryption of data to be stored and/or transferred and/or for forming of a digital signature of data to be stored and/or transferred. 42. An apparatus according to at least one of the prior claims, characterized in that the checking device can include individual data, such as a serial number of the sheet material, in an encrypted or, as the case may be, signed set of data of other data of the sheet material or, as the case may be, for the sheet material. 43. An apparatus according to at least one of the prior claims, characterized in that the checking device can forward data of the circuit of the sheet material to be checked to a spatially removed evaluation unit for checking purposes, which can evaluate the data and send a check result back to the processing apparatus. 44. An apparatus according to at least one of the prior claims, characterized in that the checking device can, in one check, preferentially, in every check of sheet circuits, transfer to such sheet circuits a new identification number for storage in a memory area of the sheet circuit provided for this purpose, with the identification number preferentially also being able to be stored in an external data base situated outside the sheet material together with individual data, such as the serial number of the respective sheet. 45. An apparatus according to at least one of the prior claims, characterized in that the checking device can compare the identification number and the individual data from the memory of the sheet material with associated data in the external data base in a checking operation. 46. An apparatus according to at least one of the prior claims, characterized in that the checking device or the external data base can regenerate and/or select the identification number from a set of predetermined identification numbers at the time of the checking operation. 47. An apparatus according to at least one of the prior claims, characterized in that, in addition to the identification number, the checking device can also transfer to the sheet circuit a time stamp and/or a location stamp of the current checking operation and/or of one or more preceding checking operations for storage in a memory area of the sheet circuit provided for this purpose and/or to store same in a memory of the checking device. 48. An apparatus according to at least one of the previous claims, characterized in that the newly generated identification number and/or the newly generated time stamp and/or location stamp depends on the current or a previous identification number and/or on the current or a previous time stamp and/or location stamp. 49. An apparatus according to at least one of the previous claims, characterized in that there are several external databases, and that the checking device can select one of the external databases for a subsequent check evaluation by means of a predetermined selection criterion which depends e.g. on the identification number and/or the time stamp and/or the location stamp. 50. An apparatus according to at least one of the previous claims, characterized in that the checking device can evaluate data obtained by a data transmission between the processing apparatus and the sheet material circuit, in dependence on data which stems from other checking operations that were performed independently of the sheet material circuit. 51. An apparatus according to at least one of the previous claims, characterized in that the checking device can compare data from the memory of the sheet material circuit with data, which are specific to the respective paper of the sheet material and/or feature substances contained therein. 52. An apparatus according to at least one of the previous claims, characterized in that the checking device can refer to data obtained by a data transmission between the processing apparatus and the sheet material circuit for adjusting checking parameters of other checking operations performed independently of the sheet material circuit. 53. An apparatus according to at least one of the previous claims, characterized in that, in a checking operation, preferentially in every checking operation, wherein sheet material is rated or classified as still fit for circulation, the checking device can transmit data to the sheet material circuit, which cause an irreversible, local change of the sheet material, whereby the data about the change can preferentially be stored in a memory of the circuit of the sheet material, and/or the checking device itself can perform such an irreversible, local change of the sheet material. 54. An apparatus according to at least one of the previous claims, characterized in that the checking device is formed such that a transmission of data and/or energy from the processing apparatus to the sheet material circuit and/or from the sheet material circuit to the processing apparatus is always possible independently of the orientation of the checking device of the sheet material and/or the transport direction (T1, T2) of the sheet material with reference to the checking device, i.e., e.g. both in longitudinal transport and in transverse transport of the sheet material. 55. An apparatus according to at least one of the previous claims, characterized in that the checking device has several segments which can alternatively be electrically interconnected, and/or the checking device of the processing apparatus is formed by a singler, for example by a separating roll, and/or the checking device of the processing apparatus has a device which produces a rotating and/or traveling electrical and/or magnetic field. 56. An apparatus according to at least one of the previous claims, characterized in that, during transport of sheets in the processing apparatus, the checking device can determine the position of the sheets in the processing apparatus in dependence on data, in particular on individual data, which are transmitted to the processing apparatus from the sheet material circuit. 57. An apparatus according to at least one of the previous claims, characterized in that the checking device can use data which are transmitted to the processing apparatus from the sheet material circuit for detecting several picks and/or the state of the sheets. 58. An apparatus according to at least one of the previous claims, characterized in that, during or after a checking operation, the checking device can transmit data to the sheet material circuit for storage in a memory of the sheet material circuit, whereby the data relate to the checking operation. 59. An apparatus according to at least one of the previous claims, characterized in that, in a checking operation, the checking device can compare paper data with circuit data of the sheet material. 60. An apparatus according to at least one of the previous claims, characterized in that the processing apparatus has a singler, a sensor and a stacker, and sheet material can be transported directly from the singler to the stacker without a separate sensor path. 61. An apparatus according to at least one of the previous claims, characterized in that a stack of sheets is clamped on one side by means of a clamping device, and that on the other side, a mechanism can single the sheets clamped on one side, and the sheet material circuits can be addressed by the checking device during the singled state. 62. An apparatus according to at least one of the previous claims, characterized by a sensor, such as a limpness sensor or hole sensor, wherein the sheet material to be checked is deformed for measurement of paper properties, whereby the bending additionally serves the purpose of supplying energy to the sheet material circuit and/or of transmitting data of the sheet material circuit to the processing apparatus. 63. An apparatus according to at least one of the previous claims, characterized in that the processing apparatus has separate transport paths for single sheet processing and for stack processing. 64. An apparatus according to at least one of the previous claims, characterized in that containers for transporting sheet material within the processing apparatus can be transported. 65. An apparatus according to at least one of the previous claims, characterized in that a processing apparatus with combined individual and stack processing has one or more output stations from which containers with sheet material deposited therein can be outputted from the apparatus for removal of the containers and/or the sheets contained therein, whereby the output stations each have assigned thereto one or more filling stations, wherein the containers are filled with sheet material before they are transported to the associated output station. 66. An apparatus according to at least one of the previous claims, characterized in that, in part of the or all the individual processing parts of the processing apparatus, such as the singler, the sensor path, the stacker or the interjacent transport paths, which are preferentially realized as modular units, only at most one deposit and/or one stack of sheet material can always be contained at the same time. 67. An apparatus according to at least one of the previous claims, characterized in that, in the apparatus, a physical separation is given by spatial spacing of different deposits during the processing of several deposits in the processing apparatus. 68. An apparatus according to at least one of the previous claims, characterized in that there is a separating means for separating a number of sheets into two subsets, whereby the separating means is equipped with an electrical circuit which has the same communication interface as the sheet material. 69. An apparatus according to at least one of the previous claims, characterized in that separating means can prevent communication of the checking device with the sheet material circuits of one of the two subsets. 70. An apparatus according to at least one of the previous claims, characterized in that a sensor for checking properties of the sheet material circuit is mounted in the same and/or a spatially spaced different area, such as in the same or, as the case may be, different module cases or processing parts, in comparison with a sensor for checking paper properties of the sheet material. 71. An apparatus according to at least one of the previous claims, characterized in that a unit for reading data from a memory of the sheet material circuit is disposed in the same and/or a spatially spaced different area as a unit for writing data to the memory of the sheet material circuit. 72. An apparatus according to at least one of the previous claims, characterized in that the writing unit is downstream of the reading unit and/or the writing unit is downstream of a sensor device, which can measure properties of the circuit and/or of the paper of the sheet material. 73. An apparatus according to at least one of the previous claims, characterized in that, in a processing operation, the checking device can only write data and/or transmit data to the sheet material circuit for writing to a part of the basically functioning memories of the sheet material circuits, which e.g. are to be checked once again and/or have been checked as false or suspicious. 74. An apparatus according to at least one of the previous claims, characterized in that, in the processing apparatus, there are a plurality of reading units for reading individual data from the sheet material circuits in the transport path of the sheet material so that the position and identity of transported sheets can be clearly traced. 75. An apparatus according to at least one of the previous claims, characterized in that the checking device can perform at least one or all checks of the sheet material, such as a check of the authenticity of the sheet material, only in dependence on data transmitted from the sheet material circuit to the processing apparatus. 76. An apparatus according to at least one of the previous claims, characterized in that a correlation of transaction data upon a deposit and/or disbursement of sheet material with measurement data for checking the associated sheet material can be performed, and that the correlation data can preferentially be stored in a memory of the sheet material circuit of at least one of the sheets of the sheet material and/or in a memory of the processing apparatus and/or in an external database. 77. An apparatus according to at least one of the previous claims, characterized in that, independently of an evaluation of signals for transmitting data and/or energy to the sheet material circuit, the checking device can determine whether a sheet material circuit is present at a predetermined position and/or in a predetermined form and/or at a predetermined location on or, as the case may be, in the sheet material paper. 78. An apparatus according to at least one of the previous claims, characterized in that, in a processing operation, the checking device can perform different checking operations at different speeds on a sheet material and/or perform different checking operations at separate times. 79. An apparatus according to at least one of the previous claims, characterized in that the checking device can perform checking operations prior to an intermediate storage of the checked sheet material at a higher speed than checking operations after the intermediate storage. 80. An apparatus according to at least one of the previous claims, characterized by an input means for input of a stack of sheet material by an operator, and a final stacker, such as a cassette, from which inputted sheet material can no longer be removed by the operator, whereby the inputted sheets can be checked by a checking unit connected to the checking device and transported directly from the input means to the final stacker, in particular in the stacked state. 81. An apparatus according to at least one of the previous claims, characterized in that, in a processing apparatus having a sheet material output function, a checking unit, which can determine the serial number or other individual data of the sheets transported from the sheet material pocket to the output pocket, is interposed between a sheet pocket and an output pocket. 82. An apparatus according to at least one of the previous claims, characterized in that the banknote processing apparatus is part of a cash register, a tabletop unit, a manual checking device, a purse and/or a pocket checking device. 83. An apparatus according to at least one of the previous claims, characterized by one or more stacker, such as storage pockets and/or cassettes, whereby the checking device is designed for automatically checking the stock of sheet material having a sheet material circuit in all of or some of the stacker. 84. An apparatus according to at least one of the previous claims, characterized in that the checking device can register all sheets having an operable sheet material circuit in the stacker and/or can register each removal and/or input of such sheets having an operable sheet material circuit into the stacker or, as the case may be, out of the stacker. 85. An apparatus according to at least one of the previous claims, characterized in that the checking device can ascertain whether sheets of only one kind, such as banknotes of only one denomination, are present in the stacker. 86. An apparatus according to at least one of the previous claims, characterized in that the processing apparatus is a separate and preferentially portable cash register unit, which can both detect goods to be bought in a purchase transaction and check banknotes for authenticity at least. 87. An apparatus according to at least one of the previous claims, characterized in that the memory of the sheet material circuit can store data about the intended use of the sheet material. 88. An apparatus according to at least one of the previous claims, characterized in that, in a processing operation, the sheet material can subsequently be provided with an additional electrical circuit. 89. An apparatus according to at least one of the previous claims, characterized in that the additional circuit has different properties from the sheet material circuit, whereby the communication interfaces are preferentially identical. 90. A method for processing sheet material, in particular banknotes, which has at least one electrical circuit, having a processing apparatus, characterized in that energy and/or data are transmitted from the apparatus to the electrical circuit and/or from the electrical circuit to the apparatus, whereby at least part of the transmitted data is used for processing. 91. A method according to claim 90, characterized in that one or more properties, such as of the authenticity and/or the denomination and/or the total value and/or the serial number or other individual data and/or the life history of the sheet material, are determined from the transmitted data and/or checked. 92. A method according to at least one of claims 90 to 91, characterized in that the properties of several sheets are measured with the stack at rest and/or with the stack moving, and/or the properties of singled sheets are measured with the sheets at rest and/or moving, and/or the properties of single sheets are measured successively and/or the properties of several, in particular all, sheets are measured simultaneously, and/or several circuits of different sheets are addressed, such as activated, by the processing apparatus simultaneously and/or serially one after the other, and/or several circuits of different addressed sheets send back response signals to the processing apparatus simultaneously and/or serially one after the other. 93. A method according to at least one of claims 90 to 91, characterized in that a circuit of one of the sheets is only activated when a circuit of another of the sheets has already emitted a response signal, and/or the circuit of a first sheet can receive data and/or energy which is emitted by the circuit of a second, in particular an adjacent, sheet in a stack, and the circuit of the first sheet is preferentially activated in dependence on the received signal of the second sheet. 94. A method according to at least one of claims 90 to 93, characterized in that the sheets of the sheet material are transported and/or processed, in particular checked, in the apparatus both singly and in stacked form. 95. A method according to at least one of claims 90 to 94, characterized in that, for transmitting energy and/or data from the sheet material circuit to the processing apparatus and/or from the processing apparatus to the sheet material circuit, contact-type or contactless coupling, inductive coupling, capacitive coupling, galvanic coupling via contacts, coupling by an electrical field, coupling by a magnetic field, optical coupling by electromagnetic waves, coupling by deformation, such as piezoelectric elements, coupling by electromechanical elements, coupling by sound and/or coupling by heat are used alone or in combination. 96. A method according to at least one of claims 90 to 95, characterized in that the same and/or a different transmission method is used for transmitting energy and/or data from the sheet material circuit to the processing apparatus as that used for transmitting energy and/or data from the processing apparatus to the sheet material circuit, and/or the same and/or a different transmission method is used for transmitting energy from the sheet material circuit to the processing apparatus and/or from the processing apparatus to the sheet material circuit as that used for transmitting data from the sheet material circuit to the processing apparatus and/or from the processing apparatus to the sheet material circuit. 97. A method according to at least one of claims 90 to 96, characterized in that several different transmission methods are available for transmitting energy and/or data from the sheet material circuit to the processing apparatus and/or for transmitting energy and/or data from the processing apparatus to the sheet material circuit. 98. A method according to at least one of claims 90 to 97, characterized in that the selection of one or more of the available different transmission methods is effected in dependence on a control signal which is preferentially transmitted to the circuit of the sheet material from the processing apparatus or to the processing apparatus from the circuit of the sheet material. 99. A method according to at least one of claims 90 to 98, characterized in that, in particular in the case of optical and/or inductive coupling for transmitting energy and/or data from the processing apparatus to the sheet material circuit, the position of the coupling field of the processing apparatus is moved, in particular in the stacking direction of the stack to be checked, to permit different sheets in a stack to be addressed successively. 100. A method according to at least one of claims 90 to 99, characterized in that, in particular in the case of inductive coupling for transmitting energy and/or data from the processing apparatus to the sheet material circuit, the strength of the coupling field of the processing apparatus is increased specifically during the checking operation to permit different sheets in a stack to be addressed successively. 101. A method according to at least one of claims 90 to 100, characterized in that individual data, such as the serial number, of one or more sheets are first determined, e.g. by a data transmission from the sheet material circuit to the processing apparatus, so that, in a further step, single sheet material circuits or a subset of all sheet material circuits can be addressed specifically by the processing apparatus. 102. A method according to at least one of claims 90 to 101, characterized in that data about the life history of the sheet material are stored in a memory of the circuit of the sheet material. 103. A method according to at least one of claims 90 to 102, characterized in that an authentication signal is transmitted to the circuit by the processing apparatus to receive from the circuit a right to perform certain processing operations, such as to read and/or change the memory contents of a memory of the circuit. 104. A method according to at least one of claims 90 to 103, characterized in that during or after a checking operation, preferentially in dependence on the result of the check, the circuit of a checked sheet is deactivated and/or at least one of optionally several connecting leads connected to the circuit is interrupted. 105. A method according to at least one of claims 90 to 104, characterized in that, in the case of sheet material having several coupling elements with different coupling frequencies, the apparatus communicates with the circuit of the sheet material on both or only one of the two frequencies, and preferentially communicates with the circuit of the sheet material on the other frequency only when communication on one of the two frequencies of the coupling elements fails. 106. A method according to at least one of claims 90 to 105, characterized in that, at a certain point in time after application to or incorporation into the sheet material, the circuit is changed so as to prevent data from being written into all or some of the memory areas of the circuit. 107. A method according to at least one of claims 90 to 106, characterized in that an oscillating circuit of the sheet material is exposed to an alternating field, and signals produced by the oscillating circuit are evaluated for checking the sheet material, e.g. for authenticity. 108. A method according to at least one of claims 90 to 107, characterized in that, for checking the contents of a container, data about the contents of the container, which are stored in a memory of the container, are compared with data about the contents of the container, which are stored in a memory of at least one of or all of the sheets in the container. 109. A method according to at least one of claims 90 to 108, characterized in that, in a processing operation, data intended to be written in the sheets of a container are transmitted to the container and stored intermediately in the memory thereof, so that the data are not written into the corresponding sheets until a later point in time after completion of the processing operation, e.g. upon removal of the sheets contained therein. 110. A method according to at least one of claims 90 to 109, characterized in that a circuit is already applied to or incorporated into a band during production of the band or only after a banding operation wherein a stack of sheets is provided with a band. 111. A method according to at least one of claims 90 to 110, characterized in that, in a checking operation, a method of anticollision detection is performed in the processing apparatus and/or in the sheet material circuit. 112. A method according to at least one of claims 90 to 111, characterized in that, for a stack measurement, the banknotes are pressed together and/or aligned flush according to one or two mutually perpendicular edges. 113. A method according to at least one of claims 90 to 112, characterized in that data intended for transmission and/or for writing to a memory of the sheet material and/or of the processing apparatus are encrypted and/or digitally signed, whereby there are preferentially one or more keys and/or sets of keys, which are alternatively used, for encrypting data to be stored and/or transmitted and/or for forming a digital signature of data to be stored and/or transmitted, and/or preferentially individual data, such as a serial number of the sheet material, are included in an encrypted or, as the case may be, signed data set of other data. 114. A method according to at least one of claims 90 to 113, characterized in that a checking operation is evaluated by the processing apparatus passing on data of the circuit of the sheet material for checking purposes to a spatially remote evaluation unit, which evaluates the data and sends back a check result to the processing apparatus. 115. A method according to at least one of claims 90 to 114, characterized in that, in a check, preferentially in every check, of sheet material circuits, a new identification number is stored in a specially provided memory area of the sheet material circuit, with the identification number preferentially also being stored together with individual data, such as the serial number of the respective sheet, in an external database located outside the sheet material. 116. A method according to at least one of claims 90 to 115, characterized in that, in a checking operation, the identification number and the individual data from the memory of the sheet material are compared with associated data in the external database, with the check being performed completely or partly, either in the sheet material circuit and/or in the processing apparatus and/or in the external database. 117. A method according to at least one of claims 90 to 116, characterized in that, at the time of the checking operation, the identification number is newly generated and/or selected from a set of predetermined identification numbers and/or that, in addition to the identification number, a time stamp and/or a location stamp of the momentary checking operation and/or of previous checking operations are stored, which are preferentially stored in the memory of the sheet material and/or in the external database. 118. A method according to at least one of claims 90 to 117, characterized in that there are several external databases, and one of the external databases is selected for a subsequent check evaluation by means of a predetermined selection criterion which depends e.g. on the identification number and/or the time stamp and/or the location stamp. 119. A method according to at least one of claims 90 to 118, characterized in that data obtained by a data transmission between processing apparatus and sheet material circuit are evaluated in dependence on data which stems from other checking operations performed independently of the sheet material circuit, and/or data obtained by a data transmission between the processing apparatus and the sheet material circuit are used for adjusting checking parameters of other checking operations performed independently of the sheet material circuit. 120. A method according to at least one of claims 90 to 119, characterized in that data from the memory of the sheet material circuit are compared with data which are specific to the respective paper of the sheet material and/or feature substances contained therein. 121. A method according to at least one of claims 90 to 120, characterized in that, in a checking operation, preferentially in every checking operation, wherein the sheet material is rated or classified as still fit for circulation, the sheet material is subjected to an irreversible, local change of the sheet material, with the data about the change preferentially being stored in a memory of the circuit of the sheet material. 122. A method according to at least one of claims 90 to 121, characterized in that, during a transport of sheets in the processing apparatus, the position of the sheets in the processing apparatus is determined in dependence on data, in particular individual data, which are transmitted to the processing apparatus from the sheet material circuit, and/or data about the checking operation are written into a memory of the sheet material circuit during or after a checking operation, and/or paper data are compared with circuit data of a sheet during a checking operation. 123. A method according to at least one of claims 90 to 122, characterized in that a transmission device of the sheet material circuit is supplied, by deformation of the sheet during singling of the sheets clamped on one side, with energy which comes from a transmission device of the processing apparatus and/or from the sheet material circuit itself, such as an associated piezoelectric element. 124. A method according to at least one of claims 90 to 123, characterized in that a physical separation is performed by spatial spacing of different deposits during the processing of several deposits in the processing apparatus. 125. A method according to at least one of claims 90 to 124, characterized in that separating means are equipped with electrical circuits which have the same communication interface and/or communication interfaces as the sheet material, and/or separating means for separating sheets into two subsets are used, which can prevent communication of the processing apparatus with the sheet material circuits of one of the two subsets. 126. A method according to at least one of claims 90 to 125, characterized in that, in a processing operation, data which e.g. are to be checked once again and/or have been checked as false or suspect of forgery, are written only into a part of the basically operating memories of the sheet material circuits. 127. A method according to at least one of claims 90 to 126, characterized in that a correlation of transaction data is performed upon a deposit and/or a disbursement of sheet material with measurement data for checking the associated sheet material and the correlation data preferentially being stored in a memory of the sheet material circuit of at least one of the sheets of the sheet material and/or in a memory of the processing apparatus and/or of an external database. 128. A method according to at least one of claims 90 to 127, characterized in that, in a processing operation on a sheet material, different checking operations are performed at different speeds and/or different checking operations are performed at separate times, in particular, checking operations before an intermediate storage of the checked sheet material take place at higher speeds than checking operations after intermediate storage. 129. A method according to at least one of claims 90 to 128, characterized in that data about the intended use of the sheet material are stored in the memory of the sheet material circuit, and/or there are different access rights for reading from and/or writing to the memory, in particular different memory areas, of the circuit of the sheet material for different users or, as the case may be, user groups. 130. A method according to at least one of claims 90 to 129, characterized in that the sheet material is subsequently provided with an additional electrical circuit in a processing operation. 131. A container, such as a safe or a cassette or a band for storing and/or transporting sheet material, comprising at least one electrical circuit and a transmission device for transmitting energy and/or data from the circuit of the container to an apparatus, which is formed for processing the container, and/or for receiving energy and/or data from such an apparatus. 132. A container according to claim 131, characterized in that the container has a processing apparatus or at least one component of a processing apparatus according to at least one of claims 1 to [?]. 133. A container according to at least one of claims 131 to 132, characterized in that the container is used in a processing apparatus according to at least one of claims 1 to [?] for receiving processed sheet material and/or outputting contained sheet material from the container. 134. A container according to at least one of claims 131 to 133, characterized in that the circuits of the sheet material in the container can communicate directly with an external processing apparatus according to at least one of claims 1 to [?]. 135. A container according to at least one of claims 131 to 134, characterized in that the contents of the container, such as the number, denomination and/or total value of the contained sheets, can be registered and optionally checked by the container itself. 136. A container according to at least one of claims 131 to 135, characterized in that data, such as about the contents of the container, can be stored in a memory of the container and/or a memory of at least one of or all of the sheets in the container. 137. A container according to at least one of claims 131 to 136, characterized in that, following a query from an external processing apparatus, the container can provide data about the sheets contained therein and/or write data into a memory of the circuit of the sheets contained therein. 138. A container according to at least one of claims 131 to 137, characterized in that the container is so formed that, in a processing operation, it can accept data intended to be written into the sheets, hold them in its memory and write the intermediately stored data into the corresponding sheets only at a later time after completion of the processing operation, e.g. upon removal of the sheets contained therein. 139. A container according to at least one of claims 131 to 138, characterized in that the transmission device of the container for transmitting energy and/or data to an external processing apparatus is based on the same and/or a different transmission method compared to a transmission device for communication with the sheet material circuits in the container. 140. Sheet material having at least one electrical circuit, comprising a device for transmitting and/or receiving energy and/or data to or, as the case may be, from an apparatus for processing the sheet material, with at least part of the transmitted energy or data being used for processing. 141. Sheet material according to claim 140, characterized in that there is a unit for transmitting energy and/or data from the sheet material circuit to the processing apparatus and another unit for receiving energy and/or data from the processing apparatus. 142. Sheet material according to at least one of claims 140 to 141, characterized in that the unit for transmitting energy and/or data from the sheet material circuit to the processing apparatus works according to the same or a different transmission method compared to the receiving unit, and/or there are different transmission units which make available different alternatively selectable transmission methods. 143. Sheet material according to at least one of claims 140 to 142, characterized in that the circuit has at least one memory, with the memory preferentially having several memory areas that are separate from one another and can be written to and/or read from only once and/or many times. 144. Sheet material according to at least one of claims 140 to 143, characterized in that an authentication system is provided which has data about different access authorizations for different users or, as the case may be, user groups for reading and/or changing memory contents of a memory of the circuit, with the authentication system preferentially being connected to a maloperation counter. 145. Sheet material according to at least one of claims 140 to 144, characterized in that there are one or more keys and/or sets of keys for encrypting data to be stored and/or transmitted and/or for forming a digital signature of data to be stored and/or transmitted. 146. Sheet material according to at least one of claims 140 to 145, characterized in that the circuit has one or more logical switches, and preferentially data related to a switching process can be stored, assigned to the respective switch. 147. Sheet material according to at least one of claims 140 to 146, characterized in that one or more different individual data which are characteristic of the particular banknote are stored and/or can be stored in the memory. 148. Sheet material according to at least one of claims 140 to 147, characterized in that a memory of the sheet material circuit contains paper data specific to the particular sheet, and/or circuit data about the circuit are incorporated in the paper and/or applied to, e.g. printed on, the paper as information, and/or the memory of the sheet material circuit stores data specific to the particular banknote, the paper data and circuit data of the particular banknote correlate, and/or these correlated data are incorporated into the paper and/or applied to, e.g. printed on, the paper as information. 149. Sheet material according to at least one of claims 140 to 148, characterized in that the sheet material circuit has a detection device, such as a device for evaluating an input voltage of the circuit, to permit detection of a data transmission from other sheets in a stack to a processing apparatus. 150. Sheet material according to at least one of claims 140 to 149, characterized in that at least one transmission device for optically transmitting energy and/or data is provided, which has an optical transmitter, such as a light-emitting diode, and/or at least one photodiode for sending and/or receiving light, and/or the sheet material has a photocell and a light source, the photocell preferentially being located on one side of the sheet material and the light source on the other side thereof. 151. Sheet material according to at least one of claims 140 to 150, characterized in that the photodiode is applied to a luminescent element, such as a single-layer or multilayer LISA element, which is optionally provided with a reflective coating, and/or the photodiode is applied to a light source, in particular a luminous surface, and/or the spectral composition and/or the time behavior, in particular the duration, height, spacing and/or sequence of pulse, depends on emitted light signals from the data to be transmitted. 152. Sheet material according to at least one of claims 140 to 151, characterized in that the sheet material has incorporated therein or applied thereto elements with a “shape memory” effect and/or piezoelectric effect and/or magnetostrictive effect, such as a composite material out of magnetostrictive and piezoelectric substances, and/or one or more capacitive coupling surfaces. 153. Sheet material according to at least one of claims 140 to 152, characterized in that the capacitive coupling surface has connected thereto an inductance Lp of defined value, which can preferentially be alternatively switched on or off, and/or the voltage occurring on an element with a piezoelectric effect is used for voltage supply to the circuit, and/or the frequency of the voltage occurring on the element with a piezoelectric effect is used as the reference frequency for producing a clock frequency of the circuit. 154. Sheet material according to at least one of claims 140 to 153, characterized in that the paper of the sheet material has a magnetic substance having a magnetic permeability significantly greater than the relative permeability of paper without said magnetic substance, and the magnetic substance is preferentially incorporated into and/or applied to the paper, such that the inductance of a coil as a coupling element of the circuit is increased and/or the substance exhibits a magnetic behavior that is direction-dependent. 155. Sheet material according to at least one of claims 140 to 154, characterized in that the sheet material has receivers for light and/or ultrasound for supplying the circuit with energy by irradiation of light or ultrasound, and/or one or more sensors for measuring environmental influences are incorporated in or applied to the sheet material 156. Sheet material according to at least one of claims 140 to 155, characterized in that the position of the circuit varies in the case of several sheets, e.g. in the case of banknotes of one currency and/or of the same or different denominations, and/or the circuit has an area of from 5 to 95% of the sheet material, preferentially from 50 to 90% or, as the case may be, 70 to 90%, and/or the circuit is located below an optically variable element. 157. Sheet material according to at least one of claims 140 to 156, characterized in that the sheet material has several coupling elements, such as a first antenna coupled directly with the circuit and a second antenna coupled with the first antenna for coupling to the processing apparatus, the several coupling elements preferentially having different coupling frequencies, which are preferentially selected specifically to the currency and/or denomination. 158. Sheet material according to at least one of claims 140 to 157, characterized in that the circuit has an integrated circuit and/or a memory and/or an electrical oscillating circuit, and/or the circuit is connected conductively via at least one line to at least one conductive capacitive coupling surface as an electrode, and/or the sheet material has one or more galvanic contact surfaces on one or both sides in each case, and/or the sheet material is provided with one or more integrated electro-optical and/or acoustic display devices, and/or the sheet material has electrical resistors for defined production of heat, and/or the circuit has a device for producing a load modulation and/or a device for voltage regulation and/or a device for anticollision detection. 159. Sheet material according to at least one of claims 140 to 158, characterized in that upon and/or after emission of a signal which the circuit emits following an external query from the processing apparatus, said circuit changes to an operating state in which it no longer reacts to the query from the processing apparatus. 160. Sheet material according to at least one of claims 140 to 159, characterized in that the sheet material has a variable denomination which is stored in a memory of the sheet material circuit. 161. A method for producing sheet material or an intermediate product for use in the production of sheet material, characterized in that the sheet material is sheet material according to at least one of claims 140 to 160 or an intermediate product, in particular according to at least one of claims 181 to 183. 162. A method according to claim 161, characterized in that a part or the total circuit is incorporated into the paper and/or applied thereto in the course of papermaking and/or subsequently, before and/or in the course of the printing of the paper, e.g. by mixing the circuit into a printing ink, and/or after completion of the printing of the paper. 163. A method according to at least one of claims 161 to 162, characterized in that the sheet material circuit is prepared on or in a transfer element which is applied to or incorporated into the sheet material e.g. by gluing, and the transfer element either remains there after application of the circuit in or to the sheet material as a component of the sheet material or is removed again. 164. A method according to at least one of claims 161 to 163, characterized in that the transfer element, e.g. in the form of a carrier foil, is provided preferentially before mounting of the circuits, with a metallization which is optionally connected electroconductively with the circuit. 165. A method according to at least one of claims 161 to 164, characterized in that the circuit is produced completely or partly by printing technology, such as by means of conducting or conductive polymers or on the basis of thin amorphous or polycrystalline silicon layers (α-Si, p-Si), on a base, such as the sheet material or the transfer element. 166. A method according to at least one of claims 161 to 165, characterized in that the circuit is produced on the basis of a combination of methods of semiconductor technology and polymer electronics, with components that are operated in the high-frequency range preferentially being produced from semiconductor technology, and components that are operated in a low frequency range from polymer electronics. 167. A method according to at least one of claims 161 to 166, characterized in that, when the circuit is produced on a base by printing technology, the base has areas made of different materials which have different affinities to printing inks. 168. A method according to at least one of claims 161 to 167, characterized in that, when the circuit is produced by printing technology on a base, such as the sheet material paper itself or the transfer element, this is smoothed e.g. by means of calendering, by coating or providing a primer coating, before application or incorporation of the circuit, and/or the base of the circuit is embossed e.g. by steel gravure printing. 169. A method according to at least one of claims 161 to 168, characterized in that, after papermaking and/or printing, one or more different individual data, which are characteristic of the particular sheet, are stored in a memory of the circuit. 170. A method according to at least one of claims 161 to 169, characterized in that all single copies of a printed sheet are provided with the circuits one after the other or in one overall step. 171. A method according to at least one of claims 161 to 170, characterized in that the circuits are incorporated into a depression for printing ink on a printing plate by being incorporated into the depression e.g. through an opening of the printing plate. 172. A method according to at least one of claims 161 to 171, characterized in that the circuits are applied to the printed sheets with the help of rolls, such as insertion rolls or press rolls, which are provided from the outside and/or inside with the circuits to be inserted. 173. A method according to at least one of claims 161 to 172, characterized in that the sheet material or the transfer element has one or more depressions into which the circuits and/or their contact surfaces are washed, and/or the circuits and/or their contact surfaces are incorporated into the depressions by the action of vibration. 174. A method according to at least one of claims 161 to 173, characterized in that a magnetic substance having a magnetic permeability, which is significantly greater than the relative permeability of the paper without this magnetic substance is added to the paper during or after papermaking, with the magnetic substance preferentially being incorporated in and/or applied to the paper such that the inductance of a coil as a coupling element of the circuit is increased, and/or the magnetic substance is present in the form of a semifinished product, which is optionally fastened to a transfer element and is provided on the paper or incorporated into the paper, e.g. a depression or a through hole in the paper, either during or after papermaking. 175. A method according to at least one of claims 161 to 174, characterized in that a papermaking screen for producing a paper web from paper pulp or a transport path for transporting a paper web has one or more magnets, which bind an applied magnetic substance in locally limited areas of the paper web. 176. A method according to at least one of claims 161 to 175, characterized in that several coupling elements for the circuit with different coupling frequencies are incorporated into or applied to the paper and/or, when a first antenna coupled directly with the circuit and a second antenna coupled with the first antenna for coupling to an external processing apparatus are incorporated into or applied to the paper, the coupling frequency of the second antenna is selected specifically to the currency and/or denomination. 177. A method according to at least one of claims 161 to 176, characterized in that at least one property, such as a resonant frequency of the circuit of the sheet material, is specifically detuned during papermaking, before, during and/or after printing. 178. A method according to at least one of claims 161 to 177, characterized in that, during production, paper data are coupled with circuit data, and the resulting data are written to a memory of the circuit and/or associated information applied to and/or incorporated into the paper, e.g. printed, and/or paper data written to the memory of the circuit and/or information associated with circuit data applied to and/or incorporated into the paper, e.g. printed. 179. An apparatus for use in the production of sheet material or for use in production of an intermediate product for use in the production of sheet material, characterized in that the apparatus is designed for carrying out the method according to any of claims 161 to 178. 180. An apparatus according to claim 179, characterized by a printer unit having a depression for incorporating printing ink, with said depression preferentially having an opening. 181. An intermediate product, such as a transfer element, for use in production of sheet material according to any of claims 140 to 160, having an electrical circuit on or in the intermediate product, which is to be applied to or incorporated into the sheet material. 182. An intermediate product according to claim 181, characterized in that the intermediate product has one or more depressions for incorporation of the circuit and/or of its contact surfaces, and/or the intermediate product has further visually visible and/or machine detectable security elements. 183. An intermediate product according to claim 181 and/or claim 182, characterized in that the intermediate product, e.g. in the form of a carrier foil, is provided with metallization which is optionally connected electroconductively to the circuit.

The invention relates to sheet material with an electrical circuit and apparatuses and methods for producing and processing such sheet material. Elaborate processing using sensory means is required when processing, such as counting and/or sorting prior art sheet material such as banknotes. It is thus the object of the present invention to specify sheet material with an electrical circuit and apparatuses and methods for producing or processing, as the case may be, same that reduce the expenses and time required to produce or process, as the case may be, the sheet material and/or facilitate and/or improve such production or processing, as the case may be, and/or render same more reliable. This object is solved by the features of the independent claims. The dependent claims describe preferred embodiments. Among other things, the object is thus solved by an apparatus and a method for processing sheet material with at least one electrical circuit, where energy and/or data are transmitted from the apparatus to the electrical circuit and/or from the electrical circuit to the apparatus and at least part of the transmitted energy or data, as the case may be, is used for the processing. A checking device is used for this purpose. Such checking device, hereinafter also referred to as a testing, reading, transmission device or unit, as the case may be, can be designed not only for the transmission of energy and/or data, but rather for the analysis of such data as well. The checking device within the meaning of the present invention can thus be used both for receiving energy and/or data and/or emitting energy and/or data and/or for testing in dependence on the energies or data, as the case may be, that are emitted or received, as the case may be. According to the general definition, the term “data” can refer both to information that, in particular, is transmitted unilaterally or bilaterally between the sheet material circuit and the processing apparatus, i.e. including information e.g. in the form of processing commands or control commands, as the case may be, that specify what is supposed to happen to the other transmitting information. Here, the “energy” serves in particular to enable such data transmission by having the processing apparatus supply the sheet material circuit with energy for example. In this context, the term “electrical circuit” can refer to the circuit itself, i.e., for example, a chip as an integrated circuit, as well as its coupling elements such as its contact surfaces, coupling antennas or coupling photodiodes, etc.. Special embodiments of the invention relate to sheet material with a circuit and one or more transmission devices for transmitting energy for the supplying of voltage into the circuit and/or one or more transmission devices for transmitting data into the circuit and/or one or more transmission devices for transmitting data out of the circuit. Here, it is possible to base each of these transmission units on diverse physical modes of action. For example, galvanic coupling via contacts, coupling by an electric field, coupling by a magnetic field, optical coupling by electromagnetic waves such as coupling by light, coupling by deformation, coupling by electromechanical elements, coupling by sound and coupling by heat can take place alone or in combination. Within the meaning of the present application, light refers to all kinds of electromagnetic radiation, although it preferably refers to visible light, but also refers to UV light, infrared light, radio waves or microwaves. Other methods such as data transmission by means of changing coefficients of optical transmission, reflection and/or absorption such as with so-called electronic paper and/or transmission of the information by load modulation of the energy that is transmitted into the circuit via a transmission device can also be used to transmit data from within the circuit. An embodiment of the invention relates to apparatuses and methods where sheet material with an electrical circuit is made available as a stack and where one or more properties of the sheet material is determined and/or captured by communication between the electrical circuit of the sheet material and the apparatus and/or where information and/or data are transmitted to the electrical circuit by the communication and stored in a memory of a banknote chip, for example. There are the two categories of measurement in stack measurement in particular with one being with a stationary stack and the other one with a moving stack. Here, a “stationary” stack or a “moving” stack, as the case may be, can be understood to refer to the cases where both the stack as a whole is stationary or moving, as the case may be, and/or individual sheets or all of the sheets of the stack are stationary or moving, as the case may be, with reference to one another. Another embodiment of the invention relates to apparatuses and methods for processing, preferably in the stationary state, sheet material having at least one electrical circuit, where an informational exchange between the electrical circuit and the apparatus of the particular sheet material to be separated next occurs prior to separation of such sheet material. The problem of jumbled talk/crosstalk can be solved e.g. by optical enabling. Additional authenticity sensors in the singler make it possible to build banknote processing machines without a measurement path. Moreover, the object is solved by sheet material having an electrical circuit and a transmission device for the transmission of energy and/or data to or from the electrical circuit, as well as apparatuses and methods for this informational exchange. It must also be emphasized that, with reference to banknotes, the sheet material according to the invention refers to both unprinted banknote paper and banknote paper that has already been printed. In another embodiment of the invention, the electrical circuit of the sheet material has at least one memory with a plurality of separate memory areas that are writable and/or readable while the sheet material is in circulation. Furthermore, the invention can provide for particular usage data to be recorded in a memory and/or read from same. Another embodiment of the invention relates to sheet material with an electrical circuit with a memory as well as apparatuses and methods for the exchange of information with the electrical circuit where PKI (Public Key Infrastructure) methods are used to secure the exchange of information and authenticate certain properties (e.g. the nominal value of a banknote). This makes simple realization of the apparatus possible since no security electronics are required. Another preferred embodiment of the invention relates to apparatuses for the exchange of information with an electrical circuit of the sheet material, with the sheet material being transported past the apparatus in order to exchange information and the exchange of information being independent of the transport and the orientation of the sheet material. According to the other main claims, the object is also achieved by containers such as a safe or a cassette or a band for the storage and/or transport of sheet material, an intermediate product, such as a transfer element for use in the production of a sheet material, a method for the production of sheet material or an intermediate product for use in the production of sheet material and by an apparatus for use in the production of sheet material or an intermediate product for use in the production of sheet material. It must be emphasized in particular that the individual features of the dependent claims and the embodiments cited in the description may be used advantageously in combination or also completely or at least partially independently of one another and of the subject matter of the main claims. The invention is described on the basis of exemplary embodiments in the following, which show: FIG. 1 A simplified, schematicized representation of the circulation of money; FIG. 2 An embodiment of the security paper in the form of a banknote according to the invention; FIG. 3 A top view of a further embodiment of the security paper in the form of a banknote according to the invention; FIG. 4 A top view of a further embodiment of the security paper in the form of a banknote according to the invention; FIG. 5 An intaglio printing plate for the incorporation of electrical circuits according to the invention in cross-section; FIG. 6 A cross-section of a document that was printed with a printing plate according to FIG. 5; FIG. 7 A schematic view of a rotary press apparatus with pre-stage and print stage; FIG. 8 An embossed foil for the self-alignment method in cross-section; FIG. 9 A cross-section of an embossed foil according to FIG. 8 with a chip stored in it; FIG. 10 A further embodiment of an embossed foil for the self-alignment method in cross-section; FIG. 11 A schematic top view of the position and location of the contact surfaces of a chip of a banknote; FIG. 12 A further embodiment of the self-alignment method; FIG. 13 A cross-section of an embossing and printing form for the method according to FIG. 12a; FIG. 14 Transfer of a multilayered printed circuit onto a substrate; FIG. 15 A top view of a further embodiment of the security paper according to the invention in the form of a banknote; FIG. 16 A top view of a further embodiment of the security paper according to the invention in the form of a banknote; FIG. 17 A section of a banknote according to FIG. 16 along A-A; FIG. 18 A schematic cross-section through a banknote with a ferromagnetic core; FIG. 19 A schematic cross-section through an apparatus for the creation of locally-defined ferromagnetic areas in a paper web; FIG. 20 A schematic view of a sieve for the creation of locally-defined ferromagnetic areas in a paper web; FIG. 21 A schematic representation of a banknote with a chip and two antennas; FIG. 22 A top view of a further embodiment of the security paper according to the invention in the form of a banknote with coil-on-chip technology; FIG. 23 An embodiment of a banknote with inductive coupling elements and optical coupling elements; FIG. 24 A schematic representation of the functional principle of a photodiode with fluorescent dyes (LISA); FIG. 25 A schematic representation of a banknote with a LISA photodiode; FIG. 26 A schematic representation of a further banknote with a LISA photodiode; FIG. 27 A magnetostrictive-piezoelectric compound material; FIG. 28 A banknote with such a magnetostrictive-piezoelectric compound material; FIG. 29 An equivalent circuit diagram of an electrical oscillating circuit permanently integrated in the banknote paper as an electronic security element; FIG. 30 An initial embodiment of a banknote with a capacitative coupling element; FIG. 31 A second embodiment of a banknote with a capacitative coupling element; FIG. 32 A top view of a further embodiment of the security paper in the form of a banknote according to the invention; FIG. 33 A schematic perspective representation of a portion of the production method of the banknote according to FIG. 22; FIG. 34 An embodiment of a banknote with galvanic contacts; FIG. 35 A further embodiment of a banknote with galvanic contacts; FIG. 36 A block circuit diagram of an inductively coupled transponder consisting of logic portion and HF interface; FIG. 37 A schematic representation of a stack of banknotes with optical energy supply; FIG. 38 A schematic representation of a cassette with a reading device for banknotes with a chip; FIG. 39 An example of a small packet of banknotes enclosed by a band; FIG. 40 A side view of the example depicted in FIG. 39; FIG. 41 A further example of a small packet of banknotes enclosed by a band; FIG. 42 An embodiment of the band holding the small packet of banknotes together; FIG. 43 A side view of the example depicted in FIG. 42; FIG. 44 An example of a stack measuring device with optical communication in top view; FIG. 45 An example of a stack measuring device with optical communication in side view; FIG. 46 An example of a stack measuring device with optical communication and inductive communication in side view; FIG. 47 In schematic view, a reading device for reading out inductively coupled banknotes with magnetic paper in a stack; FIG. 48 An example of a stack measuring device with capacitive communication in side view; FIG. 49 An equivalent circuit diagram of a stack of banknotes according to FIG. 30; FIG. 50 An equivalent circuit diagram of a stack of banknotes modified in comparison with FIG. 30; FIG. 51 A further example of a stack measuring device with capacitive communication in schematic, perspective view; FIG. 52 Two reading devices for banknotes according to FIG. 28; FIG. 53 An alternative to the banknote according to FIG. 27 with part of an associated reading device; FIG. 54 A schematic representation of an example of a check for duplicates with several databases; FIG. 55 A schematic representation of a further example of a check for duplicates with several databases; FIG. 56 A schematic representation of yet another example of a check for duplicates with several databases; FIG. 57 An initial embodiment of a banknote processing machine, for sorting banknotes in particular; FIG. 58 Embodiments of banknotes with an electrical circuit and antenna; FIG. 59 An initial embodiment of a data exchange device for a banknote processing machine according to the invention, for processing banknotes with an electrical circuit; FIG. 60 A second embodiment of a data exchange device for a banknote processing machine according to the invention, for processing banknotes with an electrical circuit; FIG. 61 A third embodiment of a data exchange device for a banknote processing machine according to the invention, for processing banknotes with an electrical circuit; FIG. 62 An embodiment of an input unit for banknotes used with a banknote processing machine according to the invention; FIG. 63 A second embodiment of a banknote processing machine, for counting and/or evaluating banknotes in particular; FIG. 64 A third embodiment of a banknote processing machine, for counting and/or evaluating banknotes in particular; FIG. 65 A schematic representation of an example of a spindle counter for banknotes; FIG. 66 An example of a money-deposit machine; and FIG. 67 A further example of a money depositing machine. Although the present invention relates to sheet material of any kind and can also be used e.g. for sheet-shaped documents of value, such as checks or tickets, it is particularly advantageous for banknotes. That is why the special problems associated with banknotes and the processing of such banknotes are dealt with in particular in the following. The idea according to the invention, as it can be realized in the embodiments referred to in the above and further described in the following, permits substantial improvement and reorganization of procedures in the entire money cycle as well as the banknote processing apparatuses used therein. Therefore, the various embodiments of the invention can best be explained and understood with reference to their particular significance in the money cycle as shown by means of its fundamental characteristics in FIG. 1. The Money Cycle When paper is produced in a paper mill 20, security paper that is suitable for banknotes is produced and provided with security features such as watermarks and/or security threads. The security paper is printed with security ink during subsequent banknote printing at the banknote printing works 21 and provided with additional security features if necessary. After banknote printing 22 and other potential production steps, the banknotes are subjected to quality assurance 23, during which their quality is checked. Faulty banknotes or banknotes that do not meet certain quality standards or only do so partially are generally destroyed immediately by being fed into a destruction device 24, a shredder in particular. The completed and checked banknotes are brought into circulation by a central bank 25, with the bank delivering them to individual commercial banks where the banknotes are either passed on to customers 34 directly at a cash counter 35 at the bank or via a money dispensing machine 27. In shops 30, the individual customers' 34 banknotes presented during payment are placed in a portable cash register 33, or they can be placed into an automatic money input device 32 that checks the banknotes that are deposited, recognizes their particular denominations and totals them if necessary. At least part of the cash obtained is then returned to the commercial banks 26, where it is credited to the particular shop's account 30. The banknotes can be deposited directly at the counter 35 or they can be deposited into a cash deposit machine 28. Combined money depositing and money dispensing machines 29, so-called recyclers, which commercial bank customers can use both for depositing and dispensing cash, are intended for smaller amounts in particular. The banknotes deposited at a commercial bank 26 are generally returned to the central bank 25 where automatic banknote processing machines 31 are used to check them for authenticity and further fitness for circulation in particular, which depends on the banknotes' degree of wear and soiling. Unfit banknotes that are no longer fit for circulation are fed into a destruction device 24, in particular a shredder, whereas banknotes rated authentic and still fit for circulation can be distributed to the commercial banks 26 again and recirculated. In the following, a number of examples are described in-more detail, and the diverse aspects of the present invention are illustrated at different stages of the money cycle by way of example. The production and design of a banknote with an electrical circuit When paper is produced at the paper mill 20 or when banknotes are produced at the banknote printing works 21, the security paper is provided with an electrical circuit e.g. an integrated circuit. When paper is produced at the paper mill 20, the integrated circuit can already be embedded in the security paper or applied to same. At the banknote printing works, the circuit is not applied to the banknote or incorporated into same, as the case may be, until the security paper is processed further. This can preferentially be effected by mixing it in with the printing ink during the printing operation and transferring it onto the document with same. Alternatively, the circuit is prepared on or in a carrier layer that is applied to the banknote or incorporated into same, as the case may be. Likewise, several electrical circuits can be produced both at the paper mill 20 and at the banknote printing works 21, or the production of one or more electrical circuits can be divided up between the paper mill 20 and the banknote printing works 21. Advantageously, the electrical circuit is produced by printing technology on the base layer, i.e. on the security paper or carrier layer, as the case may be, with two of the production steps that are normally performed separately, namely production of the circuit and subsequent application of same onto a base layer, being combined in a single step. Altogether, this procedure significantly reduces production costs. Moreover, the electrical circuit printed on the security paper or the carrier layer, as the case may be, can only be removed from the finished banknote with great difficulty, or potentially only self-destructively, so that any further use for purposes of manipulation is made significantly more difficult or impossible, as the case may be. Advantageously, the position of the electrical circuit varies slightly in every document at least, in banknotes in particular, so that the electrical circuits do not end up lying directly above one other when the documents are stacked, thereby preventing both a thickening of the stack in the region of the electrical circuits, as well as a reciprocal high-frequency-based disturbance of the individual circuits in the stack. The sheet material as security paper according to the invention preferentially consists of paper in the narrower sense, i.e. out of cotton or cellulose fibers. However, it can principally also be produced from any other kind of material containing natural fibers and/or synthetic fibers. Furthermore, the security paper can be comprised of one or more plastic foils that can optionally form a bond with a layer of the security paper consisting of fibers. Here, the electrical circuit within the meaning of the invention can comprise only a single electrical module in the simplest case or a complex electrical circuit, in particular, an integrated circuit, that comprises a few or many electrical modules. All known passive modules such as resistors, capacitors and semiconductor diodes, or active modules such as transistors and thyristors, as well as transducers, such as photodiodes and light-emitting diodes, are principally suitable as electrical modules. Preferentially used integrated circuits, so-called chips, have typical dimensions of less than I millimeter x 1 millimeter at thicknesses of between 20 and 100 microns and exhibit at least one memory for storing data among other things. However, smaller chips with an edge length of 0.3 millimeters and a thickness of less than 20 microns, for example, can also be used. The memories that are typically used can be RAM, ROM, PROM, FRAM, MRAM, EPROM, EEPROM or FIFO memories. Additionally, the circuit can be provided with a processing unit, a microprocessor in particular, for processing data. For certain applications, it is advantageous for the memories in the integrated circuit to be designed as nonvolatile and writable memories, PROM, EPROM and/or EEPROM in particular, with several separate memory areas that are writable during circulation of the banknote. The individual memory areas can be provided with different access privileges for writing and/or reading operations so that certain actions may only be allowed for certain people or devices. At least one memory area can also be configured such that several different groups of persons or entities such as commercial banks 26, money dispensing machines 27, money depositing machines 28, combined input and output machines 29, automatic money input devices 32, cash center and/or individual customers 34, have access to the memory area. Here, the memory in the circuit is segmented such that the individual memory areas remain reserved for the particular groups of persons, even if no data has yet been written to it. The memory of the circuit preferentially comprises an authentication system that contains data on different access authorizations for reading and/or modifying the contents of the memory. Preferentially, information is registered in the memory indicating by whom, when, where or by means of which apparatus or device, as the case may be, data were written into and/or read from the memory. If there is a relatively high risk of the chips being damaged and not functioning as a result during one of the possible incorporation procedures, several chips may also be incorporated. Following completion of the document, the chips may be checked for operability, and surplus chips may be removed or deactivated, as the case may be. If the chips are introduced into the document in an uncontrolled fashion, e.g. if they are added to the paper pulp and each document is equipped with a statistically fluctuating number of chips, the number of chips actually present in the document can be determined and potentially verifiably documented. Finally, stored data and/or the result of the processing of data may be used when the particular security paper's authenticity, life history or intended use is being checked, for example. In this context, the life history may comprise data on production, such as individual production steps, and/or the circulation of the sheet material, data on a prior processing operation, such as prior test results and/or data on a subsequent processing operation, such as on the issuance of the sheet material from the processing apparatus and/or the transport of the sheet material. As the chips used according to the invention are very small, there is a risk of a chip being removed from an authentic document, e.g. by being punched out, and then being inserted into a forged document as an authentic chip. In order to avoid this, it can be expedient to remove individual functions from the chip and to place them on or in the remaining surface of the document in the form of electric components distributed over a large surface. In this case, the total unit, i.e. the circuit plus additional components, preferentially takes up a surface of 5 to 95% of the document, with 50 to 90% or 70 to 90% being particularly preferred. This information can refer to the entire surface of the circuits and/or also e.g. to the size of the region of the banknote surface that is enclosed by the unit such as its coil. Distribution over a large surface has the big advantage that it prevents forged documents made by cutting banknotes up and putting them together again in a slightly shorter form, by e.g. putting 20 original banknotes back together as 21 slightly smaller banknotes. In this context, circuit distribution over a large surface may in principle constitute an operable circuit that can be addressed inductively, capacitively or also by direct contacting. The production of large-surface circuits is facilitated by the fact that, in terms of printing technology, components like transistors, diodes, etc. can also be produced by means of conducting polymers or conductive polymers, as the case may be, or on the basis of thin amorphous or polycrystalline silicon layers (α-Si, p-Si). In principle, it is also conceivable to represent the entire circuit with the aid of conductive polymers. Since the polymers are usually imprinted, it may be necessary to smooth out the rough subsurface of the security paper when the security paper is printed on directly or, as the case may be, when a separately prepared printed circuit is transferred. This can occur by means of calendering, painting or by applying a primer coat on the corresponding surface. However, measures of that kind can also be used advantageously with other embodiments of the document according to the invention. In order to be able to also produce circuits with very fine structures, such as transistor gates, by means of typographical methods, it may be advantageous to suitably engrave the region of the circuits by means of typographical methods such as steel gravure printing. This can either be performed prior to application of the organic polymer components of the circuit (pre-processing) or subsequent to the application (post-processing). With this method, one attains less stringent demands on the precision of the printing process and is thus less dependent on tolerances of the application technology. Likewise, the densely packed circuits of the silicon technology can be divided into functional units and then connected to one another via suitable lines, possibly by including simple logical elements, such as amplifiers, signal shapers or antennas. Here, both the lines and the additional elements may be produced with the aid of polymer technology. Therefore, when using this solution, a fully integrated circuit is no longer designed, but rather functional units with different tasks. Accordingly, a RAM memory element, a CPU element, a ROM memory, driver elements for the peripheral devices, sensory elements for the input of parameters, etc. might each be realized on an individual piece of silicon, for example, and the elements subsequently connected to one another. This method makes it possible to produce standard units that can be combined with another, thereby obviating the costly constant development of new chips. For certain applications, it is advantageous to provide transmission devices such as optical transmission devices, via which data and/or energy can be exchanged with the circuit. Among others, this solution achieves the advantage that an additional or alternative form of transmission besides the typically used transmission of data and energy via high-frequency fields can be created. For example, energy can be supplied via high-frequency fields, while the actual communication, i.e. the exchange of data or information, as the case may be, takes place via the circuit, e.g. by optical means. Concrete examples of the layer structure and the production of documents according to the invention are described in the following. The measures described in individual examples for reasons of clarity can be combined with one another at will. The examples only serve to illustrate particular individual aspects of the invention. EXAMPLE 01 FIG. 2 shows an embodiment of the security paper according to the invention. Parts a) and b) of the figure show sectional views parallel to the plane of the security paper or perpendicular to it, as the case may be, along the A-B line. The security paper, here a banknote 1, is provided with a circuit 3 applied to a carrier layer 10. Circuit 3 - only shown schematically in the form of a square—may be a circuit consisting of discrete modules or an integrated circuit, for example. In both cases provision is made that circuit 3 is addressable from the outside, i.e. information can be transmitted to circuit 3 from the outside or circuit 3 can transmit information to the outside, such as, for example, to a corresponding reader. Transmission devices are provided for such information exchange. In some preferred embodiments, the transmission devices are in the form of antennas, e.g. coils or dipolar antennas, via which energy and/or data may be transmitted. In the example shown, the transmission devices allow optical data transmission. Circuit 3 is equipped with an optical transmitter 4, in particular a light-emitting diode, such as a thin-film light-emitting diode (OLED or the like), and an optical receiver 5, in particular a photodiode, for this purpose. A photodiode element 6 is coupled to optical transmitter 4 or receiver 5, as the case may be, in each case. Photodiode elements 6 direct the light produced by optical transmitter 4 to the edge of banknote 1 or, as the case may be, guide the light irradiated into the area of the edge of banknote 1 to optical receiver 5. The exchange of information e.g. takes place such that the spectral composition of the light that is emitted or received, as the case may be, depends on the data to be transmitted. Preferentially, the time course, in particular pulse duration, pulse magnitude, pulse separation and/or pulse sequence of the light signals emitted or received, as the case may be, may also depend on the data to be transmitted. In the simplest case, transmission devices 4, 5 and 6 only act as an “optical switch” which, upon reception of an external light signal, switches the circuit on or enables it and/or emits a certain light signal for a certain operational state of the circuit. Further details on the possible transmission methods are described in more detail in the following. Suitable glass fibers or plastic fibers that are applied to carrier layer 10 may be used as photodiode elements 6. Alternatively, photodiode elements 6 may also be produced on carrier layer 10 by printing technology in analogy to circuit 3, for example, by applying a suitable transparent plastic by means of a printing method such as screen printing. Optical transmitter 4 or optical receiver 5, as the case may be, may also be produced by printing technology, in particular by using semiconductive and/or light-emitting organic compounds, e.g. corresponding polymers, or by applying thin amorphous or polycrystalline silicon layers (α-Si, p-Si). As may be seen in FIG. 2b, circuit 3 including transmission devices 4, 5 and 6 is applied to carrier layer 10. Application of carrier layer 10 to banknote 1 is preferentially effected by bonding, for which purpose adhesive layer 12 is provided between carrier layer 10 on the one side and banknote 1 on the other side. It is also possible to produce circuit 3 including transmission devices 4, 5 and 6, which are also referred to as coupling devices or coupling elements, as the case may be, directly on a banknote 1 by printing technology or to place same in the banknote 1 between two partial layers (not shown). A cover layer 11 that, in particular, protects circuit 3 against manipulation, moisture and/or soiling may be provided additionally in the area of circuit 3 and/or transmission devices 4, 5 and 6. Cover layer 11 and/or carrier layer 10 are preferentially designed as security elements that produce a desired optical effect. Here, carrier layer 10 or cover layer 11 itself, as the case may be, may even be constructed with several individual layers that, for example, also produce a holographic effect. Photodiode element 6 may also be formed directly by cover layer 11. Alternatively or in addition to the foregoing, carrier layer 10 and/or cover layer 11 contain special pigments that produce an optically variable effect. Liquid crystal pigments or other pigments that, for example, make use of interference effects may preferentially be used for this purpose. In this fashion, additional security features are applied to banknote 1 in addition to the electrical circuit, thereby further improving its resistance to forgery and tampering. As already explained above, an exchange of optical data and/or energy with circuit 3 may be combined with an exchange of data and/or energy via a high-frequency field. In this case, corresponding transmission devices, in particular dipolar antennas or coil-like antennas (not shown) are provided in addition to optical transmission devices 4,to 6. It is also possible to supply circuit 3 with energy by means of photovoltaic devices, in particular one or more solar cells, or paper batteries or piezoelectric elements in or on the banknote paper, which e.g. induce electrical voltage when compressing that may be used to supply energy. This may already be used to operate the circuit through the presence of natural light or artificial light, as the case may be, such that further and potentially expensive apparatuses for supplying energy may be eliminated. EXAMPLE 02 According to a further embodiment, a small, thin chip having an edge, length of approx. 0.3 millimeters and a thickness of less than 80 microns, particularly less than 20 microns, may be arranged on a security thread. Such security thread is, at least partially, completely embedded in the security paper. FIG. 3 shows an embodiment of a banknote wherein the security thread 50 is more or less woven into the security paper and comes directly to the surface of banknote 1 in certain areas called “windows” 5 1. The parts of the security thread that are completely surrounded by security paper are shown by dashed lines in FIG. 3. Here, security thread 50 may have an electroconductive coating that is designed as a dipole and serves in the chip's transmission of energy and/or data. As a security thread of this kind is practically impossible to separate from the security paper without destroying same, the chip is well protected from abusive removal in this embodiment. A further protective effect may be achieved via the information that is stored in the chip. It is therefore advantageous to store a so-called “unique feature” of the particular banknote in the chip's memory area as an identification criterion. In this context, the information is individual and characteristic of the particular banknote. For example, it may constitute the serial number or a parameter derived from same, or it may also constitute the x, y coordinate of the chip in the banknote. As the thread is never embedded at the same place relative to the banknote, the x, y coordinate is a good assignment criterion. Measurement is effected on the finished banknote by means of thread geometry and is stored on the chip in one of the final processing steps. The relation between the chip and the banknote may be structured even more clearly by storing further data such as the serial number in the chip in addition to the x, y coordinate. Additional protection against manipulation or removal of the thread, as the case may be, is provided by measurement and storage of the chip's resonance frequency. Namely, should someone succeed in fully pulling the thread out of the paper, this would lead to a stretching of the thread in any case and thus to an alteration of the resonance frequency. EXAMPLE 03 The chip or the electrical circuit, as the case may be, may also be transferred onto banknote 1 or the security paper, as the case may be, with the help of the transfer method. This type of embodiment is shown in FIG. 4. Here, the transfer element is in the shape of a strip 53 that runs parallel to the short edge of the banknote 1. In top view, one recognizes a metallic surface with recesses 54 in the shape of marks in the example shown. The integrated circuit is contained in the layer structure of this transfer element 53. Special embodiments relating to the foregoing are described in WO 02/02350, to which express reference is hereby made. Here, transfer element 53 must be anchored so well on banknote 1 that security element 53 cannot be torn off across the whole surface. This may, for example, be achieved by having transfer element 53 so thin that mechanical stability is not sufficient to tear it off completely. Further, it must be ensured that penetration of the adhesive into the paper and durability of the adhesive are so good that no mechanical and/or chemical removal is possible. Cross-linking adhesive systems may be used for this purpose, for example. The background may be smoothed by applying a primer to the paper in the area of transfer element 53. In this case, the adhesive to be used for the transfer of transfer element 53 may be selected such that it reacts with the primer, so that chemical protection is effected by the cross-linking. Additionally, the transfer element may be partially provided with intaglio printing, which results in strong local anchoring and deformation of transfer element 53. If an attempt is made to remove transfer element 53 mechanically, rated breakage will result in the area of the intaglio printing. As also shown in the prior example, additional protection may be effected via measurement of the resonance frequency and storage of same in the chip. A resetting by punching out and contacting to a counterfeit coupling surface may thus be demonstrated. Attention is drawn to the fact that transfer elements may refer to both elements such as transfer element 53 according to FIG. 4 described in the above, which serves as a security foil that is permanently affixed to the banknote paper in production, and other elements such as carrier foils 78 according to FIG. 14 that are described in more detail in the following and which are pulled off of the banknote paper after the circuits have been connected with the paper. EXAMPLE 04 FIG. 5 shows a schematic representation of another possibility for incorporating a chip into a document. In this example, the chip is transferred onto the banknote during the printing operation. This may occur both in the prepress stage, i.e. when the paper sheets are on the way to the press cylinder, during the printing operation or also when the printing sheets are being transported away after the printing operation. The basic idea of this procedure is to provide all of the individual copies of a printing sheet with the chips either one after the other or in a complete step. Diverse embodiments that may be used in both sheet feed printing and continuous printing are described in the following. FIG. 5 shows an intaglio printing plate 84 with the usual depressions 85 that the printing ink is filled into in exemplary fashion. One or more of these depressions 85 is formed such that chips 87 may be incorporated into the depression. In the example shown, one of the depressions has an opening 86, through which a chip may be supplied by means of compressed air from the back of the printing plate. This may be effected before or after the depressions 85 are filled with printing ink. Preferentially, the chips are incorporated after the depressions have been filled with printing ink so that the chip comes to lie in the volume of the printing ink and is protected by it. The document material, preferentially paper, is pressed into the depressions 85 during the printing operation and the ink is transferred onto the document as a raised application of ink. The printed document 88 is shown in FIG. 6. Chip 87 may be recognized in ink application 89, which is completely surrounded by printing ink 89. The portrayal in FIG. 5 is only intended to illustrate the basic principle. Additional measures such as the closure of opening 86 during the printing operation, the provision of measures ensuring that precisely one chip is separated in the ink cell of the printing plate each time, cleansing of the printing plate, including the area where the chips are fed, etc. are needed when it is translated into practice. As all of the copies of a printing sheet are to be equipped with chips during the printing process, the feed device is preferentially provided in multiple form, i.e. at least once per individual copy. Chip elements 87 are preferentially provided as transponder chips, i.e. they are equipped with an antenna and all of the functional elements and are fully operable on their own with no additional measures. Prior art transponder chips, for example, already exhibit an edge length of just 0.3 millimeters at a thickness of approx. 50 microns. When the transponders are transferred onto the banknote during the printing operation as described, this process step may be incorporated into the production process very well and, in addition, the chip is optimally camouflaged in the ink and well protected from chemical influences. EXAMPLE 05 With the procedure cited, the possibility to readily arrange the chips in different locations per individual copy in the printing sheet presents itself. If a printing sheet has e.g. 54 individual copies, one obtains a variational potential of 54 different sites for embedding. An additional variational potential results from each additional printing line or additional printing works, as the case may be. This proves to be especially advantageous for currencies that are issued in high piece counts and that are produced on a large number of printing lines and, potentially, at several printing works. For these currencies, the positions where chips 87 are incorporated may be varied so greatly that the likelihood of finding chips 87 arranged directly above one other in a packet of used banknotes is relatively small. Since reciprocal interference of the chips is extremely reduced, banknote packets of this type are distinctly easier to check with respect to individual banknotes 1. EXAMPLE 06 Should the unit price of transponder chips 87 permit, one may also consider embedding more than one chip 87 in a banknote. Then, the particular positions of these chips with reference to one another may also be varied by means of printing plate arrangement, thereby making it possible to switch to the other chips in case two chips should come to lie directly on top of one another or too close to one another. That means that the chips that have the least interference or are arranged most favorably, as the case may be, may always be addressed. EXAMPLE 07 The printing sheets or the particular individual copies of the printing sheets, as the case may be, may now be equipped with chips 87 in highly diverse ways. As described with regard to FIG. 5, one idea consists of incorporating the chips into the printing plate through boreholes. However, this procedure is not just limited to flat printing plates. For example, when using rotary printing, the boreholes may also originate from the interior space of the cylinder, e.g. of the press cylinder, so that the chips may be transferred from the inside of the cylinder to the corresponding depressions. EXAMPLE 08 Furthermore, it is possible to deviate from the procedure already described and already send the individual printing sheets through an insertion apparatus consisting e.g. of two cylinders that already help to affix the chips on the unprinted sheets prior to the actual printing process. FIG. 7 shows an associated rotary printing apparatus 440 from prepress stage 441 and printing stage 442 in exemplary fashion. Insertion cylinders 443 preferentially have the same diameter as press cylinder 444 and counter-pressure cylinder 445. Insertion cylinders 443 have the task of separating chips 3, transferring them to printing sheets 446 and affixing them there by means of an adhesive or the like. Subsequently, printing sheets 446 are transported into the actual printing station 442 and provided with the printed image 447, preferentially with steel gravure printing. In prepress stage 441, chips 3 are to be arranged on the printing sheets 446 such that they may be subsequently superimposed with elements of the printed image 447. In this context, the details of the printed image are to be rendered large enough to ensure that chips 3 are reliably covered with printing ink and that they are not damaged either. The tolerances occurring during printing are to be taken into account for these measures. Separation of chips 3 on cylinders 443 of prepress stage 441 and from these onto printed sheets 446 may either be effected through boreholes in at least one of cylinders 443 from the inside of the cylinder, or it may also be effected by additional elements that are used to apply chips 3 to the surface of the cylinder first and then transmit them to printing sheets 446 while printing sheet 446 is moved through rotating cylinders 443. The application may also be effected by means of e.g. a transfer strip with applied chips that is pressed on the surface of the cylinder for transfer of the chips. EXAMPLE 09 Another possibility results if the press cylinders are supplied with chips from the outside via the insertion cylinder rather than through drilled holes in the press plates from the inside of the press cylinder. In this case, insertion cylinder 443 is arranged at the circumference of press cylinder 444, i.e. in printing step 442 according to FIG. 7, similar to the counter-pressure cylinder or the inking cylinder. It transfers the chips to the areas of the individual copies that are to be equipped with the chips before or after the printing plate has been inked. The final embodiment cited makes use of several advantages of the two methods described previously. Accordingly, the chips are transferred during the printing operation, thereby achieving very effective integration in the production process of the banknotes. With this method, the chips are also positioned in the ink-containing depressions of the printing plate, preferentially in the vicinity of the surface, so that the chips are arranged in the area of the paper surface, i.e. encased in ink and well protected, following transfer to the printing sheet. As singling of the chips from the inside of the press cylinder may be quite problematic from a technical standpoint, transfer via the insertion cylinder from the outside onto the press plate is a good alternative. EXAMPLE 10 For communication with the chips arranged in the document, it is necessary to connect them to suitable contact surfaces. This normally takes place by wirebonding, i.e. the connection is produced via thin wires, preferentially made of gold, or through flip-chip technology, with the contact surfaces of the chip being applied to the external contact surfaces in the opposite fashion and connected by means of, for example, conductive adhesive or isoplanar contacting, so-called “wedge bonding”. The so-called “fluid self assembly” process, e.g. as described in U.S. Pat. No. 6,417,025 or WO 01/33621, where chips are “swept into” small depressions of a foil with the contacts facing upwards, offers an alternative technology. Contacting is subsequently effected on the upper side of the chip by means of lithographic methods. Within the scope of the invention, this technology may be used very advantageously for the production of security threads or transfer elements, as the case may be, for banknotes. However, any other desired foil elements may be equipped with a chip in this way as well. The method according to the invention is explained using the example of the production of a security thread with a chip in the following. First, a carrier foil in endless form is provided with depressions having roughly the same size as the chip to be embedded. A carrier foil 60 is shown schematically in FIG. 8. Here, carrier foil 60 is provided with trapezoidal depressions 61 that are produced by embossing, for example. In this context, depressions 61 are distributed throughout the endless foil such that the desired number of chips is contained in the security element when the foil 60 is divided into individual security elements later on. In the next step, the foil 60 thus prepared is flooded with a liquid containing the chips 62. In this context, the chips 62 are swept into the depressions 61 and self-orient in this way. FIG. 9 shows foil 60 after the chips 62 have been swept in. The chip exhibits contact surfaces 63 that still need to be contacted with the corresponding conductive paths on foil 60 by means of lithographic methods now. However, isoplanar contacting, so-called “wedge bonding”, or contacting via ink jet methods is also feasible. EXAMPLE 11 Instead of the contacting methods normally used for the chip 62 incorporated the way explained above—namely bonding, i.e. soldering/welding of contact wires, and contacting by lithographic methods, another technology can also be used that is likewise based on the principle of self alignment. The method avoids the relatively high demands on exact positioning or the high printing precision, as they are needed in the other methods, since the chips 62 to be used can have edge lengths of down to 1/10 mm. Beyond that, more or less continuous processing of the banknotes that are to be contacted is made possible. For this purpose, foil 60 is provided not only with depressions 61 for chips 62, but additionally with depressions 65 that are indicated by dashed lines in FIG. 10. After that, as already explained, chips 62 are washed in first, and then contact surfaces 64. These contact surfaces 64 preferentially consist of thin metal foils. They guide the small contact surfaces 63 on washed-in chips 62 further outward and act as distinctly larger contact surfaces, the contacting by means of lithographic methods of which does not pose any problems. An especially expedient embodiment of contact surfaces 64 is shown in FIG. 11. They have a relatively thin contact wire 64A, which has a contacting surface 64b on one end, the surface of which is larger compared to contact surfaces 63. Large-surface contacting surface 64b permits low contact resistance to the conductive paths applied by printing, in spite of the relatively poorer conductivity of the conductive printing inks used. In this context, production of the additional depressions does not lead to increased efforts for positioning, since the same tool can be used for the simultaneous production of both the depressions for chips 62 and the depressions for the contact surfaces. To ensure reliable contacting of chips 62 with the contact surfaces 64, contact surfaces 64 can be welded to chip 62 at its contact surfaces 63 with the aid of a laser, or adhesives that become conductive in the direction of the compression only after having been compressed can be used. During preparation of contact surfaces 64, care must be taken that they are formed in such a way that they can, on the one hand, be washed in at every necessary location, but that, on the other hand, no faulty contacting can occur that is caused by contact surfaces 64 washed in wrong orientation. In FIG. 11, possible wrong positions of contact surfaces are indicated by contours 64*. It is expressly noted that this method is not only restricted to the production of foil elements with chips for banknotes, or, as the case may be, to the banknotes having chips themselves, but rather that it can be used with any other desired process wherein chips that are fixed to a substrate must be contacted. This method especially lends itself to all electronic components incorporated into a carrier material by means of self alignment. EXAMPLE 12 As an alternative to or in addition to the method of self alignment by washing in chips and/or contact surfaces, a self alignment method based on vibration can also be used. This means e.g. that foil 60 and/or a storage reservoir of chips 62 and/or contact surfaces 64, where foil 60 is moved past, are vibrated in order to facilitate incorporation into the depressions 61 or 65. This method can also be executed without liquid-based washing in. EXAMPLE 13 In accordance with another variation, before the chips are washed in, a carrier foil used as a transmission element is already provided with a metallization upon which the chips are subsequently applied in a positioned fashion. This method will be explained in more detail with reference to FIG. 12A to 12d. In FIG. 12A, foil 60 with depressions 61 is shown, where a printing ink 66 that is removable by washing has been printed register-containing into depressions 61. Subsequently the entire foil is metallized preferentially by means of the vacuum vapor deposition method. FIG. 12b shows the foil 60 metallized over its entire surface, with metal layer 67 covering both foil 60 and the soluble printing ink 66. Subsequently, the foil is treated for printing ink 66 with a solvent, preferentially water. Thereby, printing ink 66 is dissolved and removed together with the metal layer 67 lying on top of it. In this fashion, a recess 68 is created in metal layer 67, as shown in FIG. 12c. Subsequently, the chips 62 are washed in. In this case, the chips must be designed such that contact surfaces 63 are disposed on the surface of chip 62 that faces metallization 67. Here, the connection between metal layer 67 and the contact surfaces of chip 62 is effected, for example, by means of anisotropically conductive adhesives or so called ACF foils. Here, the dimensioning of printing ink 66 must be selected in such a way that no short circuits between the metallized areas are possible. At the same time, the overlapping surface with the contacts of the chip must be sufficiently large. Apart from the recesses 68 shown in FIG. 12d, further demetallized areas in metal layer 67 can be produced in the same way. These demetallized and therefore transparent areas can, for example, serve as planes of sections and separation of the metallization of the individual threads during further processing. Recesses in the form of signs or any other pattern that serve as an additional visual authenticity feature in connection with the subsequent security element can likewise be produced in this way. Furthermore, metal layer 67 can be structured such that it serves as an antenna for the contactless transmission of data. Likewise, it is possible to connect the ends of metal layer 67 to an antenna structure already existing elsewhere. A special embossing die, with which both the depression 61 and the printing ink 66 are transmitted in one processing step, can be used for the production of depressions 61 and application of soluble printing ink 66. Such an embossing die 70 is shown schematically in FIG. 13. This embossing die 70 has a prominence 71 in the form of depression 61. In the plateau area of this prominence 71, a depression 72 is provided, into which printing ink 66 for the printing and embossing process is brought in. In the example shown, embossing die 70 is shown in the form of an embossing plate. The embossing die can of course also be designed in the form of a cylinder with several embossing dies designed in that way, in order to ensure continuous embossing and printing of foil 60. This embodiment has the advantage that the printing ink can be disposed in the area of depression 61 in a positioned fashion without much effort. EXAMPLE 14 Regardless of whether using the method described above or any other methods for applying the chip, contacting of the small chips used according to the invention poses a considerable problem. One solution to this problem according to the invention is based on the finding that different metals or also oxidic surfaces have different affinities for printing inks. Therefore, contacting occurs by means of fluid, electrically conductive printing inks that wet the contact surfaces, but do not wet noncontacting surfaces and withdraw from them. I.e. if the contacts of the chip, for example, are made from copper, while the remaining surface of the chip, for example, consists of silicon dioxide or aluminum, a suitable printing ink will only wet the copper surfaces, while it does not wet the silicon oxide or the aluminum and will therefore withdraw from this portion of the surface. Numerous possible materials and corresponding printing inks are known from the field of offset-printing, which can also be used with great benefit in the solution according to the invention. Thus, it is achieved that during printing of the conductive paths, there is no need to take account of the register accuracy of the printing with the interruption between the contacts. One can simply print one continuous trace over both contacts. As long as the printing ink is still liquid, it will withdraw from the interruption between the printing inks and produce two paths not connected with each other. This method therefore allows for the contacting of chips without being hindered by the low tolerance for the contacting of the contact surfaces. The necessary register accuracy thus corresponds only to roughly the size of the circuit and therefore only has to be in the order of magnitude of 150 μm or larger. This method can also be applied to chips that have already been fixed on a carrier material. It can, however, also be applied to a semifinished product, the components of which are subsequently transferred to a banknote by a processing step. In this case, by suitable design of the contacts and corresponding selection of the foils and their surface quality, one can even achieve that the printed contacts or, as the case may be, conductive paths are transferred together with the circuits. EXAMPLE 15 In FIG. 14 an embodiment of a document of value according to the invention is shown, wherein the rough surface of the document of value or security paper is smoothed by additional measures. In the example shown, the circuit element 77 is prepared on a separate carrier foil 78. For this purpose, a network of organic conductive material 79, that represents the source and drain electrodes of field effect transistors, is printed onto carrier foil 78 that can have a thickness of 23 μm for example and consists of PET for example. Electrodes 79 are printed on in such a way that they are spaced 20 μm apart. The electrodes can be executed in the form of an interlocked comb-like structure for example. In a second printing operation, a layer of a semiconductive organic material is applied over electrodes 79. It extends over both the electrodes and the intermediate areas as well. An extremely thin continuous insulator layer 81 is applied onto this layer. It has a thickness of 100 nanometers for example and is advantageously produced by means of a curtain coater or by any other suitable method. Finally, a network of gate electrodes 82 which is also produced by printing an organic conductive substance is produced on top of insulator layer 81. This final layer can also be manufactured by vapor deposition of conductive metal layers (e.g. aluminum, copper or similar); the layer can then be structured by means of etching, washing methods or other lithographic methods. The carrier foil 78 thus prepared has a series of field effect transistors that can further be connected to each other by means of suitable conductive paths. Finally, an adhesive layer 83 is applied onto this layer. Here, the adhesive can be comprised of ionomere PE dispersions which should have about 15 grams per square meter in their dry state. In the area of the circuit element 77 to be applied, security paper 75 has a primer coating 76, the extension of which is larger than the circuit element 77 to be transferred. Carrier foil 78 with circuit element layer structure 77 is laid upon this primer coating 76 over adhesive layer 83. Adhesive 83 binds with primer layer 76 by the action of heat. Subsequently, carrier foil 78 is stripped off, as also shown in FIG. 14. The circuit is now fully operable on the paper. When designing the printing cycles, one must consider which side the electrodes should be contacted from. In the method shown, the source and drain are always free on the surface, while the gate electrode lies beneath the circuit. If contacting should be performed from the surface, the semiconductive and insulating layers must be interrupted at the locations of the gate electrode in order to permit contacting. In the case that the circuit element is prepared on the smooth surface of carrier foil 78, it is potentially possible to dispense with primer layer 76 as well, since adhesive layer 83 sufficiently compensates for the surface roughness of the document of value or security paper 75. According to another embodiment, carrier foil 78 can additionally be provided with a separation layer to permit good separation of circuit element 77 from carrier layer 78. This can be comprised of a polyvinyl acetate layer having a thickness of approx. 5 μm for example. Alternatively it is also possible to produce electrodes 79 with the aid of metal layers that can be structured with any suitable methods. This can comprise etching methods, laser ablation methods, washing methods or similar. For example, a printing ink or a brushing paint normally used in paper finishing can be used as primer coating. Inks with high solids content that lead to good filling of the paper pores are suitable. For example, cross-linkable acryl dispersions can be used. After coating, security paper 75 is brought to a roughness of less than 150 milliliter/min (according to the Bendtsen measuring method) on the primer side by means of calendering. According to another embodiment, carrier foil 78 can also be embossed in a first step by means of a suitable embossing die, in order to achieve a sequence of depressions. An embossing die as shown in FIG. 13 can be used for that purpose. Chips with the desired structure are then inserted into these depressions. Subsequently, element layer structure 77 already shown in FIG. 14 is applied onto thus prepared carrier foil 78. Here, the microchips are contacted and connected to the printed circuit. EXAMPLE 16 In FIG. 15, a security element 90 is shown that consists of a plurality of cooperating electrical components. It has a chip 94 that is connected to a diode 93 via a conductive path 95. This in turn is connected with an antenna 92. A high-frequency alternating electric field, which is converted into DC voltage for the energy supply of the chip 94 by means of the diode 93, is fed in via antenna 92. Here, diode 93 can be produced by printing by using a combination of organic semiconductive compounds. In addition, it preferentially has a surface area of approx. 1 to 15 square centimeters, such as 3 centimeters×4 centimeters. Further, a thin-film diode based on α-Si or p-Si is conceivable. A security element 90 of this kind can either be transferred onto the document to be secured via the transfer method or embedded as a foil element between two further document layer materials, for example paper layers. Such a security element has the advantage that it covers a large part of the surface of the document of value and thus cannot be removed without destroying the entire document. According to an alternative embodiment, chip 94 can consist of a plurality of components. In the simplest case, electrical circuit 94 consists of a chip that comprises only a working memory and a CPU, while the second component comprises the ROM memory. The individual components are of course connected with each other via printed conductive paths. This variation has the advantage that standard components can be put together according to the particular application without having to develop a new chip. EXAMPLE 17 Instead of chip 94 shown in FIG. 15, an oscillating circuit consisting e.g. of a large surface transistor, a resistance and a capacitance can also be imprinted. Since the entire security element is produced by printing technology in this case, it can of course also be produced directly on the document. EXAMPLE 18 According to another alternative embodiment, foil 91 shown in FIG. 15 can be a pigmented white foil upon which only a memory is printed by means of semiconductive organic polymers. An information is now applied in customary fashion on top of this memory, possibly after an opaque white or colored intermediate layer. This information can be a portrait, any printed image, logos, signs or for example individualizing numbering. If one tries to alter these data by mechanical or chemical means, the effect of falsifying means will not only change the written content but will also destroy the function of the circuit hidden below. EXAMPLE 19 According to another variation, a circuit is used that receives the energy for the production of the supply voltage for the system and/or information fed in from a transmission device and/or delivers information to the transmission device. For each of these transmissions, the couplings described above can be used, such as coupling by electrical, magnetic, electromagnetic fields or coupling by deformation or, as the case may be, sound. This circuit is executed over a large surface and preferentially consists of organic materials that are e.g. printed on or embedded in the banknote material. The voltage and/or information produced by this circuit can be led directly onto a chip and can be used for the operation of same. The chip itself preferentially does not have any device to produce the supply voltage and/or for direct communication with the transmission device. If the large-surface circuit is damaged by deceitful manipulation, the entire circuit is damaged, to the effect that no supply voltage or information can be fed into the conventional chip or, as the case may be, removed from same, so that the chip is thus no longer able to function. EXAMPLE 20 The electrical circuit shown in FIG. 15 can be designed in such a way that it outputs a signal in response to an external frequency, which signal represents individualizing information of the document. The individualizing information can be recorded in a file on a host computer together with any other data. In this way, when the document is checked, it is possible to fetch not only the individualizing information stored on the document but rather also the information stored in the file of the host computer. EXAMPLE 21 Another embodiment of the document according to the invention is shown in FIGS. 16 and 17. In FIG. 16, a banknote 96 that carries a strip-shaped, optically variable element 97 is shown in a top view. In FIG. 17, this document is shown in cross-section along the line A-A. Here, it becomes clear that a printed electronic circuit 98 is disposed under the optically variable element 97. Optically variable element 97 can be any optically variable element, such as an imprint, a transmission element or also a label. Preferentially, an optical diffraction structure is used. In this case, the optically variable element 97 does not comprise only a single layer, but rather has several layers. In an attempt to remove the optically variable element, for example, in order to reuse it in a deceitful manner, printed circuit 98 is also damaged. Since same is used for machine recognition of authenticity, there is a direct connection between optical recognition and machine recognition of authenticity. Thus it is no longer possible to use optically variable element 97 to pretend authenticity, whereas the remaining document without the optically variable element could still pass the automatic authenticity check in a machine. It goes without saying that this effect can be further reinforced by interrupting the printed circuit at some locations, which are then connected by parts of the metallized hologram. Even if the circuit is not damaged during removal of the hologram, the connection between its parts would, however, be damaged. EXAMPLE 22 A circuit, which outputs a key (signature, serial number or similar) in response to an external field, is printed onto the banknote on 90% of its surface. However, the circuit is executed such that it consists of several parts that are connected by thin conductive connections. If such banknote/document is led through a machine suited for checking, it checks the number emitted by the document. Its agreement with a setpoint decides on the admission of the owner. At the same time, however, one or more of the weak conductive connections are destroyed, e.g. by punching or by an electric shock of sufficient power. With that, the banknote is canceled. It is also possible to store the state of a banknote by providing a plurality of connections to be canceled, which, together with fixed connections (which represent the key), form a partially writeable circuit. This circuit can receive different status values by the connections that can be canceled being changed. This e.g. is also advantageous for tickets that are valid for an event that lasts several days and that can be successively invalidated on a day-by-day basis. EXAMPLE 23 An additional embodiment that is expedient in the production of such a banknote consists in manufacturing and checking the chip and the banknote paper independently of one another and only combining them with one another in a later production step. Thus, the chip or, as the case may be, the chips is/are mounted e.g. on a transfer foil and/or security film of the banknote and can thus already be tested for their functionality before the chips are permanently mounted on the banknote paper, e.g. with the security film. The paper will also have been produced and tested already before connection with the chip. Thus, the print on the banknote will preferentially be applied to the paper before the chips are applied. If the transmitting and/or receiving antennas for the optical and/or inductive and/or capacitive coupling of the chip are also applied to the banknote paper itself, this step can also be executed e.g. before application of the chip. This modular manufacturing method makes it possible not to have to discard the banknote paper e.g. when a chip is defective. This reduces scrap. EXAMPLE 24 It is also possible to apply the chip with suitable electrodes of larger surfaces on a transfer foil, to test the chip there if necessary and subsequently, to connect it conductively on suitably prepared areas of the banknote. This can e.g. occur by means of a conductive adhesive that has been applied to corresponding locations of the banknote or the transfer foil beforehand. The conductive connection is also [made] possible by exerting pressure during subsequent printing processes. EXAMPLE 25 According to another idea of the present invention provision can be made, in particular in the case of an inductive coupling, as will be described in more detail in the following, to equip the paper intended for the production of banknotes 1 having a chip 3 with a magnetic permeability that is significantly greater than the relative permeability of paper. In this way, inductance of the imprinted coil can be significantly increased. For this purpose, soft magnetic materials are preferentially admixed to the banknote paper. According to the invention, this is preferentially effected by adding soft magnetic powder, so-called magnetic powder, to the fiber suspension used in paper production. In this context, the soft magnetic powder can consist of or comprise ferrite powder, amorphous or nanocrystalline metal powder, carbonyl iron powder, or any other powdered magnetic material, which should have highly permeable properties. Another possibility also consists in printing magnetic material onto the surface of the banknote as magnetic ink. Still another possibility consists in impregnating the cotton fibers in a solution that contains magnetic powder with an especially small grain size, so that the soft magnetic material is taken up, i.e. soaked up, by the cotton fibers themselves. Compared to imprinting, this variation has the advantage that a larger share of volume of the magnetic material in the banknote stack can be achieved. Furthermore, the magnetic material, which is normally dark, is advantageously less visible through the differently colored or lighter colored envelope. The magnetic material is preferentially applied to the banknote paper or incorporated in same homogenously and/or over a large surface, in particular over the whole surface. Since, in this case, the incorporated magnetic material does not necessarily serve as a separate security element, but only serves to achieve improved inductive coupling, e.g. a different denomination-specific application is not necessary either. EXAMPLE 26 If the banknote with a chip is to be coupled to the energy supply and/or if the banknote with a chip is to communicate with the reading device via an inductive coupling to an alternating magnetic field, it can be expedient to provide the banknote with a coil having an iron core. As a result, the necessary number of coil turns on the banknote having a chip can be reduced on the one hand and the currents on the exciter side of the transformer for the energy supply are not as high on the other hand, since the relative permeability μr and thus the flux in the magnetic field increases. Possibilities shall now be described for altering the magnetic properties of plastic foils or paper in general and those of banknote paper in particular in such a way that they exhibit behavior similar to that of an iron core. A fundamental problem in the use of iron cores for coils applied to paper that generate or, as the case may be, receive a flow perpendicular to the paper plane consists in the fact that the thickness of the paper is normally small in relation to the coil area. In actual practice, an iron core used in this way will tend to reduce the flow flowing through the coil rather than increase it, since it corresponds to a lying dipole that can easily be magnetized in its longitudinal direction, but is relatively hard to magnetize in a direction perpendicular to the paper plane. One embodiment of the magnetic banknote paper can be achieved by incorporating unordered braids of ferromagnetic materials with long fibers into the paper. In this unordered braid, a large number of fibers will always connect the upper side and the lower side of the banknote paper with one another and thereby achieve a magnetic “short circuit”, i.e. increase the permeability μr to the desired extent. Here, fibers lying crosswise in the plane of the banknote paper do not block the magnetic flow. Accordingly, an especially favorable embodiment of the magnetic banknote paper according to the invention is achieved if the material used as an iron core exhibits magnetic behavior that is dependent on direction. A paper designed in that way can also be used as an independent authenticity feature, besides its expedient use in connection with banknotes having a chip. An associated checking device can e.g. let two magnetic fields that are perpendicular to one other act successively on the paper and measure the magnetic flow flowing through the paper in these two situations. Whereas, for an application of that kind, it appears expedient to place the preferred direction, in which the material can be magnetized more readily, in the paper plane, in the case of application as an iron core for coils mounted on the paper plane, it is also expedient to dispose the preferred direction perpendicular to the coil plane. In the following, the preferred direction is assumed to be perpendicular to the coil plane, if not explicitly stated otherwise. A magnetic paper with directional magnetic behavior can e.g. be produced by embedding ferromagnetic fibers into the paper. If the preferred direction is to lie in the paper plane, the incorporation can be achieved well conventionally by e.g. coating the individual fibers with nonmagnetic materials and then applying them to the screen in paper production. If, however, the preferred direction is to lie perpendicular to the paper plane, it is preferential to incorporate ferromagnetic fibers having a length lying in the order of magnitude of the paper thickness, the diameter of which, however, is significantly less. Individual fibers are then formed, which can readily be magnetized in the direction perpendicular to the paper plane, but which are relatively hard to magnetize in a direction lying in the paper plane. EXAMPLE 27 The incorporation of such fibers in an ordered manner is not conceivable in the conventional manner, since the individual fibers are very thin, to the effect that they are very hard to handle, although, on the other hand, their numbers are extremely high. One possibility for incorporating the fibers consists in performing a machining metal-processing process over the screen in the paper production that produces suitably short shavings that are slung in a defined direction at a very high speed. The removal of iron by means of a grinding tool would be an example. If these shavings are additionally shot onto the paper pulp at suitable locations by means of suitable templates, this results in the possibility of incorporating the special magnetic properties into the paper at the selected locations only. Another possibility for producing paper with the desired magnetic properties consists in producing a suitable semifinished product beforehand, which is then either applied to the screen during paper production or is applied to same or inserted into a hole or into a depression in the banknote only after production of the banknote. EXAMPLE 28 In order to impede forgery, it is especially expedient to apply a so-called patch to the banknote on one or both sides, which protects the desired semifinished product for one and bears additional security features, such as, for example, a hologram, for the other. In connection with the banknote having a chip, this patch can, at the same time, be used to protect the coil, the antenna and the chip applied to the banknote against aggressive environmental influences. FIG. 18 shows in cross-section a banknote 1 having a magnetic core 431 made of ferromagnetic material 436 that has been inserted into a hole 429 of the banknote paper web 430 and is protectedly placed between two patches 432, 433 together with a coil 434. As shown in FIG. 18, it can be advantageous to design the core as thick as the combined thickness of the banknote paper and the applied coil 434. When several of such banknotes are stacked, core 431 effects a significant increase in the magnetic flux through the individual banknotes. The semifinished product described above, which can e.g. comprise core 431 and optionally coil 434 and patch 432, can now be produced in different ways. One possibility, for example, consists in joining longer ferromagnetic fibers in the form of a rope and filling this up and holding it together with a material having properties similar to that of paper pulp, i.e., in particular, it is permeable to water. This rope is then cut, e.g. with a laser, into slices that are somewhat thinner than the banknote. An alternative possibility for the production of such slices consists in the use of several layers of ferromagnetic braids, which are welded one on top of the other in a first processing step and cut into slices in the desired manner in a second processing step. These slices can now either be inserted-into holes 429 in banknote 1, as shown in FIG. 18, or already applied to the screen during paper production. Then, paper pulp will also accumulate on the individual-slices, i.e. the slices are embedded in the paper and can no longer be readily removed from same. EXAMPLE 29 An especially advantageous possibility for the production of paper with the above-described directional magnetic properties consists in using the method of self-organization. For this purpose, use is made of prior art knowledge that individual small ferromagnetic particles align themselves along the magnetic field lines when a sufficiently strong magnetic field is set up. In the same way, the ferromagnetic shavings incorporated into the paper pulp align themselves in a magnetic field acting on the paper pulp as long as the paper pulp is still sufficiently wet and the shavings are still mobile within the paper pulp. In the finished dry state of the banknote paper, the shavings are no longer mobile, so that the desired direction-dependent magnetic properties of the paper have been “learned”. FIG. 19 shows a schematic representation of the expected locally structured alignment of ferromagnetic particles 436 that appears when, by means of a magnet 435, a sufficiently strong magnetic field acts on paper web 430 lying between same. Here it can be especially advantageous if the shavings 436 incorporated into the paper pulp already have a rod-like form and can themselves readily act as magnetic dipoles. Then, a translatory movement of the shavings 436 does not have to occur in the paper pulp in all cases, but rather, it is sufficient for the shavings 436 present in paper 430 to rotate in the suitable direction. The effect occurring here within paper 430 is comparable to that occurring when the Weiss domains reverse in ferromagnetic material: The more shavings 436 have already aligned in a correct, i.e. energetically favorable direction, the greater the magnetic forces acting on the remaining shavings, which force them to align as well, will become. A particular advantage of the method described here for impressing the desired magnetic properties consists in the fact that it is relatively simple to perform this process locally, in which process the property is not only simultaneously applied to the paper, but rather can simultaneously be present in the entire paper layer at the desired location. Thus, it is not possible to readily transfer this property from one piece of paper to another. EXAMPLE 30 Two methods seem to be especially advantageous for application in the production of banknotes, application at the screen itself or after the paper web has left the screen. Potentially, a combination of both methods can also lead to even better embossing. In the application on paper web 430 that is still moist, strong magnets 435, which provide for the magnetization and thus the orientation of particles 436, are mounted above and below paper web 430. Paper web 430 thus only exhibits the desired magnetic properties at locations where magnets 435 are situated. Here, the use of solenoids is especially advantageous, since they can be switched on and off in clocked cycles, thereby permitting zones to be created, which have the desired magnetic properties in an order of magnitude defined in the desired directions. FIG. 20 shows an alternative arrangement, wherein a screen 437 is dipped into a non-depicted container out of paper pulp with sprinkled-in ferrite shavings 436. Magnets 435 are mounted on the inner face of the cylinder wall for the production of locally defined ferromagnetic areas 436 in a paper web 430. For the purpose of simplicity, strong permanent magnets 435 are preferentially used. Application on screen 437 is especially advantageous for several reasons. For one, the ferromagnetic particles 436 sprinkled into the paper preferentially settle at the places in screen 437 where magnets 435 are located, and for the other, shavings 436 are aligned evenly with the deposition. The frequent feeding of energy during paper production in the form of stirring, blowing in of air or similar promotes the efficiency of the settling and aligning process, since it further increases the mobility of the ferromagnetic shavings 436. The paper with the directional magnetic properties produced in this way can also be used to produce the semifinished product described above that is incorporated into the paper pulp or applied to the screen. EXAMPLE 31 The method of self organization can also be used very advantageously for the production of plastics, more specifically for foils with the desired direction-dependent magnetic properties, wherein the plastic goes through the learning process while it is still in a liquid state and is then stimulated to undergo polymerization while the magnetic field is still set up. In the polymerized state, the ferromagnetic shavings are no longer mobile, and the desired property has been remembered. EXAMPLE 32 A further idea for the present invention consists in the coupling frequency for inductive and/or capacitive coupling of an antenna of the banknote, which is coupled to the banknote chip having a value that is different from the banknote chip's own transponder frequency. This is particularly advantageous when each banknote has two different antennas with different resonance behaviors, with one antenna being coupled directly with the chip and the other antenna serving as an external coupling and being able to interact with the chip antenna. FIG. 21 shows an example of an associated banknote 1. In this example, chip 3 is on a security strip, such as a metallized foil strip 295 of banknote 1. Chip 3 is executed as a transponder chip and has a coupling element 296, via which e.g. communication at the frequency of f1=2.45 GHz can take place. Basically, the coupling element could also be realized externally, although the illustrated variant of a transponder with “coil-on-chip” is used particularly preferentially, wherein coupling element 296 is mounted on or, as the case may be, in the chip housing. The metallized foil strip 295 has a circuit unit 297, which is connected with two further coupling elements 298, 299. The transponder chip 3 is disposed in coupling element 299 such that it can communicate with circuit unit 297 via coupling elements 296/299. Furthermore, circuit unit 297 is in a position to communicate with an external apparatus, such as a banknote checker at a frequency of f2=13.56 MHz, via coupling elements 298. The unit consisting of transponder chip 3, circuit unit 297 and foil strip 295 is now structured such that communication is possible between a banknote checker (not shown) and chip 3 via coupling elements 298 and circuit unit 297 as well as coupling elements 299 and 296 at the frequency of f2=13.45 MHz, whereas chip 3 communicates with circuit unit 297 at the frequency of f1=2.45 GHz. Transponder chip 3 with communication frequency f1 is supplied by the chip manufacturer. Foil strip 295 is configured by the system operator or, as the case may be, by the banknote manufacturer. As coupling element 298 defines the communication frequency between the banknote and the checking device, fraudulent use of transponder chip 3 understandably will not be successful, because the checking device does not respond to its frequency. Chips 3 that have been removed from valid banknotes or stolen on the way from the chip manufacturer to the banknote manufacturer can thus not be utilized without elaborate additional measures. If foil 295 is mounted on the banknote surface such that removal without damage is excluded, a valid foil cannot be transferred operatively to other substrates. Further functionalities that are not readily accessible to an outsider, but that can be mandatory for the check, are contained in circuit unit 297, which e.g. can be produced in polymer semiconductor technology. Imitation of a foil element according to the invention or transfer of same to another substrate can thus largely be excluded. Further improvement in forgery-proofness can be achieved if metallized foil 295, on which the coil turn, antenna elements, connecting lines, etc. are “exposed” by etching technology or other means, is additionally equipped with diffractive structures or other feature materials that are not available on the market, but which likewise permit unique identification. By providing two different communication frequencies f1 and f2, the frequency predetermined by the chip manufacturer can thus be redefined. In principle, different frequencies can thus be allocated to different currencies or different denominations of a currency, on the basis of which, of course, automatic differentiation is also possible. If the geometry of coupling element 298 is frequency-dependent, this means that the resonance frequency of the elements can be defined sharply only to a limited extent by simple, printing technology measures. Thus, a deviation within a certain bandwidth must be tolerated in these cases. If, on the other hand, the resonance frequency as well is to be used as an authenticity criterion, it is possible to trim the geometry of coupling elements 298, which for example can be formed as antenna dipoles, to such an extent that the security width is dimensioned extremely narrowly. Trimming procedures of that type are known and are carried out by means of laser technology, for example. As mentioned, the foil element shown in FIG. 21 offers the possibility of addressing a transponder chip 3 that is set to frequency f1, via frequency f2. In case communication by machine with a banknote via frequency f2 is not possible for a banknote, different case scenarios are conceivable in principle, e.g. the transponder chip is defective, there is a defect in one of functional elements 297, 298, 299, the chip or the foil element is completely missing. In order to be able to further limit these possibilities for the checking device, it is conceivable for a second check with a switch to frequency f1 to be connected in series following an initial unsuccessful check of the banknote using frequency f2. If the result of the check is now positive, at least it has been proven that an authentic transponder chip is present. In case the security concept used links the transponder chip to the associated banknote through specific data stored in the chip, in which individual information provided on or in the banknote is stored in the chip (e.g. by additional storage of the serial number printed on same), the authenticity of the banknote can be established by machine nevertheless in case of a positive check of this connection. The first-described banknote check via frequency f2 is certainly that used in more simple checking devices. In case this check produces no result, the authenticity check is normally performed visually, by inspecting the authenticity features intended for the number check, such as intaglio printing, guilloche printing, watermarks, windowed security threads, holograms, etc.. The second check via frequency f2 will certainly only take place in more elaborate checking devices, wherein further authenticity features as well are recorded or, as the case may be, checked by machine anyways. This is the case in every case in automatic banknote sorting or banknote deposit apparatuses. If, as a result of this second check, it becomes possible to query the transponder and if, as a result of the assignment of the memory contents to the banknote serial number (or other individual data), the authenticity is confirmed, the banknote can be destroyed as authentic, but no longer fit for circulation, without manual access. EXAMPLE 33 Provided that the banknote has different coupling frequencies, e.g. by several different antennae being present, as was described above, according to a further variant, these can also be checked by an associated checking device, as described in even more detail by way of example in the following. Thus, for example, it may be that a checking device addresses banknotes 1 on frequencies f1 and/or f2 for purposes of reading and/or writing, in order to, for example, to check the authenticity of the banknote. This can also be used if chip 3 itself of a banknote 1 is directly coupled to two different antennas and if, consequently, the chip can be addressed directly on two different frequencies. EXAMPLE 34 In the above-described banknotes 1 with several antennas, as depicted by way of example in FIG. 21, the following idea is also particularly advantageous. As was mentioned, antenna 296 of chip 3, referred to as internal antenna 296 for short, and antenna 298 can also be coupled contactlessly, such as capacitively and/or inductively, for external coupling, referred to a external antenna 298 for short. In this case in particular, several external antennas 298 of that type can also be present on the banknote paper of each individual banknote 1 and preferentially be disposed spaced-apart on the paper. This variant has the advantage, that even when part of the external antennas 298 of a banknote 1 fail, chip 3 can still be addressed from externally. Moreover, in stacking measurements, as they are described in even more detail in the following, the particular advantage results, that if antennas of individual banknotes fail, functioning external antennas of adjacent banknotes can take over the task of the antennas that have failed, since communication with chip 3, i.e. with its internal antenna 296, takes place contactlessly here. This is also advantageous, should only one antenna be present on the banknote for contactless coupling to chip 3. EXAMPLE 35 In the following, an example is described for a banknote, the chip of which can be coupled contactlessly. As has already been mentioned, a transponder circuit of a banknote can have a transponder chip and a coupling coil, which acts as an antenna and via which the electrical energy from the field of a reading device can be coupled into the chip of the banknote or, as the case may be, data can be transmitted bidirectionally or unidirectionally. The term contactless connection is understood to mean that the chip of the banknote can be coupled contactlessly to the antenna of the banknote that is responsible for energy and/or data transmission to an external (reading) device. Now, it proves to be very advantageous, within the scope of the present invention, to use so called transponders with coil-on-chip, where e.g. galvanically deposited antenna coils are applied to the chip itself. A particularly preferred example of this has already been described in detail in connection with FIG. 21. The coil-on-chip coil will preferentially communicate contactlessly with the coupling coil of the banknote. This significantly reduces the requirements for register accuracy of the incorporation or, as the case may be, application of the coupling coil on or, as the case may be, in the banknote. In addition, the production throughput can e.g. be significantly increased compared to contact-type contactings, such as wire bonding, wedge bonding or flip-chip bonding. FIG. 22 shows a further example of such a banknote 1. This [banknote] shows a coupling coil 410 that is disposed as dipole antenna 410, by way of example, although, of course, other forms of antennas as well are conceivable. This dipole antenna 410 can withdraw electrical energy from the field of an external nondepicted reading device through inductive coupling. Through this, voltage is produced in dipole antenna 410, which in turn irradiates an electromagnetic field itself. As an example, a further transmitter 411 can also be mounted on or, as the case may be, in dipole antenna 410, the energy supply of which is ensured by dipole antenna 410. As already mentioned in another example above, transmitter 411 can e.g. also irradiate at another frequency f2 in this case. However, this is not mandatory, since, for example, time scaling, which permits sequential radiation, can also be introduced. Furthermore, on banknote 1 is located a chip 3, on which a further coupling antenna 412 is mounted, by way of example, in the form of coil 412 as a coil-on-coil chip. This chip 3 then communicates advantageously with coupling antenna 410, which itself in turn then exchanges data and/or energy with the external reading device. It hereby becomes possible to achieve that data transmission and the Chip 3's supplying of voltage do not take place by means of galvanic contacts. EXAMPLE 36 As already mentioned, the electrical circuits need not necessarily have a rewritable memory. Provided that it is desired to provide an “anonymous” banknote, wherein no data can be stored, which provides information about the current or previous owners of the banknote, the banknote's chip will not be made rewritable. This occurs by providing possibilities in the chip that prevent data from being written into the memory area as of a point in time in the banknote's life history. A suitable point in time can be completion of the banknote at the manufacturer's. The time of issue at the state central banks' e.g. is equally conceivable. To serve this purpose, it is important that no personal data of the end user be able to be stored in the chip's memory during circulation of the banknote. Technically, this task can be solved in different ways, e.g. by providing data lines in the chip, which can be interrupted deliberately at the selected time, so that, although the memory contents can still be read, it will no longer be possible to “write” into the memory cells (hardware inhibit). The same result can be achieved by placing an inhibit bit in the chip operating unit that prevents write access as of this point in time (software inhibit). It is plausible, that a memory inhibited by a hardware inhibit or software inhibit can be supplemented by another memory that can be furnished with data during circulation of the banknote. It is important that such a memory can both be read and deleted or overwritten by the end user. The memory areas associated with “transparent banknotes” can by definition only be used by authorized positions, i.e. these write/ read operations can not be used by the end user. The write locks mentioned at the onset are provided to avoid the problems resulting therefrom. In case doubts arise that a banknote with a chip, wherein the official memory exhibits a write disable during circulation of the banknote, is even expedient, these can be countered by pointing out that the data pertaining to the manufacturing process, i.e. the banknote's serial number as well as information on currency, denomination, date of manufacture, manufacturer, etc. are already very valuable for general statistical inquiries for the system operators, in particular the national banks. Personal data going beyond that are not necessary for system support. The “anonymity” of a banknote, though, can not just be disturbed by the recording of personal data. The possibility, as well, of being able to determine the possession of such banknotes without the consent of the particular holder of the banknote can already massively disturb the end user's interests. Imagine that the existence of a banknote can be detected at a greater distance via “direction-finding transmitters”. This would not only give pickpockets an excellent “working aid”. Thus, if one wishes to also prevent bearings to be determined for banknotes from a larger distance, one must make sure that the range of the transponder's transmitting unit is selected through skilled selection of the system parameters such that it is smaller than would be necessary for purposes of determining bearing. In passive radio frequency transponders (RFID), which gain their transmitting energy from the energy received, the transponder's transmitting power, and thus the transponder's range as well, can thus be increased via an increase in the transmitting power of the checking device. In order to not exceed the desired range of the transponder chip, measures can be provided in the transponder, through which the transponder's transmitting power is deliberately limited. It is also possible to alternatively or additionally adjust the range as desired through skillful selection of the transmitting frequency (gigahertz range) or, also, through specific designing of the coupling elements. In this spirit, it can also be necessary to provide capacitive coupling elements or other coupling elements, which only allow communication upon direct contact, instead of dipole antennas or oscillating circuit coils. If a banknote with a chip must be such that its bearings can not be determined, a maximum range of a few cm, preferentially of a few mm, of the Chip's RFID transmitter appears expedient. For certain applications, it can also be advantageous to provide transmission apparatuses, via which data and/or energy can be exchanged with the circuit, with the transmission occurring by optical means. Through this, one can achieve, among others, the advantage that an additional or alternative type of transmission is created besides the transmission of data and energy that typically takes place via high-frequency fields. For example, the supply of energy can then be effected via high-frequency fields, while the actual communication, i.e. the exchange of data or, as the case may be, information, with the circuit, takes place by optical means. Understandably, a communication performed by this means is extremely dependent on optimal boundary conditions. A determination of bearings or, as the case may be, unintentional monitoring must be fully excluded in this context. EXAMPLE 37 A further example for producing a banknote 1 with optical coupling is shown in FIG. 23. Such a banknote 1 can transmit data from its chip 3 to an external reading device via optical photodiodes 226a, 227a. In this context, photodiodes 226a, 227a can have e.g. exhibit a transparent light-conducting plastic, such as polycarbonate (PC) or polymethylmethacrylate (PMMA), or consist of same. To improve coupling in and relaying of an optical signal produced by chip 3, according to the invention, a product can be used that contains fluorescent dyes. Such materials are based e.g. on cumarin compounds or perylene compounds and are known as LISA (light collecting) plastics and are described e.g. in DE 40 29 167 A1. Within the meaning of the present invention, a dyed light-collecting and light-conducting polycarbonate-based foil, for example, is a LISA plastic of the kind referred to. The foil contains fluorescent dyes, which convert the light falling in into light of a longer wavelength. Although attention is especially given to the preferred variant with fluorescent dyes, phosphorescent dyes are also conceivable as an alternative. The major part of the light is reflected within the foil in accordance with the laws of reflection (total reflection) and exits again only through the edges. That is why foils made of LISA distinguish themselves by clearly visible lightness of edges. FIG. 24 shows the functional principle of this kind of photodiode made of LISA plastic. Photodiode 284, which is available in the form of a LISA foil 284 by way of example, has dye molecules 286 inside, which can be present in all or just a part of its volume. Irradiation of light from a light source 287 causes the dye molecules 286 to be stimulated to emit fluorescent radiation 288, a large share of which exits from photodiode 284 at lateral edge 289 after total reflection on the photodiode wall 285. Total reflection always occurs at the transition of LISA to air, when the sine of the angle of incidence is greater than the quotient 1/n, with n being the refractive index of the LISA plastic and nair being equal to 1. The total reflection can be unfavorable when the surface of the light conducting element is scratched or moistened with liquids. In the first case, part of the light present in LISA foil 284 will exit at many scratched places, thereby reducing the efficiency of the radiation at the desired edges of the foil. Therefore, if necessary, it can be advantageous to produce LISA foil 284 from several, particularly preferentially from at least three or precisely three partial layers having different refractive indexes. In this context, materials with high refractive indexes are used inside, and these are covered on top and below by a foil having a low refractive index Due to the different refractive indexes, part of the total reflection already occurs in the spacer between the two optical media inside the foil. Only the share that is not reflected by the inner layer transition reaches the outer layer transition and can likewise be reflected there, if the critical angle is exceeded. In this context, the critical angle calculated back to the inner layer transition is as large at the transition of the outer foil layer as the direct critical angle at the transition of the denser medium to the ambient air. The advantage of this variant has an effect when a surface is scratched and roughened. These significantly worsen the share of total reflection. However, since only a small share of maximum approx. 25% of the light rays produced in LISA foil 284 are reflected at the outer boundary surface, the foil's efficiency rises on the whole. The whole foil e.g. can first be manufactured with a greater thickness and brought to the desired thickness through stretching if direct manufacture becomes problematic. Further, it can be advantageous, if the LISA foil 284 is provided with a reflecting coating 290 on one side or both sides. In the second-cited case, the LISA foil 284 will, however, preferentially have a recess in the area of the LED to allow the irradiation of the stimulating light to enter. To increase efficiency, depicted photodiode 284 thus specifically has e.g. reflecting backside metallization 290 in the area of irradiation as a minimum. The use of several layers with different refractive indexes also offers advantages with reference to LISA foils that are metallized for the purpose of improved light utilization on the outer side. For one, the total reflection is better in terms of efficiency than the reflection on a metallized surface, for the other, scratches on metal surface 290 only affect the efficiency of LISA foil 284 to a slight degree for the same reasons as those described above. Technically, foils 284 of this type can be produced through extrusion methods or calendering methods, with the LISA dye being added at the e required concentration. In order to ensure that banknote 1 can also still communicate via photodiode 226a, 227, the plastics should be correspondingly provided with additives. For example, the plasticizer content of the foil can be increased such that the foil becomes less sensitive to banknote 1 being crumpled up by the user. An additional reflective layer can be created by incorporating and/or applying metallic layers, e.g. metallic foils. If this layer or other layers are e.g. so-called shape memory alloys, then, as a result of the memory effect, the possibility of freeing the plastic foil from deformations caused by use by means of short-term temperature increases to e.g. approx. 80° C. shall continue to exist. Polymers exhibiting the so-called shape memory effect can also be used for this purpose. It is particularly advantageous when foils that exhibit this effect are additionally provided with LISA dye. The surface of the foils should be sufficiently smooth so as to minimize scattering loss. Further, the thickness of the foil is to be adjusted to the manufacture and thickness of banknote 1. Normally, foil thicknesses of less than 50 μm are used. The LISA pigment can not just be integrated in the banknote in the form of a dyed foil, but rather, it is also possible to coat and/or print on undyed foils, such as PET foils, with LISA lacquers. It is particularly advantageous, when the security thread present in the banknote and/or another foil to be incorporated in or applied to the banknote is printed on with LISA lacquer. Application of the lacquer to the foil can also occur by using knife-coating or spin coating on individual parts of the foil. EXAMPLE 38 As shown in FIG. 25, according to one embodiment, a LISA photodiode 227′ of this type is irradiated in a banknote, analogously to photodiode 284 according to FIG. 24, by a light source present on Chip 3, such as a light-emitting diode (LED) 235. In this context, the wavelength produced by light-emitting diode 235 of the light is preferentially selected such that it corresponds to the absorption maximums of the plastic used, i.e. to the fluorescent dyes contained therein. In this context, in accordance with the representation of FIG. 25, the light exit opening of light-emitting diode 235 can be mounted on the upper side or, as the case may be, on the underside of Chip 3, but also on the narrow side of Chip 3. In order to achieve optimal light coupling, photodiode 227′ is led past light diode 235. Thus, there is a significant difference between the photodiode variant according to FIG. 25 compared to those of FIGS. 44, 45 and 23, 46, consisting in that there is not a plurality of individual photodiodes or, as the case may be, photodiode sections 226, 227, 226a, 227a, but rather, that there is only a single photodiode 227′, which preferentially extends from an edge. 289 to an opposing edge 290 of banknote 1. As a result, a large tolerance window with reference to the positioning accuracy of Chip 3 results from this arrangement according to FIG. 25, since light-emitting diode 235 merely has to be positioned within the width of the photodiode 227′ that is used. Moreover, an essential advantage of using LISA foils compared to conventional photodiodes consists in that no in-phase coupling of the light from light-emitting diode 235 into photodiode 227′ is necessary, since this is a process wherein the irradiated light is merely frequency-shifted with reference to the emitted light through the absorption by the LISA molecules. It is possible for the LISA pigments to be distributed homogeneously in the photodiode. In the variants indicated, in order to achieve the highest possible efficiency, it is will be advantageous if LED 235 is mounted over an area of photodiode 227′, which contains a higher concentration of LISA pigments. This can e.g. be translated into practice through layers of varying thickness of the LISA foil or, as the case may of the LISA lacquer or through generation of a concentration gradient of the LISA pigments within the LISA foil or, as the case may be, of the LISA lacquer. Another possibility consists in the use of a laser diode as light source 235, with e.g. an organic thin-film laser diode being particularly advantageous. In this context, a higher intensity of light is achieved, than is possible when using a conventional LED. Likewise, the use of two-dimensional LEDs is preferred, which e.g. are produced by means of thin-film technology, such as vacuum deposition, etc. To this end, e.g. LEDs with a perpendicular aperture or, as the case may be, with a square aperture can be used. This can lead to better luminous efficiency compared to point-shaped emitting LEDs. EXAMPLE 39 Another even more efficient possibility for generating light is shown in FIG. 26. In this context, a luminous surface 291 is used to generate a primary optical signal. This luminous surface 291 can e.g. be a coating. In this context, it is e.g. an organic LED (=OLED), which preferentially can be printed on, or have electroluminescent inorganic substances such as doped transition metal chalconides (sulfides such as ZnS, CdS, etc.). By applying photodiode 227′ to luminous surface 291. the optical signal, which is primarily being irradiated perpendicular to the surface of luminous surface 291, can be directed at edges 289, 290 of banknote 1 for radiation. The emission wave length of luminous surface 291 and the absorption wave length of fluorescent dye molecules 286 is adapted to an absorption maximum of the dye molecules, so that the fluorescent luminous intensity preferentially corresponds to a maximum of the dye molecules. EXAMPLE 40 In a further development that offers particular advantages in the processing of stacked banknotes, as will be described in the following, a piezoelectrical element, which is likewise a component of the banknote, is provided for the supply of an electrical circuit of a banknote. In this context, it can be a piezoelectric monocrystal (e.g. BaTiO3, PbTiO3), a piezoelectric foil (e.g. polyvinylidene fluoride—PVDF) or any other piezoelectric material (e.g. copolymer transducer of trifluoroethylene). If, for example, the piezoelectric element is present as a foil of piezoelectric material, it can e.g. be constructed as a security thread, OVD foil (optically variable element), etc.. However, it can also be a component of a compound material consisting of a foil and paper or of several foils. The two sides of the foil are at least partially vacuum metallized for the formation of electrodes. If one applies voltage to the two metallic electrodes, the thread bends itself in the rhythm of the electrical voltage. As described in greater detail in the following, for decoupling of the energy supply and response of the piezo foil, an integrated circuit in the vicinity of the foil or preferentially on the foil itself can be used, which [circuit] is conductively connected to the electrodes of the piezo foil. In one advantageous embodiment of a banknote, provision is made to mount the circuits between two uninterrupted, vacuum metallized piezo foils such that the two piezo foils are brought into association with the contacts of the electrical circuit. This can occur through a particular design of the metal layers, e.g. through use of the so-called “clear text” method. When a conductive laminated adhesive is used, it is possible to bring the contacts, which as a rule lie on one side of the electrical circuit, into contact with the two metallized piezo foils. Other similar embodiments are conceivable. In case, for example, there is an electrical circuit is available, which exhibits contacts on different sides. Through corresponding structuring of the metal layers, electrical circuits with more than two contacts can also be used. EXAMPLE 41 The electrical circuit can be operated by means of irradiated energy in the form of ultrasound, with electrical voltage being generated that is also used—potentially after temporary storage—to operate the piezo foil and optionally to communicate with a reading device. However, the circuit can also be supplied with energy by means of a photo cell and irradiated light, with electrical voltage being generated, which—potentially after intermediate storage—is also used to operate the electric circuit and the piezo foil and optionally to communication with a reading device. The electrical circuit can also be operated through the introduction of deformational work on the banknote, i.e. e.g. of elements with a piezoelectrical effect. The energy brought in can then be used—potentially after temporary storage—to operate the chip situated on the banknote and potentially to operate communication with the reading device. Precisely in conjunction with a display or an optical out-coupling of information out of the banknotes in the range of visible light, the use of deformational energy results in the advantage that even the normal user of the banknote sees a security feature in the chip of the banknote that he can discern. Slight crimping of the banknote then e.g. leads to light effects on the LISA strip[,] the blinking of LEDs or a display on the display of the banknote. EXAMPLE 42 One further idea of the present invention consists in using the magnetostrictive effect in place of the effect of magnetic induction. As is known, when a ferromagnetic crystal is magnetized a change in shape of the magnetic crystal then appears as field strength increases. This phenomenon is known as the magnetostrictive effect. The Joule effect is the most important component of magnetostriction. It is based on the fact that the so-called Weiss regions rotate in the direction of magnetization and displace their boundaries. Through this, a change in shape of the ferromagnetic core occurs, with its volume remaining constant. The magnetostrictive effect, which causes expansions in the range of 10 to 30 μm/m in the case of alloys with the components of iron, nickel or cobalt, achieves values of up to 2000 μm/m in highly magnetostrictive materials of rare-earth metal-iron alloys. Thus, the compound Tb0,3Dy0,7Fe2, which is also known as Terfenol-D©, has an energy density that is many times higher than piezoelectrical materials. Aside from metals and their alloys, molecular magnets also possess magnetostrictive properties. Molecular magnets are understood to mean larger molecules or clusters, the magnetic properties of which are determined by the coupling of metal ions usually, which [coupling] is anti-ferromagnetic as a rule. The best known representative of the magnetic clusters, which demonstrate macroscopic quanta tunneling in magnetization, is [Mn12O12(CH3COO)16(H2O)4].2CH3COOH.4H2O (abbreviated as Mn12—acetate or simply Mn12), which is of mixed valence. As described above, a magnetostrictive material experiences a longitudinal change in length upon application of a magnetic field, i.e. the direction of field and the direction of expansion run parallel. A similar effect is also known for piezoelectrical materials. When an electrical field is applied, it effects a longitudinal or also transversal change in the spatial expansion of the lattice structure. In particular, it is also known that the piezoelectric effect can be reversed, i.e. in the case of the reciprocal piezoelectric effect, an electrical voltage that can be captured can be generated on the surface through expansion or bending of a piezoelectric material. In this context, the amounts of energy that can be generated by means of a piezoelectric material can be sufficient for the operation of a chip. EXAMPLE 43 Although not limited to this, FIG. 27 shows an exemplary embodiment where a piezoelectric material is used, too, in addition to a magnetostrictive material. The materials are integrated into a composite 360 for the generation of an electrical supply voltage from a magnetic field. Here, a layer of magnetostrictive material 361 is coated with a layer of piezoelectrical material 362, which e.g. is applied in the form of a strip onto a banknote paper. An alternating magnetic field 363 flowing through the magnetostrictive material 361 causes a periodic change in length dL of the composite material 360, with the frequency of the change in length dL corresponds to the frequency of the alternating magnetic field. Preferentially, for the construction of the composite material 360, a magnetostrictive material 361 with longitudinal sensitivity is preferred, in the case of which there is a change in length parallel to the applied magnetic field, which [change], in particular, is greater than the one in the direction perpendicular to it should be. In addition, a piezoelectrical material with a lateral sensitivity is preferred, in the case of which the tapped voltage at right angles to the change in length is particularly preferentially greater than that in the direction perpendicular thereto. The electrical voltage evoked through the periodic change in length of composite 360 in piezoelectrical material 362 can be tapped at electrodes 364 at the surface of the material, which are mounted on the material. Although a separate electrode layer is also conceivable as a counterelectrode, the magnetostrictive material 361 will preferentially be used as the counterelectrode, provided this [material] exhibits sufficient electrical conductivity, like e.g. that associated with nanocrystalline metal or, as the case may be, amorphous metal. The voltage captured by means of electrodes 364 or, as the case may be, 361 can then be tapped at connections 365. In the case of use in a banknote, connections 365 will consequently be electrically connected with chip 3 of a banknote 1. The construction of the material composite according to the invention thus serves to generate an electrical alternating current, proportional to an externally applied alternating magnetic field, under avoidance of electrical conduction by means of a coil. EXAMPLE 44 FIG. 28 shows a further example where a magnetostrictive-piezoelectrical compound material 360, corresponding e.g. to that of FIG. 27, is in turn integrated in a banknote 1 and connected, in this context, with chip 3 of banknote 1 via lines 366. Here, a preferred variation is depicted, where a strip of a LISA foil 227′ can likewise be present besides magnetostrictive-piezoelectrical strip 360, as will be explained in detail within the scope of this invention. In a particularly preferred manner, there can be a single strip that comprises both LISA foil 227 as well as compound material 360 and e.g. is applied onto the banknote paper as a prefabricated unit. EXAMPLE 45 In this context, it can also already be expedient to provide an electronic security feature without the use of a chip or any other storage element for the storage of data. By dispensing with such storage elements, an associated banknote can be manufactured particularly simply and inexpensively. A further possible variation consists in the design of an electrical oscillating circuit in or, as the case may be, on the banknote paper. FIG. 29 shows an equivalent circuit diagram of such a simply-constructed electronic security feature in idealized form, where an optional optical display is also present additionally. In this context, oscillating circuit 230 specifically exhibits an inductance 231 and a capacitance 232 and is preferentially connected with a rectifying element 233 and an electrooptical reproduction device, such as an emitting diode LED or OLED 234. In principle, the equivalent circuit diagram can also exhibit still further components. A banknote with such an equivalent circuit diagram can be manufactured as was described previously in the section “Banknote with an electrical circuit”. Preferentially, the electronic components are applied to the banknote paper as a substrate typographically, such as through screen printing, ink jet printing or engraved printing by means of silver conductive paste, graphite paints or conductive polymers. Alternatively, vacuum metallized foil elements can also be used. The inductance 231 e.g. is applied onto the paper in the form of a conductor loop and the capacitance 232 is applied in the form of an electrically-conducting surface. The capacitance 232 can thus be adjusted to a predetermined value during fabrication such that a conductive surface is likewise imprinted onto the other side of the banknote paper or a metallic layer, e.g. in the form of a strip or a label form, is applied to it. Rectifying element 233 and LED 234 are likewise preferentially realized on the banknote paper typographically, in particular on the basis of semi-conductive polymers. Alternatively, Si- and/or III/V-semiconductor-thin-layer technology can also be used for the generation of the components. A different display can also be realized in place of an LED. If a banknote equipped with an integrated oscillating circuit in this manner is brought into an electronic alternating field, preferentially in the radio frequency range, such as particularly preferentially e.g. 125 KHz or 13.56 MHz, emitting diode 234 is stimulated to illuminate in the visible spectral range by the energy absorbed in the oscillating circuit. This represents an authenticity feature with a very high rate of tamperproofness. The transmitter for the radio frequency field can be realized simply and inexpensively and e.g. integrated into a manual device or tabletop device, such as a register, for the testing of bank notes. Preferentially, the performance of the transmitter is dimensioned such that it can still stimulate banknotes to illuminate within a coverage range of some 10 to 30 cm. EXAMPLE 46 FIG. 23 shows a further example of a banknote 1 according to the invention. It is distinguished in that it exhibits both an optical as well as an inductive coupling device. Specifically, chip 3, or a separate region of the banknote 1 connected to it, exhibits a device for sending out an optical signal, such as an LED 235. The optical signal can be led via one or more photodiode sections 226a and 227a, to the outside edge of banknote 1 and out-coupled there. Further, banknote 1 also has an inductive coupling device 250 in the form of a coil 250. Coil 250 is connected with chip 3, and in this context, the banknote is designed as a noncontacting RFID Transponder. Alternatively, banknote 1 can also exhibit a capacitive coupling device in place of or in addition to the inductive one, as will be described in the following by way of example. In that an inductive and/or capacitive coupling is also possible in addition to the optical coupling in the case of an individual banknote 1, measurements in a stack can be conducted significantly more reliably, as is described in more detail in the section “Stack measurement”. In addition to the inductively coupled transponders, as were described by way of example with reference to FIG. 23 in connection with an optical coupling, banknotes with a capacitively coupled transponders are also conceivable. EXAMPLE 47 The preferential construction of such a banknote 1 is depicted in FIG. 30. Here, chip 3 is conductively connected with two large-surfaced, conductive capacitive coupling surfaces 256 as electrodes 256 via two lines 255. The surface of capacitive coupling surfaces 256 is an important factor for the functional capability of capacitively coupled transponders in a stack. Coupling surfaces 256 can in fact also be integrated in the paper during paper manufacture, but they are preferentially applied onto the banknote paper. One manufacturing option, which is also of particular advantage in the manufacture of banknotes, consists in the printing technology application of such conductive surfaces 256. In this context, they can be applied over the entire surface of the carrier medium, in this case the banknote paper. They will at least take up at least 50% share of surface, preferentially at least 70% share of surface of a banknote side. As will be described more precisely, this has the advantage that the individual surfaces always overlap to form a capacitance arrangement, even in the case of a stack of banknotes with different dimensions, e.g. correspondingly different denominations. E.g. conductive lacquers, which are advantageously largely invisible visually, can be used as printing ink. Coupling surfaces 256 of graphite materials, which can likewise be applied typographically, are also conceivable as an alternative to this—at least in the case of small shares of surface. EXAMPLE 48 FIG. 31 shows a second example of a banknote 1 with a capacitively coupled transponder. In analogy to FIG. 46, it has two conductive layers 256 as capacitive coupling surfaces 256. By way of example, the banknote exhibits a hologram strip 258 with a metallic reflecting layer 257. The reflecting layer exhibits two areas 257a, 257b that are spaced-apart and galvanically decoupled from one another. Transponder chip 3, which is electrically connected with the two areas 257a, 257b via electrical lines 255, is affixed in the space between them. In certain cases in the manufacture of banknotes, metallic layers 257, such as the exemplary hologram strip 258 with metallic reflecting layer 257 in the present case, can be applied onto the banknote paper through a transfer method. It is now possible to conductively connect chip 3 with metallic layer 257 of such a hologram strip 258 in a separate working step prior to application onto the banknote paper. Here, areas 257a, 257b of metallic layer 257 are connected with chip 3 via electrical lines 255. Coupling surfaces 256 are now imprinted onto the banknote paper first. Hologram strip 258 is then applied such that an electrical connection is produced between coupling surfaces 256 printed on previously and metal coating 257 of the hologram strip 258. An alternative consists in first applying hologram strip 258 with chip 3 onto the banknote paper, in order to then print coupling surfaces 256 over hologram strip 258. These variations solve the problem that conductive dyes can not be contacted with a chip 3 by simple means using conventional procedures, such as bonding, soldering, flip-chip. It is to be emphasized that, in the above, the capacitive coupling surfaces were in fact only applied onto one side, but that they can, in principle, also be applied onto both sides of the banknote paper, which, in particular in the case of banknote stacks that have not been sorted according to their position, leads to more defined coupling relationships. EXAMPLE 49 To prevent the destruction or detachment of optically, inductively or capacitively coupling structures that are not embedded in but rather applied onto the paper, as they were described by way of example in the above, the banknotes can be provided with an uppermost cover layer to protect these structures. EXAMPLE 50 As was mentioned, a further idea consists in that a banknote exhibits a passive electrical, magnetic and/or electromagnetic structure, such as a passive oscillating circuit, which was described with reference to FIG. 29 by way of example. This passive oscillating circuit can have e.g. characteristic data, such as a resonance frequency, which is specific for the individual group of banknotes or at least for a certain group of banknotes. Thus, these oscillating circuit data can be specific e.g. for the country issuing the banknotes and/or for the denomination of banknote 1. These data can be used as an authenticity feature, in that e.g. the named resonance frequency is measured in an associated test device and compared with the expected values. In this context, provision can be made e.g. that the measured resonance frequency can only deviate very minimally, i.e. by a certain amount (e.g. ±10 Hz), from the ideally expected resonance frequency in order to be recognized as authentic. This makes falsification of the oscillating circuit more difficult. If the banknote also exhibits a chip in addition to the passive structure, an authenticity check can take place e.g. through a comparison of the measured resonance frequency with the ideally expected value, which is stored in the chip. EXAMPLE 51 Particularly in the aforementioned example as well, it is essential to be able to adjust the properties of the oscillating circuit in a targeted and selective fashion. Several methods are presented by way of example, which permit scalable detuning both during paper manufacture as well as during printing/processing of the sheet material. This can e.g. take place in that, for different banknotes, there is an oscillating circuit, which is actually manufactured uniformly in principle, the resonance frequency of which is detuned in defined fashion such that different banknotes have different resonance frequencies. As is commonly known, the resonance frequency of an oscillating circuit is directly dependent upon the total capacitance and the total inductance of same. Approximated, the resonance frequency fres of a transponder circuit can be represented through Thomson's oscillation equation for an ohmicly attenuated oscillating circuit: f res = 1 2 ⁢ π · 1 LC - R 2 4 ⁢ L 2 Here, L is the inductance, C is the capacitance and R is the ohmic resistance of the oscillating circuit. In the HF range, the frequency dependency of the inductive and capacitive resistance per se is actually no longer negligible, but Thompson's equation for an ohmicly attenuated parallel resonant circuit as here portrayed represents an acceptable approximation for illustration of the applied principles. One recognizes from the equation that the resonance frequency fres is directly dependent on the square root of inductance L, capacitance C and also ohmic load resistance R of the oscillating circuit, all of which, except R, are frequency-dependent. Thus, if one succeeds in influencing these variables in a targeted fashion, one then has a direct influence on the resonance frequency of the transponder. As depicted by way of example in FIG. 32, a banknote 1 exhibits an integrated circuit, specifically a chip 3, which can consist of a(n) Si-chip, a polymer electronic circuit, a polycrystalline chip circuit (a-Si, p-Si) and/or also of combinations. Chip 3 is connected with a region on banknote 1, wherein the targeted detuning of the resonance frequency takes place, by means of electrically conductive connection pieces 413. In this context, the region exhibits a layer 414 of thickness d1. This layer 414 can be embedded in the paper, but it can also be subsequently applied by means of transfer methods and can thus e.g. consist of a metallized foil strip 414 as well as out of a layer 414 of particularly conductive printing ink. Layer 414 must also not necessarily have the form of a strip. The following examples of application are now conceivable: EXAMPLE 52 Detuning of the resonance frequency of foil strip 414 can take place through the incorporation into the paper suspension of a defined quantity of electrically conductive substances, such as electrically conductive fibers, preferentially corresponding cellulose filaments. They can e.g. be treated with conductive carbon black and can potentially be spun fibers. Alternatively or additionally, magnetic substances can also be incorporated into the paper mass. E.g. particles such as iron shavings, but also ferrite powder, are conceivable as magnetic substances. The electrically conductive substances or, as the case may be, magnetic substances are incorporated in the paper web in a targeted fashion. This can e.g. take place through spraying onto the still-wet paper web being transported past, as a result of which corresponding strips 414 in paper 1 are formed. Here, a variation in the geometric dimensions, e.g. the width d1 of the strip 414 for the case named, can be used to vary the specific resistance (electrically conductive substances) or, as the case may be, the inductance (magnetic substances) and thus achieve targeted detuning of the resonance frequency. Thus, corresponding, scalable detuning can be produced e.g. through adjustment of the width d1 in dependence on the denomination of banknote 1. Since sheet material, e.g. security paper is generally smoothed and/or calendared during manufacture, it is conceivable that a galvanic contact does not automatically always exist between detuning strips 414 and contact lines 413. It is therefore conceivable to “lasers away” the non-conductive layer on detuning strip 414 with a laser, e.g. an excimer laser, so that the connection stretches 413 to be printed then restore the galvanic contact. EXAMPLE 53 A further example provides that the detuning is elicited through a correspondingly prepared strip 414. This is to be a thin sheet 414, which can be metallized, e.g. with aluminum; also copper or similar metals with a high vapor pressure are realizable. If this strip 414 is now applied onto the banknote paper by means of a transfer method, this thus takes place e.g. by means of a hot-seal adhesive. These lacquers and adhesives are non-conductive as a rule, which results in a galvanic interruption of the oscillating circuit. According to one variation of the invention it is therefore contemplated to first apply connection stretches 413 e.g. by imprinting with conductive printing ink and applying the strips afterwards, thus e.g. metallized foil strip 414, in a transfer method. That way, a galvanic connection is produced between connection stretches 413 and detuning strip 414. As an alternative to the hot-seal adhesives mentioned, conductive adhesives can also be used, also conductive anisotropic adhesives in particular. EXAMPLE 54 FIG. 33 shows yet a further variation, where a conductive ink or a metal are imprinted as a strip 414. This strip 414 can in turn also have e.g. a width d1 that is dependent on the denomination. If a non-conductive transfer strip 415 is now glued on, by way of example, provision can be made to provide two or more recesses 416 in transfer strip 415, which come to lie on the banknote paper in exact register after application over corresponding surfaces 417 in the printing surface, i.e. strip 414. Subsequently, e.g. a contact over recesses 416 with recesses 417 lying below can be established by imprinting with conductive ink in order to establish the galvanic contact to circuit 3, which is not depicted in FIG. 33. In this context, scaling of the specific longitudinal resistance is made possible through suitable selection of form, specifically of the width d1 of printing surface 414 and also of recesses 416. This leads to the desired detuning. EXAMPLE 55 In the following an example for a banknote with a chip is explained that can not be addressed inductively or capacitively, but rather through a galvanic, i.e. direct electrical contact. In this context, the galvanic contacting will serve the current supply of the chip 3 in particular. Above all, such banknotes are suited to stack measurement, as is further explained in the associated section. FIG. 34 shows such a banknote 1 with chip 3 that exhibits an electrically conductive layer 380 (shaded in the illustration) as a contact surface along each of its short sides. The layers 380 are thus electrically connected with the chip 3 over lines 381 that are in or on the banknote paper. The layer 380 is formed such that a conductivity of the banknote 1 across its cross section is ensured. That means that at least two contact surfaces 380 are incorporated on the upper and lower side of the banknote paper to supply the chips 3 with energy, which [surfaces] are conductively connected throughout the cross section of the banknotes and which can be connected with the voltage source through external contact clamps. To this end, the layer 380 can, by way of example be designed as a conductive track 380 that is applied on the banknote paper around the side edges such that a direct electrical contact exists between the upper and the lower side of the banknote 1. Alternatively, the layer also can not only be applied and/or incorporated on the surface of the banknote, but rather e.g. take up the entire volume of the side edge. Here, such banknotes 1 can be manufactured e.g. through the scattering in of conductive fibers, e.g. in the form of steel strips along the edges of the banknotes 1. It is likewise possible, e.g. to apply electrically conductive polymers or, as the case may be, to imprint them as conductive printing inks such that they penetrate the cross section of the paper and thus establish the desired galvanic contact. The track 380 is preferentially realized on □two opposite sides of the banknote 1, e.g. in the form of a track that surrounds the entire edge of the note 1 on the two short sides, as depicted in FIG. 34. The galvanically conductive layers 380 need not encompass the entire edge of the banknote 1. Even the execution of the contacts in the form of relatively small layers 380 already suffices if it is only ensured that these layers 380 can come in contact conductively across the entire stack. Likewise, the two layers 380 as contacts of the galvanic circuit, can also be executed on only one side of the banknote 1 in this embodiment. EXAMPLE 56 FIG. 35 shows an alternative embodiment of FIG. 34, where, in addition to the conductive contact layers 380 for energy supply, the banknotes 1 are provided with at least a third contact 382 that is only active in the surface of the banknote paper and was created e.g. through imprinting. It is augmented by a fourth contact 382 on the back side of the banknote, where the third and fourth contact 382 are not galvanically connected with one another. These contacts 382 are again connected with chip 3 via electrical conductors 383 and serve to permit chips 3 in a stack to be able to also individually reciprocally activate or, as the case may be, address themselves, as explained more closely in the section “Stack measurement”. To this end, contacts 382, just like contact layers 380, are positioned such that they lie above one another during appropriate stacking and thus establish the galvanic contact between every two bank notes that lie above one another. This can also be reinforced through ordered stacking. By way of example, the geometry of the third and fourth contacts 382 can be executed such that each surface for itself lies roughly in the middle of the element and is executed e.g. in the form of a ring or a circle. The contacts 382 can, however, also be executed as polygons or in another form. To the extent that the contacts 382 overlap with the conductors 381, an intermediately placed electrical insulation is necessary. EXAMPLE 57 In addition, it is also conceivable that one or more chips per banknote are incorporated or applied without any contacting. The chips then do not necessarily have the functionality for data transmission, thus potentially do not even need to function. The presence and/or the form and/or a surface structure, e.g. a surface pattern, and/or the position and/or the distribution of several such chips in or, as the case may be, on the banknote paper alone can serve as an authenticity feature. These chips can be very small i.e. e.g. invisible to the naked eye and optical or electrical test methods can, for example, be employed for testing. Semiconductor Technology with Polymer Electronics A further idea of the present invention consists of manufacturing transponder circuits based on a combination of procedures from semiconductor technology and polymer electronics. These ideas can be advantageously applied to all types of transponder substrates, be they rigid chip cards or also flexible substrates made of paper, polymers or metal films, etc. such as the sheet-shaped documents of value according to the invention. In this context, semiconductor technology is understood to mean all processes belonging to silicon technology or the like, which work via elementary semiconductors or compound semiconductors. Thin layer technologies in particular find application in this context. In current semiconductor circuitry technology, nearly exclusive use is made of integrated circuits of elementary semiconductors (silicon, germanium), which have been superior in the points of production technology and price thus far. Nearly all components available on the market consist of monocrystalline, doped elementary semiconductors (essentially silicon), that have been sawn out of wafers. In that context, the doping (n- or p-) is needed to maintain the electronic carrier surpluses, upon which electrical conduction in semiconductors is based. Aside from the conventional element semiconductors, there also exist so-called compound semiconductors, which are composed of elements from different main groups within the periodic system. Examples of these are GaAs, InP, InSb and others. The mobilities of these “composite semiconductors” are, in part, clearly greater than for Si or Ge. If these semiconductors are applied by means of thin-layer technology, a required bending resistance for flexible substrates can also be achieved, as is necessary for use in banknotes, etc. Passive and active components produced from these materials distinguish themselves by stability with reference to carrier frequencies up into the high GHz range. However, the disadvantage of known semiconductor technology in this context is the thickness of the monocrystals (wafer), which continue to exhibit a thickness of multiple 10 μm even after thinning, e.g. by abrading the non-active side with diamond paste, thus hampering use on/in substrates/carriers of comparable thickness, such as, e.g. paper. Moreover, the high piece counts that are required for applications in the area of security papers/smart labels are difficult to realize during application and bonding of the chips (e.g. by means of the flip-chip process). As a rule, transponder systems consist of a coil, which is applied to the substrate in several turns either typographically or by etching, for example. In the current state of the art, the transponder chips are still too thick (even after thinning) to be applied to thin substrates with thicknesses in the μm range, as is usually necessary for use in the documents of value according to the invention. In contrast, the manufacture of electronic circuits produced via polymer technology, so-called IPCs (integrated plastic circuits) of conductive polymers, proves to be advantageous in the present invention. Here, the polymers can be conductive (polyaniline) or also semiconductive (poly-3-alkylthiophene). The possibility of being able to apply the circuits required for this purpose typographically, even at minimal thicknesses in the Am range, is advantageous versus classic semiconductor technology. The big advantage of IPC lies furthermore in the possibility of applying the necessary structures to a carrier material typographically. The carrier material can be a plastic film or also a particularly smooth-surfaced paper instead. As already mentioned in another location of the present invention, all semiconductor components known from semiconductor technology, such as, e.g. diodes, transistors, etc., can also be produced from conductive polymers via polymer electronics. It then also becomes possible to produce more complicated logic circuits such as AND gates, OR gates, NAND gates or similar with these polymer electronic (polytronic for short) base elements. The critical aspect, however, is that maximum limit frequencies reach only some 100 kHz on account of the rather limited electronic carrier mobility achieved in polymer semiconductors to date. However, such frequency behavior is unsuitable for current RFID transponders according to ISO-14443 or, as the case may be, ISO-15693, which are triggered by external reading devices with frequencies of 13.56 MHz. Normally, the interface between the analog, high-frequency transmission channel of a reading device to a transponder and its digital components is realized via a high-frequency interface, also known as an HF interface, which corresponds to the classical modulator-demodulator system of a modem and is described in greater detail in the “RFID-Handbuch”, Finkenzeller, Klaus, 2nd Ed., pp. 242 ff., Hanser-Verlag, Munich, 1999. The HF-interface can serve to facilitate communication of the transponder with the reading device and the energy supply of the transponder via the high-frequency, or HF-signal for short, of the reading device, and in particular when the transponders are passive, it can do so with no energy supply of its own. In the above, the reading device's modulated HF-signal of e.g. 13.56 MHz is demodulated in the HF-interface. At the same time, the system clock of the data carrier is derived from the carrier frequency of the HF-field. As a rule, the interface disposes of a load regulator for sending the data back to the reading device. The critical aspect in this regard is that the carrier frequencies lie in the range of MHz and above. In other words, the associated circuits must then also be able to work with these frequencies. EXAMPLE 58 FIG. 36 shows a block circuit diagram of an inductively-coupled transponder 3 consisting of a logic portion 391 and HF interface 391 with a load modulator 392. In this context, the HF interface 391 is essentially formed by the analog input oscillating circuit 393 with transponder coil L and trimming capacitor C. Connected to this in series, is a rectifier 398, consisting, e.g. of a Graetz bridge 398 and a voltage stabilizer 399, preferentially a Zener diode 399. Parallel to the transponder oscillating circuit 393, a circuit 395 supplies the system clock for the data carrier. This circuit portion supplies the stabilized, equidirectional voltage Vcc, which provides the logic portion 391 with energy. Furthermore, a demodulation circuit 396 supplies a serial data stream to the logic portion 391 for further processing, as well as e.g. a load modulator 393, which sends back data to the external reading device. In this context, the logic portion 391 exhibits digital circuits 394 e.g. for control of the transponder, storage or encryption of data. According to the invention, semiconductor elements from semiconductor technology are now utilized for the high-frequency range, and polytronic elements are now utilized for the digital, low frequency range of the transponder circuit. This makes it possible to work with sufficiently high frequencies at the necessary circuit locations when using thin and flexible substrates, thereby enabling the use of transponders in banknotes and the like in a more simple manner. As a result of this, transponder circuits can be realized for RFID systems in which limitation of the clock rate to the kHz range in the polymer electronic is circumvented by the additional incorporation of conventional semiconductor circuits which have no frequency limitation, such that these transponders can also be used in the HF range (mHz and higher). Specifically, the high-frequency components of the HF interface are preferentially applied as element semiconductors or compound semiconductors, e.g. by printing, precipitation, vapor deposit or similar methods, whereas the low frequency components, such as the digital circuits of the logic portion 391, are produced by means of polymer electronics. By way of example, oscillating circuit L and C, as well as rectifier 398, and, optionally, all further components of HF interface 390 as well, are thus operated at high-frequency, i.e. e.g. at 13.56 mHz or higher. In particular, however, stabilizer 399 can also be a component of logic portion 391 and then likewise be manufactured polymer electronically and only work at frequencies in the kHz range like its remaining components 394. Likewise conceivable are designs in which both the high-frequency portion and the low frequency portion of the transponder circuit 3 are a combination of polymer electronic and conventional components. By way of example, thin-layer diodes can thus be integrated into the IPCs of load modulator 392 as well, just as polymer components can be integrated into rectifier and stabilizer circuits 398, 399. Optical and/or Acoustic Playback Devices As was described by way of the example above, a further essential embodiment of banknotes with electrical circuits can consist in the provision of one or more electrooptical and/or acoustic playback devices firmly integrated into the paper of the banknote. Aside from authenticity recognition, such devices can also serve further purposes, which are described in particular below and in even greater detail in the sections “Stack Processing” and “Commerce”. By way of example, the playback devices can have the following properties. An electrooptical display can exhibit individually or in combination e.g. a self-luminous optical display that radiates in the visible, infrared and/or UV spectral range and/or a non-self-luminous optical display and/or a display made of electronic paper and/or an LCD and/or an LED. In this context, the electrooptical display can exhibit a two-dimensional display surface, e.g. in the form of an LCD or also an approximately punctiform light source, such as a single LED. In this context, electronic paper can, be understood to mean in known fashion, for example, a flexible substrate with rotationally or slidably controllable microcapsules embedded between electrodes. The manufacture from electronic paper has the advantage that the flexibility of the banknotes, which are mostly made of paper, is not impaired. Moreover, electronic paper exists for which the display remains intact even without external energy supply. This is particularly suitable for many applications involving banknotes. In order to recognize an external manipulation of the displayed text in this case, it is advantageous for additional information concerning the intactness of the information, e.g. in the form of a check sum or similar to be displayed or, as the case may be, for a digital signature or the like to be stored in the chip of the banknote in addition to the text to be displayed. The display will preferentially be produced typographically in particular, e.g. by printing on the banknote with electronic ink, i.e. e.g. with printing ink that exhibits microencapsulated pearls. This provides a high degree of compatibility with the already known printing method for banknote production. Alternatively, an acoustic playback device such as an electrooptical sonic transmitter and/or a reciprocal piezoelectrical sonic transmitter and/or a magnetostrictive sonic transmitter can also be used in place of the electrooptical display. An advantage of such electrooptical and/or acoustical playback devices is that they constitute an authenticity feature readily verifiable by humans, which in addition can also not be deceptively imitated with copying technology. Moreover, these playback devices can also preferentially be incorporated as machine-readable security, i.e. authenticity features. Thus e.g. an associated banknote processing machine can comprise a sensor device that captures, potentially in response to stimulus of the playback device by the machine, the optical or acoustical signals emitted by the banknote, as the case may be, and compares them with those measurement signals expected for authentic banknotes. Associated banknotes will then be able to be recognized in particularly secure fashion, either automatically or by humans without the utilization of further aids, if the playback status of the playback device changes temporally. EXAMPLE 59 In the simplest case, this can consist in playback that occurs only periodically. This can occur by having the playback device supplied with current, particularly by an energy source, for example by means of a photocell, a thin-layer battery e.g. paper-based or by an inductive coupling, and having it only light up or, as the case may be, send out sonic signals when supplied with energy. The variation is particularly preferred in which playback only occurs when energy is supplied from the outside, i.e. no energy sources or energy stores are present in or on the banknote itself. In contrast to this termination of playback upon interruption of external energy supply, the case can also be advantageous in which the playback device exhibits an interface for the playback device's signal triggering, in particular along optical and/or electronic paths, which is particularly preferentially connected or connectable via a signal line to a control device integrated in the document of value or at least partially or completely external to it, which alters or can alter the playback status of the playback device in a temporally-predetermined manner. In this case, the playback status can also be changed in a predetermined manner independent of energy supply. In this context, the time until a change can e.g. be set randomly or at one or more specific points in time or set to occur at defined time intervals. EXAMPLE 60 A particularly simple example of this is a flashing display, e.g. a flashing, punctiform LED that lights up at predetermined intervals. In this context, the associated control data are preferentially stored in a memory of the control device. In addition, not only can the playback status be changed by altering the brightness or volume, as the case may be, of the playback device for example, but the information content played back can itself be changed temporally. EXAMPLE 61 In addition, a banknote can be designed such that it exhibits a photocell for energy supply on at least one side and a light-emitting element on at least the other side, each of which is connected to a chip in the banknote. In this context, as FIG. 37 shows, the banknotes 1 according to one variation can have a thin-layer photocell 400 on the one side, which is connected with the banknote's 1 chip 3 for energy supply of the chip 3. This [chip] in turn is connected to a light-emitting diode located on the other side of the banknote, such as a laser diode 401. The connections are preferentially made by way of typographically applied contact lines 403. This variation has the advantage that energy can be transmitted between adjacent banknotes in the stack, as subsequently described in detail with regard to FIG. 37 in the section “Stack Processing”. EXAMPLE 62 This can e.g. mean that the sonic transmitter plays through different playback frequencies or frequency sequences, or that different display patterns, such as signs or symbols, are played back in the case of a two-dimensional display surface. In order to facilitate the optical or acoustical differentiation of banknotes of different denominations, provision can be made for the playback statuses for different denominations to differ, e.g. through different tones, sonic frequencies or light signals. EXAMPLE 63 An alternative possibility for transmitting information out of the banknote into its surroundings consists in the use of thermal radiation generated in the banknote. To this end, in accordance with the information predetermined by the banknote's electrical circuit and slated for transmission, current is directed in the banknote through a number of electrical elements that act as resistors, which are embedded in or applied onto the banknote material, preferentially the banknote paper. It is hereby noted that this can also involve active electronic components such as transistors. Since they act as resistors for the physical principle of action, they will be designated using the term “resistors” in the following, if no explicit reference to electronic components is made. The resistors heat up through the electrical power brought into them. The temperature change evoked can then occur either directly, e.g. through the use of a thermal image camera in an optical sensor, or instead indirectly through an indicator reaction. The latter usually creates the potential for optical demonstration of the heat brought in. Even though other indicator reactions, such as alteration of the conductivity of conductive elements that are likewise incorporated in or upon the banknote paper, are supposed to be explicitly possible in the region of the demonstration according to the invention of incorporated heat according to the invention, “displays” will be spoken of in the following for the sake of simplicity. In contrast to the method described there, the display according to the invention does not, however, consist of simple LCR oscillating circuits like those according to DE 100 46 710 A1, for instance, which are caused to resonate by electromagnetic waves, but rather of active elements that represent an alterable condition of the banknote's oscillating circuit. In particular, display of the information available in the potentially present non-volatile memory of the electric circuit is provided for here as well. The current to be transmitted can also explicitly be an equidirectional current that is sent through the resistors. As stated, the voltage supply of the banknote is also explicitly not limited to the reception of electromagnetic radiation. Very interesting applications result from the use of electromagnetic transducers in particular that convert deformational energy into the electrical energy needed for the voltage supply of the banknote; these will be described in detail in the following. The resistors, through which current to heat the banknote is directed, can be arranged in various ways to display the information. Thus it is possible to arrange the resistors in simple barcode-like structures, bar-code-structures are realizable, segmental displays can be realized by way of the resistors, or it is even possible to realize pixel-based displays. The methods commonly used to trigger and realize the display of LCD notebook displays are to be used preferentially for pixel-based displays of this type. In contrast to known methods, however, for the displays described here it is also possible to produce the entire display not from conventional wafer-based electronic components, but rather from components made of other materials, such as amorphous silicon or multicrystalline silicon. Such pixel-based displays are however preferentially manufactured through the use of printable semiconductors such as organic polymers. In a printing process, a display of this type with the control lines and the transistors, as well as any potentially necessary additional resistors, which are, however, preferentially formed by the transistors themselves, can be printed and any printing ink to be potentially used, which contains the indicator material, can be applied over it subsequently. It is expedient for an indicator dye used in this way to simultaneously constitute a protective layer for the electronic components lying below it. A banknote designed in this manner can also exhibit the feature that a portion of the electrical circuit on the banknote necessary for the overall functionality stretches across a large areal portion of the banknote. As a result, manipulations on the banknote quickly lead to a circuit on the banknote that is no longer capable of functioning. Particular advantages then result for the displays on the banknote described above if the indicator substance contains features visible to the human eye, the information is rendered on the banknote in readable form, and the energy supply takes place by way of an energy carrier that is readily available to the general population, such as the deformational energy mentioned above, radio wave energy in the frequency range of mobile telephones or, however, solar energy. In this case, important information, such as the validity of a banknote or the like, can be portrayed in generally readable form on the banknote. Quality Control during the Manufacture of Paper and Banknotes An interesting area of application for the security papers or banknotes provided with a circuit lies in quality assurance 23 in the manufacture of paper or banknotes. According to the invention, provision is made to follow the path and/or the particularly occurring processing steps of the security paper or banknotes within the paper factory 20 or banknote printing works 21 in simple fashion by reading data from or writing data to the circuit at arbitrary locations or production stages without contact, particularly by means of high-frequency electromagnetic fields or optically. The data stored in the circuit preferentially consist of data identifying the particular sheet of paper or the particular banknote, such as serial number, denomination, issuing country, currency and/or production dates. By reading out these data, the particular sheet of paper or banknote can then be identified. Among other things, this plays an important role in controlling the destruction of paper sheets or individual banknotes that have not been manufactured properly and which are routed to a destruction device 24, particularly a shredder, subsequent to quality inspection. The individual sheets or banknotes slated for destruction can be identified by simple, noncontacting readout of data from the circuit right up to before the cutting tools of the shredder and can thus be traced in essentially uninterrupted fashion. In this manner, a nonauthorized removal of the security papers or banknotes slated for destruction can be particularly reliably monitored. Alternatively or in addition, the banknotes intended for destruction can be cancelled during the inspection or just before the shredder by writing the corresponding information into the memory of the banknote as already explained above. Alternatively, the entire contents of the memory can be deleted, e.g. by irradiating light from a UV flashlamp. In addition, data relating to the processing or finishing steps that are being performed or will be performed on the security paper or on the banknote can be stored in the circuit. In this case, particularly in the context of the quality assurance 23, one can, by reading out the stored data, check whether the paper or the banknote has completed all required finishing steps and whether they were executed in an orderly manner or a faulty manner. During production, it can be particularly advantageous to use larger or, as the case may be, more or all of the memory portions of the chip, even if, for a later application, only portions of the memory can be used and these portions, in turn, can only be used by different user groups or for different application purposes. In this case, the limited access privileges for the memory regions are not able to be permanently introduced until after the chip has been successfully produced, by the corresponding memory regions, for example, being permanently, e.g. by severing fuses through burning, and appropriately designed such that they are protected against writing. The invention can also be utilized to advantageous effect in the banknote processing machines provided for quality assurance 23. In these machines, the finished banknotes are provided in stacks, drawn in individually, transported along a transport path and inspected for various properties and security features. Undesirable malfunctions in which several banknotes are pulled in simultaneously and transported further and/or a jam of banknotes arises, can occur repeatedly during transport through a machine such as this, however. In these cases, it is advantageous if data, particularly the serial numbers, of the bank notes being drawn in each case are read out and stored in the machine control during their separation. These [data] can then be queried again upon correction of the malfunction and renewed set-up of the banknotes, which have been multiply drawn off or jammed, for renewed inspection, so that any unauthorized removal of banknotes during the correction of the malfunction can be readily demonstrated. Transport of Banknotes A further important area of application for the invention lies in the area of banknote transport. By noncontacting readout of the circuit located on the particular banknote using the apparatuses and methods described in greater detail below, banknotes can be identified simply and rapidly at arbitrary stages in their circulation. Data on the identity of the banknotes are registered in a central monitoring device as applicable. These data allow the path taken by a banknote during its circulation to be reconstructed. The identification and, if need be, registration of the banknotes can already take place during their manufacture, i.e. in the paper factory 20 of FIG. 1 and/or in the banknote printing works 21, or not until their circulation in the area of a central bank 25, a commercial bank 26, and/or a business 30 in various apparatuses, such as processing machines 31, money dispensing machines 27, money depositing machines 28, combined money depositing and money dispensing machines 29 or automatic money input devices 32. In general, it is also possible to install corresponding scanning apparatuses in transport vehicles, which apparatuses register the incoming and outgoing lots of banknotes. As will be explained in detail in the section, “Disabling and Enabling of Banknotes”, a further advantage of the invention is achieved in that the circuit located on the paper or, as the case may be, on the banknotes can be switched or written to in such a manner that the paper or the banknotes can be temporarily blocked from any use in machines, particularly from payment at machines. Release of the banknotes for further use in machines can first be undertaken by a central bank 25 or commercial bank 26, preferentially by entering a secret password or by triggering a particular operation in the circuit, shortly before the banknotes are once again put into circulation. Thefts or holdups in the area of paper and banknote manufacture or, as the case may be, during the transport of finished banknotes from the banknote printing works 21 to a central bank 25, and, as applicable, from it to a commercial bank 26, are thereby rendered unattractive, since disabled banknotes will be recognized as such at registers or machines equipped with the corresponding reading devices, such that a payment or deposit will be refused. Should these banknotes again be put into circulation again at another location, i.e. at locations at which no communication with the circuit is possible, at least it will be possible at a later time to recognize that the money was stolen, thus potentially allowing valuable conclusions to be drawn. The disabling of the banknotes described above is of particular advantage for the automatic dispensing machines 27, automatic deposit machines 28, combined automatic deposit and dispensing machines 29 and containers described in greater detail below, and/or also for the banknotes stored in transport vehicles, since any banknotes withdrawn illegally by break-in or sabotage and thus disabled will be readily recognized with the corresponding scanning apparatuses upon an attempt to place them in circulation. Altogether, this variation of the invention is utilizable in various applications and case scenarios. EXAMPLE 64 By way of a temporary cancellation and/or marking, it is thus also possible for the money stored in the particular devices to be acknowledged as non-interest-bearing property of the central bank 25, the so-called minimum reserve. Moreover, the registration of banknotes allows money flows of black money, stolen money or extorted money to be monitored in simple fashion. For this purpose, e.g. when money is being disbursed, the identity of the banknotes disbursed, in particular their serial numbers, together with data on the recipient, can be stored. Other applications are described more closely in the section “Disabling and Enabling of Banknotes”. Containers for the Transport of Banknotes In order to be able to utilize the invention in particularly advantageous manner during the transport of banknotes, special containers for the transport of banknotes are provided. In this context, containers in the broader sense of the word are understood to mean all devices in which banknotes can be brought together and transported. This includes in particular safes, cassettes made of metal, plastic or cardboard, paper packagings, small sacks or bags made of paper or plastic, as well as bands. These containers are usually characterized in that they can be closed in such a manner so as to render impossible an unrecognized external access without manipulation to the container. The containers, particularly cassettes, can, for example, be provided with an antenna and/or a reading, writing and/or checking unit, which is particularly able to read, alter and/or check the stored contents of the circuits of the banknotes located in the container. The necessary apparatuses and methods, explained in exemplary detail in conjunction with the testing of banknotes in stacks further below, can also be employed in such containers. In this way, data which identify the banknotes, such as the serial number, can first be read in the container, such that—depending on the particular application case - an identification of the banknotes slated for transport by means of an external inspection device can be omitted. The contents of the container are preferentially registered by the container itself and, as necessary, checked so that monitoring of the contents, in particular during transport, upon storage, upon handing over or upon transmission of the banknotes can be recognized by the container itself without the need of having to open it for this purpose. This also applies particularly to automatic tellers, where banknotes can be dispensed from cassettes and/or fed into these cassettes or other cassettes. As a result of the fact that the contents of the cassettes can always be determined completely, correct taking of inventory can even be effected during a jam or a temporary error or, as applicable, failure of checking and/or evaluation devices of the machine, without the need for the cassettes to be opened. EXAMPLE 65 Moreover, provision can be made that data, for example relating to the course of transport, are written into the memories of the circuits by the container's writing unit. In this manner, the transport route can be recorded in the banknotes. In particular, the container can exhibit walls, e.g. of electrically-insulating material such as plastic, which, at least in part, do not screen out electromagnetic fields, so that the circuits of the banknotes located in the container can also be read from, written to and/or checked from the outside by means of high-frequency alternating fields. Altogether, containers of this type allow the value, i.e. in particular the total value and/or the denomination of all the individual banknotes located in the container, to be determined at any time. During transmissions, uncertainty over the contents being handed over or time-consuming recounting is eliminated. In this way, money transfers, the handling of money and the control of money flow are made fundamentally simpler, faster and, above all, more secure. In this way, the entire monetary cycle can be monitored in an effective fashion. EXAMPLE 66 It is principally possible for the container itself, by means of its writing device, to input this information, the data referring to the value and other data concerning the banknotes, such as transactional and/or transport data, into some or all of the banknotes contained in the container. However, additional or alternative provision can also be made for the container itself to likewise store e.g. the total value of the banknotes stored in the container in a nonvolatile memory. If both possibilities are realized, a check for manipulation of the container contents can also be conducted e.g. by a comparison of the indications of total value that are stored in the banknotes with those that are stored in the container. EXAMPLE 67 For instance, in the case where the memory of the chip in the banknotes exhibits a write-only memory area that cannot be read out again directly, an examination of security against manipulation can consequently occur such that the total value present in the memory of the container is sent to the banknote for examination. If this value is the same as the value recorded in the banknote, it will be assumed that the contents of the container were not manipulated. EXAMPLE 68 Security against undetected manipulation of the container contents can be increased by using an asymmetrical PKI encryption method. For this purpose, the banknote processing machine, by which the container is filled, can, for example, write the total value of the container contents into the banknotes and/or into the container. In the above, the total value prior to input is encrypted with a private key from the filling location and can be decrypted with the public key of the banknote processing machine performing the filling after receipt of the container and, as applicable, any legally-occurring removal of the banknotes contained therein. If the total value is written into both the banknote and the container, it even becomes expedient to utilize two different private keys for the encryption of the two numbers for the total value. For instance, in the case where the chip exhibits a write-only memory area that cannot be read out again directly, but instead only responds to a query as to whether a second transmitted value is identical to a value written in initially, a check for manipulation can occur in that the potentially unencrypted total value present in the memory of the container is sent to the banknote for examination. If this value is the same as the potentially unencrypted value written into the banknote, the banknote will report this fact to the emptying banknote processing machine and the assumption will be that the contents of the container was not manipulated. This method already constitutes a certain security against undetected manipulations, since, for an undetected removal, the data for the falsified total value are written into both the container and to one or more, preferentially all, of the banknotes. Nonetheless, security can be raised even further through the use of encryption. To accomplish this, the total value of the container is written into the banknotes in a) encrypted or b) unencrypted form, and to the containers in encrypted form. On the one hand, the recipient can now decrypt the total value contained in the container with the public key from the filling location and thus determine the total value of the container at the time of filling. On the other hand, he can determine manipulations of the number written into the container by comparison of the a) decrypted or b) still-encrypted number with the contents of the banknotes. An attacker of the contents of the banknote transport containers will not succeed by combinatorial means in removing a number of banknotes and determining values for the numbers in the banknotes and the container which produce a positive comparative result subsequent to encryption. The only means with a promise of success for a thief would be to read out the encrypted numbers for the total value of a container of known contents and to empty another container with a higher total value such that its contents corresponded to that of the first one and to write the corresponding data into all the banknotes as well as into the memory of the container. EXAMPLE 69 Therefore, security here can be raised even further yet, by storing additional information in the container and/or the banknotes, which information also differs for two filled containers that have contents of like value, and by likewise encrypting this information in the way described above. For example, a combination of a portion or all of the serial numbers of the banknotes contained in the container can be used for such information. EXAMPLE 70 A further form of container for the transport of banknotes then results when a non-volatile memory of the container contains the data for a portion or all of the banknotes contained therein. For this purpose, for example, the data of all of the banknotes that are slated to be transmitted to the container are sent to the container before, during or after filling, either from the device filling the container or from the banknotes themselves. Upon inquiry by the device processing it, the container can now supply the data of the banknotes which it contains and/or data written into the banknotes which it contains. The container can, however, also be formed such that it accepts the data intended for writing into the banknotes, holds them in its memory and that the intermediately-stored data are not written into the corresponding banknotes until removal of the banknotes contained in the container. The communication with the container can take place via a transmission method that is different from the communication with the banknote; in this context, e.g. considerably higher transmission speeds can be achieved than by direct communication with the banknote. Additionally or alternatively, the container can also exhibit an identical transmission method, such as communication with the banknote; however provision can then preferentially be made to reliably prevent direct communication with the banknotes located in the container in order to unequivocally clarify responsibility for the sending and receiving of information. In this case, a reading device can communicate with a banknote, a stack of banknotes or a container in the same way. For two reasons, this makes possible communication with a significantly larger number of banknotes than is possible in unpacked form. On the one hand, because the capabilities and the reliability of anti-collision methods limit the number of banknotes that are reliably addressable without collision in a given time period. However, the container, which knows the relevant data of the banknotes it contains, can transmit these data to a readout device in a suitable form precluding all forms of collision. On the other hand, because the transport of energy for generating the supply voltage in very large quantities of banknotes is significantly more difficult to manage than the transport of energy for operating the container. EXAMPLE 71 FIG. 38 shows an example of a container 350 according to the invention. Specifically, cassette 350 has a housing 351 of known type with an optional lockable opening 352 for the insertion of banknotes 1. In this context, the banknotes can be placed upon a base plate 353. It can e.g. be designed to be adjustable in height within the cassette. According to the invention, cassette 350 contains at least one test unit 354 for optical and/or inductive and/or capacitive reading and/or writing of data from or to the electrical circuits of the banknotes 1. In this context, this checking unit 350 can be designed as indicated in the aforementioned examples and in the chapter on stack processing. It can exhibit a row of inductive coupling antennas in the direction of height H, for example, that can read data from or write it into the banknote chips. Alternatively or additionally, the floor of the cassette housing 351 or the base plate 353 can also exhibit a further test unit, for example. Band with an Electrical Circuit The properties of the containers for transport of banknotes according to the invention can also be applied in particular to the disposable containers, so-called safe bags, used in the transport of valuables. Explicit reference is also made to the meaningful application of the aforementioned properties to containers as separating agents, i.e. the use as separator cards, such as header cards during the processing of deposits. As an alternative to the variations described above, e.g. the band are also preferentially provided with an integrated electrical circuit, i.e. a chip. EXAMPLE 72 An exemplary embodiment of such a band is shown in top view in FIG. 39 and in side view in FIG. 40. Individual banknotes 1 are enclosed by the band 40 and thus held together as a small packet 43. Band 40 is designed as a strip made of flexible material, e.g. made of paper or a plastic foil, which adapts to the shape of small packet 43 and surrounds it. Band 40 is provided with a circuit 3, preferentially a chip. Beyond that, a transmission device 42 for energy transmission and/or exchange of information with circuit 3 is incorporated on band 40. Circuit 3 can already be integrated into or applied to band 40 during manufacture. Alternatively, circuit 3 can also first be applied during the banding process, during which a small prepared packet 43 is provided with the band 40, or else applied to band 40 subsequently. In this variation of the invention, circuit 3 is preferentially applied onto a backing film 41, which is applied, preferentially glued, to band 40. The band can also exhibit another arbitrary form, e.g. at least represent an envelopment of the small packet that is so full that no banknotes can be removed from the banded small packet. Transmitting unit 42, in this case an antenna coil, can likewise be applied onto backing film 41 and applied onto band 40 along with circuit 3. Preferentially, backing films that exhibit no stability of their own are used, so that they are inevitably destroyed upon removal. In this case, unauthorized removal of backing film 42 provided with circuit 3 or, as the case may be, transmitting unit 42, leads to their destruction, such that very good protection against manipulations is provided. As already mentioned, circuit 3 and/or transmitting unit 42 can be directly printed onto the band 40 in an alternative embodiment. Very good protection against manipulations is also given in this variation, since circuit 3 or the transmitting unit 42 can practically only be removed from band 40 with self destruction. EXAMPLE 73 A further embodiment of the invention is depicted in FIG. 41. In this example, the two terminal regions 44 and 45 of band 40 are glued together with a backing film 41, upon which circuit 3 and transmission unit 42 are located. Unauthorized opening of band 40 by removal of backing film 41 would have as a consequence the destruction of same, including circuit 3 and transmitting unit 42. Any manipulations are therefore readily visible and can, in addition, be easily demonstrated by checking the functionality of the circuit. EXAMPLE 74 FIGS. 42 and 43 show a further embodiment of the band 40 according to the invention in top view or side view, as the case may be. Circuit 3, situated on band 40, is provided with a transmitting unit 42, which runs along band 40 and extends over several sides of the banded small packet 43. In the example shown, transmitting unit 42, designed as a closed coil antenna, extends across four sides of the small packet, in that it surrounds said packet like a closed loop. In principle, provision can be made for chip 3 on the band 40 to exchange data with banknotes 1 in small packet 43, which likewise exhibit a chip. The resultant advantages correspond to those which were already described above in connection with containers for the transport of banknotes. Analogous to the integrated circuits in or on banknotes, chip 3 on band 40 is designed for the storage and/or processing of data. In particular, information about small packet 43 and/or individual banknotes 1 in small packet 43 are stored in chip 3 of band 40. In particular, this information concerns the transport course of a small packet, e.g. the time at which small packet 43 was at a particular location. A reconstruction of the transport can be performed from the data stored in chip 3. The data for the banknotes assigned to the band can also be contained in chip 3 of band 40. As long as the small packet is enclosed by the band, the data exchange can also preferentially only occur via chip 3 of band 40, which has great simplification and an increased read-security as a consequence, since now, each individual chip on the banknotes in the small packet no longer needs to be queried separately. The data of the individual banknotes are preferentially made available in a storage device, if necessary, after each individual banknote has been separated and checked. In this process, banknotes with a defective chip can also be captured and taken into account in the band's information. A band with an electrical circuit can be particularly advantageously employed if the data storage and transmission described in the section on containers for the transport of banknotes are incorporated into said band and communication takes place exclusively via the band's chip. In banded small packets of e.g. 100 banknotes, the number of banknotes addressable in one process step could be increased by a factor of up to 100, without generating additional time, effort and costs for more sophisticated anti-collision algorithms. In a further variation of application, the serial number of chip 3 situated on the band is brought in as a unique feature for establishing or checking the identity of the band. Before going into the preferred embodiments of processing apparatuses, etc., a plurality of concepts according to the invention shall now be described, which can be applied to great advantage in said apparatuses, but also in the other apparatuses described in this application. Stack Processing As already mentioned repeatedly in the above, a particular advantage of using banknotes with a chip or an electrical circuit is that stack processing is made possible. In this context, stack processing is understood to mean that a stack of banknotes is processed. However, stack processing also makes it possible to process a “stack” consisting of just one individual banknote as well. This means that one or more banknotes are made available in a stack and e.g. one or more properties of the banknotes are preferentially measured and/or determined in a stack. In particular, such properties also concern the total number of banknotes, the value of the individual banknotes and/or the total value of all banknotes and/or their serial numbers or other individual data that are specific and unique to the particular banknote. This method thus makes possible particularly simple determination of total value in the stack, even for banknotes of differing denominations. In comparison to the known methods, in which e.g. to determine the value of a stack of banknotes, the banknotes must first be separated and subsequently individually assessed with respect to their denomination, the method according to the invention brings enormous simplification and time-savings to stack measurements. In particular, stack processing is understood to mean the case that, in order to measure and/or then consequently determine the properties of the banknotes, measurement signals are obtained, and, as applicable, subsequently evaluated via communication with the banknotes in the stack. In this context, communication is understood to mean a signal transmission from the banknote, in particular the banknote's chip, to an external measurement or evaluation device, as the case may be and/or a signal transmission from the measurement or evaluation device, as the case may be, to the banknote, in particular the banknote's chip. Therefore, aside from the determination of banknote properties, the case can also be meant where signals are transmitted to the banknotes in the stack in order e.g. to write data to the storage area of the chips of the individual banknotes. In this context, the communication will preferentially be noncontacting. This can e.g. be achieved by inductive and/or capacitive and/or optical and/or acoustical and/or microwave coupling. By way of example, the photodiodes named above can be used in the banknote for an optical coupling. As already portrayed above, transponders, such as a coil coupled to the chip, capacitive surfaces or antenna arrangements for inductive coupling or capacitive coupling, as the case may be, in banknote paper are incorporated in and/or applied to the banknote for inductive or capacitive coupling, as the case may be. By way of example, banknotes with a capacitively coupled transponder chip can thus exhibit conductive regions on the front and/or back side, such as in the form of hologram strips containing metallic layers. The stacking of several such banknotes leads to a serial connection of capacitors, which, by way of example, can also be used for simultaneous energy supply to the individual banknotes during measurement. If e.g. each banknote exhibits an electrically conductive region, the distance between the conductive regions of two adjacent banknotes will thus be largely independent of the position in which the banknotes find themselves. This makes possible particularly readily reproducible coupling in the stack. For inductive, capacitive or optical coupling, as the case may be, the sender and/or receiver are preferentially arranged in the same region of the banknote relative to a corner and/or edge, independently of the banknote's denomination. As a result, by orientating a stack of banknotes in relation to this corner or edge, effective coupling of the individual banknotes becomes possible even for stacks with banknotes of different denominations. Furthermore, the properties of the individual banknotes are preferentially measured one after another or, as the case may be, the banknote chips are written onto one after another. For one, that can mean that, although several or all of the stacked banknotes emit a measurement signal, only the measurement signal of an individual banknote will be picked up and evaluated in an associated evaluation device at any given time. It can also mean, though, that the banknotes are only activated individually one after another to emit a measurement signal. As mentioned above, the activation of the banknotes and the subsequent emission of a measurement signal to an external evaluation device preferentially occurs according to an inductive, capacitive, optical, acoustical and/or microwave coupling method, whereby either the same or different coupling methods are used for activation and signal emission. Another method for activating banknotes in a stack individually can consist of individually activating the banknotes individually by means of pointwise illumination of a photodiode integrated into the banknote, as has been described in greater detail in the above. For this purpose, the photodiode is preferentially arranged on an edge of the banknote and the light coming from one side is irradiated onto the stack of banknotes and, one after another, onto the photodiodes of the individual banknotes. Via an optical interface, the irradiated light will cause the banknote's chip to emit, by means of a transmitter that is connected to the chip by a signal line, a response signal in response to the optical stimulus. The response signal can e.g. likewise occur through activation of a light-emitting element, such as an LED, whereby the light emitted from said element, e.g. via the photodiode through which the excitational light is irradiated into, or though a further photodiode integrated in the banknote paper, is sent outwards to an evaluation device. Alternatively, a controllable see-through window with e.g. alternating transmission or polarization is also possible as an output medium. Alternatively or additionally, the response signal can also be emitted by means of inductive and/or capacitive coupling. EXAMPLE 75 FIGS. 44 and 45 show an example of an associated measuring device, i.e. reading device 220 with optical coupling in a view from above (FIG. 44) and from the side (FIG. 45). In this context, for example, the banknotes exhibit two photodiodes 226, 227 incorporated in the banknote paper, both of which are connected to a roughly centrally-incorporated chip 3 by means of a non-depicted optical interface. In this context, chip 228 can be activated by irradiation from both photodiodes 226 and 227 and sends the response light into the other particular photodiode by means of a non-depicted optical transmitter, such as an LED. In this case it is preferable that one LED apiece be present for each of photodiodes 226, 227, which can be selectively stimulated to emit light by chip 3. In order to avoid the necessity of a targeted deflection of the emitted light beam to either the one or the other photodiode, the response light can also be sent out to both photodiodes 226, 227, in particular by a single LED. As an alternative to the two photodiodes 226, 227, it is also possible to use a continuous photodiode, upon which the chip is applied, e.g. glued or hot-pressed, so that in-coupling and out-coupling of the data does indeed take place on the common photodiode, but input and output are performed separately at the two ends. A separation of the signals can be accomplished in known fashion by data systems technology or with optical filters. The device 220 comprises a base surface 221 and two side walls 222, 223. Banknotes 1 are laid down on the base surface 221 in flush stacks and oriented in relation to left side wall 222. A light source, such as a laser 224, adjustable in height H, is arranged in or on left side wall 222. For this purpose, e.g. laser diodes 224 are used that generate a focal point in the area of left [bank]note edge 225 in a magnitude corresponding to the diameter of the left photodiode 226 of e.g. 0.03-0.08 mm. For measuring the banknote properties, laser 224 is moved by automatic drive from below to height H, so that the light beam emitted by it successively passes over the output region 225 of photodiode 226 of all banknotes 1 in the stack once. In this way, the LEDs of banknotes 1 are successively activated by means of chip 3 and in each case emit light through the other photodiode 227, which light is captured by a detector 229 that is integrated in or on the inner side of the right side wall 223 allocating the stack of banknotes. In this context, detector 229 exhibits e.g. a CCD surface, the dimensions of which extend over roughly the entire height H of the potential stack region. Whereas in the above, the case was described where laser 224 is moved to height H, the successively-occurring focusing of the laser beams on the individual photodiodes 226 can also be realized with a stationary laser by means of correspondingly-adjustable imaging optics and/or in that several laser diodes are distributively arranged in side wall 222 at height H, which diodes can be selectively activated successively to emit light. Moreover, it is also not imperative to work with a punctiform focal point. Since banknotes 1 are usually not in exactly flush orientation in the stack, photodiode 226, which is roughly punctiform in cross section, of an individual banknote 1 would then be struck better if the light beam were focused in the shape of a strip, in other words, if the light beam extended in a direction roughly perpendicular to stack direction H and to the illuminated sides of the banknotes 225. In this case, the stimulus light can be reliably focused on the individual photodiodes 226 without the effort of additional post-adjustment for individual banknotes 1, even in case of positional shifts of the individual banknotes 1 in the stack relative to one another and/or in case of stacks with mixed denominations, where the photodiodes 226 lie in different positions on the side of the illuminated banknotes 225. In these and also in all other cases where an optical response signal is generated for measurement, the denomination of the emitting banknotes 1 can be determined in simple fashion by frequency analysis, specifically via recognition of the specific wavelength and/or modulation pattern of the optical response signal captured e.g. in detector 229, provided the light frequencies emitted by the banknotes are designed to be nominal-value-specific. EXAMPLE 76 FIG. 46 shows an example of a modified version of measuring device 220 from FIGS. 44 and 45 in a view from the side. Measuring device 220′ serves to examine banknotes by the stack, with both optical, as well as inductive and/or capacitive coupling elements, as described by way of example by means of FIG. 23. Coupling of the banknotes by inductive means or capacitive means, as the case may be, requires a lesser adjustment effort than optical coupling, e.g. as per FIGS. 44, 45, since the inductive coupling or capacitive coupling, as the case may be, is less dependent upon the exact placement of the banknotes in the stack. By having readout of the banknotes take place by optical means, however, this process, on account of the negligible interaction of the out-coupling signals of the individual banknotes in the stack, is more readily possible than e.g. with the help of the anti-collision method described below for inductive coupling. Although analogous action is therefore also advantageous for a capacitive coupling, the following will deal specifically with an inductive coupling. The measuring device 220′ of FIG. 46 distinguishes itself from those of FIGS. 44 and 45 in that it exhibits a device 251 for generating an inductive alternating field, such as a coil 251 as coupling antenna, instead of a light source 224. In this context, coil 251 preferentially extends essentially parallel to the stack area 221 for banknotes 1 and is so designed that the magnetic field lines generated run essentially perpendicular to the surface of coil 251. Although a variation is indeed depicted in which coil 251 is mounted above the stack of banknotes, but said coil would preferentially be present on or in the base surface 221, upon which the banknotes 1 to be checked are stacked. In order to supply the stacked banknotes 1, which can be manufactured in accordance with FIG. 23, in the measuring device 220′ with energy, an alternating magnetic field is generated through coil 251 at a frequency preferred for the RFID system 3, 250 of the banknotes 1 for an effective coupling of 13.56 mHz. The field strength of this magnetic field will be multiple times greater than that which would be necessary for the energy supply of an individual banknote 1. In addition, it is possible to send data to chips 3 in the banknotes 1 by modulating the alternating magnetic field. In this context, all banknotes can be addressed simultaneously, i.e. be coupled. The high field strength required, as well as the strong inductive interaction between the individual banknotes in the stack, hamper the sending back of data from chips 3 to the reading device 220′. A variation to the solution of this problem consists in a load modulation of the chip. Preferred, however, is the depicted variation with optical signal out-coupling, by which the signal generated by the LED of the banknotes is directed through photodiodes 226a, 227a to the edge of the banknotes. One advantage of sending the signal to two opposite edges via photodiodes 226a, 227a is that the orientation of the banknotes in the stack is inconsequential to the measurement. That means e.g. that device 220′ can also check a stack in which banknotes 1 with the front side pointing up and down are present simultaneously. The out-coupled optical signals are received by a sensor 229, which is preferentially a CCD sensor 229 with a rectilinear resolution, so that a plurality of optical signals can be simultaneously received and evaluated in parallel. The transmission of data by the emission of optical signals can be initiated via control data that are sent to the chips via the inductive coupling. The separate, parallel evaluation of the signals sent from the individual banknotes 1 in the stack via the photodiodes 227a makes possible the simultaneous readout, processing and storage of the data from all banknotes 1 in a stack. EXAMPLE 77 The following is a variation for reading devices with inductive coupling. Although the coupling antenna 251 is preferentially arranged above or, as the case may be, below the stack of banknotes in the embodiment according to FIG. 46, provision can also be made for it to be situated on the side of a stack of banknotes 1 to be examined. In analogy to the variation according to FIG. 45, provision can e.g. also be made for such a coupling antenna to be height-adjustable in direction H lateral to the stack of banknotes, exactly like light source 224, which functions as an optical coupling antenna. Alternatively, provision can also again be made for several coupling antennas arranged in rows that extend in direction H, i.e. roughly perpendicular to the stack area 221. In this case, according to the height of the banknote stack to be checked, the stack measurement can be performed by moving the coupling antenna up in height or, as the case may be, by successive activation of the coupling antennas arranged in rows, such that only a limited number of banknotes of the stack are supplied with sufficient energy and addressed in each case. In this context, to the extent that the field strength of the coupling antennas is selected to be sufficiently small, it can, in the ideal case, be achieved that only one individual banknote, i.e. the banknote closest to the coupling antenna, is addressed at a time. Otherwise, it can at least be achieved that only a limited number of banknotes in a stack are addressed simultaneously, as a result of which any potentially necessary anti-collision measures are simpler and faster to execute on account of the lower number of transponders coupled in. In other words, agents are thus introduced to “displace” the external checking unit spatially, specifically translationally, in order to be able to address other transponders in the stack in temporal succession. Moreover, in comparison to optical coupling, this variation of inductive coupling provides the advantage of lesser adjustment effort and places fewer demands on exact orientation and positioning of the banknotes in the stack. EXAMPLE 78 As an alternative or to supplement the preceding examples, provision can also be made that the banknotes 1 are additionally provided with a device for inductive out-coupling. Thus, chips 3 can e.g. exhibit a device for the generation of a load modulation. This makes possible the readout of chip data from individual, non-stacked banknotes 1 by means of inductive coupling over a stack measuring device, i.e. stack reading device, even beyond those described by way of example in the above. This is e.g. an advantage for mobile reading devices or also in [cash] registers, as will be more closely described in the following sections. If signal coupling is possible using both inductive as well as optical means, various methods of selection or, as the case may be, switching between the optical coupling and the inductive coupling are conceivable. For one, it is conceivable that both methods are simultaneously activated or will become activated, upon stimulation of the banknotes, e.g. through inductive coupling by means of coil 251. In this case, both types of reading devices, i.e. with inductive sensors or, as the case may be, optical sensors, can be employed without the need for a switching procedure or the like. However, this variation has the disadvantage that the parallel operation of both coupling methods increases the energy requirement for chips 3. Therefore, only one of the two inherently possible methods is preferentially selected. Within this meaning, e.g. a selection or switching between inductive coupling, i.e. load modulation, and optical coupling can take place by way of a specific control signal, which is sent to chip 3. In addition, it is possible to define one of the two methods as preferential, which method is always active initially, as soon as chip 3 is supplied with energy. In this case, when the method not defined as preferential is used, switching by means of a control signal sent to the chip 3 would likewise take place. Such a control signal would preferentially be cryptographically encrypted to only allow readout in reading devices 220′ intended for this purpose. A further variation for activation or, as the case may be, switching consists in using specific switch-on sequences or codes which are not contained in normal data transmission from the measuring device to the chip. These can, for example, be realized in that, for a bit encrypting, specific codes that are not contained in the transmission of “1-”, “0-”, “Start-” and “Stop-”signals are reserved and can therefore come into exclusive use for switching the transmission method. In this case, but also particularly in the case where, aside from optical and inductive coupling, capacitive signal transmission from the chip to the reading device is possible, the chips will be prompted by specific control signals to use a coupling method specific to the particular signal. Alternatively, it is also conceivable that many different transmission methods are available to the reading devices 220′, and that the selection of one of the transmission methods occurs in dependency upon a control signal that is transmitted to reading devices 220′ from chip 3. EXAMPLE 79 Moreover, it is possible that a unique banknote identifier, such as the serial number, is initially read out, preferentially in parallel, from all or a partial quantity of several banknotes during a stack measurement in order to then, in a further step, be able to address individual banknotes via their serial numbers in a targeted manner. However, this approach is also principally applicable to the testing of individual banknotes. EXAMPLE 80 Banknotes with photodiodes, e.g. of LISA plastic, as was previously described in relation to the FIGS. 23, 25, and 26, by way of example, are particularly suited to stack measurement. In this context, for both the use of an LED 235 as well as for the luminous surface 291, the emitted light intensity is altered, i.e. modulated, in order to transmit data from banknote 1 to an external reading device 229. In that context, the simplest type of modulation is preferentially employed, that is, the turning-on and turning-off of a light signal, such as so-called “on-off keying” for a 100% ASK modulation (amplitude keying), as it is e.g. described in Finkenzeller's book: “RFID-Handbuch”, pp. 156 to 164, 2000, Carl Hanser Verlag Munich Vienna, ISBN 3-446-21278-7. However, multi-step modulation, e.g. corresponding to bit encrypting via gray shades, is also possible for both the (large-surface) LED 235, as well as for the luminous surface 291. The readout of the optically modulated data can occur e.g. via a sensor 229, as it was described with reference to FIGS. 44, 45 or, as the case may be, 46. Sensor 229 can be both a CCD field (a charge-coupled device), as well as a line sensor (e.g. a photodiode array). Photodiode 226, 227, 226a, 227a, 227′ is consequently primarily used for the transmission of data, in the form of modulated light signals, to a reading device 220′. A particular property of luminescent materials consists in that an attenuation of the emitted radiation with a defined time constant is observed upon turning off the absorbed radiation. This effect also appears during the modulation of the absorbed radiation for the purpose of data transmission. A further idea therefore consists in capturing and analyzing the attenuation behavior of the radiation emitted from the fluorescent dyes 286 by a reading device, such as sensors 229. When using other materials or illuminants for the purpose of forging a banknote 1, a different attenuation behavior at the pulse edges is to be expected. This makes it is possible to recognize forgeries of this type and to handle the banknote 1 accordingly. A banknote 1 according to the invention, as was described in the above by way of example, is addressed in the stack e.g. inductively or capacitively and responds through the photodiode. Particularly in the singled condition, provision can be made to likewise address same inductively or capacitively, but also responds in this way. Therefore, this variation represents a banknote 1 with two interface possibilities/response possibilities. EXAMPLE 81 As was explained, according to the invention, it is also possible that banknotes are read out in the stack by means of inductive coupling. In this context, it has been shown that the resonance frequency of transponders in the stack follows the following function: f total = f indiv . N Here, N is the number of transponders, i.e. banknotes 1 with chip 3 in the stack, findiv. is the resonance frequency of an individual transponder and ftotal is the resulting resonance frequency. Optimal energy coupling in the banknote stack can then be achieved if the measuring device transmits on the resulting resonance frequency ftotal. However, in the case of large stacks, the resulting resonance frequency ftotal assumes very low values. At a resonance frequency of 21 MHz of an individual transponder, for example, 2.1 MHz result for a stack of 100 banknotes 1 and but 0.66 MHz result for a stack of 1000 banknotes 1 with chip 3. In order to keep the processing speed in a stack low, it is, however, desirable to select the working frequency of the measuring device as high as possible, preferentially e.g. at 13.56 MHz. The maximum achievable resonance frequency of an individual transponder 3 with a coil consisting of at least one turn, as a rule, however, is not higher than 30 MHz. Higher resonance frequencies can not be realized in a simple manner due to the inductance values that are predetermined by the design as well as the additionally present parasitic capacitances. An increase in the resulting resonance frequency by increasing the resonance frequencies of the individual transponders in the stack is thus possible in principle, although it is not practicable in all cases. In order to be able to nonetheless address a stack of transponders 3 outside the resulting resonance frequency ftotal, high magnetic field strengths prove to be expedient. Beyond that, it is advantageous to adjust the diameter of the transmitting antenna, such as transmitting antenna 251 in FIG. 46, to the diameter of the antenna in the banknote, such as of coil 250 in the banknote 1 according to FIG. 23, so as to optimize the magnetic coupling between transmitting antenna 252 and transponders 3. The course of the field strength in a coil in the X direction can e.g. be calculated according to Finkenzeller's book: “RFID-Handbook”, pp. 61 ff., 2000, Carl Hanser Verlag Munich Vienna, ISBN 3-446-21278-7. Here, it can be recognized that at a distance x, that is larger than the radius of the coil, the magnetic field becomes strongly inhomogeneous and rapidly loses intensity. By contrast, with very large stacks of e.g. 1000 banknotes, the height of the stack is already greater than the coil radius. A homogenous magnetic field can thus no longer be readily generated by means of a simple arrangement of coils. An improvement can be achieved if the volume taken up by the banknote stack exhibits higher magnetic permeability than the surrounding space, i.e. normally the air. To accomplish this, the banknotes are equipped with a magnetic permeability, as was already described previously. EXAMPLE 82 A reading device 280 for the readout of inductively coupled banknotes 1 with magnetic paper in the stack is depicted in FIG. 47. The manufacture and properties of such a magnetic paper have already been dealt with in detail in the above. For readout of the banknotes in the stack, a homogenous field is generated that penetrates through the stack. By way of example, the stack is therefore brought into a ferrite core 28 1. In principle, soft magnetic materials are also possible, but the ferrite core 281 is preferentially formed of a hard magnetic material, in particular ferrite or amorphous or, as the case may be, nanocrystalline metal. Here, materials with greater permeability are preferentially employed. A coil 251 generates a strong, high-frequency magnetic field 282. The magnetic field lines 282 are directed through the magnetic paper of banknotes 1 and subsequently through ferrite core 281, so that the field lines run completely through the ferrite core and, in that context, at least in the region of the stacked banknotes 1, a homogenous magnetic field is developed, which preferentially traverses the stack vertically in direction X. In this context, ferrite core 281 is preferentially led along either the narrow sides or the longitudinal sides of banknotes 1 so that it forms a ring that is open in the Y direction, i.e. in a direction Y perpendicular to the plane of the sheet in FIG. 47. In this way, reading device 280 can very easily be filled with a stack of banknotes 1 in the Y direction and also be emptied again so that machine processing is possible with no trouble. A preferable, successively-occurring activation of the individual banknotes in a stack can also be realized in advantageous manner in that the banknotes reciprocally activate themselves one after another. In this case, after the activation cascade has been launched through activation of an initial banknote of the stack, all others can consequently reciprocally activate themselves without further intervention from the outside. In this context, it is advantageous to conduct the activation by means of light, as described in the following more precisely, and to feed the energy necessary for this into the stack of the banknotes by means of electromagnetic waves. Naturally, the banknotes require corresponding receiving elements to be able to take up the energy made available by means of the electromagnetic waves. EXAMPLE 83 A particularly preferential example for such an internal activation is that the first-activated, e.g. lowermost banknote of the stack sends out light that is captured by the second-lowermost banknote, which, after this activation, in turn sends out light that is received by the third-lowermost banknote, etc.. In particular, the banknote will, in preferential manner, thus exhibit an optical transmitter and an optical receiver in such a case as well. In this context, the activated banknotes preferentially each send out a coded light signal, which e.g. contains information about the own value, or as the case may be, the total value of all hitherto activated banknotes. Consequently, only the light signal sent out by the last-activated banknote in the stack still needs to be measured to obtain information, for example, about the total value of the stack. Therefore, e.g. only the underside of the lowermost banknote is irradiated with light from the outside to activate this lowermost banknote and the light signal sent out by the last-activated banknote, i.e. the light exiting from the upper side of the uppermost banknote of the stack, is captured as a measurement signal. In this context, the transmitter and the receiver of the banknotes are preferentially mounted on opposite sides of the banknote paper. In the case of measurement in the aforementioned manner, they should be stacked in like orientation and location. If, on the other hand, a banknote can be activated through illumination from both the underside as well as from the upper side, and particularly also in the case that it sends out light both upwardly as well as downwardly, the aforementioned method can thus also be carried out independent of the location and orientation of the individual banknotes in the stack. In this context, the energy supply of the individual banknotes advantageously takes place through an electrical or magnetic field, with corresponding receiving devices in the banknotes. Through optical feedback to respective preceding (operable) banknotes, it is possible here, in the absence of such a reply, to presume defective banknotes. This can also be demonstrated particularly simply in that, for an interruption of the activation cascade, no outgoing light signal of the last banknote that is measurable as such is generated, and thus can [not] be measured. This variation offers the possibility to be able to simply recognize whether defective banknotes are present in a stack. In this case, the signal chain is interrupted and thus, at the other end, no outgoing signal appears or, as the case may be, not the expected outgoing signal as for an uninterrupted chain. EXAMPLE 84 With reference to FIG. 37, a measurement method for banknotes is now described, in which energy can be transmitted between adjacent banknotes in the stack by optical means. Specifically, an electromagnetic wave 402, that can be visible light, but also IR radiation and UV radiation, is irradiated onto photocell 400 of the uppermost banknote 1 in the stack. A current is generated in this [banknote] through the external photoelectric effect. With this current, chip 3 is then be supplied with energy via contact circuit 403, in which case typical voltages in chip 3 lie in the range of up to 5 V. After chip 3 of the uppermost banknote 1 has been supplied with energy, it will send out light by means of laser diode 401 on the underside, which in turn will be received by photocell 400 situated on the upper side of the banknote 1 lying directly thereunder, to in turn supply its chip with energy. This [chip] will then, in analogous fashion, transmit energy to the banknote lying thereunder, etc.. In this context, the light source for illuminating a photocell 400 of one of the outermost banknotes 1 in the stack can, by way of example, be integrated in a deposit surface of a reading device, upon which the banknotes are deposited in a stack, as is e.g. described in analogous fashion for capacitive coupling in relation to FIG. 48. To achieve positional independence, photocell 400 and laser diode 401 are preferentially arranged in the center of the banknote surface and/or particularly mounted on the two sides of individual banknotes 1. In this context, data transmission to an external reading device can take place by all of the methods described within the scope of the present invention. However, the data are preferentially out-coupled in another way, such as by electromagnetic means. Alternatively however, the chip can also transmit data to the outside by means of piezoelectrical coupling or also surface waves. Moreover, the laser diode 401 can not only be used for the energy supply of an adjacent banknote 1, but also for data transmission to this [banknote], if it sends out a modulated e.g. pulsed light signal 404 that, aside from energy, also transmits data. Furthermore, provision can be made that chip 3 first transmits its information to the outside to the reading device before it, by means of light-emitting diode 6, supplies energy to and activates chip 3 of banknote 1 situated thereunder. Consequently, chips 3 of banknote 1 can be operated sequentially. As a result of this, e.g. anticollision problems are able to be avoided in a simple way even in the case of inductive out-coupling. Although in the above, in particular, the case was described that the properties of individual banknotes are measured one after another, it is also conceivable to simultaneously measure the properties of several, in particular of all banknotes of the stack or, as the case may be, to simultaneously write to the chips of several banknotes. In this context, the coupling methods can be designed as analog inductive, capacitive and or optical. EXAMPLE 85 In the case of an optical coupling for the use of banknotes with photodiodes that e.g. lead into a side edge of the banknote paper, it is e.g. possible, through illumination of the entire surface of the banknotes from the side, to illuminate the photodiodes of several, in particular of all banknotes, and to consequently activate these almost simultaneously. Through the stimulation, they are stimulated to send out light, and the light sent out from the banknotes analyzed as an optical response signal. In the case of the device according to FIGS. 44 and 45, this could for example be realized in that, in the presence of several laser diodes, which are distributively arranged in the sidewall 222 at height H, these are not successively, but rather simultaneously activated to send out light. In addition, illumination of the entire surface of the banknote stack in the region of side edges 225 can continue to already suffice here, without the need to focus the illuminating light on the individual photodiodes in each case. This simplifies the arrangement. In this context, during evaluation of the measurement signals of detector 229, the signals that are not generated through the response light exiting out of photodiodes 227, but instead through the illuminating light of light source 224 that is not in-coupled into photodiodes 226, are, by means of reference measurement, considered disturbing signals. In a particularly simple case, this can occur in that the response signals of individual banknotes 1 each send out light at a different wavelength than the illumination light. A particular advantage of the use described in more detail in the preceding examples by way of example of an optical coupling between the evaluation device and the banknote consists in that undesired influencing of the individual signals does not occur. This means e.g. that the light signals, which are sent out from the individual banknotes, are not altered by the presence of the light signals of the other banknotes. For example, if upon activation of all banknotes of the stack to send out light simultaneously, the light sent out from all banknotes is measured summed-up by means of a detector, particularly at the same point in time or in the same time period, the properties of the banknote stack can thus be determined through evaluation of the total signal. If the light radiation sent out e.g. for all banknotes, regardless of denomination, has the same intensity and/or if the light radiation sent out for different denominations has a different frequency or, as the case may be, a different frequency spectrum, conclusions on the number of banknotes can be drawn through evaluation of the measured total intensity or, as the case may be, on the basis of frequency analysis of the measured intensity, conclusions can also be drawn on the number of banknotes per denomination and thus on the total value of the banknote stack. In addition, it is to be particularly emphasized that the preceding embodiments of the optical communications by means of photodiodes for stack measurement can also be advantageously employed for banknotes without a chip. EXAMPLE 86 Thus, e.g. in place of an LED controlled through the banknote chip, e.g. a color filter can also be used that only lets through and/or reflects a portion of the irradiated wavelengths. If e.g. as in FIGS. 44 and 45, the photodiode goes through the banknote paper, a corresponding color filter can e.g. be incorporated in the photodiode, which, upon irradiation with white light, e.g. only allows a red wavelength range through. In particular, the individual denominations will exhibit filters with different transmission properties. In the case of an optical coupling with and without a chip, visible and/or ultraviolet and/or infrared wavelengths can be used in this context. While, it was moreover explained in the above, to radiate the optical response signal at the [bank]note edge, it can then also be out-coupled perpendicularly through such a transparent window if the banknote paper exhibits transparent windows. To this end, e.g. a reflective and/or a dispersive element is incorporated in a foil of which the transparent window consists. This reflective or, as the case may be, dispersive element will out-couple light, which, for example, is irradiated into the plane of the paper by means of a photodiode, perpendicular to the plane of the paper through the transparent window. EXAMPLE 87 If the coupling does not take place optically, but rather inductively or capacitively, a reciprocal disturbance can arise during simultaneous data transmission from several transmitters to one receiver if no suitable countermeasures are taken. That means e.g. that in the case when the chips of several banknotes stimulate their inductive or, as the case may be, capacitive elements to send out signals simultaneously, the individual signals can no longer be clearly differentiated by a reading device of the evaluation device. However, this problem can be solved by the use of anticollision methods, as known in the realm of RFID (Radio Frequency Identification) systems and described e.g. in Finkenzeller's book: “RFID-Handbuch”, pp. 170-192, 2000, Carl Hanser Verlag Munich Vienna, ISBN 3-446-21278-7. In the customary manner, an “anticollision method” is thus understood to mean a method, which enables the troublefree handling of a case of multiple access to several transponders. It has become evident in that context, that for the stack measurement of sheet material with a chip according to the invention, depending on the case of application, various of the known anticollision methods can be applied particularly advantageously. Time Division Multiple Access [TDMA] method is especially suited for counting and value determination in the stack, in which [method] the entire available transmission channel capacity is temporally divided among the participants, i.e. all banknote transponders situated within range. The dynamic S-ALOHA method or, as the case may be, the dynamic binary search method are particularly preferred in this context. EXAMPLE 88 In the event, though, that the transponders of the banknotes of different denominations are adjusted to different transmission frequencies, the Time Division Multiple Access method is also preferentially used to determine if counterfeit banknotes or banknotes of an undesired denomination are contained in the stack. Through a frequency analysis of the summed-up total signal, one may, even in the case of simultaneous reception of signals from several banknotes, draw conclusions about which and, optionally, how many banknotes-denominations are situated in the stack. A general advantage of the variation where there are banknotes of different coupling frequencies, is that, by way of example, there is less overlap of the individual signals for an inductive coupling, and e.g. a temporal separation of the signals through different response-times and/or response-time-periods can also be possible in dependence on the frequency. Consequently, this advantage results for a stack measurement even if there are different delays in the reaction times in response to the signals received from the outside for different banknotes, e.g. even for the same coupling frequencies. Likewise, a lesser signal overlap can e.g. be realized in that the antenna position and/or antenna orientation on the banknote paper varies from banknote to banknote. Thus, provision can be made that the position of e.g. dipole antennas varies through rotation by certain angular amounts for different banknotes. This variation can e.g. also be denomination-specific. Usually, banknotes in the stack can initially only be addressed simultaneously via an inductive or, as the case may be, capacitive coupling. Through a control signal designed for that purpose, the banknotes can be induced to transmit their serial number or another signal that uniquely identifies the banknotes to the reading device. As soon as e.g. the serial number of the individual banknotes in the stack is known, it is also possible to address the individual banknotes in targeted fashion through appropriate control signals, in that they are individually selected and addressed e.g. through the transmission of the serial number as a parameter for the control signal. All other banknotes that do not correspond to this parameter of the control signal, will then usually not react or at least react differently, i.e. send out other response signals. It is also possible that the serial numbers of all, or at least a portion, of the banknotes of a stack were already determined by other means prior to the stack measurement. This can e.g. then be the case if, in a banknote processing apparatus, through the readout of chip data or also by other means as well, e.g. by scanning of the print image, the serial numbers of the individual banknotes are known, which are subsequently stacked as a stack and e.g. placed in cassettes. The banknotes can then be addressed in targeted fashion and individually by appropriate reading devices, such as in the banknote processing apparatus or the cassette, in a simple way that avoid anticollision problems. In the case of operation of a stack of capacitively coupled banknotes corresponding to the equivalent circuit diagram of FIG. 49, increasing distance from the beginning of the stack, i.e. from the place where energy is fed in, leads to a rapid decline in the available supply voltage. In the case of stacks with a few tens or hundreds of banknotes, a difference of one or more powers of ten can arise between the voltage fed in at the beginning of the stack and the available voltage (voltage transmission) at the last banknote in the stack. However, the voltage transmission is strongly dependent on the current uptake of the individual chips in the banknotes, as well as upon the input capacitance of the chips. Thus, the voltage transmission differs by one or more powers of ten, depending on whether all chips in the stack are switched on or switched off. EXAMPLE 89 Therefore, a further idea of the present invention consists in, that transponder chips 3, which were already able to be read out, are switched to a currentless, so-called “power-saving” or “sleep” mode. These are initially predominantly banknotes 1 at the beginning of the chain, i.e. at the shortest distance to the stimulating energy source, since there is always sufficient energy for operation of the transponder chip 3 available here. By switching off the transponder chips 3 that have been read, banknotes 1 at the end of the stack can subsequently also obtain sufficient energy for operation. In this context, the voltage to be supplied at the entrance of the stack should preferentially be selected higher, by the factor of the voltage transmission, than the minimum supply voltage of an individual transponder chip 3. For the previously-named example, a voltage of at least some 200 V would thus have to be fed in at the entrance of the stack to still be able to supply the last transponder of the stack with 1.8 V. To ensure the operation of all transponders, independent of their random position in the stack, chips 3 are preferentially equipped with a voltage control, such as a serial control unit, which can cover this voltage range. In the case of higher working frequencies, the difference in the voltage transmission between switched-on and switched-off transponder chips becomes increasingly less on account of the high pass properties of such a banknote stack. In the case of sufficiently high operating frequency, it is therefore no longer necessary to switch off the transponder chips. It is, however, to be noted that, in the case of higher frequencies, increasingly higher currents also occur at the entrance of the stack, which, on the other hand, would lead to a larger dimensioning of the reading devices. If the full operational voltage, i.e. a sufficiently high voltage, is applied at the entrance of the banknote stack in order to supply the last transponder in the stack with energy as well, all transponders in the stack are thereby thus placed in a ready-to-operate state. The attempt to communicate with the transponders in the stack initially leads to a multiple access of the transponders to the reading device. To be able to address the transponders individually, these [transponders] must initially be “singled” by the reading device by means of an anticollision algorithm. In this context, for a large number of transponders, correspondingly many iterations of the anticollision algorithm used must be run through. Even if it is assumed in this context that a transponder, once selected and read, is deactivated and no longer takes part in the following iteration loops, a considerable number of iterations still arise for a large number of simultaneously active transponders, e.g. over 600 iterations in the case of approx. 100 transponders, i.e. banknotes in the stack. This leads to a high expenditure of time to select a single transponder. To optimally shorten the time necessary for readout of the transponders in a stack, a further idea of the present invention consists in placing only a few transponders of a stack in an active condition at the beginning of the scanning process, and to activate further transponders only at a later point in time. This is preferentially achieved in that the supply voltage applied to the stack is gradually increased during the measurement process. EXAMPLE 90 Preferentially, therefore, a stack of banknotes 3 is initially fed with a voltage Umin that corresponds to the response sensitivity of the individual transponders in the stack, such as 1.8 V. In this way, only some few transponders at the beginning of the stack are supplied with sufficient energy for operation. The selection of individual transponders by means of an anticollision algorithm can then be carried out with very few iteration loops. The transponders that have already been read out are then deactivated and no longer take part in any further communications, e.g. further iterations. Thus, each transponder that has emitted its feedback can be separated from the energy supply through an electronic circuit on the chip or in a second circuit on banknote 1 connected with such chip. Therefore, it is preferentially not only switched “mute” for a certain time, but taken out of operation completely instead. In this way it is achieved that the inductance and/or capacitance and the ohmic load of chip 3 is taken out of the chain for a certain time, or preferentially, until the energy supply of the stack is switched off, e.g. by disabling a transistor. As a result, its influence on the energy supply of the bordering transponders also diminishes, i.e. these are now better supplied with energy. After each completed interaction with a transponder in the stack, the voltage at the entrance to the stack is increased by a value of ΔU, for which preferentially applies: Δ ⁢ ⁢ U = U max - U min N . Here, Umax is the maximum input voltage on the stack which is necessary to still address the last transponder in the stack. Umax is the minimum supply voltage of an individual transponder chip and N is the number of transponders in the stack. By successively increasing the voltage at the entrance to the stack, it is ensured that, little by little, even the transponder chips lying further below in the stack are supplied with sufficient energy until all transponder chips have finally been read. Provided the voltage can be balanced finely enough, it is thus even possible to manage without any anticollision, i.e. it is always only one individual chip in the stack that responds in each case. The described method of the gradual increase of the energy sent thus allows circuits in chip 3 to be provided without energy regulation in the entrance, which leads to a simplification of the integrated circuits in comparison to the previously described variation with voltage regulation in chip 3. The method of the separation of the energy supply according to the invention is more simply realizable than a control of the input voltage in chip 3. EXAMPLE 91 FIG. 48 shows, in schematic fashion, an example of a reading device 220″ for the capacitive coupling of banknotes 1 with chip 3 which exhibit capacitive coupling surfaces 256, as were described by way of example in relation to FIGS. 30, 31. Reading device 220″ exhibits a deposit surface 221, upon which a stack of banknotes 1 are automatically or manually deposited. An electrode 263 is permanently integrated in the base surface. Electrode 263 can preferentially exhibit two coupling surfaces, the dimensions of which essentially correspond to coupling surfaces 256 of banknote 1. In this context, deposit surface 221 can be executed with at least a lateral boundaries 222, to thus simplify the positioning of banknotes 1 with respect to electrode 263 of reading device 220″. In this context, this apparatus can also serve to test individual, non-stacked banknotes 1, which must be placed on depositi surface 221 for readout. An arrangement of this type in particular allows the readout of smaller stacks of e.g. 1 to 30 banknotes. A constant supply voltage can in fact be applied, but a supply voltage, which e.g. continuously or intermittently increases during the ongoing measurement process in the aforementioned way, will be preferentially applied to the two electrodes. Through the self-increasing supply voltage, an increasingly larger number of banknotes in the stack can be addressed. An advantage of a capacitive coupling in comparison to an inductive coupling consists in that it leads to fewer cases of mutual influencing of the individual banknote transponders in a stack among themselves and thus to an analytic more accurately predictable effect. Among other things, this variation is also of advantage for a stack measurement in automatic tellers in particular, specifically in their input pocket and in cassettes. EXAMPLE 92 A further idea for capacitive coupling consists of inserting, in a stack of banknotes 1 with capacitive coupling surfaces 256, at least one electrode into the stack, in order to have to address fewer banknotes simultaneously. Thus, e.g. in the case of device 220″ according to FIG. 48, there can be one or more retractable and extensible electrodes, which are sufficiently thin—in particular at their front region as well, which is intended to be extended into a banknote stack to be tested—in order to not fold or jam the banknotes. These can e.g. be incorporated at predetermined heights [with respect] to base surface 221, in order to move such an electrode into the stack for measurement when stacking a large number of banknotes e.g. all 100 banknotes. EXAMPLE 93 FIG. 49 shows, by way of example, the electrical equivalent circuit diagram of a stack with two capacitively coupled banknotes 1 stacked on top of one another, where the circuit depicted in the first, left banknote 1 in FIG. 49, is also present for the merely schematically indicated, second banknote 1. The circuit diagram of the stack can naturally also be expanded in the form of a series connection of quadripoles (No. 1 in FIG. 49) for a larger number of banknotes 1 in the stack. If two banknotes are stacked on top of one another, a capacitance Ck thus arises between any two electrodes presently lying on top of one another, i.e. coupling surfaces 256. By mounting two electrodes 256 on one banknote side, two coupling capacitors are thus available to each banknote 1. For chip 3, however, the two coupling capacitances appear as a serial connection of the individual capacitances, for which ffreason only ½ Ck is effective in the equivalent circuit diagram. The capacitance Cp represents the sum of the input capacitance of transponder chip 3 and all parasitic capacitances and RL [represents] the input resistance of chip 3. This system of the stacking of banknotes according to FIG. 30 is principally operable. However, it exhibits the disadvantage that the available supply voltage decreases very quickly toward the end of the chain, i.e. banknotes 1 in the stack. As a result, very high voltages must be fed in at the entrance of the stack in order to make sufficient energy available for the operation of a chip 3 at the end of the stack as well. EXAMPLE 94 According to a further idea, an inductance Lp of defined value is connected in parallel to parasitic capacitance Cp in order to improve energy transmission in the stack. A valid equivalent circuit diagram for this purpose, illustrated in analogy to FIG. 49, is depicted in FIG. 50. The dashed line with the reference character “3” identifies the region of the influencing variables of chip 3. In this context, the value of inductance Lp is preferentially selected such that the phase angle of the i2 current generated through parasitic capacitance Cp is compensated within the stack through inductance Lp. A typical value for Lp amounts to roughly 0.3 μH. In this context, when dimensioning, care must be taken that the individual elements in the stack are capacitively coupled among one another and reciprocally influence each other in respect of their effect. The common resonance frequency fres of the banknote, determined by the elements Cp and Lp (parallel oscillating circuit), therefore does not correspond to the operating frequency fb of the stack, but rather lies about one or more powers of ten higher. The selected circuit configuration yields a bandpass filter of the Nth order for a stack of N banknotes 1. A stack of 100 banknotes 1 corresponds to a bandpass filter of the 100th order; a stack of 1000 banknotes 1 to a bandpass filter of the 1000th order. As simulated calculations show, by switching in the inductance Lp, significantly better properties with respect to energy transmission result than for the arrangement according to FIG. 49. The improved arrangement is depicted in FIG. 50. EXAMPLE 95 If a banknote outside of the stack is read by means of capacitive coupling, Cp and Lp together with coupling capacitance Ck form an oscillating circuit. Since the resultant resonant frequency of this oscillating circuit lies some powers of ten above the usually employed working frequency for capacitively coupled systems, the readout of banknote 1 outside of the stack is usually impaired by the additional inductance Lp. Therefore provision is made to design the inductance Lp such that it can be switched on or switched off, e.g. by chip 3, according to the operating state of the banknote 1. The inductance Lp is preferentially in a switched off state in the initial state of the chip, so that it is designed for the examination of one individual [bank]note in particular. If banknote 1 is read out in a stack, the inductance Lp will thus connected to it additionally by chip 3. Alternatively, the opposite embodiment, i.e. that inductance Lp is not switched off until there is a pending examination of an individual note, is naturally possible as well. It is also conceivable that the inductance is switched on or switched off prior to a stack measurement or an individual note measurement in each case and again switched back to the original state after the measurement. Various methods of switching are conceivable in this context. It is also possible to have repeated sending-out of a special command, i.e. control signal, in order to successively induce chips 1 in a stack to switch on inductance Lp. Energy transmission is successively increased, e.g. corresponding to the previously described method, to reach all the banknotes starting at the beginning of the stack. The use of different frequency ranges to read out chips 3 in the stack or outside of the stack is an alternative or addition to this. Thus e.g. a frequency of 50 MHz to read out one individual banknote 1 over a certain distance, and another frequency of e.g. 13.56 MHz to read out in the stack, can be used. Here, chips 3 have a unit to recognize the frequency of the signal being applied. If an operating frequency is detected, which is used for the reading in the stack, the inductance Lp is thus automatically connected to it additionally in order to optimize energy transmission in the stack. In this way, energy transmission in the stack is successively built up from the beginning of the stack after application of a reading signal. A further alternative or supplement consists in the evaluation of other physical parameters in chip 3. By way of example, it is thus conceivable, for instance, to equip chip 3 with optical sensors which must be addressed additionally for reading outside of the stack to prevent an inductance Lp from being connected additionally. Thus, provision can be made e.g. that reading in the stack is usually conducted in a darkened environment, i.e. a largely lighttight, closed housing in order to permit inductance Lp to be switched on. In this way, energy transmission in the stack is once again successively built from the beginning of the stack after application of a reading signal. E.g. the following two methods are possible for realizing the necessary inductance Lp. EXAMPLE 96 The inductance Lp can either be applied to the chip 3 through galvanic deposition (“coil-on-chip”) or integrated on the chip itself (“on-silicon”) or realized externally on the banknote. Alternatively, inductance Lp is simulated by an electronic circuit in chip 3. Circuits which allow a rotation of the phase angle of i2 current are suited for this purpose. The so-called “gyrator circuit” is suited for this purpose. One arrangement for communication with chip 3 in the stack fundamentally comprises an energy source as the sending unit, i.e. specifically, a voltage source and an associated modulator that permits data to be transferred to chips 3 of the banknotes, as well as a receiving unit to be able to receive the data sent back from chips 3. In the case of associated reading devices, the sending unit and the receiving unit can use the same coupling unit, i.e. antenna that serves both for transmission of data and for reception of data. This can, however, make expensive circuits necessary in order to decouple the various signals from one another. EXAMPLE 97 A further idea of the present invention, which serves for the optimization of the arrangements for the reception of the transmitted data, therefore consists in separating the sending unit, specifically the voltage source provided for it, and the receiving unit from one another and equipping each of them with their own coupling units as antennas. An example for a possible embodiment is depicted in FIG. 51. Here, energy and data are coupled in on one side, in FIG. 5 1, for example, the upper side in the stack of banknotes 1. In this context, for in-coupling, device 270 comprises an in-coupling electrode 271 in the form of a pair of capacitive coupling surfaces 271, which preferentially correspond in form to the dimensions of coupling surfaces 256 of the banknotes 1, as depicted in FIGS. 30 and 31. The coupling surfaces 271 are connected with a unit 272 with a voltage source and a modulator. The readout of data sent from banknotes 1, such as their serial number, takes place through coupling on the opposite side of the stack. Receiving unit 273 likewise exhibits two capacitive coupling surfaces 271 a, which are connected to an evaluation unit 273. Optionally, a further receiving unit 274 can also be incorporated parallel to the voltage source 272, as depicted in FIG. 51. EXAMPLE 98 Based on the technical method of the preceding chapters, an anticollision method can be realized which permits the readout of data that is uniquely associated with a specific chip 3, such as the serial number of the chip, for instance, within only one iteration loop. The method is based on bit-wise arbitration of the serial data stream. To this end, chips 3 preferentially have a receiving unit, by means of which data, e.g. from the reading device 270 with a voltage source and a modulator according to FIG. 51, can be detected and evaluated. Further, chips 3 can preferentially have a circuit for load modulation. In this context, both ohmic load modulation as well as capacitive load modulation can be used. In addition, chips 3 have a unique serial number or the like, which is only used by one individual banknote in each case. According to the invention, a bit coding with the properties RZ (return to zero), such as a so-called Manchester code or modified Miller code, for instance, is preferentially used for the data transfer from chips 3 to the receiving device. The anticollision method described in the following can in fact also be conducted with NRZ (non return to zero) encrypting, but RZ codings are preferred on account of easier detectability of a collision that has occurred. Details on the modulation method and coding method can, by way of example, be taken from Finkenzeller's book [manual]: “RFID-Handbuch”, 2002, Carl Hanser Verlag Munich Vienna, ISBN 3-446-22071-2, pp. 189-198. In addition, the chips 3 can have a detection apparatus, which permits individual chip 3, to recognize whether, during the transmission of a logical “0” or “1” to reading device 270, a signal that is logically inverse in each case—i.e. “1” or “0”—is simultaneously transmitted through a further chip 3 in the banknote stack. To this end, the input voltage of chip 3 is evaluated preferentially, since it is influenced within the entire stack by the load modulation of an arbitrary chip 3 in the stack, such that the load modulation of each individual chip 3 in the stack can be detected by both a reading device 270 as well as by all other chips 3 in a banknote stack. According to a further idea, the banknotes 1 in the stack are initially all called upon, through a specific signal or command of reading device 270, e.g. through modulation of the energy fed into the stack, to begin with the synchronous transmission of their unique serial numbers to reading device 270. During the transmission of the own data, chips 3 continually detect the input voltage upon signals of other chips 3 in the stack. If, during the transmission of a “1” or “0” bit, a collision is determined through detection of the signal at the entrance to chip 3, a portion of chips 3 then immediately breaks off the transmission of their own serial numbers. The type of coding, as well as the definition of the algorithm to be applied can be used to define which bit value is considered dominant in each case. In case, by way of example, the bit value “1” is defined as dominant, then all chips with a “0” in the corresponding location will immediately break off further transmission of their own serial number in the case of a collision. This method is preferentially executed for each bit to be transferred, so that, ultimately, only a single chip 3 in the stack can transmit a complete serial number. To be able to successively read out the serial numbers of all chips 3 in a stack, the following two methods can be employed, for example: As soon as a chip has successfully transmitted its own serial number, it switches to an operating state, in which it no longer reacts to a further signal or command to transmit the serial number, so that it will no longer take part in subsequent iterations. For very large stacks of e.g. 100 to 1000 banknotes 1, it is conceivable that a load modulation signal generated by the last banknotes in the stack can no longer be detected by banknotes 1 at the beginning of the stack, i.e. near voltage source 271. Then, it will potentially no longer be readily possible for chips 3 to switch off automatically. For this case, a command is therefore preferentially provided, by means of which a chip 3, by sending out its serial number, as a rule the serial number which was recognized in the preceding iteration step, is switched, by reading device 270, into an operating state in which it no longer reacts to a further signal or command to transmit the serial number. EXAMPLE 99 Numerous variations are conceivable in relation to the aforementioned embodiments. One possibility consists of mounting an additional receiving device parallel to the voltage source at the beginning of the stack, as was described in relation to FIG. 51. Through comparison of the, potentially different, sum signals that appear at the entrance and the exit of the stack in the case of load modulation, problems in the reciprocal detection of the banknote—e.g. through signals that are too weak on account of spacing that is too large in the stack—can be recognized and countermeasures initiated. EXAMPLE 100 Aside from the preferential variation according to the invention of feeding the stack with energy from only one side through a voltage source, the possibility also exists to supply the stack with energy from both sides via the capacitive coupling. The procedure described results in that, through the readout and (self-) switching-off of chip 3, the number of the simultaneously “sending” chips 3 is successively reduced during the processing of the stack. In the initial phase, on account of the large number of chips 3 that remain active, the influence of the load modulation can cause the supply voltage of chips 3 at the end of the stack to “break down” during the data transmission of the chips 3. According to the invention, chips 3 should therefore immediately break off the data transmission in the current iteration and wait for the next signal or command to transfer their serial number if they fall below a minimum voltage, such as through detection of the input level or, in the extreme case, the appearance of a “power-on-reset”. However, in case e.g. at a later point in time of the processing of the stack, there are still correspondingly few chips 3 participating in the data transmission, chips 3 at the end of the stack can also completely transmit their serial number without a breakdown of the supply voltage. EXAMPLE 101 The method described is based on the participating chips 3 themselves working through the anticollision. However, methods are known according to which a reading device carry outs recognition of an anticollision and works through a corresponding algorithm. One such method, by way of example, is the binary search tree, the so-called “binary search”, as explained, for example, in Finkenzeller's book: “RFID-Handbuch”, 2002, Carl Hanser Verlag Munich Vienna, ISBN 3-446-22071-2, pp. 189-198. A very advantageous variation according to a further idea of the present invention can consist in combining both methods, i.e. the previously described arbitration method e.g. with such a binary search tree. This is then particularly expedient if, on the basis of the high number of the chips in the stack of e.g. 100 to 1000 banknotes, it can no longer be assumed that all participating chips can still detect each other. In this context, the advantage of the combination with an external reading device for anticollision detection is that it can be constructed of technically more elaborate circuitry in order to also recognize weaker signals. According to a variation, provision can therefore be made to use a suitable code for reliable anticollision detection by a reading device, such as a Manchester code. Furthermore, according to the invention, provision can be made to combine both methods such that a pre-selection is already made through the autonomous switching-off of the chips, remaining collisions can be resolved through the reading device by means of the method of the binary search tree. EXAMPLE 102 Particularly in the above-described case of inductive and/or capacitive coupling, it can already suffice if, in a measurement process, not all banknotes are recognized, but rather only a portion of the banknotes of a stack are recognized or, as the case may be, examined in noncontacting fashion. Thus, e.g. recognition of an individual illegal banknotes that are, e.g. stolen money or extorted money, can suffice so that a quantity of banknotes to be examined is recognized as suspicious. An identification of all banknotes is not necessary in this case. This applies likewise for the case where merely the existence of banknotes, which are e.g. hidden in a suitcase or the like, needs to be ascertained. In the case of a customs inspection it can, by way of example, suffice, if the banknotes per se are detected, particularly in a large amount and/or with a higher total value. This likewise does not require each individual note to be identified. It is to be emphasized that the previously mentioned optical, inductive and/or capacitive coupling methods can also be used to carry out a signal transmission to and/or from individual banknotes. Although the aforementioned coupling methods are thus specially designed for stack processing, they can also be used for the processing of individual, e.g. singled banknotes, for example, in the processing apparatuses described in this application as well, such as the banknote sorting apparatuses and/or counting apparatuses and/or money depositing machines and/or money dispensing machines and/or registers and/or manual testing devices. EXAMPLE 103 As was already mentioned, the supply of an electrical circuit of a banknote by means of a piezoelectrical element, that likewise is la component of the banknote, offers particular advantages in the processing of stacked banknotes. In that context, e.g. a transducer generates a continuous high-frequency ultrasonic signal for the voltage supply of the electrical circuit. The equally-frequent alternating voltage that thus occurs on the piezo element is rectified and serves as the supply voltage of the electrical circuit. The frequency of the alternating voltage tapped by the piezo element can simultaneously be used as the reference frequency for generation of the clock frequency on the microchip. In a further development of the invention, at least a portion of the energy is directed to an input capacitor, as a result of which it is charged. After a time that is sufficient to completely charge the input capacitor in the microchip, the ultrasonic signal of the sensor is switched off. This switching-off is recognized by the microchip, whereupon it now generates an ultrasonic signal itself to thereby transmit data to the sensor. Here, the same piezoelectrical coupling element can be used as was previously employed for reception of the signal from the interrogation device. For data transmission from the sensor to the electrical circuit it is also possible to alter, i.e. to modulate, the physical parameters of the ultrasonic wave, i.e. amplitude, frequency or phase position to the tact of the data to be transmitted. In this context, known methods, such as ASK (amplitude shift keying), FSK (frequency shift keying) and PSK (phase shift keying) can be used, as described e.g. in Finkenzeller's book: “RFID-Handbuch”, pp. 156-164, 2000, Carl Hanser Verlag Munich Vienna, ISBN 3-446-21278-7. To design the circuit technology for modulation of the signals in the electrical circuit of the banknote as simply as possible, amplitude shift keying (ASK) is particularly suited. If an ultrasonic wave encounters a piezoelectrical element, a portion of the ultrasonic wave passes through the piezoelectrical element unhindered (transmission). A small portion of the acoustic wave is absorbed by the elements and converted into electrical energy. Another small portion of the acoustic wave is reflected from the element and thus returns to the ultrasonic transmitter (sensor). From the known reversibility of the piezoelectrical effect, results a repercussion of the electrical properties of the electrical circuit connected to the piezoelectrical element on the reflection properties of the piezoelectrical element. Thus, through alteration of the input impedance of the connected electrical circuit, the ultrasonic wave reflected from the piezoelectrical element can be altered in magnitude and phase position. Through the alteration of the input impedance of the electrical circuit in the tact of the data to be transmitted, a reflection modulation (backscatter modulation) can be generated that can be interpreted through the sensor, i.e. demodulated. The reflected signal is now received at the sensor, parallel to the generation of a continuous ultrasonic signal. Through the modulation of the reflected signal with data, a frequency spectrum arises that is likewise received through the sensor. After filtering out of the frequency of the continuous ultrasonic signal, the received frequency spectrum can be easily demodulated and from it, the sent data recovered. A second possibility consists in sending out a very high-frequency interrogation pulse alongside the continuous ultrasonic signal. Differences in the amplitude and the phase position of the received reflections of two successive interrogation impulses allow conclusions to be drawn on the alterations, which are due to modulation, of the reflection properties of the electrical circuits. Starting from a “reference reflection” in the unmodulated state of the electrical circuit, alterations of the amplitude and phase of the reflected interrogation impulse can be interpreted as logical “0” and “1” sequences. Expediently, the frequency of the interrogation impulse is selected such that it represents a multiple of the bit rate of the data transmission. The method according to the invention is further developed in such fashion that the electrical circuit sends data back to the sensor on a second ultrasonic frequency via the piezoelectrical element. The use of a second piezoelectrical element is also possible. EXAMPLE 104 In a further development according to the invention, banknotes are arranged in a stack, with a layering sequence of paper-piezo element-paper arises. If such a layering sequence is scanned with a high-frequency ultrasonic interrogation pulse, the layering sequence can then be reconstructed from the reflections. The attainable resolution is dependent upon the frequency of the interrogation pulse and, in the case of suitable frequency, lies in the order of the banknote thickness: Ultrasonic Frequency Axial Resolution 10 MHz 160 μm 20 MHz 80 μm 50 MHz 30 μm 75 MHz 20 μm In this way, individual banknotes, whose thickness usually lies in the range of 80 μm, can readily be differentiated. In a further development of detection in the stack according to the invention, the banknotes are initially stimulated with a continuous low frequency ultrasonic signal in order to ensure the voltage supply of the electrical circuits. The reflection coefficient of the individual layers is determined with a second, high-frequency interrogation pulse. Through the electrical circuits in the banknotes, the reflection factor of the piezoelectrical element is now modulated in the tact of the data to be transmitted (e.g. serial number and denomination of the banknote). As a result of the different delay time of the signals reflected from the individual banknotes in the stack, the assignment of a signal to the spatial position of the banknote in the stack is possible. Through the interpretation of the individual, temporally-altered reflection factors as data stream, it is possible to carry out a data transmission to the sensor of all banknotes simultaneously (in parallel). Through the defined relation of the individual reflections to the actual locational position of the piezo element in the stack, a precise assignment of the received data to the individual banknotes in the stack is possible. The sequence of the received serial numbers thus represents their actual sequence in the stack. A further possibility consists in the focusing of ultrasonic waves. In this way it is possible to focus an interrogation pulse on a single banknote in a stack, for instance, and to read it out in targeted fashion. Through the focusing of the continuous ultrasonic signal serving the energy supply of the electrical circuits onto an individual banknote, it is further possible to activate individual electrical circuits in targeted fashion. All other electrical circuits in a stack are without voltage supply at this time and thus inactive. EXAMPLE 105 As an alternative to the previously described method, it is also possible to realize the addressing or the detection in the transmission mode. EXAMPLE 106 In a further development, provision is made to supply the electrical circuits with energy through a continuous ultrasonic signal. This signal is also used for the transmission of data from the sensor to the electrical circuit. For data transmission from the electrical circuit to the sensor, an electrical, magnetic or electromagnetic coupling is used. To this end, the electrical circuit generates, by means of an oscillation apparatus, a high-frequency voltage, which is fed into a corresponding coupling element. In this context, this is preferentially a frequency in the microwave range (e.g. 2.45 GHz), the coupling element can already readily be a component of the electrical circuit at these frequencies, in case it is designed as an integrated circuit. EXAMPLE 107 Good propagation (low damping) of ultrasonic waves is only present in solid materials or fluids. In gases (air), one must reckon with poor dispersal (high damping). Therefore, in the case of a further development, a design is provided, wherein the ultrasonic transmitter (sensor) is followed by an adaptation layer, upon which the banknote or banknotes slated to be assessed follow. These, in turn, are followed by an adaptation layer, and finally an acoustical absorber. In this context, the banknotes are pressed between the two adaptation layers in a mechanical apparatus with as great a force as possible in order to achieve the best acoustic coupling possible between the individual layers. The acoustic absorber, which is likewise connected to the banknote stack via an adaptation layer, is located on the side opposite the ultrasonic transmitter (sensor). The object of this absorber is to completely absorb the acoustic wave going through the banknote stack in order to suppress interfering reflections. Particular advantages result in the described use of ultrasound for the evaluation of electrical circuits of banknotes, in particular in the case of application in metallic housings, such as in the described transportation containers or in vaults. As described above, the piezoelectrical element can be present as a foil of piezoelectrical material. If both sides of the sheet are at least partially attenuated metallically for the formation of the electrodes, then the filament can bend in the rhythm of the electrical voltage through application of voltage to the two metallic electrodes. In this context, it sends out sonic waves. In this context, however, the fact that, when high-frequency ultrasonic signals are used, the oscillations of the foil no longer lie in the range of audibility, so that reproduction of an audible signal through the foil is not possible, is problematic in certain cases. To avoid this, the energy supply and the response of the piezo foil are decoupled so that the irradiation of the necessary energy for the operation of the piezo foil does not disturb the response of the piezo foil. As already described, this takes place e.g. such that an integrated circuit is used additionally, which [integrated circuit] is conductively connected with the electrode of the piezo foil, is integrated in the vicinity of the sheet or preferentially on the sheet itself. To this end, the irradiated frequency can lie above the band of audibility and even in the range of up to a few gigahertz. The irradiated energy is directed to the circuit and there elicits a response at a different frequency. Alternatively, the energy is stored for a short time and subsequently used for the generation of a time-shifted response. The advantage of this embodiment lies in the fact that irradiation of the energy and reception of the response do not interfere with one another and that, thus, better and more reliable operation of the circuit becomes possible. In another embodiment, the energy can also be irradiated as ultrasound. The sonic waves would then have to be picked up and rectified by a portion of the piezo foil acting as microphone, after which the resulting voltage could be used for operation of a circuit. This would then elicit the response of the piezo foil. A corresponding mode of operation would also be possible through the irradiation of light onto a photoelectric cell instead of ultrasound. By way of example, the response of the electrical circuit is now directed onto the electrodes on the one side of the foil on the one hand, and onto the metal layer on the other side of the foil on the other hand. This makes it possible to make the response of the circuit audible or, as the case may be, demonstrable through vibrations of the sheet in the audible range or in the ultrasonic range. EXAMPLE 108 In an exemplary embodiment, a sequence of data is stored in the electrical circuit, the transmission of which [data] onto the piezo element or, as the case may be, the piezo foil, generates a tone or a sound. This can comprise a simple sinus tone, but also speech, sounds, etc.. By way of example, a rustling sound, which copies the crackling of a real banknote and is reproduced sufficiently loudly, can be generated. Likewise, comprehensible messages can be generated, e.g. the denomination of the banknote: 10 , etc.. The sonic oscillations emitted by the piezo element can comprise audible tones and/or represent sonic waves that can be demonstrated by the use of measurement technology. By way of example, an ultrasonic signal can be generated that is picked up by a microphone and tested via a control circuit. In a simplified embodiment, provision is made for a high-frequency electromagnetic signal to be received by means of an antenna. The energy obtained in this context is used for the operation of a frequency generator, the output of which is connected with the piezo element, which e.g. emits a tone that corresponds to the high-frequency electromagnetic signal or, as the case may be, is derived from same. Provision can also be made that the electrical circuit contains stored information which determines frequency and/or intensity of the signals, which are emitted by the piezo element or, as the case may be, by the piezo foil. Through irradiation from sonic waves, the piezo element or, as the case may be, by the piezo foil is stimulated to give off electrical voltages. The corresponding electrical charge is used to supply the integrated circuit and induces it, in accordance with the stored data, to send out a message, work off a program, etc. and to modulate a signal on the piezo foil. In this context, the irradiated energy can also be stored briefly and then serves in the temporally-displaced delivery of a response via the circuit and the piezo foil, while the irradiated frequency can, in the meantime, be switched off. EXAMPLE 109 As already shown in the above, a particular problem consists in feeding a stack of banknotes with sufficient energy for the operation of all of the chips contained therein. A further solution is therefore presented in the following, in the context of which, by means of electromagnetic fields, particularly in the low frequency range of less than 100 KHz, energy for the operation of the transponder chips in a stack of banknotes can be effectively transmitted. For one, this can occur in that an electrical alternating voltage is generated from an external magnetic field by means of induction in a coil of a banknote, which [voltage] supplies the chip with energy and/or data, as has already been described. However, this requires the realization of a coil with several turns on a banknote. Alternatively, the frequency of the magnetic field can also be selected sufficiently high to be able to use a coil with only a few turns. Effective energy transmission through magnetic induction requires working frequencies in the range >10 MHz which e.g. can only be realized by elaborate means through polymer electronics. EXAMPLE 110 One idea of the present invention therefore consists in using the magnetostrictive effect in place of the effect of magnetic induction. As a result, no large-surface coils are needed on the banknotes and working frequencies in ranges of a few 10 KHz can be selected. In this way, for one, the necessary circuits in the banknote with a chip can also be realized by means of polymer electronics, and for the other, the electronics for generating the necessary fields can also be realized more simply. If e.g. the compound materials according to FIG. 27 or, as the case may be, FIG. 28 are used, generation of a sufficiently high electrical alternating voltage, which is proportional to an alternating magnetic field 363 applied from the outside, is thus possible while at the same time avoiding electrical induction. Strong alternating magnetic fields, which flow through the volume of a stack in the vertical direction at high-frequency ranges of e.g. more than 10 MHz, are needed when coils are used for the energy supply of the banknotes, particularly in the case of readout in the stack. In the case of the solution with magnetostrictive materials, it is already sufficient, compared to the foregoing, to generate a locally strong alternating magnetic field, which particularly or exclusively flows through magnetostrictive metal strips 360, as depicted in FIG. 28 by way of example. Since magnetostrictive metal strips 360 exhibit significantly higher magnetic permeability than the carrier material, i.e. the paper of banknote 1, it is by contrast easier to direct a large portion of the generated magnetic flux through the active magnet strips. The requirement of having to generate a sufficiently strong magnetic field in a small portion of volume in comparison to the total volume of the banknote stack simplifies the development of a suitable reading device. Moreover, the field does not have to flow through the stack in a vertical stack direction, but rather only in a horizontal direction, which can simplify integration in a banknote processing apparatus. The method according to the invention preferentially works in frequency ranges of less than 100 KHz, typically of a few 10 KHz, thus also permitting the use of chips on the basis of polymer electronics. This further permits the development of simple reading electronics, since even “NF” amplifiers can be used for the generation of the necessary electrical power. EXAMPLE 111 Two possible built-on accessories of suitable reading devices 370 for such banknotes are depicted in FIG. 52. In this context, for the generation of a sufficiently strong magnetic field, a magnetic field generation unit 371, e.g. in the form of a horseshoe 371, i.e. a U-shaped component 371 made of highly permeable material, upon which an exciter coil 372 is wound, is used in each case. This in turn is fed with an alternating current by the output amplifiers of reading device 370. In this context, the magnetic field should be generated to be so wide that it can also act on the strips 363 of banknotes that are not stacked flush or, as the case may be, banknotes of varying formats. Upper FIG. 52a shows a reading device 370 for a single banknote or a small number of banknotes, such as can occur at a register. A mechanical apparatus 373 in the form of e.g. a right-angled stop on a depositing surface 374 ensures that a banknote 1 lying on the deposit is held in the right position. In this context, the magnetic field generation unit 371 is preferentially situated underneath the depositing surface 374. FIG. 52b shows a reading device 370 for use in a banknote processing machine, i.e. in particular an apparatus for automatic counting and/or sorting of banknotes. The fundamental design corresponds to reading device 370 according to FIG. 52a, but the limbs of magnetic field generation unit 371 are arranged such that its magnetic field 363 can simultaneously penetrate strips 360 of the stacked banknotes in this region. Here, stacked banknotes 1 are depicted as semi-transparent for better clarity. It is e.g. also conceivable that such a reading device is integrated in an input pocket of a sorting and/or counting apparatus or, as the case may be, an automatic teller, with the banknotes, which are stacked, being slid in between the limbs, i.e. the magnetic pole 374 of the magnetic field generation unit 371, or transported there. If the strip 360 to be tested is not integrated centrally on the banknote paper, reading devices 370 according to FIG. 52 can then exhibit a second magnetic field generation unit 371 which is positioned at the alternative possible position of strip 360. A positional invariance of the banknote 1 during testing is thus obtained. In this case, e.g. in the case of the arrangement according to FIG. 18b) in the case of integration in an input pocket of a processing apparatus, the banknotes are placed in the hollow formed by units 371 or transported into same. Since the effect described according to the invention is also reversible, strip 360 can, upon appropriate control by chip 3, also be used additionally or alternatively in this arrangement in order to send data from banknote 1 back to the reading devices 370 according to FIG. 52. For this purpose e.g. load modulation or a signal at half of the working frequency can be used. The reading devices described have the advantage that banknotes 1 can no longer be read out over a greater distance. As a result, the anonymity of an owner can be ensured particularly simply and reliably, in particular, pocket reading devices are used. EXAMPLE 112 As was already described in relation to FIG. 28, the method with photodiodes, preferentially LISA photodiodes, as described at another location of this invention, can also be used for readout of banknotes 1. A suitable readout device to this end for reading in the stack is depicted in FIG. 53. By way of example, in the case that LISA photodiode 227′ and compound strip 360 are arranged such that they overlap or are at least lie very close together, a deviating prism 375 is used to ensure a separation of magnetic field lines 363 from light beams 288. Among other things, this also permits the sensitive electronics for the detection of the LISA emissions such as, e.g. a CCD camera, to be effectively shielded against the magnetic fields of magnetic field generation unit 37 1. The deviation prism is preferentially mounted between magnetic pole 374 and banknotes 1 to be tested. One possibility for increasing the efficiency e.g. of this arrangement consists in setting the frequency of alternating magnetic field 363 equal to the mechanical resonance frequency of compound material 360. Upon stimulation by an alternating magnetic field 363, a magnetostrictive metal strip 361 exhibits pronounced acoustic resonance frequencies, which exhibit particularly large amplitudes of mechanical vibration. This effect is also to be expected in compound material 360. Through the coating with additional materials, such as strips 362, 364, a damping occurs, however, as a result of which the resonance effects manifest themselves less strongly. EXAMPLE 113 As an alternative to the above-described variations, provision can also be made that the voltage supply and/or communication of the banknote with the reading device takes place through a contact-type electrical connection. In this context, the voltage supply and communication from the reading device into the banknote can occur via the contact surfaces, while communication from the banknote to the reading device takes place in another form, such as optically or inductively. The individual banknotes will preferentially exhibit contact surfaces on both sides, among other things, for the purpose of simultaneous contacting of more than one banknote. In this context, the contact surfaces of the two sides will be electrically connected to one another for galvanic coupling. To this end, the stack to be measured will preferentially be pressed together in order to achieve better contact between adjacent banknotes. If the contact surfaces are all arranged centrally, and if they are thus at least located at the center, i.e. the intersection of the lateral diagonals of the banknote, or are at least symmetrically arranged in relation to this center, contacting of banknotes is possible in all four positions, for which e.g. their front side and back side and left side and right side are exchanged any way whatsoever. Here e.g. banknotes 1 can be utilized, which are depicted in FIG. 34 or, as the case may be, 35. To contact a stack of such banknotes 1, the stack must be pressed together such that layers 380 of all banknotes 1 in the stack are electronically conductively connected. The two outermost, i.e. the uppermost and the lowermost contact layers 380 are then each contacted from the outside by an electrical contact clamp. An energy supply of this type permits the number of direct contacts 380 (galvanic contacts) to be reduced to just two in the simplest case. Naturally, solutions with more than two contacts 380 are also possible, if this offers advantages. Preferentially, contacting of a processing device to a banknote 1 will take place via contacts 380, which are significantly larger than chip 3 and preferentially at least 1 cm2 in size. This makes it possible to galvanically address a stack of banknotes 1 of any thickness whatsoever simultaneously. This galvanic coupling preferentially serves in the energy supply of the chip 3. Driving of the chip and data transmission can then optionally also take place via another method, e.g. a noncontacting inductive or optical coupling. Consequently, control and/or data transmission can take place independently of the energy supply. This has the advantage of being able to keep the intensity of the electromagnetic fields low, since no power supply of the chips must take place by this means. In the case that the elements of the stack must be stacked without regard to their orientation, the polarity of the applied energy supply must be observed. This can e.g. be compensated for, in that an alternating current is applied to galvanic contacts 380 and that the chip or, as the case may be, line 381 exhibits an associated rectifier. Alternatively, a DC voltage can also be applied. In addition, it is preferred that the contacted banknotes situated in a stack can communicate with one another directly, as has already been described in relation to an optical coupling by way of example. To this end, e.g. banknotes 1 according to FIG. 35 can also be used. These can be contacted such that chips 3 are successively addressed, i.e. e.g. activated. Here, by way of example, the entire banknote stack can initially be supplied with energy by connecting voltage to the outermost conductive contact strips 380. In this context, if all chips 3 are deactivated first, then, by additional contacting e.g. of the upper third contact 382 of the uppermost banknote 1 in the stack, a transistor or another suitable switch element of chip 3 of this banknote 1 is supplied with a control signal, which enables the switch element and thereby activates chip 3 of uppermost banknote 1. Subsequently, banknote 1 lying thereunder is activated a control signal of chip 3 of the uppermost banknote 1 being sent out via the fourth contact 382 located on the underside of uppermost banknote 1. The precondition in this context consists in that contacts 382 of individual banknotes 1 in the stack are positioned such that the third contact or, as the case may be, the fourth contact 383 lie one over another in the case of suitable stacking and thus establish the galvanic contact between two banknotes each lying one over another. In this context, the third and fourth contacts 383 are particularly preferentially designed the same and/or can fulfill the same function, in order to be independent of the position of individual banknotes 1 in the stack. By way of example, this method thereby allows the energy supply to be applied galvanically to the entire banknote stack simultaneously, while banknotes 1 can be activated successively in the manner mentioned. Here as well, preferentially e.g. only one of banknote chips 3 at a time can be simultaneously active. Disabling and Enabling of Banknotes As was already briefly mentioned above, a further essential idea of the present invention consists of writing about the validity of a note into a memory of the banknote chip, e.g. of an EEPROM or a PROM. EXAMPLE 114 It is in principle conceivable, for example, that a code be written by banks authorized to do so to the memory of the banknote, which marks the banknote, so that this condition will be recognized for such banknote chips by the associated reading devices, and so that the banknotes can then be classified as marked or invalid. Disabling and enabling is thus effected by changing at least one dedicated bit in the memory of the banknote chip. In order to also be able to recognize this marking or status setting, as the case may be, without a reading device, the state of validity can be additionally displayed on an optical or acoustic display device integrated into the banknote paper, such as an LED or LCD display. In the simplest case, a suitable bistable display such as an LED in the banknote, which is switched on or off in the case of an invalid note, will suffice. Said display device can have properties as described in a following chapter entitled “Commerce.” The superordinate idealistic value of a banknote is, however, to be seen in its anonymity and its neutrality. If the authenticity of the paper's features is to already suffice within this meaning in order to be able to use the banknote unreservedly as a means of exchange in any given transaction, the “temporary” invalidation of banknotes as relevant for the end consumer is to a large extent prohibited. Despite the theoretical possibility of an occasional “disabling” in an authentic banknote, this possibility is thus prohibited, at least as regards the end consumer. Nevertheless, this technical possibility offers entirely new security concepts. If one is to actually utilize the technically “invisible” information of the banknote chip memory, that the note is “disabled,” the central offices within the banknote circulation can in fact receive valuable information from this. Since it is possible for a machine to read out the chip data, data can be collected during the normal processing of the banknotes in banknote sorting machines, e.g. of the central banks, and the “switches” can then be reset. EXAMPLE 115 If, for example, banknotes are deactivated prior to transport from one location to another, then banknotes which were stolen during an armed robbery of such a transport can be easily identified. This can be effected e.g. during the transport of banknotes from the banknote printing works to an issuing central bank and/or from the central bank to a commercial bank. EXAMPLE 116 It is furthermore also conceivable that the banknotes not be enabled until immediately prior to their being dispensed to a customer in a bank or from an automatic teller. This can preferentially also be done online by an organization authorized to do so, such as a central bank, via a remote data link between the banknote chip and a central bank computer as described in greater detail in the present application. EXAMPLE 117 Moreover, in the case of e.g. extortion money, such data as will lead to time-delayed disabling, and e.g. deactivation of an associated display can be written into the memory of a banknote chip, so that same only becomes marked as invalid and can be recognized after a time delay after the money has been transferred to a blackmailer. The delayed disabling can be achieved e.g. by means of a counter contained in an integrated circuit of the banknote, which marks the notes as invalid only after e.g. ten days. Alternatively, it can also be provided that an expiration date as of which the banknote loses its validity is written into the memory of the banknote chip. This validity date can then be checked by the associated reading devices. This disabling and enabling of banknotes by writing data to a memory of the chip will preferentially be effected in the stack here as described above. The validity status of a banknote will be further indicated, e.g. following a lapse of the expiration date, by an optical and/or acoustic display device permanently integrated in the banknote paper as described in detail in a following chapter entitled “Commerce.” EXAMPLE 118 It is furthermore conceivable that when payments are made with such banknotes marked by the chip data as being special, e.g. invalid, such as when deposits are made in a bank or when payments are made at a business such as a gas station, this state is recognized by the associated checking devices reading out the chip data, and thus a camera coupled with the register terminal is activated in order to be able to record the suspicious payment operation, i.e. in particular the person making the deposit. EXAMPLE 119 Apart from the writing of data which provides information on the validity of the banknote into the banknote chip, data on other administrative states can also be stored. Here, it is possible to have e.g. data on states such as “in storage,” “in transport,” or “stolen”. EXAMPLE 120 Also, especially in conjunction hereto, provision can be made that chip 3 of a banknote 1 has several logical switches, memory cells in general, which preferentially also hold sufficient data available in the “switched” state to induce the “switching operation;” i.e., concerning, for example, by whom or, as applicable, by which device, when, where and/or why the switching operation was carried out. This means e.g. that chip 3 not only has a single switch or chip data characterizing same, as the case may be, which serve to fully disable the banknote, but that several switches are provided for different users in each case in accordance with the associated chip data, in order to disable chip 3 of banknote 1, for example, for certain groups of people or actions. Users can e.g. be central banks, securities transport firms, commercial banks or customers. For this purpose, different memory areas can in turn be provided in the chip for different users. In addition, the switch does not necessarily have to be assigned only a binary signal that e.g. can only assume the “valid” or “invalid” state, as the case may be. One can additionally realize the storing of additional data for information. This can, for example, be data concerning by whom and/or when and/or where the switch of the particular banknote was used. Further, identifying data can be stored in the memory upon changes to the contents of the memory data, e.g. relating to changes in the display condition of the optical and/or acoustical display, which indicate by whom and/or with which device and/or when and/or where the associated data was entered into the memory, in order to be able to clearly follow and control the changes made when the memory contents are read out, even at a later point in time. In the case of activation or, as the case may be, deactivation of banknotes, the writing devices e.g. will be available solely at the system operators' that is responsible for same, such as the central banks, securities transport firms or other cash handling service undertakings, so that memory data on the current validity of the banknote can only be changed by persons authorized to do so. This can be achieved by having the data stored in the chip such that it is encrypted and/or marked, or password-protected, as the case may be, and such that it can only be changed given knowledge of the password or, as the case may be, of the encryption algorithm or, as the case may be, only with special writing devices adjusted to writing the associated chip data to the particular banknote. The PKI system described above, for example, can be utilized for this purpose. It is additionally possible for the digital signature or the key for access to the encrypted data, as the case may be, to be saved in a separate chip, which is not a component of a banknote. The separate chip can e.g. serve to check the access authorization for certain users or certain actions, as the case may be, as specified in the following. This chip can e.g. be a component of an external chip card, which must be inserted into a checking device having read functions and/or write functions for banknote chips or connected to same, as the case may be, in order to check the required access authorization. This has the advantage that, upon a conceivably necessary code change, only chip cards, of which there is but a limited number, and not all the banknotes will need to be replaced. EXAMPLE 121 Circuits having the properties cited in the above are suited to several applications within the overall circulation of money. In a case of extortion, the chip memory “switch” reserved for state central banks can be provided with the information, “04.17.2002, Extortion, Case: Code word”, in a state central bank. Only state central banks (SCB) can write, read and delete this information in the banknote chips. Banknote sorting machines at the state central banks check all banknotes flowing back into the monetary circulation for authenticity and their fitness for circulation, i.e. state of preservation. Should the SCB switch of each banknote now also be checked within the context of this routine, the banknotes assigned to the above-cited extortion case can be filtered out. Such data is not perceptible to the ordinary consumer; it is also irrelevant to the consumer, since the banknotes are still authentic and thus valid. EXAMPLE 122 Further, the memory can e.g. encompass an authentication system which contains data on different access authorizations for reading and/or reading or writing chip data and/or for changing the data contents of the memory. It can e.g. be necessary to input into the associated reading and/or writing device a code necessary for a certain group of users or testing devices, as the case may be, and/or for the performing of a specific action. The entered code is preferentially compared for a match with the reference data stored in the chip itself in order to enable access authorization. The reference data is preferentially saved in a memory area, which cannot be read from the outside without special authorization. In order to legitimize itself for the actions, the corresponding processing device, must enter the code, optionally upon prompting by the banknote chip. Also of preferable advantage in such a case is use of a maloperation counter. The chip of banknote 1 can specifically contain at least one non-volatile error counter which cannot be written to from the outside. Upon each unsuccessful attempt to transmit the code, it counts ahead by one, although it preferentially resets upon successful entering of a suitable code. An exception is made in the case of the error counter reaching or exceeding, as the case may be, a fixed value. In this case, the banknote is marked by a status which documents the attempted manipulations and which cannot be reset. This can e.g. lead to occasional or permanent, i.e. irreversible, deactivation i.e. prevent certain chip actions. According to one variant, after the error counter's fixed maximum number has been exceeded, the chip e.g. irreversibly no longer allows any more chip functions to be executed except for querying the status of the chip. Provision can be made that the cited codes be different for each banknote and/or that they are stored or will be stored, as the case may be, in a central database. The associated reference data are preferentially stored in a ROM memory area during production of the banknote. It can further be provided that the code is randomly regenerated after every action or at least after a given number of actions, which require the use of the code, and stored in the chip and e.g. transferred to the central database. In this case, it can also be provided that, for example, the chip of the banknote needs to be legitimized at a reading device, in that the code which is stored therein is transferred to said reading device, which in turn transfers the code it reads to the central database, which e.g. only returns a Yes/No statement as to whether the code for the corresponding banknote which can be, for example, additionally uniquely marked by an unalterable serial number, is correct. A connection to the central database can e.g. be established via cell phone or a GSM connection. In many cases, it is expedient for the transponders of the banknotes to respond and communicate one after the other. This is especially necessary when querying and processing the individual data of the individual banknotes. In other cases wherein a defined number of banknotes are to be furnished with standard data e.g. prior to a securities transport with the data, “Securities transport from location A to B, date, time, transport company, transport number, transport truck, unit of quantity, etc.,”, it is of great advantage to provide a majority or all of the banknotes with the data in parallel i.e., at the push of a button all at the same time. After the transport has been concluded, the data can likewise be simultaneously deleted again for all banknotes “at the push of a button” or, as the case may be, all the “switches” can be reset. For parallel writing/deleting of information, it can be necessary for the banknote transponders to have a further interface which is particularly optimized to this mode of operation. This applies in particular for banknotes having an optical interface for serial processing, e.g. photodiodes. EXAMPLE 123 Given a case where there are different access authorizations for different users in order to perform different actions and/or for different memory areas, it can also be provided that at least one memory area is rewritable and in essence freely accessible to all. This can e.g. be utilized to the end that anyone, thus also any private person, is able to write, read and change data, which is then sent off in a form similar to a “message in a bottle.” It is likewise conceivable to store advertising information, gift promises (“Use this banknote at XY department store and you will receive a 3% discount”), games, etc. The data can be written into this kind of memory area as text and/or symbols and/or images and/or sounds and/or games. These can then be optically and/or acoustically reproduced, either by means of a display device integrated within the banknote itself or by means of an external device. Remote Data Transfer Another idea of the present invention consists of having a remote data connection in order to transfer data between a banknote checking device and an evaluation device at a spatially remote location. The checking device can in particular also be a device described in the present invention for the recognition and/or checking of banknote chips, with the device being able to read data from the chip and/or write data to it. This remote data transfer can be effected via a telephone connection such as a fixed line connection, a mobile link, or via a network connection, e.g. the Internet or an intranet connection. This data transfer can e.g. be either unilateral or bilateral in this context. EXAMPLE 124 When, for example, a banknote checking device is integrated into a cellular phone or also when stationary terminals, such as money depositing and/or disbursing machines at banks or retail stores, have such a device for remote data transfer, it is conceivable to enable a secure data transfer from and/or to a center, e.g. a central bank or a trust center, e.g. via a GSM connection. For example, direct communication between the chip of the banknote and a computer at the central bank can thereby be established. Authentication between the banknote chip and the central bank computer can ensure that specific, pre-defined actions can only be performed by the organizations authorized to do so, in this case e.g. the central bank. The following includes possibilities of application in this respect: EXAMPLE 125 A check of the chip data can be performed online. This means that the evaluation of such data, e.g. for checking the authenticity of banknote chips, is not performed by the on-site checking device, but instead at a remote central bank or the like via the remote data connection, and the only feedback from the central bank to the checking device is the result of the check. This has the advantage that the central bank can keep better secret of the evaluation algorithms and that an unauthorized third party cannot simply conclude the details of the executed checking operations simply by an analysis of the checking devices as such. EXAMPLE 126 The above-cited data on administrative states, such as the validity of the banknote, which are preferentially stored in its chip, can be additionally or alternatively stored in the central database such that they are assigned to the particular banknote. A variant of this consists in that the data such as the serial numbers of stolen banknotes are collected centrally in the database. If, in this case, banknotes are deactivated for transport, this can then prevent the stolen banknotes from subsequently being “put back into operation” without being noticed. Recognition of Duplicates A problem inherent to banknotes is the possibility of their being forged with a corresponding effort. This problem also exists with banknotes having a chip, since it can be assumed in this connection that the chip can also be duplicated given the correspondingly large effort. Particularly when using large-surface circuits made from polymer electronics or polycrystalline silicon, there is the risk of a re-design and, connected with same, the production of one or more copies of the chip for the purpose of bringing forgeries into circulation. In contrast to forged chip cards, a forged banknote is immediately put into circulation and is thereafter no longer in the possession of the counterfeiter. This increases the incentive and, thus, the risk of a forgery. Therefore, there is a need to be able to recognize duplicates of banknotes. EXAMPLE 127 A possibility for this purpose consists of having a new code always being written into a memory area of the banknote chip provided for this purpose in each case, during one, preferentially during each online check of banknotes. Online check is hereby understood to mean in particular a checking operation wherein the checking device for banknotes is linked to a remote computer system via an online connection in order to perform a data comparison with a central database, as described in greater detail in the following. Feasible as online connections are network connections such as fixed line or cellular telephone, Internet or intranet connections. In this context, the code can be a random number representing an arbitrary letter, digit and/or symbol combination. The random number is preferentially generated for the first time at the time of the check. This random number is likewise stored in a central database, e.g. of the central bank, and assigned to the serial number or another unique and constant identification of the particular banknote. Upon each further online check of the banknote, the random number in the banknote chip is compared with the associated entry in the central database. The comparison is preferentially performed in the computer of the central bank in order to be able to more effectively prevent manipulations. If a disparity of the random number is determined for a given serial number, it can then be assumed that there is at least one duplicate of the checked banknote or that the duplicate was tested, as the case may be. If a match is determined for the random numbers, the banknote can then be assessed as being authentic. In this case, a new random number is generated and saved in the banknote chip and in the central database. Thus, forged duplicates of circulating banknotes can be recognized in a reliable manner. In order to ensure that the memory of a banknote chip can be written to, the newly-generated random number is preferentially first written to the banknote chip and then read out again. If saving of the new value in the banknote was successful, the entry in the central database will then also be updated. Only then, will the banknote be recognized as authentic and a corresponding display be output on the reading device. An additional possibility consists of registering unsuccessful writing attempts in a maloperation counter. This enables the prompt recognition and sorting out of chips having defective memory cells or also of duplicates having a read-only memory, which would, however, not have been recognized as authentic anyway. Briefly summarized, the idea thus consists of storing a random number in both the banknote chip as well as in a database. Upon each check of the banknote chip, the random numbers are first compared, specifically e.g. upon each successful check, consequently, a new random number is generated and stored in the banknote chip as well as in the database. If the two random numbers do not match, the banknote is then classified as a suspected forgery and handled accordingly. EXAMPLE 128 Instead of the random number, the banknote can also be assigned e.g. a transaction number TAN upon each transaction. The TAN is thereby derived from a number of digits, with the number of all possible TANs being larger than the number of all possible serial numbers, i.e. the TAN is a very long and randomly-generated number and thus not easily guessed. The difference from the random number consists of the fact that the TANs were already generated previously and become invalid after use. It is not mandatory to establish a relationship to a serial number, since a TAN alone can also represent a feature of validity. The following will describe possible problems in the realization of this duplicate recognition and their possible solutions. EXAMPLE 129 A possibility for illegally ascertaining the random number exists in the so-called “brute force” attack wherein all conceivable possible combinations are queried from the database for as long as necessary until a correct random number is determined. The smaller the available memory in the banknote chip, and thus the length of the random number, the easier this process is. In order to prevent this, a time stamp is saved in both the banknote chip as well as in the database, i.e. data on the time of the last query. Additionally, the ID number or the IP address, as the case may be, of at least the most recent querying checking unit to the database, preferentially, however, a longer history on the last query, can be stored in the database. In place of the ID number or IP address, as the case may be, all other data can also be used which allows referencing back to the particular checking unit and/or location, i.e. the institution such as the particular business or bank where the checking unit is installed and/or to the last queried database. This additional data will be termed “location stamp” for short. With each query of the database, a frequency check is now preferentially executed, e.g. by means of a maloperation counter, which will be described in greater detail in the context of these present applications. That means that queries, where combinations of serial number and random number are thus retrieved and compared to the entries in the database, are recorded in a maloperation counter if the random number for a given serial number is invalid. If it appears that a serial number has been repeatedly erroneously queried within a short time by just one checking unit, there is then cause for suspicion that an attempt is being made to determine a valid random number by means of a brute force attack. To prevent this, the checking unit or the associated banknote processing device, as the case may be, can be temporarily taken off the network or the communication between database and checking unit decelerated such that an attack cannot be carried out within an acceptable amount of time. If, however, it appears that a serial number has been repeatedly erroneously queried by diverse checking units, then the suspicion of an already circulating forgery, possibly in larger quantities, suggests itself. EXAMPLE 130 A possible problem which can arise when checking banknotes via a central database is a very large number of simultaneous accessing of this database. In order to circumvent this problem, provision can be made for distributing the data among several databases DB. FIG. 54 shows an example of this case. There are N databases DB. When a banknote BNC is checked by a checking unit, the checking unit then sends the serial number and the current random number RNDt=0 of the banknote being checked to one of the databases. The particular database DB to which the test data is sent can, for one, be made dependent on a further identification number as a criterion for selecting one of the databases 1 . . . N, which is stored together with the random number in the chip of the banknote to be checked. The identification number can also be a part of the random number itself; e.g. its last two digits. One database DB will then always be responsible for checking a certain group of identification numbers. Should a new random number RNDt=1 be generated during a query, it thus thereby becomes certain, with which database the next query will take place upon the next check. In the example shown in FIG. 54, the 1st database DB writes and assigns a random number RNDt=1 to checked banknote BNC, which corresponds to the 4th database DB. Therefore, the associated data record on the checked banknote BNC, e.g. at least data on the serial number and random number, must be transferred via data line from the 1st database DB to the 4th database DB. In contrast to only one database, there is a resulting decrease in traffic volume, i.e. the number of accesses, by a factor of 2/N, with N representing the number of databases in the overall system. With this system, each checking unit can access any database within the system. In this context, the databases are preferentially present on separate computers, in particular also at separate locations. It is possible that the checking units can access all possible databases via different databases. For the data comparison, however, it is preferential for one individual checking unit to be connected to a front-end computer, which is assigned to several checking units and which in turn establishes a connection to the individual databases 1 . . . N. The individual checking unit thus only needs to establish a single data link to the front-end computer in each case and not to all the databases at the same time; e.g. upon a deposit transaction. EXAMPLE 131 A further possibility of reducing accessing of a single database consists of a spatial distribution of the databases, with the distribution possibly being made e.g. by countries, provinces, cities or the like. In this context, each database serves a subset of checking units. Any arbitrary, e.g. cross-border, access is not possible for the checking units, since there is a fixed assignment between checking unit and database. In this scenario, the banknote chip contains at least one other entry on the database last queried apart from the random number and an optional time stamp. When the banknote is dispensed by a central bank or the like, the valid data record is stored in only one of the databases assigned to the particular central bank. In addition, it can be provided that all the databases within one system are networked together and, that a comparison can be made among the data records they contain if necessary. In the following, a concrete example of such a scenario will be explained with reference to FIG. 55. Here, it is assumed that a banknote BNC#255 having the exemplary serial number #255 is stored in database DB1. Upon a check at a terminal PE1 at time t=1, the stored data record is compared with the data record stored in database DB 1. If the check is successful, a new random number RNDt=1 is then generated and stored together with the location stamp and time stamp, i.e. in this case, the time t=1 and database DE1 data, in banknote BNC#255 as well as in database DB1. If banknote BNC#255 in the example now leaves the “catchment area” of database DB 1 and is found in the catchment area of DB2 at time t=2, then the data record associated with said banknote BNC#255 will initially be missing from said database DB2. However, the location stamp in banknote BNC#255 can serve to establish that a corresponding data record is present in database DB 1. By a comparison of databases DB 1 and DB2, the relevant data record can now be transferred to database DB2. The data record can then subsequently either be deleted from database DB1 or a corresponding reference to the “border crossing” of banknote BNC#255 can be stored in database DB1. On the basis of the data record now found in database DB2, the authenticity of banknote BNC#255 is checked and a new data record with a new random number RNDt=2 as well as a new location stamp and time stamp is written into database DB2 as well as banknote BNC#255. In contrast to a single database DB, there is a resulting decrease in traffic volume (i.e., the number of accesses) by a factor of 2/N, with N representing the number of databases in the overall system. In addition, cross-border flows of money can also be detected. Additional security is provided by means of the time stamp and location stamp in the banknote. EXAMPLE 132 A further scenario for an attack consists of making the chip in the banknote unusable by writing absurd data to it. As already illustrated elsewhere in the invention, provision can be made for circumventing this problem by signing the data record to be written to the chip e.g. with a public key in a so-called “public key” procedure. The chip only needs knowledge of a public key to check the authenticity of the data record and to reject the data record if necessary. An additional possibility consists of including the serial number of the banknote chip itself in the marked data record. In this way, the copying of—inherently valid data records—of other banknotes is also prevented. A further possibility consists of safeguarding reading and/or writing access to the banknote chip by means of a derived PIN number. In the simplest case, the PIN is derived from the serial number of the banknote. A further possibility consists of including the particularly valid random number RND in the PIN computation so that the PIN will also change upon each check of the banknote. EXAMPLE 133 A further attack scenario consists of copying data from the chip of an authentic banknote, transferring it to a duplicate, and subsequently destroying the authentic chip, which still remains a component of an actual authentic banknote. According to the invention, it can therefore be provided that the serial number of a banknote is detected at a suitable checking unit in a different way than by reading the chip data, e.g. optically by means of a camera such as a line sensor. Especially in the case of a defective chip, a corresponding notation as to suspected forgery is then stored in the database. EXAMPLE 134 Another attack scenario which is just as possible consists of manipulating a checking unit in such a way that, a data comparison between the banknote and the database is activated first when a banknote is presented. Given an appropriate manipulation, it is then conceivable that the new data record, i.e. the new random number in particular, is not written back to the banknote chip, but instead, the data records are collected in the checking unit so they can be used to program counterfeit chips at a later point in time. In order to prevent such a procedure, provision can be made for not only storing the current data record in the banknote chip, but older data records as well, in order to keep a history of testing operations as a life history of the banknotes. Older data records are likewise saved to the particular database in order to produce a history of the banknote. Moreover, the identification number, such as the IP address, etc. of the querying checking unit, can also be stored in the database. In this context, it is possible, by a statistical evaluation of the data records saved in the database for instance, to discover evidence of possibly manipulated checking units. A further possibility thus consists of saving historical data records on former testing operations on the banknote as well as in the database. According to another variant, it can also be provided that the historical data records of the banknote are not to be read out or written to directly. This can e.g. be achieved in that the memory of the banknote chip is an FIFO memory (“first-in-first-out”), with the older data records being pushed through the memory each time a data record is updated with a random number and, as applicable, a time stamp and a location stamp. FIG. 56 shows an example of this variant wherein the current data record “n” of banknote BNC, which was created during the previous check at time t=0, is compared with the corresponding data record “n” in database DB when the check at time t=1 in checking unit PE is performed. Upon successful check, a new data record “n+1” is thus generated and stored with the time data, t=1, both in database DB as well as in the chip of banknote BNC. In order to check that the new data record was actually written to the banknote chip and not intercepted by the terminal, i.e. checking unit PE, the new “n+1” data record is preferentially linked to at least one data record of the history by an algorithm. Here a function of the last n data records is output for a fixed small n. Ideally, this is a so-called “one way” function or a cryptographic hash function. Alternatively, with limited resources, simpler functions can also be computed. This operation is performed in banknote BNC as well as in database DB and the results subsequently compared. Since checking unit PE disposes of no knowledge of the history, manipulation at this point can effectively be made more difficult. A further improvement of the writing control can be effected by keeping a history indefinitely. For this purpose, the oldest data record in each case, which in turn contains information about preceding data records, is fed to a random number generator PRG. The result can e.g. be stream encryption, a so-called “stream cipher,” where the stream cipher output is used to compare the data from the banknote chip and the database. Apart from a random number generator PRG, there is also the possibility of computing a checksum such as a so-called “cyclic redundancy checksum” CRC, since, here as well, the entire history, i.e. older data records, enter into the results. A pseudo random number generator can also be used to compute the random number, which is customarily configured as a counter having a sequential circuit for feedback as is e.g. described in the book by Finkenzeller K., “RFID-Handbuch”, ISBN 3-446-22071-2, 3rd Ed., 2002, pages 228 to 231. It can thus be provided that the coding of the sequential circuit—and thus the underlying algorithm—be changed in the chip of banknote BNC if necessary. For this purpose, the sequential circuit can be disposed with a programmable memory, such as an EEPROM. It is furthermore preferentially provided that the generator polynomial of a possibly utilized checksum CRC also be changed in the manner described above. Changing the sequential circuit or the generator polynomial in a banknote chip can be triggered by an own (write) command, where the new parameters are generated by database DB and transferred to banknote BNC by checking unit PE while said banknote is being checked. EXAMPLE 135 According to the invention, it can further be provided that the banknote disposes of at least one additional, redundant, identical memory. A writing operation, e.g. to update the data records, will first be performed in one of the identical memories, subsequently, the data is copied e.g. into a primary memory area provided for same. The corresponding status of the writing operation is marked and recorded in the banknote chip by flags, so that at least the original status of the memory can be restored in the banknote in case the writing operation is aborted, e.g. if an interruption in voltage supply to the banknote chip occurs. EXAMPLE 136 It is further possible to irreversibly alter the properties of the banknote chip. A possibility for this consists of burning through so-called “fuses.” In so doing, it is possible to have sufficiently high amperage flow through the fuse. It is, however, also possible to burn through the fuses e.g. with a laser. A possibility consists of the provision of a quantity, e.g. an array of as many fuses as possible, which are preferentially burned through according to a random pattern, with the number of fuses increasing the number of possible combinations and thus the security as well as the number of possible checking cycles. The status of the arrays in turn is preferentially saved in the central database. EXAMPLE 137 A further possibility for duplicate recognition without testing the chip data can be achieved by irreversible, local altering of a banknote or a feature of the banknote. It can thus be provided that a marking, e.g. an ink dot, is applied, e.g. imprinted at a random location on the banknote upon each testing operation of a banknote in a suitable checking unit. In contrast to a usual identification of banknotes which are no longer fit for circulation, e.g. banknotes to be destroyed, the alteration according to the invention will thus be effected above all when the note is assessed as further fit for circulation or is classified a priori as further fit for circulation due to the lack of a status check. The ink used for that purpose shall preferentially be machine readable and not recognizable in the visible spectral range. In addition, the position of all dots of ink already present on the banknote is recorded in a database with an assignment to the particular banknote e.g. in turn via its serial number, and rechecked during a subsequent check. EXAMPLE 138 Although not mandatory, it can also be provided in the afore-mentioned case that this data in turn, is stored in a chip of the banknote. This enables a check of the clear assignment of banknote paper to banknote chip. This can particularly effectively prevent unallowed removal of the chip from a banknote and insertion of the chip into another banknote paper. EXAMPLE 139 As an alternative to the afore-mentioned examples, wherein the banknote is selectively altered by application of markings, magnetic, especially hard-magnetic particles, can also be brought into the banknote paper in order to provide same with a locally different magnetization. In this context, it is provided that the magnetization pattern is altered according to the random principle in a reading/testing operation and that the particular current pattern is deposited in the database. EXAMPLE 140 A further alternative possibility consists of removing from the banknote markings, e.g. imprinted dots of ink, already applied during production of the banknote; in a random or also in a predetermined order. A laser, for example, with which the dots of ink can be removed, can be used for this purpose. EXAMPLE 141 Still another possibility consists of furnishing the banknote completely or at least in a portion thereof with a changeable, e.g. heat-activatable surface. During each checking operation, a pattern can be written on the banknote, e.g. with a laser beam, which is changed in a random order or also in a predetermined order. It is possible in particular to configure the heat-activatable surface to be very small, with the dots applied with the laser being of a microscopic, non-visible scale. EXAMPLE 142 Finally, a further possibility involves altering the structure of the banknote paper itself; e.g. with a laser. One can thus provide for burning dots into the paper or burning it away completely in order to produce recesses such as holes in the banknote. These will, again, preferentially be of a microscopic, non-visible scale. Banknote Processing Machines Banknote processing machines are machines which perform worksteps fully or partly automatically with a number of banknotes transferred to them. Such worksteps can e.g. consist in counting the banknotes, determining their value, sorting them according to currency and/or value and/or position and/or quality, stacking them, packing them, checking them for authenticity or even destroying the banknotes. Banknote processing machines can also perform a combination of several such worksteps. Banknote processing machines according to the invention can be divided into three different classes according to their procedure when processing banknotes: into banknote processing machines with individual processing, where the individual banknotes are separated, processed successively and subsequently deposited again, preferentially stacked, into banknote processing machines with stack processing, where entire groups of banknotes are all processed quasi at the same time without them being physically separated completely from one another, and into banknote processing machines with combined individual/stack processing, where processing by the banknote processing machine can be effected via both individual processing as well as stack processing, is possible. In this context, banknote processing machines are conceivable, which alternatively provide both processing possibilities, banknote processing machines that perform both processing possibilities on the banknotes to be processed or banknote processing machines that allow every possible combination of processing possibilities. That is why, in contrast to the banknote processing machines that are realized at present, stack processing must be designed significantly more efficiently in addition to individual processing. In the following, examples predominantly relating to banknote processing machines with individual processing are described. EXAMPLE 143 FIG. 57 shows the principle structure of a device 100 for processing sheet material having an electrical circuit or, as the case may be, a banknote processing machine for processing banknotes having an electrical circuit. Banknote processing machine 100 has an input unit 110 into which the banknotes are inserted in stacks. A singler 111, which takes individual banknotes out of input unit 110 and transfers same to a transport system 120, is connected to input unit 110. Singler 111 can be configured, for example, as a suction singler, i.e. singler 111 separates the banknotes by means of negative pressure, or it can be configured as a friction wheel singler. Singler 111 can be disposed, as depicted, at the upper end of input unit 110 and separate the uppermost banknote of the stack of banknotes in each case. Likewise, an arrangement at the lower end of input unit 110 is possible, such that the particular lowermost note of the banknote stack will always be separated. Transport system 120 transports the individual banknotes through a sensor unit 145, which determines data from the banknotes, which e.g. permits conclusions to be drawn on authenticity, condition, currency, denomination, etc.. The determined data of the banknotes is transferred to a operating unit 160, which evaluates the data, thereby controlling the further flow of the banknotes through banknote processing machine 100. In this context, operating unit 160 acts on switches 121 to 124, which are components of transport system 120 and allow the banknotes to be placed in output units 130 to 138 according to the predetermined criteria. Output units 130 to 138 can be constructed, for example, as spiral slot stackers, which stack the banknotes, which are to be filed, in stacker 131, 133, 135, 137 by means of rotating units 130, 132, 134, 136, which have spiral slots. A further output unit 138 can be formed by a shredder, which thereby serves to destroy banknotes in poor condition, for example severely soiled banknotes, by means of shredding 139. Banknote processing machine 100 can be controlled by a user via operating unit 166, which can consist of, for example, a display and a keyboard. Data Exchange Devices For processing banknotes having electrical circuits, banknote processing machine 100 has special transfer devices in sensor unit 145, also referred to as data exchange devices, which permit a transfer of energy and/or data with the electrical circuit of the banknotes, i.e. e.g. reading and/or writing of data from and/or to the electrical circuit. For communication, the banknote likewise has transfer devices, such as an antenna linked to the electrical circuit. EXAMPLE 144 FIG. 58a shows, for example, a banknote 1 having an electrical circuit 3 as well as an antenna 7, with antenna 7 and/or electrical circuit 3 being affixed in and/or on banknote 1. Antenna 7 is configured as a dipole antenna and is oriented toward the short side of banknote 1. Contingent upon the orientation of the banknote during transport through transport system 120, in transport direction T1 parallel to the long side of banknote 1 or in transport direction T2 parallel to the short side of banknote 1, different requirements result for the data exchange device in sensor unit 145. Upon affixing antenna 7 to banknote 1 as depicted in FIG. 58b, these requirements act conversely. The data exchange device of sensor unit 145 is therefore constructed in such a manner that, independent of the orientation of antenna 7 of banknote 1 and/or the orientation of the data exchange device of sensor unit 145 and/or the transport direction T1, T2, data exchange between the data exchange device of sensor unit 145 and electrical circuit 3 of banknote 1 is always possible. A further possibility consists of determining the orientation and/or position of antenna 7 of banknote 1 during transport through transport system 120 and controlling the data exchange device of sensor unit 145 accordingly in order to enable data exchange. Other sensors present in sensor unit 145, sensors which record the optical information of banknote 1, for example, can be used for this purpose, for example. Another possibility consists of designing the data exchange device of sensor unit 145 and banknote 1 in such a manner that the data exchange device of sensor unit 145 and electrical circuit 3 of banknote 1 are coupled inductively or capacitively for the data exchange. This, for example, can be effected by means of electroconductive coupling surfaces in the data exchange device of sensor unit 145 and banknote 1. A data exchange device for banknote processing machine 100 is proposed which enables communication with an electrical circuit 3 both in longitudinal as well as also transverse transport, i.e. when transporting along the long side T1 as well as the short side T2 of banknote 1, and independently of the orientation of antenna 7 of electrical circuit 3 of banknote 1. EXAMPLE 145 According to FIG. 59, a further embodiment of a data exchange device 142 consists of electroconductive segments 150 to 156, which are disposed to be insulated from one another. FIG. 59a depicts data exchange device 142 at that point in time at which electrical circuit 3 of the nondepicted banknote, of which electrical circuit 3 is a component, is at the height of segment 152. One branch of antenna 7 lies in the area of segments 150, 151, the other branch in the area of segments 153 to 156. In order to enable communication of data exchange device 142 with electrical circuit 3, segments 150 and 151 are connected to one another electroconductively 157a. Segments 153 to 156 are likewise connected to one another electroconductively 158a. In this way, segments 150, 151 and 153 to 156, which are connected to one another electroconductively, serve as an antenna or coupling surface for the data exchange with electrical circuit 3 via its antenna 7. For this purpose, electrical connections 157a and 158a are connected to operating unit 160. Since banknote 1 is moved by transport system 120 of banknote processing machine 100, the position of antenna 7 of banknote 1 changes. In the case depicted in FIG. 59a, wherein antenna 7 is transported in the direction T perpendicular to segments 150 to 156 of data exchange device 142, the position of antenna 7 relative to the individual segments 150 to 156 changes. FIG. 59b depicts data exchange device 142 at a later point in time, at which banknote 1, and thus antenna 7 as well as electrical circuit 3, have been transported further by transport system 120 in comparison to the representation in FIG. 59a. At this point in time, electrical circuit 3 is at the height of segment 154. Therefore, segments 150 to 153 are electroconductively connected with one another 157b on the one hand. On the other hand, segments 155 and 156 are electroconductively coupled with one another 158b. In this way, the electroconductively-connected segments 150 to 153 as well as 155 and 156 serve as an antenna or coupling surfaces for the data exchange with electrical circuit 3 via its antenna 7. Electrical connections 157a and 158a are additionally connected to operating unit 160. In order to ensure that the correct segments 150 to 156 are electroconductively connected to one another at all times, the position of banknote 1 being transported by transport system 120 is determined so that the interconnecting of segments 150 to 156 occurs synchronously to the movement of banknote 1, or antenna 7 and circuit 3, as the case may be. The position of banknote 1 can e.g. be derived from the known transport speed of transport system 120 when the location of banknote 1 is precisely determined at a specific point in time; for example, by means of light barriers disposed in the transport path of transport system 120. The operating unit can then control the above-described electrical connection of the individual segments 150 to 156. For this purpose, operating unit 160 can, for example, control electronic switches such as transistors or electromechanical switches such as relays, which are connected to segments 150 to 156 in order to produce connections 157 and 158. Further, the orientation of banknote 1 or antenna 7, as the case may be, is determined. The orientation of banknote 1 is usually known, since banknote processing machine 100 transports banknotes 1 either along their long side or along their short side. If the type of banknotes to be processed is known, e.g. a certain currency, then the position and orientation of the banknote's antenna 7 is also known. If same is not known, a conductivity sensor of sensor unit 145 can be additionally used, for example, to determine the position and orientation of antenna 7 in order to control the described electrical connection of segments 150 to 156 of data exchange device 142. Once it has been or, as described, once it is ascertained that antenna 7 is at the height of e.g. segment 153 and transported along direction T, as depicted in FIG. 59c, and parallel to segments 150 to 156, segments 150 to 152 will be electroconductively connected to one another 157c. Segments 154 to 156 are likewise electroconductively connected to one another 158c. Electrical connections 157c and 158c are—as described above—connected to operating unit 160 in order to enable an evaluation of electrical circuit 3. Further monitoring or changing of electrical connections 157c and 158c can be omitted in this case, since the position of circuit 3 or antenna 7, as the case may be, does not change relative to the segments of data exchange device 142. EXAMPLE 146 FIG. 60 shows a still further embodiment of a data exchange device for a banknote processing machine 100 according to the invention for the processing of banknotes 1 having an electrical circuit 3. The data exchange device is formed from singler 111 of banknote processing machine 100, for example from the singling roller. The data exchange device consists of two electroconductive roller bodies 142a and 142b, which form the singling roller and are connected to an electrical insulation 142c. The two roller bodies 142a and 142b are connected to operating unit 160 for the data exchange. The data exchange between electrical circuit 3 of banknote 1 and data exchange device 142a,b occurs upon the separation of banknote 1 from input unit 110 via singler 111 (FIG. 57). When banknote 1 is detected by singler 11, a branch of antenna 7 lies in the area of the one roller body 142a, the other branch of antenna 7 lies in the area of the other roller body 142b, so that operating unit 160 can exchange data with electrical circuit 3 of banknote 1 via data exchange device 142a,b. EXAMPLE 147 FIG. 61 shows a still further embodiment of a data exchange device for a banknote processing machine 100 according to the invention for the processing of banknotes 1 having an electrical circuit 3. The data exchange device is formed from electroconductive surfaces 142a,b, which are disposed along the transport system 120 of banknote processing machine 100. Electroconductive surfaces 142a,b of the data exchange device are electrically insulated from one another and have an oblique gradient in transport direction T1, T2. It is thereby ensured that data exchange will occur between electrical circuit 3, 3′ of banknote 1 and data exchange device 142a,b when banknote 1 is transported past data exchange device 160 by transport system 120, independently of the orientation of antenna 7, 7′ of banknote 1 and independently of the direction of transport T1, T2. Thus, operating unit 160 can exchange data with electrical circuit 3, 3′ of banknote 1 via data exchange device 142a,b. EXAMPLE 148 In a further variant, data exchange device 142 of banknote processing machine 100 comprises a device which generates a rotating and/or migrating electrical and/or magnetic field. An antenna structure, for example, which functions according to the so-called “phased array” principle, can be used for this purpose. This data exchange device 142 allows data exchange between the banknote's electrical circuit 3, independently of the orientation, position or shape of antenna 7 of banknote 1 and independently of any possible position or transport direction of banknote 1 in transport system 120 of banknote processing machine 100. EXAMPLE 149 The arrangements and structures described for data exchange device 142 can also be utilized for banknote 1. For example, antenna 7 can be disposed obliquely on and/or in banknote 1 in order to enable data exchange with data exchange device 142 independently of the orientation and transport of banknote 1. In addition, other deviating antenna structures can be provided, e.g. a cross-shaped dipole antenna or a closed (e.g. annular, circular, polygonal, particularly rectangular) or a ridged antenna structure. The data exchange device 142 described above can also be disposed in the area of singler 111 and/or input unit 110 instead of in the area of transport system 120 or also additionally thereto and e.g. be a component of a second sensor unit 140 (FIG. 57). EXAMPLE 150 FIG. 62 depicts an input unit 110, into which banknotes 1 are inserted. At location 111, banknotes 1 are detected by singler 111, separated and transferred to transport system 120 in the direction T. Data exchange device 142 for data exchange with electrical circuit 3 of banknote 1 is situated in the area of input unit 110. Data exchange device 142 has a structure and a functionality as described above. Data exchange can occur in the inactive state with the next banknote 1 to be separated, i.e. with the uppermost or the lowermost banknote, depending upon whether singler 111 separates from above or below. It is, however, also possible to conduct the data exchange during the separation of the particular banknote 1 to be separated and to e.g. make use of the movement of banknote 1 during separation when same is moved passed data exchange device 142. As described above, the singler, preferentially singling roller 111 itself can also comprise data exchange device 142. However, an exchange of data can also be effected with several or all banknotes in input unit 110. In that context, the procedures described below must be applied to avoid collisions or crosstalk, as the case may be. The problem of mixed-up talk/crosstalk can also be solved by always having only one banknote selectively communicate with data exchange device 142. In order to achieve this, provision can be made to always enable only one banknote for data exchange with data exchange device 142. This can be particularly advantageously achieved if the next banknote 1 to be separated is enabled for data exchange with data exchange device 142. To enable, it is particularly expedient to utilize a transfer method deviating from that for the data exchange with data exchange device 142. For example, provision can be made to effect enabling by optical means, e.g. by irradiating with light. For this purpose, a photocell is provided on transponder chip 3 which, when sufficiently lit with enough brightness, electrically enables the function of the transponder. Should a light source be located in singling unit 110, which illuminates the next banknote to be separated in the area of chip 3, same enables the units necessary for communication, whereby data exchange is enabled. This luminosity of the light source is to be measured in such a way that the light passing through the separated banknote and striking the next banknote is so weak that it can only just not yet be enabled for the next banknote. It is expedient to also provide measures in chips 3, e.g. in the form of threshold values, which optimize the photosensitivity of the photocells to this situation. Care must be taken that the banknotes are disposed in such a way in the singler for this communication that the photoelectric cells of chips 2 are disposed in the direction of the light source. EXAMPLE 151 Optical activation of the next banknote 1 to be separated is effected by illuminating a portion of or the entire surface of banknote 1 with light, since, at this time (prior to separation), banknote 1 is openly available in input unit 110 due to the fact that it constitutes—as described above, depending upon separation from above or below - the uppermost or the lowermost banknote of the banks notes in input unit 110. As depicted in FIG. 62, a light source 141 can be provided for this purpose, which fully or partially illuminates the surface of the next banknote 1 to be separated. The light strikes an optoelectric component, a photo transistor, for example, which can be a component of electrical circuit 3 of banknote 1, and enables electrical circuit 3 for data exchange with data exchange device 142. Illumination with light can also occur at selective points if the precise location of the optoelectric component in input unit 110 is known so precisely. The use of one or more photodiodes in the banknotes represents a further possibility, as described at the outset. In that context, the light of light source 141 is guided to the optoelectric component, for which purpose an end of the photodiode or photodiodes is coupled to said optoelectric component. The other end or ends of the photodiode, for example, can terminate at one or more edges of the banknote. The light from a light source can then be selectively coupled to one of the edges of one or more of the banknotes in order to effect the enabling. The light can be coupled particularly advantageously when the front edge, viewed in transport direction T, of the banknote 1 just being grasped by singler 111 is illuminated in an area outside of input unit 110, since only the edge of this banknote 1 that has just been separated—and thus the photodiode—can be selectively illuminated in this area, with which only electrical circuit 3 of said banknote 1 is activated for the data exchange. If, the banknotes are to be separated anyway in banknote processing machine 100, however, the solution preferred is the one where no photodiode is needed, since selective communication is then possible with exactly the lowermost or uppermost banknote, as the case may be. In order to ensure in this case that the next, e.g. viewed from singler 111, the second banknote, is not activated in this case, a threshold is to be provided, as previously mentioned, which ensures that the light which has already passed through one banknote is insufficient for activation of the next banknote. EXAMPLE 152 As further illustrated further in FIG. 62, the second sensor unit 140 can contain further sensors 143. For example, sensor 143 can be an optical sensor that captures the surface of the particular separated banknote 1 and the signals of which are evaluated by operating unit 160. Conclusions as to the condition of banknote 1 can, for example, be drawn from the optical appearance of the surface of banknote 1, e.g. relating to soiling or damages. Further evaluations also allow conclusions e.g. as to the authenticity and/or the currency or, as the case may be, the denomination of banknote 1. Additional sensors can also be provided in the second sensor unit 140 in the area of singler 111 and/or input unit 110 for checking authenticity or other properties of banknote 1. EXAMPLE 153 The early recognition of banknote 1 or certain features of banknote 1 prior to and/or during separation allows operating unit 160 to make pre-settings for further components of banknote processing machine 100, which can facilitate, accelerate or improve further processing. For example, operating unit 160 can pre-set sensor unit 145 for the check of a certain currency and/or denomination, as a result of which a faster or more precise check is enabled. The structure or function, as the case may be, of data exchange device 142, light source 141, as well as additional sensors external sensor device 145, described above in connection with the second sensor unit 140, which is disposed in the area of singler 111 and/or input unit 110, is also applicable to the banknotes that have bee deposited and/or are to be deposited in output units 130 to 137. EXAMPLE 154 The data exchange between the banknote and the checking device can signify reading on the one hand and writing on the other hand. As is known, can be read out in an especially short period of time when EEPROM memories are used. In contrast, however, writing data takes a relatively long time. Depending on whether only reading or also writing is now to be effected, one must check whether same is also readily possible without hindering the checking sequence. In this context, one must take into account that, when a high-performance sorting machine with a processing speed of e.g. 40 banknotes/second is used, the idle time for each banknote exposed next in each case lasts a maximum of 1/40 second. All planned measures are to be coordinated according to the aforementioned, i.e., locations in the sorting machine are to be selected for the individual writing operations, which take these facts into account. The banknotes stay the longest in spiral slot stackers 130, 132, 143, 136 (FIG. 57). For writing operations, therefore, it appears especially expedient to provide the “writing devices” in the individual slots of the spiral slot stackers. This enables data exchange with electrical circuit 3 of the banknote to be deposited while same is situated in a spiral slot of rotating units 130, 132, 134, 136. Since usually only one banknote is found at a time in a spiral slot, provision can also be made to optically enable said banknote, or, as the case may be, its electrical circuit, as described above. Further, as likewise described above, further sensors can be provided in rotating units 130, 132, 134, 136. It is moreover possible to shield the individual spiral slots from one another, e.g. by the use of electroconductive surfaces that form a type of Faraday cage. It is likewise possible to provide data exchange devices in stacker 131, 133, 135, 137. In this case, data exchange can be performed with several banknotes that have been deposited or, as the case may be, with the banknote last deposited in stacker 131, 133, 135, 137 in each case. Since the surface of the particularly last stored banknote in stacker 131, 133, 135, 137 is freely accessible, i.e. not covered by other banknotes, an above-described enabling of data exchange can be effected. Further, as likewise described above, further sensors can be provided in the area of stacker 131, 133, 135, 137. To improve, e.g. accelerate, the processing of banknotes 1 having an electrical circuit 3 in banknote processing machine 100, provision can be made to distribute the data exchange between banknote 1 and banknote processing machine 100. For this purpose, a separation of reading and writing operations can be effected, for example. EXAMPLE 155 In this context, for example, data is read from the electrical circuit 110 of banknote 1 by means of the second sensor unit 140 in the area of singler 111 or, as the case may be, input unit 110. Data can then be written to electrical circuit 3 of banknote 1 in the sensor unit 140 mounted in transport system 120 and/or in the data exchange devices of output units 130 to 137. Likewise, a further separation of the reading operation and/or the writing operation is actually possible. For example, only a certain part of the information from electrical circuit 3 of banknote 1, can be read out in second sensor unit 140, e.g. the serial number, while the rest of the data, which is required for processing in banknote processing machine 100, is read out in sensor unit 145. In the same way, arbitrary distributions can be made between reading and writing operations as well as between the data exchange devices mounted at the different locations that have been described. In other words, the processing device for the receipt of energy and/or data from the sheet material circuit will have a receiving device, which is located in the same or another processing part of the processing device as the transfer device for the transfer of energy and/or data from the processing device to the sheet material circuit, with “processing parts” or also “processing station” preferentially being understood to mean modular components of the device having different processing functions, such as input, singler, transport path, sensor path, stacker and/or deposit means. Intelligent Light Barriers In order to be able to better monitor the individual steps of processing of the banknotes in banknote processing machine 100, light barriers 161 to 165 are provided, which capture the transport of the banknotes through banknote processing machine 100 and forward same to operating unit 160 for processing. Further light barriers can be provided at additional locations along transport system 120 if necessary, in particular, sensor units 140 and 145 can also be regarded as light barriers and their signals evaluated accordingly. It is thus possible to determine the particular location of a banknote after separation in the transport system, when the signals of light barriers 161 to 165 are evaluated by operating unit 160. EXAMPLE 156 A further improvement of monitoring can be achieved if data exchange devices are provided at the positions at which light barriers 161 to 165 are mounted instead of or in addition to the light barriers. Such light barriers 161 to 165 will be referred to as intelligent light barriers 161 to 165 in the following. It thereby becomes possible to read out the unique data of the banknote to be processed, e.g. the serial number, from the electrical circuit of each banknote at the start of processing in banknote processing machine 100. Same can be effected in sensor devices 140 or 145, for example. Along the further course along transport system 120, the unique data is again read out by sensor device 145 and intelligent light barriers 161 to 165 and forwarded to operating unit 160, which logs same for monitoring purposes. Such an intelligent light barrier can in particular also be used to recognize whether there are several banknotes that are overlapping one in the transporter. Thereby, precise monitoring of the processing of the banknotes in banknote processing machine 100 is possible at every point in time. Particularly in the case of malfunctions, such as jamming of the banknotes, for example, better assignment of the individual banknotes is thus possible. This is especially important when banknotes stemming from different depositors are processed at the same time. In this case, when banknotes from different deposits are mixed, it is possible to assign each banknote to the deposit from which it originated, since the corresponding unique data (serial number) are detected during separation and stored in operating unit 160. If a malfunction and along with it intermixing of the banknotes occurs, the serial numbers of the individual banknotes serve to restore the original assignment. Likewise, during preparation of a deposit for processing by the banknote processing machine, the owner or, as the case may be, legal owners (e.g. name and/or account number), can be recorded in the electrical circuits of the banknotes, either by the depositor itself or at the site of the banknote processing machine, or, as the case may be, during transport to said site. Should malfunctions occur in the course of processing, such as jams or a mix-up of the order of the banknotes (so-called crossovers), the assignment of a banknote to a depositor can be restored automatically. This can be effected by having an operator who reads the serial numbers of the banknotes and compare them to the log, which contains data on the affiliation of the intermixed banknotes to the particular deposits as displayed on operating unit 166. It is, however, also possible to re-feed the intermixed banknotes into input unit 110. They will then be automatically allocated to the particular deposit in accordance with the log of operating unit 160. However, it is also possible to write the information into a “write-only” type memory area in order to maintain the anonymity of the depositor. In cases of uncertainty, the information then be checked for validity and put out only within the chip. Destruction of Banknotes with Electrical Circuits Special security is necessary when monitoring the destruction of banknotes by means of shredder 138, as removal of banknotes from transport system 120 by manipulation prior to their destruction must be prevented. For this reason, disposal or, as the case may be, shredding has usually only been performed by central banks to date. By contrast, the procedure according to the invention also allows this to be accomplished by cash centers or other cash handling service undertakings. EXAMPLE 157 In order to prevent this, provision is made according to a further example to dispose intelligent light barrier 165 in direct proximity to or as part of shredder 138. It thereby becomes possible to recognize that banknotes are removed prior to destruction by shredder 138, since, otherwise, the signal of intelligent light barrier 165 does not report the expected banknote to operating unit 160. If intelligent light barriers 161 to 165 as well as sensor units 140 and 145 capture the serial numbers of the banknotes, as described above, operating unit 160 can generate and save and preferentially transfer to a central database a list of all of the banknotes to be destroyed. If banknotes later surface in the circulation of money later on, the serial numbers of which are on said list, this is then a case of forged banknotes with serial numbers identical to the destroyed banknotes. It is also possible to delete from the list the serial numbers captured by intelligent light barrier 165 and forwarded to the operating unit, since their destruction is ensured. The latter list can be stored in addition to or in place of the first-cited list for subsequent monitoring. In order to also make the electrical circuits unfit for later abuse following destruction of banknote 139, shredder 138 can, for example, be formed such that the electrical circuits are also reliably destroyed. For this purpose, provision can also be made to subject the remains 139 of the banknotes to further treatment, e.g. have them burned, in order to ensure destruction of the electrical circuits. It is likewise possible to configure intelligent light barrier 165 such that it destroys the electrical circuit or marks it as no longer valid by means of an irreversible writing operation. This can be achieved, for example, by a so-called fuse which is irreversibly burned through by means of a suitable current flow in order to rule out further use. Further, it is therefore also possible to perform a comparison with the cited list or lists, which contain the serial numbers of all of the destroyed banknotes. If one of these serial numbers surfaces at a later point in time, this is a case of manipulation. In order to enable this comparison and the above-cited monitoring of banknotes removed prior to destruction, a central database, which contains all the serial numbers of all the banknotes deemed to be destroyed. This, for example, can be done via a network connection, e.g. the Internet. Serial numbers in the database can be checked as necessary via the network connection. Alternatively, it is also possible to delete the banknotes from databases on all valid banknotes. Should banknotes surface during processing in banknote processing machine 100, the electrical circuit of which cannot communicate with the data exchange device, e.g. because the banknote's electrical circuit or antenna is defective, these banknotes can be transported, guided by control device 160, from transport system 120 to shredder 138 for destruction, since they are no longer usable due to the damage. In order to prevent abuse, however, by having other features of these banknotes checked by evaluating the signals of sensor unit 145 by operating unit 160, it is ensured that the banknotes are not counterfeit banknotes or banknotes where the above-cited irreversible writing operation for marking of the destruction has been performed. However, provision can also be made for banknotes having electrical circuits that cannot be evaluated to be sent to a special deposit means, e.g. stacker 131, wherein all suspicious banknotes or non-processable banknotes are deposited for a manual examination. The analysis thereby enabled can, for example, allow conclusions to be drawn in the case of frequent occurrence of defective or absent electrical circuits. Utilization of Data of the Electrical Circuit A variety of further data can also be read and written apart from the reading and/or writing operations described to this point in the context of the data exchange between the banknote's electrical circuit and the data exchange device of the banknote processing machine. For example, data can be exchanged in order to determine the presence of a banknote. Further, the currency and/or the denomination of the banknote, i.e. the denomination can be contained in the data. EXAMPLE 158 The data described can additionally be utilized for the counting, sorting and accounting of the processed banknotes. By means of the evaluation of the data contained in the electrical circuit of the banknote alone or in addition to the information obtained by operating unit 160 from the signals of sensor unit 145 and/or 140, processing security is increased and can be additionally safeguarded by means of the thorough monitoring by means of intelligent light barriers 161 to 165 as described above. Missing or non-assignable, i.e. recognizable, banknotes thus barely occur anymore. EXAMPLE 159 Further, the data of the electrical circuit can be used for processing for in order to determine the state of the banknotes. For this purpose, test data can also be written into the electrical circuit. For example, data about the production date of the particular banknote, the date the banknote entered circulation or the date of its last determination of condition can be written into the electrical circuit. Further data such as information about production-relevant parameters, e.g. color deviations, etc., previous checking procedures of the banknote, i.e. signals of the sensors of sensor unit 145 or their evaluation by operating unit 160, are written into and stored in one or more dedicated memory areas of the electrical circuit. EXAMPLE 160 The stored data can be utilized for a later examination and e.g. determination of condition. For example, conclusions regarding the note's likely condition can be drawn from the date of manufacture and/or the date of entry into circulation and/or the date of the last determination of condition or check, since statistical connections between circulation time and banknote condition have been well researched and known. Of course, the result of the last condition check can also be stored and used for these conclusions. In this case, elaborate optical sensors for examining the state of the banknote could be done without in this case, since the condition can merely be estimated on the basis of the stored data. Alternatively, every more elaborate check can also be applied merely to the subset of the dubious, expired or specially-marked banknotes. EXAMPLE 161 As mentioned previously, the statistical connections between circulation time and banknote state of the banknote are actually relatively well-known. However, particularly on the part of manufacturers of banknotes, there is a need to gain more exact and reliable statements on the actual causes of banknote wear in order to effect improvements in production that improve the durability of banknotes. For this purpose, provision can be made for one or more sensors to be integrated in the banknote paper to measure environmental influences. These sensors can serve to measure chemical, physical or mechanical variables. Sensors, which measure humidity, temperature, salt content, pH value, bacterial infestation or fungal infestation, damages or tears, can be used, for example. Said sensors can be preferentially integrated either into the chip itself or realized separately at another place of the banknote paper by means of thin layer technology. In a simple embodiment, it can be e.g. an FET transistor mounted in such a manner that its gate electrode enters into a reaction with the material to be detected on account of a special pre-treatment or coating. In this context, the sensors will be connected to a chip of the banknote. Here, the chip will have a writable memory, such as an EEPROM, in order to store the measured values recorded by the sensors. The values, preferentially saved at regular intervals, e.g. daily, can be read out and evaluated at a later point in time by organizations authorized to do so, such as the central banks, when the particular banknote, which is in circulation again, is received by them. It is not mandatory for all of the banknotes entering circulation to be equipped with the integrated sensors. It can already suffice to furnish only a portion of the banknotes with sensors in order to obtain sufficient measurement data for a reliable evaluation. EXAMPLE 162 From the data stored in the electrical circuit of the banknote, such as information about production-relevant parameters, data from previous checking procedures or the sensor data, adjustments to the measurement parameters can be performed, in dependence on the stored data, by operating unit 160. In this way, the afore-mentioned color deviations, for example, can be taken into account when checking the signals of optical sensors, as a result of which the measurement result and thus processing of the banknotes by banknote processing machine 100 is improved. EXAMPLE 163 The presence and/or the position and/or the authenticity of specific e.g. optical and/or magnetic locally present security features of banknote 1 can also be stored in chip 3 of banknote 1 during manufacture of banknote 1. By reading out the chip data when such banknotes 1 are checked, one can achieve that checking will be performed more accurately at that particular place only, i.e. e.g. at a higher resolution. By way of example, for this purpose, for example, data on the location of the features on banknote 1 can be transferred by operating unit 160 according to FIG. 57 of sensor unit 145 in order to check such features at the pre-determined location only. It thereby becomes possible, for example, to avoid an elaborate preliminary check to determine the presence and location of the features, as e.g. is necessary according to WO 01/60047 A2. It thereby becomes possible to design the detection methods in banknote processing machines for such locally variant features significantly more simply. EXAMPLE 164 Further, the data stored in the electrical circuit allow later processing of banknotes, which could not be clearly assigned and which, as described above, can for example be in output stacker 131. This data can be evaluated and taken into account during a later manual appraisal by an operator, as a result of which the appraisal is normally simplified, since the operator immediately recognizes which feature of the banknote appears suspicious. Deposit Processing Further advantages of storing processing-relevant data result when processing deposits, which each consist of several banknotes and stem from different depositors, so-called deposits. The banknotes of these deposits are usually separated from one another by separator cards, with the separator cards, for example, being able to contain data about the depositor. The data can e.g. be stored in electrical circuits of the separator cards, which are configured like the electrical circuits for banknotes like those described until now. Such separator cards can potentially be dispensed with if the data of the electrical circuits of the banknotes of the different deposits are available for processing in processing machine 100. EXAMPLE 165 For that purpose, provision can be made that the depositor writes data to the electrical circuit, by which the banknotes can be identified as being associated with the particular depositor. Such data can, for example, be an account number or a customer number. The data can, for example, be written to the electrical circuit when the depositor receives the banknotes and e.g. places them in a cash register. During processing in processing machine 100, the data identifying the depositor can thus be used at any point in time in order to determine the depositor of the particular banknote. EXAMPLE 166 A further possibility consists in, for example, recording the serial number or another unique feature of the particular first and/or last banknote of a deposit and to assign this serial number or, as the case may be, these serial numbers to the particular depositor, for example, by means of operating unit 166. During processing in banknote processing machine 100, the serial number of each banknote is then read during or after singling by the data exchange device in sensor unit 140 or, as the case may be, singler 111 or sensor unit 145, and operating unit 160 assigns the banknotes to the particular depositor when the recorded serial numbers appear. Moreover, all banknotes of the particular depositor can be marked by banknote processing machine 100, by the data characterizing the depositor being written to the electrical circuit of the banknotes, so that same can be recognized as being associated with a certain depositor at any time during processing. EXAMPLE 167 Moreover, provision can be made for banknotes 1, which cannot be recognized because e.g. their chip 3 is defective, to be automatically sorted out and handled separately. Thus, their serial numbers e.g. can be scanned separately and then stored separately for further processing. Authenticity Check and Data Security To improve and safeguard the checking of authenticity and/or the data stored in the electrical circuit of the banknotes to be processed or parts of this data, in particular authenticity features, value or, as the case may be, denomination, serial number, etc., the data can be stored in encrypted form in the electrical circuit of the banknote and/or with a digital signature or, as the case may be, the data exchange between the banknote and the banknote processing machine can take place in encrypted or digitally signed form. Likewise, the data can be stored in a special area of a memory of the banknote's electrical circuit, which is access protected. This data can then only be read or, as the case may be, written when the data exchange device utilized is correspondingly authorized. In order to check this, provision can be made for mutual authentication between the banknote and the banknote processing machine or, as the case may be, between the electrical circuit and the data exchange device to be carried out. This can e.g. take place according to the so-called challenge response procedure, with or without integration of a certificate. PKI (Public Key Infrastructure) methods are especially suited to encryption, since they in particular enable a simple realization of the banknote processing machine, since no specially-protected security electronics are necessary for storage of the keys for decrypting the data. Rather, PKI constitutes a so-called asymmetrical encrypting procedure, wherein the data is encrypted using a secret key, whereas a so-called public key, i.e. a generally-accessible key, is used for decrypting. In this case, the secret keys could be kept at the particular national central banks, the public keys in the banknote processing machines. If data encrypted by the banknote processing machine are also to be written into the electrical circuit of the banknote, it needs the secret key or its own secret key in order to e.g. be able to encrypt special data for processing in the banknote processing machine or a processing step that is downstream. It is likewise possible to provide the data or portions of the data with a digital signature. For this purpose, a secret key is used to generate and likewise store in the electrical circuit a digital signature about the data stored in the electric memory of the banknote or, as the case may be, about a hash value formed from the data. Checking the data is now possible by checking the digital signature with a public key. Different sets of keys can be used for the described encrypting of the data or, as the case may be, the forming of digital signatures, e.g. as described in the above for different applications and/or users; likewise, different sets of keys from secret and public keys can also be used for different currencies, series, denominations, etc. The described procedures for securing the data or portions of the data can be applied individually or, in order to increase security, in a desired combination. To further improve the checking of authenticity of banknotes, provision can be made for the electrical circuit, which contains the above-described encrypted or decrypted data, to contain further data, in particular in encrypted form, derived from features, which are permanently connected with the banknote and individualize same. In the simplest case, this can be the banknote's serial number, which e.g. is stored in encrypted form and/or with a digital signature in the electrical circuit. EXAMPLE 168 During checking in banknote processing machine 100, the serial number of the banknote is read from the banknote's electrical circuit e.g. by sensor unit 140 and/or sensor unit 145 by means of data exchange device 142 and decrypted in operating unit 160, e.g. by means of the above-described PKI method. At the same time, sensor unit 140 and/or sensor unit 145 detects the serial number printed on the banknote by means of an optical sensor, e.g. sensor 143. If the two serial numbers match, this indicates an authentic banknote; otherwise, a forgery must be assumed. For a more precise check, a banknote suspected of being forged is e.g. transported in the first output stacker 131 in order to—as described above—permit a manual check of the banknote. For this purpose, data stored in the electrical circuit or in operating unit 160 can be drawn upon, which e.g. provide information on the results of the check by sensor units 140 and/or 145. Instead of using features of the banknote that are visible to the human eye, such as the serial number for improving the authenticity check, features which are not readily recognizable, can also be used. Such features can be, for example, special materials which e.g. are luminescent, exhibit special magnetic properties, etc. The presence of these materials can then be proved by means of excitation by e.g. ultraviolet light or infrared light or magnetic excitation and be detected by corresponding sensors, e.g. also biochip sensors, and evaluated by operating unit 160. Further, such materials can be used to carry out coding e.g. in the form of a bar code, with the information that is coded with the features—as described above with respect to the serial numbers—being stored in the electrical circuit for a comparison, so as to check authenticity. Instead of disposing the features on or in the banknote in an ordered form, e.g. the bar code mentioned, the features can also be disposed randomly or pseudo-randomly on or in the banknote. The particular distribution of the features is determined, e.g. by the use of corresponding sensors, in this case and stored thereafter in the electrical circuit of the associated banknote. The above-described procedures for the protection of data can be used for this purpose. As described in the above, it is thus possible for chip 3 to contain the data specific to the particular banknote 1, which e.g. can also comprise data about the paper, or, as the case may be, the feature substances contained therein, of banknote 1. Alternatively or additionally, it is also conceivable to permanently apply, in particular to print, onto the banknote the information, which couples banknote-specific paper data with chip data, such as the associated serial numbers of chip 3, which may or also may not correspond to the serial number imprinted on the banknote. This can be effected e.g. by printing on a bar code or a passive oscillating circuit. As described in detail in the scope of this application, the information is preferentially encrypted and/or digitally signed in order to be able to prevent forgery of the imprint correlating paper data with chip data. Paper data also refer to data about the paper of the sheet material and/or the feature substances contained therein and chip data refer to data about the chip, such as its serial number, etc.. An advantage of this variant consists in that the manufacture of such banknotes can take place simply and quickly. The data individually marking the chip, e.g. its serial number, which are established by the chip manufacturer, are e.g. simply read out from the chip in the end phase of banknote production and then imprinted e.g. in the form of a bar code, coupled with paper data, such as the serial number, which is established by the banknote manufacturer. This procedure avoids elaborate writing onto the chip during banknote production in comparison to the reading operation. Special features, as described above in connection with the checking for authenticity of the banknote, can also be used for further tasks. EXAMPLE 169 For example, the features can exhibit a certain dependence on external influences, e.g. a fluorescence effect can become weaker over time. A feature of this type can be utilized to make statements about changes to the banknote in order to e.g. be able to sort out banknotes that are no longer fit for circulation. Further features, as described, are stored in the electrical circuit of the banknote, can be used to check the intactness of the banknote. For example, if a pattern or a random distribution of features over essentially the entire surface of the banknote is saved, a comparison with the features detected anew during processing in the banknote processing machine can be used to determine whether the banknote is intact. The data of these features thus serve as a so-called “snip protection”, which allows checking for the completeness of banknotes, or, as the case may be, the detection of parts of banknotes parts that do not belong together. EXAMPLE 170 Further, it is possible to improve the above-described data security and authenticity check by means of electrical circuits, which e.g. are founded on the basis of silicon technology or on the basis of organic semiconductors. In this context, in the detection of authenticity, a premise starting with the check for the presence of the electric circuit, and going all the way to more complex procedures taking into account serial numbers and/or statement of value (also referred to as denomination or denomination)—as described above—is being assumed. In the case of sole checking of the electrical circuit, a banknote processing machine or, as the case may be, its sensor can be deceived if the electrical circuit of an authentic banknote is removed from same and e.g. applied to a neutral sheet of paper or a copy. Additionally, the banknote without an electrical circuit can still be used further; e.g. in a person-to-person exchange, since in this case, the absence of the electrical circuit would not be noticed. The described combination of serial number and electrical circuit already improves security. Electrical circuits with a memory that can only be written to once (a so-called WORM memory) are sufficient for this purpose. It is thus possible, for example, to store the serial number and the statement of value on a banknote in the way known in the art. Further, an additional value is determined from other features of a banknote. However, a random number e.g. would also be suitable as an additional value. For example, a banknote with an electrical circuit can contain the serial number of the banknote, the denomination and a check digit in the electrical circuit. By means of a secret algorithm, e.g. that described above, the check digit is derived from the data in the electrical circuit (denomination and serial number) and additional information. The derived check digit is subsequently compared with the check digit of the electrical circuit. Further features of the banknote can be used for safeguarding, e.g. the statement of value of the banknote decrypted from a secret feature. These further features can be feature stored on a security thread as an optical, mechanical, magnetic or other code, measurement values can also be used, which are determined in the detection of a secret feature substance. This secret feature substance can cover the surface of the banknote, but it can also be applied to, applied on or incorporated in certain locations in a localized fashion. Likewise, a feature derived from the thickness profile or the dieprint of a banknote can be used. The format of the banknote, the position of the printed image, etc., can also be used. Further features can also be derived from random measurement values, which can be determined on the banknote (so-called unique features). Thus, the transmission of the light on a certain small surface unit of the banknote can be determined, just as positional deviations of printed characters or other components of the banknote, such as security thread, optically-variable element, etc. When linking the denomination and the serial number with one or more of the described other features, a measurable property derived from the check of the feature or of the other features, e.g. an intensity of a measuring signal of the other features, can be advantageously referred to. It is thus e.g. possible to depict a banknote's statement of value by a certain number of points or strips or by the positions of the other feature. In this case, the detection of the other feature allows a conclusion to be drawn; e.g. as to denomination, in which case the distribution (e.g. quantity, density) of the other feature can also vary at individual locations within significant tolerance limits, which, however, are immaterial, since it essentially suffices to faultlessly prove the presence of the other feature at the relevant locations. In actual practice, the minimum intensity necessary for this purpose is nearly always exceeded considerably. Therefore, additional information can be gained from the values of the intensity of the feature at the required locations, which, in a suitable fashion, can be stored or used to derive the check digit. It is also possible to save the result of the check of the other feature as such in the banknote's electrical circuit. This is then particularly advantageous when the measuring results of the test are derived from a secret feature or feature substance. Direct knowledge of the particular value would then be harmless, because the origin of this value is of course unknown, since it is derived from the secret feature or feature substance by measurement. Linking of the features then consists in storing them together in the electrical circuit. What is essential is that the procedure according to the invention creates a connection between the features that are easily read (e.g. denomination and serial number) on the one hand and a certain individual piece of the documents, represented by certain properties specific to this piece. Linking of the stored features to a feature on the banknote determined in another way will cause a checking result to result that varies from one banknote to the other, even when several banknotes have the same denominations or serial numbers, which is actually not possible, but occurs frequently with forgeries. If a counterfeiter e.g. were to produce forgeries with self-manufactured electrical circuits, these would have to at least contain the correct data as to denomination and serial number. Even if this were to succeed, though, an own check digit would still need to be determined and stored for each banknote. This impedes forgeries so much that they are scarcely to be expected any more. This would also still be the case if the significance of the check digit were known to forgers. If one uses e.g. the data of the value coded on a security thread as the other feature, then the stored features would force the data of the thread to be read as well. In another embodiment, one could also include further properties of a document in the check. By optical, magnetic or capacitive scanning of the cross profile of a banknote, e.g. a property that is typical for each banknote can be derived, which stands for the individuality of the banknote like a fingerprint. This measured value can be stored in the electrical circuit and compared later at any time with the measured value of renewed capacitive scanning (unique feature). Similarly, a feature can be derived from the position of an OVD (optically-variable element) strip and saved. In a special embodiment, the denomination of a banknote is not stored in the electrical circuit. Instead, the serial number and the other feature are linked by means of an algorithm, and the result of such linking is stored in the electrical circuit. If the algorithm is concealed, only a suitable sensor can infer the serial number and/or the denomination of the banknote from the stored data. This would even impede a forgery in the case where suitable electrical circuits are available for the forgeries and where they can be provided with data. PKI procedures, wherein the properties measured on the banknote are entered in the chip of the banknote encrypted with the aid of a “secret key” and/or signed digitally, are particularly advantageous. The device checking for authenticity decodes with the aid of the public key and/or checks the signature. EXAMPLE 171 When a banknote is produced, the serial number is stored in plain text in a circuit situated therein. Further, the distance from the first printed character in the upper left corner to the left edge of the banknote is determined. This value A is rounded to two digits (e.g. 3.243 mm would result in the value of 32). The serial number is now calculated modulo A and the result (a number between 0 and 31) likewise written into the integrated circuit. Here, “A” can be any two-digit number. EXAMPLE 172 A bit code, which represents the numbers between 1 and 8, is generated on a security thread by means of magnetic printing ink. This value A is read during a check and first linked with the denomination B=denomination modulo A A value “B” between 0 and 7 results. The serial number is now multiplied by this value and a further modulo operation follows, so that the following results: C=(serial number * B) modulo X A fixed value can be used for X, but a different value determined from the information contents of the banknote can also be used. Result C is written into and stored in the integrated circuit. EXAMPLE 173 In a metallic layer, e.g. a metallized strip, fine interruptions are generated in the metallization, which are almost invisible to the naked eye. The spacing of these interruptions is determined and a digital number derived therefrom. The result is linked in a suitable fashion with e.g. serial number and/or denomination. The result of the linking is stored in the integrated circuit. EXAMPLE 174 A suitable quantity of a fluorescent feature substance is added in the manufacture of a banknote paper. Following printing and insertion of the integrated circuit, the serial number and the denomination are stored in the electrical circuit. Further, the intensity of the fluorescence caused by the feature substance is determined by a suitable sensor and likewise stored in the electrical circuit. EXAMPLE 175 On a share, the serial number as well as the security identification number of the share are imprinted. These data are also stored in an integrated circuit situated in the share. Further, a random number in the form of a digital code (perhaps a bar code) is mounted by means of a non-visible feature substance. This random number is linked to the serial number and the result of the linking is likewise stored in the IC. When checking the share, the serial number and the identification number are read from the IC and compared with the stored data. Further, the non-visible random number is read by a corresponding sensor and linked to the stored data. The result of this linking must then agree with the stored result. If one uses a three-digit random number xyz, then multiplication by an eight-digit serial number would deliver a result with 11 to 12 digits. This procedure is naturally also applicable to other papers of value such as banknotes. EXAMPLE 176 In a banknote printing works, an identifier of the electrical circuit is read by a numbering machine, i.e. a printing technology device, which provides banknotes with serial numbers, and printed on the particular banknote directly, or in a form altered by means of an algorithm, as plain text and/or bar code and/or pixel code or as another two-dimensional code. Since this is only possible at a very low processing speed with the high-pressure numbering machines normally used, numbering is performed by means of ink jet methods or other digital printing methods or by means of laser. EXAMPLE 177 In the banknote printing works, an identifier of the electrical circuit is read and an optical structure that can be generated variably (e.g. lattice, hologram) is and transferred to the particular banknote uniquely assigned and a laterally resolved structural or chemical change is preferentially applied or incorporated. EXAMPLE 178 In the banknote printing works, an identifier of the electrical circuit is read and a magnetic structure that can be generated variably is transferred to the particular banknote uniquely assigned and preferentially an individual one-dimensional or two-dimensional perforation is incorporated, preferentially by means of laser. EXAMPLE 179 An oscillating circuit is situated on the banknote, which is preferentially realized by printing technology. In this context, several capacity surfaces, i.e. electroconductive surfaces, which preferentially consist of transparent conductive material, are electroconductively connected with one another. If the surfaces (e.g. n pieces) are at a particular ratio of size of 2:1, then 2n states can be coded. Thus, e.g. a check digit can be realized. By means of a laser, the surfaces, or portions thereof, can be separated from the oscillating circuit so that the desired coding can be effected. The particular advantage in this context consists in that the check digit can be determined contactlessly for a check via the resonance frequency of the oscillating circuit. Instead of the hitherto-described electrical circuits, optical memories, e.g. TESA-ROM©, are also suited as a security element for storing the above-described data and/or features. The three last-named examples are preferentially utilized in the case where the chip/IC has no memory area that can be written to by the user (e.g. ROM, WORM types). The examples described are, however, also applicable to other types of memory without a chip/IC, such as magnetic or optical types of memory (e.g. TESA-ROM). EXAMPLE 180 In order to preserve the anonymity of a banknote with an electrical circuit, and, at the same time, enable monitoring of banknotes for certain properties, in particular their previous owners or, as the case may be, bearers, provision can be made to provide the electrical circuit on the banknote with a write-only memory area, which cannot be read out directly. In this case, provision is made that a comparison is performed of the information stored in the banknote with other predetermined information in the banknote or, as the case may be, its electrical circuit. Here, the banknote or, as the case may be, its electrical circuit merely generates a signal, which indicates whether the compared informations correspond. Thus, the informations, which are to be checked, must be known, as a result of which anonymity of the banknote is given completely. At the same time, however, each banknote can be marked (e.g. banknotes from extortions, disenabling during transport, etc.) without this being detectable by an unauthorized user of the banknote (blackmailer, robber of the transport, etc.). In the context of standard evaluations by banks, e.g. after robberies, a series of identifications that have been made known can be checked. In this connection, it is particularly advantageous to provide several different memory areas, which can be written into in each case, e.g. one stack, according to different authorizations. Further, for example, a depositor of a deposit can suitably mark his banknotes beforehand. If discrepancies are detected by the institution processing the deposit, the owners can be ascertained after the markings used by them, e.g. code numbers, are made known. EXAMPLE 181 The write-only memory area can be used particularly advantageously to store information in the banknote such as the above-described random number or the different code numbers for access to the different functions of the banknote chip. For security-critical applications, the use of the write-only memory area in combination with the described error counter and the disabling or, as the case may be, marking of the banknote upon exceeding of abortive attempts, e.g. of the input of a code number for access to the banknote, proves to be advantageous. Small Banknote Processing Machines By making use of the above-described electrical circuits and the forgery-proof features of the banknotes, which are jointly incorporated in the authenticity check of the banknotes, as well as use of the corresponding data exchange devices, even especially compact banknote processing machines can be realized, which are more efficient and more reliable than previous banknote processing machines of comparable size. Such banknote processing machines are depicted in FIGS. 63 and 64. EXAMPLE 182 FIG. 63 shows a second embodiment of a banknote processing machine, particularly for counting and/or evaluating banknotes with an electric circuit. Banknotes 1, which are to be counted and/or checked for authenticity and/or the total value or, as the case may be, the denomination of which is to be determined, are inserted into an input unit 110. For that purpose, banknotes 1 are grasped by singler 111 and singled and transported 1b via a transport path 120 into a stacker 131. Further stackers, which also permit sorting, are possible, but not depicted. The respective banknote 1a to be singled next, the lowermost banknote in this case, is detected by sensor unit 140 and the signals of sensor unit 140 are evaluated by an operating unit 160. The evaluation takes place as described above in connection with FIGS. 57-61. In particular, a sensor unit can also be present in singler 111, instead of or in addition to sensor unit 140, as described in connection with FIG. 60. Given appropriate interpretation of the banknote processing machine, a separate transport system 120 can be dispensed with. In this case, the banknotes are transported directly from singler 111 into stacker 131. The banknotes can be processed alternatively along their long side or along their short side. A special advantage of the banknote processing machine according to FIG. 63 consists in the integration of the sensor unit in the area of the singler or, as the case may be, of the input unit. As a result, a measurement path or even the entire transport system can be omitted, to the effect that a particularly simple and compact structure results. The small banknote processing machine designed in this way can, thus, depending on its internal structure, belong to the class of the banknote processing machines for processing single notes or to the class of banknote processing machines with stack processing. By the use of banknotes according to the invention, however, more complex tasks can also be performed by banknote processing machines with stack processing, as the following example illustrates. EXAMPLE 183 FIG. 64 shows a third embodiment of a banknote processing machine, particularly for the counting and/or evaluating of banknotes with an electrical circuit. Here, a stack of banknotes 1 which are to be counted and/or checked for authenticity and/or the total value or, as the case may be, denomination of which is to be determined, are paged through in the direction T. A sensor unit 140 detects the banknotes la or, as the case may be, exchanges data with the electrical circuit, with the sensor signals being evaluated by an operating unit 160—as described above in connection with FIGS. 57-61. The evaluated banknotes 1b are held until all banknotes 1 are processed. In this context, the checking of the banknotes for authenticity can take place after the authenticity features of the banknote have been detected and the corresponding data of the electrical circuit read out, by comparing the detected authenticity features with the data read out. Since the electrical circuit cannot be removed from the banknote and the authenticity features are forgery-proof, when the detected authenticity features and the read-out data match, this reliably yields the authenticity of the checked banknote. EXAMPLE 184 FIG. 65 shows a further example of a so-called spindle counting machine 402, the essential points of which correspond to the construction according to FIG. 64. A stack of banknotes 1 is inserted into the spindle counting machine 420 and clamped and held there by holding device(s) 421. The stack is then situated at position la depicted by dashes. A mechanism 422 now singles banknotes 1 at the other side and counts them. Here, the counted banknotes 1 are grasped by rods 424 disposed on spindle 423, singled and crimped. After successful counting, the stack of banknotes, which is still clamped, is situated at position lb. Upon request, machine 420 releases the stack so that it can be removed. If suitable information transfer devices are present inside and outside of the banknote, the principle described here of the small banknote processing machine with stack processing can be utilized very advantageously in order to be able to address the banknotes individually in the phase of deformation. The banknotes can be enabled very simply here by optical means, or can be addressed only during the page-through time period via electromagnetic waves by suitable communication devices. EXAMPLE 185 The above-described energy gain from the deformation of the banknote, e.g. by elements with a piezoelectric effect, is now particularly advantageous here, since the banknote receives the energy at exactly that point in time when it can and should be addressed individually. Thus, anti-collision procedures can be avoided or, as the case may be, designed distinctly more efficiently. In addition, through this processing method, the number of banknotes not provided with a functional circuit or only provided with a non-operational one is determined without any additional effort. The described spindle counting machine thus allows simple processing by a banknote processing system without transport, during which the banknotes can nevertheless be addressed individually. EXAMPLE 186 If stack processing of banknotes driven by deformation energy is to be carried out at a banknote processing machine, a further alternative to the above example is offered, according to which the entire stack of banknotes 1 is clamped on both sides, similarly as in a vice, and the ends are moved relative to one another in periodic oscillations. Reading-out of the information from the banknote then takes place preferentially by means of light or electromagnetic waves. EXAMPLE 187 This form of energy feed by deformation energy can also be utilized expediently for single-note processing of banknotes by machine. Banknote 1 can e.g. be detected at a place in the banknote processing machine where the banknote is deformed by the shape of the transport path. Such places can preferentially be situated everywhere where banknote 1 performs a change of direction or, alternatively, banknote 1 can be supplied with energy by the protrusion of the rollers driven with the transport speed of banknote 1 into the transport path of the note, which crimp same. A combination with a limpness sensor e.g. is especially advantageous, as e.g. described in the applicant's DE 195 436 74 A1, where the sheet is crimped and stimulated to oscillate by the banknote to be checked being contacted periodically by a rotary roller with several edges or, as the case may be, brushes, piezo elements or lever systems. Such a limpness sensor or any other sensor, such as also a hole sensor, where the banknote to be checked is deformed for measurement(s) of paper properties, can hereby also be simultaneously used in a targeted way for the chip's energy supply and/or for reading out chip data, since the banknotes are deformed anyways for measurement of the paper properties and since a voltage in the banknote is thereby induced, which can supply the chip with energy. EXAMPLE 188 Different kinds of banknote processing machines with stack processing are also conceivable, which perform jobs, which hitherto could not be performed this easily. Such solutions consist in e.g. marking of all banknotes contained in a stack or a container for transport, collective switching-on or, as the case may be, switching-off of banknotes, group-wise recording of serial numbers in chips during banknote production and/or the evaluation of the special banknote data written in during production and quality control for static purposes. For banknotes of variable denomination, a stack of worthless—i.e., with a value of “0” written on them—“blank” banknotes can even have the banknote values required for a delivery written on them. Some of the above-described security features, e.g. the random number that is written in, even allow reliable determination of the authenticity of the banknote in banknote processing machines with stack processing. EXAMPLE 189 Banknote processing machines, which communicate with stacks of banknotes in their singler and/or in the stackers, reckon among the class of banknote processing machines with combined individual and stack processing. Another form of the banknote processing machines with combined individual and stack processing preferentially provides own transport paths for both kinds of processing. Here, e.g. following input and, if necessary, a first stack processing, the banknotes are singled in the singler of the banknote processing machine and the individual banknotes are transported, e.g. by means of belt drives or roller drives. In addition, however, there exists in the banknote processing machine a further form of transport, wherein entire groups of banknotes are transported together, loosely or preferentially in transport containers, within the machine. The transport containers can e.g. be filled up at stations, which correspond to the stackers of conventional banknote processing machines with individual processing; that is, e.g. spira-pocket stackers. The transport containers can either have their own drive or, however, also be driven by the banknote processing machine. A particular advantage then results when the transport containers contain a memory, which contains processing steps to be conducted and/or that have been conducted on the banknotes and/or data about these banknotes contained therein. In particular, the variants described in the section entitled “Containers for banknote transport” may also be expedient for the transport container of such a banknote processing machine. A version of the transport container in a form, which offers possibilities so that the banknote processing machine can deposit banknotes therein as well as be able to again single the banknotes out of the same containers again, is particularly advantageous is. However, the bands of banknote packets can also be explicitly regarded as transport containers. In order to achieve a uniform throughput, the stack transport can be distinctly slower than the single transport, whereby it is less susceptible to malfunction. EXAMPLE 190 In addition, banknote processing machines with combined individual and stack processing can be realized in a more modular fashion, compared to those with purely individual processing. Namely, the individual modules can transfer the transport containers to one another, due to the optionally low transport speed and higher mechanical stability of a transport container with greater mechanical tolerances, than would be possible with individual banknotes. For example, an input station, an output station, a sensor station, a sorting station, a manual reworking station, a destruction station, a banding station, a packing station, etc. are possible as such modules. EXAMPLE 191 Banknote processing machines with combined individual and stack processing permit tasks to be performed, which can not be performed by banknote processing machines with only stack processing. Such tasks consist e.g. in the sorting or packing of banknotes, the detecting and evaluating banknotes by sensors and the reliable recognition and destruction of banknotes without an electrical circuit according to the invention. EXAMPLE 192 On the other hand, tasks can also be solved with banknote processing machines with combined individual and stack processing which cannot be solved or can only be solved given very large effort by those with individual transport. This includes e.g. the provision of transport containers in a waiting position, in order to thus be able to temporarily store larger quantities of banknotes if jams or errors in certain parts of the machine limit the function of these machine parts. This thus allows processing to continue in the banknote processing machine while jams are being remedied, which can significantly increase machine throughput. Several input stations for banknotes on one machine are also conceivable. If the waiting positions for the transport containers have sufficiently large capacity, it is even possible to have a greater number of operators inputting banknotes at the input stations than the machine's nominal processing rate would allow. The transport containers situated in the waiting position can then be processed automatically at times of lower machine utilization, e.g. at night. In the same manner, the manual rework banknotes at the banknote processing machine can be automatically singled yet another time and reprocessed, whereby the rate of manual banknotes can be distinctly reduced. EXAMPLE 193 In current banknote processing machines with individual processing, stackers are used, where the operator of the banknote processing machine removes the processed banknotes, and where a fixed assignment exists between the stacker and the sorting class. These stackers frequently still need to be run in pairs, in order not to have to halt the machine in those periods during which a stacker can not be charged with banknotes, e.g. during the removal of processed banknotes. The resulting potentially large number of stackers and their spatial extent can lead to a banknote processing machine becoming so long that its operator can only remove processed packets if he stands up and leaves his workstation for the input of banknotes. In order to prevent this complication for the operator, which, in the long-term, also becomes noticeable in reduced machine throughput, a banknote processing machine with combined individual and stack processing can exhibit one or more output stations, which are situated in direct proximity to the operator, and in which the containers, which have been made ready for removal, are pushed out of the machine. Thus, several filling stations, wherein the containers are filled and subsequently transported to the associated output station, are assigned to at least one of the output stations from which the containers are output to the operator. Admittedly, the machine is not necessarily smaller spatially, but it can be designed distinctly more ergonomically. Great advantages can also result in the destruction of banknotes if the banknotes to be destroyed can be moved directly out of the transport containers into the shredder, whereby neither jams in the transport system with effects on the shredder, nor disturbances from banknotes erroneously being moved into the shredder are possible. The aforementioned variants, e.g. for stack transport in separate containers within the banknote processing machine, are also expediently applicable to banknotes without an electrical circuit. The use of banknotes according to the invention, however, enables distinct facilitation in realization. EXAMPLE 194 For example, the sensor data and/or sorting classes determined by the sensor station, which can then be utilized by the sorting station, can be written into the banknotes. Such a procedure ensures that the container situated in the waiting position can be further processed without a loss of information after leaving the sensor path, even after major machine malfunctions. Even a continuation of the processing at another machine is possible. EXAMPLE 195 Particular advantages result in deposit processing of banknotes by banknote processing machines with combined individual and stack processing. An idea, which can also be employed with banknotes without an electrical circuit, consists in that individual processing stations, such as the singler, the sensor path, the stackers and the interjacent transport paths, which are preferentially realized as modular units, never contain more than one stack at the same time. This makes it possible to reliably avoid a mixing of different deposits. Thus, for example, if a jam occurs in a transport path, which must be remedied, there will thus be no need for a hard-to-effect assignment of the jammed banknotes to the different deposits, since banknotes of only a single deposit can be found in the transport path in each case. Due to the expected increasing shifting of condition sorting tasks from the central banks to the commercial banks or cash centers, deposit processing in shredder mode will gain in importance. However, the banknotes to be destroyed, are certain to include a relatively large share of non-operable electrical circuits, since these are preferentially sorted out as no longer fit for circulation. By physical separation now being given by the spatial spacing of different deposits, the risk of so-called crossovers of such banknotes, i.e. a mixing up of the original banknote order, can be reliably avoided. EXAMPLE 196 Preparation of the individual deposits for going through the machine will preferentially already take place in the singler. These can [also] be separated from each other by separating means, e.g. separator cards (U.S. Pat. No. 5,917,930), separate separating and information means (WO 02/29737), or separating means designed as container(s) (EP 1 1195 725 A2). Advantageously, the separating means and/or information means are equipped with electrical circuits, which have the same communication interface as the banknotes according to the invention. Advantages can be also, if the separating means can prevent the banknote processing machine from communicating with the banknotes. When coupled with electromagnetic fields, it is e.g. conceivable for the separating means to be electroconductive; e.g. a separator card made of metal, such as aluminum. With this, the banknote processing machine can communicate with all the banknotes of the current deposit to be processed, but not, however, with the banknotes of the next deposit separated by the separator card. Even if the banknotes are present in stacks and are separated from one another in the stack by separator cards, this makes it possible to achieve e.g. inductive coupling and processing of only a single deposit in the stack. With such shielding, the retention of the separating means prior to separation can also be realized very effectively, e.g. in accordance with EP 1 253 560 A2. As soon as communication with the separating means of a deposit no longer achieves any responses, the singler is halted. After the machine has idled, separation can be restarted. This pause, during which no banknotes are separated, can be used to communicate with the banknotes and the separating means and/or information means of the next deposit. Commercial Bank As has been described in the above, the commercial banks constitute an essential component of the institutions of the circulation of money and are responsible for, among other things, dispensing cash, e.g. to trade and consumers or, as the case may be, for receiving cash, which is deposited by same. Within a broader sense, this is also understood to mean other service providers for cash handling, such as valuables transport entrepreneurs or so-called cash centers. In particular, money depositing machines, money disbursing machines and combined money depositing/money disbursing machines (moneychanger(s) or recycler(s)) and the above-described small counting and/or sorting devices are used to perform these transactions. It is to be noted that, within the meaning of the present invention, input “and/or” output machines or, as the case may be, payment machines are understood to mean payment machines, money depositing machines, as well as combined money depositing and payment machines. Money Depositing Machines Money depositing machines can, for example, be constructed such that they comprise an input device for the input of banknotes to be deposited and a transport device for transporting said input banknotes to a deposit device. The input device can be designed as a single note draw-in module for accepting only single notes or also as a stack input module for accepting stacks, i.e. several stacked banknotes. In this context, the storage device can exhibit a temporary storage, e.g. a foil storage, wherein the deposited banknotes are stored temporarily until such time as the depositor gives his final consent for actual withholding of the banknotes deposited in the current transaction. In particular, the deposit device will further comprise an end deposit means, such as a cassette described in greater detail in the above, wherein the deposited banknotes, optionally after temporary storage in the temporary storage are supplied to the end deposit means by means of the transport device and input. Here, the transport of the deposited banknotes can either take place singly and/or also in stacks. EXAMPLE 197 FIG. 66 shows an example of such a money depositing machine 200, into which banknotes 1 can be deposited. Here, money depositing machine 200 comprises an input pocket 201 with an attached singler 202, a sensor device 203 for the checking of singled banknotes 1, a foil storage 204 as a temporary storage, a return pocket 205, into which the banknotes 1 not accepted by sensor device 203 or the banknotes 1 stored in foil storage 204 upon abortion of a current transaction are output again, an end cassette 206, wherein the banknotes 1 accepted by sensor device 203 and situated in foil storage 204 are ultimately stored following confirmation of a current transaction by the depositor, and a control unit 207, which controls the individual components of the money depositing machine 200 via signal lines depicted by dashes. Here, control unit 207, among other things, on the basis of measurement signals of sensor unit 203, determines data such as the total value and/or the amount per denomination of banknotes deposited in a transaction. Money depositing machine 200 can be designed to accept both conventional banknotes without a chip as well as those with a chip. In order to check the authenticity and fitness for circulation of the deposited banknotes, sensor device 203 therefore comprises e.g. a magnetic sensor, a UV sensor and/or an infrared sensor for measuring the associated banknote paper properties, which, of course, is understood to mean not only the properties of the paper itself, but e.g. also the properties of the feature substances incorporated therein. In this context, a sensory system for checking chip properties can be mounted in the same area, e.g. in the same module housing as a sensory system for checking paper properties, although it is also of advantage additionally or alternatively if these two types of sensory systems are spaced spatially, e.g. accommodated in different module housings and/or particularly in different parts of processing, such as was explained by way of example in connection with a chip check in the singler. Money depositing machine 200 can exhibit further components, as they e.g. were described in the above as a component of banknote counting and/or banknote sorting machines, for reading out from and/or writing to the chips of banknotes with a chip 1. Thus, for example, a reading unit, which e.g. checks the presence of and, optionally, the operability of banknote chip 3 and/or reads chip data such as the serial number, the denomination and/or data about authenticity and/or previous checking operations of the particular banknote 208, can be present in the area of singler 202 and/or in sensor device 203. An aforementioned intelligent light barrier e.g. can also be used. As was described above with reference to the banknote sorting and/or banknote counting devices, such data e.g. can be used to pre-adjust sensor modules that are downstream. Especially in the case of there being several reading units 208 mounted in the transport path of banknotes 1, the path of the banknotes 1 deposited in machine 200 can be clearly followed in a particularly simple and reliable way by reading the serial number or other individual data, as is not the case with known systems. EXAMPLE 198 If it is ensured by the production process of the banknotes that the chip cannot be removed from the banknote paper without loss of its functional ability and, thus, that a fraudulent incorporation of the chip into authentic or forged banknote paper of a higher denomination can be prevented, it is e.g. also possible for the authenticity of the banknote chips and/or the denomination of the deposited banknotes to be able to be determined without further optical or other measurements just by reading out the associated chip data. EXAMPLE 199 If the device is not designed for banknotes without a chip, but only for depositing banknotes with a chip, the device can also dispense with the presence of the associated sensor components for measuring magnetic, UV and/or infrared properties. Such a testing system, where a signal coupling between the chip and the sensor unit and/or the receiving unit of an external evaluation device is only used for measurement or essentially only used for measurement, can, for example, then preferentially also be used when the depositor is known and/or determinable and the authenticity and/or the condition of the deposited banknotes is controlled only later e.g. in a competent state central bank. EXAMPLE 200 In such a case, where the chip check itself indicates the presence of an authentic banknote, and where the banknote proves to be a forgery during a subsequent check, because e.g. the chip was incorporated into worthless paper, the depositor can then be retraced later via the serial number. For this purpose, data on the depositor can be stored in a memory of the banknote's chip and/or in a separate database. This is a special example for a case, wherein a correlation of transaction data, such as data on the depositing person, the location and the time of deposit with the measurement data of the sensor device is expedient, by e.g. this data being assigned and saved together. In this connection, e.g. data about the depositor, the time of the deposit, about the authenticity, the condition, the denomination and/or the serial number of the individual banknotes, the total value of the deposited banknotes and/or the intended use of the deposited money, such as data about the account, to which it is to be credited, are summarized. EXAMPLE 201 Given an anonymous deposit, however, the chip check does not suffice in those cases wherein such forgeries cannot be reliably excluded. Moreover, in the money depositing machine, a write device 209, with which data can be written into chip 3 of banknotes 1, will preferentially be present downstream of sensor device 203. Such data will be e.g. information, measured or, as the case may be, determined by sensor device 203, about test data and/or transaction data about the particular deposit transaction. Writing-in of such data will preferentially occur after temporary storage, when the banknotes are transported from temporary storage 204 to stacking cassette 206. As a result, an unnecessary write operation can be avoided, in case the banknotes are returned to the depositor into pocket 205 upon abortion of a current transaction. EXAMPLE 202 Further, it is also possible for such data to be written into not all of, but only part of the basically functioning banknote chips. Thus, e.g. data can be written into only those banknote chips which potentially or very likely should or, as the case may be, need to be checked once more subsequently. In this context, these can be e.g. banknotes suspect of forgery, which do exhibit a functioning chip, but the data of which, though, indicates a forgery (see the “Recognition of duplicates” section) or the paper of which appears suspect of forgery. These banknotes suspect of forgery are preferentially stored in machine 200 and/or cassette 206 separately from the banknotes not suspect of forgery. EXAMPLE 203 It can occur that, e.g. due to signs of aging, the chip of an otherwise authentic banknote is defective or not identifiable. These banknotes can, for example, be immediately output to the depositor and/or also stored separately in machine 200 or, as the case may be, retained in cassette 206 so that they can be checked later by means of other devices or procedures and possibly credited to the customer. Alternatively or additionally, it is also possible in the case of the banknote check not being limited to a chip check, that the check of e.g. authenticity and the determination of denomination is effected by means of the basically known check of the banknotes' paper properties. Thus, provision can also be made to read the serial number of the banknotes by means of an optical scanner as a camera system and to store these together with the other data about the retained banknotes in a memory of the automatic teller or, as the case may be, of the cassette. EXAMPLE 204 In order, for example, in a transitional period after the introduction of banknotes with a chip, during which older banknotes without a chip are also to still be accepted as an authentic means of payment, provision can be made that, during an automatic check, e.g. by means of a scanner, the serial number on the banknote paper is always read or at least read in the case where a check is not recognized or not checked as authentic. This [serial number] is then preferentially compared with data, which give details about those banknotes, which were still put into circulation in a regular fashion without a chip. This check can either take place locally in the checking device itself or by means of a remote data transfer via a comparison with data in a central database. Moreover, provision can be made to achieve differentiation between authentic banknotes without a chip and authentic banknotes with a defective chip or, as the case may be, an antenna in that a two-dimensional image of the banknote, especially of those areas where the chip or, as the case may be, its antenna should be situated, is gained by means of a camera system. In this context, other common procedures, such as acoustic, electrical or other procedures, which permit detection of the presence of a chip, can also be used. EXAMPLE 205 A further special embodiment is given when the banknote check is constructed multiple-staged, in particular two-staged. This means e.g. that different checking procedures are performed at different speeds and/or different checking procedures are performed at separate times. In particular, this can also mean that there is one checking and/or evaluation process before and another one after temporary storage in temporary storage 209. Thus, it is thus particularly preferential for e.g. the determination of value, chip authenticity and/or assignment of the serial numbers to the depositor in the sensor device 203 to take place prior to storage in temporary storage 203, while the authenticity check, e.g. of the banknote paper features or print banknote print features and/or the condition check is effected after the temporary storage. An advantage of this kind of an procedure consists in that the subsequent checking steps, such as the check of condition, can take place at a slower speed than the checking steps prior to the temporary storage. This makes it possible for the depositor to have the deposit transaction completed quickly with the temporary storage and to have the condition check of the banknotes deposited during the transaction to be performed only slowly in a period by no later than by the beginning of the next deposit transaction. Due to the time saving, a significantly more inexpensive checking and evaluation device can thus also be used, which does perform checks such as the condition check accurately, but does so more slowly. At the same time, however, it is ensured that settlement of accounts with the customer, i.e. confirmation and thus completion of the deposit process, for example,.takes place quickly and consequently, that the transaction time for the customer can decline. Therefore, e.g. a sensory system, which requires 1-5 seconds to evaluate one banknote, can also be used for the condition check. Within the meaning of this concept, it is also possible e.g. to already record data by means of associated sensors prior to temporary storage, but to evaluate at least part of these data only later, e.g. partially or fully after completion of the deposit transaction for the customer. Thus, it is possible e.g. for a camera that contains sensor unit 203, to take an optical, two-dimensional picture of at least a partial area of the individually-deposited banknotes and for the data to be evaluated, e.g. with regard to the presence of tears, dirt or stains, only later in order to determine condition. If, in that context, banknotes are e.g. classified as no longer fit for circulation, they can then be stored in machines 200 and/or cassette 206 separately from the banknotes which are still fit for circulation. In the case of banknotes with a chip, it is alternatively or additionally also possible to mark the banknotes that are fit for circulation and/or the banknotes that are not fit for circulation by writing associated data into the chip and storing these separately or together with the other banknotes. Due to the possibility of writing check data into the chip, simpler storage without the need for separate storage of banknotes that are not fit for circulation and banknotes that are fit for circulation can thus be produced It is to be emphasized that the aforementioned system of the multi-staged check can also be advantageously used with all other machines where banknotes are deposited. It is especially emphasized that this method is not limited to the use of banknotes with a chip, but rather that it can also be used with all banknotes without a chip. EXAMPLE 206 Furthermore, as mentioned above, a money depositing machine is preferred that identifies the retained banknotes as disabled prior to their final storage in the cassette. This has the advantage that money stolen from the machine after it is broken open is not considered authentic and that it is therefore of no value to the thief, at least not if such disabling is also reproduced optically and/or acoustically or, as the case may be, reproducibly for humans without machine checking. Otherwise, this identifier of the banknotes, which continue to be considered authentic may at least help to better follow the circulation of these banknotes upon a subsequent check of the banknote by machine. EXAMPLE 207 A further particularly advantageous embodiment provides for the banknotes to be fed in as a stack and processed in the stack, i.e. checked via measurement, among others. The methods and components of the apparatuses with which such a measurement in the stack can be carried out were explained and described by way of example previously in the section “Stack Measurement”. If e.g. the value of the stack is determined without singling, direct transport into the end cassette can take place with the money depositing machine. Singling, the transport of individual notes, the sensor technology for individual notes and escrow can consequently be eliminated. The reliability of such a device increases significantly due to the significantly simplified construction. In addition, the price can be reduced drastically. An example of such a money depositing machine 210 is schematically illustrated in FIG. 67. It comprises an input pocket 211, wherein banknotes 1 with a chip are deposited as a stack onto a deposit surface 215. The banknotes 1 loaded into pocket 211 are measured as a stationary stack by means of a checking device 212 controlled by a control device 213. In this context, checking device 212 will be constructed and function in a manner as was described above in the section “Stack Measurement”. In particular, this measurement will comprise a value determination for the determination of the total value of the deposited stack. Furthermore, the other, aforementioned processing steps can also be carried out by checking device 212, such as an authenticity check and/or a check of condition and/or a writing of check data and/or transactional data to the chip of the deposited banknotes. Subsequently, the banknotes 1 thus tested are deposited stacked in the banknote cassette 214. This can e.g. occur in that a non-depicted electromechanical actuator is switched on and driven by the control device 213, by means of which drive the deposit surface 215, upon which the banknotes 1 in the input pocket 211 rest, is pulled away, such that the banknotes 1 in cassette 214 potentially fall upon the already stacked banknotes deposited therein. Subsequently, deposit surface 215 is again moved back to the position depicted in FIG. 67, upon which surface banknotes can again be deposited during a subsequent transaction. In order to prevent unauthorized removal of banknotes after a check, but still prior to final storage in cassette 214, input pocket 211 will preferentially be lockable e.g. via a cover 216 that is pivotable by means of an electromechanical adjustment drive. This means that cover 216 is or, as the case may be, will be opened at the beginning of a deposit process to enable the insertion of the banknotes 1 to be deposited, and that, in particular prior to the beginning of the stack measurement, cover 216 will be closed to prevent an unauthorized access to the banknotes 1. EXAMPLE 208 A further variation consists in the following: In many countries, lawmakers provide that, in the case of money depositing machines, banknotes that are considered suspect of forgery must be deposited in a separate pocket in order e.g. to ensure that banknotes that have actually been forged can be destroyed following a technical criminal investigation. The necessity of the separate pocket results in a not inconsiderable increase in costs for such money depositing machines, since the pockets themselves not only need to be constructed, but in addition, the entire transport path of the money depositing machines must also be modified such that the pocket can be filled with banknotes. Apart from this, the increase in space requirement for the money depositing machines is also not inconsiderable. The necessity for such a separate pocket can be eliminated through the use of the banknotes according to the invention. To that end, the fact of the suspect of forgery is written into the memory area of each banknote suspect of forgery during the check in the deposit machines. This writing-in should preferentially be irreversible for the owner of the machine. Only the central bank can possess the privilege of lifting the counterfeit suspicion in case the suspicion is not confirmed after a closer investigation. This can be implemented e.g. through the use of various access privileges to the memory of the banknote. The operator of the money depositing machines could then e.g. be obligated to check the banknotes removed from the money depositing machines with a reading device and to send the banknotes reported as suspect of forgery to the central bank. If the banknote contains its own display for displaying its condition, it would also be de facto impossible for the operator of the money depositing machine to proceed otherwise, since the banknotes would have been clearly identified as suspect of forgery. A further possibility consists in the use of PKI encryption methods. The number of banknotes marked as suspect of forgery and/or other data, such as the time of emptying, an emptying counter of the machine that cannot be manipulated by the operator, etc. are encrypted by the machine with a public key assigned to the machine and can be decrypted at the central bank with the private key assigned to the machine. For example, the operator can be forced by law to effect uninterrupted delivery of such reports, with the variable portions, such as the time stamp or, as the case may be, the counter of the encrypted data being able to cancel the points of attack for a manipulation, because this would prevented data from older transactions from being used once more. Combined Money Depositing and Money Dispensing Machines In the case of combined money-deposit and money dispensing machines, such as money changers or, in particular, recyclers, the aforementioned embodiments that were described in relation to money depositing machines can be applied. This also applies in particular to the case where the deposited banknotes are not again dispensed and therefore e.g. also need not be stored separately by denomination. The aforementioned principles can, however, also be used for a recycler wherein the deposited banknotes are stored separately by denomination to be able to output them once again in subsequent money dispensing transactions. Thus, the reading/writing of chip data, the multistage checking method or, as the case may be, the stack processing also prove to be particularly advantageous here, for example. Since only the actual input process and output process should occur quickly in a recycler, e.g. the sorting of banknotes stored intermediately by denomination can in turn also take place at a slower speed. I.e. the singling of the e.g. banknotes inputted and measured in the stack can potentially also be conducted after completion of the transaction. Furthermore, deposited banknotes that are outputted again should be checked for their authenticity in every case. Money Dispensing Machines In the case of money dispensing machines, too, some of the aforementioned concepts, which were described in relation to money depositing machines and combined money depositing and money disbursing machines can be adopted. Thus, the reading/writing of chip data and stack processing also prove to be particularly advantageous in this case, for example. Thus, the serial numbers of all banknotes stored in the supply cassettes of the money dispensing machine are captured e.g. by readout of the associated chip data and either stored in a database internal to the machine or in a database connected from the outside by means of a data line. EXAMPLE 209 A particular improvement to the currently known systems then results if one unequivocally follows which banknote amounts have already been disbursed and which ones are still located in the machine momentarily. This can be effected in that a serial number reader is interposed between the memory area of the banknote to be dispensed and the output pocket, which [reader] reads the serial numbers or other individual data of all of the banknotes subsequently dispensed. This is then expedient if the correlation between the serial number and the denomination was known or e.g. was determined or, as the case may be, measured in an automatic teller or another external apparatus. EXAMPLE 210 In addition, the money flow can be controlled in that check data such as the banknote serial numbers, together with transactional data, such as data about the recipient, are stored when money is disbursed. The concept of temporary cancellation of the banknotes can likewise be advantageously applied. Thus, through prior writing to their chips, the banknotes inputted into the money dispensing machines by the commercial bank will be marked as cancelled and thus without value. By interposing a writing unit now for writing to the banknotes that are to be dispensed in an ongoing transaction between the deposit area of the banknotes to be dispensed and the output pocket, the banknotes to be dispensed immediately afterwards are enabled again by writing the associated data to the banknotes' chip. EXAMPLE 211 In addition, provision can also be made to determine only the denomination of all of the banknotes situated in the automatic tellers, in place of or in addition to the serial numbers. Here, e.g. the aforementioned measurement methods can be realized and utilized. In particular, a stack measurement of the banknotes stored in the automatic teller is thus expedient. This can in turn also be realized as a type of self control, so that the momentary amounts of cash in the automatic teller are always determinable on the basis of a stack measurement by a measurement device or, as the case may be, an evaluation device contained within the automatic teller or, as the case may be, its storage cassettes. This make it possible for the cash stored within the machines to be acknowledged as a minimum reserve and thus as non-interest-bearing property of the Land Central Bank [FRG]. In known money dispensing machines, the commercial bank that inputs and stores the banknotes in the automatic tellers for later output to the customers must pay interest on these [banknotes] to the issuing Land Central Bank, since it cannot be continuously clarified which banknotes actually inputted into the machines at a certain point in time are still situated in the machines at later points in time, and which are not. By means of the unequivocal self control it can, however, always be clearly demonstrated which cash amounts were still located in the money dispensing machines when or, as the case may be, exactly when they were dispensed. This method will mean significant savings for the commercial banks. Commerce Cash registers, or registers for short, are used in all areas of commerce such as in supermarkets or department stores. As is commonly known, these registers serve to accept the customer's cash intended in payment for purchased goods and to deposit it in the register and to in turn give out change from the cash holdings in the register. In larger businesses, money depositing machines, wherein, for example, the cash holdings of the respective registers are inputted and automatically counted and reconciled, are used as well to levy and reconcile the individual registers of a department store. Money Depositing Machines in Commerce Within the meaning of the present invention, such money depositing machines preferentially have properties as were previously described in the section “Commercial banks/money depositing machines”. Moreover, it is also conceivable to use the above-described combined money depositing and money dispensing machines to not only reconcile the individual registers, but to also simultaneously dispense the necessary (cash) change, e.g. for the next day. In comparison to the use of such devices with money depositing function at commercial banks, these devices for use in commerce will preferentially be not be designed as variations that are installed such that they are stationary, but rather as mobile i.e. transportable variations. If the device within this meaning e.g. is equipped with a rack on rollers, it can thus be readily moved between the various registers of a department store to be able to levy and clear the cash holdings directly on location, without the need to first refill the cash that was taken out of the register to be reconciled e.g. into a cassette and to transport it to a money depositing machine installed such that it is stationary in another room. Registers Since cash is likewise inputted and dispensed at registers, embodiments as described above for money depositing machines, money dispensing machines and combined money depositing and money dispensing machines can also be realized for these [registers]. In that context, the checking of banknote properties through communication between the chip of the banknotes and an evaluation device, e.g. by optical, inductive or capacitive means, is once again of particular advantage. In this context, particular reference is once again made to the use of a “light barrier” and/or processing in the stack. Here, the evaluation device can either be present as completely integrated in or on/at the register and/or at least partially external to it. EXAMPLE 212 Reading device 220″ of FIG. 48 for the checking of banknotes with capacitive coupling elements can thus be used for banknote checking at registers. An associated device can e.g. be present externally or integrated into the register itself. By depositing a stack of banknotes on the depositing surface 221, the authenticity and/or the value can be checked rapidly, for example. Further, the use of banknotes with a chip allows particularly reliable, automatic inventory or, as the case may be, monitoring of the register. This can e.g. be realized in that the register contains a device to be able to register each removal or insertion of banknotes. EXAMPLE 213 For one, this can take place in that it is recognized whether banknotes are taken out of the deposit area of the register or insertion into it. This is e.g. accomplished by at least one checking unit installed in the register as a type of light barrier, which determines, e.g. by means of optical, inductive or capacitive coupling with the banknote chip, whether same leave the deposit area of the register or not. Specifically, this can e.g. be determined by checking whether the banknote chips come into a certain predefined coverage range of the coupling or move out of same. Aside from the determination of the presence of such banknotes that have been deposited and/or dispensed, the checking unit can e.g. preferentially also be designed such that it reads properties such as the serial numbers of the banknotes and/or checks their authenticity. The authenticity check can e.g. also take place through the recognition of the chip and/or the checking of chip data. EXAMPLE 214 Additionally or alternatively, provision can be made to ascertain the respective momentary stock of cash in the register itself. I.e. it is not directly ascertained whether banknotes are being taken in or, as the case may be, dispensed, but rather which Banknotes are situated in the register momentarily. To this end it can e.g. likewise comprise one or more checking units that, through communication with the banknotes in the register, determine their authenticity and/or number and/or serial number and/or total value. In this way, a type of self control of the cash holdings inside can also be realized for registers. In this context, the cash holdings thus determined can also be displayed on a display surface of the register. If the banknotes in the register are deposited cleanly by denomination, i.e. the banknotes of different denominations are deposited separately in different slots, it can also suffice to merely determine the momentary number of banknotes per slot, for example by means of one of the aforementioned stack measurement methods. Among other things, several of the slots, in particular each slot, will exhibit an individual checking unit in this case as well. If it is predetermined which denomination of banknotes are, or, as the case may be, are supposed to be in which slot, the total value of banknotes per denomination and/or the total value of all banknotes of an arbitrary denomination can be determined e.g. by means of an evaluation device integrated in the register or connected to it by a signal line. In case the contents of a register can be determined free of doubt in this way, it is simple to document filling or removal by the register personnel at any time. One can therefore dispense with the currently customary procedure of personalized register drawers for banknotes. EXAMPLE 215 E.g. in such a case, in order to prevent that the operating staff of the register unintentionally deposit banknotes incorrectly, e.g. insert a 10 e note in the slot for 20 notes, the register will preferentially be provided with a checking unit that determines whether banknotes of only one individual denomination are present in the respective slot. By way of example, the case of an inductive or capacitive coupling to the banknote chip is explained. If the transponders of the banknotes of different denominations each exhibit a different frequency behavior, then e.g. an anticollision method that determines whether “false” response frequencies, i.e. signals from banknotes of incorrect denominations, are measured in the respective slot, will be able to be used to advantage. Alternatively or additionally, a deposit surface corresponding to surface 221 of FIG. 48 can also be present in each of the individual slots to be able to determine and monitor the inventory of banknotes in the individual slots. EXAMPLE 216 A further particularity of registers, as opposed to the money depositing machines or, as the case may be, money dispensing machines used in commercial banks, is that, not only must the capture of the amount of money taken in occur in registers, but also a comparison with the amount to be paid per se, i.e. the total value of the purchased goods, with the difference in the amounts being paid out again as change. For that reason, the banknotes deposited in the register and/or taken in and/or dispensed from same are preferentially not only captured, but rather a comparison with the fixed total value of the purchased goods takes place e.g. by means of scanning of the barcodes on the price tags of the purchased goods. That means that e.g. in an evaluation device, a check is performed to determine whether the operating staff member takes too much and/or too little change from the register during a sales transaction. An incorrect disbursement of change can e.g. be displayed through an optical and/or acoustical warning. To the extent that the taking in and dispensing of coins is not also recognized automatically, no exact counterbalance can be conducted in this case. At least, however, one can determine whether or not banknotes with a total value that exceeds the amount of change due were dispensed. Through above-described monitoring it can also be ensured that no money is removed from the register at a certain point in time or in a certain period of time, e.g. when no sales transaction is being carried out momentarily. EXAMPLE 217 In order to also potentially be able to determine inconsistencies subsequently, it is preferentially possible for all of or a portion of the data captured by the checking unit to be stored in connection with a time capture for later evaluation. EXAMPLE 218 The checking unit for the recognition and checking of banknote chips can also be connected with the scanner for the purchased goods. To the extent that the goods e.g. are likewise equipped by means of a transponder instead of an optical barcode, the scanner for the goods can simultaneously also fulfill the function of the checking unit for the recognition and checking of the banknote chips. That means that a single device or, as the case may be, components of the register can suffice for both the recording of the goods as well as the recording of the banknotes. EXAMPLE 219 The checking unit for the recognition and checking of banknote chips, as was described in the above, can not only be integrated in permanently installed registers, but rather in mobile registers, cassettes or strongboxes as well. EXAMPLE 220 According to a further preferred example, information on the intended use of the banknotes are stored in the memory of the chips of the banknotes. In this context, data with reference to the intended use are particularly preferentially displayed with an electrooptical and/or acoustical display device that e.g. is integrated in the banknote paper. Through the fact that the information on the intended use are also displayed such that they are visually visible or acoustically, one can, upon circulation of the money, also immediately recognize without additional aids whether the banknotes are disabled for a certain intended use. EXAMPLE 221 Thus data, which indicate that the banknotes are only to be exchanged for certain goods or groups of goods, can be stored or are stored in the chip memory or, as the case may be, can be displayed or are displayed on the display, so that, for banknotes that e.g. are dispensed by the parents to their children as pocket money, symbols are displayed in the display that indicate that no goods such as alcohol or cigarettes can be purchased with the respective money. In this case as well, provision can further be made that the checking units of the registers, which are set in accordance with the aforementioned, read the relevant memory contents of the banknote chips and refuse the acceptance of such banknotes in the payment process for excluded goods. EXAMPLE 222 According to a further preferred embodiment, the display is used as an informational surface or an advertising surface on which information is depicted. In particular, an intended use for the document of value can be displayed. In this case, the use of the banknote it is not completely unrestricted, but rather a certain use such as the purchase in certain businesses or of certain goods is considered preferential or limited or excluded. This display of the intended use can function mandatorily or merely as a recommendation. In addition, e.g. correspondingly adjusted checking apparatuses may refuse the acceptance of such documents of value in the payment process for goods excluded by the display. Through the fact that the information on the intended use are displayed in visually visible fashion, one can, during circulation of the money, also immediately recognize without additional aids whether the banknotes have been released for a certain intended use. EXAMPLE 223 In an embodiment, provision is made that a consumer can, at certain terminals intended for consumers, which are set up and operated by the company, call up the status of banknotes received. Likewise, manual devices that are offered commercially can find application for this purpose. To this end, a particular addressing and associated storage area is provided in the electrical circuit of the banknote, under which the company can write and store information for this banknote in the electrical circuit. This can be the serial number (that is optically visible on the BN for everyone), but also information about another intended use (e.g. gratuity, bonus, prize). The consumer can then retrieve the status of the banknote at the described devices. In this context, provision can also be made that the consumer likewise writes information under the particular address, e.g. his name, home address, customer number, etc. To this end, the company writes informations to the electrical circuit of the banknote under the respective addressing. This can e.g. take place in that the company provides randomly selected banknotes, the serial numbers of which it has previously read in and e.g. stored on a data processing system, with an identifier prior to the dispensing of change at the registers. As described above, this informations are stored under the particular address so that these addressed informations are only read out at customer terminals provided by the company for that purpose and/or at the registers of the company. It is also conceivable that manual devices could be obtained by customers, with the help of which the customer could then read out the status of the banknotes received by him. This can take place on the premises of the company, but it is also conceivable that the customer calls up these informations e.g. at home by means up of an additional device or a network connection such as an Internet connection or a mobile radiotelephone connection (GSM, UMTS, etc.). The information given out (e.g. presence of prize or no prize) is directly displayed or transmitted to the customer. A banknote provided with a prize is enabled (erased) again by the company after handing out the prize, preferentially at the register or at the customer terminal, for this purpose, the particular address is again enabled. Afterwards, the banknote can also be given back to the customer again. In order to be able to translate the procedural procedure described into practice, EEPROMs (electrically erasable programmable ROMs) are preferentially used as the memory of the electrical circuit of the banknote. However, magnetic and/or optical memory devices that are writable or, as the case may be, rewritable and erasable are also conceivable. EXAMPLE 224 A further potential application example for a banknote with an electrical circuit is a tracking and tracing process. Here, the banknote or, as the case may be, its electrical circuit is previously provided with an identifier, e.g. through storage of the serial number. If the consumer then brings the banknote into the vicinity of one of the customer terminals described above, a register or a manual reading device, such register or device recognizes whether the banknote is specifically marked. For department store chains, this tracking must expressly not be limited to one branch. One can e.g. imagine that the customer in Department Store A in City B is given a marked banknote, but that it is first examined for an identifier mark at a terminal during a subsequent visit to Department Store C in City D. In this context, provision is made that the customer sends e.g. an SMS (short message service) to the department store via mobile telephone or internet application when he recognizes that the banknote is marked, and in a countermove thereupon receives a message whether a prize is associated with the present banknote and/or what type of prize is involved in this context. EXAMPLE 225 A further example relates to a lottery function (similar to a raffle). Here, certain banknotes are marked and provided with a lottery ticket number as in a raffle. If the customer then checks the number during his visit to the department store he can see whether his BN is marked (“prize”) or not (“dud”). Here, the prize can be visualized at a terminal, or the customer receives a message about his prize via SMS, surface mail etc. and it is later personally handed out or shipped. EXAMPLE 226 In a particular application, provision can be made that the customer enters the serial number of his banknote received at the participating company on an internet page provided specifically for that purpose. He may then leave e.g. his name, address or similar. The company conducts a type of lottery at periodic intervals in which certain serial numbers are selected as prizes. EXAMPLE 227 A particular form of the application according to the invention can e.g. also be that a casino or a gambling establishment gives out special coupons, jetons or stamps (special bank notes are also conceivable) upon the cashing of a check or during the exchange of cash at the beginning of a visit to the casino, which [items] are likewise marked by means of a chip. During certain games of chance (e.g. at the roulette table, but also other conceivable games such as blackjack, baccarat, slot machine, etc.), the jeton, the stamp or even the banknote are then examined for an identifier mark and, as applicable, the prize or bonus is handed out or credited to the customer. EXAMPLE 228 In a further application example, provision can be made that a company writes a gratuity to the banknote in addition to the denomination of the marked banknote. E.g. a marked 50 note contains an additional gratuity of 10 that can then be redeemed in the same company, even at a later time, e.g. upon the purchase of a further article. This function can also be combined with the customer cards frequently issued nowadays, which can likewise have an electrical circuit. In this context, by means of specially marked banknotes, acquired gratuities can be transferred to the customer card or be credited directly upon the purchase of goods. In this context, it is particularly expressly provided that the above-described terminals for the recognition of the identifier marks of the banknotes can also simultaneously write to or read customer cards. EXAMPLE 229 In this context, it is possible that a business e.g. allows its logo to be depicted on the display by writing corresponding data to the electronic memory of the banknote chip and accepts the banknotes thus marked as discount coupons upon purchase. For a banknote with a denomination of 100 , the customer would receive e.g. goods in the value of 110 upon purchase. In case the business does not wish to reissue the coupon-banknote again, it will subsequently erase the displayed information which marks the coupon in that, e.g. control signals, which alter and/or erase the usage data in the memory of the chip of the banknotes in appropriate fashion, are transmitted to the chip of the banknote with the checking unit of the register. EXAMPLE 230 In addition, if e.g. goods of lesser value than the denomination of the banknotes are purchased in the department store, the usage information can thus preferentially be applied to the change that will be dispensed to the customer. Consequently, the deposited banknote is automatically recognized in the register during the deposit process and, via a writing device integrated in the register or externally to it, the change is marked by means of a noncontacting coupling to the chip of the change in correspondence to the intended use displayed for the deposited banknote. In this context and in the above-described variations, the chip can not only be situated in the banknotes, but also in coins. In this context, the coin is preferentially nonconducting, e.g. except for the components of the chip and the antenna necessary for a transponder function, and e.g. manufactured of hard plastic. EXAMPLE 231 A display of the banknote can also be advantageously used to indicate the momentary validity of a banknote. By way of example, it is conceivable that a code of correspondingly authorized banks can be written into the memory of the control device integrated in the banknotes, which [code] completely limits the use of the banknote, i.e. renders the banknote temporarily or permanently void. This state will be recognized by the associated reading devices for such banknotes, and the banknotes then classified as not authentic. However, to be able to also recognize this invalidity without a reading device, the validity state is additionally depicted on the display. In this case, e.g. an LED in the banknote that is turned on or turned off for an invalid banknote already suffices. Preferentially, e.g. correspondingly-adjusted checking devices that are e.g. integrated into the register or mounted externally to it may refuse the acceptance of such documents of value during the payment process of goods that are excluded as per the display. EXAMPLE 232 Preferentially, an apparatus will be provided that serves to process such sheet-shaped documents of value, wherein a writable memory such as an EPROM, EEPROM, and a display device is integrated, which displays an informational content optically and/or acoustically, with the apparatus being provided with a writing device for the writing of data to the memory in order to be able to alter a display condition of the display device e.g. in the aforementioned way by changing a data content of the memory. The high-quality inventory check, authenticity check, and/or value check conducted by way of the communication with the banknote chip can, e.g. in the aforementioned cases, take place offline and/or online. This means that the evaluation device for the evaluation of the measurement data of the checking unit(s) is either integrated in the register itself or present outside of it and connected to the register via a signal line. The signal line can be wireless and/or wire-bound. In an external evaluation, the checking unit of the register will preferentially be connected with a central evaluation device by means of a network connection, such as an intranet connection, internet connection, fixed network connection or mobile radiotelephone connection, which evaluates and checks the data from several registers. EXAMPLE 233 The data can e.g. be used to automatically capture the inventory of the individual registers so that before, when a prescribed minimum number of notes of a certain denomination is reached or fallen short of, such banknotes can be delivered in a timely fashion to the respective register. EXAMPLE 234 In addition, the readout of the chip data from a banknote stored and/or placed in a register can be used e.g. for a capture of its serial numbers. Thus by way of example, the appearance of previously registered banknotes, e.g. that stem from an extortion for ransom money, can quickly be determined. Again, the evaluation takes place either “offline” in the register system itself, or “online” via a connection to an external database. In the latter case, the system is also suited for the determination of general data about the circulation of cash such as distribution speed, dwell time, etc.. EXAMPLE 235 If non-identifiable or, as the case may be, defective banknote chips appear during the payment procedures, the banknotes on which are present further e.g. visually discernible or tactilely palpable security features will thus be checked manually by register personnel or with the help of separate checking devices and/or ones that are also integrated in the register or at least connected to it. In case the register holdings are automatically monitored, the necessary data, such as the quantity of banknotes with a defective chip placed in a slot and/or their denomination, can be inputted by means of an input unit and transmitted to the evaluation device of the register. In this context, the banknotes with a defective chip are preferentially also stored in the register separately from the banknotes with an operable chip so that they are sorted out more readily and not dispensed to the customers again. EXAMPLE 236 The chip 3 of a banknote 1 will typically contain information on the denomination of the banknote 1. In this context, a further idea of the present invention consists in providing such banknotes 1 with an alterable denomination. In this context, this alterable denomination can e.g. be displayed by means of optical or acoustic display devices likewise described within the scope of this invention. In this context, the denomination that is stored in encrypted form in chip 3 should only be able to be altered by correspondingly authorized persons or, as the case may be, institutions with the aid of special reading devices, or as the case may be, writing devices that recognize the encryption code. This can e.g. be used to transfer the denomination of a banknote or a portion thereof from one banknote to another by means of an associated reading-writing device. Further, this can e.g. be used to the end that the equivalent value of banknote 1 or a portion thereof is transferred and credited to an account. It is likewise conceivable that the equivalent value of banknotes 1 with chip 3 contained in a container, such as a cassette or a vault of an automatic teller, is transferred to an account while the banknotes are stored in the container. By way of example, not until or shortly before issuance, are the banknotes then again equipped with the respectively appropriate denomination. In this way, the insurance premium necessary in principle or, as the case may be, interest can be avoided. So as to be able to still produce information about the momentary denomination of a certain banknote, even during a chip failure, the associated data, that is data on the denomination in conjunction with a unique feature, e.g. the serial number of the banknote, should be stored in an external database, such as a database that is central for a certain region. EXAMPLE 237 It is likewise conceivable that the checking device according to FIG. 37 is integrated in a cash register and, in fact, preferentially in several or all deposit slots. The light source, such as a laser diode for the activation of an outermost banknote in the stack will again preferentially be integrated in the base of the respective deposit slots to illuminate the bottommost banknote in the deposit slot from below e.g. after closing of the register drawer. Here there can be an automatic switch that is coupled to the closing process of the drawer and activates the laser diodes. To achieve a better contacting between the individual banknotes in the stack, provision can be made for these to be pressed together with a clamp in the deposit slot. Preferentially, the banknote illuminated first, i.e. bottommost in the stack, will now send its information to the checking unit of the deposit slot. After checking or, as the case may be, registration, the next successive banknote lying above is supplied with energy as described, in turn sends information to the checking unit in the drawer, etc.. At the end, the status of the banknotes situated in the register drawer can thus be readily evaluated e.g. by serial numbers, denomination, quantity, total value, etc. and e.g. displayed on a register display. Consumer Since the chip of the banknote is only readable by machine, a person using cash can only then obtain increased security against forgeries if (s)he uses a suitable checking device. Advantageously, this device communicates with the chip of the banknote in order to e.g. check the value and/or the authenticity of the banknotes. As in the register systems, an additional brief visual or tactile check by the person remains unaffected by this as a rule. A check of just a few features can already be sufficient since, in this application, as in the application in registers, a visual check of the banknotes to be examined is additionally carried out by the operating staff. EXAMPLE 238 By way of example, this can be merely a check for the presence of the features described in greater detail in the above that aid the authenticity check, and/or it can merely be a check of the chip data by communication with the chip to provide a reliable, but cost-effective checking device. EXAMPLE 239 Such checking devices are preferentially designed as portable manual checking devices. These can be carried along by the user as a compact, separate device or instead also be integrated e.g. in a key ring, glasses case, pocketknife, mobile telephone, cigarette case or a lighter etc.. This has the advantage that the consumer can also take the device with him when shopping, for example. In this context, aside from denomination and/or authenticity, e.g. the aforementioned information on intended use can be checked exclusively or particularly by means of the communication with the banknote chip as well. EXAMPLE 240 In addition, such a device for the consumer can also be integrated in a change purse that serves to receive cash. The necessary energy supply of the checking unit is preferentially achieved by a compact battery, such as a button cell or a thin layer battery or a thin layer accumulator, or instead by a photovoltaic element that is attached to the outer side of the change purse. Energy supply by a piezo transducer is also conceivable, however. The checking unit can, at typically lesser dimensions, be designed like the checking units of the manual checking devices and/or the registers. I.e. preferentially, e.g. each removal or addition of banknotes from or, as the case may be, to the change purse can also be monitored and/or its banknote content monitored. EXAMPLE 241 The aforementioned display devices can also be present in the checking devices themselves or the devices connected to them. Thus, the intended use e.g., an advertisement or the validity of the banknotes can be determined through the readout of chip data by the checking device and then displayed on the checking device. This is e.g. is of advantage for the variation wherein the checking the unit is integrated in a mobile telephone and thus the display of the mobile telephone is used for the display e.g. of the aforementioned data. EXAMPLE 242 A particular need also exists for checking devices for the blind. These can e.g. be integrated in a manual device or, as the case may be, a change purse as was described in the preceding examples. By way of example, if the banknote here is introduced to the checking the unit, then a signal output occurs which is different for different denominations. In this context, the reality of a signal output can already be viewed as a simpler demonstration of authenticity for the blind. The signal output occurs either as a clearly audible acoustical signal, such as a buzz tone, or else over a vibration generator that vibrates and whose signals can be clearly perceived tactilely. Preferentially, no signal output occurs while the banknotes are located in the coin purse, which e.g. can be controlled through software or realized in that the geometry of the checking unit is so designed that it does not react to banknotes in the interior of the coin purse. If necessary, it is, however, also feasible to display the entire contents of the coin purse. By way of example, this stack reading can be triggered via an affixed pressure switch, with the signal output being coded or, as the case may be, modulated in a suitable manner or taking place directly via a speech module. As a further alternative, it is conceivable to separate the acoustical signal output from the checking unit. Thus e.g. an earpiece can be connected with the checking unit via a cable. However, it is also possible to only make the necessary energy and trigger available via the checking the unit. If the banknotes e.g. are equipped with a piezoelectrical foil element (e.g. PVDF) coupled to the transponder of the banknote, the banknote to be checked can itself emit a suitable acoustical signal. This an also then apply correspondingly if the banknotes e.g. are equipped with a magnetostrictive foil element, so that the banknote to be checked can itself emit a suitable vibratory signal. The Handling of Banknotes with a Defective Chip For all areas of the handling of banknotes wherein banknotes with defective or missing electrical circuits can appear, the question arises as to how the banknotes without such operable electrical circuit, hereinafter referred to as banknote circuit for short, can be processed along with the other bank notes in a consistent work process. In this context, possible areas of the aforementioned handling of banknotes that e.g. come into question include: the production of banknotes, banknote processing, the acceptance of banknotes at money depositing machines of commercial banks or of commerce, the acceptance of banknotes at register systems, the transport of such accepted banknotes or the destruction of such banknotes. To be able to process the banknotes without operable banknote circuits in all of these processes in the same style and manner as the banknotes with operable banknote circuits, it is possible to subsequently provide these banknotes with an operable circuit, termed additional circuit for short. In this context, it is fundamentally possible to use an electrical additional circuit that is identical to the banknote circuit employed in the banknotes. However, this approach holds problems, since the possibility of subsequently attaching such additional circuits to banknotes also offers points of attack for potential forgeries. Therefore, the banknotes are preferentially provided with additional circuits that are different than the banknote circuits that are usually used. In this context, the additional circuit will in fact preferentially have a communication interface identical to that used in the banknote circuits of the banknotes, so as to ensure that these additional circuits, too, can react to interrogations of a reading device in the desired manner. In any event, they will, however, differ from the banknote circuits to such an extent, e.g. through their response signals to the interrogation for data of the circuit and/or over the functions implemented in the additional circuit, that confusion is ruled out. A simple differentiation consists e.g. in the return of the serial number “0” and/or the return message of the banknote value of null upon interrogation by an external reading device. Such a banknote will immediately be able to be recognized as subsequently provided with an additional circuit by an appropriate reading device and only be addressed with the functions implemented on it. On the other hand, such a banknote without an operable banknote circuit can, however, also place other demands on an additional circuit that the normal banknote circuit cannot meet. Since e.g. forgeries also often do not have a correctly functioning banknote circuit, the additional circuit can e.g. have a larger memory area than the banknote circuit, with additional data, which e.g. could be helpful to a technical criminal investigation, being able to be recorded in the additional circuit. One obvious possibility of mounting such an additional circuit on the banknote consists in the use of suitable auxiliary carriers that contain the additional circuit and are connected with the banknote, or enclose same. Such auxiliary carriers could e.g. be the bands likewise described within the scope of the present invention, but it could also be pockets into which the banknotes are inserted. A preferred embodiment of the above described auxiliary carrier consists in the use of adhesives that are attached to the banknotes, for which reason only the adhesives will be dealt with by way of example in the following. The adhesives can either be inseparably associated with the banknote, or instead, again detached and reused after the steps of handling have taken place. Even if the use of the adhesives with an electrical additional circuit only appears to cause unnecessary costs at first, in this way, the entire handling process for the banknotes can, however, become significantly cheaper. Various possibilities of use will now be explained. In banknote processing, many of the advantages described further above for the banknote with a circuit according to the invention are present to a significantly greater extent if the assumption can be made that all of the processed banknotes have an operable circuit. Thus e.g. an intelligent light barrier can only then reliably recognize the transport of overlapping banknotes or, instead, a mix-up in the order of banknotes if all banknotes exhibit an operable circuit. Accordingly, to increase the reliability of processing, the adhesive can be attached at banknote processing machines with individual processing or those with combined individual processing and stack processing, e.g. during or immediately after singling, after an attempt at communication in the singler itself has failed, and the banknote is then processed individually or in groups with the same process reliability. Exclusive stack processing of such banknotes, as well, remains possible in those cases where the adhesives were attached to the banknote in previous process steps affecting the banknote e.g. by the depositor. In order to e.g. be able to perform here the marking of banknotes suspect of having been counterfeited described further above, provision can be preferentially made to attach an above-described adhesive label to the banknotes without circuit, which [banknotes] can in principle be considered suspect of forgery, in order to write the data about the forgery suspicion into the memory of the circuit. With this, the report to be generated on the register contents described below can in some circumstances be avoided. Even the variation of attaching adhesives with electrical circuits to the banknotes prior to destruction can have substantial advantages in relation to the tamperproofness of the destruction process. If all of the banknotes to be destroyed have circuits, i.e. of banknote circuits and/or additional circuits, the light barriers will thus be able to reliably uncover manipulations to the banknote flow prior to the mechanical destruction. In particular, such a procedure presents itself for the destruction of print-fresh reject banknotes, where only a small number of defective circuits is to be expected.

20050128

20101214

20050714

57259.0

SHAPIRO, JEFFREY ALAN

DEVICES AND METHOD FOR THE PRODUCTION OF SHEET MATERIAL

UNDISCOUNTED

ACCEPTED

ACCEPTED

Protein

A polypeptide isolated from S. pyogenes is described, having IgG cysteine protease activity. The protease is designated IdeS, Immunoglobulin G-degrading enzyme of S. pyogenes. A polypeptide comprises SEQ ID NO: 1 and variants and fragments thereof having IgG cysteine protease activity or the ability to generate an immune response against S. pyogenes in an individual. Polynucleotides encoding these polypeptides and the polypeptides may be used in generating an immune response in an individual. IdeS protease inhibitors may be used in the treatment of S. pyogenes infection.

1-26. (canceled) 27. A polypeptide comprising: (a) the amino acid sequence of SEQ ID NO: 1; (b) a variant thereof having at least 50% identity to the amino acid sequence of SEQ ID NO: 1 and having IgG cysteine protease activity; (c) a fragment of either thereof having IgG cysteine protease activity; or (d) a fragment of (a) or (b) which is capable of generating an immune response to S. pyogenes in an individual. 28. An antibody or a fragment thereof capable of specifically binding a polypeptide as defined in claim 27. 29. A method for identifying an agent that modulates IgG cysteine protease activity of a polypeptide having the amino acid sequence of SEQ ID NO: 1 comprising: (i) contacting a polypeptide as defined in claim 27 and IgG with a test substance under conditions that would permit IgG cysteine protease activity in the absence of the test substance; and (ii) determining thereby whether the test substance modulates the said activity. 30. A method according to claim 29 wherein step (ii) comprises determining whether the test substance inhibits the cysteine protease activity of the polypeptide of SEQ ID NO: 1. 31. A method according to claim 30 further comprising formulating a test substance so identified with a pharmaceutically acceptable carrier. 32. A method of treating S. pyogenes infection in a human or animal, which method comprises administering to the human or animal a therapeutically or prophylactically effective amount of an antibody according to claim 28. 33. A method according to claim 32 wherein the individual is suffering from impetigo, pharyngitis, septicemia, necrotizing fascitis, or Streptococcal toxic shock syndrome. 34. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and/or diluent and: (a) a polypeptide according to claim 27; or (b) an antibody or fragment thereof capable of specifically binding the polypeptide (a). 35. A composition according to claim 34 which is a vaccine composition comprising a polypeptide according to claim 27 and a pharmaceutically acceptable carrier. 36. A method for diagnosing S. pyogenes infection in a human or animal comprising: (i) contacting a sample taken from the human or animal and a polypeptide according to claim 27 or an antibody or fragment thereof capable of specifically binding said polypeptide; and (ii) detecting any antibody-polypeptide complexes formed; wherein the presence of antibody-polypeptide complexes is an indicator of infection. 37. A method according to claim 36 wherein the polypeptide or the antibody is labelled. 38. A method of generating Fc or Fab fragments of IgG comprising contacting IgG with a polypeptide according to claim 27. 39. A method for detecting IgG in a sample, comprising: (i) contacting the sample with a polypeptide according to claim 27 under conditions that permit the IgG specific cysteine protease activity of the polypeptide; and (ii) monitoring for the presence of IgG specific cleavage fragments; wherein the presence of the specific cleavage fragments is indicative of IgG in the sample. 40. A method according to claim 38 wherein the IgG is human IgG. 41. A method of producing a polypeptide according to claim 27 comprising: (i) culturing a host cell comprising or transformed with a polynucleotide comprising a sequence which encodes a polypeptide as defined in claim 27 or with an expression vector comprising a polynucleotide comprising a sequence which encodes a polypeptide as defined in claim 27, under conditions which permit expression of the polypeptide; and (ii) recovering the polypeptide from the host cell culture, 42. A method of generating a protective immune response against S. pyogenes in an individual comprising administering to the individual a polypeptide according to claim 27.

FIELD OF THE INVENTION The invention relates to a new Streptococcus pyogenes protein which displays IgG cysteine protease activity. The invention further relates to the treatment, vaccination and diagnosis of S. pyogenes infection and to the development of new tools for biotechnology. BACKGROUND OF THE INVENTION S. pyogenes (Group A streptococcus) is an important human bacterial pathogen best known as the cause of skin and throat infections. Streptococcal infections vary in severity from relatively mild diseases, like impetigo and pharyngitis, to serious life threatening conditions such as septicemia, necrotizing fascitis, and streptococcal toxic-shock syndrome (Bisno and Stevens, 1996; Cunningham, 2000). Sequelae to S. pyogenes skin and throat infections include serious conditions such as acute rheumatic fever and post-streptococcal glomerulonephritis. S. pyogenes expresses cell wall-anchored surface proteins with the ability to interact with abundant extracellular human proteins such as albumin, IgG, IgA, fibrinogen, fibronectin, and α2-macroglobulin (for references see Navarre and Schneewind, 1999). Many of these protein-protein interactions are mediated by members of the M-protein family. SUMMARY OF THE INVENTION The present inventors have identified, purified and characterised a new extracellular cysteine protease produced by S. pyogenes. The protease, designated IdeS (Immunoglobulin G-degrading enzyme of S. pyogenes) displays a high specificity for IgG, cleaving in the hinge region of the immuno globulin. The protease cleaves not only IgG bound to the bacterial surface by IgGFc-binding proteins, but also opsonising IgG, and so appears to have a role in helping S. pyogenes to evade the host immune system. The inventors have shown that IdeS is expressed in both the logarithmic and stationary phases of bacterial growth, and in a number of clinically relevant S. pyogenes strains, including those of the M1, M12 and M55 serotypes. Antibodies to IdeS were found in individuals suffering from S. pyogenes infection, with those found in convalescent sera capable of blocking IdeS enzymatic activity. IdeS is therefore of use in the treatment and diagnosis of conditions associated with S. pyogenes infection. The protease is also useful for developing new biotechnological tools. Accordingly the invention provides a polypeptide comprising: (a) the amino acid sequence of SEQ ID NO: 1; (b) a variant thereof having at least 50% identity to the amino acid sequence of SEQ ID NO: 1 and having IgG cysteine protease activity; or (c) a fragment of either thereof having IgG cysteine protease activity. The invention also provides a polypeptide for use in generating an immune response in an individual comprising: (a) the amino acid sequence of SEQ ID NO: 1; (b) a variant thereof having at least 50% identity to the amino acid sequence of SEQ ID NO: 1 and having IgG cysteine protease activity; or (c) a fragment of either thereof which is capable of generating an immune response to S. pyogenes in an individual. In another aspect the invention provides a polynucleotide which comprises: (a) SEQ ID NO: 3 or a complementary sequence thereto; (b) a sequence which hybridises under stringent conditions to the sequence defined in (a); (c) a sequence which is degenerate as a result of the genetic code to a sequence as defined in (a) or (b); (d) a sequence having at least 60% identity to a sequence as defined in (a), (b) or (c); or (e) a fragments of any of the sequences (a), (b), (c) or (d), and which encodes a polypeptide having IgG cysteine protease activity or capable of generating an immune response against S. pyogenes in an individual. The invention also relates to expression vectors comprising a polynucleotide of the invention and host cells transformed with such expression vectors. In another aspect, the invention relates to a method for identifying an agent that modulates IgG cysteine protease activity of a polypeptide having the amino acid sequence of SEQ ID NO: 1 comprising: (i) contacting a polypeptide as defined above and IgG with a test substance under conditions that would permit IgG cysteine protease activity in the absence of the test substance; and (ii) determining thereby whether the test substance modulates the said activity. Inhibitors of the cysteine protease of the invention, for example identifiable by the other method are provided for use in the treatment of S. pyogenes infection. The polypeptides of the invention may be used in a method of generating Fc or Fab fragments of IgG comprising contacting IgG with the polypeptide. The invention also relates to a method of generating an immune response in an individual comprising administering a polypeptide, polynucleotide or expression vector of the invention. Preferably, the polypeptide or polynucleotide is used to generate a protective immune response. Methods of treating S. pyogenes infection are also described, comprising administering an antibody or an IdeS protease inhibitor to an individual. BRIEF DESCRIPTION OF THE FIGURES FIG. 1 shows the amino acid sequence found in the hinge region of human IgG including the cleavage site for IdeS. FIG. 2 shows a schematic representation of an open reading frame (ORF) encoding IdeS isolated from S. pyogenes AP1, including a putative signal sequence and RGD motif. FIG. 3 shows survival factors for S. pyogenes bacteria in macrophage like cells, after incubation of the bacteria in immune or non-immune plasma, and with or without IdeS. FIG. 4 shows IdeS cleavage of IgG bound to S. pyogenes bacterial surface. BRIEF DESCRIPTION OF THE SEQUENCES SEQ D NO:1 is an amino acid sequence encoding IdeS isolated from S. pyogenes AP1. SEQ ID NO:2 is an amino acid sequence encoding IdeS isolated from S. pyogenes AP1, including a putative signal sequence. SEQ ID NO:3 is nucleic acid sequence encoding IdeS, isolated from S. pyogenes AP1 (including a signal sequence). SEQ ID NO:4 is PCR primer Ide1. SEQ ID NO:5 is PCR primer Ide2. SEQ ID NO:6 is PCR primer Ide5x SEQ ID NO:7 is PCR primer Ide3x SEQ ID NO:8 is N terminal amino acid sequence of an IdeS human IgG cleavage product. SEQ ID NO:9 is N terminal amino acid sequence of IdeS isolated from S. pyogenes AP1. SEQ ID NO:10 is a cell wall attachment signal found in a number of bacterial proteins. DETAILED DESCRIPTION OF THE INVENTION The invention provides certain polypeptides. In particular, in accordance with the invention these polypeptides may be used in the prophylaxis and diagnosis of infection by S. pyogenes strains. Polypeptides in accordance with the invention are those which comprise the amino acid sequence of SEQ ID NO:1 and display IgG cysteine protease activity, together with functional variants, derivatives and fragments thereof. The invention also relates to variants and fragments of SEQ ID NO:1 which have the ability to generate an immune response in an individual and in particular those which generate antibodies having the ability to block the enzymatic activity of IdeS, or to generate a protective immune response. Preferably, the polypeptide comprises the sequence of SEQ ID NO:1. The polypeptide may additionally include a signal sequence as in SEQ ID NO:2. Variant polypeptides are those for which the amino acid sequence varies from that in SEQ ID NO:1, but which retain the same essential character or basic functionality as IdeS. The variant polypeptides may therefore display IgG cysteine protease activity or the ability to generate an immune response in an individual. In particular such variants include those which are able to generate antibodies having the ability to block the enzymatic activity of IdeS, or to generate a protective immune response. Typically, polypeptides with more than about 50%, 55% or 65% identity preferably at least 80% or at least 90% and particularly preferably at least 95%, at least 97% or at least 99% identity, with the amino acid sequence of SEQ ID NO:1 are considered variants of the protein. Such variants may include allelic variants and the deletion, modification or addition of single amino acids or groups of amino acids within the protein sequence, as long as the peptide maintains a basic functionality of IdeS. The inventors have also found that it is possible to provide mutants of IdeS, in which mutation in the catalytic domain removes the cysteine protease activity of the protein. Such a mutant may comprise replacement or deletion of the catalytic cysteine residue at position 94 (C94) of IdeS. For example, cysteine may be replaced with glycine. The utility of such variants is described in more detail below. The invention also relates to variants of fragments of such a mutated IdeS, but which maintain other functions of IdeS, such as the ability to generate an immune response or bind to IgG Amino acid substitutions may be made, for example from 1, 2 or 3 to 10, 20 or 30 substitutions. The modified polypeptide generally retains activity as an IgG-specific cysteine protease. Conservative substitutions may be made, for example according to the following Table. Amino acids in the same block in the second column and preferably in the same line in the third column may be substituted for each other. ALIPHATIC Non-polar G A P I L V Polar-uncharged C S T M N Q Polar-charged D E K R AROMATIC H F W Y Preferably the polypeptides comprise a cysteine residue and a histidine residue at a spacing typically found in cysteine proteases. For example, in SEQ ID NO: 1, these residues are found at a spacing of about 130aa, as is typically found in cysteine proteases. Shorter polypeptide sequences or fragments are within the scope of the invention. For example, a peptide of at least 20 amino acids or up to 50, 60, 70, 80, 100, 150 or 200 amino acids in length is considered to fall within the scope of the invention as long as it demonstrates a basic functionality of IdeS. In particular, but not exclusively, this aspect of the invention encompasses the situation when the protein is a fragment of the complete protein sequence and may represent an IgG-binding region or an epitope. Such fragments may not retain IgG cysteine protease activity. Polypeptides of the invention may also be chemically modified, e.g. post-translationally modified. For example, they may be glycosylated or comprise modified amino acid residues. They may be modified by the addition of histidine residues to assist their purification or by the addition of a signal sequence to promote insertion into the cell membrane. It may be desirable to provide the peptides or proteins in a form suitable for attachment to a solid support. The proteins or peptides may thus be modified to enhance their binding to a solid support for example by the addition of a cystine residue. Such modified polypeptides fall within the scope of the term “polypeptide” of the invention. Typically, polypeptides for use in accordance with the invention display immunoglobulin cysteine protease activity, and in particular IgG cysteine protease activity. Preferably, the polypeptide cleaves IgG in the hinge region and more particularly in the hinge region of the heavy chain. Preferably, cleavage results in production of Fc and Fab fragments of IgG. Preferably the activity is specific for IgG. The cysteine protease activity may be determined by means of a suitable assay. For example, a test polypeptide may be incubated with IgG at a suitable temperature such as 37° C. The starting materials and the reaction products may then be analysed by SDS PAGE to determine whether the desired IgG cleavage product is present. Typically this cleavage product is a 31 kDa fragment. Typically there is no further degradation of IgG after this first cleavage. The cleavage product may be subjected to N-terminal sequencing to verify that cleavage has occurred in the hinge region of IgG. Preferably the N-terminal sequence comprises the sequence in SEQ ID NO:8. The cysteine protease activity of the polypeptides can be further characterised by inhibition studies. Preferably, the activity is inhibited by the peptide derivateZ-LVG-CHN2 and/or by iodoacetic acid both of which are protease inhibitors. However, the activity is generally not inhibited by E64. The cysteine protease activity of the polypeptides is generally IgG-specific in that the polypeptides may not degrade the other classes of Ig, namely IgM, IgA, IgD and IgE, when incubated with these immunoglobulins under conditions that permit cleavage of IgG. In preferred embodiments the polypeptide has the ability to cleave human, rabbit or goat IgG, and preferably does not have the ability to cleave murine IgG. The invention also relates to mutant IdeS, in which the catalytic cysteine protease activity has been reduced or lost. The absence of cysteine protease activity may be assayed as described for non-mutant IdeS. Such mutants may retain the ability to bind IgG. Binding of IgG can be assayed by binding studies, for example immobilising IdeS, and contacting said immobilised IdeS with IgG, and monitoring for the presence of any bound IgG. Such a mutant may display no cysteine protease activity or reduced cysteine protease activity compared to a polypeptide not so modified. According to one aspect of the invention, the polypeptides provided are capable of generating an immune response, preferably a protective immune response to S. pyogenes in an individual. These polypeptides are useful for inclusion in vaccines targeting S. pyogenes infection. In preferred embodiments, the polypeptide generates antibodies which have the ability to block the enzymatic activity of IdeS. This activity may be monitored, for example as described for IdeS activity, in which IdeS or a variant thereof retaining IgG cysteine protease activity is incubated with IgG in the presence of the generated antibody. Cleavage of IgG by IdeS can be monitored as before. The polypeptides can also be used to generate antibodies which can be used in the diagnosis or treatment by immunotherapy of S. pyogenes infection. Such polypeptides may comprise an epitope of the IdeS polypeptide and may not otherwise demonstrate the IgG cysteine protease activity. Preferably the polypeptides are fragments. For example, the fragments may be at least 6 amino acids in length, preferably at least 10, such as at least 12 or 15 or up to 20, 30 or 40 amino acids. Longer fragments such as up to 60 or 150 aa in length may also be used. A peptide for generating an immune response may be identified by immunisation studies. For example, a candidate peptide may be administered to an animal and subsequently the antibody or T-cell response generated which is specific for the peptide may be determined. Antiserum generated following administration of a peptide to an animal may be evaluated for the ability to bind the peptide or to bind IdeS. Subsequently the animal may be challenged with S. pyogenes to evaluate whether a protective immune response has been generated. Polypeptides of the invention may be in a substantially isolated form. It will be understood that the polypeptide may be mixed with carriers or diluents which will not interfere with the intended purpose of the polypeptide and still be regarded as substantially isolated. A polypeptide of the invention may also be in a substantially purified form, in which case it will generally comprise the polypeptide in a preparation in which more than 50%, e.g. more than 80%, 90%, 95% or 99%, by weight of the polypeptide in the preparation is a polypeptide of the invention. A protein or peptide of the invention may be labelled with a revealing label. The revealing label may be any suitable label which allows the protein or peptide to be detected. Suitable labels include radioisotopes such as 125I, 35S or enzymes, antibodies, polynucleotides and linkers such as biotin. Labelled polypeptides of the invention may be used in diagnostic procedures such as immunoassays. In such assays it may be preferred to provide the peptides attached to a solid support, for example, the surface of an immunoassay well or dipstick. The present invention also relates to such labelled and/or immobilized polypeptides packaged in the form of a kit in a container. The kit may optionally contain other suitable reagent(s), control(s) or instructions and the like. Polypeptides for use in the present invention may be isolated from suitable IdeS expressing strains of S. pyogenes. Suitable strains may be identified by a number of techniques. For example, S. pyogenes strains may initially be tested for the presence an ideS gene. Polynucleotide primers or probes may be designed based on for example, SEQ ID Nos 1, 2 or 3. Suitable primers are set out in SEQ ID NOs 4, 5, 6 and 7. The presence of the ides gene can then be verified by PCR using the primers or by hybridisation of the probes to genomic DNA of the S. pyogenes strain. S. pyogenes strains expressing active IdeS can be identified by assaying for IgG cysteine protease activity in the culture supernatant. Preferably inhibitor E64 is added to the supernatant to inhibit any SpeB cysteine protease activity. The present inventors have shown that at least five strains tested express active IdeS: strains AP1, AP12, AP255, KTL3 and SF370. Preferably the expressing strain is selected from AP1, AP12 and AP55. Isolation and purification of IdeS from an expressing S. pyogenes culture is typically on the basis of IgG cysteine protease activity. Preferably the purification method involves an ammonium sulphate precipitation step and an ion exchange chromatography step. According to one method, the culture medium is fractionated by adding increasing amounts of ammonium sulphate. The amounts of ammonium sulphate may be 10 to 80%. Preferably the culture medium is fractionated with 50% ammonium sulphate, and the resulting supernatant is further precipitated with 70% ammonium sulphate. Pelleted proteins may then be subjected to ion exchange chromatography, for example by FPLC on a Mono Q column. Eluted fractions may be assayed for IgG cysteine protease activity and peak activity factions may be pooled. Fractions may be analysed by SDS PAGE. For example, an N-terminal sequence can be obtained from the SDS PAGE protein band. Fractions may be stored at −20° C. Polypeptides for use in the invention may also be prepared as fragments of such isolated proteins. Further, the proteins and peptides of the invention may also be made synthetically or by recombinant means as discussed below. The amino acid sequence of proteins and polypeptides of the invention may be modified to include non-naturally occurring amino acids or to increase the stability of the compound. When the proteins or peptides are produced by synthetic means, such amino acids may be introduced during production. The proteins or peptides may also be modified following either synthetic or recombinant production. The proteins or peptides of the invention may also be produced using D-amino acids. In such cases the amino acids will be linked in reverse sequence in the C to N orientation. This is conventional in the art for producing such proteins or peptides. A number of side chain modifications are known in the art and may be made to the side chains of the proteins or peptides of the present invention. Such modifications include, for example, modifications of amino acids by reductive alkylation by reaction with an aldehyde followed by reduction with NaBH4, amidination with methylacetimidate or acylation with acetic anhydride. The invention also relates to polynucleotides encoding the above polypeptides, and their use in medicine. In particular the invention relates to polynucleotides comprising or consisting of (a) the coding sequence of SEQ ID NO:3 or a complementary sequence thereto; (b) sequence which hybridises under stringent conditions to the sequences defined in (a); (c) sequence which is degenerate as a result of the genetic code to sequence as defined in (a) or (b); (d) sequence having at least 60% identity to sequences defined in (a) (b) or (c); and (e) fragments of the above sequences. Typically the polynucleotide is DNA. However, the invention may comprise RNA polynucleotides. The polynucleotides may be single or double stranded, and may include within them synthetic or modified nucleotides. A polynucleotide of the invention can hybridize to the coding sequence or the complement of the coding sequence of SEQ ID NO: 3 at a level significantly above background. Background hybridization may occur, for example, because of other DNAs present in a DNA library. The signal level generated by the interaction between a polynucleotide of the invention and the coding sequence or complement of the coding sequence of SEQ ID NO: 3 is typically at least 10 fold, preferably at least 100 fold, as intense as interactions between other polynucleotides and the coding sequence of SEQ ID NO: 3. The intensity of interaction may be measured, for example, by radiolabelling the probe, e.g. with 32P. Selective hybridisation may typically be achieved using conditions of medium to high stringency. However, such hybridisation may be carried out under any suitable conditions known in the art (see Sambrook et al, 1989. For example, if high stringency is required suitable conditions include from 0.1 to 0.2×SSC at 60° C. up to 65° C. If lower stringency is required suitable conditions include 2×SSC at 60° C. The coding sequence of SEQ ID NO: 3 may be modified by nucleotide substitutions, for example from 1, 2 or 3 to 10, 25, 50 or 100 substitutions. The polynucleotide of SEQ ID NO: 3 may alternatively or additionally be modified by one or more insertions and/or deletions and/or by an extension at either or both ends. Additional sequences such as signal sequences may also be included. The modified polynucleotide generally encodes a polypeptide which has IgG specific cysteine protease activity. Alternatively, a polynucleotide encodes an epitope portion of an IdeS polypeptide. Degenerate substitutions may be made and/or substitutions may be made which would result in a conservative amino acid substitution when the modified sequence is translated, for example as shown in the Table above. A nucleotide sequence which is capable of selectively hybridizing to the complement of the DNA coding sequence of SEQ ID NO: 3 will generally have at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to the coding sequence of SEQ ID NO: 3 over a region of at least 20, preferably at least 30, for instance at least 40, at least 60, more preferably at least 100 contiguous nucleotides or most preferably over the full length of SEQ ID NO: 3. For example the UWGCGQPackage provides the BESTFIT program which can be used to calculate homology (for example used on its default settings) (Devereux et al (1984) Nucleic Acids Research 12, p387-395). The PILEUP and BLAST algorithms can be used to calculate homology or line up sequences (typically on their default settings), for example as described in Altschul (1993) J. Mol. Evol. 36:290-300; Altschul et al (1990) J. Mol. Biol. 215:403-10. Software for performing BLAST analyses is publicly available through the National Centre for Biotechnology Information (http://www.ncbi.nlm.nih.gov/). This algorithm involves first identifying high scoring sequence pair (HSPs) by identifying short words of length W in the query sequence that either match or satisfy some positive-valued threshold score T when aligned with a word of the same length in a database sequence. T is referred to as the neighbourhood word score threshold (Altschul et al, 1990). These initial neighbourhood word hits act as seeds for initiating searches to find HSPs containing them. The word hits are extended in both directions along each sequence for as far as the cumulative alignment score can be increased. Extensions for the word hits in each direction are halted when: the cumulative alignment score falls off by the quantity X from its maximum achieved value; the cumulative score goes to zero or below, due to the accumulation of one or more negative-scoring residue alignments; or the end of either sequence is reached. The BLAST algorithm parameters W, T and X determine the sensitivity and speed of the alignment. The BLAST program uses as defaults a word length (W) of 11, the BLOSUM62 scoring matrix (see Henikoff and Henikoff (1992) Proc. Natl. Acad. Sci. USA 89: 10915-10919) alignments (B) of 50, expectation (E) of 10, M=5, N=4, and a comparison of both strands. The BLAST algorithm performs a statistical analysis of the similarity between two sequences; see e.g., Karlin and Altschul (1993) Proc. Natl. Acad. Sci. USA 90: 5873-5787. One measure of similarity provided by the BLAST algorithm is the smallest sum probability (P(N)), which provides an indication of the probability by which a match between two nucleotide or amino acid sequences would occur by chance. For example, a sequence is considered similar to another sequence if the smallest sum probability in comparison of the first sequence to the second sequence is less than about 1, preferably less than about 0.1, more preferably less than about 0.01, and most preferably less than about 0.001. Any combination of the above mentioned degrees of sequence identity and minimum sizes may be used to define polynucleotides of the invention, with the more stringent combinations (i.e. higher sequence identity over longer lengths) being preferred. Thus, for example a polynucleotide which has at least 90% sequence identity over 25, preferably over 30 nucleotides forms one aspect of the invention, as does a polynucleotide which has at least 95% sequence identity over 40 nucleotides. Polynucleotide fragments, such as those suitable for use as probes or primers will preferably be at least 10, preferably at least 15 or at least 20, for example at least 25, at least 30 or at least 40 nucleotides in length. They will typically be up to 40, 50, 60, 70, 100 or 150 nucleotides in length. Probes and fragments can be longer than 150 nucleotides in length, for example up to 200, 300, 400, 500, 600, 700 nucleotides in length, or even up to a few nucleotides, such as five or ten nucleotides, short of the coding sequence of SEQ D NO: 3. Polynucleotides according to the invention may be produced recombinantly, synthetically, or by any means available to those of skill in the art. They may also be cloned by standard techniques. The polynucleotides are typically provided in isolated and/or purified form. In general, primers will be produced by synthetic means, involving a step wise manufacture of the desired nucleic acid sequence one nucleotide at a time. Techniques for accomplishing this using automated techniques are readily available in the art. Longer polynucleotides will generally be produced using recombinant means, for example using PCR (polymerase chain reaction) cloning techniques. This will involve analyzing a pair of primers (e.g. of about 15-30 nucleotides) to a region of the ideS gene which it is desired to clone, bringing the primers into contact with DNA obtained from a bacterial cell, performing a polymerase chain reaction under conditions which bring about amplification of the desired region, isolating the amplified fragment (e.g. by purifying the reaction mixture on an agarose gel) and recovering the amplified DNA. The primers may be designed to contain suitable restriction enzyme recognition sites so that the amplified DNA can be cloned into a suitable cloning vector. Suitable primers are for example, those in SEQ ID Nos 4, 5, 6 or 7. Such techniques may be used to obtain all or part of the ideS gene sequence described herein. Although in general the techniques mentioned herein are well known in the art, reference may be made in particular to Sambrook et al, Molecular Cloning: A Laboratory Manual, 1989. The polynucleotides according to the invention have utility in production of the polypeptides according to the invention, which may take place in vitro, in vivo or ex vivo. The polynucleotides may be used as therapeutic or immunisation agents in their own right or may be involved in recombinant protein synthesis. Polynucleotides of the invention may be used as a primer, e.g. a PCR primer, a primer for an alternative amplification reaction, a probe e.g. labelled with a revealing label by conventional means using radioactive or non-radioactive labels, or the polynucleotides may be cloned into vectors. Polynucleotides or primers of the invention may carry a revealing label. Suitable labels include radioisotopes such as 32P or 35S, enzyme labels, or other protein labels such as biotin. Such labels may be added to polynucleotides or primers of the invention and may be detected using techniques known per se. Polynucleotides or primers of the invention or fragments thereof, labelled or unlabelled, may be used by a person skilled in the art in nucleic acid-based tests for detecting or sequencing ideS in a sample. Such tests for detecting generally comprise bringing a sample containing DNA or RNA into contact with a probe comprising a polynucleotide or primer of the invention under hybridizing conditions and detecting any duplex formed between the probe and nucleic acid in the sample. Such detection may be achieved using techniques such as PCR or by immobilizing the probe on a solid support, removing nucleic acid in the sample which is not hybridized to the probe, and then detecting nucleic acid which has hybridized to the probe. Alternatively, the sample nucleic acid may be immobilized on a solid support, and the amount of probe bound to such a support can be detected. The probes of the invention may conveniently be packaged in the form of a test kit in a suitable container. In such kits the probe may be bound to a solid support where the assay formats for which the kit is designed requires such binding. The kit may also contain suitable reagents for treating the sample to be probed, hybridizing the probe to nucleic acid in the sample, control reagents, instructions, and the like. The polynucleotides of the invention may be incorporated into a recombinant replicable vector. The vector may be used to replicate the nucleic acid in a compatible host cell. Therefore, polynucleotides of the invention may be made by introducing a polynucleotide of the invention into a replicable vector, introducing the vector into a compatible host cell and growing the host cell under conditions which bring about replication of the vector. Preferably the vector is an expression vector comprising a nucleic acid sequence that encodes a polypeptide of the invention. Such expression vectors are routinely constructed in the art of molecular biology and may for example involve the use of plasmid DNA and appropriate initiators, promoters, enhancers and other elements, which may be necessary, and which are positioned in the correct orientation, in order to allow for protein expression. Other suitable vectors would be apparent to persons skilled in the art. By way of further example in this regard we refer to Sambrook et al. 1989. Polynucleotides according to the invention may also be inserted into the vectors described above in an antisense orientation in order to provide for the production of antisense RNA. Anti sense RNA or other antisense polynucleotides or interfering RNA, iRNA may also be produced by synthetic means. Such antisense polynucleotides or iRNA may be used as test compounds in the assays of the invention or may be useful in a method of treatment of the human or animal body by therapy. Preferably, a polynucleotide of the invention or for use in the invention in a vector is operably linked to a control sequence which is capable of providing for the expression of the coding sequence by the host cell, i.e. the vector is an expression vector. The term “operably linked” refers to a juxtaposition wherein the components described are in a relationship permitting them to function in their intended manner. A regulatory sequence, such as a promoter, “operably linked” to a coding sequence is positioned in such a way that expression of the coding sequence is achieved under conditions compatible with the regulatory sequence. The vectors may be for example, plasmid, virus or phage vectors provided with a origin of replication, optionally a promoter for the expression of the said polynucleotide and optionally a regulator of the promoter. The vectors may contain one or more selectable marker genes, for example an ampicillin resistence gene in the case of a bacterial plasmid or a resistance gene for a fungal vector. Promoters and other expression regulation signals may be selected to be compatible with the host cell for which expression is designed. For example, yeast promoters include S. cerevisiae GAL4 and ADH promoters, S. pombe nmt1 and adh promoter. Mammalian promoters include the metallothionein promoter which can be induced in response to heavy metals such as cadmium. Viral promoters such as the SV40 large T antigen promoter or adenovirus promoters may also be used. All these promoters are readily available in the art. Mammalian promoters, such as β-actin promoters, may be used. Tissue-specific promoters are especially preferred. Viral promoters may also be used, for example the Moloney murine leukaemia virus long terminal repeat (MMLV LTR), the rous sarcoma virus (RSV) LTR promoter, the SV40 promoter, the human cytomegalovirus (CMV) IE promoter, adenovirus, HSV promoters (such as the HSV IE promoters), or IPV promoters, particularly the HPV upstream regulatory region (URR). Viral promoters are readily available in the art. The vector may further include sequences flanking the polynucleotide giving rise to polynucleotides which comprise sequences homologous to eukaryotic genomic sequences, preferably mammalian genormic sequences, or viral genomic sequences. This will allow the introduction of the polynucleotides of the invention into the genome of eukaryotic cells or viruses by homologous recombination. In particular, a plasmid vector comprising the expression cassette flanked by viral sequences can be used to prepare a viral vector suitable for delivering the polynucleotides of the invention to a mammalian cell. Other examples of suitable viral vectors include herpes simplex viral vectors and retroviruses, including lentiviruses, adenoviruses, adeno-associated viruses and HPV viruses. Gene transfer techniques using these viruses are known to those skilled in the art. Retrovirus vectors for example may be used to stably integrate the polynucleotide giving rise to the polynucleotide into the host genome. Replication-defective adenovirus vectors by contrast remain episomal and therefore allow transient expression. Vectors may be used in vitro, for example for the production of DNA or RNA or used to transfect or transform a host cell, for example, a mammalian host cell. The vectors may also be adapted to be used in vivo, for example in a method of gene therapy or nucleic acid immunisation. Expression vectors may be transformed into a suitable host cell to provide for expression of a polypeptide or polypeptide fragment of the invention. The host cell, transformed or transfected with an expression vector as described above, is cultivated under conditions to allow for expression of the polypeptide or fragment, and the expressed polypeptide or fragment is recovered. Isolation and purification may be carried out as described above. Host cells will be chosen to be compatible with the vector and will preferably be bacterial. Host cells may also be cells of a non-human animal, or a plant transformed with a polynucleotide of the invention. According to another aspect, the present invention also relates to antibodies capable of specific binding to a polypeptide of the invention. Such antibodies are for example useful in purification, isolation or screening methods or indeed as therapeutic agents in their own right. Antibodies may be raised against specific epitopes of the polypeptides according to the invention. An antibody, or other compound, “specifically binds” to a protein when it binds with preferential or high affinity to the protein for which it is specific but does substantially bind not bind or binds with only low affinity to other proteins. A variety of protocols for competitive binding or immunoradiometric assays to determine the specific binding capability of an antibody are well known in the art (see for example Maddox et al, J. Exp. Med. 158, 1211-1226, 1993). Such immunoassays typically involve the formation of complexes between the specific protein and its antibody and the measurement of complex formation. For the purposes of this invention, the term “antibody”, unless specified to the contrary, includes fragments which bind a polypeptide of the invention. Such fragments include Fv, F(ab′) and F(ab′)2 fragments, as well as single chain antibodies. Furthermore, the antibodies and fragment thereof may be chimeric antibodies, CDR-grafted antibodies or humanised antibodies. Antibodies of the invention can be produced by any suitable method. Means for preparing and characterising antibodies are well known in the art, see for example Harlow and Lane (1988) “Antibodies: A Laboratory Manual”, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. For example, an antibody may be produced by raising antibody in a host animal against the whole polypeptide or a fragment thereof, for example an antigenic epitope thereof, herein after the “imunogen”. A method for producing a polyclonal antibody comprises immunising a suitable host animal, for example an experimental animal, with the immunogen and isolating immunoglobulins from the animal's serum. The animal may therefore be inoculated with the immunogen, blood subsequently removed from the animal and the IgG fraction purified. A method for producing a monoclonal antibody comprises immortalising cells which produce the desired antibody. Hybridoma cells may be produced by fusing spleen cells from an inoculated experimental animal with tumour cells (Kohler and Milstein (1975) Nature 256, 495-497). An immortalized cell producing the desired antibody may be selected by a conventional procedure. The hybridomas may be grown in culture or injected intraperitoneally for formation of ascites fluid or into the blood stream of an allogenic host or immunocompromised host. Human antibody may be prepared by in vitro immunisation of human lymphocytes, followed by transformation of the lymphocytes with Epstein-Barr virus. For the production of both monoclonal and polyclonal antibodies, the experimental animal is suitably a goat, rabbit, rat or mouse. If desired, the immunogen may be administered as a conjugate in which the immunogen is coupled, for example via a side chain of one of the amino acid residues, to a suitable carrier. The carrier molecule is typically a physiologically acceptable carrier. The antibody obtained may be isolated and, if desired, purified. Antibodies, both monoclonal and polyclonal, which are directed against polypeptides of the invention are particularly useful in diagnosis. Antibodies may be used in a method for detecting polypeptides of the invention in a biological sample. Generally such a method comprises (a) incubating a biological sample with the antibody under conditions which allow for the formation of an antibody-antigen complex; and (b) determining whether antibody-antigen complex comprising the antibody is formed. A sample may be for example a tissue extract, blood, serum and saliva. Similarly, a polypeptide of the invention may be used to detect the presence of anti-IdeS antibodies in a sample, for example to provide an indicator of S. pyogenes infection. Preferably, a polypeptide of the invention for use in accordance with this aspect of the invention comprises a mutant polypeptide which does not have cysteine protease activity or has reduced cysteine protease activity, but maintains the ability to bind IgG. Antibodies or polypeptides of the invention may be bound to a solid support and/or packaged into kits in a suitable container along with suitable reagents controls, instructions, etc. Antibodies or polypeptides may be linked to a revealing label and thus may be suitable for use in methods of in vivo imaging. Antibodies, including antibody fragments are also useful in passive immunotherapy. Monoclonal antibodies in particular, may be used to raise anti-idiotype antibodies. Anti-idiotype antibodies are immunoglobulins which carry an “internal image” of the antigen of the infectious agent against which protection is desired. Techniques for raising anti-idiotype antibodies are well known in the art. These anti-idiotype antibodies may also be useful for treatment of S. pyogenes, as well as for an elucidation of the immunogenic regions of polypeptides of the invention. The invention is also concerned with modulatory agents which modulate the IgG cysteine protease activity and/or expression of the present polypeptides, in particular, agents which inhibit the activity. The agents may bind to the polypeptides. The agents may modulate IgG binding of the polypeptides and/or cysteine protease activity. The present inventors have shown that inhibitors of IdeS include iodoacetic acid and Z-LVG-CHN2 and also antibodies to IdeS. Modulatory agents may be identified in screening methods using the present polypeptides. In general such screening methods comprise: (i) contacting a polynucleotide of the invention, a vector of the invention, a polypeptide of the invention or a cell of the invention and a test substance under conditions that would permit IgG cysteine protease activity in the absence of the test substance; and (ii) determining thereby whether the said substance modulates the activity and/or expression of the polypeptide. Any suitable assay format may be used. Assay formats which allow high through put screening are preferred. The assay may be carried out on a cell harbouring the polynucleotide or vector or on a cell extract comprising the polynucleotide or vector. The cells may express the polypeptide naturally or the polypeptide may be recombinantly expressed. The cell or cell extract will typically allow transcription and translation of the polynucleotide or vector in the absence of a test substance. The assay may also be carried out using a polypeptide of the invention. The polypeptide may be in a purified preparation or for example in a culture supernatant. Most preferably such an assay would be carried out in a single well of a plastics microtitre plate so that high through-put screening may be carried out. Typically the polypeptide is incubated with a test substance in the dark at a temperature of 25 to 42° C. The enzyme reaction is commenced by addition of IgG. Reaction products may then be analysed by SDS PAGE. In addition to the polypeptide, test substance and IgG substrate, the reaction mixture may contain a suitable buffer. A suitable buffer includes any suitable biological buffer that can provide buffering capability at a pH conducive to the reaction requirements of the enzyme. The assay of the invention may be carried out at any temperature at which the polypeptide, in the absence of inhibitor, is active. Typically the assay will be carried out in the range of from 25 to 42° C., in particular at 37° C. Typically control assays are carried out in the absence of the test substance. The substance tested may be tested with any other polypeptide/enzyme to exclude the possibility that the substance is a general inhibitor of gene expression or enzyme activity. Control experiments may be carried out on cells which do not express the polypeptide of the invention to establish whether the desired responses are the result of inhibition or activation of the polypeptide. Preferably the assay is carried out in the presence of E64, an inhibitor of the SpeB cysteine protease, particularly where S. pyogenes cells are used in the assay. Assays can also be carried out using constructs comprising an IdeS gene promoter operably linked to a heterologous coding sequence, to identify compounds which modulate expression of IdeS at the transcriptional level. A promoter means a transcriptional promoter. IdeS promoters can be isolated via methods known to those skilled in the art and as described above. The term “heterologous” indicates that the coding sequence is not operably linked to the promoter in nature; the coding sequence is generally from a different organism to the promoter. The promoter may be fused directly to a coding sequence or via a linker. The linker sequence may comprise a sequence having enhancer characteristics, to boost expression levels. Preferably the promoter is operably linked to the coding sequence of a reporter polypeptide. The reporter polypeptide may be, for example, the bacterial polypeptide β-glucuronidase (GUS), green fluoresent protein (GFP), luciferase (luc), chloramphenicol transferase (CAT) or β-galactosidase (lacZ). Promoter:reporter gene constructs such as those described above can be incorporated into a recombinant replicable vector. The vector may be used to replicate the nucleic acid construct in a compatible host cell. The vectors may be, for example, plasmid, virus or phage vectors provided with an origin of replication. Any host cell may be used in which the promoter is functional, but typically the host cell will be a cell of the species from which the promoter derives. The promoter:reporter gene constructs of the invention may be introduced into host cells using conventional techniques. Thus the invention provides a method for identifying a modulator of IdeS expression. Typically a promoter:reporter polypeptide construct or a cell harbouring that construct will be contacted with a test substance under conditions that would permit the expression of the reporter polypeptide in the absence of the test substance. Any reporter polypeptide may be used, but typically GUS or GFP are used. GUS is assayed by measuring the hydrolysis of a suitable substrate, for example 5-bromo-4-chloro-3-indolyl-β-D-glucoronic acid (X-gluc)or 4-methylumbelliferyl-β-glucuronide (MUG). The hydrolysis of MUG yields a product which can be measured fluorometrically. GFP is quantified by measuring fluorescence at 590 nm after excitation at 494 nm. These methods are well known to those skilled in the art. Test substances may also be assayed directly for binding to a polypeptide of the invention. For example, a radiolabelled test substance can be incubated with a polypeptide of the invention and binding of the test substance to the polypeptide monitored. Non-specific binding of the test substance may also be determined by carrying out a competitive binding assay. Substance that inhibit the interaction of a polypeptide of the invention with IgG may also be identified using a protein interaction assay such as immunoprecipitation or an ELISA based technique. A test substance which modulates the expression or activity of a polypeptide of the invention may do so by binding directly to the relevant gene promoter, thus inhibiting or activating transcription of the gene. Inhibition may occur by preventing the initiation or completion of transcription. Activation may occur, for example by increasing the affinity of the transcription complex for the promoter. Alternatively a modulator may bind to a protein which is associated with the promoter and is required for transcription. A substance which modulates the activity of the polypeptide may do so by binding to the enzyme. Such binding may result in activation or inhibition of the protein. Inhibition may occur, for example, if the modulator resembles the substrate and binds at the active site of the enzyme. The IgG is thus prevented from binding to the same active site and the rate of catalysis is reduced by reducing the proportion of enzyme molecules bound to substrate. A modulator which inhibits activity may do so by binding to the substrate. Suitable test substances which can be tested in the above assays include combinatorial libraries, defined chemical entities and compounds, peptide and peptide mimetics, oligonucleotides and natural product libraries, such as display (e.g. phage display libraries) and antibody products. Typically, organic molecules will be screened, preferably small organic molecules which have a molecular weight of from 50 to 2500 daltons. Candidate products can be biomolecules including, saccharides, fatty acids, steroids, purines, pyrimidines, derivatives, structural analogs or combinations thereof. Candidate agents are obtained from a wide variety of sources including libraries of synthetic or natural compounds. Known pharmacological agents may be subjected to directed or random chemical modifications, such as acylation, alkylation, esterification, amidification, etc. to produce structural analogs. Test substances may be used in an initial screen of, for example, 10 substances per reaction, and the substances of these batches which show inhibition or activation tested individually. Test substances may be used at a concentration of from 1 nM to 1000 μM, preferably from 1 μM to 100 μM, more preferably from 1 μM to 10 μM. Preferably, the activity of a test substance is compared to the activity shown by a known activator or inhibitor. A modulator of expression and/or activity of the present polypeptide is one which produces a measurable reduction or increase in expression and/or activity in assays such as those described above. Thus, modulators may be inhibitors or activators of expression and/or activity. Preferred inhibitors are those which inhibit expression and/or activity by at least 10%, at least 20%, at least 30%, at least 40% at least 50, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% or at least 99% at a concentration of the inhibitor of 1 μg ml−1, 10 μg ml−1, 100 μg ml−1, 500 μg ml−1, 1 mg ml−1, 10 mg ml−1, 100 mg ml−1. Preferred activitors are those which activate expression and/or activity by at least 10%, at least 25%, at least 50%, at least 100%, at least, 200%, at least 500% or at least 1000% at a concentration of the activator 1 μg ml−1, 10 μg ml−1, 100 μg ml−1, 500 μg ml−1, 1 mg ml−1, 10 mg ml−1 , 100 mg ml−1. The percentage inhibition or activation represents the percentage decrease or increase in expression/activity in a comparison of assays in the presence and absence of the test substance. Any combination of the above mentioned degrees of percentage inhibition or activation and concentration of inhibitor or activator may be used to define an inhibitor or activator of the invention, with greater inhibition or activation at lower concentrations being preferred. The present invention provides the polypeptides, polynucleotides, antibodies and agents described above for use in therapy or prophylexis. In particular, the polypeptides, polynucleotides, antibodies and agents are useful for the treatment of S. pyogenes infection of a human or animal. Treatment may be therapeutic or prophylactic. Preferably, the infecting S. pyogenes strain is an IdeS-expressing strain. Such strains may be identified as described above. Typically the strain is of the M1, M12 or M55 serotype. Examples of suitable strains include AP1, AP12, AP55, KTL3 and SF370. In a preferred embodiment, the strain is of M1 serotype, such as AP1. Conditions which may be usefully targeted include those associated with acute infection and also sequelae following acute infection. Examples include but are not limited to impetigo, pharyngitis, septicaemia, necrotizing fascitis, streptococcal toxic-shock syndrome, acute rheumatic fever and post-streptoccal glomerulonephritis. Preferably the individual to be treated is human. The invention additionally provides pharmaceutical compositions comprising the polypeptides, polynucleotides, antibodies or agents of the invention and a pharmaceutically acceptable carrier or diluent. Formulation with standard pharmaceutically acceptable carriers and/or excipients may be carried out using routine methods in the pharmaceutical art. For example, an active substance may be dissolved in physiological saline or water for injections. The exact nature of a formulation will depend upon several factors including the particular substance to be administered and the desired route of administration. Suitable types of formulation are fully described in Remington's Pharmaceutical Sciences, Mack Publishing Company, Eastern Pennsylvania, 17th Ed. 1985, the disclosure of which is included herein of its entirety by way of reference. The substances may be administered by enteral or parenteral routes such as via oral, buccal, anal, pulmonary, intravenous, intra-arterial, intramuscular, intraperitoneal, topical or other appropriate administration routes. The polypeptides and polynucleotides of the invention are useful for prophylactic treatment of individuals. Typically the polypeptide or polynucleotide used represents or encodes an epitope of IdeS. In general, the polypeptide or polynucleotide is capable of generating an immune, in particular a protective immune reponse in the individual to be treated. Preferably antibodies that have the ability to block the IgG enzymatic activity of IdeS are generated. Such polypeptides and polynucleotides may be identified by the methods described above. Generally for such uses, the polypeptides, polynucleotides are incorporated in vaccine compositions. Vaccines may be prepared from one or more of the proteins or peptides of the invention and a physiologically acceptable carrier or diluent. Typically, such vaccines are prepared as injectables, either as liquid solutions or suspensions; solid forms suitable for solution in, or suspension in, liquid prior to injection may also be prepared. The preparation may also be emulsified, or the protein encapsulated in a liposome. The active immunogenic ingredient may be mixed with an excipient which is pharmaceutically acceptable and compatible with the active ingredient. Suitable excipients are, for example, water, saline, dextrose, glycerol, ethanol, of the like and combinations thereof. In addition, if desired, the vaccine may contain minor amounts of auxiliary substances such as wetting or emulsifying agents, pH buffering agents, and/or adjuvants which enhance the effectiveness of the vaccine. Examples of adjuvants which may be effective include but are not limited to: aluminium hydroxide, N-acetyl-murainyl-L-threonyl-D-isoglutamine (thr-MDP), N-acetyl-nor-muramyl-L-alanyl-D-isoglutamine (CGP 11637, referred to as nor-iMP), N-acetylmuramyl-L-alanyl-D-isoglutaminyl-L-alanine-2-(1′-2′-dipalmitoyl-sn-glycero-3-hydroxyphosphoryloxy)-ethylamine (CGP 19835A, referred to as MTP-PE), and RIBI, which contains three components extracted from bacteria, monophosphoryl lipid A, trehalose dimycolate and cell wall skeleton WL+TDM+CWS) in a 2% squalene/Tween 80 emulsion. The effectiveness of an adjuvant may be determined by measuring the amount of antibodies directed against an immunogenic polypeptide containing an IdeS antigenic sequence resulting from administration of this polypeptide in vaccines which are also comprised of the various adjuvants. The vaccines are conventionally administered parentally, by injection, for example, either subcutaneously or intramuscularly. Additional formulations which are suitable for other modes of administration include suppositories, oral formulations and formulations for transdermal administration. For suppositories, traditional binders and carriers may include, for example, polyalkylene glycols or triglycerides; such suppositories may be formed from mixtures containing the active ingredient in the range of 0.5% to 10%, preferably 1% to 2%. Oral formulations include such normally employed excipients as, for example, pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, magnesium carbonate, and the like. These compositions take the form of solutions, suspensions, tablets, pills, capsules, sustained release formulations or powders and contain 10% to 95% of active ingredient, preferably 25% to 70%. Where the vaccine composition is lyophilised, the lyophilised material may be reconstituted prior to administration, e.g. a suspension. Reconstitution is preferably effected in buffer. Capsules, tablets and pills for oral administration to a patient may be provided with an enteric coating comprising, for example, Eudragit “S”, Eudragit “L”, cellulose acetate, cellulose acetate phthalate or hydroxypropylmethyl cellulose. Vaccine compositions suitable for delivery by needleless injection, for example, transdermally, may also be used. The proteins or peptides of the invention may be formulated into the vaccine as neutral or salt forms. Pharmaceutically acceptable salts include the acid addition salt (formed with free amino groups of the peptide) and which are formed with inorganic acids such as, for example, hydrochloric or phosphoric acids, or such organic acids such as acetic, oxalic, tartaric and maleic. Salts formed with the free carboxyl groups may also be derived from inorganic bases such as, for example, sodium, potassium, ammonium, calcium, or ferric hydroxides, and such organic bases as isopropylamine, trimethylamine, 2-ethylanino ethanol, histidine and procaine. The vaccines are administered in a manner compatible with the dosage formulation and in such amount will be prophylactically and/or therapeutically effective. The quantity to be administered, which is generally in the range of 5 μg to 100 mg, preferably 250 μg to 10 mg of antigen per dose, depends on the subject to be treated, capacity of the subject's immune system to synthesize antibodies, and the degree of protection desired. Precise amounts of active ingredient required to be administered may depend on the judgement of the practitioner and may be peculiar to each subject. The vaccine may be given in a single dose schedule, or preferably in a multiple dose schedule. A multiple does schedule is one in which a primary course of vaccination may be 1-10 separate doses, followed by other doses given at subsequent time intervals required to maintain and or reinforce the immune response, for example at 1 to 4 months for a second dose, and if needed, a subsequent dose(s) after several months. The dosage regimen will also, at least in part, be determined by the need of the individual and be dependent upon the judgement of the practitioner. The nucleotide sequences of the invention and expression vectors can also be used as vaccine formulations as outlined above. Preferably, the nucleic acid, such as RNA or DNA, in particular DNA, is provided in the form of an expression vector, which may be expressed in the cells of the individual to be treated. The vaccines may comprise naked nucleotide sequences or be in combination with cationic lipids, polymers or targeting systems. The vaccines may be delivered by any available technique. For example, the nucleic acid may be introduced by needle injection, preferably intradermnally, subcutaneously or intramuscularly. Alternatively, the nucleic acid may be delivered directly across the skin using a nucleic acid delivery device such as particle-mediated gene delivery. The nucleic acid may be administered topically to the skin, or to mucosal surfaces for example by intranasal, oral, intravaginal or intrarectal administration. Uptake of nucleic acid constructs may be enhanced by several known transfection techniques, for example those including the use of transfection agents. Examples of these agents includes cationic agents, for example, calcium phosphate and DEAE-Dextran and lipofectants, for example, lipofectam and transfectam. The dosage of the nucleic acid to be administered can be altered. Typically the nucleic acid is administered in the range of 1 pg to 1 mg, preferably to 1 pg to 10 μg nucleic acid for particle mediated gene delivery and 10 μg to 1 mg for other routes. Inhibitory agents, for example, identified according to the above screening methods may also be useful in preventing or treating infection-associated conditions. These agents may be formulated with standard pharmaceutically acceptable carriers and/or excipients using routine methods. The antibodies and agents of the invention may be useful for therapeutic treatment of S. pyogenes infections. Antibodies of the invention, both polyclonal and monoclonal, which are neutralising, are useful in passive immunotherapy. Monoclonal antibodies in particular, may be used to raise anti-idiotype antibodies as above. These anti-idiotype antibodies may also be useful for treatment of S. pyogenes, as well as for an elucidation of the immunogenic regions of polypeptides of the invention. Antibody fragments, for example, Fab fragments, may also be useful in immunotherapy of S. pyogenes infection. The antibodies of the invention may be formulated with a pharmaceutically acceptable carrier and delivered in the same way as set out for the vaccine compositions. Preferably the antibody is administered in an amount effective to ameliorate S. pyogenes infection in the individual. Inhibitors of IdeS activity, for example those identified by the above screening methods may be useful for therapeutic treatment of S. pyogenes infections. These agents may be formulated with standard pharmaceutically acceptable carriers and/or excipients using routine methods and delivered in the same way as set out for the vaccine compositions. The inhibitor is administered to an individual in a therapeutically effective amount. The dose of an inhibitor may be determined according to various parameters, especially according to the substance used; the age, weight and condition of the patient to be treated; the route of administration; and the required regimen. A physician will be able to determine the required route of administration and dosage for any particular patient. In one aspect, an S. pyogenes infection may be treated by administration of both an antibody and an inhibitory agent. The antibody and the agent may be administered simultaneously, separately, or sequentially. Accordingly the invention also relates to products in which both antibody and agent are supplied for use in such a treatment regimen. The invention is also concerned with the diagnosis of S. pyogenes infection in an individual, preferably a human. The polypeptides and antibodies of the invention may be used for such diagnosis. The polypeptides may be used to detect antibodies specific to the polypeptides in the individual or vice versa, thus determining infection. Polypeptides suitable for use in diagnosis are those which retain specific antibody binding capability. For example, such polypeptides typically comprise an epitope of IdeS. Suitable polyp eptides can be identified by the methods described above. Antibodies for use in diagnosis may be identified and produced by the methods described above. The diagnostic method may be practised in vitro or in vivo. Preferably the method is carried out in vitro using a sample taken from the individual to be tested for S. pyogenes infection. A sample may be for example a tissue extract, blood, serum or saliva. Generally, the method may involve (i) contacting a biological sample taken from the individual with a polypeptide or antibody of the invention under conditions that allow for the formation of an antibody-polypeptide complex; and (ii) determining whether antibody-polypeptide complex is formed. Typically the polypeptides or antibodies for use in testing are suitably labelled. Suitable label and detection systems are known in the art. The polypeptides or antibodies may be bound to a solid support and/or packaged into kits in a suitable container along with suitable reagents, controls, instructions, etc. Antibodies may also be linked to a revealing label and thus may be suitable for use in methods of in vitro imaging. In a further aspect, the present polypeptides may provide useful tools for biotechnology. For example, the polypeptides may be used for specific in vito cleavage of IgG, in particular human IgG. In such a method, the polypeptide may be incubated with the sample containing IgG under conditions which permit the specific cysteine protease activity to occur. Specific cleavage can be verified, and the cleavage products isolated using the methods described above. The method of the invention can be used in particular to generate Fc and Fab fragments. The polypeptides may be used to cleave IgG in a sample, for example in a method to remove IgG from a sample. Such methods may be used to assist in removing immunoglobulin from a sample, or to remove IgG in the purification of other immunoglobulin. Modified polypeptides of the invention which no longer have cysteine protease activity may be used to bind and isolate or purify IgG. For example, such polypeptide may be bound to a solid support and a sample containing IgG contacted with the support under conditions which allow IgG to bind to the polypeptide. Such a method may also be used to remove IgG from a sample, the remainder of the sample, free of IgG being collected for subsequent use or analysis. IgG may subsequently be desorbed from the solid support if required. The polypeptides may also be used to detect IgG in a sample. In general such a detection method involves incubating the polypeptide with the sample under conditions which permit IgG-specific binding and cleavage. The presence of IgG can be verified by detection of the specific IgG cleavage products as above. EXAMPLES Materials and Methods Unless indicated otherwise, the methods used are standard biochemistry and molecular biology techniques. Examples of suitable methodology textbooks include Sambrook et al., Molecular Cloning, A Laboratory Manual (1989) and Ausubel et al., Current Protocols in Molecular Biology (1995), John Wiley and Sons, Inc. Bacterial Strains and Growth Conditions S. pyogenes strains used in this study are listed in Table I. IgG cleavage (in the presence PCR Strain M-serotype Reference or source of E64) product SF370 1 (Suvorov and Feretti, 1996; (+/−) + Ferretti et al., 2001) AP1 1 WHO Prague collectiona + + AL1 1 speB mutant of AP1 (Collin + ndd and Olsén, 2001a) BMJ71 1 mga mutant of AP1 + nd (Kihlberg et al., 1995) KTL3 1 Finnish institute for health (+) + AP4 4 WHO Prague collection − + M5 5 Sequencing in progessb − + AP6 6 WHO Prague collection − + AP12 12 WHO Prague collection + + AP49 49 WHO Prague collection − + AP53 53 WHO Prague collection − + AP55 55 WHO Prague collection + + AP57 57 WHO Prague collection − + Streptococci were routinely grown in Todd Hewitt broth (TH) (Difco) at 37° C. in 5% CO2. Strains BMJ71 and AL1 were grown in the presence of 10 μg/ml tetracycline or 150 μg/ml kanamycin, respectively. In some cases bacteria were grown in the presence of the cysteine proteinase inhibitor trans-epoxysuccinyl-L-leucylamido-(4-Guanidino) butane (E64) (Sigma). SDS-PAGE Analysis and N-Terminal Sequence Determination Proteins of S. pyogenes growNth media were precipitated with trichloroacetic acid (final concentration 5%), washed twice with 1 ml acetone, and resuspended in sample buffer. Proteins were separated by 12% SDS-PAGE (all SDS-PAGEs in this work were performed under reducing conditions) and stained with Coomassie Blue. For N-terminal amino acid sequence analysis proteins were separated by 10% SDS-PAGE electrophoresis and blotted onto a PVDF membrane using 10 mM CAPS buffer, 10% methanol. Proteins were visualized in 0.1% Coomassie Blue R-250, 50% methanol. After destaining in 50% methanol, membranes were dried, protein bands cut out with a scalpel and stored at −20° C. until sequencing. Sequencing was performed at Eurosequence Company (Groningen, The Netherlands). Purification of IdeS IdeS was purified by growing bacteria to an OD620 of ˜0.4 and fractionating the culture supernatant with 50% ammonium sulfate. The resulting precipitate was discarded and ammonium sulfate was added to the remaining supernatant to a final concentration of 70%. The second precipitate was resuspended in {fraction (1/100)} of the starting volume with 20 nM Tris-HCl, pH 8.0, and dialyzed against the same buffer. The material was further fractionated by FPLC on a Mono Q column (Pharmacia). Proteins were eluted by a linear NaCl gradient, and a peak eluted at 0.1M NaCl was found to contain the IdeS activity. Corresponding fractions were collected, analyzed by SDS-PAGE, and saved at −20° C. until use. IdeS Activity Assays For standard IdeS activity assays, bacteria cultures were grown to OD620=0.4. Bacteria were pelleted by centrifugation and supernatants were sterile-filtered through a 0.22 μm membrane (Millipore) prior to use. For activity assays, 254 μl of supernatant were mixed with 5 μl of IgG (10 mg/ml, Sigma) and the volume was adjusted with PBS to 100 μl. For screening of IdeS activity in different S. progenes strains, E64 was added to a final concentration of 40 μM. The mixtures were incubated at 37° C. for 30 min and samples were analyzed by 12% SDS-PAGE. For cleavage assays of different classes of Ig, purified IdeS (0.3 μg/ml) was incubated with 3 μg Ig for 2 h at 37° C., and analyzed by 12% SDS-PAGE analysis. PCR Analysis of Genomic DNA for Identification of ides To analyze the presence of the ideS gene in different streptococcal isolates, PCR template DNA was prepared by boiling S. pyogenes bacteria for 5 min in sterile water. Cell debris was removed by centrifugation and 1 μl of the boiled lysate was used with PCR primers Ide1 (5′-CGT TAC TTC CGT TTG GAT CCA AGG-3′) and Ide2 (5′-GAA ATA GCT ACT TCT CGA GCG GAA TT-3′). PCR products were analyzed by agarose (1%) gel electrophoresis. Recombinant Expression of IdeS in E. coli For PCR amplification of ideS, template DNA was prepared by boiling S. pyogenes bacteria (strain AP1) in sterile water. The cell debris was removed by centrifugation and 5 μl of the boiled lysate was used with PCR primers Ide5X (5′-TCG GTA GAT CGT GGG ATC CTA GCA GAT AGT-3′) creating a BamHI restriction site, and Ide3X (5′-CGG AAT TCT TAA TTG GTC TGA TTC CAA C-3′), creating an EcoRI restriction site. A PCR fragment covering bp 79-1020 of the intact ideS gene was generated, cleaved with restriction enzymes, and cloned into the corresponding sites of plasmid pGEX-5X-3 (Amersham Pharmacia Biotech). The resulting plasmid was transformed into Escherichia coli strain BL21 (DE3) pLysS, according to standard protocols (Sambrook et al., 1989). Protein expression was induced by addition of 0.1 mM isopropyl-β-D-thiogalactopyranoside (IPTG) at an OD620 of ˜0.2. Growth was continued for 3 h, and lysates were prepared by freezing bacterial pellets at −70° C., followed by resuspension in PBS. Cell debris was removed by centrifugation and 2 μl of supernatant was incubated with 5 μl of IgG (10 mg/ml) in PBS, and separated by 12% SDS-PAGE for analysis of recombinantly expressed IdeS. Proteinase Inhibition Assays Partially purified IdeS (0.3 μg/ml) was incubated with either 20 nM iodoacetic acid, Z-LVG-CHN2 (Björck et al., 1989) at 0.4 mg/ml in 1% DMSO, or E64 (40 μM). The tubes were kept in the dark and incubated for 30 min at room temperature. As controls, IdeS was also kept in phosphate buffered saline (PBS) or in 1% DMSO, the solvent for Z-LVG-CHN2. After 30 min, 5 μl of 10 mg/ml IgG (Sigma) were added, and the volume was adjusted to 100 μl with PBS. Incubation was continued for 60 min at 37° C. The reaction was stopped by the addition of SDS-PAGE sample buffer and samples were analyzed by 12% SDS-PAGE. Cell Culture and Infection of Eukaryotic Cells The murine macrophage-like cell line RAW 264.7 was cultured in RPMI 1640 medium (Life Technologies), supplemented with 10% FCS, and antibiotics (100 units/ml−1 penicillin; 100 μg ml−1 streptomycin), at 5% CO2 with 100% relative humidity. To study phagocytic killing, S. pyogenes strain AP1 was grown overnight at 37° C. AP1 bacteria were incubated with either imune or non-immune plasma, washed and treated with IdeS or a buffer control, for 2 h at 37° C. Subsequently, bacteria were washed and diluted in antibiotic-free cell culture medium prior to infection. Cell lines were carefully washed in antibiotic-free cell culture medium and bacteria were added (0.1-1 bacteria/cell) to confluent RAW264.7 cells. Infections were synchronized by gentle centrifugation at 400 g for 3 min by incubation at 37° C. Ten minutes after infection, the cell cultures were carefully washed in antibiotic-free medium to remove non-adherent bacteria (time 0 h). Control cells were lysed in ice-cold lysis buffer (0.1% Tween), diluted, and spread onto TH plates. Parallel cell cultures were incubated at 37° C. for 1 h. Subsequently, growth media was removed and cells were lysed and treated as described above. For analysis of bacterial survival the number of surviving bacteria after 1 h was divided by the number of adherent bacteria at time 0 h. Results S. pyogenes Secretes an IgG-Cleaving Enzyme Distinct from SpeB, the Classical Streptococcal Cysteine Proteinase The proteolytic activity of extracellular enzymes of S. pyogenes strain AP1, was analyzed by growing AP1 bacteria in Todd Hewitt (TH) medium supplemented with 10% human plasma. Following growth to stationary phase, bacteria were removed by centrifugation and the supernatant was subjected to SDS-PAGE (all SDS-PAGE's in this work were performed under reducing conditions). The band pattern was compared to the pattern of human plasma proteins that had not been in contact with bacteria (data not shown). The bacterial supernatant contained a protein band of approximately 31 kDa, which was absent in the plasma control. The N-terminal sequence of this protein was determined to GPSVFLFP, which corresponds to amino acids 237-244 of the hinge region of human IgG1 (FIG. 1). Recent work has shown that the streptococcal cysteine proteinase, SpeB, cleaves IgG at this site. However, most strains of S. pyogenes, including AP1, do not express the speb gene in TH medium. Moreover, the proteolytic activity of SpeB is efficiently blocked by the specific cysteine proteinase inhibitor E64, but E64 did not inhibit the cleavage of IgG when added to the AP1 growth medium, as evidenced by the continued generation of the 31 kDa IgG cleavage product (data not shown). In addition, growth medium from the isogenic SpeB deficient mutant strain AL1, also contained IgG-cleaving activity. Taken together, these data demonstrate that SpeB is not responsible for the cleavage of IgG in TH medium. The streptococcal strain AP1 studied here, expresses a surface-associated C5a peptidase, and the IgGFc binding proteins, H and M1. The genes encoding these surface proteins are controlled by the transcriptional activator Mga, and BMJ71 is an isogenic mutant of AP1, carrying a Tn916 insertion within the maga gene. The 31 kDa IgG cleavage product is also generated in growth medium of BMJ71, showing that the proteolytic activity is not under Mga control. Purification and Sequence Characteristics of IdeS, a Novel Proteinase of S. pyogenes As the IgG proteolytic activity was found in the growth medium of strain AP1 we fractionated culture medium proteins after bacterial growth by adding increasing amounts of ammonium sulfate (10 to 80%). These initial experiments revealed that precipitates of 60 to 70% ammonium sulfate contained most of the IgG-cleaving activity. For purification, the growth medium was fractionated with 50% ammonium sulfate, the resulting pellet was discarded and the ammonium sulfate concentration in the supernatant was adjusted to 70%. Proteins pelleted by this second precipitation were subjected to ion-exchange chromatography and peak fractions were tested for enzymatic activity. Maximum IgG-cleaving activity was eluted at 0.1M NaCl and the corresponding fractions contained a major band of approximately 34 kDa as judged by SDS-PAGE. This protein band was excised and subjected to N-terminal sequence analysis. The sequence obtained, DSFSANQEIRY, was used to search the Streptococcal Genome Sequencing Project (SGSP) database. A perfect match was found in an open reading frame of 339 amino acids designated SPy0861. The obtained N-terminal sequence corresponds to amino acids 30-40 (FIG. 2) and was preceded by a potential signal sequence of 29 amino acids as predicted by the SignalP algorithm. The protein does not contain a cell wall attachment signal (LPXTGX), a common feature of cell wall-anchored proteins of S. pyogenes, and the predicted size of the protein, without the potential signal sequence, is 34.9 kDa, which is in accordance with the size of the purified protein estimated by SDS-PAGE. Apart from the putative signal sequence, the protein has an RGD motif at amino acids 214-216 (FIG. 2). This motif is important for ligand recognition by integrins, and a variety of bacterial and viral pathogens have been shown to bind to host cell integrins. The full-length putative protein sequence was used in a similarity search against the DDBJ/EMBL/GenBank database using a BLASTp algorithm. This search revealed no similarities to any prokaryotic protein and a weak similarity (24% identity in a region of 204 amino acid residues) to human MAC-1 integrin alpha M precursor (Arnaout et al., 1988). Due to the absence of any previously reported function, and based on the enzymatic activity against human IgG, the protein was denoted IdeS, for Immunoglobulin degrading enzyme of Streptococcus pyogenes. To further confirm that the identified IdeS protein has IgG cleaving activity, the ideS gene was cloned in plasmid pGEX-5X-3 (Amersham Pharmacia Biotech) and expressed in Escherichia coli. Partially purified lysates were incubated with IgG and analyzed by SDS-PAGE. Lysates from E. coli carrying the ideS gene generated the 31 kDa IgG-derived band, whereas extracts from cells carrying only a plasmid control did not cleave IgG (data not shown). IdeS is a Novel Cysteine Proteinase Highly Specific for IgG We noticed that the sequence of the IdeS protein contains a single cysteine residue at position 94 (FIG. 2). Despite the lack of sequence homology to other cysteine proteinases, IdeS also has a histidine residue at a distance (His 224) from the cysteine, which is often found in other cysteine proteinases, although the enzymatic activity was not inhibited by the cysteine proteinase inhibitor E64. The peptide derivate Z-LVG-CHN2, structurally based on the inhibitory reactive site of cystatin C and carrying a diazomethyl ketone group to inactivate the sulfhydryl group of the catalytic cysteine, has previously been shown to irreversibly inhibit papain and SpeB. Moreover, cysteine proteinases are also inactivated by iodoacetic acid through an irreversible modification of the catalytic sulfhydryl group. We therefore investigated whether treatment with these specific inhibitors would affect the enzymatic activity of IdeS. Analysis of IgG incubated with IdeS alone or with IdeS preincubated with inhibitors, revealed that Z-LVG-CHN2 and iodoacetic acid efficiently inhibited the activity of IdeS whereas E64 had no effect on the enzyme (data not shown). The activity of IdeS, its sequence characteristics, and inhibition profile, establish IdeS as a new member of the cysteine proteinase family. Recently the streptococcal cysteine proteinase SpeB was shown to cleave the heavy chains of all classes of human immunoglobulins; IgG, IgM, IgA, IgD, and IgE. In contrast, when human IgG, IgM, IgA, IgD, or IgE, were incubated with purified IdeS for 2 h at 37° C., only IgG was degraded (data not shown). We also analyzed the activity of IdeS against the different subclasses of IgG, and found that all were susceptible for IdeS digestion, although, when compared to the other subclasses, IgG2 was less efficiently digested (not shown). The high specificity of IdeS is further emphasized by the observation that only the 31 kDa IgG-derived band and no additional degradation products could be identified following incubation of human plasma with purified IdeS. Although it cannot be excluded that the enzyme has other substrates, these data show that IdeS has a higher degree of specificity for IgG than any previously described proteinase. Distribution and Expression of the ideS Gene in S. pyogenes Strains The distribution of ideS among S. pyogenes strains was investigated by PCR analysis using primers designed to amplify the internal coding region of ideS. We analyzed chromosomal DNA preparations from 11 S. pyogenes strains of 9 different M serotypes, and were able to amplify identical PCR fragments of the expected size from all strains (Table I, data not shown). However, when analyzing the cleavage of IgG during bacterial growth in TH medium, only five of the tested strains expressed the IgG-degrading activity (AP1, KTL3, SF370, AP12, and AP55), and among these strains KTL3 and SF370 showed weak activity. Thus, although the IdeS gene seems to be present in all S. pyogenes isolates, expressed enzyme activity under the conditions used here, is restricted to some strains and varies even within the same M serotype (Table I). The secretion pattern of the IgG-cleaving activity during growth of strain AP1 in TH medium was also investigated. Samples were taken from the growth medium at different time points during bacterial growth, and tested for enzymatic activity against IgG. IgG-degrading activity started to appear in samples taken during early logarithmic growth phase, and the activity increased during logarithmic growth as determined from the degree of IgG cleavage. The enzymatic activity did not further increase in stationary phase supernatants but appeared to be persistent at a constant level (FIG. 3). Fc-Mediated Phagocytosis and Killing of S. pyogenes is Inhibited by IdeS Opsonizing IgG antibodies bound to surface antigens of S. pyogenes will expose their Fc regions to complement factor C1q and Fcγ-receptors of phagocytic cells, and thereby facilitate phagocytosis and killing of the bacteria. To test the hypothesis that IdeS by proteolytic cleavage of IgG, could interfere with this defense mechanisms, AP1 bacteria were incubated with either human immune or non-immune plasma. After incubation bacteria were washed and incubated with IdeS, or with a buffer control, followed by another washing step to remove IdeS and degradation products. Confluent RAW264.7 macrophage-like cells were then infected with these bacteria at ˜0.1-1 bacteria/cell. Infections were synchronized by gentle centrifugation and cells were lysed immediately to determine the number of cfu's at time zero. In parallel infections, cell cultures were carefully washed to remove non-adherent bacteria and incubations were continued for 1 h, after which cells were lysed and the number of cfu's was determined. The ratios of cfu's at time 1 h, divided by the number of cfu's at time zero were determined as survival factors and are shown in FIG. 3. The relatively short incubation time was chosen to minimize IgG independent phagocytosis. While bacteria incubated in non-immune plasma survived contact with macrophage-like cells, the number of bacteria, which had been exposed to opsonizing immunoglobulins in immune plasma was significantly reduced (p<0.03) in the presence of macrophages. However, this effect was abolished when bacteria carrying opsonizing IgG were treated with IdeS prior to incubation with phagocytes (FIG. 3). AP1 bacteria express surface proteins that bind several abundant human plasma proteins. As previously reported, following plasma absorptions, the major protein bands eluted from AP1 bacteria represent albumin, fibrinogen, and IgG heavy and light chains. The same protein pattern was obtained following absorption of non-immune or immune plasma, and in both cases IgG was cleaved by IdeS, generating IgGFc fragments, which under the reducing conditions used, give rise to the 31 kDa band (data not shown). These Fc fragments are associated with IgGFc-binding proteins, interactions that efficiently block their capacity to bind complementation factor C1q. However, as shown in FIG. 3, IdeS protects bacteria preincubated with plasma containing specific IgG antibodies. These antibodies are bound to the streptococcal surface via their antigen-binding Fab regions, suggesting that cleavage of this IgG population by IdeS will result in the removal of Fc fragments from the bacterial surface. These data demonstrate that cleavage of IgG by IdeS can occur at the bacterial surface and that IgG cleavage by IdeS increases the capacity of S. pyogenes to evade phagocytic cells. The streptococcal cysteine proteinase SpeB, is well-established as a virulence determinant, and SpeB was recently shown to cleave the hinge region of IgG and to degrade the heavy chains of all human immunoglobulin classes. Therefore, the discovery of an additional extracellular cysteine proteinase in S. pyogenes was unexpected. However, at least under laboratory conditions, SpeB is not expressed until S. pyogenes reaches stationary growth phase, which makes a possible function of SpeB as an enzyme cleaving opsonizing IgG questionable. Thus, it should be important for such a proteinase to be present continuously during infection. IdeS production starts already during early logarithmic growth and continues into late stationary growth phase, which makes the enzyme more suitable to remove opsonizing IgG from the bacterial surface. Still, the actions of IdeS and SpeB could well be complementary. In fact, the identification and characterization of IdeS might explain some previous and puzzling observations. IdeS is not affected by the cysteine proteinase inhibitor E64, but is inhibited by a synthetic peptide derivative (Z-LVG-CHN2), structurally based on the proteinase-binding center of cystatin C, a human cysteine proteinase inhibitor. Z-LVG-CHN2 and E64 both irreversibly block the proteolytic activity of SpeB, but only Z-LVG-CHN2 inhibited streptococcal growth in vitro and in vivo. However, the observation that IdeS is inhibited by Z-LVG-CHN2, but not by E64, suggests that the previously observed effect of Z-LVG-CHN2 on S. pyogenes growth and virulence, could be due to interference with both SpeB and IdeS. In severe invasive S. pyogenes infections, strains of the M1 serotype are the most common, and the AP1 strain studied here and expressing IdeS, is of this serotype. Strains of serotypes M12 and M55, also producing proteolytically active IdeS under the growth conditions used, are phylogenetically closely related, and represent clinically relevant strains often connected with post-streptococcal glomerulonephritis. This correlation suggests a role for IdeS both during acute infections and in aseptic sequelae following acute S. pyogenes infections. IgG is the dominant Ig class and IgGFc has important functions in complement activation and recruitment of phagocytic cells. Moreover, Fcγ receptors are expressed by all immunologically active cells. It seems that S. pyogenes has evolved a specific IgG-cleaving enzyme, and its specificity underlines a potential role for IdeS in preventing contact between S. pyogenes and phagocytes, by cleaving opsonizing IgG in the hinge region. Opsonizing IgG antibodies bind to various S. pyogenes surface structures via the Fab regions. However, most S. pyogenes strains express surface proteins of the M protein family with affinity for IgGFc. The AP1 strain studied here has two such proteins, proteins H and MI, which are structurally closed related. Large amounts of these IgGFc-binding proteins are present at the bacterial surface, and bind IgG with high affinity. As a result, AP1 bacteria surrounded by plasma or inflammatory exudate, are covered with IgG bound to these proteins through the IgGFc-binding proteins. This IgG population will be present in vast amounts compared to antigen specific IgG bound to the bacterial surface via Fab. However, the data reported here demonstrate that IdeS not only cleaves opsonizing antibodies, but also IgG bound to the surface via Fc. Results of Further Studies 1) Substrate Specificity IdeS exhibits high substrate specificity and has so far been found to cleave only IgG. We examined whether IdeS could have additional substrates e.g. eukaryotic plasma proteins. An extensive search for additional substrates and natural occurring inhibitors was performed. i) Species Restrictions IdeS was found to cleave human, rabbit and goat IgG, but not murine IgG, although the primary amino acid sequences at the cleavage site are conserved between the species. ii) Cleavage or Other Human Proteins No cleavage products could be detected when IdeS was incubated with whole human plasma or with fibrinogen, fibronectin, albumin, transferrin, lactoferrin, laminin, H-kininogen, α 1-antitrypsin, aprotinin, cystatin D or cystatin C. No cleavage products could be observed when cystatin C from either chicken, rat or mouse were incubated with IdeS. iii) Activity Towards Natural and Synthetic Peptides Incubation of IdeS with antimicrobial peptide LL-37 or a synthetic peptide homologous to amino acids 234 to 241 of human IgG did not reveal any degradation of the peptides. Neither was the synthetic peptide Z-LVG-CHN2, which inhibits IdeS activity, cleaved by excess IdeS. Thus, to date the only known substrate for IdeS is IgG. However, we found that a Fc-fragment generated by papain cleavage, including 12 amino acids of the hinge region is cleaved by IdeS, suggesting that the recognition site of IdeS on human IgG is located in the Cγ2 region of the molecule. The Cγ2-Cγ3 interphase region of IgG has been ruled out as binding site for IdeS, as streptococcal proteins H and G, both of which bind to this region, cannot inhibit IdeS activity. 2) Neutralizing Antibodies Against the Enzymatic Activity of IdeS An extensive analysis of antibody titers against IdeS in 80 healthy blood donors and 70 patients suffering from invasive S. pyogenes infections was performed. All blood donors showed detectable antibody levels against IdeS, emphasizing that IdeS is expressed iii vivo during the course of streptococcal infections. Patients with invasive S. pyogenes infections showed significantly higher acute phase antibody levels against IdeS (mean ELISA index increase from 0.64 in blood donors to 1.24 in patient sera; p<0.05). Several serum samples from patients recovering from streptococcal infections (pharyngitis and sepsis) show increased antibody titers against IdeS compared to acute phase titers. Antibodies in the majority of the convalescent sera analyzed, but not in all, had the ability to block the enzymatic activity of IdeS. This finding is a very strong indication for the importance of the enzymatic activity in vivo.

<SOH> BACKGROUND OF THE INVENTION <EOH>S. pyogenes (Group A streptococcus) is an important human bacterial pathogen best known as the cause of skin and throat infections. Streptococcal infections vary in severity from relatively mild diseases, like impetigo and pharyngitis, to serious life threatening conditions such as septicemia, necrotizing fascitis, and streptococcal toxic-shock syndrome (Bisno and Stevens, 1996; Cunningham, 2000). Sequelae to S. pyogenes skin and throat infections include serious conditions such as acute rheumatic fever and post-streptococcal glomerulonephritis. S. pyogenes expresses cell wall-anchored surface proteins with the ability to interact with abundant extracellular human proteins such as albumin, IgG, IgA, fibrinogen, fibronectin, and α 2 -macroglobulin (for references see Navarre and Schneewind, 1999). Many of these protein-protein interactions are mediated by members of the M-protein family.

<SOH> SUMMARY OF THE INVENTION <EOH>The present inventors have identified, purified and characterised a new extracellular cysteine protease produced by S. pyogenes . The protease, designated IdeS (Immunoglobulin G-degrading enzyme of S. pyogenes ) displays a high specificity for IgG, cleaving in the hinge region of the immuno globulin. The protease cleaves not only IgG bound to the bacterial surface by IgGFc-binding proteins, but also opsonising IgG, and so appears to have a role in helping S. pyogenes to evade the host immune system. The inventors have shown that IdeS is expressed in both the logarithmic and stationary phases of bacterial growth, and in a number of clinically relevant S. pyogenes strains, including those of the M1, M12 and M55 serotypes. Antibodies to IdeS were found in individuals suffering from S. pyogenes infection, with those found in convalescent sera capable of blocking IdeS enzymatic activity. IdeS is therefore of use in the treatment and diagnosis of conditions associated with S. pyogenes infection. The protease is also useful for developing new biotechnological tools. Accordingly the invention provides a polypeptide comprising: (a) the amino acid sequence of SEQ ID NO: 1; (b) a variant thereof having at least 50% identity to the amino acid sequence of SEQ ID NO: 1 and having IgG cysteine protease activity; or (c) a fragment of either thereof having IgG cysteine protease activity. The invention also provides a polypeptide for use in generating an immune response in an individual comprising: (a) the amino acid sequence of SEQ ID NO: 1; (b) a variant thereof having at least 50% identity to the amino acid sequence of SEQ ID NO: 1 and having IgG cysteine protease activity; or (c) a fragment of either thereof which is capable of generating an immune response to S. pyogenes in an individual. In another aspect the invention provides a polynucleotide which comprises: (a) SEQ ID NO: 3 or a complementary sequence thereto; (b) a sequence which hybridises under stringent conditions to the sequence defined in (a); (c) a sequence which is degenerate as a result of the genetic code to a sequence as defined in (a) or (b); (d) a sequence having at least 60% identity to a sequence as defined in (a), (b) or (c); or (e) a fragments of any of the sequences (a), (b), (c) or (d), and which encodes a polypeptide having IgG cysteine protease activity or capable of generating an immune response against S. pyogenes in an individual. The invention also relates to expression vectors comprising a polynucleotide of the invention and host cells transformed with such expression vectors. In another aspect, the invention relates to a method for identifying an agent that modulates IgG cysteine protease activity of a polypeptide having the amino acid sequence of SEQ ID NO: 1 comprising: (i) contacting a polypeptide as defined above and IgG with a test substance under conditions that would permit IgG cysteine protease activity in the absence of the test substance; and (ii) determining thereby whether the test substance modulates the said activity. Inhibitors of the cysteine protease of the invention, for example identifiable by the other method are provided for use in the treatment of S. pyogenes infection. The polypeptides of the invention may be used in a method of generating Fc or Fab fragments of IgG comprising contacting IgG with the polypeptide. The invention also relates to a method of generating an immune response in an individual comprising administering a polypeptide, polynucleotide or expression vector of the invention. Preferably, the polypeptide or polynucleotide is used to generate a protective immune response. Methods of treating S. pyogenes infection are also described, comprising administering an antibody or an IdeS protease inhibitor to an individual.

20041130

20100223

20050602

72817.0

BASKAR, PADMAVATHI

"IDES, AN IGG-DEGRADING ENZYME OF STREPTOCOCCUS PYOGENES"

UNDISCOUNTED

ACCEPTED

ACCEPTED

Diffusion film, electrode having the diffusion film, and process for producing diffusion film

A diffusion membrane contains uncalcined polytetrafluoroethylene (PTFE), calcined PTFE and a conductive substance. An electrode has the diffusion layer (membrane) and a catalyst layer disposed thereon. A process for producing diffusion membranes comprises dispersing uncalcined PTFE, calcined PTFE and a conductive substance in a dispersion medium, removing the dispersion medium, adding a liquid lubricant followed by kneading, compressing the resultant kneaded product (preferably a rod-shaped preform) to expand the same into a membrane, and removing the liquid lubricant. The diffusion membrane preferably contains 1 to 30 wt % of the uncalcined PTFE and 5 to 30 wt % of the calcined PTFE. The conductive substance is desirably a combination of graphite and carbon black. The diffusion membrane is free from local variation in properties, has suitable mass producibility and can be produced inexpensively.

1. A diffusion membrane comprising uncalcined polytetrafluoroethylene, calcined polytetrafluoroethylene and a conductive substance. 2. The diffusion membrane as claimed in claim 1, which contains the uncalcined polytetrafluoroethylene in an amount of 1 to 30 wt % and the calcined polytetrafluoroethylene in an amount of 5 to 30 wt %. 3. The diffusion membrane as claimed in claim 1, wherein the conductive substance is a combination of graphite and carbon black. 4. The diffusion membrane as claimed in claim 1, which contains the conductive substance in an amount of 50 to 90 wt %. 5. An electrode comprising: a diffusion layer membrane comprising uncalcined polyetetraflouroethylene, calcined polyetetraflouroethylene and a conductive substance; and a catalyst layer disposed on the diffusion layer. 6. A process for producing diffusion membranes, said process comprising dispersing uncalcined polytetrafluoroethylene, calcined polytetrafluoroethylene and a conductive substance in a dispersion medium, removing the dispersion medium, adding a liquid lubricant followed by kneading, compressing the resultant kneaded product to extend the same into a membrane, and removing the liquid lubricant. 7. The diffusion membrane as claimed in claim 2, wherein the conductive substance is a combination of graphite and carbon black. 8. The diffusion membrane as claimed in claim 2, which contains the conductive substance in an amount of 50 to 90 wt %. 9. The diffusion membrane as claimed in claim 3, which contains the conductive substance in an amount of 50 to 90 wt %. 10. The electrode of claim 5, wherein the diffusion layer membrane contains uncalcined polytetrafluoroethylene in an amount of 1 to 30 wt % and the calcined polytetrafluoroethylene is present in an amount of 5 to 30 wt %. 11. The electrode of claim 10, wherein the diffusion layer membrane contains a conductive substance in an amount of 50 to 90 wt %. 12. The electrode of claim 5, wherein the diffusion layer membrane contains a conductive substance in an amount of 50 to 90 wt %.

FIELD OF THE INVENTION The present invention relates to a diffusion membrane, an electrode having the diffusion membrane, and a process for producing diffusion membranes. More particularly, the invention relates to a diffusion membrane that is combined with a Pt- or Pt/Ru alloy-containing catalyst layer and is used in preparing a diffusion layer member which constitutes an electrode for fuel cells, electric double layer capacitors or the like, and also relates to an electrode having the diffusion membrane and a process for producing diffusion membranes. BACKGROUND OF THE INVENTION Fuel cells have many types such as phosphoric acid fuel cells, molten carbonate fuel cells, solid electrolyte fuel cells, solid polymer electrolyte fuel cells and alkaline fuel cells. Particularly, the ion-exchange membrane fuel cells (solid polymer electrolyte fuel cells) are of great interest recently because they operate at a high current density of 3 to 6 A/cm2. The ion-exchange membrane fuel cells have a polymer ion-exchange membrane comprised of a fluororesin with a sulfonic group (—SO3H) in a side chain. The membrane is disposed between an anode electrode (fuel electrode) and a cathode electrode (air electrode) to form an assembly. Outside the assembly major surfaces are provided current collectors that also function as flow channels for the fuel (H2) and oxidizer (air). The electrodes are composed of carbon on which a catalyst such as platinum or platinum-ruthenium alloy is supported for promoting the electrode reactions. The electrode reactions at the anode and the cathode are shown as follows: Anode reaction: H2→2H++2e− Cathode reaction: 1/202+2H++2e−→H2O The hydrogen ions (H+) move from the anode to the cathode through the ion-exchange groups in the membrane with water molecule. The electrode reactions take place at the three-phase (liquid/gas/solid) interface among the electrolytic solution (liquid), air (gas) and catalyst layer (solid). The three-phase (liquid/gas/solid) interface must be adequately formed to prevent the electrode reaction rates from being controlled by the gas diffusion. Therefore, the electrodes are made porous and coated with water-repellent polytetrafluoroethylene (PTFE) resin. Combination of a diffusion layer and a catalyst layer is called a gas diffusion electrode. Its function is to bring the fuel (H2) and gas (oxygen O2) into even contact with the catalyst layer such as of platinum. The gas diffusion electrodes (particularly the diffusion layers) have another function of transmitting the electrons created at the catalyst layers, and therefore are required to have conductivity. Furthermore, the diffusion layers have a function of distributing the gas to the catalyst layer, and therefore include a great number of pores. For the need of ensuring the ion conductivity of the ion-exchange membrane and of hydration, humidified fuel (H2) is fed. The gas diffusion electrodes have water repellency to prevent the moisture for ion conductivity from clogging the pores in the diffusion layers to block the gas diffusion. As described above, the gas diffusion electrodes for use in the fuel cells and other electrochemical devices are required to have gas diffusibility, gas permeability, water repellency and conductivity. The diffusion membranes (layers) are generally produced by coating an electrode material such as a porous carbon fiber membrane or porous carbon paper with a dispersion mixture that contains carbon powder, polytetrafluoroethylene (PTFE) and a dispersion medium, by means of spraying or printing technique. In such conventional processes, the coating of the porous carbon fiber membrane or porous carbon paper with a dispersion mixture that contains uncalcined polytetrafluoroethylene, conductive carbon and a dispersion medium is followed by repetitive rolling. This requires complex and multiple steps and increases the processing cost. Moreover, the above process is complicated and has great difficulty in controlling the application of the dispersion mixture so as to achieve uniform properties throughout the resultant diffusion layer. It is also insufficient in terms of mass production capability for the diffusion membranes (layers). Furthermore, the porous carbon fiber membranes or porous carbon papers are expensive to cause cost problems. To solve such problems, JP-A-2001-85280 (patent publication (i)) owned by the present applicant proposes a production process for polytetrafluoroethylene-containing sheet electrodes and a sheet electrode obtained by the process. This process comprises rolling a rod-shaped preform into a sheet electrode, wherein the preform comprises carbon fine powder, polytetrafluoroethylene and a liquid lubricant and has a specific relation with respect to the maximum length in the compression direction and that in a crosswise direction perpendicular to the compression direction. The above process is capable of manufacturing uniform sheet electrodes through a simple step and enables cost reduction and mass production. However, the method of JP-A-2001-85280 (patent publication (i)) using the conventional raw materials, namely, uncalcined polytetrafluoroethylene and conductive carbon results in a diffusion membrane (layer) which has unfavorably high volume resistance and insufficient electron conductivity and gas permeability. This can be rationalized by the excessive binding effect of the uncalcined polytetrafluoroethylene whose intended purpose is to impart water repellency. Furthermore, the method has difficult membrane production and is unsuitable for continuous mass production of membranes. Under these circumstances, the present inventors earnestly carried out studies of a low cost process for mass production of diffusion membranes that have sufficient water repellency and no regional variation in properties. As a result, they have found that a resin composition containing uncalcined polytetrafluoroethylene, calcined polytetrafluoroethylene and a conductive substance can solve all the aforesaid problems by its capability of giving diffusion layers that have adequate water repellency and no local variation in properties, at reduced cost and with mass producibility. The present invention has been accomplished based on this finding. JP-A-S52-97133 (patent publication (ii)) discloses a gas diffusion electrode including a sheet of a carbon material that contains a specific amount of carbon fibrils held together with a fluororesin, wherein the fibril lengths and diameters have a specific ratio. It also discloses a production process for gas diffusion electrodes comprising kneading and rolling the carbon material, the fluororesin and an auxiliary into a sheet and bonding the sheet with a catalyst layer mainly composed of an electrode catalyst and a binder, wherein the auxiliary is removed before or after the catalyst layer is bonded. The gas diffusion electrode as described in the above patent publication is relatively thin and satisfactory in mechanical strength as mentioned also in JP-B-S63-19979 (patent publication (iv)), but the gas permeability thereof is insufficient. JP-A-S58-165254 (patent publication (iii)) discloses a process for producing fuel-cell gas diffusion electrodes that comprises forced filling of carbon powder, a catalyst and ethylene tetrachloride resin into pores of a porous fiber membrane by means of suction force from below one side of the membrane. JP-B-S63-19979 (patent publication (iv)) discloses a gas diffusion electrode material that is a fine porous network structure. This material comprises a number of polytetrafluoroethylene resin minute nodes containing conductive substance powder and a number of polytetrafluoroethylene resin fibrils containing no conductive substance powder that extend from each node to form three-dimensionally linked nodes, wherein all the minute nodes contact with each other or are in series at parts thereof. JP-B-H01-12838 (patent publication (v)) discloses a gas and liquid permeable electrode material resulting from the bonding of a liquid permeable membrane that contains conductive substance powder in minute nodes and a conductive porous substrate of specific flexural strength. The liquid permeable membrane is a porous polytetrafluoroethylene resin membrane that has a number of minute nodes dimensionally linked through many fibrils with formation of a spiderweb network among the minute nodes. The minute nodes contact with each other or are in series at parts thereof. JP-B-H05-52031 (patent publication (vi)) discloses a gas diffusion electrode material comprising: a plurality of conductive powder-containing layers that are constituted of a number of polytetrafluoroethylene resin minute nodes containing conductive substance powder and substantially connected with each other, and a number of polytetrafluoroethylene resin fibrils that extend from each node and tridimensionally link the nodes; and a layer that is disposed between the plurality of layers and is constituted of a number of polytetrafluoroethylene resin minute nodes containing no conductive powder and a number of polytetrafluoroethylene resin fibrils extending from each node to tridimensionally link the nodes. These layers are directly engaged by pressure whereby the conductive powder-containing minute nodes are pressed and dispersed into among the fibrils that link the minute nodes containing no conductive substance powder. Consequently, electric conduction is achieved as a result of partial contact between the conductive powder-containing minute nodes or by the jumping effect. However, these patent publications (ii) to (vi) provide gas diffusion electrode materials that are unsatisfactory in any of gas permeability, water repellency, mass producibility, production costs, conductivity and uniformity. The present invention aims to solve the aforesaid problems related to the background art. It is an object of the invention to provide a low cost diffusion membrane that employs neither the expensive porous carbon fiber membrane nor porous carbon paper and has sufficient water repellency, uniform properties throughout the layer and suitable mass producibility. It is another object of the invention to provide an electrode having a diffusion membrane (layer) with the above properties. It is a further object of the invention to provide an efficient and low cost process for producing diffusion membranes having the above properties. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a schematic view illustrating a contact condition of uncalcined PTFE fibers, carbon black, graphite powder and calcined PTFE powder in a diffusion membrane (sheet) according to the present invention. DISCLOSURE OF THE INVENTION A diffusion membrane according to the present invention comprises uncalcined polytetrafluoroethylene, calcined polytetrafluoroethylene and a conductive substance. Preferably, the diffusion membrane contains the uncalcined polytetrafluoroethylene in an amount of 1 to 30 wt % and the calcined polytetrafluoroethylene in an amount of 5 to 30 wt %. The conductive substance is preferably a combination of graphite and carbon black. Preferably, the diffusion membrane contains the conductive substance in an amount of 50 to 90 wt %. An electrode according to the present invention includes: any diffusion layer (membrane) as described above; and a catalyst layer (membrane) disposed on the diffusion layer. A process for producing diffusion membranes according to the present invention comprises dispersing uncalcined polytetrafluoroethylene, calcined polytetrafluoroethylene and a conductive substance in a dispersion medium, removing the dispersion medium, adding a liquid lubricant followed by kneading, compressing the resultant kneaded product (preferably a rod-shaped preform) to extend the same into a membrane, and removing the liquid lubricant. The present invention enables low cost mass production of diffusion membranes having adequate water repellency and no regional variation in properties without use of the expensive porous carbon fiber membrane or porous carbon paper. Since the diffusion membrane is made of other than the expensive porous carbon fiber membrane and porous carbon paper, the electrode of the invention can be efficiently mass produced at a reduced cost while ensuring uniform properties throughout all the area. The production process for diffusion membranes according to the invention enables efficient production of diffusion membranes having the above properties. PREFERRED EMBODIMENTS OF THE INVENTION Hereinbelow, the diffusion membrane, electrode having the same, and production process for diffusion membranes according to the invention will be described in detail. Diffusion Membrane (Layer) The diffusion membrane (layer) of the invention contains uncalcined fluoropolymer resin, preferably uncalcined polytetrafluoroethylene (PTFE), and calcined fluoropolymer resin, preferably calcined polytetrafluoroethylene, and further a conductive substance. Exemplary fluoropolymer resins include polytetrafluoroethylene (PTFE), modified PTFE, PVdF, ETFE, PCTFE, FEP and PFA, with PTFE being preferable from the viewpoints of diffusion membrane's heat resistance, chemical resistance and water repellency. Production steps and raw materials for the diffusion membrane will be discussed in detail in the following exemplary embodiment which employs PTFE, preferable fluoropolymer resin in the invention. Uncalcined Fluoropolymer Resin (Uncalcined PTFE) The uncalcined fluoropolymer resin, preferably uncalcined PTFE, may be in the form of dispersion or powder. In view of dispersion properties, a dispersion is preferable. Process for preparing the uncalcined PTFE is not particularly limited. For example, fine powder or an emulsion polymer such as a dispersion polymer, and a mixture thereof with molding powder obtained from a suspension polymerization may be used. The uncalcined fluoropolymer resin, preferably PTFE, will generally range in mean particle diameter (p from 0.1 to 0.5 μm, and preferably from 0.2 to 0.4 μm in view of dispersion properties. Calcined Fluoropolymer Resin (Calcined PTFE) The calcined fluoropolymer resin, preferably calcined PTFE, may take various forms, including powder and fibers. The powder form is preferable since it leads to improved water repellency of the resulting diffusion membrane (layer) and uniform dispersion. The calcined PTFE powder may be obtained by heating uncalcined PTFE powder at temperatures ranging from the melting point to below the decomposition temperature of PTFE, optionally with pressurization. Unlike the uncalcined PTFE, the calcined PTFE powder particles have fusion marks on their surfaces. The calcined PTFE powder particles are often fusion bonded with each other at at least part of their surfaces. The calcined and thereby fusion bonded PTFE generally has adequate spacings. The calcined PTFE powder will desirably range in mean particle diameter φ from 5 to 100 μm, and preferably from 10 to 50 μm. The calcined PTFE is superior in shear strength to the uncalcined PTFE. The fluoropolymer resin powder may be partially or completely replaced with a water repellent substance contributable to the water repellency, such as silicone rubber. When the uncalcined PTFE in the form of fibers and the calcined PTFE powder are used in combination (preferably in a ratio as described later), the resultant resin composition for diffusion layer can be easily sheeted into a diffusion membrane (layer) with excellent membrane producibility. Thus, the sheet diffusion membranes will have good mass producibility. Further, the resultant diffusion membrane (layer) displays excellent water repellency and has much more improved gas diffusibility and permeability as compared to when the PTFE consists of the uncalcined PTFE without addition of the calcined PTFE powder. The above PTFE combination is preferable also because the electrode having the diffusion layer has a smaller volume resistance (Ω·cm). Conductive Substance The conductive substance may have any form such as powder or fibers. Examples of the preferred conductive carbon substances include graphite powder, carbon black, expanded graphite powder, activated carbon powder and carbon fibers. These conductive substances may be used singly or in combination of two or more kinds. In the invention, graphite and carbon black are preferably used in combination as the conductive substances. This combined use is preferable because provided that the amount of the conductive substance is equal (unvaried), the volume resistance of the resulting diffusion membrane (layer) can be lowered. The graphite (plumbago or black lead) may be natural (natural plumbago) or artificial (artificial plumbago or artificial black lead). The graphite power will desirably have a mean particle diameter of 1 to 500 μm, preferably 5 to 200 μm, and more preferably 10 to 100 μm. While the graphite particle diameters are on the order of μm, the carbon black has extremely small particle diameters on the order of nm (about 1/1000 of the graphite powder). For example, its mean particle diameter p will desirably range from 1 to 500 nm, and preferably from 5 to 100 nm. The combined use of conductive substances different in mean particle diameters leads to higher gas permeability of the resultant diffusion membrane (layer) and also results in that the electrode having the diffusion layer can enable higher performance of fuel cells or other electrochemical devices. The diffusion membrane of the invention desirably contains: 1 to 30 wt %, preferably 10 to 20 wt % of the uncalcined PTFE, 5 to 30 wt %, preferably 10 to 20 wt % of the calcined PTFE, and 50 to 90 wt %, preferably 60 to 80 wt % of the conductive substance. When the conductive substance is a combination of the carbon black and graphite, the carbon black desirably accounts for 5 to 30 wt %, preferably 10 to 20 wt %, and the graphite desirably accounts for 70 to 95 wt %, preferably 80 to 90 wt % of the combined carbon black and graphite (100 wt %). When the aforesaid components have the above-specified amounts, the diffusion membrane (layer) and the gas diffusion electrode having the diffusion layer will display sufficient water repellency and superior gas diffusibility, gas permeability and conductivity. Particularly, the above quantitative relation between the uncalcined PTFE and calcined PTFE enables appropriate control of diffusion membrane producibility while maintaining adequate water repellency of the resultant diffusion membrane (layer). Consequently, continuous sheet production becomes possible and mass producibility of diffusion membranes may be enhanced, leading to reduction in product costs. The resin composition for the production of diffusion membranes (layers) (diffusion membrane (layer) resin composition) may contain a dispersion medium, a liquid lubricant and the like in addition to the aforesaid components. The dispersion media include water; aliphatic monohydric alcohols such as methanol and ethanol; and aliphatic polyhydric alcohols such as ethylene glycol, propylene glycol and glycerol. Suitable liquid lubricants include water; aliphatic monohydric alcohols such as methanol and ethanol; aliphatic polyhydric alcohols such as ethylene glycol, propylene glycol and glycerol; and white oils. They may be used singly or in combination of two or more kinds. The diffusion membrane (layer) resin composition may be prepared by combining the aforesaid components in arbitrary order, followed by stirring or mixing according to the conventional procedure. In an embodiment of the present invention, the diffusion membrane may contain the uncalcined PTFE fibers, calcined PTFE powder, graphite powder and carbon black. The diffusion membrane in this embodiment has a structure as illustrated in FIG. 1. The uncalcined PTFE fibers tangle with the graphite powder particles, etc. and consequently these are substantially all connected with each other. Further, the carbon black fine particles are filled around the uncalcined PTFE fibers and thereby the graphite powder and the carbon black powder are substantially electrically connected. Moreover, the calcined PTFE particles are filled in the spacings created among the other components to impart adequate water repellency to the sheet (membrane). The diffusion membrane contains the uncalcined PTFE, calcined PTFE and conductive substance in the identical amounts (ratios) to those in the diffusion layer resin composition. The above diffusion membrane may be produced by dispersing the uncalcined fluoropolymer resin (preferably uncalcined PTFE), the calcined fluoropolymer resin (preferably calcined PTFE) and the conductive substance in the dispersion medium, removing the dispersion medium, adding the liquid lubricant followed by kneading, compressing the resultant kneaded product (preferably a rod-shaped preform) to extend the same into a membrane, and removing the liquid lubricant. The rod-shaped preform prepared in the invention desirably contains the liquid lubricant in an amount of 5 to 70 wt %, preferably 10 to 65 wt %, and more preferably 30 to 65 wt % of the total weight thereof. These amounts of the liquid lubricant are preferable because the rod-shaped preform may be compressed as described later to give a uniform sheet diffusion membrane for electrode without any cracks or breakage. There are some possible methods to obtain the rod-shaped preform containing the liquid lubricant in the above amounts. One is to knead the conductive substance and the uncalcined and calcined fluorine-containing resins together with the liquid lubricant and shape the resultant kneaded product into such form by extrusion. It is also possible that the rod-shaped preform is produced with a smaller amount of the liquid lubricant than the desired level and is soaked in the liquid lubricant. The rod-shaped preform is preferably such that the composition of the components and the density are uniform at any area. Extrusion of the rod-shaped preform is preferably performed under conditions so that the residual internal stress will be small and the differences in density and liquid lubricant content in the longer direction of the rod-shaped preform will be minor. The rod-shaped preform produced in the invention preferably has a rod, or bar shape. Particularly, a long rod such as circular, rectangular or elliptic cylinder shape in which the cross section configuration perpendicular to the longer direction and the size thereof are constant, is preferable because of easiness in uniformly producing the sheet diffusion membrane for electrode. In the invention, the rod-shaped preform, preferably in the figuration as described above, is compressed to give a sheet diffusion membrane for electrode. In the compressing, the rod-shaped preform is desirably spread out not to a sheet (plate) of large thickness but directly to a sheet of desired thickness in one operation. The compressing may be accomplished by any known method and at any temperatures not higher than the boiling point of the liquid lubricant. Particularly, rolling at such temperatures, preferably from 20 to 200° C., more preferably from 20 to 100° C., and even more preferably from 20 to 90° C. is desirable because the liquid lubricant will not cause foaming and the sheet diffusion membrane for electrode and electrode sheet may be produced without cracks. The above compressing conditions are preferably fixed in order to produce uniform sheet diffusion membranes for electrode or electrode sheets as described later. In the case of rolling, the roll desirably has a uniform temperature distribution and a fixed temperature during the rolling. The compressing, in the case of rolling, is desirably performed at a high compression stress of 0.05 to 2 t/cm, preferably 0.1 to 2 t/cm. This high compression stress gives a sufficient strength to the sheet electrode. As a result of the rolling, the preform is desirably spread out to 5 to 1000 times, preferably about 10 to 200 times longer than the original length (rod strength: length in the longer direction of the rod-shaped preform). The compressing is followed by drying. The drying is carried out at temperatures capable of volatilizing the liquid lubricant used and lower than the decomposition temperature of the fluoropolymer resin such as PTFE. The drying temperature will range from 80 to 320° C., preferably from 150 to 300° C. depending on the drying time and the types of the fluoropolymer resins. The drying may be performed in an atmosphere of air or an inert gas. The long sheet of electrode diffusion membrane obtained as described above may be cut into the desired size and shape appropriate for the application as an electrode diffusion membrane. The electrode diffusion membrane should be in the form of sheet. Other conditions such as thickness, area and shape are not particularly limited and may be appropriately designed depending on the size and electric capacity of a fuel cell in which the electrode diffusion membrane is employed. The sheet diffusion membrane for electrode may be used in wide range of cells or batteries using carbon electrodes. It is particularly suitable for use as a diffusion membrane for polarized fuel cell electrodes. In the invention, the diffusion layer resin composition may be mixed with platinum-supported carbon as a catalyst layer component, whereby the gas diffusion layer and the catalyst layer may be integrated. Electrode The electrode according to the present invention has a layer made from the diffusion membrane and a catalyst layer disposed on the diffusion layer (membrane). (For example, the electrode possesses the diffusion layer (membrane) comprising the uncalcined PTFE, calcined PTFE and conductive substance (preferably carbon black and graphite), and a catalyst layer provided on the diffusion layer (membrane)). The catalyst layer essentially consists of carbon black on which a catalyst such as platinum or platinum-ruthenium alloy is supported for promoting the electrode reaction. Such electrodes may be prepared by the conventional methods, including those disclosed in JP-B-S63-19979, JP-B-H01-12838 and JP-B-H05-52031. The above description illustrates embodiments of the diffusion membrane, electrode and production process for diffusion membranes in which the fluoropolymer resins are the uncalcined PTFE and calcined PTFE. However, the present invention may be suitably carried out using other uncalcined and calcined fluoropolymer resins in place of the uncalcined PTFE and calcined PTFE. Such alternative fluoropolymer resins include modified PTFE, PVdF, ETFE, PCTFE, FEP and PFA. Effects of the Invention The invention enables reduction in material costs in the production of diffusion membranes and electrodes having the diffusion layers. This is achieved by replacement of the expensive porous carbon fiber membrane or porous carbon paper with a combination of low cost conductive substances of graphite and carbon black and also due to a combined use of uncalcined PTFE and calcined PTFE as the fluoropolymer resins. Further, the combined use of the uncalcined PTFE and calcined PTFE permits appropriate control of diffusion membrane producibility from the resin composition for diffusion layer while maintaining adequate water repellency of the resultant diffusion membrane (layer). Consequently, a sheet having sufficient water repellency and no local variation in properties such as electric properties may be produced continuously to improve mass producibility of the sheet diffusion membranes, also leading to reduction in production costs of diffusion membranes and electrodes. The electrode according to the invention includes the layer made from the diffusion membrane and the catalyst layer disposed thereon and has the above-described excellent properties. Since the diffusion layer is made of other than the expensive porous carbon fiber membrane and porous carbon paper, the electrode of the invention can be inexpensively mass produced with efficiency. The production process for diffusion membranes of the invention can effectively produce diffusion membranes having the above properties. EXAMPLES Hereinbelow, the present invention will be described in greater detail by the following Examples. However, it should be construed that the invention is in no way limited to the Examples. Examples 1-4 and Comparative Examples 1-2 Graphite of 35 μm mean particle diameter, carbon black of 50 nm mean particle diameter, uncalcined polytetrafluoroethylene (PTFE) of 0.2 μm mean particle diameter and calcined PTFE of 20 μm mean particle diameter were dispersed and mixed in water in amounts (wt %) shown in Table 1. The mixtures were each dried and combined with 40 wt % (based on the dried mixture) of an alcohol as a liquid lubricant, followed by kneading. The kneaded products were each expanded by a rolling machine at a roll temperature of 80° C. and a pressure of 440 kg/cm2 to give a sheet of 0.40 mm thickness, 150 mm width and 1 m length. The sheets were each dried in air at 150° C. for 30 minutes to yield a sheet diffusion membrane. The sheet diffusion membranes of Examples 1-4 and Comparative Examples 1-2 were tested to determine their volume resistances. The results are set forth in Table 1. TABLE 1 Carbon Calcined Uncalcined Volume Graphite black PTFE PTFE resistance (wt %) (wt %) (wt %) (wt %) (Ω · cm) Ex. 1 70 — 20 10 1.565 Ex. 2 70 — 10 20 2.447 Comp. 70 — 0 30 6.771 Ex. 1 Ex. 3 50 20 20 10 0.655 Ex. 4 50 20 10 20 0.880 Comp. 50 20 0 30 0.919 Ex. 2 The volume resistance was measured by the four-point probe method.

<SOH> BACKGROUND OF THE INVENTION <EOH>Fuel cells have many types such as phosphoric acid fuel cells, molten carbonate fuel cells, solid electrolyte fuel cells, solid polymer electrolyte fuel cells and alkaline fuel cells. Particularly, the ion-exchange membrane fuel cells (solid polymer electrolyte fuel cells) are of great interest recently because they operate at a high current density of 3 to 6 A/cm 2 . The ion-exchange membrane fuel cells have a polymer ion-exchange membrane comprised of a fluororesin with a sulfonic group (—SO 3 H) in a side chain. The membrane is disposed between an anode electrode (fuel electrode) and a cathode electrode (air electrode) to form an assembly. Outside the assembly major surfaces are provided current collectors that also function as flow channels for the fuel (H 2 ) and oxidizer (air). The electrodes are composed of carbon on which a catalyst such as platinum or platinum-ruthenium alloy is supported for promoting the electrode reactions. The electrode reactions at the anode and the cathode are shown as follows: Anode reaction: H 2 →2H + +2e − Cathode reaction: 1/20 2 +2H + +2e − →H 2 O The hydrogen ions (H + ) move from the anode to the cathode through the ion-exchange groups in the membrane with water molecule. The electrode reactions take place at the three-phase (liquid/gas/solid) interface among the electrolytic solution (liquid), air (gas) and catalyst layer (solid). The three-phase (liquid/gas/solid) interface must be adequately formed to prevent the electrode reaction rates from being controlled by the gas diffusion. Therefore, the electrodes are made porous and coated with water-repellent polytetrafluoroethylene (PTFE) resin. Combination of a diffusion layer and a catalyst layer is called a gas diffusion electrode. Its function is to bring the fuel (H 2 ) and gas (oxygen O 2 ) into even contact with the catalyst layer such as of platinum. The gas diffusion electrodes (particularly the diffusion layers) have another function of transmitting the electrons created at the catalyst layers, and therefore are required to have conductivity. Furthermore, the diffusion layers have a function of distributing the gas to the catalyst layer, and therefore include a great number of pores. For the need of ensuring the ion conductivity of the ion-exchange membrane and of hydration, humidified fuel (H 2 ) is fed. The gas diffusion electrodes have water repellency to prevent the moisture for ion conductivity from clogging the pores in the diffusion layers to block the gas diffusion. As described above, the gas diffusion electrodes for use in the fuel cells and other electrochemical devices are required to have gas diffusibility, gas permeability, water repellency and conductivity. The diffusion membranes (layers) are generally produced by coating an electrode material such as a porous carbon fiber membrane or porous carbon paper with a dispersion mixture that contains carbon powder, polytetrafluoroethylene (PTFE) and a dispersion medium, by means of spraying or printing technique. In such conventional processes, the coating of the porous carbon fiber membrane or porous carbon paper with a dispersion mixture that contains uncalcined polytetrafluoroethylene, conductive carbon and a dispersion medium is followed by repetitive rolling. This requires complex and multiple steps and increases the processing cost. Moreover, the above process is complicated and has great difficulty in controlling the application of the dispersion mixture so as to achieve uniform properties throughout the resultant diffusion layer. It is also insufficient in terms of mass production capability for the diffusion membranes (layers). Furthermore, the porous carbon fiber membranes or porous carbon papers are expensive to cause cost problems. To solve such problems, JP-A-2001-85280 (patent publication (i)) owned by the present applicant proposes a production process for polytetrafluoroethylene-containing sheet electrodes and a sheet electrode obtained by the process. This process comprises rolling a rod-shaped preform into a sheet electrode, wherein the preform comprises carbon fine powder, polytetrafluoroethylene and a liquid lubricant and has a specific relation with respect to the maximum length in the compression direction and that in a crosswise direction perpendicular to the compression direction. The above process is capable of manufacturing uniform sheet electrodes through a simple step and enables cost reduction and mass production. However, the method of JP-A-2001-85280 (patent publication (i)) using the conventional raw materials, namely, uncalcined polytetrafluoroethylene and conductive carbon results in a diffusion membrane (layer) which has unfavorably high volume resistance and insufficient electron conductivity and gas permeability. This can be rationalized by the excessive binding effect of the uncalcined polytetrafluoroethylene whose intended purpose is to impart water repellency. Furthermore, the method has difficult membrane production and is unsuitable for continuous mass production of membranes. Under these circumstances, the present inventors earnestly carried out studies of a low cost process for mass production of diffusion membranes that have sufficient water repellency and no regional variation in properties. As a result, they have found that a resin composition containing uncalcined polytetrafluoroethylene, calcined polytetrafluoroethylene and a conductive substance can solve all the aforesaid problems by its capability of giving diffusion layers that have adequate water repellency and no local variation in properties, at reduced cost and with mass producibility. The present invention has been accomplished based on this finding. JP-A-S52-97133 (patent publication (ii)) discloses a gas diffusion electrode including a sheet of a carbon material that contains a specific amount of carbon fibrils held together with a fluororesin, wherein the fibril lengths and diameters have a specific ratio. It also discloses a production process for gas diffusion electrodes comprising kneading and rolling the carbon material, the fluororesin and an auxiliary into a sheet and bonding the sheet with a catalyst layer mainly composed of an electrode catalyst and a binder, wherein the auxiliary is removed before or after the catalyst layer is bonded. The gas diffusion electrode as described in the above patent publication is relatively thin and satisfactory in mechanical strength as mentioned also in JP-B-S63-19979 (patent publication (iv)), but the gas permeability thereof is insufficient. JP-A-S58-165254 (patent publication (iii)) discloses a process for producing fuel-cell gas diffusion electrodes that comprises forced filling of carbon powder, a catalyst and ethylene tetrachloride resin into pores of a porous fiber membrane by means of suction force from below one side of the membrane. JP-B-S63-19979 (patent publication (iv)) discloses a gas diffusion electrode material that is a fine porous network structure. This material comprises a number of polytetrafluoroethylene resin minute nodes containing conductive substance powder and a number of polytetrafluoroethylene resin fibrils containing no conductive substance powder that extend from each node to form three-dimensionally linked nodes, wherein all the minute nodes contact with each other or are in series at parts thereof. JP-B-H01-12838 (patent publication (v)) discloses a gas and liquid permeable electrode material resulting from the bonding of a liquid permeable membrane that contains conductive substance powder in minute nodes and a conductive porous substrate of specific flexural strength. The liquid permeable membrane is a porous polytetrafluoroethylene resin membrane that has a number of minute nodes dimensionally linked through many fibrils with formation of a spiderweb network among the minute nodes. The minute nodes contact with each other or are in series at parts thereof. JP-B-H05-52031 (patent publication (vi)) discloses a gas diffusion electrode material comprising: a plurality of conductive powder-containing layers that are constituted of a number of polytetrafluoroethylene resin minute nodes containing conductive substance powder and substantially connected with each other, and a number of polytetrafluoroethylene resin fibrils that extend from each node and tridimensionally link the nodes; and a layer that is disposed between the plurality of layers and is constituted of a number of polytetrafluoroethylene resin minute nodes containing no conductive powder and a number of polytetrafluoroethylene resin fibrils extending from each node to tridimensionally link the nodes. These layers are directly engaged by pressure whereby the conductive powder-containing minute nodes are pressed and dispersed into among the fibrils that link the minute nodes containing no conductive substance powder. Consequently, electric conduction is achieved as a result of partial contact between the conductive powder-containing minute nodes or by the jumping effect. However, these patent publications (ii) to (vi) provide gas diffusion electrode materials that are unsatisfactory in any of gas permeability, water repellency, mass producibility, production costs, conductivity and uniformity. The present invention aims to solve the aforesaid problems related to the background art. It is an object of the invention to provide a low cost diffusion membrane that employs neither the expensive porous carbon fiber membrane nor porous carbon paper and has sufficient water repellency, uniform properties throughout the layer and suitable mass producibility. It is another object of the invention to provide an electrode having a diffusion membrane (layer) with the above properties. It is a further object of the invention to provide an efficient and low cost process for producing diffusion membranes having the above properties.

<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>FIG. 1 is a schematic view illustrating a contact condition of uncalcined PTFE fibers, carbon black, graphite powder and calcined PTFE powder in a diffusion membrane (sheet) according to the present invention. detailed-description description="Detailed Description" end="lead"?

20040616

20080205

20050811

60501.0

WALLS, CYNTHIA KYUNG SOO

DIFFUSION FILM, ELECTRODE HAVING THE DIFFUSION FILM, AND PROCESS FOR PRODUCING DIFFUSION FILM

UNDISCOUNTED

ACCEPTED

ACCEPTED

Clamping assembly and a hydraulic coupler comprising it

The invention relates to a clamping assembly for a coupler, which comprises at least one clamping module (11) having a clamping jaw (12) designed for connecting a coupler (10) to a complementary means (13), and an actuating system (14) proper to the said jaw and comprising a device of the screw/nut type (15) driven by a motor (16), and is characterized in that the actuating system (14) is connected directly to the jaw and the said jaw (12) is swivel-mounted on a support (25) about a fixed point (26) defined by the said support, the latter being intended to be fixed to the coupler. The invention also relates to a coupler comprising the said clamping assembly.

1. A coupler which is adapted to be coupled to a complementary means for the transfer of a fluid from the coupler to the complementary means, the coupler comprising: a body for the passage of the fluid; a plurality of clamping modules which are positioned around the body; each clamping module comprising a clamping jaw which is designed for coupling the coupler to the complementary means, and an actuating system which is connected to said jaw; each actuating system comprising a device of the screw/nut type and a motor for driving said device; wherein each jaw and the actuating system associated therewith are each swivel-mounted on a support which is fixed to the body about a fixed first pivotal axis defined by the support; and wherein said jaw and the device of the screw/nut type associated therewith are directly pivotally articulated to each other about a second pivotal axis situated at a fixed distance from the first pivotal axis. 2. A coupler according to claim 1, characterized in that the device of the screw/nut type comprises a screw which engages a bush-nut and is driven by the motor by means of a chain. 3. A coupler according to claim 1, characterized in that it comprises three or more clamping modules. 4. A coupler according to claim 1, characterized in that the support comprises a horizontal section defining the fixed pivotal axis of the jaw and a vertical section defining the fixed pivotal axis of the actuating system. 5. A coupler according to claim 1 4, characterized in that it consists of a hydraulic coupler and the motor is also a hydraulic motor. 6. A coupler according to claim 1 further comprising: a hydraulic unit (50) which is fluidly connected to each motor and which includes a fluid distribution circuit and a controlling means for controlling the supply of fluid to the motors in order to cause swiveling of the jaws associated with the motors; wherein the controlling means controls the supply of fluid to the motors according to a series arrangement for as long as the jaws do not exert any clamping force on the complementary means and according to a parallel arrangement when the jaws exert a clamping force on the complementary means. 7. A coupler according to claim 6, characterized in that the controlling means control the supply of fluid to the motors according to a parallel arrangement in order to overcome the clamping force applied by the jaws to the complementary means during unclamping of the jaws. 8. A coupler according to claim 6, characterized in that the controlling means are sensitive to the pressure increase in the hydraulic unit resulting from the clamping force applied by the jaws to the complementary means, and are able to generate the transition from the series arrangement to the parallel arrangement when the pressure reaches a predetermined value. 9. A coupler according to claim 6, characterized in that the controlling means comprise a slide valve which includes a return spring and a pressure limiter which includes a return spring and which is installed upstream of the slide valve in the fluid distribution circuit. 10. A coupler according to claim 9, characterized in that the hydraulic unit comprises a selector which is arranged in the fluid distribution circuit so as to provide fluid connection between the inlet of the first of the motors, and the pressure limiter, wherein the fluid distribution circuit supplies the motors in two opposite directions depending on whether the connector is acting in clamping or unclamping mode. 11. A coupler according to claim 6, characterized in that the hydraulic unit has a fluid connection to a central unit for supply of oil constituting the said fluid. 12. A coupler according to claim 1 further comprising: sealing means adapted to ensure fluid-tightness of the connection of the coupler to the complementary means; means for protecting the sealing means; the protecting means being movable between a first position before connection, in which the protecting means project beyond the sealing means in the direction of connection, and a second position after connection, in which the protecting means are no longer projecting relative to the sealing means; and damping means which permanently urge the protecting means towards their first position. 13. A coupler according to claim 12, further comprising retaining means for preventing the protecting means from going beyond the first position in the direction of connection. 14. A coupler according to claim 12, characterized in that the sealing means comprise at least one ring seal and the protecting means comprise a movable ring that encircles the seal. 15. A coupler according to claim 12, characterized in that the sealing means comprise at least one ring seal and the protecting means comprise a plurality of thrusters surrounding the seal. 16. A coupler according to claim 14, characterized in that the damping means comprises one selected from the group consisting of a spring washer, helical springs, spring washers, gas spring jacks or hydraulic dampers, which are interposed between the protecting means and the body of the coupler.

The present invention relates in a general way to couplers. As is well known, a coupler is a mechanical assembly comprising clamping modules, intended in particular for applying a preclamping force so as to provide mechanical linkage and fluid-tightness between an articulated product loading and unloading arms, in particular for fluid products, for example petroleum products (liquefied natural gas etc.), and a complementary means installed on a ship. The present invention relates more particularly to the case when the coupler is a hydraulic coupler with several clamping modules, in practice three or more, capable of conveying liquid products at very low temperatures (down to −196° C.). According to a known arrangement, each clamping module comprises a clamping jaw designed for connecting the coupler to a complementary means, such as a manifold, and an actuating system proper to the said jaw and comprising a device of the screw/nut type driven by a motor. The jaw is carried by a system of rods articulated at one of its ends, on a support, the actuating system acting upon the system of rods in order to impel the jaw towards a clamping position or to bring it back to a resting position. However, in devices of this type that are already known, the forces transmitted by the rods depend on the thickness of the manifold flange at the clamping location which, in practice, varies from one location to another on the flange. As a result the clamping is often insufficient or excessive. The present invention relates, in a general way, to an arrangement that makes it possible to provide, more simply and more reliably, clamping effected by means of the said clamping modules and leading in addition to other advantages. More precisely, it relates to a clamping assembly for a coupler, comprising at least one clamping module having a clamping jaw designed for connecting the coupler to a complementary means, and an actuating system proper to the said jaw and comprising a device of the screw/nut type driven by a motor, characterized in that the actuating system is connected directly to the jaw and the said jaw is mounted on a support in such a way that it can swivel about a fixed point defined by the said support, the latter being intended to be fixed to the coupler. In other words, the actuating system acts directly upon the clamping jaw. Having eliminated an intermediary (the rods), it becomes possible to obtain much greater clamping forces than previously, with a system that is simpler and more reliable than the known systems. Moreover, with the clamping assembly according to the invention, the coupler can be used in more situations. According to preferred characteristics relating to this arrangement: the device of the screw/nut type is articulated on the jaw at a second point located a fixed distance from the said fixed point; and/or the device of the screw/nut type comprises a screw that engages in a bush with an internal thread and is driven by the motor by means of a chain; and/or the coupler is a hydraulic coupler and the motor is a hydraulic motor; and/or the actuating system is carried by the support. Furthermore, the arrangement according to the invention lends itself advantageously to a development that is original per se, according to which the assembly comprises several clamping modules whose motors have a fluid connection to a hydraulic unit comprising a fluid distribution circuit and control means designed for controlling the supply of fluid to the motors by the hydraulic unit, so as to cause the jaws associated with the motors to swivel, according to a serial arrangement of the motors so long as the jaws do not exert any clamping force on the complementary means and according to a parallel arrangement of the motors when the said jaws exert a clamping force. This development gives a high speed of manoeuvre (serial arrangement of the motors), as well as a large clamping force at the appropriate time (parallel arrangement of the motors). According to preferred characteristics relating to this development: the controlling means are, in addition, able to control supply to the motors according to a parallel arrangement so as to overcome the clamping force applied by the jaws to the complementary means, during unclamping of the jaws; and/or the controlling means are sensitive to the increase in pressure in the hydraulic unit, resulting from the clamping force applied by the jaws to the complementary means, and are able to generate the transition from a serial arrangement of the motors to a parallel arrangement of them when the pressure reaches a predetermined value; and/or the controlling means comprise a slide valve provided with a return spring and a pressure limiter with a return spring, installed upstream of the slide valve in the fluid distribution circuit and with fluid connection to the said slide valve; and/or the hydraulic unit comprises a selector installed in the circuit so as to provide fluid connection between the inlet of the first of the motors in the direction of feed of the latter and the pressure limiter, the fluid distribution circuit supplying the motors according to two opposite directions depending on whether it is operating in clamping or unclamping; and/or the fluid distribution circuit comprises a main unit for supply of oil constituting the said fluid. The arrangement according to the invention also lends itself to another development that is original per se, and can be combined advantageously with the preceding one, and according to which the coupler comprises sealing means that are intended to ensure fluid-tightness of the connection of the coupler to the complementary means, means for protecting the sealing means, movable between a first position before connection, in which the said protecting means go beyond the sealing means in the direction of connection, and a second position after connection, in which the said protecting means are no longer projecting relative to the sealing means, and damping means that permanently exert a force on the protecting means impelling them towards their first position. With this development there is maximum limitation of the risks connected with relative movements and impacts at the time of connection. According to preferred characteristics relating to this development: the coupler comprises means that hold back the protecting means, preventing the said protecting means from going beyond the first position in the direction of connection; and/or the sealing means comprise at least one ring seal and the protecting means comprise a movable ring that surrounds the seal or seals; and/or the sealing means comprise at least one ring seal and the protecting means comprise several thrusters encircling the seal or seals; and/or the damping means consist of a single spring washer, helical springs, spring washers, gas spring jacks or hydraulic dampers interposed between the protecting means and the body of the coupler. The invention also relates to a hydraulic coupler, comprising a clamping assembly as defined above and fixed to the body of the said coupler. The characteristics and advantages of the invention will become clearer from the description that is to follow, by way of an example, referring to the appended schematic drawings, where: FIG. 1 is a side view with partial section of a hydraulic coupler equipped with a clamping assembly according to the invention and a complementary means, in the non-connected position; FIG. 2 is a view similar to FIG. 1, and shows the connected position of the hydraulic coupler and of the complementary means; FIG. 3, on a larger scale, is a top view with partial section of the clamping module in FIG. 2; FIG. 4 is a view in longitudinal section of the top half of the front part of the coupler in FIGS. 1 and 2 and illustrates the protecting means of the sealing means of the said coupler; and FIGS. 5 to 10 are schematic diagrams of the hydraulic unit supplying the motors of the clamping modules according to the invention, and illustrate the various stages in operation of this unit. In the embodiment shown, the hydraulic coupler 10 according to the invention comprises a clamping module 11 having a clamping jaw 12 designed for connecting the coupler 10 to a complementary means 13, and an actuating system 14 proper to the said jaw and comprising a device of the screw/nut type 15 driven by a motor 16. In practice, the clamping modules are three in number, fixed to the periphery of hydraulic coupler 10 and distributed uniformly around the latter and constituting a clamping assembly by which coupler 10 can be connected to the complementary means 13. The said complementary means 13 is, here, a manifold, which can be replaced with a closing cover when the loading arm equipped with coupler 10 is to be put in the storage position. As the actuating system 14 is well-known, it will not be described in detail here. It will simply be pointed out that in the embodiment illustrated (see FIG. 3), the device of the screw/nut type 15 comprises a screw 17 that engages in a bush with an internal thread 18 and is driven by the motor 16 by means of a chain 19 transmitting the rotary motion of motor 16 to screw 17 by means of a driving sprocket 20 rigidly locked with the output shaft of motor 16 and a driven sprocket 21 integral with a piece of shaft 22 that is an extension of screw 17. The latter is housed in a cylindrical casing 23, to which a housing 24 is fixed, for housing the chain 19 and sprockets 20 and 21, the motor 16 being fixed to the said housing 24. Furthermore, the bush with internal thread 18 is slidably guided in the cylindrical casing 23. According to the invention, each jaw 12 has a swivel mounting on a support 25 about a fixed point 26 defined by the said support 25, the latter being fixed to the hydraulic coupler 10, in the present case by welding. The device of the screw/nut type 15 is also articulated on jaw 12 at a second point 27 located a fixed distance from point 26, by means of a cylindrical component 28 fixed to one end of the bush with internal thread 18, intended to receive a spindle (not shown in FIG. 3). The actuating system 14 in its turn has a swivel mounting on support 25, by means of spindle-receiving disks 29 fixed on the cylindrical casing 23. It should also be pointed out that support 25 is formed by two plates 30 that are symmetrical relative to a longitudinal median plane intersecting at right angles the swivelling axes of clamping module 11, which receive between them the actuating system 14 as well as the jaw 12 which is, in its turn, formed by two plates 31 that are symmetrical relative to the said plane. More precisely, each plate 30 of support 25 comprises a vertical section 32 (see FIGS. 1 and 2), on which the actuating system 14 is swivel-mounted, and a horizontal section 33 defining the fixed point 26. Each horizontal section 34 is reinforced, in the region of the fixed point 26, by an outer plate 34 welded onto the adjacent plate 30. Each plate 31 of jaw 12 comprises, according to a general configuration as right-angled triangle, two holes through which spindles pass, one for the spindle housed in cylindrical component 28 and defining the swivel point 27 and the other for the journal 35 defining the fixed swivel point 26. Holes aligned with the aforementioned holes are of course also provided in the support plates 25. A clamp 36 carrying a sliding block 37 is fixed to jaw 12. It, too, is formed from two plates 38 that are symmetrical relative to the aforesaid plane, each being fixed to one of the plates 31 forming jaw 12. It should be pointed out, in this connection, that these plates 38 extend along the side of the substantially triangular plates 31 closest to the hydraulic coupler 10 and they also have a hole through which journal 35 passes. Furthermore, it should also be noted that the sliding block makes it possible to connect the hydraulic coupler 10 to several different diameters of flanges 39 of manifold 13. In practice, and such is the case in the embodiment shown here, these diameters are generally three in number. Thus, the jaw 12 is pivotably mounted on the support 25 about a low fixed point 26 (proximal point with respect to the coupler 10) defined by the support 25, the device of screw/nut type 15 is articulated directly on the jaw 12 at a high point 27 (distal point with respect to the coupler 10) defined by the jaw 12 and situated at a fixed distance from the low fixed point 26 and the actuating system 14 is itself articulated on the support 25 in the vicinity of the high point 27. It will also be noted that the clamp 36 of the jaw 12 forms a projection roughly with respect to a third point defined by the jaw 12 and forming a triangle with the low and high points. Furthermore, the extension of each jaw 12 and of the device 15 of screw/nut type which is associated with it is in the same general direction as that of the body, here cylindrical, of the coupler 10. Moreover, hydraulic coupler 10 is equipped with a system that protects its seals, as can best be seen in FIG. 4. In the embodiment shown, the said hydraulic coupler 10 comprises a protecting ring 40 that is movable relative to its annular front face 41 and positioned around its ring seals 42 and 43 housed in grooves. Compression springs, only one of which is visible in FIG. 4, bearing the reference sign 44, are placed between this ring 40 and the body 45 of coupler 10 and act in the axial direction, permanently holding the ring 40 and the body 45 of coupler 10 apart. In practice, the ring has a groove 46 forming a seat for one of the ends of these springs 44, whereas the body 45 of coupler 10 has an opposite face 47 that is recessed relative to the front face 41 and forms a seat for the opposite end of the said springs 44. When coupler 10 is in the closed position (see FIG. 2) on a flange 39 of manifold 13, the springs 44 are compressed and flange 39 is in contact with seals 42 and 43 and a front face 48 of ring 40 located on the side of the latter opposite to that with the groove 46. When coupler 10 is in the open position (see FIG. 1), ring 40 abuts against the centring guides 49 of coupler 10, just one of which is visible in FIG. 4. In this position, the springs 44 are pre-compressed and not completely released. When coupler 10 is brought closer to flange 39, the seals 42 and 43 are recessed relative to the face 48 of ring 40 and so are protected from any impacts due to flange 39 to be connected. The energy of these impacts is absorbed by the work of compression of springs 44. Then, during closing of the jaws 12 of coupler 10, springs 44 are compressed by the clamping force exerted by the clamping modules 11. It will be appreciated, in this connection, that the reactive force of ring 40 on flange 39, created by springs 44, makes it possible to eliminate any relative radial movements that could, without this protecting system, cause deterioration of seals 42 and 43 by friction. In the closed position, the supporting force of seals 42 and 43 is equal to the clamping force of jaws 12 minus the force of compression of springs 44. In practice, therefore, the clamping force of jaws 12 must be chosen in such a way that it is much greater than the force of compression of springs 44. Moreover, various types of damping springs can be used: a single spring washer with the same diameter as the groove of ring 40, one or a number of helical springs, one or a number of spring washers, gas spring jacks or hydraulic dampers. According to a variant of this protecting system, ring 40 can be replaced with thrusters positioned around seals 42 and 43 and connected to the damping means defined above. Other solutions for abutment can also be used, such as pins fixed to the body 45 and equipped with a head retaining ring 40. For supplying oil to the hydraulic motors 16 of the clamping modules 11, a hydraulic unit with a fluid distribution circuit is also provided, as is best seen in FIGS. 5 to 10. The said hydraulic unit 50 comprises, according to the invention, a slide valve 51 provided with a return spring and a pressure limiter 52 with a return spring, installed upstream of valve 51 in the distribution circuit and with fluid connection to the said valve 51. The hydraulic unit 50 also has a selector 54 arranged in the fluid distribution circuit to provide fluid connection between the inlet of the first of the motors 161-163, in their direction of supply, and pressure limiter 52. Depending on whether the unit is acting for clamping or unclamping of jaws 12, the first motor is motor 161 or 163. The said hydraulic unit 50 is in addition supplied with oil by a central unit 55 comprising a distributor 56 and two non-return valves with controllable throttling 57, connected respectively to a closing line and an opening line connecting the central unit 55 to hydraulic unit 50. As can be seen in FIGS. 5 to 10, the fluid distribution circuit of hydraulic unit 50 is designed for supplying all the motors 161-163 with the oil flow and pressure that they require, and at any time. According to the invention, for this purpose the hydraulic unit 50 operates according to the series/parallel principle. More precisely, during the stages of approach for closing, the clamping modules 11 with jaws 121-123 manoeuvre rapidly. For this, the hydraulic unit operates in series (low pressure and high flow rate). For clamping onto a flange 39, the unit operates in parallel (high pressure and low flow rate). When coupler 10 is clamped on a flange 39, for unclamping it the hydraulic unit 50 has to supply a lot of pressure to each of the motors 161-163: therefore it operates in parallel. As soon as all of the clamping modules 11 are unclamped, hydraulic unit 50 changes to series operation to give quick opening. Series/parallel changeover of hydraulic unit 50 occurs in relation to the forces transmitted and to be transmitted to the clamping modules 11. It is the slide valve inside hydraulic unit 50 that permits changeover either to series operation or to parallel operation. The position of this slide valve depends on the forces transmitted by the clamping modules 11. When there is no force acting on the clamping modules 11, hydraulic unit 50 puts itself in the series position. As soon as a clamping module 11 forces or presses against something (flange, stop etc.), the supply pressure of the series circuit increases and moves the slide valve towards its position for supplying motors 161-163 in parallel, so as to deliver the maximum available pressure to each of these motors. Modules 11 then have a low speed but a high transmissible force. Conversely, when there is no longer any force on any one of the clamping modules 11, the internal pressure of hydraulic unit 50 decreases and thus allows the slide valve to move to its series position. The operation of hydraulic unit 50 will now be described in greater detail, referring to FIGS. 5 to 10. FIG. 5: (Coupler 10 in the Open Position) No movement is “demanded” from coupler 10. There is no circulation of oil in the hydraulic circuit. In this state (rest), the hydraulic unit is systematically in the series position. The slide valve of unit 50 is pushed towards the left by its return spring. FIG. 6: (Coupler 10 in Course of Closing) During this approach phase, no force of resistance is received by the clamping modules 11. Hydraulic unit 50 therefore operates in series, so that there is rapid movement of modules 11. The oil leaving motor 16, goes into motor 162 after briefly passing through hydraulic unit 50, then leaves it again and enters the unit and then motor 163, before returning to the central unit 55. FIG. 7: (Coupler 10 in the Clamping Phase) During the clamping phase, a resistance appears at the jaws 121-123, giving rise to an increase in the hydraulic pressure of the circuit. The pressure will therefore push the valve slide in hydraulic unit 50 towards the right in the diagrams. At that moment, unit 50 will therefore change over to the parallel position, which means that each motor 161-163 will be supplied directly by the central unit 55 and not by the preceding motor. The flow will therefore be divided as a function of the number of motors. On the other hand the pressure will increase. At the outlet of each motor 161-163, the oil returns directly to the central unit 55. FIG. 8: (Coupler 10 Closed) Once coupler 10 is closed, oil circulation stops. The slide valve in unit 50 therefore goes back to the series position (displaced towards the left in the diagrams), under the action of its return spring. FIG. 9: (Unclamping of Coupler 10) At the moment of opening, it is necessary to overcome the forces due to clamping. These forces have the effect of raising the pressure within the hydraulic circuit, and therefore of causing unit 50 to change to the parallel position (the pressure displaces the valve slide of unit 50 towards the right in the diagrams). Each jaw 121-123 therefore has a high oil pressure at its disposal, which enables them to be unclamped. FIG. 10: (Opening of Coupler 10) Once coupler 10 is unclamped, there is no longer any force to be overcome. The internal pressure of the hydraulic circuit decreases, causing the valve slide in unit 50 to move towards the left in the diagrams. During this opening phase, unit 50 is in the series position, permitting rapid movement of jaws 121-123. In practice, it may be noted, as a non-limiting example, that for a maximum outlet pressure of central unit 55 of about 150.105 Pa, the pressure value causing the slide to move from a position in series to a position in parallel is about 80-90.105 Pa. In the embodiment shown in FIGS. 5 to 9, movement of the slide from a series position to a parallel position depends on whether the pressure limiter is in the open or closed position, these positions depending in their turn on the return spring chosen for the said limiter 52. However, in other embodiments it would be possible for the slide valve 51 to be designed so that it changes from one position to the other by an appropriate choice of return spring for it. In this case it will not be necessary to employ a pressure limiter 52. It would also be possible, in another embodiment, to employ detectors of the position of the jaws or of the pressure at motors 161-163 and electric control of slide valve 51. The actuating system 14 may also be borne by a support different to that on which is mounted the jaw 12 associated with it. The support or supports may, moreover, also be formed integrally with the coupler. Of course, the present invention is not limited to the embodiment that has been described and illustrated, but encompasses all variants of execution.

20040618

20100420

20050609

68507.0

BOCHNA, DAVID

CLAMPING ASSEMBLY AND A HYDRAULIC COUPLER COMPRISING IT

UNDISCOUNTED

ACCEPTED

ACCEPTED

Substituted quinazoline derivatives as inhibitors of aurora kinases

The invention provides quinazoline derivatives of formula (I): in the preparation of a medicament for use in the inhibition of Aurora kinase and also novel quinazoline derivatives, processes for their preparation, pharamceutical compositions containing them and their use in therapy.

1. Use of a compound of formula (I): or a salt, ester or amide thereof; where: X is O or S, S(O) or S(O)2, or NR6 where R6 is hydrogen or C1-6alkyl; R5 is a group of formula (a) or (b): where * indicates the point of attachment to the group X in formula (I); R1, R2, R3, R4 are independently selected from hydrogen, halo, cyano, nitro, trifluoromethyl, C1-3alkyl, —NR7R8 or —X1R9; R7 and R8 are independently hydrogen or C1-3alkyl; X1 is a direct bond, —O—, —CH2—, —OCO—, carbonyl, —S—, —SO—, —SO2—, —NR10CO—, —CONR11—, —SO2NR12—, —NR13SO2— or —NR14—; R10, R11, R12, R13 and R14 are independently hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl; R9 is selected from one of the following groups: 1) hydrogen or C1-5alkyl which may be unsubstituted or which may be substituted with one or more groups selected from hydroxy, fluoro or amino; 2) C1-5alkylX2COR15 (wherein X2 represents —O— or —NR16— (in which R15 represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R16 represents C1-3alkyl, —NR17R18 or —OR19 (wherein R17, R18 and R19 which may be the same or different each represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl)); 3) C1-5alkylX3R20 (wherein X3 represents —O—, —S—, —SO—, —SO2—, —OCO—, —NR21CO—, —CONR22—, —SO2NR23—, —NR24SO2— or —NR25— (wherein R21, R22, R23, R24 and R25 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R20 represents hydrogen, C1-3alkyl, cyclopentyl, cyclohexyl or a 5- or 6-membered saturated heterocyclic group with 1 or 2 heteroatoms, selected independently from O, S and N, which C1-3alkyl group may bear 1 or 2 substituents selected from oxo, hydroxy, halo and C1-4alkoxy and which cyclic group may bear 1 or 2 substituents selected from oxo, hydroxy, halo, C1-4alkyl, C1-4hydroxyalkyl and C1-4alkoxy); 4) C1-5alkylX4C1-5alkylX5R26 (wherein X4 and X5 which may be the same or different are each —O—, —S—, —SO—, —SO2—, —NR27CO—, —CONR28—, —SO2NR29—, —NR30SO2— or —NR31— (wherein R27, R28, R29, R30 and R31 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R26 represents hydrogen or C1-3alkyl); 5) R32 (wherein R32 is a 5- or 6-membered saturated heterocyclic group (linked via carbon or nitrogen) with 1 or 2 heteroatoms, selected independently from O, S and N, which heterocyclic group may bear 1 or 2 substituents selected from oxo, hydroxy, halo, C1-4alkyl, C1-4hydroxyalkyl, C1-4alkoxy, C1-4alkoxyC1-4alkyl and C1-4alkylsulphonylC1-4alkyl); 6) C1-5alkylR32 (wherein R32 is as defined hereinbefore); 7) C2-5alkenylR32 (wherein R32 is as defined hereinbefore); 8) C2-5alkynylR32 (wherein R32 is as defined hereinbefore); 9) R33 (wherein R33 represents a pyridone group, a phenyl group or a 5- or 6-membered aromatic heterocyclic group (linked via carbon or nitrogen) with 1, 2 or 3 heteroatoms selected from O, N and S, which pyridone, phenyl or aromatic heterocyclic group may carry up to 5 substituents on available carbon atoms selected from hydroxy, halo, amino, C1-4alkyl, C1-4alkoxy, C1-4hydroxyalkyl, C1-4aminoalkyl, C1-4alkylamino, C1-4hydroxyalkoxy, carboxy, trifluoromethyl, cyano, —CONR34R35 and —NR36COR37 (wherein R34, R35, R36 and R37, which may be the same or different, each represents hydrogen, C1-4alkyl or C1-3alkoxyC2-3alkyl)); 10) C1-5alkylR33 (wherein R33 is as defined hereinbefore); 11) C2-5alkenylR33 (wherein R33 is as defined hereinbefore); 12) C2-5alkynylR33 (wherein R33 is as defined hereinbefore); 13) C1-5alkylX6R33 (wherein X6 represents —O—, —S—, —SO—, —SO2—, —NR38CO—, —CONR39—, —SO2NR40—, —NR41SO2— or —NR42— (wherein R38, R39, R40, R41 and R42 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC1-3alkyl) and R33 is as defined hereinbefore); 14) C2-5alkenylX7R33 (wherein X7 represents —O—, —S—, —SO—, —SO2—, —NR43CO—, —CONR44—, —SO2NR45—, —NR46SO2— or —NR47— (wherein R43, R44, R45, R46 and R47 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R33 is as defined hereinbefore); 15) C2-5alkynylX8R33 (wherein X8 represents —O—, —S—, —SO—, —SO2—, —NR48CO—, —CONR49—, —SO2NR45—, —NR5SO2— or —NR52— (wherein R48, R49, R50, R51 and R52 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R33 is as defined hereinbefore); 16) C1-3alkynylX9C1-3alkylR33 (wherein X9 represents —O—, —S—, —SO—, —SO2—, —NR53CO—, —CONR14—, —SO2NR51—, —NR56SO2— or —NR57— (wherein R53, R54, R55, R56 and R57 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R33 is as defined hereinbefore); 17) C1-3alkylX9C1-3alkylR32 (wherein X9 and R23 are as defined hereinbefore); 18) C1-5alkyl optionally substituted by 1, 2 or 3 halo; 19) C1-5alkylX10C1-5alkylX11R90 (wherein X10 and X11, which may be the same or different, are each —O—, —S—, —SO—, —SO2—, —NR91CO—, —CONR92—, —SO2NR93—, —NR94SO2— or —NR95— (wherein R91, R92, R93, R94 and R95 each independently represents C1-5alkyl, C1-3alkyl (substituted by 1, 2 or 3 halo, C1-4alkyl or C1-4alkoxy groups (and where there are 2 C1-4alkoxy groups the C1-4alkyl groups of alkoxy may together form a 5- or 6-membered saturated heterocyclic group having 2 oxygen atoms)), C2-5alkenyl, C2-5alkynyl, C3-6cycloalkyl (optionally substituted by halo, hydroxy, C1-3alkyl or C1-4hydroxyalkyl), C3-6cycloalkylC1-3alkyl (optionally substituted by halo, hydroxy, C1-3alkyl or C1-4hydroxyalkyl) or C1-3alkoxyC2-3alkyl) and R90 represents hydrogen or C1-3alkyl); 20) C3-6cycloalkyl; 21) R96 (wherein R96 is a 5- or 6-membered heterocyclic group which may be saturated or unsaturated (linked via carbon or nitrogen) with 1 or 2 heteroatoms, selected independently from O, S and N which heterocyclic group may bear 1 or 2 substitutents selected from C1-4hydroxyalkyl, C1-4alkyl, hydroxy and C1-4alkoxyC1-4alkyl; 22) C1-5alkylR96 (wherein R96 is defined hereinbefore); and where: R60, R61 and R62 are independently hydrogen, nitro, cyano, halo, oxo, amino, trifluoromethyl, C1-4alkoxymethyl, di(C1-4alkoxy)methyl or C1-6alkanoyl or a group selected from C1-10alkyl, C2-10alkenyl, C2-10alkynyl, heterocyclyl, heterocyclylC1-10alkyl, C1-10alkoxy, arylC1-10alkyl, aryl, C3-10cycloalkyl, C3-10cycloalkenyl and C3-10cycloalkynyl (which group is optionally substituted by 1, 2 or 3 substituents independently selected from halo, C1-4alkyl (optionally substituted by 1, 2 or 3 halo), mercapto, hydroxy, carboxy, C1-10alkoxy, nitro, cyano, aryl, heteroaryl, heteroaryloxy, C2-10alkenyloxy, C2-10alkynyloxy, C1-4alkoxyC1-4alkoxy, aryloxy (where the aryl group may be substituted by halo, nitro, or hydroxy), amino, cyano, nitro, mono- or di(C1-6alkyl)amino, oximino or S(O)y where y is 0, 1, 2 or 3), or a group selected from ═CR78R79, C(O)xR77, OR77, S(O)yR77, NR78R79, C(O)NR78R79, OC(O)NR78R79, ═NOR77 NR77C(O)xR78, —NR77CONR78R79, —N═CR78R79, S(O)yNR78R79 or —NR77S(O)yR78 or a group selected from phenyl, benzyl or a 5- to 6-membered heterocyclic group with 1, 2 or 3 heteroatoms, selected independently from O, S and N, which heterocyclic group may be aromatic or non-aromatic and may be saturated (linked via a ring carbon or nitrogen atom) or unsaturated (linked via a ring carbon atom), which phenyl, benzyl or heterocyclic group may bear on one or more carbon ring atoms up to 5 substituents selected from hydroxy, halo, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino, nitro, C2-4alkanoyl, C1-4alkanoylamino, C1-4alkoxycarbonyl, C1-4alkylsulphanyl, C1-4alkylsulphinyl, C1-4alkylsulphonyl, carbamoyl, N-C1-4alkylcarbamoyl, N,N-di(C1-4alkyl)carbamoyl, aminosulphonyl, N-C1-4alkylaminosulphonyl, N,N-di(C1-4alkyl)aminosulphonyl, C1-4alkylsulphonylamino, and a saturated heterocyclic group selected from morpholino, thiomorpholino, pyrrolidinyl, piperazinyl, piperdinyl, imidazolidinyl and pyrazolidinyl, which saturated heterocyclic group may bear 1 or 2 substituents selected from oxo, hydroxy, halo, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino, nitro and C1-4alkoxycarbonyl, or a group of sub-formula (k): or a group of sub-formula (II): or a group of sub-formula (VI): where: p and q are independently 0 or 1; r is 0, 1, 2, 3 or 4; R1′ and R1″ are independently hydrogen, hydroxy, halo, cyano, C1-10alkyl, C3-10cycloalkyl, C2-10alkenyl or C2-10alkynyl (wherein C1-10alkyl, C3-10cycloalkyl, C2-10alkenyl and C2-10alkynyl are optionally substituted by halo, nitro, cyano, hydroxy, trifluoromethyl, amino, carboxy, carbamoyl, mercapto, sulphamoyl, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C3-6cycloalkyl, C3-6cycloalkenyl, C1-4alkoxy, C1-4alkanoyl, C1-4alkanoyloxy, C1-4alkanoylamino, N,N-di(C1-4alkanoyl)amino, N-(C1-4alkyl)carbamoyl, N,N-di(C1-4alkyl)carbamoyl, C1-4alkylS, C1-4alkylS(O), C1-4alkylS(O)2, C1-4alkoxycarbonyl, N-(C1-4alkyl)sulphamoyl, N,N-di(C1-4alkyl)sulphamoyl, C1-4alkylsulphonylamino or heterocyclyl); or R1′ and R1″ can together form a 3- to 6-membered ring which may be saturated or unsaturated; T is C═O, SOn (where n is 0, 1 or 2), C(═NOR)CO, C(O)C(O), C═NCN or CV═NO; V is independently R63 or N(R63)R64; R63 and R64 are independently selected from hydrogen, —(CH2)q.R70 (q′ is 0 or 1), aryl (optionally substituted by 1, 2 or 3 C1-6alkyl (optionally substituted by 1, 2 or 3 hydroxy groups)), C1-10alkyl (optionally substituted by 1, 2 or 3 groups independently selected from aryl or heterocyclic group where aryl and heterocyclic group are optionally substituted by 1, 2, or 3 groups independently selected from C1-6alkyl, nitro, cyano, halo, oxo, ═CR78R79, C(O)1R77, OR77, S(O)yR77, NR78R79, C(O)NR78R79, OC(O)NR78R79, ═NOR77, —NR77C(O)xR78, —NR77CONR78R79—N═CR78R79, S(O)yNR78R79, —NR77S(O)yR78) or a group selected from C1-10alkyl, C2-10alkenyl, C2-10alkynyl, heterocyclyl, C1-10alkoxy, C1-10alkyl, aryl, C3-10cycloalkyl, C3-10cycloalkenyl and C3-10cycloalkynyl (which group is optionally substituted by 1, 2 or 3 groups independently selected from C1-6alkyl, C1-4alkoxy, trifluoromethyl, trifluoromethoxy, difluoromethyl, difluoromethoxy, nitro, cyano, halo, oxo, ═CR78R79, C(O)xR77, OR77, S(O)yR77, NR78R79, C(O)NR78R79, OC(O)NR78R79, ═NR77, —NR77C(O)xR78, —NR77CONR78R79, —N═CR78R79, S(O)yNR78R79—NR77S(O)yR78); or R63 and R64 together with the nitrogen atom to which they are attached form a heterocyclic ring which ring is aromatic or non-aromatic and which is optionally substituted by hydroxy, C1-6alkoxy or C1-6alkyl (optionally substituted by hydroxy); R70 is hydrogen, hydroxy (other than when q is 0), C1-6alkyl, C1-6alkoxy, amino, N-C1-6alkylamino, N,N-di(C1-6alkyl)amino, C2-6hydroxyalkoxy, C1-6alkoxyC2-6alkoxy, aminoC2-6alkoxy, N-C1-6alkylaminoC2-6alkoxy, N,N-di(C1-6alkyl)aminoC2-6alkoxy, C3-7cycloalkyl (optionally substituted by 1 or 2 oxo or thioxo substitutents) or of formula (III): —K-J (III) K is a bond, oxy, imino, N-(C1-6alkyl)imino, oxyC1-6alkylene, iminoC1-6alkylene, N-(C1-6alkyl)iminoC1-6alkylene, —NHC(O), —SO2NH—, —NHSO2—, —NHC(O)—C1-6alkylene-, —OCO— or C2-4alkenylene; J is aryl, heteroaryl or heterocyclyl (where hetrocyclyl is optionally substituents by 1 or 2 oxo or thioxo substituents); and wherein any aryl, heteroaryl or heterocyclyl group in a R70 group is optionally substituted by 1, 2, 3 or 4 groups selected from hydroxy, halo, trifluoromethyl, cyano, mercapto, nitro, amino, carboxy, carbamoyl, formyl, aminosulphonyl, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, —O—(C1-3alkyl)-O—, C1-6alkylS(O)n— (where n is 0, 1 or 2), N-C1-6alkylamino, N,N-di(C1-6alkyl)amino, C1-6alkoxycarbonyl, N-C1-6alkylcarbamoyl, N,N-di(C1-6alkyl)carbamoyl, C2-6alkanoyl, C1-6alkanoyloxy, C1-6alkanoylamino, N-C1-6alkylaminosulphonyl, N,N-di(C1-6alkyl)aminosulphonyl, C1-6alkylsulphonylamino and C1-6alkylsulphonyl-N-C1-6alkyl)amino or by 1, 2, 3 or 4 groups selected from: a group of formula (IV) —B1—(CH2)p′-A1 (IV) (wherein A1 is halo, hydroxy, C1-6alkoxy, cyano, amino, C1-6alkylamino, di(C1-6alkyl)amino, carboxy, C1-6alkoxycarbonyl, carbamoyl, N-C1-6alkylcarbamoyl or N,N-di(C1-6alkyl)carbamoyl; p′ is 1, 2, 3, 4, 5 or 6; and B1 is a bond, oxy, imino, N-(C1-6alkyl)imino or —NHC(O)—; with the proviso that p is 2 or more unless B1 is a bond or —NHC(O)—); and a group of formula (V) -E1-D1 (V) (wherein D1 is aryl, heteroaryl or heterocyclyl (where heterocyclyl is optionally substituted by 1 or 2 oxo or thioxo substituents) and E1 is a bond, C1-6alkylene, oxyC1-6alkylene, oxy, imino, N-(C1-6alkyl)imino, iminoC1-6alkylene, N-(C1-6alkyl)iminoC1-6alkylene, C1-6alkylene-oxyC1-6alkylene, C1-6alkylene-iminoC1-6alkylene, C1-6alkylene-N-(C1-6alkyl)-iminoC1-6alkylene, —NHC(O)—, —NHSO2—, —SO2NH— or —NHC(O)—C1-6alkylene-, and any aryl, heteroaryl or heterocyclyl group in a substituent on D1 is optionally substituted with 1, 2, 3 or 4 groups selected from hydroxy, halo, C1-6alkyl, C1-6alkoxy, carboxy, C1-6alkoxycarbonyl, carbamoyl, N-C1-6alkylcarbamoyl, N,N-di(C1-6alkyl)carbamoyl, C2-6alkanoyl, amino, C1-6alkylamino and di(C1-6alkyl)amino); and any of the R70 groups defined hereinbefore which comprises a CH2 group which is attached to 2 carbon atoms or a CH3 group which is attached to a carbon atom optionally bears on each said CH2 or CH3 group a substituent selected from hydroxy, amino, C1-6alkoxy, C1-6alkylamino, di(C1-6alkyl)amino and heterocyclyl; R71 and R72 are independently selected from hydrogen or C1-6alkyl or R71 and R72 together form a bond; R73 is OR74 or NR75R76; R74, R75 and R76 are independently C1-10alkyl, C2-10alkenyl, C2-10alkynyl, aryl, heterocyclyl, C1-10alkoxy, arylC1-10alkyl, C3-10cycloalkyl, C3-10cycloalkenyl, C3-10cycloalkynyl, each of which is optionally substituted by 1, 2, 3 or 4 groups selected from nitro, cyano, halo, oxo, ═CR78R79, C(O)xR77, OR77, S(O)yR77, NR78R79, C(O)NR78R79, OC(O)NR78R79, ═NOR77, —NR77C(O)xR78, —NR77CONR78R79—N═CR78R79, S(O)yNR78R79 or —NR77S(O)yR78 where y is 0, 1, 2 or 3; or R74, R75 and R76 are independently heterocyclyl optionally substituted by C1-4alkyl, C2-4alkenyl, C2-4alkynyl and C3-6cycloalkyl; or R75 and R76 together with the nitrogen to which they are attached form an aromatic or non-aromatic ring which optionally contains 1, 2 or 3 further heteroatoms independently selected from N, O and S; R77, R78 and R79 are independently selected from hydrogen or a group selected from C1-10alkyl, C2-10alkenyl, C2-10alkynyl, aryl, heterocyclyl, C1-10alkoxy, arylC1-10alkyl, C3-10cycloalkyl, C3-10cycloalkenyl, C3-10cycloalkynyl where the group is optionally substituted by halo, C1-4perhaloalkyl, mercapto, hydroxy, carboxy, C1-10alkoxy, aryl, heteroaryl, heteroaryloxy, C2-10alkenyloxy, C2-10alkynyloxy, C1-6alkoxyC1-6alkoxy, aryloxy (where the aryl group may be substituted by halo, nitro, or hydroxy), cyano, nitro, amino, mono- or di(C1-6alkyl)amino, oximino or S(O)y where y is 0, 1, 2 or 3; or R78 and R79 together form a ring which optionally contains further heteroatoms such as S(O)y oxygen and nitrogen, x is an integer of 1 or 2, y is 0, 1, 2 or 3 which ring is optionally substituted by 1, 2 or 3 groups independently selected from halo, C1-4perhaloalkyl, mercapto, hydroxy, carboxy, C1-10alkoxy, aryl, heteroaryl, heteroaryloxy, C2-10alkenyloxy, C2-10alkynyloxy, C1-6alkoxyC1-6alkoxy, aryloxy (where the aryl group may be substituted by halo, nitro, or hydroxy), cyano, nitro, amino, mono- or di(C1-6alkyl)amino, oximino or S(O)y where y is 0, 1, 2 or 3; in the preparation of a medicament for use in the inhibition of Aurora kinase. 2. Use according to claim 1 wherein Aurora kinase is Aurora-A kinase. 3. Use according to claim 1 or 2 wherein R9 is hydrogen, C3-6cycloalkyl, —C1-5alkyl-O—C1-3alkyl or a 5- to 6-membered saturated heterocyclic group (linked via carbon or nitrogen) with 1 or 2 heteroatoms selected independently from O, S or N which heterocyclic group is optionally substituted by C1-4alkyl or R9 is a 5- or 6-membered aromatic heterocyclic group (linked via carbon or nitrogen) with 1, 2 or 3 heteroatoms or R9 is —C1-5alkylR32, C1-5alkylR96, C1-5alkyl (optionally substituted by halo), —C1-5alkyl-R20, —C1-5alkyl-NHR20, —C1-5alkyl-N(C1-3alkyl)—R20, —C1-5alkyl-NH—C1-5alkyl-OH, —C1-5alkyl-N(C1-3alkyl)-C1-5alkyl-OH and —C1-5alkyl-NR95—C1-5alkyl-OH and wherein R32, R96, R20 and R95 are as defined in claim 1. 4. Use according to any one of the preceding claims wherein X1 is —O—. 5. Use according to any one of the preceding claims wherein R1 is hydrogen, methoxy, N-(C1-5alkyl)piperidin-4-yloxy, prop-2-yloxy or methoxyethoxy; R2 is hydrogen or methoxy; and R4 is hydrogen. 6. A method for inhibiting Aurora kinase in a warm blooded animal, such as man, in need of such treatment, which comprises administering to said animal an effective amount of a compound as defined in claim 1, or a pharmaceutically acceptable salt or an in vivo hydrolysable ester thereof. 7. A compound of formula (IA): or a salt, ester or amide thereof; wherein X is as defined in claim 1; R1′, R2′, R3′, R4′ are equivalent to R1, R2, R3, R4 as defined in claim 1; and R5a is equivalent to R5 as defined in claim 1; provided that one of R60, R61 and R62 of R5a is other than hydrogen and that if R61 is other than hydrogen, it is not a group selected from: phenylC1-3alkyl, heteroaryl or optionally substituted phenyl; and C3-5cycloalkyl, C3-5cycloalkylC1-3alkyl, C2-5alkenyl or optionally substituted C1-4alkyl; where optional substitutents for phenyl and C1-4alkyl are C1-4alkyl, halo, methoxy, nitro or trifluoromethyl. 8. A compound according to claim 7 wherein R60 and R62 are both hydrogen and R61 is a group of sub-formula (k): wherein R1′ and R1″ are independently hydrogen or C1-3alkyl; T is C═O; q is 1; and V is N(R63)R64. 9. A compound according to claim 8 wherein R64 is hydrogen or C1-3alkyl and R63 is aryl optionally substituted by 1 or 2 substituents independently selected from halo, C1-4alkyl, C1-4alkoxy, trifluoromethyl, trifluoromethoxy, hydroxy, nitro, difluoromethyl, difluoromethoxy and cyano. 10. A compound according to claim 9 wherein R61 is —CH2—COR64-J and wherein J is phenyl optionally substituted by 1 or 2 halo. 11. A compound according to any one of claims 8 to 10 wherein R9 is hydrogen, C3-6cycloalkyl, —C1-5alkyl-O—C1-3alkyl or a 5- to 6-membered saturated heterocyclic group (linked via carbon or nitrogen) with 1 or 2 heteroatoms selected independently from O, S or N which heterocyclic group is optionally substituted by C1-4alkyl or R9 is a 5- or 6-membered aromatic heterocyclic group (linked via carbon or nitrogen) with 1, 2 or 3 heteroatoms or R9 is —C1-5alkylR32, —C1-5alkylR96, C1-5alkyl (optionally substituted by halo), —C1-5alkyl-OR20, —C1-5alkyl-NHR20, —C1-5alkyl-N(C1-3alkyl CR20, —C1-5alkyl-NH—C1-5alkyl-OH, —C1-5alkyl-N(C1-3alkyl)-C1-5alkyl-OH and —C1-5alkyl-NR95—C1-5alkyl-OH and wherein R32, R96, R20 and R95 are as defined in claim 1. 12. A compound according to any one of claims 8 to 11 wherein R1 is hydrogen, methoxy, N-(C1-5alkyl)piperidin-4-yloxy, prop-2-yloxy or methoxyethoxy; R2 is hydrogen or methoxy; and R4 is hydrogen. 13. Use of a compound as defined in any one of claims 7 to 12 as a medicament. 14. Use of a compound as defined in any one of claims 8 to 12 in the preparation of a medicament for use in the inhibition of Aurora kinase. 15. Use according to claim 14 wherein Aurora kinase is Aurora-A kinase. 16. A pharmaceutical composition comprising a compound according to any one of claims 7 to 12, or a pharmaceutically acceptable salt thereof in combination with a pharmaceutically acceptable carrier. 17. A process for the preparation of a compound according to claim 7 comprising the step of: a) when X is NH, reacting a compound of formula (VII) where R1, R2, R3, and R4 are R1′, R2′, R3′, and R4′ as defined in claim 7 and; R85 is a group NR86R87 where R86 and R87 are independently selected from C1-4alkyl, with a compound of formula (VIII) H2N—R5 (VIII) where R5′ is a group R5a as defined in claim 7 or a precursor group thereof; and thereafter if desired or necessary, converting a precursor group R5′ to a group R5 or R5a and/or modifying substituents on the group R5 or R5a; or b) when X is as defined in claim 6, reacting a compound of formula (X) where R1′, R2″, R3″, and R4′ are equivalent to a group R1′, R2′, R3′ and R4′ as defined in claim 6 or a precursor thereof, and R85 is a leaving group, with a compound of formula (XI) H—X—R5 (XI) and R5 is R5a as defined in claim 6: and thereafter if desired or necessary converting a group R1′, R2″, R3″ or R4′ to a group R1′, R2′, R3′, and R4′ respectively or to a different such group.

The present invention relates to certain quinazoline derivatives for use in the treatment of certain diseases in particular to proliferative disease such as cancer and in the preparation of medicaments for use in the treatment of proliferative disease, to novel quinazoline compounds and to processes for their preparation, as well as pharmaceutical compositions containing them as active ingredient. Cancer (and other hyperproliferative disease) is characterised by uncontrolled cellular proliferation. This loss of the normal regulation of cell proliferation often appears to occur as the result of genetic damage to cellular pathways that control progress through the cell cycle. In eukaryotes, an ordered cascade of protein phosphorylation is thought to control the cell cycle. Several families of protein kinases that play critical roles in this cascade have now been identified. The activity of many of these kinases is increased in human tumours when compared to normal tissue. This can occur by either increased levels of expression of the protein (as a result of gene amplification for example), or by changes in expression of co activators or inhibitory proteins. The first identified, and most widely studied of these cell cycle regulators have been the cyclin dependent kinases (or CDKs). Activity of specific CDKs at specific times is essential for both initiation and coordinated progress through the cell cycle. For example, the CDK4 protein appears to control entry into the cell cycle (the G0-G1-S transition) by phosphorylating the retinoblastoma gene product pRb. This stimulates the release of the transcription factor E2F from pRb, which then acts to increase the transcription of genes necessary for entry into S phase. The catalytic activity of CDK4 is stimulated by binding to a partner protein, Cyclin D. One of the first demonstrations of a direct link between cancer and the cell cycle was made with the observation that the Cyclin D1 gene was amplified and cyclin D protein levels increased (and hence the activity of CDK4 increased) in many human tumours (Reviewed in Sherr, 1996, Science 274: 1672-1677; Pines, 1995, Seminars in Cancer Biology 6: 63-72). Other studies (Loda et al., 1997, Nature Medicine 3(2): 231-234; Gemma et al., 1996, International Journal of Cancer 68(5): 605-11; Elledge et al. 1996, Trends in Cell Biology 6; 388-392) have shown that negative regulators of CDK function are frequently down regulated or deleted in human tumours again leading to inappropriate activation of these kinases. More recently, protein kinases that are structurally distinct from the CDK family have been identified which play critical roles in regulating the cell cycle and which also appear to be important in oncogenesis. These include the newly identified human homologues of the Drosophila aurora and S. cerevisiae Ip11 proteins. The three human homologues of these genes Aurora-A, Aurora-B and Aurora-C (also known as aurora2, aurora1 and aurora3 respectively) encode cell cycle regulated serine-threonine protein kinases (summarised in Adams et al., 2001, Trends in Cell Biology. 11(2): 49-54). These show a peak of expression and kinase activity through G2 and mitosis. Several observations implicate the involvement of human aurora proteins in cancer. This evidence is particularly strong for Aurora-A. The Aurora-A gene maps to chromosome 20q13, a region that is frequently amplified in human tumours including both breast and colon tumours. Aurora-A may be the major target gene of this amplicon, since Aurora-A DNA is amplified and mRNA overexpressed in greater than 50% of primary human colorectal cancers. In these tumours Aurora-A protein levels appear greatly elevated compared to adjacent normal tissue. In addition, transfection of rodent fibroblasts with human Aurora-A leads to transformation, conferring the ability to grow in soft agar and form tumours in nude mice (Bischoff et al., 1998, The EMBO Journal. 17(11): 3052-3065). Other work (Zhou et al., 1998, Nature Genetics. 20(2): 189-93) has shown that artificial overexpression of Aurora-A leads to an increase in centrosome number and an increase in aneuploidy, a known event in the development of cancer. Other work has shown an increase in expression of Aurora-B (Adams et al., 2001, Chromsoma. 110(2):65-74) and Aurora-C (Kimura et al., 1999, Journal of Biological Chemistry, 274(11): 733440) in tumour cells when compared to normal cells. Importantly, it has also been demonstrated that abrogation of Aurora-A expression and function by antisense oligonucleotide treatment of human tumour cell lines (WO 97/22702 and WO 99/37788) leads to cell cycle arrest and exerts an antiproliferative effect in these tumour cell lines. Additionally, small molecule inhibitors of Aurora-A and Aurora-B have been demonstrated to have an antiproliferative effect in human tumour cells (Keen et al. 2001, Poster #2455, American Association of Cancer research annual meeting). This indicates that inhibition of the function of Aurora-A (and possibly Aurora-B) will have an antiproliferative effect that may be useful in the treatment of human tumours and other hyperproliferative diseases. Further, inhibition of Aurora kinases as a therapeutic approach to these diseases may have significant advantages over targeting signalling pathways upstream of the cell cycle (e.g. those activated by growth factor receptor tyrosine kinases such as epidermal growth factor receptor (EGFR) or other receptors). Since the cell cycle is ultimately downstream of all of these diverse signalling events, cell cycle directed therapies such as inhibition of Aurora kinases would be predicted to be active across all proliferating tumour cells, whilst approaches directed at specific signalling molecules (e.g. EGFR) would be predicted to be active only in the subset of tumour cells which express those receptors. It is also believed that significant “cross talk” exists between these signalling pathways meaning that inhibition of one component may be compensated for by another. A number of quinazoline derivatives have been proposed hitherto for use in the inhibition of various kinases. For example, WO 96/09294, WO 96/15118 and WO 99/06378 to describe the use of certain quinazoline compounds as receptor tyrosine kinase inhibitors, which may be useful in the treatment of proliferative disease and WO 00/21955 discloses certain quinazoline derivatives as inhibitors of the effects of VEGF. Quinazoline derivatives have also been disclosed for use in the inhibition of Aurora-A kinase. WO 02/00649 discloses quinazoline derivative beaming a 5-membered heteroaromatic ring where the ring is, in particular, substituted thiazole or substituted thiophene. However despite the compounds of WO 02/00649 there still exists the need for further compounds having Aurora kinase inhibitory properties. The applicants have been successful in finding a novel series of compounds which inhibit the effects of the Aurora kinases and in particular Aurora-A kinase and which are thus of use in the treatment of proliferative disease such as cancer, in particular in such diseases such as colorectal or breast cancer where Aurora kinases are known to be active. According to one aspect of the present invention there is provided the use of a compound of formula (I) or a salt, ester or amide thereof; where: X is O or S, S(O) or S(O)2, or NR6 where R6 is hydrogen or C1-6alkyl; R5 is a group of formula (a) or (b): where * indicates the point of attachment to the group X in formula (I); R1, R2, R3, R4 are independently selected from hydrogen, halo, cyano, nitro, trifluoromethyl, C1-3alkyl, —NR7R8 or —X1R9; R7 and R8 are independently hydrogen or C1-3alkyl; X1 is a direct bond, —O—, —CH2—, —OCO—, carbonyl, —S—, —SO—, —SO2—, —NR10CO—, —CONR11—, —SO2NR12—, —NR13SO2— or —NR14—; R10, R11, R12, R13 and R14 are independently hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl; R9 is selected from one of the following groups: 1) hydrogen or C1-5alkyl which may be unsubstituted or which may be substituted with one or more groups selected from hydroxy, fluoro or amino; 2) C1-5alkylX2COR15 (wherein X2 represents —O— or —NR16— (in which R15 represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R16 represents C1-3alkyl, —NR17R18 or —OR19 (wherein R17, R18 and R19 which may be the same or different each represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl)); 3) C1-5alkylX3R20 (wherein X3 represents —O—, —S—, —SO—, —SO2—, —OCO—, —NR21CO—, —CONR22—, —SO2NR23—, —NR24SO2— or —NR25— (wherein R21, R22, R23, R24 and R25 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R20 represents hydrogen, C1-3alkyl, cyclopentyl, cyclohexyl or a 5- or 6-membered saturated heterocyclic group with 1 or 2 heteroatoms, selected independently from O, S and N, which C1-3alkyl group may bear 1 or 2 substituents selected from oxo, hydroxy, halo and C1-4alkoxy and which cyclic group may bear 1 or 2 substituents selected from oxo, hydroxy, halo, C1-4alkyl, C1-4hydroxyalkyl and C1-4alkoxy); 4) C1-5alkylX4C1-5alkylX5R26 (wherein X4 and X5 which may be the same or different are each —O—, —S—, —SO—, —SO2—, —NR27CO—, —CONR28—, —SO2NR29—, —NR30SO2— or —NR31— (wherein R27, R28, R29, R30 and R31 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R26 represents hydrogen or C1-3alkyl); 5) R32 (wherein R32 is a 5- or 6-membered saturated heterocyclic group (linked via carbon or nitrogen) with 1 or 2 heteroatoms, selected independently from O, S and N, which heterocyclic group may bear 1 or 2 substituents selected from oxo, hydroxy, halo, C1-4alkyl, C1-4hydroxyalkyl, C1-4alkoxy, C1-4alkoxyC1-4alkyl and C1-4alkylsulphonylC1-4alkyl); 6) C1-5alkylR32 (wherein R32 is as defined hereinbefore); 7) C2-5alkenylR32 (wherein R32 is as defined hereinbefore); 8) C2-1alkynylR32 (wherein R32 is as defined hereinbefore); 9) R33 (wherein R33 represents a pyridone group, a phenyl group or a 5- or 6-membered aromatic heterocyclic group (linked via carbon or nitrogen) with 1, 2 or 3 heteroatoms selected from O, N and S, which pyridone, phenyl or aromatic heterocyclic group may carry up to 5 substituents on available carbon atoms selected from hydroxy, halo, amino, C1-4alkyl, C1-4alkoxy, C1-4hydroxyalkyl, C1-4aminoalkyl, C1-4alkylamino, C1-4hydroxyalkoxy, carboxy, trifluoromethyl, cyano, —CONR34R35 and —NR36COR37 (wherein R34, R35, R36 and R37 which may be the same or different, each represents hydrogen, C1-4alkyl or C1-3alkoxyC2-3alkyl)); 10) C1-5alkylR33 (wherein R33 is as defined hereinbefore); 11) C2-5alkenylR33 (wherein R33 is as defined hereinbefore); 12) C2-5alkynylR33 (wherein R33 is as defined hereinbefore); 13) C1-5alkylX6R33 (wherein X6 represents —O—, —S—, —SO—, —SO2—, —NR38CO—, —CONR39—, —SO2NR40—, —NR41SO2— or —NR42— (wherein R38, R39, R40, R41 and R42 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R33 is as defined hereinbefore); 14) C2-5alkenylX7R33 (wherein X7 represents —O—, —S—, —SO—, —SO2—, —NR43CO—, —CONR44—, —SO2NR45—, —NR46SO2— or —NR47— (wherein R43, R44, R45, R46 and R47 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R33 is as defined hereinbefore); 15) C2-5alkynylX8R33 (wherein X8 represents —O—, —S—, —SO—, —SO2—, —NR48OC—, —CONR49—, —SO2NR50—, —NR51SO2— or —NR52— (wherein R48, R49, R50, R51 and R52 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R33 is as defined hereinbefore); 16) C1-3alkylX9C1-3alkylR33 (wherein X9 represents —O—, —S—, —SO—, —SO2—, —NR53CO—, —CONR54—, —SO2NR15—, —NR56SO2— or —NR57— (wherein R53, R54, R55, R56 and R57 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R33 is as defined hereinbefore); 17) C1-3alkylX9C1-3alkylR32 (wherein X9 and R28 are as defined hereinbefore); 18) C1-5alkyl optionally substituted by 1, 2 or 3 halo; 19) C1-5alkylX10C1-5alkylX11R90 (wherein X10 and X11, which may be the same or different, are each —O—, —S—, —SO—, —SO2—, —NR91CO—, —CONR92—, —SO2NR93—, —NR94SO2— or —NR95— (wherein R91, R92, R93, R94 and R95 each independently represents C1-5alkyl, C1-3alkyl (substituted by 1, 2 or 3 halo, C1-4alkyl or C1-4alkoxy groups (and where there are 2 C1-4alkoxy groups the C1-4alkyl groups of alkoxy may together form a 5- or 6-membered saturated heterocyclic group having 2 oxygen atoms)), C2-5alkenyl, C2-5alkynyl, C3-6cycloalkyl (optionally substituted by halo, hydroxy, C1-3alkyl or C1-4hydroxyalkyl), C3-6cycloalkylC1-3alkyl (optionally substituted by halo, hydroxy, C1-3alkyl or C1-4hydroxyalkyl) or C1-3alkoxyC2-3alkyl) and R90 represents hydrogen or C1-3alkyl); 20) C3-6cycloalkyl; 21) R96 (wherein R96 is a 5- or 6-membered heterocyclic group which may be saturated or unsaturated (linked via carbon or nitrogen) with 1 or 2 heteroatoms, selected independently from O, S and N which heterocyclic group may bear 1 or 2 substitutents selected from C1-4hydroxyalkyl, C1-4alkyl, hydroxy and C1-4alkoxyC1-4alkyl; 22) C1-5alkylR96 (wherein R96 is defined hereinbefore); and where: R60, R61 and R62 are independently hydrogen, nitro, cyano, halo, oxo, amino, trifluoromethyl, C1-4alkoxymethyl, di(C1-4alkoxy)methyl or C1-6alkanoyl or a group selected from C1-10alkyl, C2-10alkenyl, C2-10alkynyl, heterocyclyl, heterocyclylC1-10alkyl, C1-10alkoxy, arylC1-10alkyl, aryl, C3-10cycloalkyl, C3-10cycloalkenyl and C3-10cycloalkynyl (which group is optionally substituted by 1, 2 or 3 substituents independently selected from halo, C1-4alkyl (optionally substituted by 1, 2 or 3 halo), mercapto, hydroxy, carboxy, C1-10alkoxy, nitro, cyano, aryl, heteroaryl, heteroaryloxy, C2-10alkenyloxy, C2-10alkynyloxy, C1-4alkoxyC1-4alkoxy, aryloxy (where the aryl group may be substituted by halo, nitro, or hydroxy), amino, cyano, nitro, mono- or di(C1-6alkyl)amino, oximino or S(O)y where y is 0, 1, 2 or 3), or a group selected from ═CR78R79, C(O)xR77, OR77, S(O)yR77, NR78R79, C(O)NR78R79, OC(O)NR78R79, ═NOR77, —NR C(O)xR78, —NR77CONR78R79, —N═CR78R79, S(O)yNR78R79 or —NR77S(O)yR78 or a group selected from phenyl, benzyl or a 5- to 6-membered heterocyclic group with 1, 2 or 3 heteroatoms, selected independently from O, S and N, which heterocyclic group may be aromatic or non-aromatic and may be saturated (linked via a ring carbon or nitrogen atom) or unsaturated (linked via a ring carbon atom), which phenyl, benzyl or heterocyclic group may bear on one or more carbon ring atoms up to 5 substituents selected from hydroxy, halo, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino, nitro, C2-4alkanoyl, C1-4alkanoylamino, C1-4alkoxycarbonyl, C1-4alkylsulphanyl, C1-4alkylsulphinyl, C1-4alkylsulphonyl, carbamoyl, N-C1-4alkylcarbamoyl, N,N-di(C1-4alkyl)carbamoyl, aminosulphonyl, N-C1-4alkylaminosulphonyl, N,N-di(C1-4alkyl)aminosulphonyl, C1-4alkylsulphonylamino, and a saturated heterocyclic group selected from morpholino, thiomorpholino, pyrrolidinyl, piperazinyl, piperdinyl, imidazolidinyl and pyrazolidinyl, which saturated heterocyclic group may bear 1 or 2 substituents selected from oxo, hydroxy, halo, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino, nitro and C1-4alkoxycarbonyl, or a group of sub-formula (k): or a group of sub-formula (II): or a group of sub-formula (VI): where: p and q are independently 0 or 1; r is 0, 1, 2, 3 or 4; R1′ and R1″ are independently hydrogen, hydroxy, halo, cyano, C1-10alkyl, C3-10cycloalkyl, C2-10alkenyl or C2-10alkynyl (wherein C1-10alkyl, C3-10cycloalkyl, C2-10alkenyl and C2-10alkynyl are optionally substituted by halo, nitro, cyano, hydroxy, trifluoromethyl, amino, carboxy, carbamoyl, mercapto, sulphamoyl, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C3-6cycloalkyl, C3-6cycloalkenyl, C1-4alkoxy, C1-4alkanoyl, C1-4alkanoyloxy, C1-4alkanoylamino, N,N-di(C1-4alkanoyl)amino, N-(C1-4alkyl)carbamoyl, N,N-di(C1-4alkyl)carbamoyl, C1-4alkylS, C1-4alkylS(O), C1-4alkylS(O)2, C1-4alkoxycarbonyl, N-(C1-4 alkyl)sulphamoyl, N,N-di(C1-4alkyl)sulphamoyl, C1-4alkylsulphonylamino or heterocyclyl); or R1′ and R1″ can together form a 3- to 6-membered ring which may be saturated or unsaturated; T is C═O, SOa (where n is 0, 1 or 2), C(═NOR)CO, C(O)C(O), C═NCN or CV═NO; V is independently R63 or N(R63)R64; R63 and R64 are independently selected from hydrogen, —(CH2)q.R70 (q′ is 0 or 1), aryl (optionally substituted by 1, 2 or 3 C1-6alkyl (optionally substituted by 1, 2 or 3 hydroxy groups)), C1-10alkyl (optionally substituted by 1, 2 or 3 groups independently selected from aryl or heterocyclic group where aryl and heterocyclic group are optionally substituted by 1, 2, or 3 groups independently selected from C1-6alkyl, nitro, cyano, halo, oxo, ═CR78R79, C(O)xR77, OR77, S(O)yR77, NR78R79, C(O)NR78R79, OC(O)NR78R79, ═NOR77, —NR77C(O)xR78, —NR77CONR78R79, —N═CR78R79, S(O)yNR78R79, —NR77S(O)yR78) or a group selected from C1-10alkyl, C2-10alkenyl, C2-10alkynyl, heterocyclyl, C1-10alkoxy, C1-10alkyl, aryl, C3-10cycloalkyl, C3-10cycloalkenyl and C3-10cycloalkynyl (which group is optionally substituted by 1, 2 or 3 groups independently selected from C1-6alkyl, C1-4alkoxy, trifluoromethyl, trifluoromethoxy, difluoromethyl, difluoromethoxy, nitro, cyano, halo, oxo, ═CR78R79, C(O)xR77, OR77, S(O)yR77, N C(O)NR78R79, OC(O)NR78R79, ═NOR77, —NR77C(O)xR71, —NR77CONR78R79, —N═CR78R79, S(O)yNR78R79, NR77S(O)yR78); or R63 and R64 together with the nitrogen atom to which they are attached form a heterocyclic ring which ring is aromatic or non-aromatic and which is optionally substituted by hydroxy, C1-6alkoxy or C1-6alkyl (optionally substituted by hydroxy); R70 is hydrogen, hydroxy (other than when q is 0), C1-6alkyl, C1-6alkoxy, amino, N-C1-6alkylamino, N,N-di(C1-6alkyl)amino, C2-6hydroxyalkoxy, C1-6alkoxyC2-6alkoxy, aminoC2-6alkoxy, N-C1-6alkylaminoC2-6alkoxy, N,N-di(C1-6alkyl)aminoC2-6alkoxy, C3-7cycloalkyl (optionally substituted by 1 or 2 oxo or thioxo substitutents) or of formula (III): —K-J (III) K is a bond, oxy, imino, N-(C1-6alkyl)imino, oxyC1-6alkylene, iminoC1-6alkylene, N-(C1-6alkyl)iminoC1-6alkylene, —NHC(O), —SO2NH—, —NHSO2—, —NHC(O)C1-6alkylene-, —OCO— or C2-4alkenylene; J is aryl, heteroaryl or heterocyclyl (where hetrocyclyl is optionally substituents by 1 or 2 oxo or thioxo substituents); and wherein any aryl, heteroaryl or heterocyclyl group in a R70 group is optionally substituted by 1, 2, 3 or 4 groups selected from hydroxy, halo, trifluoromethyl, cyano, mercapto, nitro, amino, carboxy, carbamoyl, formyl, aminosulphonyl, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, —O—(C1-3alkyl)—O—, C1-6alkylS(O)n— (where n is 0, 1 or 2), N-C1-6alkylamino, N,N-di(C1-6alkyl)amino, C1-6alkoxycarbonyl, N-C1-6alkylcarbamoyl, N,N-di(C1-6alkyl)carbamoyl, C2-6alkanoyl, C1-6alkanoyloxy, C1-6alkanoylamino, N-C1-6alkylaminosulphonyl, N,N-di(C1-6alkyl)aminosulphonyl, C1-6alkylsulphonylamino and C1-6alkylsulphonyl-N-(C1-6alkyl)amino or by 1, 2, 3 or 4 groups selected from: a group of formula (IV) —B1—(CH2)p-A1 (IV) (wherein A1 is halo, hydroxy, C1-6alkoxy, cyano, amino, C1-6alkylamino, di(C1-6alkyl)amino, carboxy, C1-6alkoxycarbonyl, carbamoyl, N-C1-6alkylcarbamoyl or N,N-di(C1-6alkyl)carbamoyl; p′ is 1, 2, 3, 4, 5 or 6; and B1 is a bond, oxy, imino, N-(C1-6alkyl)imino or —NHC(O)—; with the proviso that p is 2 or more unless B1 is a bond or —NHC(O)—); and a group of formula (V) -E1-D1 (V) (wherein D1 is aryl, heteroaryl or heterocyclyl (where heterocyclyl is optionally substituted by 1 or 2 oxo or thioxo substituents) and E1 is a bond, C1-6alkylene, oxyC1-6alkylene, oxy, imino, N-(C1-6alkyl)imino, iminoC1-6alkylene, N-(C1-6alkyl)iminoC1-6alkylene, C1-6alkylene-oxyC1-6alkylene, C1-6alkylene-iminoC1-6alkylene, C1-6alkylene-N-(C1-6alkyl)-iminoC1-6alkylene, —NHC(O)—, —NHSO2—, —SO2NH— or —NHC(O)—C1-6alkylene-, and any aryl, heteroaryl or heterocyclyl group in a substituent on D1 is optionally substituted with 1, 2, 3 or 4 groups selected from hydroxy, halo, C1-6alkyl, C1-6alkoxy, carboxy, C1-6alkoxycarbonyl, carbamoyl, N-C1-6alkylcarbamoyl, N,N-di(C1-6alkyl)carbamoyl, C2-6alkanoyl, amino, C1-6alkylamino and di(C1-6alkyl)amino); and any of the R70 groups defined hereinbefore which comprises a CH2 group which is attached to 2 carbon atoms or a CH3 group which is attached to a carbon atom optionally bears on each said CH2 or CH3 group a substituent selected from hydroxy, amino, C1-6alkoxy, C1-6alkylamino, di(C1-6alkyl)amino and heterocyclyl; R71 and R72 are independently selected from hydrogen or C1-4alkyl or R71 and R72 together form a bond; R73 is OR74 or NR75R76; R74, R75 and R76 are independently C1-10alkyl, C2-10alkenyl, C2-10alkynyl, aryl, heterocyclyl, C1-10alkoxy, arylC1-10alkyl, C3-10cycloalkyl, C3-10cycloalkenyl, C3-10cycloalkynyl, each of which is optionally substituted by 1, 2, 3 or 4 groups selected from nitro, cyano, halo, oxo, ═CR78R79, C(O)R77, OR77, S(O)yR77, NR78R79, C(O)NR78R79, OC(O)NR78R79, ═NOR77, NR77C(O)xR71, —NR77CONR78R79, —N═CR78R79, S(O)yNR78R79 or NR77S(O)yR78 where y is 0, 1, 2 or 3; or R74, R75 and R76 are independently heterocyclyl optionally substituted by C1-4alkyl, C2-4alkenyl, C2-4alkynyl and C3-6cycloalkyl; or R75 and R76 together with the nitrogen to which they are attached form an aromatic or non-aromatic ring which optionally contains 1, 2 or 3 further heteroatoms independently selected from N, O and S; R77, R78 and R79 are independently selected from hydrogen or a group selected from C1-10alkyl, C2-10alkenyl, C2-10alkynyl, aryl, heterocyclyl, C1-10alkoxy, arylC1-10alkyl, C3-10cycloalkyl, C3-10cycloalkenyl, C3-10cycloalkynyl where the group is optionally substituted by halo, C1-4perhaloalkyl such as trifluoromethyl, mercapto, hydroxy, carboxy, C1-10alkoxy, aryl, heteroaryl, heteroaryloxy, C2-10alkenyloxy, C2-10alkynyloxy, C1-6alkoxyC1-6alkoxy, aryloxy (where the aryl group may be substituted by halo, nitro, or hydroxy), cyano, nitro, amino, mono- or di(C1-6alkyl)amino, oximino or S(O)y where y is 0, 1, 2 or 3; or R78 and R79 together form a ring which optionally contains further heteroatoms such as S(O)y oxygen and nitrogen, x is an integer of 1 or 2, y is 0, 1, 2 or 3 which ring is optionally substituted by 1, 2 or 3 groups independently selected from halo, C1-4perhaloalkyl such as trifluoromethyl, mercapto, hydroxy, carboxy, C1-10alkoxy, aryl, heteroaryl, heteroaryloxy, C2-10alkenyloxy, C2-10alkynyloxy, C1-6alkoxyC1-10alkoxy, aryloxy (where the aryl group may be substituted by halo, nitro, or hydroxy), cyano, nitro, amino, mono- or di(C1-6alkyl)amino, oximino or S(O)y where y is 0, 1, 2 or 3; in the preparation of a medicament for use in the inhibition of Aurora kinase. Also provided is the use of a compound of formula (I) in the preparation of a medicament for use in the inhibition of Aurora-A kinase. Also provided is the use of a compound of formula (I) in the preparation of a medicament for use in the inhibition of Aurora-B kinase. In particular, medicaments containing compounds of the present invention are useful in the treatment of proliferative disease such as cancer, and in particular cancers where Aurora-A is upregulated such as colon or breast cancers. In a further aspect the present invention provides the use of a compound of formula (I) or a salt, ester or amide thereof; where X is O, or S, S(O) or S(O)2, or NR6 where R6 is hydrogen or C1-6alkyl; R5 is a group of formula (a) or (b): R60, R61 and R62 are independently selected from hydrogen or a substituent group and * indicates the point of attachment to the group X in formula (I); R1, R2, R3, R4 are independently selected from, halo, cyano, nitro, trifluoromethyl, C1-3alkyl, —NR7R8 (wherein R7 and R8, which may be the same or different, each represents hydrogen or C1-3alkyl), or —X1R9 (wherein X1 represents a direct bond, —O—, —CH2—, —OCO—, carbonyl, —S—, —SO—, —SO2—, —NR10CO—, —CONR11—, —SO2NR12—, —NR13SO2— or —NR14— (wherein R10, R11, R12, R13 and R14 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl), and R9 is selected from one of the following groups: 1) hydrogen or C1-5alkyl which may be unsubstituted or which may be substituted with one or more groups selected from hydroxy, fluoro or amino, 2) C1-5alkylX2COR15 (wherein X2 represents —O— or —NR16— (in which R15 represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R16 represents C1-3alkyl, —NR17R18 or —OR19 (wherein R17, R18 and R19 which may be the same or different each represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl)); 3) C1-5alkylX3R20 (wherein X3 represents —O—, —S—, —SO—, —SO2—, —OCO—, —NR21CO—, —CONR22—, —SO2NR23—, —NR24SO2— or —NR25— (wherein R21, R22, R23, R24 and R25 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R20 represents hydrogen, C1-3alkyl, cyclopentyl, cyclohexyl or a 5-6-membered saturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which C1-3alkyl group may bear 1 or 2 substituents selected from oxo, hydroxy, halogeno and C1-4alkoxy and which cyclic group may bear 1 or 2 substituents selected from oxo, hydroxy, halogeno, C1-4alkyl, C1-4hydroxyalkyl and C1-4alkoxy); 4) C1-5alkylX4C1-5alkylX5R26 (wherein X4 and X5 which may be the same or different are each —O—, —S—, —SO—, —SO2—, —NR27CO—, —CONR28—, SO2NR29—, —NR30SO2— or —NR1— (wherein R27, R28, R29, R30 and R31 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R26 represents hydrogen or C1-3alkyl); 5) R32 (wherein R32 is a 5-6-membered saturated heterocyclic group (linked via carbon or nitrogen) with 1-2 heteroatoms, selected independently from O, S and N, which heterocyclic group may bear 1 or 2 substituents selected from oxo, hydroxy, halogeno, C1-4alkyl, C1-4hydroxyalkyl, C1-4alkoxy, C1-4alkoxyC1-4alkyl and C1-4alkylsulphonylC1-4alkyl); 6) C1-5alkylR32 (wherein R32 is as defined hereinbefore); 7) C2-5alkenylR32 (wherein R32 is as defined hereinbefore); 8) C2-5alkynylR32 (wherein R32 is as defined hereinbefore); 9) R33 (wherein R33 represents a pyridone group, a phenyl group or a 5-6-membered aromatic heterocyclic group (linked via carbon or nitrogen) with 1-3 heteroatoms selected from O, N and S, which pyridone, phenyl or aromatic heterocyclic group may carry up to 5 substituents on an available carbon atom selected from hydroxy, halogeno, amino, C1-4alkyl, C1-4alkoxy, C1-4hydroxyalkyl, C1-4aminoalkyl, C1-4alkylamino, C1-4hydroxyalkoxy, carboxy, trifluoromethyl, cyano, —CONR34R35 and —NR36COR37 (wherein R34, R35, R36 and R37, which may be the same or different, each represents hydrogen, C1-4alkyl or C1-3alkoxyC2-3alkyl)); 10) C1-5alkylR33 (wherein R33 is as defined hereinbefore); 11) C2-5alkenylR33 (wherein R33 is as defined hereinbefore); 12) C2-5alkynylR33 (wherein R33 is as defined hereinbefore); 13) C1-5alkylX6R33 (wherein X6 represents —O—, —S—, —SO—, —SO2—, —NR38CO—, —CONR39—, —SO2NR40—, —NR41SO2— or —NR42— (wherein R38, R39, R40, R41 and R42 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R33 is as defined hereinbefore); 14) C2-5alkenylX7R33 (wherein X9 represents —O—, —S—, —SO—, —SO2—, —NR43CO—, —CONR44—, —SO2NR45—, —NR46SO2— or —NR47— (wherein R43, R44, R45, R46 and R47 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R33 is as defined hereinbefore); 15) C2-5alkynylX8R33 (wherein X8 represents —O—, —S—, —SO—, —SO2—, —NR48CO—, —CONR49—, —SO2NR50—, —NR51SO2— or —NR52— (wherein R48, R49, R50, R51 and R52 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R33 is as defined hereinbefore); 16) C2-3alkylX9C1-3alkylR33 (wherein X9 represents —O—, —S—, —SO—, —SO2—, —NR53CO—, —CONR54—, —SO2NR55—, —NR56SO2— or —NR57— (wherein R53, R54, R55, R1 and R57 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R33 is as defined hereinbefore); and 17) C1-3alkylX9C1-3alkylR32 (wherein X9 and R23 are as defined hereinbefore): in the preparation of a medicament for use in the inhibition of aurora 2 kinase. In this specification the term alkyl when used either alone or as a suffix or prefix includes straight-chain and branched-chain saturated structures comprising carbon and hydrogen atoms. Unless otherwise stated, these groups may contain up to 10 carbon atoms (C1-10alkyl), preferably up to 6 carbon atoms (C1-6alkyl) and more preferably up to 4 carbon atoms (C1-4alkyl). References to individual alkyl groups are specific for the straight-chain version only and references to individual branched-chain alkyl groups such as t-butyl are specific for the branched chain version only. For example C1-4alkyl includes the examples of methyl, ethyl, propyl, butyl and tert-butyl where the ethyl, propyl and butyl groups may be bonded at the 1 or 2 position (e.g. prop-1-yl and prop-2-yl). A similar analysis of alkyl groups having different ranges of carbon atoms can be performed. Similarly the terms alkenyl and alkynyl refer to unsaturated straight-chain or branched-chain structures containing for example from 2 to 10 carbon atoms (C2-10alkenyl and C2-10alkynyl) and preferably from 2 to 6 carbon atoms (C2-6alkenyl and C2-6alkynyl) and more preferably 2 to 4 carbon atoms (C2-4alkenyl and C2-4alkynyl). Again references to individual groups are specific for the straight-chain version only and references to individual branched-chain groups are specific for the branched chain version only. The above comment concerning the bonding position of alkyl is applicable to alkenyl and alkynyl groups. Cyclic moieties such as cycloalkyl, cycloalkenyl and cycloalkynyl are similar in nature but have at least 3 carbon atoms, the following terms thus being used in the specification to indicate the minimum and maximum number of carbon atoms in the rings: C3-10cycloalkyl, C3-10cycloalkenyl and C3-10cycloalkynyl and preferably C3-6cycloalkyl, C3-6cycloalkenyl and C3-6cycloalkynyl and most preferably C3-4cycloalkyl. Terms such as alkoxy comprise alkyl groups as is understood in the art and thus contain up to 10 carbon atoms (C1-10alkoxy), preferably up to 6 carbon atoms (C1-6alkoxy) and more preferably up to 4 carbon atoms (C1-4alkoxy). The term halo includes fluoro, chloro, bromo and iodo. References to aryl groups include aromatic carbocyclic groups such as phenyl and naphthyl. The terms heterocyclyl and heterocyclic group include (unless specifically stated) aromatic or non-aromatic rings and may comprise more than one ring (e.g. they are monocyclic, bicyclic or tricyclic and preferably they are monocyclic and bicyclic), for example containing from 4 to 20, suitably from 5 to 8 ring atoms, at least one of which is a heteroatom such as oxygen, sulphur or nitrogen. Examples of such groups include furyl, thienyl, pyrrolyl, pyrrolidinyl, imidazolyl, triazolyl, thiazolyl, tetrazolyl, oxazolyl, isoxazolyl, pyrazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, quinolinyl, isoquinolinyl, quinoxalinyl, benzothiazolyl, benzoxazolyl, benzothienyl or benzofuryl. Heteroaryl refers to those heterocyclyl groups described above which have an aromatic character. The term aralkyl refers to aryl substituted alkyl groups such as benzyl. Other expressions used in the specification include hydrocarbyl which refers to any structure comprising carbon and hydrogen atoms. For example, these may be alkyl, alkenyl, alkynyl, aryl, heterocyclyl, alkoxy, aralkyl, cycloalkyl, cycloalkenyl or cycloalkynyl. The tern functional group refers to reactive substituents such as nitro, cyano, halo, oxo, ═CR78R79, C(O)xR77, OR77, S(O)yR77, NR78R79, C(O)NR78R79, OC(O)NR78R79, NOR77, —NR77C(O)xR78, —NR77CONR78R79, —N═CR78R79, S(O)yNR78R79 or —NR77S(O)yR78 where R77, R78 and R79 are independently selected from hydrogen or optionally substituted hydrocarbyl, or R78 and R79 together form an optionally substituted ring which optionally contains further heteroatoms such as S(O)y oxygen and nitrogen, x is an integer of 1 or 2, y is 0, 1, 2 or 3. Suitable optional substituents for hydrocarbyl groups R77, R78 and R79 include halo, perhaloalkyl such as trifluoromethyl, mercapto, hydroxy, carboxy, alkoxy, aryl, heteroaryl, heteroaryloxy, alkenyloxy, alkynyloxy, alkoxyalkoxy, aryloxy (where the aryl group may be substituted by halo, nitro, or hydroxy), cyano, nitro, amino, mono- or di-alkyl amino, oximino or S(O)y where y is as defined above. Suitable optional substituents for any hydrocarbyl group, heterocyclyl group or C1-10alkoxy group (unless specifically stated) include halo, perhaloalkyl such as trifluoromethyl, mercapto, hydroxy, carboxy, alkoxy, aryl, heteroaryl, heteroaryloxy, alkenyloxy, alkynyloxy, alkoxyalkoxy, aryloxy (where the aryl group may be substituted by halo, nitro, or hydroxy), cyano, nitro, amino, mono- or di-alkyl amino, oximino or S(O)y where y is as defined above. Where optional substituents are chosen from one of more groups or substituents it is to be understood that this definition includes all substituents being chosen from one of the specified groups i.e. all substitutents being the same, or the substituents being chosen from two or more of the specified groups i.e. the substituents not being the same. Preferably one or more means 1, 2, 3 or 4 but one or more may also means 1, 2 or 3 or 1 or 2. Where a compound of formula (I), formula (IA) or formula (IB) contains more than one specific R group it is to be understood that each selection made for such a group is independent from any other selection made for that same group, for example when a compound of formula (I) contains more than one R77 group, each R77 group can the same as the other R77 groups or different. Within this specification composite terms are used to describe group comprising more than one functionality such as C1-3alkoxyC2-3alkyl. Such terms are to be interpreted as is understood in the art. Unless specifically stated the bonding atom of a group may be any atom of that group so for example propyl includes prop-1-yl and prop-2-yl. Suitable values for any of the R groups (R1 to R96) or any part or substitutents for such groups include:— for C1-3alkyl: methyl, ethyl and propyl for C1-4alkyl: C1-3alkyl, butyl and tert-butyl for C1-5alkyl: C1-4alkyl, pentyl and 2,2-dimethylpropyl for C1-6alkyl: C1-5alkyl, hexyl and 2,3-dimethylbutyl for C1-10alkyl: C1-6alkyl, octanyl and decanyl for C2-4alkenyl: vinyl, allyl and but-2-enyl for C2-4alkenylene CH═CH—, —CH2—CH═CH—, —CH═CH—CH2— and —CH2—CH═CH—CH2— for C2-5alkenyl: C2-4alkenyl and 3-methylbut-2-enyl for C2-6alkenyl: C2-5alkenyl and 3-methylpent-2-enyl for C2-10alkenyl: C2-6alkenyl and octenyl for C2-4alkynyl: ethynyl, propargyl and prop-1-ynyl for C2-5alkynyl: C2-4alkynyl and pent-4-ynyl for C2-6alkynyl: C2-5alkynyl and 2-methylpentynyl for C2-10alkynyl: C2-6alkynyl and oct-4-ynyl for C3-6cycloalkyl: cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl for C3-7cycloalkyl: C3-6cycloalkyl and cyclopentyl for C3-10cycloalkyl: C3-7cycloalkyl and cyclononyl for C3-6cycloalkenyl: cyclobutenyl, cyclopentenyl, cyclohexenyl and cyclohex-1,4-dienyl for C3-10cycloalkenyl: C3-6cycloalkenyl, cycloheptenyl and cyclooctenyl for C3-10cycloalkynyl: cyclodecynyl for C3-6cycloalkylC1-3alkyl: cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclopropylethyl and cyclobutylethyl for C1-3alkoxy: methoxy, ethoxy and propoxy for C1-4alkoxy: C1-3alkoxy, butoxy and tert-butoxy for C1-6alkoxy: C1-4alkoxy, 3,3-dimethylpentoxy and hexyloxy for C1-10alkoxy: C1-6alkoxy, 2,2,4,4-tetramethylpentoxy for C2-10alkenyloxy: allyloxy, but-2-enyloxy, 3-methylbut-2-enyloxy, 3-methylpent-2-enyloxy and octenyloxy for C2-10alkynyloxy: propargyloxy, pent-4-ynyloxy and oct-4-ynyloxy for aryl: phenyl and naphthyl for arylC1-10alkyl: benzyl, phenethyl, naphylmethyl and naphthylethyl for arylC1-6alkyl: benzyl, phenethyl, naphylmethyl and naphthylethyl for aryloxy: phenoxy and naphthyloxy for heteroaryl: furyl, thienyl, pyrrolyl, pyrazolyl, pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl and quinolinyl for heteroaryloxy: pyridyloxy and quinolinyloxy for heterocyclyl: furyl, thienyl, pyrrolyl, pyrrolidinyl, imidazolyl, triazolyl, thiazolyl, tetrazolyl, oxazolyl, isoxazolyl, pyrazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, quinolinyl, isoquinolinyl, quinoxalinyl, benzothiazolyl, benzoxazolyl, benzothienyl or benzofuryl for heterocyclylC1-6alkyl: furylmethyl, thienylethyl, pyrrolylethyl, pyridlymethyl and pyrimidinylethyl for C1-4hydroxyalkyl: hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 3-hydroxypropyl, 1-hydroxyprop-2-yl and 1-hydroxy-2-methylprop-2-yl for C1-3alkoxyC2-3alkyl: methoxyethyl, ethoxyethyl and methoxypropyl for C1-4alkoxyC1-4alkyl: methoxymethyl, ethoxymethyl, methoxyethyl, ethoxyethyl, methoxypropyl and ethoxybutyl for C1-4alkoxymethyl: methoxymethyl, ethoxymethyl, propoxymethyl and prop-2-oxymethyl for di(C1-4alkoxy)methyl: dimethoxymethyl and diethoxymethyl for C1-4hydroxyalkoxy: 2-hydroxyethoxy, 3-hydroxypropoxy and 2-hydroxypropoxy for C2-6hydroxyalkoxy: 2-hydroxyethoxy, 3-hydroxypropoxy and 4-hydroxybutoxy for C1-4alkoxyC1-4alkoxy: methoxymethoxy, methoxyethoxy, ethoxyethoxy, propoxymethoxy and propoxyethoxy for C1-6alkoxyC2-6alkoxy: methoxyethoxy and ethoxybutoxy for C1-4aminoalkyl: aminomethyl, aminoethyl, 3-aminopropyl and 2-aminopropyl for C1-4alkyl amino: methylamino, ethylamino and propylamino for C1-6alkylamino: C1-4alkylamino and 2-methylbutyl amino for di(C1-4alkyl)amino: dimethylamino, N-methyl-N-ethylamino and diethylamino for di(C1-6alkyl)amino: N-methyl-N-pentylamino for aminoC2-6alkoxy: aminoethoxy and 3-aminopropoxy for N-C1-6alkylaminoC2-6alkoxy: N-ethylaminoethoxy for N,N-di(C1-6alkyl)aminoC2-6alkoxy: N,N-dimethylaminoethoxy for C2-4alkanoyl: acetyl and propionyl for C1-4alkanoyl: acetyl and propionyl for C2-6alkanoyl: C2-4alkanoyl and pentanoyl for C1-6alkanoyl: C1-4alkanoyl and hexanoyl for C1-3alkanoyloxy: acetyloxy and propionyloxy for C1-4alkanoyloxy: C1-3alkanoyloxy and butanoyloxy for C1-6alkanoyloxy: C1-4alkanoyloxy and hexanoyloxy for C1-4alkanoylamino: acetylamino and propionylamino for C1-6alkanoylamino: C1-4alkanoylamino and pentanoylamino for N,N-di(C1-4alkanoyl)amino: N,N-diacetylamino for C1-4alkoxycarbonyl: methoxycarbonyl, ethoxycarbonyl and tert-butoxycarbonyl for C1-6alkoxycarbonyl: C1-4alkoxycarbonyl and pentoxycarbonyl for N-C1-6alkylcarbamoyl: N-methylcarbamoyl and N-ethylcarbamoyl for N,N-di(C1-6alkyl)carbamoyl: N,N-dimethylcarbamoyl and N,N-diethylcarbamoyl for C1-4alkylsulphonylC1-4alkyl: methylsulphonylmethyl and methylsulphonylethyl for C1-4alkylsulphanyl: methylsulphanyl and ethylsulphanyl for C1-4alkylsulphinyl: methylsulphinyl and ethylsulphinyl for C1-4alkylsulphonyl: methylsulphonyl and ethylsulphonyl for N-C1-4alkylcarbamoyl: N-methylcarbamoyl and N-ethylcarbambyl for N,N-di(C1-4alkyl)carbamoyl: N,N-dimethylcarbamoyl and N-ethyl-N-methylcarbamoyl for N-(C1-4alkyl)aminosulphonyl: N-methylaminosulphonyl and N-ethylaminosulphonyl for N-(C1-6alkyl)aminosulphonyl: N-(C1-4alkyl)aminosulphonyl and N-hexylaminosulphonyl for N,N-di(C1-4alkyl)aminosulphonyl: N,N-dimethylaminosulphonyl for N,N-di(C1-6alkyl)aminosulphonyl: N,N-di(C1-4alkyl)aminosulphonyl and N-hexyl-N-methylaminosulphonyl for C1-4alkylsulphonylamino: methylsulphonylamino and ethylsulphonylamino for C1-6alkylsulphonylamino: C1-4alkylsulphonylamino and hexylsulphonylamino for C1-6alkylsulphonyl-N-(C1-6alkyl)amino: methylsulphonyl-N-ethylamino for N-(C1-6alkyl)imino: N-methylimino and N-ethylimino for iminoC1-6alkylene: iminomethylene and iminoethylene for C1-6alkylene-iminoC1-6alkylene: methyleneiminomethylene for N-(C1-6alkyl)iminoC1-6alkylene: N-ethyliminomethylene for C1-6alkylene-N-(C1-6alkyl)iminoC1-6alkylene: ethylene-N-methyliminomethylene for C1-6alkylene: methylene, ethylene and propylene for oxyC1-6alkylene: oxymethylene, oxyethylene and oxypropylene for C1-6alkylene oxyC1-6alkylene: methyleneoxyethylene. Within the present invention it is to be understood that a compound of the formula (I), formula (IA) or formula (IB) or a salt, ester or amide thereof may exhibit the phenomenon of tautomerism and that the formulae drawings within this specification can represent only one of the possible tautomeric forms. It is to be understood that the invention encompasses any tautomeric form which has Aurora kinase inhibition activity and in particular Aurora-A kinase or Aurora-B kinase inhibition activity and is not to be limited merely to any one tautomeric form utilized within the formulae drawings. The formulae drawings within this specification can represent only one of the possible tautomeric forms and it is to be understood that the specification encompasses all possible tautomeric forms of the compounds drawn not just those forms which it has been possible to show graphically herein. The possibility of tautomeric forms is particular pertinent for R5 when R62 is hydrogen. It is also to be understood that, insofar as certain compounds of the invention may exist in optically active or racemic forms by virtue of one of more racemic carbon or sulphur atom, the invention includes in its definition any such optically active or racemic form which possesses Aurora kinase inhibitory activity and in particular Aurora-A kinase inhibitory activity. The synthesis of optically active forms may be carrier out by standard techniques of organic chemistry well known in the art, for example by synthesis from optically active starting materials or by resolution of a racemic form. It is also to be understood that certain compounds of the formula (I), formula (IA) or formula (IB) and salts thereof can exist in solvated as well as unsolvated forms such as, for example, hydrated forms. It is to be understood that the invention encompasses all such solvated forms which have Aurora kinase inhibition activity and in particular Aurora-A kinase inhibition activity. Compounds of the present invention have been named using computer software (ACD/Name version 6.6 or ACD/Name batch version 6.0). Preferred values of X, R1, R2, R3, R4 and R5 are as follows. Such values may be used where appropriate with any of the definitions, claims or embodiments defined hereinbefore or hereinafter. In one aspect of the invention X is NR6 or O. In another aspect X is NH. In one aspect of the invention R6 is hydrogen or C1-3alkyl. In another aspect R6 is hydrogen. In one aspect of the invention R1 is hydrogen or —X1R9. In another aspect R1 is hydrogen or —X1R9 where X1 is a direct bond, —O—, —NH— or —NMe— and R9 is selected from a group 1), 3), 5), 9) or 20) as defined above. In a yet another aspect R1 is hydrogen or —X1R9 where X1 is a direct bond, —O— or —NH— and R9 is hydrogen, C1-5alkyl, C3-6cycloalkyl, C1-5alkyl-O—C1-3alkyl or a 5- to 6-membered saturated heterocyclic group (linked via carbon or nitrogen) with 1 or 2 heteroatoms selected independently from O, S or N which heterocyclic groups is optionally substituted by C1-4alkyl or a 5- or 6-membered aromatic heterocyclic group (linked via carbon or nitrogen with 1, 2 or 3 heteroatoms. In a further aspect R1 is hydrogen, methoxy, N-(C1-5alkyl)piperidin-4-yloxy, prop-2-yloxy or methoxyethoxy. In an even further aspect R1 is hydrogen. In one aspect of the invention R2 is hydrogen, halo or —X1R9. In a further aspect of the invention R2 is hydrogen, halo or —X1R9 where X1 is a direct bond or —O— and R9 is a group 1) as defined above. In yet another aspect R2 is hydrogen, halo, hydroxy, methoxy or —OC1-3alkyl (optionally substituted by 1 or 2 hydroxy or halo). In a further aspect R2 is hydrogen or methoxy. In one aspect R3 is —X1R9. In another aspect R3 is —X1R9 where X1 is —O— and R9 is selected from a group 3), 4), 6), 18), 19) or 22) as defined above. In yet another aspect R3 is —X1R9 where X1 is —O— and R9 is C1-5alkylR32, C1-5alkylR96, C1-5alkyl (optionally substituted by halo), —C1-5alkyl-OR20, —C1-5alkyl-NHR20, —C1-5alkyl-N(C1-3alkyl)-R20, —C1-5alkyl-NH—C1-5alkyl-OH, —C1-5alkyl-N(C1-3alkyl)-C1-5alkyl-OH and —C1-5alkyl-NR95—C1-5alkyl-OH. In yet another aspect R3 is —X1R9 where X1 is —O— and R9 is —C1-5alkylR32 (where R32 is pyrrolidinyl, piperidinyl or piperazinyl each being optionally substituted by hydroxy, hydroxymethyl, 2-hydroxyethyl, methyl or 2-(ten-butoxy)ethyl), C1-5alkyl-NHR20, C1-5alkyl-NH—C1-5alkyl-OH, —C1-5alkyl-N(C1-3alkyl)-C1-5alkyl-OH and —C1-5alkyl-NR95—C1-5alkyl-OH. In a further aspect R3 is 3-morpholinopropoxy, 3-chloropropoxy, 3-[N-ethyl-N-(2-hydroxyethyl)amino]propoxy, 3-(2-hydroxymethylpyrrolidin-1-yl)propoxy, 3-(piperidin-1-yl)propoxy, 3-(pyrrolidin-1-yl)propoxy, 3-(N-(2-hydroxyethyl)amino]propoxy, 3-[N-(2-hydroxy-1,1-dimethylethyl)amino}propoxy, 3-[N-methyl-N-(2-hydroxyethyl)amino)propoxy, 3-[N-(1-hydroxymethyl-2-methylpropyl)amino]propoxy, 3-(4-methylpiperazin-1-yl)propoxy, 3-[N-(2-hydroxy-1-methylethyl)amino]propoxy, 3-[N-(4-hydroxybutyl)amino]propoxy, 3-(4-hydroxypiperidin-1-yl)propoxy, 3-[2-(2-hydroxyethyl)piperidin-1-yl]propoxy, 3-[4-(2-hydroxyethyl)piperazin-1-yl]propoxy, 3-[4-(2-hydroxyethyl)piperidin-1-yl]propoxy, 3-(3-hydroxypiperidin-1-yl)propoxy, 3-[N-2-(hydroxybutyl)amino]propoxy, 3-(4 hydroxymethylpiperidin-1-yl)propoxy, 3-[N-(3-hydroxy-2,2-methylpropyl)amino]propoxy, 3-[N-(1-hydroxymethylcyclopent-1-yl)amino]propoxy, 3-[N-(2-hydroxypropyl)amino]propoxy, 3-(3-hydroxypyrrolidin-1-yl)propoxy, 3-[N-(2-fluoroethyl)-N-(2-hydroxyethyl)amino]propoxy, 2-[1-(2-hydroxyethyl)piperidin-4-yl]ethoxy, 3-[N-(2-hydroxyethyl)-N-propylamino]propoxy, 3-[N-(2-hydroxyethyl)-N-(prop-2-yl)amino]propoxy, 3-[N-(2-hydroxyethyl)-N-isobutylamino]propoxy, 3-[N-(2-hydroxyethyl)-N-neopentylamino]propoxy, 3-[N-allyl-N-(2-hydroxyethyl)amino]propoxy, 3-[N-(2-hydroxyethyl)-N-(prop-2-yn-1-yl)amino]propoxy, 3-[N-cyclopropyl-N-(2-hydroxyethyl)amino]propoxy, 3-[N-cyclopropylmethyl-N-(2-hydroxyethyl)amino]propoxy, 3-[N-cyclobutyl-N-(2-hydroxyethyl)amino]propoxy, 3-[N-cyclopentyl-N-(2-hydroxyethyl)amino]propoxy, 3-[N-(2,2-dimethoxyethyl)-N-(2-hydroxyethyl)amino]propoxy, 3-[N-(2,2-difluoroethyl)-N-(2-hydroxyethyl)amino]propoxy, 3-[N-(2-hydroxyethyl)-N-(3,3,3-trifluoropropyl)amino]propoxy, 3-[N-cyclobutylmethyl-N-(2-hydroxyethyl)amino]propoxy, 3-[N-(2-hydroxyethyl)-N-(2-methoxyethyl)amino]propoxy, 3-[N-(1,3-dioxolan-2-ylmethyl)-N-(2-hydroxyethyl)amino]propoxy, 4-chlorobutoxy, 4-[(2-hydroxymethyl)pyrrolidin-1-yl]butoxy, 4[N-(2-hydroxyethyl)-N-isobutylamino]butoxy, 1-(2-tert-butoxyethyl)pyrrolidin-2-ylmethoxy, 1-(2-hydroxyethyl)pyrrolidin-2-ylmethoxy, 3-[N-2-(hydroxyethyl)-N-(iso-butyl)amino]propoxy, 3-[N-2-(hydroxyethyl)-N-(neopentyl)amino]propoxy, 3-CN-2-(hydroxyethyl)-N-(tert-butyl)amino]propoxy, methoxy and methoxyethoxy. In one aspect of the invention R32 is a 5- or 6-membered saturated heterocyclic group (linked via carbon or nitrogen) with 1 or 2 heteroatoms selected independently from O, S, and N which group is optionally substituted by 1 or 2 substituents selected from C1-4hydroxyalkyl, C1-4alkyl, hydroxy and C1-4alkoxyC1-4alkyl. In another aspect R32 is morpholino, pyrrolidinyl, piperidinyl or piperazinyl each being optionally substituted by hydroxy, hydroxymethyl, 2-hydroxyethyl, methyl or 2-(tert-butoxy)ethyl. In a further aspect R32 is 2-hydroxymethylpyrrolidin-1-yl, piperidin-1-yl, pyrrolidin-1-yl, 4-methylpiperazin-1-yl, 4-hydroxypiperidin-1-yl, 2-(2-hydroxyethyl)piperidin-1-yl, 4-(2-hydroxyethyl)piperazin-1-yl, 4-(2-hydroxyethyl)piperidin-1-yl, 4-hydroxymethylpiperidin-1-yl, 3-hydroxypyrrolidin-1-yl, 1-(2-hydroxyethyl)piperidin-4-yl, 1-(2-tert-butoxyethyl)pyrrolidin-2-yl and 1-(2-hydroxyethyl)pyrrolidin-2-yl. In one aspect of the invention R20 is C1-3alkyl (optionally substituted by hydroxy) or cyclopentyl (optionally substituted by C1-4hydroxyalkyl). In a further aspect R20 is 2-hydroxyethyl, 1-hydroxyprop-2-yl, 2-hydroxyprop-1-yl and 1-hydroxymethylcyclopentyl. In one aspect of the invention R95 is methyl, ethyl, 2-fluoroethyl, prop-1-yl, prop-2-yl, isobutyl, neopentyl, allyl, propargyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, cyclobutylmethyl, methoxyethyl, 1,3-dioxolan-2-ylmethyl and 2,2-dimethoxyethyl. In one aspect of the invention R96 is 4,5-dihydro-1H-imidazoyl optionally substituted by hydroxy or C1-4hydroxyalkyl. In one aspect of the invention R4 is hydrogen. In one aspect of the invention X1 is a direct bond, —O— or —N(C1-3alkyl)-. In another aspect X1 is —O—. In one aspect of the invention R9 is a group selected from group 1), 3), 4), 5), 6), 9), 18), 19), 20) and 22). In another aspect R9 is hydrogen, C3-6cycloalkyl, —C1-5alkyl-O—C1-3alkyl or a 5- to 6-membered saturated heterocyclic group (linked via carbon or nitrogen) with 1 or 2 heteroatoms selected independently from O, S or N which heterocyclic group is optionally substituted by C1-4alkyl or R9 is a 5- or 6-membered aromatic heterocyclic group (linked via carbon or nitrogen) with 1, 2 or 3 heteroatoms or R9 is —C1-5alkylR32, —C1-5alkylR96, C1-5alkyl (optionally substituted by halo), —C1-5alkyl-OR20, —C1-5alkyl-NHR20, —C1-5alkyl-N(C1-3alkyl)-R20, —C1-5alkyl-NH—C1-5alkyl-OH, —C1-5alkyl-N(C1-3alkyl)-C1-5alkyl-OH and —C1-5alkyl-NR95—C1-5alkyl-OH. In one aspect of the invention R60 is hydrogen, nitro, halo, cyano, oxo or C1-3alkyl. In another aspect R60 is a group of sub-formula (k) as defined above. In a further aspect R60 is hydrogen. In one aspect of the invention R61 is a group selected from hydrogen, cyano, nitro halo, C1-6alkyl, aryl, arylC1-6alkyl, heterocyclyl, heterocyclylC1-6alkyl (where aryl and heterocyclyl of the latter four groups are optionally substituted by 1, 2 or 3 substitutents independently selected from halo, hydroxy, mercapto, carboxy, C1-4alkyl (optionally substituted by 1, 2 or 3 halo), aryl, heteroaryl, amino, cyano, nitro, C1-4alkylamino, di(C1-4alkyl)amino and S(O)y where y is 0, 1 or 2), a group of sub-formula (k) as defined above, a group of sub-formula (II) as defined above and a group of formula (VI) as defined above. In another aspect R61 is a group of sub-formula (k) as defined above. In yet a further aspect of the invention R61 is J, —(CH2)-J, —(CH2)2-J, —O-J, —(CH2)—O-J, —O—(CH2)-J, —(CH2)—O—(CH2)-J, —CO-J, —(CH2)—CO-J, —CO—(CH2)-J, —(CH2)—CO—(CH2)-J, —S-J, —(CH2)—S-J, —S—(CH2)-J, —(CH2)S—(CH2)-J, —SO-J, —(CH2)—SO-J, —SO—(CH2)-J, —(CH2)—SO—(CH2)-J, —SO2-J, —(CH2)—SO2-J, —SO2—(CH2)-J, —(CH2)—SO2—(CH2)-J, —(NR1′)CO-J, —(CH2)(NR1′)CO-J, —(NR1′)CO—(CH2)-J, —(CH2)—(NR1′)CO—(CH2)-J, —(NR1′)SO2-J, —(CH2)—(NR1′)SO2-J, —(NR1′)SO2—(CH2)-J, —(CH2)—(NH1′)SO2—(CH2)-J, —NR64-J, —(CH2)—NR64-J, —NR64—(CH2)-J, —(CH2)—NR64—(CH2)-J, —CONR64-J, —(CH2)—CONR64-J, —CONR64—(CH2)-J, —(CH2)—CONR64—(CH2)-J, —SO2NR64-J, —(CH2)—SO2NR64-J, —SO2NR64—(CH2)-J, —(CH2)—SO2NR64—(CH2)-J, —NR1′CO—NH-J, —(CH2)—NR1′CO—NH-J, —NR1′CO—NH—(CH2)-J, —(CH2)—NR1′CO—NH—(CH2)-J, —NR1′CO—N(C1-4alkyl)-J, —(CH2)—NR1′CO—N(C1-4alkyl)-J, —NR1′CO—N(C1-4alkyl)-(CH2)-J, —(CH2)—NR1′CO—N(C1-4alkyl)-(CH2)-J, —NR1′CO-J, —(CH2)—NR1′CO—O-J, —NR1′CO—(CH2)-J, —(CH2)—NR1′C—O—(CH2)-J, OCO-J, —CH2—OCO-J, —CH═CH-J, —CH2—CH═CH-J, —CH═CH—CH2-J and —CH2—CH═CH—CH2-J. In yet a further aspect R61 is —CONR64-J or —(CH2)CONR64-J. In another aspect R61 is —(CH2)CONR64-J. In one aspect of the invention R62 is a group selected from hydrogen, cyano, nitro halo, C1-6alkyl, aryl, arylC1-6alkyl, heterocyclyl, heterocyclylC1-6alkyl (where aryl and heterocyclyl of the latter four groups are optionally substituted by 1, 2 or 3 substitutents independently selected from halo, hydroxy, mercapto, carboxy, C1-6alkyl (optionally substituted by 1, 2 or 3 halo), aryl, heteroaryl, amino, cyano, nitro, C1-6alkylamino, di(C1-6alkyl)amino and S(O)y where y is 0, 1 or 2), a group of sub-formula (K) as defined above, a group of sub-formula (II) as defined above and a group of formula (VI) as defined above. In another aspect R62 is a group of sub-formula (k) as defined above. In yet another aspect of the invention R62 is hydrogen, halo or C1-3alkyl. In a further aspect R62 is hydrogen. Preferred values of R1′, R1″, p, T, V, r and R70 are as follows. Such values may be used where appropriate with any of the definitions, claims or embodiments defined hereinbefore or hereinafter. In one aspect of the invention R1′ is hydrogen or C1-3alkyl. In one aspect of the invention R1″ is hydrogen or C1-3alkyl. In one aspect of the invention p is 1. In one aspect of the invention T is C═O, SOn (where n is 0, 1 or 2), C(═NOR)CO, C(O)C(O) or C═NCN. In another aspect T is C═O. In one aspect of the invention q is 1. In one aspect of the invention V is N(R63)R64. In one aspect of the invention R63 is —(CH2)q.R70 or aryl or heteroaryl where the latter two groups are optionally substituted by 1 or 2 substituents independently selected from halo, C1-4alkyl, C1-4alkoxy, trifluoromethyl, trifluoromethoxy, hydroxy, nitro, difluoromethyl, difluoromethoxy and cyano. In another aspect R63 is aryl optionally substituted by 1 or 2 substituents independently selected from halo, C1-4alkyl, C1-4alkoxy, trifluoromethyl, trifluoromethoxy, hydroxy, nitro, difluoromethyl, difluoromethoxy and cyano. In one aspect of the invention R64 is hydrogen or C1-3alkyl. In another aspect R64 is hydrogen. In one aspect of the invention R70 is a group of formula (III) —K-J. In one aspect of the invention K is a bond, oxy, imino, N-(C1-4alkyl)imino, oxyC1-4alkylene, iminoC1-4alkylene and N-(C1-4alkyl)iminoC1-4alkylene. In another aspect K is a bond. In one aspect of the invention J is aryl or heteroaryl which are both optionally substituted by 1, 2 or 3 substitutents selected from halo, C1-3alkyl, C3-4cycloalkyl, C3-4cycloalkylC1-3alkyl, cyano and C1-3alkoxy. In another aspect J is a group select from phenyl, pyridyl, pyrimidinyl, furyl, thienyl and pyrrolyl which group is optionally substituent by 1 or 2 substituents selected from halo, methyl, ethyl, methoxy, cyano, cyclopropyl and cyclopropylmethyl. In yet another aspect J is phenyl optionally substituted by 1 or 2 halo. In a further aspect of the invention J is 3-fluorophenyl, 2,3-difluorophenyl, 3,5-difluorophenyl, 3-chlorophenyl, 3-methoxyphenyl, phenyl, 4-fluorophenyl, 3,5-dichlorophenyl, 5-chloro-2-methoxyphenyl, 3-trifluoromethylphenyl, 3-hydroxyphenyl, 3-nitrophenyl, 4-bromo-2-fluorophenyl, 3,5-dimethoxyphenyl, 3-chloro-2-fluorophenyl, 2-fluoro-3-trifluormethylphenyl, 3,4-difluorophenyl, 2,4-difluorophenyl, 3-chloro-4-fluorophenyl, 2-difluoromethoxyphenyl, 3-cyanophenyl, 3-bromophenyl, 5-indanzolyl and 5-methylpyridin-2-yl. Preferably R4 is hydrogen. Suitably R1 is hydrogen or a group set out for R2 or R3 below. Frequently, R1 is hydrogen. In a preferred embodiment, at least one group R1, R2 or R3, preferably R3, comprises a chain of at least 3 and preferably at least 4 optionally substituted carbon atoms or heteroatoms such as oxygen, nitrogen or sulphur. Most preferably the chain is substituted by a polar group which assists in solubility. Suitably R3 is a group X1R9. Preferably in this case, X1 is oxygen and R9 is selected from a group of formula (1) or (10) above. Particular groups R9 are those in group (1) above, especially alkyl such as methyl or halo substituted alkyl, or those in group (10) above. In one preferred embodiment, at least one of R2 or R3 is a group —OC1-5alkylR33 and R33 is a heterocyclic ring such as an N-linked morpholine ring such as 3-morpholinopropoxy. Suitably R2 is selected from, halo, cyano, nitro, trifluoromethyl, C1-3alkyl, —NR9R10 (wherein R9 and R10, which may be the same or different, each represents hydrogen or C1-3alkyl), or a group —X1R11. Preferred examples of —X1R11 for R2 include those listed above in relation to R3. Other examples for R2 and R3 include methoxy or 3,3,3-trifluoroethoxy. Preferably X is NH or O and is most preferably NH. In one aspect of the invention, one of R60, R61 or R62 is a substituent group and the others are either hydrogen or a small substituent such as C1-3 alkyl, for instance methyl. Suitably R62 is hydrogen. Preferably R61 is other than hydrogen. Suitable substituents for groups R5 include optionally substituted hydrocarbyl, optionally substituted heterocylyl or a functional group as defined above. In particular, R60, R61 or R62 is a group of sub-formula (k) where p and q are independently 0 or 1 and wherein R1′ and R1″ are independently hydrogen, hydroxy, optionally substituted alkyl, optionally substituted cycloalkyl, halogen, cyano, optionally substituted alkyl, optionally substituted alkyenyl. The optionally substituted alkyl or alkynyl may be substituted with halo, nitro, cyano, hydroxy, trifluoromethyl, amino, carboxy, carbamoyl, mercapto, sulphamoyl, C1-4 alkyl, C2-4alkenyl, C2-4 alkynyl, C3-6 cycloalkyl, C3-4 cycloalkenyl, C1-4 alkoxy, C1-4 alkanoyl, C1-4 alkanoyloxy, N-(C1-4 alkyl), N(C1-4 alkyl)2, C1-4 alkanoylamino, (C1-4 alkanoyl)2amino, N-(C1-4alkyl)carbamoyl, N,N-(C1-4)2carbamoyl, C1-4)S, C1-4S(O), (C1-4alkyl)S(O)2, (C1-4)alkoxycarbonyl, N-(C1-4 alkyl)sulphamoyl, N,N-C1-4 alkyl)sulphamoyl, C1-4 alkylsulphonylamino, or heterocyclyl. R is preferably C1-4 alkyl, C2-4alkenyl, or C2-4 alkynyl, and R1′ can form with R1″ a 3 to 6 membered ring. T is C═O, SOn, C(═NOR)CO, C(O)C(O), C═NCN, CV═NO or wherein n=0, 1 or 2 and V is independently R63 or N(R63)R64 wherein R63 and R64 are independently selected from hydrogen, optionally substituted hydrocarbyl or optionally substituted heterocyclyl, or R63 and R64 together with the nitrogen atom to which they are attached form an optionally substituted heterocyclic ring. Examples of groups for R63 and R64 include the group —(CH2)qR70 where q and R70 are as defined below in relation to formula (II). Suitably one of R63 or R64 is hydrogen, or methyl, ethyl or propyl optionally substituted with hydroxy and preferably one of R63 or R64 is hydrogen. In this case, the other is suitably a larger substituent for example of at least 4 carbon or heteroatoms, and is optionally substituted hydrocarbyl or optionally substituted heterocyclyl. Particular optionally substituted hydrocarbyl groups for R63 or R64 include alkyl, cycloalkyl, alkenyl, or aryl any of which is optionally substituted with a functional group as defined above, or in the case of aryl groups, with an alkyl group and in the case of alkyl group, with an aryl or heterocyclic group either of which may themselves be optionally substituted with alkyl or a functional group. Examples of optionally substituted aryl groups R63 or Re include phenyl optionally substituted with one or more groups selected from C1-6 alkyl group such as methyl or ethyl (either of which may be optionally substituted with a functional group such as hydroxy), or a functional group as defined above (such as halo like fluoro, chloro or bromo, hydroxy, alkoxy such as methoxy, trifluoromethyl, nitro, cyano, trifluoromethoxy, CONH2, C(O)CH3, amino, or dimethylamino). When R63 or R64 is an optionally substituted alkyl group, it is suitably a C1-6alkyl group, optionally substituted with one or more functional groups (such as cyano, hydroxy, alkoxy, in particular methoxy, COOalkyl such as COOCH3), or aryl optionally substituted with a functional group as defined above (in particular in relation to R63 or R64 themselves, or an optionally substituted heterocyclic group such as N-methylpyrrole. When R63 and R64 is optionally substituted cycloalkyl, it is suitable cyclohexyl optionally substituted with a functional group such as hydroxy. When R63 and R64 is optionally substituted alkenyl, it is suitably prop-2-enyl. When R63 or R64 is optionally substituted heterocyclyl, or R63 and R64 together form a heterocyclic group, then this may be aromatic or non-aromatic and includes in particular, piperidine, piperazine, morpholino, pyrrolidine or pyridine any of which may be optionally substituted with a functional group such as hydroxy, alkoxy such as methoxy, or alkyl such as methyl which may itself be substituted with for instance a hydroxy group. Alternatively at least one of R60, R61 or R62 is a functional group, and in particular, one of R60, R61 or R62 is a functional group a group of formula (CR2)pC(O)xR77 where R, p, x and R77 are as defined above, and in particular x is 2 and R77 is hydrogen or alkyl such as methyl. Alternatively, R5 is substituted by one or more groups selected from nitro, halo, C1-6alkyl, optionally substituted C1-4 alkoxy, C1-4alkoxymethyl, di(C1-4alkoxy)methyl, C1-6alkanoyl, trifluoromethyl, cyano, amino, C2-4alkenyl, C2-6alkynyl, a phenyl group, a benzyl group or a 5-6-membered heterocyclic group with 1-3 heteroatoms, selected independently from O, S and N, which heterocyclic group may be aromatic or non-aromatic and may be saturated (linked via a ring carbon or nitrogen atom) or unsaturated (linked via a ring carbon atom), and which phenyl, benzyl or heterocyclic group may bear on one or more ring carbon atoms up to 5 substituents selected from hydroxy, halogeno, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino, nitro, C2-4alkanoyl, C1-4alkanoylamino, C1-4alkoxycarbonyl, C1-4alkylsulphanyl, C1-4alkylsulphinyl, C1-4alkylsulphonyl, carbamoyl, N-C1-4alkylcarbamoyl, N,N-di(C1-4alkyl)carbamoyl, aminosulphonyl, N-C1-4alkylaminosulphonyl, N,N-di(C1-4alkyl)aminosulphonyl, C1-4alkylsulphonylamino, and a saturated heterocyclic group selected from morpholino, thiomorpholino, pyrrolidinyl, piperazinyl, piperidinyl imidazolidinyl and pyrazolidinyl, which saturated heterocyclic group may bear 1 or 2 substituents selected from oxo, hydroxy, halogeno, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino, nitro and C1-4alkoxycarbonyl. Suitably R5 is substituted with at least one group which has at least 4 atoms which may be carbon or heteroatoms forming a chain. A particular example of such a substituent is optionally substituted alkoxy or alkoxy methyl. Suitable substituents for the alkoxy group include those listed above in relation to R77, R78 and R79. A further particular substituent group for R5 is a group of sub-formula (II) where p and q are independently 0 or I, and r is 0, 1, 2, 3 or 4 and, R1′, R1″ and T are as previously defined above; R70 is hydrogen, hydroxy (other than where q is 0), C1-6alkyl, C1-6alkoxy, amino, N-C1-6alkylamino, N,N-(C1-6alkyl)2amino, hydroxyC2-6alkoxy, C1-6alkoxyC2-6alkoxy, aminoC2-6alkoxy, N-C1-6alkylaminoC2-6alkoxy, N,N-(C1-6alkyl)2aminoC2-6alkoxy or C3-7cycloalkyl, or R70 is of the Formula (III): —K-J (III) wherein J is aryl, heteroaryl or heterocyclyl and K is a bond, oxy, imino, N-(C1-6alkyl)imino, oxyC1-6alkylene, iminoC1-6alkylene, N-(C1-6alkyl)iminoC1-6alkylene, —NHC(O)—, —SO2NH—, —NHSO2— or —NHC(O)—C1-6alkylene-, and any aryl, heteroaryl or heterocyclyl group in a R70 group may be optionally substituted by one or more groups selected from hydroxy, halo, trifluoromethyl, cyano, mercapto, nitro, amino, carboxy, carbamoyl, formyl, sulphamoyl, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, —O—(C1-3alkyl)-O—, C1-6alkylS(O)n— (wherein n is 0-2), N-C1-6alkylamino, N,N-(C1-6alkyl)2amino, C1-6alkoxycarbonyl, N-C1-6alkylcarbamoyl, N,N-(C1-6alkyl)2carbamoyl, C2-6alkanoyl, C1-6alkanoyloxy, C1-6alkanoylamino, N-C1-6alkylsulphamoyl, N,N-(C1-6alkyl)2sulphamoyl, C1-6alkylsulphonylamino and C1-6alkylsulphonyl-N-(C1-6alkyl)amino, or any aryl, heteroaryl or heterocyclyl group in a R70 group may be optionally substituted with one or more groups of the Formula (IV): —B1—(CH2)p-A1 (IV) wherein A1 is halo, hydroxy, C1-6alkoxy, cyano, amino, N-C1-6alkylamino, N,N-(C1-6alkyl)2amino, carboxy, C1-6alkoxycarbonyl, carbamoyl, N-C1-6alkylcarbamoyl or N,N-(C1-6alkyl)2carbamoyl, p is 1-6, and B1 is a bond, oxy, imino, N-(C1-6alkyl)imino or —NHC(O)—, with the proviso that p is 2 or more unless B1 is a bond or —NHC(O)—; or any aryl, heteroaryl or heterocyclyl group in a R70 group may be optionally substituted with one or more groups of the Formula (V): -E1-D1 (V) wherein D1 is aryl, heteroaryl or heterocyclyl and E1 is a bond, C1-6alkylene, oxyC1-6alkylene, oxy, imino, N-(C1-6alkyl)imino, iminoC1-6alkylene, N-(C1-6alkyl)-iminoC1-6alkylene, C1-6alkylene-oxyC1-6alkylene, C1-6alkylene-iminoC1-6alkylene, C1-6alkylene-N-(C1-6alkyl)-iminoC1-6alkylene, —NHC(O)—, —NHSO2—, —SO2NH— or —NHC(O)—C1-6alkylene-, and any aryl, heteroaryl or heterocyclyl group in a substituent on D1 may be optionally substituted with one or more groups selected from hydroxy, halo, C1-6alkyl, C1-6alkoxy, carboxy, C1-6alkoxycarbonyl, carbamoyl, N-C1-6alkylcarbamoyl, N-(C1-6alkyl)2carbamoyl, C2-alkanoyl, amino, N-C1-6alkylamino and N,N-(C1-6alkyl)2amino, and any C3-7cycloalkyl or heterocyclyl group in a R70 group may be optionally substituted with one or two oxo or thioxo substituents, and any of the R70 groups defined hereinbefore which comprises a CH2 group which is attached to 2 carbon atoms or a CH3 group which is attached to a carbon atom may optionally bear on each said CH2 or CH3 group a substituent selected from hydroxy, amino, C1-6alkoxy, N-C1-6alkylamino, N,N-(C1-6alkyl)2amino and heterocyclyl. A preferred example of a substituent of formula (II) is a group where q is 0. A particular example of a group R70 in formula (II) is phenyl. Another preferred substituent group for R5 is a group of formula (VI) where R71 and R72 are independently selected from hydrogen or C1-6alkyl, or R71 and R72 together form a bond, and R73 is a group OR74, NR75R76 where R74, R75 and R76 are independently selected from optionally substituted hydrocarbyl or optionally substituted heterocyclic groups, and R75 and R76 may additionally form together with the nitrogen atom to which they are attached, an aromatic or non-aromatic heterocyclic ring which may contain further heteroatoms. Suitable optional substituents for hydrocarbyl or heterocyclic groups R74, R75 and R76 include functional groups as defined above. Heterocyclic groups R74, R75 and R76 may further be substituted by hydrocarbyl groups. In particular, R71 and R72 in sub-formula (VI) are hydrogen. Particular examples of R73 are groups OR74 where R74 is C—4alkyl. Further examples of R73 are groups of formula NR75R76 where one of R75 or R76 is hydrogen and the other is optionally substituted C1-6alkyl, optionally substituted aryl or optionally substituted heterocyclyl. In particular, one of R75 or R76 is hydrogen and the other is C1-4alkyl optionally substituted with trifluoromethyl, C1-3 alkoxy such as methoxy, cyano, thioC1-4alkyl such as methylthio, or heterocyclyl optionally substituted with hydrocarbyl, such as indane, furan optionally substituted with C1-4 alkyl such as methyl. In another embodiment, one of R75 or R76 is hydrogen and the other is an optionally substituted heterocyclic group such as pyridine, or a phenyl group optionally substituted with for example one or more groups selected from halo, nitro, alkyl such as methyl, or alkoxy such as methoxy. A preferred class of compounds is of formula (I) wherein: X is NH; R1 is hydrogen, methoxy, N-(C1-5alkyl)piperidin-4-yloxy, prop-2-yloxy or methoxyethoxy; R2 is hydrogen or methoxy; R3 is 3-morpholinopropoxy, 3-chloropropoxy, 3-[N-ethyl-N-(2-hydroxyethyl)amino]propoxy, 3-(2-hydroxymethylpyrrolidin-1-yl)propoxy, 3-(piperidin-1-yl)propoxy, 3-(pyrrolidin-1-yl)propoxy, 3-(N-(2-hydroxyethyl)amino]propoxy, 3-[N-(2-hydroxy-1,1-dimethylethyl)amino]propoxy, 3-[N-methyl-N-(2-hydroxyethyl)amino]propoxy, 3-[N-(1-hydroxymethyl-2-methylpropyl)amino]propoxy, 3-(4-methylpiperazin-1-yl)propoxy, 3-[N-(2-hydroxy-1-methylethyl)amino]propoxy, 3-[N-(4-hydroxybutyl)amino]propoxy, 3-(4-hydroxypiperidin-1-yl)propoxy, 3-[2-(2-hydroxyethyl)piperidin-1-yl]propoxy, 3-[4-(2-hydroxyethyl)piperazin-1-yl]propoxy, 3-[4-(2-hydroxyethyl)piperidin-1-yl]propoxy, 3-(3-hydroxypiperidin-1-yl)propoxy, 3-[N-2-(hydroxybutyl)amino]propoxy, 3-(4-hydroxymethylpiperidin-1-yl)propoxy, 3-[N-(3-hydroxy-2,2-dimethylpropyl)amino]propoxy, 3-[N-(1-hydroxymethylcyclopent-1-yl)amino]propoxy, 3-[N-(2-hydroxypropyl)amino]propoxy, 3-(3-hydroxypyrrolidin-1-yl)propoxy, 3-[N-(2-fluoroethyl)-N-(2-hydroxyethyl)amino]propoxy, 2-[1-(2-hydroxyethyl)piperidin-4-yl]ethoxy, 3-[N-(2-hydroxyethyl)-N-propylamino]propoxy, 3-[N-(2-hydroxyethyl)-N-(prop-2-yl)amino]propoxy, 3-[N-(2-hydroxyethyl)-N-isobutylamino]propoxy, 3-[N-(2-hydroxyethyl)-N-neopentylamino]propoxy, 3-[N-allyl-N-(2-hydroxyethyl)amino]propoxy, 3-[N-(2-hydroxyethyl)-N-(prop-2-yn-1-yl)amino]propoxy, 3-[N-cyclopropyl-N-(2-hydroxyethyl)amino]propoxy, 3-[N-cyclopropylmethyl-N-(2-hydroxyethyl)amino]propoxy, 3-[N-cyclobutyl-N-(2-hydroxyethyl)amino]propoxy, 3-[N-cyclopentyl-N-(2-hydroxyethyl)amino]propoxy, 3-[N-(2,2-dimethoxyethyl)-N-(2-hydroxyethyl)amino]propoxy, 3-[N-(2,2-difluoroethyl)-N-(2-hydroxyethyl)amino]propoxy, 3-[N-(2-hydroxyethyl)-N-(3,3,3-trifluoropropyl)amino]propoxy, 3-[N-cyclobutylmethyl-N-(2-hydroxyethyl)amino]propoxy, 3-[N-(2-hydroxyethyl)-N-(2-methoxyethyl)amino]propoxy, 3-[N-(1,3-dioxolan-2-ylmethyl)-N-(2-hydroxyethyl)amino]propoxy, 4-chlorobutoxy, 4-[(2-hydroxymethyl)pyrrolidin-1-yl]butoxy, 4-[N-(2-hydroxyethyl)-N-isobutylamino]butoxy, 1-(2-tert-butoxyethyl)pyrrolidin-2-ylmethoxy, 1-(2-hydroxyethyl)pyrrolidin-2-ylmethoxy, 3-[N-2-(hydroxyethyl)-N-(iso-butyl)amino]propoxy, 3-[N-2-(hydroxyethyl)-N-(neopentyl)amino]propoxy, 3-[N-2-(hydroxyethyl)-N-(tert-butyl)amino]propoxy, methoxy and methoxyethoxy; R4 is hydrogen; R60 is hydrogen; R61 is a group of sub-formula (k) as defined above; R62 is hydrogen; R1′ is hydrogen or C1-3alkyl; R1″ it hydrogen or C1-3alkyl; p is 1; T is C═O; q is 1; V is N(R63)R64; R63 is —(CH2)q.R70 or aryl or heteroaryl where the latter two groups are optionally substituted by 1 or 2 substituents independently selected from halo, C1-4alkyl, C1-4alkoxy, trifluoromethyl, trifluoromethoxy, hydroxy, nitro, difluoromethyl, difluoromethoxy and cyano; R64 is hydrogen; R70 is a group of formula (III) —K-J; K is a bond; and J is 3-fluorophenyl, 2,3-difluorophenyl, 3,5-difluorophenyl, 3-chlorophenyl, 3-methoxyphenyl, phenyl, 4-fluorophenyl, 3,5-dichlorophenyl, 5-chloro-2-methoxyphenyl, 3-trifluoromethylphenyl, 3-hydroxyphenyl, 3-nitrophenyl, 4-bromo-2-fluorophenyl, 3,5-dimethoxyphenyl, 3-chloro-2-fluorophenyl, 2-fluoro-3-trifluormethylphenyl, 3,4-difluorophenyl, 2,4-difluorophenyl, 3-chloro-4-fluorophenyl, 2-difluoromethoxyphenyl, 3-cyanophenyl, 3-bromophenyl, 5-indanzolyl and 5-methylpyridin-2-yl. A further preferred class of compounds is of formula (I) wherein: X is NR6 or O; R6 is hydrogen or C1-3alkyl; R1 is hydrogen or —X1R9 where X1 is a direct bond, —O— or —NH— and R9 is hydrogen, C1-5alkyl, C3-6cycloalkyl, —C1-5alkyl-O—C1-3alkyl or a 5- to 6-membered saturated heterocyclic group (linked via carbon or nitrogen) with 1 or 2 heteroatoms selected independently from O, S or N which heterocyclic groups is optionally substituted by C1-4alkyl or a 5- or 6-membered aromatic heterocyclic group (linked via carbon or nitrogen with 1, 2 or 3 heteroatoms; R2 is hydrogen, hydroxy, halo, methoxy or —OC1-3alkyl (optionally substituted by 1 or 2 hydroxy or halo); R3 is —X1R9 where X1 is —O— and R9 is —C1-5alkylR32, —C1-5alkylR96, C1-5alkyl (optionally substituted by halo), —C1-5alkyl-OR20, —C1-5alkyl-NHR20, —C1-5alkyl-N(C1-3alkyl)-R20, —C1-5alkyl-NH—C1-5alkyl-OH, —C1-5alkyl-N(C1-3alkyl)-C1-5alkyl-OH and —C1-5alkyl-NR95—C1-5alkyl-OH; R32 is morpholino, pyrrolidinyl, piperidinyl or piperazinyl optionally substituted by hydroxymethyl, 2-hydroxyethyl, methyl, hydroxy or 2-(tert-butoxy)ethyl; R20 is C1-3alkyl optionally substituted by hydroxy) or cyclopentyl (optionally substituted by C1-4hydroxyalkyl); R95 is methyl, ethyl, 2-fluoroethyl, prop-1-yl, prop-2-yl, isobutyl, neopentyl, allyl, propargyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, cyclobutylmethyl, methoxyethyl, 1,3-dioxolan-2-ylmethyl and 2,2-dimethoxyethyl; R96 is 4,5-dihydro-1H-imidazoyl optionally substituted by C1-4hydroxyalkyl; R4 is hydrogen; R60 is hydrogen; R61 is J, —(CH2)-J, —(CH2)2-J, —O-J, —(CH2)-J, —(CH2)-J, —(CH2) (CH2)-J, —CO-J, —(CH2)—CO-J, —CO—(CH2)-J, —(CH2)—CO—(CH2)-J, —S-J, —(CH2)S-J, —S—(CH2)-J, —(CH2)—S—(CH2)-J, —SO-J, —(CH2)—SO-J, —SO—(CH2)-J, —(CH2)—SO—(CH2)-J, —SO2-J, —(CH2)—SO2-J, —SO2—(CH2)-J, —(CH2)—SO2—(CH2)-J, —(NR1′)CO-J, —(CH2)—(NR1′)CO-J, —(NR1′)CO—(CH2)-J-(CH2)—(NR1′)CO—(CH2)-J, —(NR1′)SO2-J, —(CH2)—(NR1′)SO2-J, —(NR1′)SO2—(CH2)-J-(CH2)—(NR1′)SO2—(CH2)-J, —NR64-J, —(CH2)—NR64-J, —NR64—(CH2)-J, —(CH2)—NR64—(CH2)-J, —CONR64-J, —(CH2)—CONR64-J, —CONR64—(CH2)-J, —(CH2)—CONR64—(CH2)-J, —SO2NR64-J, —(CH2)—SO2NR64-J, —SO2NR64—(CH2)-J, —(CH2)—SO2NR64—(CH2)-J, —NR1′CO—NH-J, —(CH2)—NR1′CO—NH-J, —NR1′CO—NH—(CH2)-J, —(CH2)—NR1′CO—NH—(CH2)-J, —NR1′CO—N(C1-4alkyl)-J, —(CH2)—NR1′CO—N(C1-4alkyl)-J, —NR1′CO—N(C1-4alkyl)-(CH2)-J, —(CH2)—NR1′CON(C1-4alkyl)-(CH2)-J, —NR1′CO-J, —(CH2)—NR1′CO—O-J, —NR1′CO—O—(CH2)-J, —(CH2)—NR1′CO—O—(CH2)-J, —OCO-J, —CH2—OCO-J, —CH═CH-J, —CH2CH═CH-J, —CH═CH—CH2-J and —CH2CH═CH—CH2-J; R62 is hydrogen, halo or C1-3alkyl; R1′ is hydrogen or C1-3alkyl; R64 is hydrogen or C1-3alkyl; and J is a group select from phenyl, pyridyl, pyrimidinyl, furyl, thienyl and pyrrolyl which group is optionally substituent by 1 or 2 substituents selected from halo, methyl, ethyl, methoxy, cyano, cyclopropyl and cyclopropylmethyl. In another aspect of the invention, preferred compounds are any one of: 2-(3-{[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)-N-phenylacetamide; N-(3-fluorophenyl)-2-(3-{[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetamide; 2-(3-{[7-(3-chloropropoxy)-6-methoxyquinazolin-4-yl]amino}-1H-pyrazol-5-yl)-N-(3-fluorophenyl)acetamide; 2-(3-{[7-(3-chloropropoxy)-6-methoxyquinazolin-4-yl]amino}-1H-pyrazol-5-yl)-N-(3,5-difluorophenyl)acetamide; 2-(3-{[7-(3-chloropropoxy)-6-methoxyquinazolin-4-yl]amino}-1H-pyrazol-5-yl)-N-(2,3-difluorophenyl)acetamide; N-(3-chlorophenyl)-2-(3-{[7-(3-chloropropoxy)-6-methoxyquinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetamide; 2-{3-[(7-{3-[ethyl(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide; N-(3-fluorophenyl)-2-{3-[(7-{3-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3-fluorophenyl)-2-(3-{[6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetamide; N-(3-fluorophenyl)-2-(3-([6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin 4-yl]amino)-1H-pyrazol-5-yl)acetamide; N-(3-fluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3-fluorophenyl)-2-{3-[(7-{3-[(2-hydroxy-1,1-dimethylethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3-fluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(methyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3-fluorophenyl)-2-(3-{[7-(3-{[1-(hydroxymethyl)-2-methylpropyl]amino}propoxy)-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3-fluorophenyl)-2-[3-({6-methoxy-7-{3-(4-methylpiperazin-1-yl)propoxy]quinazolin-4-yl}amino)-1H-pyrazol-5-yl}acetamide; N-(3-fluorophenyl)-2-{3-[(7-{3-[(2-hydroxy-1-methylethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3-fluorophenyl)-2-{3-[(7-{3-[(4-hydroxybutyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3-fluorophenyl)-2-[3-({7-{3-(4-hydroxypiperidin-1-yl)propoxy]-6-methoxyquinazolin-4-yl}amino)-1H-pyrazol-5-yl}acetamide; N-(3-fluorophenyl)-2-{3-[(7-{3-[2-(2-hydroxyethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3-fluorophenyl)-2-{3-[(7-{3-[4-(2-hydroxyethyl)piperazin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3-fluorophenyl)-2-{3-[(7-{3-[4-(2-hydroxyethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3-fluorophenyl)-2-[3-({7-[3-(3-hydroxypiperidin-1-yl)propoxy]-6-methoxyquinazolin-4-yl}amino)-1H-pyrazol-5-yl]acetamide; N-(3-fluorophenyl)-2-{3-[(7-{3-[(2-hydroxybutyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3-fluorophenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3-fluorophenyl)-2-{3-[(7-{3-[(3-hydroxy-2,2-dimethylpropyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3-fluorophenyl)-2-(3-{[7-(3-{[1-(hydroxymethyl)cyclopentyl]amino}propoxy)-6-methoxyquinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetamide; N-(3-fluorophenyl)-2-{3-[(7-{3-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3-fluorophenyl)-2-(3-{[7-(3-{[(2S)-2-hydroxypropyl]amino}propoxy)-6-methoxyquinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetamide; N-(3-fluorophenyl)-2-(3-{[7-{3-[(2R)-2-hydroxypropyl]amino}propoxy)-6-methoxyquinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetamide; N-(3-fluorophenyl)-2-{3-[(7-{3-[(3S)-3-hydroxypyrrolidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3-fluorophenyl)-2-{3-[(7-{3-[(3R)-3-hydroxypyrrolidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; 2-{3-[(7-{3-[(2-fluoroethyl)(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide; N-(3-fluorophenyl)-2-{3-[(7-{2-[1-(2-hydroxyethyl)piperidin-4-yl]ethoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3-fluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(propyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3-fluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(isopropyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3-fluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(isobutyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; 2-{3-[(7-{3-[(2,2-dimethylpropyl)(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide; 2-{3-[(7-{3-[allyl(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide; N-(3-fluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(prop-2-yn-1-yl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; 2-{3-[(7-{3-[cyclopropyl(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide; 2-{3-[(7-{3-[(cyclopropylmethyl)(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide; 2-{3-[(7-{3-[cyclobutyl(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide; 2-{3-[(7-{3-[cyclopentyl(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide; 2-{3-[(7-{3-[(2,2-dimethoxyethyl)(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide; 2-{3-[(7-{3-[(2,2-difluoroethyl)(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide; N-(3-fluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(3,3,3-trifluoropropyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; 2-{3-[(7-{3-[(cyclobutylmethyl)(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide; N-(3-fluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(2-methoxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; 2-{3-[(7-{3-[(1,3-dioxolan-2-ylmethyl)(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide; 2-(3-{[7-(4-chlorobutoxy)-6-methoxyquinazolin-4-yl]amino}-1H-pyrazol-5-yl)-N-(3-fluorophenyl)acetamide; N-(3-fluorophenyl)-2-{3-[(7-{4[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]butoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3-fluorophenyl)-2-{3-[(7-{4-[(2-hydroxyethyl)(isobutyl)amino]butoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; 2-{3-[(7-{[(2R)-1-(2-tert-butoxyethyl)pyrrolidin-2-yl]methoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide; N-(3-fluorophenyl)-2-{3-[(7-{[(2R)-1-(2-hydroxyethyl)pyrrolidin-2-yl]methoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3,5-difluorophenyl)-2-(3-{[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetamide; N-(3,5-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3,5-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxy-1,1-dimethylethyl)amino]propoxy}-6-methoxyquinazolin 4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3,5-difluorophenyl)-2-[3-({6-methoxy-7-{3-(4-methylpiperazin-1-yl)propoxy]quinazolin-4-yl}amino)-1H-pyrazol-5-yl}acetamide; N-(3,5-difluorophenyl)-2-{3-[(7-{3-[ethyl(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3,5-difluorophenyl)-2-{3-[(7-{3-[2-(2-hydroxyethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3,5-difluorophenyl)-2-{3-[(7-{3-[4-(2-hydroxyethyl)piperazin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3,5-difluorophenyl)-2-{3-[(7-{3-[4-(2-hydroxyethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3,5-difluorophenyl)-2-[3-({7-[3-(3-hydroxypiperidin-1-yl)propoxy]-6-methoxyquinazolin-4-yl}amino)-1H-pyrazol-5-yl]acetamide; N-(3,5-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxybutyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3,5-difluorophenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3,5-difluorophenyl)-2-{3-[(7-{3-[(3-hydroxy-2,2-dimethylpropyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3,5-difluorophenyl)-2-{3-[(7-{3-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3,5-difluorophenyl)-2-{3-[(7-{3-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3,5-difluorophenyl)-2-{3-[7-(3-{[(2S)-2-hydroxypropyl]amino}propoxy)-6-methoxyquinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetamide; N-(3,5-difluorophenyl)-2-(3-{[7-(3-{[(2R)-7-2-hydroxypropyl]amino}propoxy)-6-methoxyquinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetamide; N-(3,5-difluorophenyl)-2-{3-[(7-{3-[(3S)-3-hydroxypyrrolidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3,5-difluorophenyl)-2-{3-[(7-{3-[(3R)-3-hydroxypyrrolidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3,5-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(isobutyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3,5-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(propyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; 2-{3-[(7-{3-[allyl(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3,5-difluorophenyl)acetamide; N-(3,5-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(prop-2-yn-1-yl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3,5-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(isopropyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3,5-difluorophenyl)-2-{3-[(7-{3-[(2,2-dimethylpropyl)(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; 2-{3-[(7-{3-[cyclobutyl(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3,5-difluorophenyl)acetamide; 2-{3-[(7-{3-[(cyclopropylmethyl)(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3,5-difluorophenyl)acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2,2-dimethylpropyl)(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(propyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(isobutyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; 2-{3-[(7-{3-[cyclobutyl(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(2,3-difluorophenyl)acetamide; 2-{3-[(7-{3-[cyclopentyl(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(2,3-difluorophenyl)acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(prop-2-yn-1-yl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; 2-{3-[(7-{3-[(cyclopropylmethyl)(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(2,3-difluorophenyl)acetamide; 2-{3-[(7-{3-[(cyclobutylmethyl)(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(2,3-difluorophenyl)acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2,2-dimethoxyethyl)(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[4-(2-hydroxyethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(2,3-difluorophenyl)-2-[3-({7-[3-(4-hydroxypiperidin-1-yl)propoxy]-6-methoxyquinazolin-4-yl}amino)-1H-pyrazol-5-yl]acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[4-(2-hydroxyethyl)piperazin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(2-methoxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; 2-{3-[(7-{3-[allyl(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(2,3-difluorophenyl)acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(1,3-dioxolan-2-ylmethyl)(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[ethyl(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(isopropyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxy-1,1-dimethylethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{[(2R)-1-(2-hydroxyethyl)pyrrolidin-2-yl]methoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3-chlorophenyl)-2-{3-[(7-{3-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3-chlorophenyl)-2-{3-[(7-{3-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3-chlorophenyl)-2-[3-({7-{3-(3-hydroxypiperidin-1-yl)propoxy]-6-methoxyquinazolin-4-yl}amino)-1H-pyrazol-5-yl}acetamide; N-(3-chlorophenyl)-2-{3-[(7-{3-[ethyl(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; 2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-methoxyphenyl)acetamide; 2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-phenylacetamide; N-(4-fluorophenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3,5-dichlorophenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(5-chloro-2-methoxyphenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; 2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-[3-(trifluoromethyl)phenyl]acetamide; 2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-hydroxyphenyl)acetamide; 2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-nitrophenyl)acetamide; 2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-1H-indazol-5-ylacetamide; N-(4-bromo-2-fluorophenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3-chlorophenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(2-fluorophenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3,5-dimethoxyphenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; 2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(5-methylpyridin-2-yl)acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3-chloro-2-fluorophenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(2,5-difluorophenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-[2-fluoro-5-(trifluoromethyl)phenyl]-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3,4-difluorophenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(2,4-difluorophenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3-chloro-4-fluorophenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-[2-(difluoromethoxy)phenyl]-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3-cyanophenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3-bromophenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[ethyl(2-hydroxyethyl)amino]propoxy}quinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(isopropyl)amino]propoxy}quinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]propoxy}quinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(isopropyl)amino]propoxy}quinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(prop-2-yn-1-yl)amino]propoxy}quinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(isobutyl)amino]propoxy}quinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2,2-dimethylpropyl)(2-hydroxyethyl)amino]propoxy}quinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(3-fluorophenyl)-2-[3-({5-{[1-(2-hydroxyethyl)piperidin-4-yl]oxy}-7-[3-(4-methylpiperazin-1-yl)propoxy]quinazolin-4-yl}amino)-1H-pyrazol-5-yl]acetamide; N-(3-fluorophenyl)-2-[5-({7-methoxy-5-[(1-methylpiperidin-4-yl)oxy]quinazolin-4-yl}amino)-1H-pyrazol-3-yl]acetamide; N-(2,3-difluorophenyl)-2-{3-[(5,7-dimethoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; 2-(3-{[5,7-bis(2-methoxyethoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)-N-(2,3-difluorophenyl)acetamide; N-(2,3-difluorophenyl)-2-(3-{[5-isopropoxy-7-(2-methoxyethoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetamide; N-(3-fluorophenyl)-2-(3-{[5-isopropoxy-7-(2-methoxyethoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetamide; N-(3-fluorophenyl)-2-{3-[(5-{[1-(2-hydroxyethyl)piperidin-4-yl]oxy}-7-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; 2-{3-[(5,7-dimethoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide; 2-(3-{[5,7-bis(2-methoxyethoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)-N-(3-fluorophenyl)acetamide; N-(3-fluorophenyl)-3-[(7-{3-[(2-hydroxyethyl)(isobutyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazole-5-carboxamide; and N-(2,3-difluorophenyl)-3-[(7-{3-[(2-hydroxyethyl)(isobutyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazole-5-carboxamide. In a further aspect of the invention, even more preferred compounds are any one of: N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2,2-dimethylpropyl)(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(propyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(isobutyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; 2-{3-[(7-{3-[cyclobutyl(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(2,3-difluorophenyl)acetamide; 2-{3-[(7-{3-[cyclopentyl(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(2,3-difluorophenyl)acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(prop-2-yn-1-yl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; 2-{3-[(7-{3-[(cyclopropylmethyl)(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(2,3-difluorophenyl)acetamide; 2-{3-[(7-{3-[(cyclobutylmethyl)(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(2,3-difluorophenyl)acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2,2-dimethoxyethyl)(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[4-(2-hydroxyethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(2,3-difluorophenyl)-2-[3-({7-[3-(4-hydroxypiperidin-1-yl)propoxy]-6-methoxyquinazolin-4-yl}amino)-1H-pyrazol-5-yl]acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[4-(2-hydroxyethyl)piperazin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(2-methoxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; 2-{3-[(7-{3-[allyl(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(2,3-difluorophenyl)acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(1,3-dioxolan-2-ylmethyl)(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[ethyl(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{0.3-[(2-hydroxyethyl)(isopropyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxy-1,1-dimethylethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide; and N-(2,3-difluorophenyl)-2-{3-[(7-{[(2R)-1-(2-hydroxyethyl)pyrrolidin-2-yl]methoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide. The present invention relates to the compounds of formula (I), formula (IA) or formula (IB) as defined herein as well as to the salts thereof. Salts for use in pharmaceutical compositions will be pharmaceutically acceptable salts, but other salts may be useful in the production of compounds of formula (I), formula (IA) or formula (IB) and their pharmaceutically acceptable salts. Suitable pharmaceutically acceptable salts of compounds of formula (I), formula (IA) or formula (IB) include acid addition salts such as methanesulphonate, fumarate, hydrochloride, hydrobromide, citrate, maleate and salts formed with phosphoric and sulphuric acid. There may be more than one cation or anion depending on the number of charged functions and the valency of the cations or anions. Where the compound of formula (I), formula (IA) or formula (IB) includes an acid functionality, salts may be base salts such as an alkali metal salt for example sodium, an alkaline earth metal salt for example calcium or magnesium, an organic amine salt for example triethylamine, morpholine, N-methylpiperidine, N-ethylpiperidine, procaine, dibenzylamine, N,N-dibenzylethylamine, ethanolamine, diethanolamine or amino acids for example lysine. A preferred pharmaceutically acceptable salt is a sodium salt. The invention also provides for an in vivo hydrolysable ester of a compound of formula (I), formula (IA) or formula (IB) containing carboxy or hydroxy group. Such an ester is, for example, a pharmaceutically acceptable ester which is hydrolysed in the human or animal body to produce the parent acid or alcohol. Suitable pharmaceutically acceptable esters for carboxy include C1-6alkyl esters such as methyl or ethyl esters, C1-6alkoxymethyl esters for example methoxymethyl, C1-6alkanoyloxymethyl esters for example pivaloyloxymethyl, phthalidyl esters, C3-8cycloalkoxy-carbonyloxyC1-6alkyl esters for example 1-cyclohexylcarbonyloxyethyl; 1,3-dioxolen-2-onylmethyl esters for example 5-methyl-1,3-dioxolen-2-onylmethyl; and C1-6alkoxycarbonyloxyethyl esters for example 1-methoxycarbonyloxyethyl and may be formed at any carboxy group in the compounds of this invention. An in vivo hydrolysable ester of a compound of formula (I), formula (IA) or formula (IB) containing a hydroxy group includes inorganic esters such as phosphate esters and α-acyloxyalkyl ethers and related compounds which as a result of the in vivo hydrolysis of the ester breakdown to give the parent hydroxy group. Examples of α-acyloxyalkyl ethers include acetoxymethoxy and 2,2-dimethylpropionyloxymethoxy. A selection of in vivo hydrolysable ester forming groups for hydroxy include alkanoyl, benzoyl, phenylacetyl and substituted benzoyl and phenylacetyl, alkoxycarbonyl (to give alkyl carbonate esters), dialkylcarbamoyl and N-(dialkylaminoethyl)-N-alkylcarbamoyl (to give carbamates), dialkylaminoacetyl and carboxyacetyl. Suitable amides are derived from compounds of formula (I), formula (IA) or formula (IB) which have a carboxy group which is derivatised into an amide such as a N-C1-6alkyl and N,N-di-(C1-6alkyl)amide such as N-methyl, N-ethyl, N-propyl, N,N-dimethyl, N-ethyl-N-methyl or N,N-diethylamide. Preferred compounds of formula (I), formula (IA) or formula (IB) are those that are stable in mouse, rat, or human serum, preferably those that are stable in human serum. Esters which are not in vivo hydrolysable may be useful as intermediates in the production of the compounds of formula (I), formula (IA) or formula (IB). Compounds of formula (I), formula (IA) or formula (IB) may be prepared by various methods which would be apparent from the literature. For example compounds of formula (I), formula (IA) or formula (IB) where X is NH may be prepared by reacting a compound of formula (VII) where R1, R2, R3, and R4 are R1, R2, R3, and R4 as defined in relation to formula (I) or formula (IB) or R1′, R2′, R3′, and R4′ as defined in relation to formula (IA) and R85 is a group NR86R87 where R86 and R87 are independently selected from alkyl such as methyl, with a compound of formula (VI) H2N—R5′ (VIII) where R5′ is a group R5 as defined in relation to formula (I) or a group R5′ as defined in relation to formula (IA) or a precursor group thereof; and thereafter if desired or necessary, converting a precursor group R5′ to a group R5 or R5a and/or modifying substituents on the group R5 or R5a. The reaction is suitably effected in an organic solvent such as an acetic acid at elevated temperatures, conveniently at the reflux temperature of the solvent. Examples of reactions in which a precursor group R5′ is converted to a group R5 or R5a and/or substituents on the group R5 or R5a are modified are standard chemical reactions, such as conversion of esters to acids, and thereafter, if required to the preferred amides. Examples of such reactions are provided hereinafter. Compounds of formula (VII) are suitably prepared by reacting a compound of formula (IX) with an appropriate acetal such as N,N-dimethylformamide dimethyl acetal. The reaction is suitably effected in an organic solvent such as benzene, at elevated temperature, conveniently at the reflux temperature of the solvent. Alternatively compounds of formula (I), formula (IA) or formula (IB) may be prepared by reacting a compound of formula (X) where R1′, R2″, R3″, and R4′ are equivalent to a group R1, R2, R3 and R4 as defined in relation to formula (I) or formula (IB) or R1′, R2′, R3′ and R4′ as defined in relation formula (IA) or a precursor thereof, and R85 is a leaving group, with a compound of formula (XI) H—X—R5 (XI) where X as defined in relation to formula (I) or formula (IA) and R5 is R5 as defined in relation to formula (I) or R5a as defined in relation to formula (IA): and thereafter if desired or necessary converting a group R1′, R2″, R3″ or R4′ to a group R1, R2, R3 and R4 respectively or a group R1′, R2′, R3′ and R4′ respectively or to a different such group. Suitable leaving groups for R85 include halo such as chloro, mesylate and tosylate. The reaction is suitably effected in an organic solvent such as an alcohol like isopropanol, at elevated temperatures, conveniently at the reflux temperature of the solvent. The conversion of a group R1′, R2″, R3″ or R4′ to a group R1, R2, R3 and R4 respectively or to a group R1′, R2′, R3′ and R4′ respectively or to a different such group, may be particularly useful in connection with the preparation of compounds of formula (I), formula (IA) or formula (IB) where these groups are complex in nature and examples of these preparations are provided hereinafter. In a particular embodiment, R1′, R2″, R3″ or R4′ are groups R1, R2, R3 and R4 respectively. Compounds of formula (X) and (XI) are either known compounds or they can be derived from known compounds by conventional methods which would be apparent from the literature. Alternatively, compounds of formula (I), formula (IA) or formula (IB) where X is NH may be prepared by rearranging a compound of formula (XII) where R1, R2, R3 and R4 are R1, R2, R3 and R4 as defined in relation to formula (I) or formula (IB) or R1′, R2′, R3′ and R4′ as defined in relation to formula (IA) and R5′ is as defined in relation to formula (VIII) above, and thereafter if desired or necessary, converting a precursor group R5′ to a group R5 or R5a and/or modifying substituents on the group R5 or R5a, for example as described generally above. The rearrangement reaction is suitably effected in an organic solvent such as an alkyl alcohol, in particular methanol, ethanol or cyclohexanol, acetic acid, or dimethylformamide, using a strong base such as sodium hydride, sodium hydroxide, sodium acetate, sodium methylate, or dimethylamine. Elevated temperatures, for example of from 20′-120° C. and preferably at about 75° C. are employed. Compounds of formula (XII) are suitably obtained by reacting a compound of formula (XIII) where R1, R2, R3 and R4 are R1, R2, R3 and R4 as defined in relation to formula (I) or formula (IB) or R1′, R2′, R3′ and R4′ as defined in relation to formula (IA) and R86 is an alkyl group such as methyl; with a compound of formula (XV) H2N—R5 (XIV) where R5′ is as defined in relation to formula (VIII). The reaction is suitably effected in an organic solvent such as methylene chloride, in the presence of a salt such as pyridinium hydrochloride. Moderate temperatures for example of from 0°-50° C. and conveniently ambient temperature are employed. Compounds of formula (XIII) are suitably prepared by reacting a compound of formula (IX) as defined above, with a trialkylorthoformate such as trimethylorthoformate. The reaction is suitably effected at elevated temperature, for example of from 50° C. to 120° C., and preferably at about 100° C., in the presence of a catalytic amount of an acid such as p-toluene sulphonic acid. Compounds of formula (IX) are either known compounds or they can be prepared by conventional methods. In particular, compounds of formula (IX) may be prepared by reduction of the corresponding nitro compound of formula (XV) where R1, R2, R3 and R4 are R1, R2, R3 and R4 as defined in relation to formula (I) or formula (IB) or R1′, R2′, R3′ and R4′ as defined in relation to formula (IA). Suitable reaction conditions are illustrated hereinafter. Compounds of formula (XV) may be obtained by nitration of a compound of formula (XVI) for example, using nitric acid as the nitrating agent. Again, suitable reaction conditions are illustrated hereinafter. The nitrile of formula (XVI) may be derived by reaction of the corresponding formamide with hydroxylamine as illustrated hereinafter. It will be appreciated that certain of the various ring substituents in the compounds of the present invention may be introduced by standard aromatic substitution reactions or generated by conventional functional group modifications either prior to or immediately following the processes mentioned above, and as such are included in the process aspect of the invention. Such reactions and modifications include, for example, introduction of a substituent by means of an aromatic substitution reaction, reduction of substituents, alkylation of substituents and oxidation of substituents. The reagents and reaction conditions for such procedures are well known in the chemical art. Particular examples of aromatic substitution reactions include the introduction of a nitro group using concentrated nitric acid, the introduction of an acyl group using, for example, an acyl halide and Lewis acid (such as aluminium trichloride) under Friedel Crafts conditions; the introduction of an alkyl group using an alkyl halide and Lewis acid (such as aluminium trichloride) under Friedel Crafts conditions; and the introduction of a halogen group. Particular examples of modifications include the reduction of a nitro group to an amino group by for example, catalytic hydrogenation with a nickel catalyst or treatment with iron in the presence of hydrochloric acid with heating; oxidation of alkylthio to alkylsulphinyl or alkylsulphonyl. It will also be appreciated that in some of the reactions mentioned herein it may be necessary/desirable to protect any sensitive groups in the compounds. The instances where protection is necessary or desirable and suitable methods for protection are known to those skilled in the art. Conventional protecting groups may be used in accordance with standard practice (for illustration see T. W. Green, Protective Groups in Organic Synthesis, John Wiley and Sons, 1991). Thus, if reactants include groups such as amino, carboxy or hydroxy it may be desirable to protect the group in some of the reactions mentioned herein. A suitable protecting group for an amino or alkylamino group is, for example, an acyl group, for example an alkanoyl group such as acetyl, an alkoxycarbonyl group, for example a methoxycarbonyl, ethoxycarbonyl or t-butoxycarbonyl group, an arylmethoxycarbonyl group, for example benzyloxycarbonyl, or an aroyl group, for example benzoyl. The deprotection conditions for the above protecting groups necessarily vary with the choice of protecting group. Thus, for example, an acyl group such as an alkanoyl or alkoxycarbonyl group or an aroyl group may be removed for example, by hydrolysis with a suitable base such as an alkali metal hydroxide, for example lithium or sodium hydroxide. Alternatively an acyl group such as a t-butoxycarbonyl group may be removed, for example, by treatment with a suitable acid as hydrochloric, sulphuric or phosphoric acid or trifluoroacetic acid and an arylmethoxycarbonyl group such as a benzyloxycarbonyl group may be removed, for example, y hydrogenation over a catalyst such as palladium-on-carbon, or by treatment with a Lewis acid for example boron tris(trifluoroacetate). A suitable alternative protecting group for a primary amino group is, for example, a phthaloyl group which may be removed by treatment with an alkylamine, for example dimethylaminopropylamine, or with hydrazine. A suitable protecting group for a hydroxy group is, for example, an acyl group, for example an alkanoyl group such as acetyl, an aroyl group, for example benzoyl, or an arylmethyl group, for example benzyl. The deprotection conditions for the above protecting groups will necessarily vary with the choice of protecting group. Thus, for example, an acyl group such as an alkanoyl or an aroyl group may be removed, for example, by hydrolysis with a suitable base such as an alkali metal hydroxide, for example lithium or sodium hydroxide. Alternatively an arylmethyl group such as a benzyl group may be removed, for example, by hydrogenation over a catalyst such as palladium-on-carbon. A suitable protecting group for a carboxy group is, for example, an esterifying group, for example a methyl or an ethyl group which may be removed, for example, by hydrolysis with a base such as sodium hydroxide, or for example a t-butyl group which may be removed, for example, by treatment with an acid, for example an organic acid such as trifluoroacetic acid, or for example a benzyl group which may be removed, for example, by hydrogenation over a catalyst such as palladium-on-carbon. The protecting groups may be removed at any convenient stage in the synthesis using conventional techniques well known in the chemical art. Compounds of formula (I) and formula (IA) are inhibitors of Aurora kinase and in particular Aurora A kinase. As a result, these compounds can be used to treat disease mediated by these agents, in particular proliferative disease. According to a further aspect of the present invention there is provided a method for inhibiting Aurora kinase in a warm blooded animal, such as man, in need of such treatment, which comprises administering to said animal an effective amount of a compound of formula (I), formula (IA) or formula (IB), or a pharmaceutically acceptable salt, or an in vivo hydrolysable ester thereof. There is further provided a method of inhibiting Aurora-A kinase as described above and a method of inhibiting Aurora-B kinase as described above. A further aspect of the invention relates to a method of treating a human suffering from a disease in which inhibition of Aurora kinase is beneficial, comprising the steps of administering to a person in need thereof a therapeutically effective amount of a compound of formula (I), formula (IA) or formula (IB). In particular it is envisaged that inhibition of Aurora-A kinase will be beneficial although inhibition of Aurora-B kinase may also be beneficial. Certain compounds of formula (I) are novel and these form a further aspect of the invention. Thus the invention further comprises a compound of formula (IA) or a salt, ester or amide thereof; where X is as defined in relation to formula (I); R1′, R2′, R3′, R4′ are equivalent to R1, R2, R3, R4 as defined in relation to formula (I) and R5a is equivalent to R5 defined in relation to formula (I). Also provided is a compound of formula (IA) or a salt, ester or amide thereof; where X is as defined in relation to formula (I); R1′, R2′, R3′, R4′ are equivalent to R1, R2, R3, R4 as defined in relation to formula (I); and R5a is equivalent to R5 as defined in relation to formula (I); provided that one of R60, R61 and R62 of R5a is other than hydrogen and that if R61 is other than hydrogen, it is not a group selected from: phenylC1-3alkyl, heteroaryl or optionally substituted phenyl; and C3-5cycloalkyl, C3-5cycloalkylC1-3alkyl, C2-5alkenyl or optionally substituted C1-4alkyl; where optional substitutents for phenyl and C1-4alkyl are C1-4alkyl, halo, methoxy, nitro or trifluoromethyl. In a particular aspect of the invention R61 of a compound of formula (IA) is —O-J, —(CH2)—O-J, —O—(CH2)-J, —(CH2)—O—(CH2)-J, —CO-J, —(CH2)—O-J, —CO—(CH2)-J, —(CH2)—CO—(CH2)-J, —S-J, —(CH2)S-J, —S—(CH2)-J, —(CH2)S—(CH2)-J, —SO-J, —(CH2)—SO-J, —SO—(CH2)-J, —(CH2)—SO—(CH2)-J, —S—(CH2)—SO2-J, —SO2—(CH2)-J, —(CH2)—SO2—(CH2)-J, —(NR1′)CO-J, —(CH2)—(NR1′)CO-J, —(NR1′)CO—(CH2)—(CH2)—(NR1′)CO—(CH2)-J, —(NR1′)SO2-J, —(CH2)—(NR1′)SO2-J, —(NR1′)SO2—(CH2)-J, —(CH2)(NR1′)SO2—(CH2)-J, —NR64-J, —(CH2)—NR64-J, —NR64—(CH2)-J, —(CH2)—NR64—(CH2)-J, —CONR64-J, —(CH2)—CONR64-J, —CONR64—(CH2)-J, —(CH2)—CONR64—(CH2)-J, —SO2NR64-J, —(CH2)—SO2NR64-J, —SO2NR64—(CH2)-J, —(CH2)—SO2NR64—(CH2)-J, —NR1′CONH-J, —(CH2)—NR1′CO—NH-J, —NR1′CO—NH—(CH2)-J, —(CH2)—NR1′CO—NH—(CH2)-J, —NR1′CO—N(C1-4alkyl)-J, —(CH2)—NR1′CO—N(C1-4alkyl)-J, —NR1′CO—N(C1-4alkyl)-(CH2)-J, —(CH2)—NR1′CO—N(C1-4alkyl)-(CH2)-J, —NR1′CO-J, —(CH2)—NR1′CO-J, —NR1′CO—O—(CH2)-J, —(CH2)—NR1′CO—O—(CH2)-J, —OCO-J, —CH2—OC—O-J, —CH═CH-J, —CH2—CH═CH-J, —CH═CH—CH2-J and —CH2—CH═CH—CH2-J. Other aspects of the invention relating to a compound of formula (IA) are the preferred values of X, R1, R2, R3, R4 and R5 as described above. Where R5a is a pyrazole group, it carries a substitutent of formula (k), (II) of (VI) above, (ii) that where x is NH and R5′ is a substituted pyrazolone or tetrazolyl group, at least one of R1′, R2′, R3′ and R4′ is other than hydrogen; or (iii) that where X is O and R5a is 1-methyl-4-nitro-1H-imidazol-5-yl, at least one of R1′, R2′, R3′ and R4′ is other than hydrogen.] Preferably at least one of R1′, R2′, R3′ and R4′ is other than hydrogen. In particular, R5a is substituted by at least one group of formula (k), (II) of (VI) above. Other preferred or particular groups and substitutents in formula (IA) are as set out for the equivalent groups in formula (I) above. Additionally a compound of formula (IB) is provided: wherein R1, R2, R3 and R4 are as defined in relation to formula (I); and Ar is indazole or pyridine (optionally substituted by methyl) or aryl (optionally substituted by 1 or 2 substitutents independently selected from halo, methoxy, trifluoromethyl, hydroxy, nitro, cyano and difluoromethoxy). Preferred values of R1, R2, R3 and R4 are as described above. Also provided is a compound of Formula (XVa): wherein R is phenyl, 3 fluorophenyl, 3,5-difluorophenyl, or 3-chlorophenyl; and R′ is morpholin-4-yl, ethyl(2-hydroxyethyl)amino, (2S)-2(hydroxymethyl)pyrrolidin-1-yl, piperidin-1-yl, pyrrolidin-1-yl, (2-hydroxyethyl)amino, (2-hydroxy-1,1-dimethylethyl)amino, methyl(2-hydroxyethyl)amino, (1-(hydroxymethyl)-2-methylpropyl)amino, 4-methylpiperazin-1-yl, (2-hydroxy-1-methylethyl)amino, (4-hydroxybutyl)amino, 4-hydroxypiperidin-1-yl 2-(2-hydroxyethyl)piperidin-1-yl, 4-(2-hydroxyethyl)piperazin-1-yl, 4-(2-hydroxyethyl)piperidin-1-yl, 3-hydroxypiperidin-1-yl, (2-hydroxybutyl)amino 4-(hydroxymethyl)piperidin-1-yl, (3-hydroxy-2,2-dimethylpropyl)amino (1-(hydroxymethyl)cyclopentyl)amino, (2R)-2-(hydroxymethyl)pyrrolidin-1-yl ((2R)-2-hydroxypropyl)amino, ((2S)-2-hydroxypropyl)amino, (3R)-3-hydroxypyrrolidin-1-yl (3S)-3-hydroxypyrrolidin-1-yl, pyrrolidin-1-yl, (2-hydroxyethyl)amino, (2-hydroxy-1,1-dimethylethyl)amino, 4-methylpiperazin-1-yl, ethyl(2-hydroxyethyl)amino, 4-(2-hydroxyethyl)piperidin-1-yl, 4-(2-hydroxyethyl)piperazin-1-yl, 4-(2-hydroxyethyl)piperidin-1-yl, 3-hydroxypiperidin-1-y, (2-hydroxybutyl)amino, 4-(hydroxymethyl)piperidin-1-yl, (3-hydroxy-2,2-dimethylpropyl)amino, (2R)-2-(hydroxymethyl)pyrrolidin-1-yl, (2S)-2-(hydroxymethyl)pyrrolidin-1-yl, ((2R)-2-hydroxypropyl)amino, ((2S)-2-hydroxypropyl)amino (3R)-3-hydroxypyrrolidin-1-yl, (3S)-3-hydroxypyrrolidin-1-yl, (2S)-2-(hydroxymethyl)pyrrolidin-1-yl, 3-hydroxypiperidin-1-yl, (2R)-2-(hydroxymethyl)pyrrolidin-1-yl, or ethyl(2-hydroxyethyl)amino; or a pharmaceutically acceptable salt, ester or amide thereof. Further provided is a compound of formula (IA) as defined herein for use as a medicament. According to yet a further aspect of the invention there is provided a compound of the formula (IA) as defined herein, or a pharmaceutically acceptable salt or an in vivo hydrolysable ester thereof, for use in a method of treatment of the human or animal body by therapy. In particular, the compounds are used in methods of treatment of proliferative disease such as cancer and in particular cancers such as colorectal or breast cancer where Aurora-A is upregulated. The compounds are also useful in the treatment of disease where Aurora-B kinase inhibition is beneficial. A compound of formula (IA) also has use in the preparation of a medicament for use in the inhibition of Aurora kinase and in particular a medicament for the treatment of disease where Aurora kinase inhibition is beneficial. Preferably Aurora-A kinase is inhibited but the invention also provides for such use where Aurora-B kinase is inhibited. The invention also provides a pharmaceutical composition comprising a compound of formula (IA) as defined herein, or a pharmaceutically acceptable salt, or an in vivo hydrolysable ester thereof, in combination with a pharmaceutically acceptable carrier. Preferred or particular compounds of formula (IA) for use in the compositions of the invention are as described above in relation to preferred compounds of formula (I). A compound of formula (IB) also has use as a medicament, use in a method of treatment of proliferative diseases and use in the preparation of a medicament for use in the inhibition of Aurora kinase whereby each use is distinct and is as described above for a compound of formula (IA). The compositions of the invention may be in a form suitable for oral use (for example as tablets, lozenges, hard or soft capsules, aqueous or oily suspensions, emulsions, dispersible powders or granules, syrups or elixirs), for topical use (for example as creams, ointments, gels, or aqueous or oily solutions or suspensions), for administration by inhalation (for example as a finely divided powder or a liquid aerosol), for administration by insufflation (for example as a finely divided powder) or for parenteral administration (for example as a sterile aqueous or oily solution for intravenous, subcutaneous, intramuscular or intramuscular dosing or as a suppository for rectal dosing or as a dispersed dosage form). The compositions of the invention may be obtained by conventional procedures using conventional pharmaceutical excipients, well known in the art. Thus, compositions intended for oral use may contain, for example, one or more colouring, sweetening, flavouring and/or preservative agents. Suitable pharmaceutically acceptable excipients for a tablet formulation include, for example, inert diluents such as lactose, sodium carbonate, calcium phosphate or calcium carbonate, granulating and disintegrating agents such as corn starch or algenic acid; binding agents such as starch; lubricating agents such as magnesium stearate, stearic acid or talc; preservative agents such as ethyl or propyl p-hydroxybenzoate, and anti-oxidants, such as ascorbic acid. Tablet formulations may be uncoated or coated either to modify their disintegration and the subsequent absorption of the active ingredient within the gastrointestinal track, or to improve their stability and/or appearance, in either case, using conventional coating agents and procedures well known in the art. Compositions for oral use may be in the form of hard gelatin capsules in which the active ingredient is mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate or kaolin, or as soft gelatin capsules in which the active ingredient is mixed with water or an oil such as peanut oil, liquid paraffin, soya bean oil, coconut oil, or preferably olive oil, or any other acceptable vehicle. Aqueous suspensions generally contain the active ingredient in finely powdered form together with one or more suspending agents, such as sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose, sodium alginate, polyvinyl-pyrrolidone, gum tragacanth and gum acacia; dispersing or wetting agents such as lecithin or condensation products of an alkylene oxide with fatty acids (for example polyoxyethylene stearate), or condensation products of ethylene oxide with long chain aliphatic alcohols, for example heptadecaethyleneoxycetanol, or condensation products of ethylene oxide with partial esters derived from fatty acids and a hexitol such as polyoxyethylene sorbitol monooleate, or condensation products of ethylene oxide with long chain aliphatic alcohols, for example heptadecaethyleneoxycetanol, or condensation products of ethylene oxide with partial esters derived from fatty acids and a hexitol such as polyoxyethylene sorbitol monooleate, or condensation products of ethylene oxide with partial esters derived from fatty acids and hexitol anhydrides, for example polyethylene sorbitan monobleate. The aqueous suspensions may also contain one or more preservatives (such as ethyl or propyl p-hydroxybenzoate, anti-oxidants (such as ascorbic acid), colouring agents, flavouring agents, and/or sweetening agents (such as sucrose, saccharine or aspartame). Oily suspensions may be formulated by suspending the active ingredient in a vegetable oil (such as arachis oil, olive oil, sesame oil or coconut oil) or in a mineral oil (such as liquid paraffin). The oily suspensions may also contain a thickening agent such as beeswax, hard paraffin or cetyl alcohol. Sweetening agents such as those set out above, and flavouring agents may be added to provide a palatable oral preparation. These compositions may be preserved by the addition of an anti-oxidant such as ascorbic acid. Dispersible or lyophilised powders and granules suitable for preparation of an aqueous suspension or solution by the addition of water generally contain the active ingredient together with a dispersing or wetting agent, suspending agent and one or more preservatives. Suitable dispersing or wetting agents and suspending agents are exemplified by those already mentioned above. Additional excipients such as sweetening, flavouring and colouring agents, may also be present. The pharmaceutical compositions of the invention may also be in the form of oil-in-water emulsions. The oily phase may be a vegetable oil, such as olive oil or arachis oil, or a mineral oil, such as for example liquid paraffin or a mixture of any of these. Suitable emulsifying agents may be, for example, naturally-occurring gums such as gum acacia or gum tragacanth, naturally-occurring phosphatides such as soya bean, lecithin, an esters or partial esters derived from fatty acids and hexitol anhydrides (for example sorbitan monooleate) and condensation products of the said partial esters with ethylene oxide such as polyoxyethylene sorbitan monooleate. The emulsions may also contain sweetening, flavouring and preservative agents. Syrups and elixirs may be formulated with sweetening agents such as glycerol, propylene glycol, sorbitol, aspartame or sucrose, and may also contain a demulcent, preservative, flavouring and/or colouring agent. The pharmaceutical compositions may also be in the form of a sterile injectable aqueous or oily suspension, solutions, emulsions or particular systems, which may be formulated according to known procedures using one or more of the appropriate dispersing or wetting agents and suspending agents, which have been mentioned above. A sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally-acceptable diluent or solvent, for example a solution in polyethylene glycol. Suppository formulations may be prepared by mixing the active ingredient with a suitable non-irritating excipient which is solid at ordinary temperatures but liquid at the rectal temperature and will therefore melt in the rectum to release the drug. Suitable excipients include, for example, cocoa butter and polyethylene glycols. Topical formulations, such as creams, ointments, gels and aqueous or oily solutions or suspensions, may generally be obtained by formulating an active ingredient with a conventional, topically acceptable, vehicle or diluent using conventional procedure well known in the art. Compositions for administration by insufflation may be in the form of a finely divided powder containing particles of average diameter of, for example, 30 μm or much less preferably 5 μm or less and more preferably between 5 μm and 1 μm, the powder itself comprising either active ingredient alone or diluted with one or more physiologically acceptable carriers such as lactose. The powder for insufflation is then conveniently retained in a capsule containing, for example, 1 to 50 mg of active ingredient for use with a turbo-inhaler device, such as is used for insulation of the known agent sodium cromoglycate. Compositions for administration by inhalation may be in the form of a conventional pressurised aerosol arranged to dispense the active ingredient either as an aerosol containing finely divided solid or liquid droplets. Conventional aerosol propellants such as volatile fluorinated hydrocarbons or hydrocarbons may be used and the aerosol device is conveniently arranged to dispense a metered quantity of active ingredient. For further information on Formulation the reader is referred to Chapter 25.2 in Volume 5 of Comprehensive Medicinal Chemistry (Corwin Hansch; Chairman of Editorial Board), Pergamon Press 1990. The amount of active ingredient that is combined with one or more excipients to produce a single dosage form will necessarily vary depending upon the host treated and the particular route of administration. For example, a formulation intended for oral administration to humans will generally contain, for example, from 0.5 mg to 2 g of active agent compounded with an appropriate and convenient amount of excipients which may vary from about 5 to about 98 percent by weight of the total composition. Dosage unit forms will generally contain about 1 mg to about 500 mg of an active ingredient. For further information on Routes of Administration and Dosage Regimes the reader is referred to Chapter 25.3 in Volume 5 of Comprehensive Medicinal Chemistry (Corwin Hansch; Chairman of Editorial Board), Pergamon Press 1990. The size of the dose for therapeutic or prophylactic purposes of a compound of the formula (I), formula (IA) or formula (IB) will naturally vary according to the nature and severity of the conditions, the age and sex of the animal or patient and the route of administration, according to well known principles of medicine. As mentioned above, compounds of the formula (I), formula (IB) or formula (IA) are useful in treating diseases or medical conditions which are due alone or in part to the effects of Aurora-A kinase and also due alone or in part to the effects of Aurora-B kinase. In using a compound of the formula (I), formula (IA) or formula (IB) for therapeutic or prophylactic purposes it will generally be administered so that a daily dose in the range, for example, 0.5 mg to 75 mg per kg body weight is received and but a range of 0.1 mg to 75 mg may also be required, given if required in divided doses. In general lower doses will be administered when a parenteral route is employed. Thus, for example, for intravenous administration, a dose in the range, for example, 0.5 mg to 30 mg per kg body weight will generally be used but a range of 0.1 mg to 25 mg may be required. Similarly, for administration by inhalation, a dose in the range, for example, 0.5 mg to 25 mg per kg body weight will be used. A further aspect of the invention comprises a compound of formula (I), formula (IA) or formula (IB) as defined above, or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof, for use in the preparation of a medicament for the treatment of proliferative disease. Preferred compounds of formula (I), formula (IA) or formula (IB) for this purpose are as described above. In addition to their use in therapeutic medicine, a compound of formula (I) or formula (IA) and the pharmaceutically acceptable salt is also useful as pharmacological tool in the development and standardisation of in vitro and in vivo test systems for the evaluation of the effects of inhibitors of cell cycle activity in laboratory animals such as cats, dogs, rabbits, monkeys, rats and mice, as part of the search fro new therapeutic agents. The treatment defined hereinbefore may be applied as a sole therapy or may involve, in addition to the compound of the invention, conventional surgery or radiotherapy or chemotherapy. Such chemotherapy may include one or more of the following categories of anti-tumour agents:— (i) antiproliferative/antineoplastic drugs and combinations thereof, as used in medical oncology, such as alkylating agents (for example cis-platin, carboplatin, cyclophosphamide, nitrogen mustard, melphalan, chlorambucil, busulphan and nitrosoureas); antimetabolites (for example antifolates such as fluoropyrimidines like 5-fluorouracil and tegafur, raltitrexed, methotrexate, cytosine arabinoside and hydroxyurea; antitumour antibiotics (for example anthracyclines like adriamycin, bleomycin, doxorubicin, daunomycin, epirubicin, idarubicin, mitomycin-C, dactinomycin and mithramycin); antimitotic agents (for example vinca alkaloids like vincristine, vinblastine, vindesine and vinorelbine and taxoids like taxol and taxotere); and topoisomerase inhibitors (for example epipodophyllotoxins like etoposide and teniposide, amsacrine, topotecan and camptothecin); (ii) cytostatic agents such as antioestrogens (for example tamoxifen, toremifene, raloxifene, droloxifene and iodoxyfene), anti androgens (for example bicalutamide, flutamide, nilutamide and cyproterone acetate), LHRH antagonists or LHRH agonists (for example goserelin, leuprorelin and buserelin), progestogens (for example megestrol acetate), aromatase inhibitors (for example as anastrozole, letrozole, vorazole and exemestane) and inhibitors of 5α-reductase such as finastertde; (iii) Agents which inhibit cancer cell invasion (for example metalloproteinase inhibitors like marimastat and inhibitors of urokinase plasminogen activator receptor function); (iv) inhibitors of growth factor function, for example such inhibitors include growth factor antibodies, growth factor receptor antibodies (for example the anti-erbb2 antibody trastuzumab [Herceptin™] and the anti-erbb1 antibody cetuximab [C225]), farnesyl transferase inhibitors, tyrosine kinase inhibitors and serine-threonine kinase inhibitors, for example inhibitors of the epidermal growth factor family (for example EGFR family tyrosine kinase inhibitors such as N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-morpholinopropoxy)quinazolin-4-amine (gefitinib, AZD1839), N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazoliniamine (erlotinib, OSI-774) and 6-acrylamido-N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)quinazolin-4-amine (CI 1033)), for example inhibitors of the platelet-derived growth factor family and for example inhibitors of the hepatocyte growth factor family; (v) antiangiogenic agents such as those which inhibit the effects of vascular endothelial growth factor, (for example the anti-vascular endothelial cell growth factor antibody bevacizumab [Avastin™], compounds such as those disclosed in International Patent Applications WO 97/22596, WO 97/30035, WO 97/32856 and WO 98/13354) and compounds that work by other mechanisms (for example linomide, inhibitors of integrin αvβ3 function and angiostatin); (vi) vascular damaging agents such as Combretastatin A4 and compounds disclosed in International Patent Applications WO 99/02166, WO00/40529, WO 00/41669, WO01/92224, WO02/04434 and WO02/08213; (vii) antisense therapies, for example those which are directed to the targets listed above, such as ISIS 2503, an anti-ras antisense; (viii) gene therapy approaches, including for example approaches to replace aberrant genes such as aberrant p53 or aberrant BRCA1 or BRCA2, GDEPT (gene-directed enzyme pro-drug therapy) approaches such as those using cytosine deaminase, thymidine kinase or a bacterial nitroreductase enzyme and approaches to increase patient tolerance to chemotherapy or radiotherapy such as multi-drug resistance gene therapy; and (ix) immunotherapy approaches, including for example ex-vivo and in-vivo approaches to increase the immunogenicity of patient tumour cells, such as transfection with cytokines such as interleukin 2, interleukin 4 or granulocyte-macrophage colony stimulating factor, approaches to decrease T-cell anergy, approaches using transfected immune cells such as cytokine-transfected dendritic cells, approaches using cytokine-transfected tumour cell lines and approaches using anti-idiotypic antibodies. Such conjoint treatment may be achieved by way of the simultaneous, sequential or separate dosing of the individual components of the treatment. Such combination products employ the compounds of this invention within the dosage range described hereinbefore and the other pharmaceutically-active agent within its approved dosage range. As stated hereinbefore the compounds of the invention inhibit the serine-threonine kinase activity of Aurora kinase and in particular of Aurora-A kinase and/or Aurora-B kinase and thus inhibit the cell cycle and cell proliferation. These properties may be assessed, for example, using one or more of the procedures set out below: (a) In Vitro Aurora-A Kinase Inhibition Test This assay determines the ability of a test compound to inhibit serine-threonine kinase activity. DNA encoding Aurora-A may be obtained by total gene synthesis or by cloning. This DNA may then be expressed in a suitable expression system to obtain polypeptide with serine-threonine kinase activity. In the case of Aurora-A, the coding sequence was isolated from cDNA by polymerase chain reaction (PCR) and cloned into the BamH1 and Not1 restriction endonuclease sites of the baculovirus expression vector pFastBac HTc (GibcoBRL/Life technologies). The 5′ PCR primer contained a recognition sequence for the restriction endonuclease BamH1 5′ to the Aurora-A coding sequence. This allowed the insertion of the Aurora-A gene in frame with the 6 histidine residues, spacer region and rTEV protease cleavage site encoded by the pFastBac HTc vector. The 3′ PCR primer replaced the Aurora-A stop codon with additional coding sequence followed by a stop codon and a recognition sequence for the restriction endonuclease Not1. This additional coding sequence (5′ TAC CCA TAC GAT GTT CCA GAT TAC GCT TCT TAA 3′) encoded for the polypeptide sequence YPYDVPDYAS. This sequence, derived from the influenza hemagglutin protein, is frequently used as a tag epitope sequence that can be identified using specific monoclonal antibodies. The recombinant pFastBac vector therefore encoded for an N-terminally 6 his tagged, C terminally influenza hemagglutin epitope tagged Aurora-A protein. Details of the methods for the assembly of recombinant DNA molecules can be found in standard texts, for example Sambrook et al. 1989, Molecular Cloning—A Laboratory Manual, 2nd Edition, Cold Spring Harbor Laboratory press and Ausubel et al. 1999, Current Protocols in Molecular Biology, John Wiley and Sons Inc. Production of recombinant virus can be performed following manufacturer's protocol from GibcoBRL. Briefly, the pFastBac-1 vector carrying the Aurora-A gene was transformed into E. coli DH10Bac cells containing the baculovirus genome (bacmid DNA) and via a transposition event in the cells, a region of the pFastBac vector containing gentamycin resistance gene and the Aurora-A gene including the baculovirus polyhedrin promoter was transposed directly into the bacmid DNA. By selection on gentamycin, kanamycin, tetracycline and X-gal, resultant white colonies should contain recombinant bacmid DNA encoding Aurora-A. Bacmid DNA was extracted from a small scale culture of several BH10Bac white colonies and transfected into Spodoptera frugiperda Sf21 cells grown in TC100 medium (GibcoBRL) containing 10% serum using CellFECTIN reagent (GibcoBRL) following manufacturer's instructions. Virus particles were harvested by collecting cell culture medium 72 hrs post transfection. 0.5 mls of medium was used to infect 100 ml suspension culture of Sf21s containing 1×107 cells/ml. Cell culture medium was harvested 48 hrs post infection and virus titre determined using a standard plaque assay procedure. Virus stocks were used to infect Sf9 and “High 5” cells at a multiplicity of infection (MOI) of 3 to ascertain expression of recombinant Aurora-A protein. For the large scale expression of Aurora-A kinase activity, Sf21 insect cells were grown at 28° C. in TC100 medium supplemented with 10% foetal calf serum (Viralex) and 0.2% F68 Pluronic (Sigma) on a Wheaton roller rig at 3 r.p.m. When the cell density reached 1.2×106 cells ml−1 they were infected with plaque-pure Aurora-A recombinant virus at a multiplicity of infection of 1 and harvested 48 hours later. All subsequent purification steps were performed at 4° C. Frozen insect cell pellets containing a total of 2.0×108 cells were thawed and diluted with lysis buffer (25 mM HE PES (N-[2-hydroxyethyl]piperazine-N′-[2-ethanesulphonic acid]) pH7.4 at 4° C. 100 mM KCl, 25 mM NaF, 1 mM Na3VO4, 1 mM PMSF (phenylmethylsulphonyl fluoride), 2 mM 2-mercaptoethanol, 2 mM imidazole, 1 μg/ml aprotinin, 1 μg/ml pepstatin, 1 μg/ml leupeptin), using 1.0 ml per 3×107 cells. Lysis was achieved using a dounce homogeniser, following which the lysate was centrifuged at 41,000 g for 35 minutes. Aspirated supernatant was pumped onto a 5 mm diameter chromatography column containing 500 μl Ni NTA (nitrilo-tri-acetic acid) agarose (Qiagen, product no. 30250) which had been equilibrated in lysis buffer. A baseline level of UV absorbance for the eluent was reached after washing the column with 12 ml of lysis buffer followed by 7 ml of wash buffer (25 mM HEPES pH7.4 at 4° C., 100 mM KCl, 20 mM imidazole, 2 mM 2-mercaptoethanol). Bound Aurora-A protein was eluted from the column using elution buffer (25 mM HEPES pH7.4 at 4° C., 100 mM KCl, 400 mM imidazole, 2 mM 2-mercaptoethanol). An elution fraction (2.5 ml) corresponding to the peak in UV absorbance was collected. The elution fraction, containing active Aurora-A kinase, was dialysed exhaustively against dialysis buffer (25 mM HEPES pH7.4 at 4° C., 45% glycerol (v/v), 100 mM KCl, 0.25% Nonidet P40 (v/v), 1 mM dithiothreitol). Each new batch of Aurora-A enzyme was titrated in the assay by dilution with enzyme diluent (25 mM Tris-HCl pH7.5, 12.5 mM KCl, 0.6 mM DTT). For a typical batch, stock enzyme is diluted 1 in 666 with enzyme diluent & 20 μl of dilute enzyme is used for each assay well. Test compounds (at 10 mM in dimethylsulphoxide (DMSO) were diluted with water & 10 μl of diluted compound was transferred to wells in the assay plates. “Total” & “blank” control wells contained 2.5% DMSO instead of compound. Twenty microlitres of freshly diluted enzyme was added to all wells, apart from “blank” wells. Twenty microlitres of enzyme diluent was added to “blank” wells. Twenty microlitres of reaction mix (25 mM Tris-HCl, 78.4 mM KCl, 2.5 mM NaF, 0.6 mM dithiothreitol, 6.25 mM MnCl2, 6.25 mM ATP, 7.5 μM peptide substrate [biotin-LRRWSLGLRRWSLGLRRWSLGLRRWSLG]) containing 0.2 μCi [γ33P]ATP (Amersham Pharmacia, specific activity ≧2500 Ci/mmol) was then added to all test wells to start the reaction. The plates were incubated at room temperature for 60 minutes. To stop the reaction 100 μl 20% v/v orthophosphoric acid was added to all wells. The peptide substrate was captured on positively-charged nitrocellulose P30 filtermat (Whatman) using a 96-well plate harvester (TomTek) & then assayed for incorporation of 33P with a Beta plate counter. “Blank” (no enzyme) and “total” (no compound) control values were used to determine the dilution range of test compound which gave 50% inhibition of enzyme activity. In this test, the compounds of the invention give 50% inhibition of enzyme activity at concentrations of 0.0001 μM to 1.5 μM and in particular compound 8 in Table 3 gave 50% inhibition of enzyme activity at a concentration of 0.01 μM and compound 13 in Table 3 gave 50% inhibition of enzyme activity at a concentration of 0.001 μM. (b) In Vitro Aurora-B Kinase Inhibition Test This assay determines the ability of a test compound to inhibit serine-threonine kinase activity. DNA encoding Aurora-B may be obtained by total gene synthesis or by cloning. This DNA may then be expressed in a suitable expression system to obtain polypeptide with serine-threonine kinase activity. In the case of Aurora-B, the coding sequence was isolated from cDNA by polymerase chain reaction (PCR) and cloned into the pFastBac system in a manner similar to that described above for Aurora-A (i.e. to direct expression of a 6-histidine tagged Aurora-B protein). For the large scale expression of Aurora-B kinase activity, Sf21 insect cells were grown at 28° C. in TC100 medium supplemented with 10% foetal calf serum (Viralex) and 0.2% F68 Pluronic (Sigma) on a Wheaton roller rig at 3 r.p.m. When the cell density reached 1.2×106 cells ml−1 they were infected with plaque-pure Aurora-B recombinant virus at a multiplicity of infection of 1 and harvested 48 hours later. All subsequent purification steps were performed at 4° C. Frozen insect cell pellets containing a total of 2.0×108 cells were thawed and diluted with lysis buffer (50 mM HEPES (N-[2-hydroxyethyl]piperazine-N′-[2-ethanesulphonic acid]) pH7.5 at 4° C., 1 mM Na3VO4, 1 mM PMSF (phenylmethylsulphonyl fluoride), 1 mM dithiothreitol, 1 μg/ml aprotinin, 1 μg/ml pepstatin, 1 μg/ml leupeptin), using 1.0 ml per 2×107 cells. Lysis was achieved using a sonication homogeniser, following which the lysate was centrifuged at 41,000 g for 35 minutes. Aspirated supernatant was pumped onto a 5 mm diameter chromatography column containing 1.0 ml CM sepharose Fast Flow (Amersham Pharmacia Biotech) which had been equilibrated in lysis buffer. A baseline level of UV absorbance for the eluent was reached after washing the column with 12 ml of lysis buffer followed by 7 ml of wash buffer (50 mM HEPES pH7.4 at 4° C., 1 mM dithiothreitol). Bound Aurora-B B protein was eluted from the column using a gradient of elution buffer (50 mM HEPES pH7.4 at 4° C., 0.6 M NaCl, 1 mM dithiothreitol, running from 0% elution buffer to 100% elution buffer over 15 minutes at a flowrate of 0.5 ml/min). Elution fractions (1.0 ml) corresponding to the peak in UV absorbance was collected. Elution fractions were dialysed exhaustively against dialysis buffer (25 mM HEPES pH7.4 at 4° C., 45% glycerol (v/v), 100 mM KCl, 0.05% (v/v) IGEPAL CA630 (Sigma Aldrich), 1 mM dithiothreitol). Dialysed fractions were assayed for Aurora-B kinase activity. Each new batch of Aurora-B enzyme was titrated in the assay by dilution with enzyme diluent (25 mM Tris-HCl pH7.5, 12.5 mM KCl, 0.6 mM DTT). For a typical batch, stock enzyme is diluted 1 in 40 with enzyme diluent & 20 μl of dilute enzyme is used for each assay well. Test compounds (at 10 mM in dimethylsulphoxide (DMSO) were diluted with water & 10 μl of diluted compound was transferred to wells in the assay plates. “Total” & “blank” control wells contained 2.5% DMSO instead of compound. Twenty microlitres of freshly diluted enzyme was added to all wells, apart from “blank” wells. Twenty microlitres of enzyme diluent was added to “blank” wells. Twenty microlitres of reaction mix (25 mM Tris-HCl, 78.4 mM KCl, 2.5 mM NaF, 0.6 mM dithiothreitol, 6.25 mM MnCl2, 37.5 mM ATP, 25 μM peptide substrate [biotin-LRRWSLGLRRWSLGLRRWSLGLRRWSLG]) containing 0.2 μCi [γ3P]ATP (Amersham Pharmacia, specific activity ≧2500 Ci/mmol) was then added to all test wells to start the reaction. The plates were incubated at room temperature for 60 minutes. To stop the reaction 100 μl 20% v/v orthophosphoric acid was added to all wells. The peptide substrate was captured on positively-charged nitrocellulose P30 filtermat (Whatman) using a 96-well plate harvester (TomTek) & then assayed for incorporation of 33P with a Beta plate counter. “Blank” (no enzyme) and “total” (no compound) control values were used to determine the dilution range of test compound which gave 50% inhibition of enzyme activity. (c) In Vitro Cell Proliferation Assay This and other assays can be used to determine the ability of a test compound to inhibit the growth of adherent mammalian cell lines, for example the human tumour cell line SW620 (ATCC CCL-227). This assay determines the ability of at test compound to inhibit the incorporation of the thymidine analogue, 5′-bromo-2′-deoxy-uridine (BrdU) into cellular DNA. SW620 or other adherent cells were typically seeded at 1×105 cells per well in L-15 media (GIBCO) plus 5% foetal calf serum, 1% L-glutamine (100 μl/well) in 96 well tissue culture treated 96 well plates (Costar) and allowed to adhere overnight. The following day the cells were dosed with compound (diluted from 10 mM stock in DMSO using L-15 (with 5% FCS, 1% L-glutamine). Untreated control wells and wells containing a compound known to give 100% inhibition of BrdU incorporation were included on each plate. After 48 hours in the presence/absence of test compound the ability of the cells to incorporate BrdU over a 2 hour labelling period was determined using a Boehringer (Roche) Cell Proliferation BrdU ELISA kit (cat. No. 1 647 229) according to manufacturers directions. Briefly, 15 μl of BrdU labelling reagent (diluted 1:100 in media—L-15, 5% FCS, 1% L-glutamine) was added to each well and the plate returned to a humidified (+5% CO2) 37° C. incubator for 2 hours. After 2 hours the labelling reagent was removed by decanting and tapping the plate on a paper towel. FixDenat solution (50 μl per well) was added and the plates incubated at room temperature for 45 mins with shaking. The FixDenat solution was removed by decanting and tapping the inverted plate on a paper towel. The plate was then washed once with phosphate buffered saline (PBS) and 100 μl/well of Anti-BrdU-POD antibody solution (diluted 1:100 in antibody dilution buffer) added. The plate was then incubated at room temperature with shaking for 90 min. Unbound Anti-BrdU-POD antibody was removed by decanting and washing the plate 4 times with PBS before being blotted dry. TMB substrate solution was added (100 μl/well) and incubated for approximately 10 minutes at room temperature with shaking until a colour change was apparent. The optical density of the wells was then determined at 690 nm wavelength using a Titertek Multiscan plate reader. The values from compound treated, untreated and 100% inhibition controls were used to determine the dilution range of a test compound that gave 50% inhibition of BrdU incorporation. The compounds of the invention are active at 0.001 μM to 10 μM in this test and in particular compound 8 in table 3 was active at 0.086 μM and compound 13 in table 3 was active at 0.079 μM. (d) In Vitro Cell Cycle Analysis Assay This assay determines the ability of a test compound to arrest cells in specific phases of the cell cycle. Many different mammalian cell lines could be used in this assay and SW620 cells are included here as an example. SW620 cells were seeded at 7×1 cells per T25 flask (Costar) in 5 ml L-15 (5% FCS, 1% L-glutamine). Flasks were then incubated overnight in a humidified 37° C. incubator with 5% CO2. The following day, 5 μl of L-15 (5% FCS, 1% L-glutamine) carrying the appropriate concentration of test compound solubilised in DMSO was added to the flask. A no compound control treatments was also included (0.5% DMSO). The cells were then incubated for a defined time (24 hours) with compound. After this time the media was aspirated from the cells and they were washed with 5 ml of prewarmed (37° C.) sterile PBSA, then detached from the flask by brief incubation with trypsin and followed by resuspension in 5 ml of 1% Bovine Serum Albumin (BSA, Sigma-Aldrich Co.) in sterile PBSA. The samples were then centrifuged at 2200 rpm for 10 min. The supernatant was aspirated to leave 200 μl of the PBS/BSA solution. The pellet was resuspended in this 200 μl of solution by pipetting 10 times to create a single cell suspension. One ml of ice-cold 80% ethanol was slowly added to each cell suspension and the samples stored at −20° C. overnight or until required for staining. Cells were pelleted by centrifugation, ethanol aspirated off and pellets resuspended in 200 μl PBS containing 100 μg/ml RNAse (Sigma Aldrich) & 10 μg/ml propidium Iodide (Sigma Aldrich). Cell suspensions were incubated at 37° C. for 30 min, a further 200 μl PBS added and samples stored in the dark at 4° C. overnight. Each sample was then syringed 10 times using 21-guage needle. The samples were then transferred to LPS tubes and DNA content per cell analysed by Fluorescence activated cell sorting (FACS) using a FACScan flow cytometer (Becton Dickinson). Typically 30,000 events were counted and recorded using CellQuest v1.1 software (Verity Software). Cell cycle distribution of the population was calculated using Modfit software (Verity Software) and expressed as percentage of cells with 2N (G0/G1), 2N-4N(S phase) and with 4N (G2/M) DNA content. The following Scheme illustrates the general method for making compounds of the present invention. The invention will now be illustrated in the following non limiting examples, in which standard techniques known to the skilled chemist and techniques analogous to those described in these examples may be used where appropriate, and in which, unless otherwise stated: (i) evaporations were carried out by rotary evaporation in vacuo and work up procedures were carried out after removal of residual solids such as drying agents by filtration; (ii) operations were carried out at ambient temperature, typically in the range 18-25° C. and in air unless stated, or unless the skilled person would otherwise operate under an atmosphere of an inert gas such as argon; (iii) column chromatography (by the flash procedure) and medium pressure liquid chromatography (MPLC) were performed on Merck Kieselgel silica (Art. 9385); (iv) yields are given for illustration only and are not necessarily the maximum attainable; (v) the structures of the end products of the formula (I) were generally confirmed by nuclear (generally proton) magnetic resonance (NMR) and mass spectral techniques; proton magnetic resonance chemical shift values were measured in deuterated dimethyl sulphoxide (DMSO d6) (unless otherwise stated) on the delta scale (ppm downfield from tetramethylsilane) using one of the following four instruments Varian Gemini 2000 spectrometer operating at a field strength of 300 MHz Bruker DPX300 spectrometer operating at a field strength of 300 MHz JEOL EX 400 spectrometer operating at a field strength of 400 MHz Bruker Avance 500 spectrometer operating at a field strength of 500 MHz. Peak multiplicities are shown as follows: s, singlet; d, doublet; dd, double doublet; t, triplet; q, quartet; qu, quintet; m, multiplet; br s, broad singlet; (vi) robotic synthesis was carried out using a Zymate XP robot, with solution additions via a Zymate Master Laboratory Station and stirred via a Stem RS5000 Reacto-Station at 25° C.; (vii) work up and purification of reaction mixtures from robotic synthesis was carried out as follows: evaporations were carried out in vacuo using a Genevac HT 4; column chromatography was performed using either an Anachem Sympur MPLC system on silica using 27 mm diameter columns filled with Merck silica (60 μm, 25 g); the structures of the final products were confirmed by LCMS on a Waters 2890/ZMD micromass system using the following and are quoted as retention time (RT) in minutes: Column: waters symmetry C18 3.5 μm 4.6×50 mm Solvent A: H2O Solvent B: CH3CN Solvent C: MeOH+5% HCOOH Flow rate: 2.5 ml/min Run time: 5 minutes with a 4.5 minute gradient from 0-100% C Wavelength: 254 nm, bandwidth 10 nm Mass detector: ZMD micromass Injection volume 0.005 ml (viii) Analytical LCMS for compounds which had not been prepared by robotic synthesis was performed on a Waters Alliance HT system using the following and are quoted as retention time (RT) in minutes: Column: 2.0 mm×5 cm Phenomenex Max-RP 80A Solvent A: Water Solvent B: Acetonitrile Solvent C: Methanol/1% formic acid or Water/1% formic acid Flow rate: 1.1 ml/min Run time: 5 minutes with a 4.5 minute gradient from 0-95% B+constant 5% solvent C Wavelength: 254 nm, bandwidth 10 nm Injection volume 0.005 ml Mass detector: Micromass ZMD (ix) Preparative high performance liquid chromatography (HPLC) was performed on either Waters preparative LCMS instrument, with retention time (RT) measured in minutes: Column: β-basic Hypercil (21×100 mm) 5 μm Solvent A: Water/0.1% Ammonium carbonate Solvent B: Acetonitrile Flow rate: 25 ml/min Run time: 10 minutes with a 7.5 minute gradient from 0-100% B Wavelength: 0.254 nm, bandwidth 10 nm Injection volume 1-1.5 ml Mass detector: Micromass ZMD Gilson preparative HPLC instrument, with retention time (RT) measured in minutes: Column: 21 mm×15 cm Phenomenex Luna2 C18 Solvent A: Water+0.1% trifluoracetic acid, Solvent B: Acetonitrile+0.1% trifluoracetic acid Flow rate: 21 ml min Run time: 20 minutes with various 10 minute gradients from 5-100% B Wavelength: 254 nm, bandwidth 10 nm Injection volume 0.1-4.0 ml (x) intermediates were not generally fully characterised and purity was assessed by thin layer chromatography (TLC), HPLC, infra-red (IR), MS or NMR analysis. TABLE 1 (xvii) Compound X 1 phenyl 2 3-fluorophenyl TABLE 2 (xviii) Compound X 3 3-fluorophenyl 4 3,5-difluorophenyl 5 2,3-difluorophenyl 6 3-chlorophenyl TABLE 3 (xix) Compound X Y 7 3-fluorophenyl 3-[ethyl(2-hydroxyethyl)amino]propoxy 8 3-fluorophenyl 3-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]propoxy 9 3-fluorophenyl 3-piperidin-1-ylpropoxy 10 3-fluorophenyl 3-pyrrolidin-1-ylpropoxy 11 3-fluorophenyl 3-[(2-hydroxyethyl)amino]propoxy 12 3-fluorophenyl 3-[(2-hydroxy-1,1-dimethylethyl)amino]propoxy 13 3-fluorophenyl 3-[(2-hydroxyethyl)(methyl)amino]propoxy 14 3-fluorophenyl 3-([1-(hydroxymethyl)-2- methylpropyl]amino)propoxy 15 3-fluorophenyl 3-(4-methylpiperazin-1-yl)propoxy 16 3-fluorophenyl 3-[(2-hydroxy-1-methylethyl)amino)propoxy 17 3-fluorophenyl 3-[(4-hydroxybutyl)amino]propoxy 18 3-fluorophenyl 3-(4-hydroxypiperidin-1-yl)propoxy 19 3-fluorophenyl 3-[2-(2-hydroxyethyl)piperidin-1-yl]propoxy 20 3-fluorophenyl 3-[4-(2-hydroxyethyl)piperazin-1-yl]propoxy 21 3-fluorophenyl 3-[4-(2-hydroxyethyl)piperidin-1-y]propoxy} 22 3-fluorophenyl 3-(3-hydroxypiperidin-1-yl)propoxy] 23 3-fluorophenyl 3-[(2-hydroxybutyl)amino]propoxy 24 3-fluorophenyl 3-[4-(hydroxymethyl)piperidin-1-yl]propoxy 25 3-fluorophenyl 3-[(3-hydroxy-2,2-dimethylpropyl)amino]propoxy 26 3-fluorophenyl 3-{[1-(hydroxymethyl)cyclopentyl]amino}propoxy 27 3-fluorophenyl 3-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]propoxy 28 3-fluorophenyl 3-{[(2S)-2-hydroxypropyl]amino}propoxy 29 3-fluorophenyl 3-{[(2R)-2-hydroxypropyl]amino}propoxy 30 3-fluorophenyl 3-[(3S)-3-hydroxypyrrolidin-1-yl]propoxy 31 3-fluorophenyl 3-[(3R)-3-hydroxypyrrolidin-1-yl]propoxy 32 3-fluorophenyl 3-[(2-fluoroethyl)(2-hydroxyethyl)amino]propoxy 33 3-fluorophenyl 2-[1-(2-hydroxyethyl)piperidin-4-yl]ethoxy 34 3-fluorophenyl 3-[(2-hydroxyethyl)(propyl)amino]propoxy 35 3-fluorophenyl 3-[(2-hydroxyethyl)(isopropyl)amino]propoxy 36 3-fluorophenyl 3-[(2-hydroxyethyl)(isobutyl)amino]propoxy 37 3-fluorophenyl 3-[(2,2-dimethylpropyl)(2-hydroxyethyl) amino]propoxy 38 3-fluorophenyl 3-[allyl(2-hydroxyethyl)amino]propoxy 39 3-fluorophenyl 3-[(2-hydroxyethyl)(prop-2-yn-1-yl)amino]propoxy 40 3-fluorophenyl 3-[cyclopropyl(2-hydroxyethyl)amino]propoxy 41 3-fluorophenyl 3-[(cyclopropylmethyl)(2- hydroxyethyl)amino]propoxy 42 3-fluorophenyl 3-[cyclobutyl(2-hydroxyethyl)amino]propoxy 43 3-fluorophenyl 3-[cyclopentyl(2-hydroxyethyl)amino]propoxy 44 3-fluorophenyl 3-[(2,2-dimethoxyethyl)(2- hydroxyethyl)amino]propoxy 45 3-fluorophenyl 3-[(2,2-difluoroethyl)(2-hydroxyethyl)amino]propoxy 46 3-fluorophenyl 3-[(2-hydroxyethyl)(3,3,3-trifluoropropyl)amino] propoxy 47 3-fluorophenyl 3-[(cyclobutylmethyl)(2- hydroxyethyl)amino]propoxy 48 3-fluorophenyl 3-[(2-hydroxyethyl)(2-methoxyethyl)amino]propoxy 49 3-fluorophenyl 3-[(1,3-dioxolan-2-ylmethyl)(2-hydroxyethyl)amino] propoxy 50 3-fluorophenyl 4-chlorobutoxy 51 3-fluorophenyl 4-(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]butoxy 52 3-fluorophenyl 4-[(2-hydroxyethyl)(isobutyl)amino]butoxy 53 3-fluorophenyl (2R)-1-(2-terr-butoxyethyl)pyrrolidin-2-yl]methoxy 54 3-fluorophenyl (2R)-1-(2-hydroxyethyl)pyrrolidin-2-yl]methoxy 55 3,5-difluorophenyl 3-pyrrolidin-1-ylpropoxy 56 3,5-difluorophenyl 3-[(2-hydroxyethyl)amino]propoxy 57 3,5-difluorophenyl 3-[(2-hydroxy-1,1-dimethylethyl)amino]propoxy 58 3,5-difluorophenyl 3-(4-methylpiperazin-1-yl)propoxy 59 3,5-difluorophenyl 3-[ethyl(2-hydroxyethyl)amino]propoxy 60 3,5-difluorophenyl 3-[2-(2-hydroxyethyl)piperidin-1-yl]propoxy 61 3,5-difluorophenyl 3-[4-(2-hydroxyethyl) piperazin-1-yl]propoxy 62 3,5-difluorophenyl 3-[4-(2-hydroxyethyl)piperidin-1-yl]propoxy 63 3,5-difluorophenyl 3-(3-hydroxypiperidin-1-yl)propoxy 64 3,5-difluorophenyl 3-[(2-hydroxybutyl)amino]propoxy 65 3,5-difluorophenyl 3-[4-(hydroxymethyl)piperidin-1-yl]propoxy 66 3,5-difluorophenyl 3-[(3-hydroxy-2,2-dimethylpropyl)amino]propoxy 67 3,5-dif1uorophenyl 3-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]propoxy 68 3,5-ditluorophenyl 3-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]propoxy 69 3,5-difluorophenyl 3-{[(2S)-2-hydroxypropyl]amino}propoxy 70 3,5-difluorophenyl 3-{[(2R)-2-hydroxypropyl]amino}propoxy 71 3,5-difluorophenyl 3-[(3S)-3-hydroxypyrrolidin-1-yl]propoxy 72 3,5-difluorophenyl 3-[(3R)-3-hydroxypyrrolidin-1-yl]propoxy 73 3,5-difluorophenyl 3-[(2-hydroxyethyl)(isobutyl)amino]propoxy 74 3,5-difluorophenyl 3-[(2-hydroxyethyl)(propyl)amino]propoxy 75 3,5-difluorophenyl 3-[allyl(2-hydroxyethyl)amino]propoxy 76 3,5-difluorophenyl 3-[(2-hydroxyethyl)(prop-2-yn-1-yl)amino]propoxy 77 3,5-difluorophenyl 3-[(2-hydroxyethyl)(isopropyl)amino]propoxy 78 3,5-difluorophenyl 3-[(2,2-dimethylpropyl)(2- hydroxyethyl)amino]propoxy 79 3,5-difluorophenyl 3-[cyclobutyl(2-hydroxyethyl)amino]propoxy 80 3,5-difluorophenyl 3-[(cyclopropylmethyl)(2- hydroxyethyl)amino]propoxy 81 2,3-difluorophenyl 3-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]propoxy 82 2,3-difluorophenyl 3-[(2,2-dimethylpropyl)(2- hydroxyethyl)amino]propoxy 83 2,3-difluorophenyl 3-[(2-hydroxyethyl)(propyl)amino]propoxy 84 2,3-difluorophenyl 3-[(2-hydroxyethyl)(isobutyl)amino]propoxy 85 2,3-difluorophenyl 3-[cyclobutyl(2-hydroxyethyl)amino]propoxy 86 2,3-difluorophenyl 3-[cyclopentyl(2-hydroxyethyl)amino]propoxy 87 2,3-difluorophenyl 3-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]propoxy 88 2,3-difluorophenyl 3-[(2-hydroxyethyl)(prop-2-yn-1-yl)amino]propoxy 89 2,3-difluorophenyl 3-[(cyclopropylmethyl)(2- hydroxyethyl)amino]propoxy 90 2,3-difluorophenyl 3-[(cyclobutylmethyl)(2- hydroxyethyl)amino]propoxy 91 2,3-difluorophenyl 3-[(2,2-dimethoxyethyl)(2- hydroxyethyl)amino]propoxy 92 2,3-difluorophenyl 3-[4-(2-hydroxyethyl)piperidin-1-yl]propoxy 93 2,3-difluorophenyl 3-(4-hydroxypiperidin-1-yl)propoxy 94 2,3-difluorophenyl 3-[4-(2-hydroxyethyl)piperazin-1-yl]propoxy 95 2,3-difluorophenyl 3-[(2-hydroxyethyl)(2-methoxyethyl)amino]propoxy 96 2,3-difluorophenyl 3-[allyl(2-hydroxyethyl)amino]propoxy 97 2,3-difluorophenyl 3-[(1,3-dioxolan-2-ylmethyl)(2- hydroxyethyl)amino]propoxy 98 2,3-difluorophenyl 3-[ethyl(2-hydroxyethyl)amino]propoxy 99 2,3-difluorophenyl 3-[(2-hydroxyethyl)(isopropyl)amino]propoxy 100 2,3-difluorophenyl 3-[(2-hydroxy-1,1-dimethylethyl)amino]propoxy 101 2,3-difluorophenyl (2R)-1-(2-hydroxyethyl)pyrrolidin-2-yl]methoxy 102 3-chlorophenyl 3-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]propoxy 103 3-chlorophenyl 3-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]propoxy 104 3-chlorophenyl 3-(3-hydroxypiperidin-1-yl)propoxy 105 3-chlorophenyl 3-[ethyl(2-hydroxyethyl)amino]propoxy TABLE 4 (xx) Compound X 106 3-methoxyphenyl 107 phenyl 108 4-fluorophenyl 109 3,5-dichiorophenyl 110 2-methoxy-5-chlorophenyl 111 3-(trifluoromethyl)phenyl 112 3-hydroxyphenyl 113 3-nitrophenyl 114 5-indazolyl 115 2-fluoro-4-bromophenyl 116 3-chlorophenyl 117 2-fluorophenyl 118 3,5-dimethoxyphenyl 119 6-(3-picolinyl) 120 2,3-difluorophenyl 121 2-fluoro-3-chlorophenyl 122 2,5-difluorophenyl 123 2-fluoro-5- (trifluoromethyl)phenyl 124 3,4-difluorophenyl 125 2,4-difluorophenyl 126 3-chloro-4-fluorophenyl 127 2-(difluoromethoxy)phenyl 128 3-cyanophenyl 129 3-bromophenyl TABLE 5 (xxi) Compound R Y 130 2,3-difluorophenyl 3-[ethyl(2-hydroxyethyl)amino]propoxy 131 2,3-difluorophenyl 3-[isopropyl(2-hydroxyethyl)amino]propoxy 132 2,3-difluorophenyl 3-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]propoxy 133 2,3-difluorophenyl 3-[propyl(2-hydroxyethyl)amino]propoxy 134 2,3-difluorophenyl 3-[propargyl(2-hydroxyethyl)amino]propoxy 135 2,3-difluorophenyl 3-[isobutyl(2-hydroxyethyl)amino]propoxy 136 2,3-difluorophenyl 3-[neopentyl(2-hydroxyethyl)amino]propoxy TABLE 6 (xxii) Compound R Y Z 137 3-fluorophenyl 3-(4-methylpiperazin-1- (1-(2-hydroxyethyl)- yl)propoxy piperidin-4-yl)oxy 138 3-fluorophenyl methoxy (1-methyl-piperidin-4-yl)oxy 139 2,3- methoxy methoxy difluorophenyl 140 2,3- 2-methoxyethoxy 2-methoxyethoxy difluorophenyl 141 2,3- 2-methoxyethoxy isopropoxy difluorophenyl 142 3-fluorophenyl 2-methoxyethoxy isopropoxy. 143 3-fluorophenyl methoxy (1-methyl-piperidin-4-yl)oxy 144 3-fluorophenyl methoxy methoxy 145 3-fluorophenyl 2-methoxyethoxy 2-methoxyethoxy TABLE 7 (xxiii) Compound X Y 146 3-fluorophenyl 3-[(2-hydroxyethyl) (isobutyl)amino]propoxy 147 2,3- 3-[(2-hydroxyethyl)(isobutyl) difluorophenyl amino]propoxy EXAMPLE 1 Preparation of Compound 1 in Table 1—2-(3-{[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)-N-phenylacetamide (5-((6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-yl)amino)-1H-pyrazol-3-yl) acetic acid (300 mg, 0.68 mmol) in dimethylformamide (5 ml) was reacted with aniline (62 μl, 0.68 mmol) in the presence of O-(7-azabenzotriazol-1-yl)N,N,N′,N′-tetramethyl-uronium hexafluorophosphate (260 mg, 0.68 mmol) and diisopropylethylamine (420 μl, 2.38 mmol) at 40° C. for 36 h. The solvent was evaporated in vacuo, water was added to the residue and the mixture was acidified (with 6.0 N hydrochloric acid) to pH 34. The water was evaporated and the residue was dissolved in methanol, adsorbed on silica gel, and purified by chromatography on silica gel. Elution with methanol:ammonia:dichloromethane (9:1:90) to yield compound 1 in table 1 (216 mg, 62% yield): 1H-NMR (DMSO d6, TFA): 8.92 (s, 1H), 8.26 (s, 1H), 7.55-7.62 (m, 2H), 7.20-7.25 (m, 3H), 7.03 (m, 1H), 6.80 (s, 1H), 4.28 (m, 2H), 3.95-4.05 (m, 2H), 3.97 (m, 3H), 3.79 (s, 2H), 3.65 (m, 2H), 3.45-3.55 (m, 2H), 3.30 (m, 2H), 3.12 (m, 2H), 2.20-2.30 (m, 2H): MS (+ve ESI): 518.6 (M+H)+. (5-((6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-yl)amino)-1H-pyrazol-3-yl)acetic acid, used as the starting material, was obtained as follows: a) 4-chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline (227 mg, 0.64 mmol) in pentan-2-ol (12 ml) and 6.0 N hydrochloric acid (0.25 ml, 1.5 mmol) was heated at 120° C. for 2 hours in the presence of methyl(5-amino-1H-pyrazol-3-yl)acetate (100 mg, 0.64 mmol). The reaction mixture was cooled, the solid was collected by filtration, dried and purified by chromatography on silica gel, eluting with methanol:ammonia:dichloromethane (9:1:90) to yield methyl(5-((6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-yl)amino)-1H-pyrazol-3-yl)acetate (251 mg, 85% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.37 (s, 1H), 6.82 (s, 1H), 4.32 (m, 2H), 4.01-4.10 (m, 2H), 4.01 (s, 3H), 3.86 (s, 2H), 3.70-3.80 (m, 2H), 3.69 (s, 3H), 3.50-3.60 (m, 2H), 3.35 (m, 2H), 3.18 (m, 2H), 2.28-2.40 (m, 2H): MS (+ve ESI): 457.6 (M+H)+. b) Methyl(5-((6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-yl)amino)-1H-pyrazol-3-yl)acetate (2.44 g, 5.35 mmol) in methanol (61 ml) and 2.0 N aqueous sodium hydroxide solution (61 ml, 122 mmol) was heated at 80° C. for 4 hours. The reaction mixture was cooled; the methanol was evaporated in vacuo and 6.0 N hydrochloric acid was added (to acidify the mixture to pH 3-4). The residual methanol was evaporated in vacuo, and the solid was purified by chromatography over an Oasis copolymer (Waters) to yield 5-((6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-yl)amino)-1H-pyrazol-3-yl)acetic acid (1.64 g, 36% yield): 1H-NMR (DMSO d6, TFA): 8.97 (s, 1H), 8.30 (s, 1H), 7.33 (s, 1H), 6.80 (s, 1H), 4.31 (m, 2H), 4.09 (m, 2H), 4.08 (s, 3H), 3.75 (s, 2H), 3.68 (m, 2H), 3.50-3.60 (m, 2H), 3.35 (m, 2H), 3.15 (m, 2H), 2.20-2.38 (m, 2H): MS (+ve ESI): 443.6 (M+H)+. EXAMPLE 2 Preparation of Compound 2 in Table 1—N-(3-fluorophenyl)-2-(3-{[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetamide An analogous reaction to that described in example 1, but starting with 3-fluoroaniline (37 μl, 0.41 mmol) yielded compound 2 in table 1 (34 mg, 19% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.60-7.70 (m, 1H), 7.32-7.42 (m, 2H), 7.32 (s, 1H), 6.85-6.92 (m, 1H), 6.83 (s, 1H), 4.30 (m, 2H), 4.00-4.10 (m, 2H), 4.01 (s, 3H), 3.85 (s, 2H), 3.69 (m, 2H), 3.50-3.60 (m, 2H), 3.35 (m, 2H), 3.16 (m, 2H), 2.25-2.40 (m, 2H): MS (+ve ESI): 536.6 (M+H)+. EXAMPLE 3 Preparation of Compound 3 in Table 2—2-(3-{[7-(3-chloropropoxy)-6-methoxyquinazolin-4-yl]amino}-1H-pyrazol-5-yl)-N-(3-fluorophenyl)acetamide (5-((7-(3-chloropropoxy)-6-methoxyquinazolin-4-yl)amino)-1H-pyrazol-3-yl)acetic acid (7.83 g, 20 mmol) in dimethylformamide (78 ml) was reacted with 3-fluoroaniline (2.44 g, 22 mmol) in the presence of 1-(3-dimethylamino-propyl)-3-ethylcarbodiimide hydrochloride (4.2 g, 22 mmol), 2-hydroxypyridin-1-oxide (2.22 g, 20 mmol) and diisopropylethylamine (2.8 g, 22 mmol) at 50° C. for 1.7 hours. The solvent was removed by evaporation in vacuo, the residue was triturated with water (twice), and purified by chromatography on silica gel, eluting with dichloromethane:methanol (95:3 to 85:15) to give compound 3 in table 2 (4.5 g, 46% yield) as a beige solid: 1H-NMR (DMSO d6): 8.47 (s, 1H), 8.02 (s, 1H), 7.60-7.68 (m, 1H), 7.40 (m, 2H), 7.20-7.30 (s, 1H), 6.88 (m, 1H), 6.84 (s, 1H), 4.27 (m, 2H), 3.96 (s, 3H), 3.84 (m, 2H), 3.78 (s, 2H), 2.26 (m, 2H): MS (+ve ESI): 485.6 (M+H)+. (5-((7-(3-chloropropoxy)-6-methoxyquinazolin-4-yl)amino)-1H-pyrazol-3-yl)acetic acid, used as the starting material, was obtained as follows: a) A mixture of 4-benzyloxy-3-methoxybenzaldehyde (157 g, 649 mmol), sodium acetate (106 g, 1.29 mol), hydroxylamine hydrochloride (90 g, 1.29 mol) and acetic acid (500 ml) was heated at reflux for 21 hours. The solvent was evaporated and ice/water (1000 ml) was added to the residue forming a sticky solid. The mixture was neutralised with aqueous sodium hydroxide solution then extracted with dichloromethane (2×500 ml). The organic solution was washed with 1.0 N sodium hydroxide (100 ml), brine (100 ml) and then dried over magnesium sulphate. Solvent evaporation in vacuo, trituration of the residue with hexane:ethyl acetate (3:1) and collection of the solid by suction filtration yielded 4-benzyloxy-3-methoxybenzonitrile (123 g, 80% yield) as a brown solid: 1H-NMR (DMSO d6): 7.38 (m, 7H), 7.19 (m, 1H), 5.18 (s, 2H), 3.80 (s, 3H): MS (−ve ESI): 238 (M−H). b) Acetic acid (17 ml) was added slowly to nitric acid (40 ml, 440 mmol) at 5° C. Powdered 4-benzyloxy-3-methoxybenzonitrile (10 g, 42 mmol) was added and the mixture warmed to 23° C. over 10 minutes. An exotherm occurred and the temperature was controlled at <30° C. using an ice bath. The mixture was stirred at 23° C. for 20 hours then poured into ice/water (1000 ml). After stirring for two hours the yellow solid was collected by suction filtration, washed with water and dried to yield 4-benzyloxy-3-methoxy-6-nitrobenzonitrile (10.1 g, 85% yield) as a yellow solid: 1H-NMR (DMSO d6): 7.95 (s, 1H), 7.70 (s, 1H), 7.40 (m, 5H), 5.30 (s, 2H), 3.95 (s, 3H): MS (−ve ESI): 283 (M−H)−. c) A mixture of 4-benzyloxy-3-methoxy-6-nitrobenzonitrile (46 g, 162 mmol), sodium bicarbonate (95 g, 1.13 mol), water (750 ml), dichloromethane (550 ml) and tetrabutylammonium chloride (30 g, 108 mmol) was rapidly stirred at 20° C. and treated portionwise with sodium dithionite (66 g, 379 mmol) over 2 hours. The mixture was stirred for a further 1 hour then the phases separated. The aqueous phase was extracted with dichloromethane (2×200 ml) and the combined organic solution washed with water (300 ml) and dried over magnesium sulphate. The solution was concentrated to 250 ml and 4.0 N hydrochloric acid in 1,4-dioxane (150 ml, 0.6 mol) added. The reaction was then diluted with diethyl ether (1000 ml) and cooled on ice. The resulting solid was collected by suction filtration and washed with diethyl ether. The solid was stirred in methanol (1000 ml) and sodium bicarbonate solution (800 ml) added (pH 8) and the mixture stirred for 1 hour. The solid was collected by suction filtration, washed with water, methanol and dried in vacuo to yield 2-amino-4-(benzyloxy)-5-methoxybenzonitrile (34 g, 82% yield) as light brown solid: 1H-NMR (DMSO d6): 7.40 (m, 5H), 6.90 (s, 1H), 6.50 (s, 1H), 5.60 (br s, 2H), 5.02 (s, 2H), 3.65 (s, 3H): MS (+ve ESI): 254 (M+H)+. d) 2-amino-4-(benzyloxy)-5-methoxybenzonitrile (100 g, 394 mmol) in toluene (1400 ml) was treated with dimethylformamide dimethylacetal (100 ml, 940 mmol) at reflux with slow distillation of solvent to maintain the internal temperature at 105° C. After 3 hours the solution was cooled and filtered to remove a small amount of solid. The filtrate was evaporated in vacuo, the residue triturated with diethyl ether, the solid collected by suction filtration and dried in vacuo to yield N′-(5-(benzyloxy)-2-cyano-4-methoxyphenyl)-N,N-dimethylimidoformamide (110 g, 90% yield) as a brown solid: 1H-NMR (DMSO d6): 7.90 (s, 1H), 7.40 (m, 5H), 7.10 (s, 1H), 6.88 (s, 1H), 5.15 (s, 2H), 3.70 (s, 3H), 3.02 (s, 3H), 2.95 (s, 3H): MS (+ve ESI): 310 (M+H)+. MS (−ve ESI): 308 (M−H)−. e) N′-(5-(benzyloxy)-2-cyano-4-methoxyphenyl)-N,N-dimethylimidoformamide (110 g, 356 mmol) and trifluoroacetic acid (600 ml) were heated at reflux for 15 minutes. The reaction was evaporated in vacuo and then azeotroped with toluene. The residue was triturated with diethyl ether and the solid collected by suction filtration. The solid was dried in vacuo to yield N′-(2-cyano-5-hydroxy-4-methoxyphenyl)-N,N-dimethylimidoformamide (112 g, 95% yield) as a light brown trifluoroacetate salt: 1H-NMR (DMSO d6): 8.39 (s, 1H), 7.38 (s, 1H), 6.90 (s, 1H), 3.80 (s, 3H), 3.25 (s, 3H), 3.17 (s, 3H): MS (+ve ESI): 220 (M+H)+. MS (−ve ESI): 218 (M−H)−. f) A mixture of N′-(2-cyano-5-hydroxy-4-methoxyphenyl)-N,N-dimethylimidoformamide (21.9 g, 66 mmol), caesium carbonate (998 g, 300 mmol) and 1-bromo-3-chloropropane (11 ml, 110 mmol) in acetonitrile (300 ml) was heated at reflux for 1 hour. The reaction mixture was cooled and the solvent evaporated in vacuo. Water (200 ml) was added and this was extracted with dichloromethane (2×150 ml). The organic solution was washed with brine (50 ml) and dried over magnesium sulphate. The solvent was evaporated in vacuo and the residue triturated with diethyl ether. The solid was collected by suction filtration and dried in vacuo to yield N′-(5-(3-chloropropoxy)-2-cyano-4-methoxyphenyl)-N,N-dimethylimidoformamide (17.7 g, 91% yield) as a white solid: 1H-NMR (DMSO d6): 8.89 (s, 1H), 7.07 (s, 1H), 6.75 (s, 1H), 4.15 (t, 2H), 3.77 (t, 2H), 3.70 (s, 3H), 3.05 (s, 3H), 2.95 (s, 3H), 2.18 (m, 2H): MS (+ve ESI): 296.4 (M+H)+. g) N′-(5-(3-chloropropoxy)-2-cyano-4-methoxyphenyl)-N,N-dimethylimidoformamide (230 mg, 0.78 mmol) in acetic acid (0.7 ml) was heated with methyl(5-amino-1H-pyrazol-3-yl)acetate (110 mg, 0.74 mmol) at reflux for 1 hour. The mixture was cooled, the acetic acid was evaporated in vacuo, and the residue purified by chromatography on silica gel, eluting with methanol:ammonia:dichloromethane (9:1:90), to yield methyl(5-((7-(3-chloropropoxy)-6-methoxyquinazolin-4-yl)amino)-1H-pyrazol-3-yl)acetate (219 mg, 69% yield) as a cream solid: 1H-NMR (DMSO d6, TFA): 8.93 (s, 1H), 8.28 (s, 1H), 7.32 (s, 1H), 6.80 (s, 1H), 4.02 (m, 2H), 4.00 (s, 3H), 3.75-3.85 (m, s, 4H), 3.65 (s, 3H), 2.30 (m, 2H), 1.90 (s, 3H): MS (+ve ESI): 406.5 (M+H)+. h) Methyl(5-((7-(3-chloropropoxy)-6-methoxyquinazolin-4-yl)amino)-1H-pyrazol-3-yl)acetate (100 mg, 0.247 mmol) in tetrahydrofuran (1.2 ml)/water (0.6 ml), was stirred with lithium hydroxide (21 mg, 0.493 mmol) at ambient temperature for 18 hours. The mixture was acidified with 6.0 N hydrochloric acid to pH 4 and the solid was recovered by filtration, washed with water and dried to yield (5-((7-(3-chloropropoxy)-6-methoxyquinazolin-4-yl)amino)-1H-pyrazol-3-yl)acetic acid (72 mg, 75% yield) as a beige solid: 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.28 (s, 1H), 7.32 (s, 1H), 6.80 (s, 1H), 4.33 (m, 2H), 4.00 (s, 3H), 3.83 (m, 2H), 3.74 (s, 2H), 2.40-2.50 (m, 2H): MS (+ve ESI): 392.5, 394.5 (M+H)+. Alternatively, N′-(5-(3-chloropropoxy)-2-cyano-4-methoxyphenyl)-N,N-dimethylimidoformamide (14.78 g, 50 mmol) in acetic acid (40 ml) was heated at reflux with (5-amino-1H-pyrazol-3-yl)acetic acid (8.1 g, 57.5 mmol) for 1.5 h. The reaction mixture was cooled to ambient temperature, water (250 ml) was added to the mixture and the solid was recovered by suction filtration. The solid was washed with 1) water, ii) ethyl acetate and iii) diethyl ether and dried in vacuo at 50° C. to yield (5-((7-(3-chloropropoxy)-6-methoxy-quinazolin-4-yl)amino)-1H-pyrazol-3-yl)acetic acid as a yellow solid (13.6 g, 69% yield): i) (5-amino-1H-pyrazol-3-yl)acetic acid (3.02 g, 0.022 mmol) in methanol (32 ml) was added to a mixture of methanol (32 ml) and thionyl chloride (3.15 ml) at 0° C. The resulting mixture was stirred for 18 hours, evaporated and the residue purified by chromatography on silica gel, eluting with methanol:ammonia:dichloromethane (9:1:90), to yield methyl(5-amino-1H-pyrazol-3-yl)acetate (1.58 g, 48% yield): 1H-NMR (CDCl3): 5.52 (s, 1H), 3.70 (s, 3H), 3.61 (s, 2H). EXAMPLE 4 Preparation of Compound 4 in Table 2—2-{3-[7-(3-chloropropoxy)-6-methoxyquinazolin-4-yl]amino}-1H-pyrazol-5-yl)-N-(3,5-difluorophenyl)acetamide A suspension of 3-{[7-(3-chloropropoxy)-6-methoxyquinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetic acid (3.91 g, 10 mmol) in dimethylformamide (20 ml) was reacted with 3,5-difluoroaniline (1.42 g, 11 mmol) in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodimide hydrochloride (2.01 g, 10.5 mmol) and 2-hydroxypyridine-1-oxide (1.11 g, 10 mmol) at 60° C. for 1.75 hours. The solvent was evaporated in vacuo and the residue was triturated twice with water. The resulting wet paste was dissolved in a mixture of dichloromethane:methanol (80:20), adsorbed onto silica gel and purified by chromatography on silica gel, eluting with dichloromethane:methanol (95:5 to 85:15) to yield compound 4 in table 2 (2.45 g, 49% yield) as a beige solid: 1H-NMR (DMSO d6): 8.47 (s, 1H), 8.02 (s, 1H), 7.36 (m, 2H), 7.20 (s, 1H), 6.94 (t, 1H), 6.84 (s, 1H), 4.27 (m, 2H), 3.96 (s, 3H), 3.83 (m, 2H), 3.79 (s, 2H), 2.27 (m, 2H): MS (+ve ESI): 503.5, 505.5 (M+H)+. EXAMPLE 5 Preparation of compound 5 in table 2-2-{3-[7-(3-chloropropoxy)-6-methoxyquinazolin-4-yl]amino}-1H-pyrazol-5-yl)-N-(2,3-difluorophenyl)acetamide 3-{[7-(3-chloropropoxy)-6-methoxyquinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetic acid (3.91 g, 10 mmol) was suspended in pyridine (20 ml) in the presence of 2,3-difluoroaniline (1.55 g, 12 mmol) under argon at 0° C. Phosphorus oxychloride (1.53 g, 10 mmol) in ethyl acetate (2 ml) was slowly added at 0° C. and the resulting mixture was allowed to warm to ambient temperature over 1.5 hours. The reaction mixture was diluted with ethyl acetate (150 ml) and diethyl ether (50 ml) resulting in the precipitation of a red solid. The solid was recovered by suction filtration, dried and re-suspended in water (100 ml). The mixture was cooled to 0° C. and the pH adjusted to 7 by addition of 1.5 N aqueous ammonium hydroxide solution. After 15 minutes stirring, the solid was recovered, dried, and purified by chromatography on silica gel. Elution with dichloromethane:methanol (95/5) and increased polarity to dichloromethane:methanolic ammonia (95:2) yielded compound 5 in table 2 as a pink solid (2.55 g, 50% yield): 1H-NMR (DMSO d6, TFA): 8.94 (s, 1H), 8.28 (s, 1H), 7.73 (m, 1H), 7.33 (s, 1H), 7.15-7.22 (m, 1H), 6.84 (s, 1H), 4.30 (m, 2H), 4.00 (s, 3H), 3.94 (s, 2H), 3.84 (m, 2H), 2.30 (m, 2H): MS (+ve ESI): 503.9 (M+H)+. EXAMPLE 6 Preparation of Compound 6 in Table 2—N-(3-chlorophenyl)-2-(3-{[7-(3-chloropropoxy)-6-methoxyquinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetamide 3-{[7-(3-chloropropoxy)-6-methoxyquinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetic acid (1.3 g, 3 mmol) vas dissolved in dimethylformamide (13 ml) and reacted with 3-chloroaniline (536 mg, 4.2 mmol) in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodimide hydrochloride (919 mg, 3.9 mmol) and 2-hydroxypyridine-1-oxide (433 mg, 3.9 mmol) at 50° C. for 1.5 hours. The solvent was evaporated in vacuo and the residue purified by chromatography on silica gel. Elution with dichloromethane:methanol (95:5) and increased polarity to dichloromethane:methanol (9:1) yielded compound 6 in table 2 (710 mg, 47% yield): 1H-NMR (DMSO d6, TFA): 8.94 (s, 1H), 8.28 (s, 1H), 7.85 (s, 1H), 7.48 (d, 1H), 7.35 (dd, 1H), 7.31 (s, 1H), 7.13 (dd, 1H), 6.83 (s, 1H), 4.32 (m, 2H), 4.00 (s, 3H), 3.84 (m, 2H), 3.83 (s, 2H), 2.30 (m, 2H): MS (+ve ESI): 501.44 (M+H)+. EXAMPLE 7 Preparation of Compound 7 in Table 3—2-{3-[(7-{3-[ethyl(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide 2-(5-((7-(3-chloropropoxy)-6-methoxyquinazolin-4-yl)amino) 1H-pyrazol-3-yl)-N-(3-fluorophenyl)acetamide (97 mg, 0.2 mmol) in dimethylacetamide (1 ml) was reacted with 2-(ethylamino)ethanol (53 mg, 0.6 mmol) at 90° C. for 8 hours. The mixture was cooled and purified by preparative LCMS to yield compound 7 in table 3 (36 mg, 33% yield): 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.29 (s, 1H), 7.62-7.65 (m, 1H), 7.25-7.40 (m, 3H), 6.83-6.90 (m, 1H), 6.83 (s, 1H), 4.30 (m, 2H), 4.00 (s, 3H), 3.84 (s, 2H), 3.77 (m, 2H), 3.20-3.40 (m, 6H), 2.25 (m, 2H), 1.26 (t, 3H): MS (+ve ESI): 538.6 (M+H)+. EXAMPLE 8 Preparation of Compound 8 in Table 3—N-(3-fluorophenyl)-2-{3-[(7-{3-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 7, but starting with L-prolinol (121 mg, 0.25 mmol) yielded compound 8 in table 3 (86 mg, 62% yield) as an off-white solid: 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.29 (s, 1H), 7.60-7.70 (m, 1H), 7.28-7.40 (m, 3H), 6.85-6.92 (m, 1H), 6.82 (s, 1H), 4.31 (m, 2H), 4.00 (s, 3H), 3.84 (s, 2H), 3.70-3.80 (m, 1H), 3.50-3.70 (m, 4H), 3.10-3.30 (m, 2H), 2.20-2.40 (m, 2H), 2.05-2.20 (m, 1H), 1.95-2.10 (m, 1H), 1.85-1.95 (m, 1H), 1.70-1.85 (m, 1H): MS (+ve ESI): 550.6 (M+H)+. EXAMPLE 9 Preparation of Compound 9 in Table 3—N-(3-fluorophenyl)-2-(3-{[6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin 4-yl]amino}-1H-pyrazol-5-yl)acetamide An analogous reaction to that described in example 7, but starting with piperidine (85 mg, 1 mmol) yielded compound 9 in table 3 (31 mg, 23% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.65 (d, 1H), 7.34 (m, 2H), 7.32 (s, 1H), 6.90 (m, 1H), 6.83 (s, 1H), 4.30 (m, 2H), 4.00 (s, 3H), 3.85 (s, 2H), 3.54 (d, 2H), 3.27 (m, 2H), 2.96 (m, 2H), 2.90 (m, 2H), 1.84 (m, 2H), 1.60-1.80 (m, 3H), 1.42 (m, 1H): MS (+ve ESI): 534.6 (M+H)+. EXAMPLE 10 Preparation of Compound 10 in Table 3—N-(3-fluorophenyl)-2-{3-[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetamide An analogous reaction to that described in example 7, but starting with pyrrolidine (71 mg, 1 mmol) yielded compound 10 in table 3 (58 mg, 45% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.64 (d, 1H), 7.35 (m, 2H), 7.33 (s, 1H), 6.90 (m, 1H), 6.84 (s, 1H), 4.30 (m, 2H), 4.00 (s, 3H), 3.85 (s, 2H), 3.68 (m, 2H), 3.31 (m, 2H), 3.10 (m, 2H), 2.28 (m, 2H), 1.91 (m, 2H): MS (+ve ESI): 520.6 (M+H)+. EXAMPLE 11 Preparation of Compound 11 in Table 3—N-(3-fluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 7, but starting with ethanolamine (61 mg, 1 mmol) yielded compound 11 in table 3 (80 mg, 77% yield): 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.29 (s, 1H), 7.37 (d, 1H), 7.34 (m, 2H), 7.31 (s, 1H), 6.95 (m, 1H), 6.83 (s, 1H), 4.30 (m, 2H), 4.00 (s, 3H), 3.85 (s, 2H), 3.68 (m, 2H), 3.16 (m, 2H), 3.09 (m, 2H), 2.21 (m, 2H): MS (+ve ESI): 509.5 (M+H)+. EXAMPLE 12 Preparation of Compound 12 in Table 3—N-(3-fluorophenyl)-2-{3-[(7-{3-[(2-hydroxy-1,1-dimethylethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 7, but starting with 2-amino-2-methyl-1-propanol (89 mg, 1 mmol) yielded compound 12 in table 3 (47 mg, 35% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.62 (m, 1H), 7.34 (m, 2H), 7.32 (s, 1H), 6.88 (m, 1H), 6.84 (s, 1H), 4.32 (m, 2H), 4.00 (s, 3H), 3.85 (s, 2H), 3.46 (s, 2H), 3.10 (m, 2H), 2.10 (m, 2H), 1.24 (s, 6H): MS (+ve ESI): 538.6 (M+H)+. EXAMPLE 13 Preparation of Compound 13 in Table 3—N-(3-fluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(methyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 7, but starting with 2-(methylamino)ethanol (75 mg, 1 mmol) yielded compound 13 in table 3 (88 mg, 67% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.3 (s, 1H), 7.64 (d, 1H), 7.35 (m, 2H), 7.33 (s, 1H), 6.90 (m, 1H), 6.84 (s, 1H), 4.30 (m, 2H), 4.01 (s, 3H), 3.85 (s, 2H), 3.77 (t, 2H), 3.15-3.45 (m, 4H), 2.38 (s, 3H), 2.30 (m, 2H): MS (+ve ESI): 524.6 (M+H)+. EXAMPLE 14 Preparation of Compound 14 in Table 3—N-(3-fluorophenyl)-2-(3-{[7-(3-{[1-(hydroxymethyl)-2-methylpropyl]amino}propoxy)-6-methoxyquinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetamide An analogous reaction to that described in example 7, but starting with 2-amino-3-methylbutan-1-ol (103 mg, 1 mmol) yielded compound 14 in table 3 (40 mg, 29% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.63 (d, 1H), 7.65 (m, 2H), 7.62 (s, 1H), 6.90 (m, 1H), 6.83 (s, 1H), 4.32 (m, 2H), 4.00 (s, 3H), 3.85 (s, 2H), 3.75 (dd, 1H), 3.66 dd, 1H), 3.23 (m, 2H), 3.03 (m, 2H), 2.27 (m, 2H), 2.08 (m, 1H), 1.02 (d, 3H), 0.97 (d, 3H): MS (+ve ESI): 552.6 (M+H)+. EXAMPLE 15 Preparation of Compound 15 in Table 3—N-(3-fluorophenyl)-2-[3-({6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinazolin-4-yl}amino)-1H-pyrazol-5-yl]acetamide An analogous reaction to that described in example 7, but starting with 1-methylpiperazine (100 mg, 1 mmol) yielded compound 15 in table 3 (51 mg, 37% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.65 (d, 1H), 7.38 (m, 2H), 7.35 (s, 1H), 6.88 (m, 1H), 6.84 (s, 1H), 4.31 (m, 2H), 3.20-4.10 (m, 8H), 4.01 (s, 3H), 3.85 (s, 2H), 3.40 (m, 2H), 2.95 (s, 3H), 2.30 (m, 2H): MS (+ve ESI): 549.6 (M+H)+. EXAMPLE 16 Preparation of Compound 16 in Table 3—N-(3-fluorophenyl)-2-{3-[(7-{3-[(2-hydroxy-1-methylethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 7, but starting with 2-amino-1-propanol (75.1 mg, 1 mmol) yielded compound 16 in table 3 (80 mg, 61% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.64 (d, 1H), 7.36 (m, 2H), 7.34 (s, 1H), 6.88 (m, 1H), 6.84 (s, 1H), 4.32 (m, 2H), 4.01 (s, 3H), 3.85 (s, 2H), 3.69 (dd, 0.1H), 3.50 (dd, 1H), 3.33 (m, 1H), 3.18 (m, 2H), 2.23 (m, 2H), 1.23 (d, 3H): MS (+ve ESI): 524.6 (M+H)+. EXAMPLE 17 Preparation of Compound 17 in Table 3—N-(3-fluorophenyl)-2-{3-[(7-{3-[(4-hydroxybutyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 7, but starting with 4-aminobutan-1-ol (89 mg, 1 mmol) yielded compound 17 in table 3 (56 mg, 42% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.64 (d, 1H), 7.34 (m, 2H), 7.32 (s, 1H), 6.90 (m, 1H), 6.84 (s, 1H), 4.30 (m, 2H), 4.01 (s, 3H), 3.85 (s, 2H), 3.45 (t, 2H), 3.14 (m, 2H), 2.98 (m, 2H), 2.20 (m, 2H), 1.67 (m, 2H), 1.50 (m, 2H): MS (+ve ESI): 538.6 (M+H)+. EXAMPLE 18 Preparation of Compound 18 in Table 3—N-(3-fluorophenyl)-2-[3-({7-[3-(4-hydroxypiperidin-1-yl)propoxy]-6-methoxyquinazolin-4-yl}amino)-1H-pyrazol-5-yl]acetamide An analogous reaction to that described in example 7, but starting with piperidin-4-ol (101 mg, 1 mmol) yielded compound 18 in table 3 (75 mg, 57% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.29 (s, 1H), 7.64 (m, 1H), 7.36 (m, 2H), 7.34 (s, 1H), 6.90 (m, 1H), 6.83 (s, 1H), 4.29 (t, 2H), 4.00 (s, 3H), 3.85 (s, 2H), 3.66 (m, 1H), 3.55 (d, 1H), 3.40 (m, 1H), 3.12-3.35 (m, 3H), 3.00 (t, 1H), 2.80 (m, 2H), 2.00 (m, 1H), 1.75-1.95 (m, 2H), 1.60 (m, 1H): MS (+ve ESI): 550.6 (M+H)+. EXAMPLE 19 Preparation of Compound 19 in Table 3—N-(3-fluorophenyl)-2-{3-[(7-{3-[2-(2-hydroxyethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 7, but starting with 2-(2-hydroxy-ethyl)piperidine (129 mg, 1 mmol) yielded compound 19 in table 3 (63 mg, 44% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.63 (d, 1H), 7.34 (m, 2H), 7.32 (s, 1H), 6.90 (m, 1H), 6.83 (s, 1H), 4.30 (m, 2H), 4.00 (s, 3H), 3.85 (s, 2H), 3.10-3.70 (m, 7H), 2.20-2.30 (m, 2H), 2.00-2.20 (m, 1H), 1.60-1.90 (m, 6H), 1.50 (m, 1H): MS (+ve ESI): 578.7 (M+H)+. EXAMPLE 20 Preparation of Compound 20 in Table 3—N-(3-fluorophenyl)-2-{3-[(7-{3-[4-(2-hydroxyethyl)piperazin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 7, but starting with 2-piperazin-1-ylethanol (130 mg, 1 mmol) yielded compound 20 in table 3 (69 mg, 48% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.63 (d, 1H), 7.36 (s, 1H), 7.34 (m, 2H), 6.90 (m, 1H), 6.84 (s, 1H), 4.31 (m, 2H), 2.70-4.10 (m, 8H), 4.01 (s, 3H), 3.85 (s, 2H), 3.79 (m, 2H), 3.40 (m, 2H), 3.35 (m, 2H), 2.29 (m, 2H): MS (+ve ESI): 579.6 (M+H)+. EXAMPLE 21 Preparation of Compound 21 in Table 3—N-(3-fluorophenyl)-2-{3-[(7-{3-[4-(2-hydroxyethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide Analogous reaction to that described in example 7, but starting with 4-(2-hydroxyethyl)piperidine (129 mg, 1 mmol) yielded compound 21 in table 3 (91 mg, 63% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.64 (d, 1H), 7.35 (m, 2H), 7.33 (s, 1H), 6.88 (m, 1H), 6.84 (s, 1H), 4.30 (m, 2H), 4.00 (s, 3H), 3.85 (s, 2H), 3.55 (m, 2H), 3.48 (m, 2H), 3.25 (m, 2H), 2.98 (m, 2H), 2.28 (m, 2H), 1.90 (m, 2H), 1.70 (m; 1H), 1.40 (m, 4H): MS (+ve ESI): 578.7 (M+H)+. EXAMPLE 22 Preparation of Compound 22 in Table 3—N-(3-fluorophenyl)-2-[3-({7-[3-(3-hydroxypiperidin-1-yl)propoxy]-6-methoxyquinazolin-4-yl}amino)-1H-pyrazol-5-yl]acetamide An analogous reaction to that described in example 7, but starting with piperidin-3-ol (101 mg, 1 mmol) yielded compound 22 in table 3 (65 mg, 47% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.29 (s, 1H), 7.62 (d, 1H), 7.38 (m, 2H), 7.34 (m, 2H), 7.34 (s, 1H), 6.90 (m, 1H), 6.84 (s, 1H), 4.28 (m, 2H), 4.10 (m, 1H), 4.00 (s, 3H), 3.85 (s, 2H), 2.80-3.50 (m, 6H), 1.30-2.40 (m, 6H): MS (+ve ESI): 550.6 (M+H)+. EXAMPLE 23 Preparation of Compound 23 in Table 3—N-(3-fluorophenyl)-2-{3-[(7-{3-[(2-hydroxybutyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 7, but starting with 1-aminobutan-2-ol (89 mg, 1 mmol) yielded compound 23 in table 3 (79 mg, 59% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.29 (s, 1H), 7.64 (d, 1H), 7.32-7.41 (m, 2H), 7.32 (s, 1H), 6.90 (t, 1H), 6.83 (s, 1H), 4.30 (t, 2H), 4.01 (s, 3H), 3.85 (s, 2H), 3.68 (m, 1H), 3.16 (t, 2H), 3.09 (d, 1H), 2.83 (t, 1H), 2.25 (m, 2H), 1.45 (m, 2H), 0.92 (t, 3H): MS (+ve ESI): 538.6 (M+H)+. EXAMPLE 24 Preparation of Compound 24 in Table 3—N-(3-fluorophenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 7, but starting with 4-(hydroxymethyl)piperidine (115 mg, 1 mmol) yielded compound 24 in table 3 (80 mg, 57% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.63 (m, 1H), 7.36 (m, 3H), 6.90 (m, 1H), 6.84 (s, 1H), 4.30 (t, 2H), 4.01 (s, 3H), 3.85 (s, 2H), 3.62 (d, 2H), 3.32 (d, 2H), 3.27 (m, 2H), 2.98 (t, 2H), 2.29 (m, 2H), 1.90 (d, 2H), 1.67 (m, 1H), 1.42 (m, 2H): MS (+ve ESI): 564.6 (M+H)+. EXAMPLE 25 Preparation of Compound 25 in Table 3—N-(3-fluorophenyl)-2-{3-[(7-{3-[(3-hydroxy-2,2-dimethylpropyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 7, but starting with 3-amino-2,2-dimethylpropan-1-ol (103 mg, 1 mmol) yielded compound 25 in table 3 (63 mg, 46% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.29 (s, 1H), 7.64 (d, 1H), 7.31-7.41 (m, 2H), 7.35 (s, 1H), 6.90 (t, 1H), 6.83 (s, 1H), 4.30 (t, 2H), 4.01 (s, 3H), 3.85 (s, 2H), 3.29 (s, 2H), 3.16 (t, 2H), 2.92 (t, 2H), 2.28 (m, 2H), 0.95 (s, 6H): MS (+ve ESI): 552.7 (M+H)+. EXAMPLE 26 Preparation of Compound 26 in Table 3—N-(3-fluorophenyl)-2-(3-{[7-(3-{[1-(hydroxymethyl)cyclopentyl]amino}propoxy)-6-methoxyquinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetamide An analogous reaction to that described in example 7, but starting with (1-amino-cyclopentyl)methanol (115 mg, 1 mmol) yielded compound 26 in table 3 (69 mg, 49% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.64 (d, 1H), 7.32-7.41 (m, 3H), 6.90 (t, 1H), 6.83 (s, 1H), 4.32 (t, 2H), 4.01 (s, 3H), 3.85 (s, 2H), 3.48 (s, 2H), 3.12 (m, 2H), 2.23 (m, 2H), 1.68-1.83 (m, 6H), 1.59 (m, 2H): MS (+ve ESI): 564.6 (M+H)+. EXAMPLE 27 Preparation of Compound 27 in Table 3—N-(3-fluorophenyl)-2-{3-[(7-{3-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 7, but starting with D-prolinol (101 mg, 1 mmol) yielded compound 27 in table 3 (61 mg, 44% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.65 (d, 1H), 7.31-7.41 (m, 2H), 7.34 (s, 1H), 6.90 (t, 1H), 6.84 (s, 1H), 4.31 (t, 2H), 4.01 (s, 3H), 3.85 (s, 2H), 3.77 (m, 1H), 3.53-3.68 (m, 4H), 3.15-3.30 (m, 2H), 2.30 (m, 2H), 2.13 (m, 1H), 2.02 (m, 1H), 1.90 (m, 1H), 1.78 (m, 1H): MS (+ve ESI): 550.6 (M+H)+. EXAMPLE 28 Preparation of Compound 28 in Table 3—N-(3-fluorophenyl)-2-(3-{[7-(3-{[(2S)-2-hydroxypropyl]amino}propoxy)-6-methoxyquinazolin-4-yl]amino}-1H-pyrazol 5-yl)acetamide An analogous reaction to that described in example 7, but starting with (S)-(+)-1-aminopropan-2-ol (75 mg, 1 mmol) yielded compound 28 in table 3 (70 mg, 53% yield): 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.29 (s, 1H), 7.64 (d, 1H), 7.31-7.40 (m, 2H), 7.32 (s, 1H), 6.90 (t, 1H), 6.83 (s, 1H), 4.30 (t, 2H), 4.01 (s, 3H), 3.95 (m, 1H), 3.85 (s, 2H), 3.15 (t, 2H), 3.05 (dd, 1H), 2.83 (dd, 1H), 2.23 (m, 2H), 1.15 (d, 3H): MS (+ve ESI): 524.6 (M+H)+. EXAMPLE 29 Preparation of Compound 29 in Table 3—N-(3-fluorophenyl)-2-{3-[7-(3-{[(2R)-2-hydroxypropyl]amino}propoxy)-6-methoxyquinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetamide An analogous reaction to that described in example 7, but starting with (R)-(−)-1-aminopropan-2-ol (75 mg, 1 mmol) yielded compound 29 in table 3 (80 mg, 61% yield): 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.29 (s, 1H), 7.64 (d, 1H), 7.31-7.40 (m, 2H), 7.31 (s, 1H), 6.90 (t, 1H), 6.83 (s, 1H), 4.30 (t, 2H), 4.01 (s, 3H), 3.95 (m, 1H), 3.85 (s, 2H), 3.15 (m, 2H), 3.06 (d, 1H), 2.83 (dd, 1H), 2.24 (m, 2H), 1.14 (d, 3H): MS (+ve ESI): 524.6 (M+H)+. EXAMPLE 30 Preparation of Compound 30 in Table 3—N-(3-fluorophenyl)-2-{3-[(7-{3-[(3S)-3-hydroxypyrrolidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 7, but starting with (S)-(−)-3-hydroxypyrrolidine (87 mg, 1 mmol) yielded compound 30 in table 3 (84 mg, 63% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.65 (d, 1H), 7.30-7.40 (m, 3H), 6.88 (t, 1H), 6.84 (s, 1H), 4.43-4.51 (m, 1H), 4.29 (m, 2H), 4.02 (s, 3H), 3.86 (s, 2H), 3.73 (m, 2H), 3.02-3.53 (m, 4H), 2.27 (m, 3H), 1.85-2.04 (m, 1H): MS (+ve ESI): 536.6 (M+H)+. EXAMPLE 31 Preparation of Compound 31 in Table 3—N-(3-fluorophenyl)-2-{3-[(7-{3-[(3R)-3-hydroxypyrrolidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]w1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 7, but starting with (R)-(+)-3-hydroxypyrrolidine (87 mg, 1 mmol) yielded compound 31 in table 3 (70 mg, 52% yield): 1H-NMR (DMSO d6, TFA): 10.45 (s, 1H), 10.18 (s, 1H), 8.46 (s, 1H), 7.98 (br s, 1H), 7.63 (d, 1H), 7.32-7.41 (m, 2H), 7.34 (s, 1H), 7.15 (s, 1H), 6.91 (t, 1H), 6.83 (br s, 1H), 4.69 (s, 1H), 4.15-4.24 (m, 3H), 3.94 (s, 3H), 3.76 (s, 2H), 2.72 (dd, 1H), 2.41-2.64 (m, 4H), 2.34 (dd, 1H), 1.91-2.04 (m, 3H), 1.55 (m, 1H): MS (+ve ESI): 536.6 (M+H)+. EXAMPLE 32 Preparation of Compound 32 in Table 3—2-{3-[(7-{3-[(2-fluoroethyl)(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide An analogous reaction to that described in example 7, but starting with 2-((2-fluoroethyl)amino)ethanol (180 mg, 1.68 mmol) and carrying out the reaction in N-methyl pyrrolidinone at 100° C. for 8 hours yielded compound 32 in table 3 (12 mg, 5% yield): 1H-NMR (DMSO d6): 10.45 (s, 1H), 10.18 (s, 1H), 8.47 (s, 1H), 8.00 (s, 1H), 7.63 (d, 1H), 7.37 (m, 1H), 7.35 (s, 1H), 7.15 (s, 1H), 6.91 (t, 1H), 6.83 (s, 1H), 4.54 (t, 1H), 4.43 (t, 1H), 4.37 (t, 1H), 4.18 (t, 2H), 3.95 (s, 3H), 3.77 (s, 2H), 3.46 (dd, 2H), 2.78 (t, 1H), 2.70 (t, 1H), 2.60 (t, 2H), 2.52 (t, 2H), 1.92 (m, 2H): MS (+ve ESI): 556.4 (M+H)+. 2-((2-fluoroethyl)amino)ethanol used as starting material was obtained as follows: Potassium carbonate (22 g, 159 mmol) was added to a solution of ethanolamine (4.75 ml, 78.7 mmol) and 1-bromo-2-fluoroethane (10.0 g, 78.7 mmol) in dioxane (100 ml) and the reaction mixture was heated at 80° C. for 10 hours. The reaction was concentrated and purified by chromatography on silica gel. Elution with dichloromethane:methanol (95:5) and increased polarity to dichloromethane:methanol:ammonia (90:5:5) yielded 2-((2-fluoroethyl)amino)ethanol (7.94 g, 74% yield). This compound was further purified by distillation under reduced pressure to give 2-((2-fluoroethyl)amino)ethanol (3.44 g, 32% yield): 1H-NMR (DMSO d6, TFA): 9.94 (br s, 1H), 4.79 (t, 1H), 4.68 (t, 1H), 3.67 (t, 2H), 3.37 (d, 1H), 3.30 (d, 1H), 3.07 (d, 2H). EXAMPLE 33 Preparation of Compound 33 in Table 3—N-(3-fluorophenyl)-2-{3-[(7-{2-[1-(2-hydroxyethyl)piperidin-4-yl]ethoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide 2-{3-[(7-{2-[1-(2-ten-butoxyethyl)piperidin-4-yl]ethoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide (160 mg, 0.25 mmol) was reacted with trifluoroacetic acid (3 ml) in dichloromethane (3 ml) at 40° C. for 1 hour. The solvent was evaporated, the residue dissolved in a mixture of dichloromethane:methanol. Hydrogen chloride (2.0 N in ether, 0.4 ml) was added resulting in the precipitation of a beige solid which was isolated and purified by preparative LCMS to yield compound 33 in table 3 as a beige solid (95 mg, 58% yield): 1H-NMR (DMSO d6, TFA): 8.94 (s, 1H), 8.29 (s, 1H), 7.63 (m, 1H), 7.35 (m, 3H), 6.89 (m, 1H), 6.83 (s, 1H), 4.24 (m, 2H), 3.99 (s, 3H), 3.85 (s, 2H), 3.76 (m, 2H), 3.52 (d, 2H), 3.26 (m, 1H), 3.14 (m, 2H), 2.98 (t, 2H), 1.94 (d, 2H), 1.81 (m, 2H), 1.57 (m, 2H): MS (+ve ESI): 564.2 (M+H)+. 2-{3-[(7-{2-[1-(2-tert-butoxyethyl)piperidin-4-yl]ethoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide used as starting material was obtained as follows. a) 4-(2-hydroxyethyl)piperidine (1.94 g, 15 mmol) in dimethylformamide (20 ml) was reacted with 2-(2-bromoethoxy)-2-methylpropane (3.13 g, 17.3 mmol) at 50° C. for 15 hours. The mixture was cooled and the solid removed by filtration. The solid was washed with ethyl acetate and the organics were washed with water, dried (magnesium sulphate) and concentrated to give 2-(1-(2-tert-butoxy ethyl)piperidin-4-yl)ethanol as a yellow oil (2.35 g, 100% yield): 1H-NMR (DMSO d6, TFA): 3.63 (m, 2H), 3.40-3.50 (m, 4H), 3.20 (m, 2H), 2.93 (t, 2H), 1.84 (d, 2H), 1.50-1.70 (m, 1H), 1.30-1.45 (4H), 1.18 (s, 9H). b) N′-(2-cyano-5-hydroxy-4-methoxyphenyl)-N,N-dimethylimidoformamide (876 mg, 4 mmol) in dichloromethane (2 ml) was reacted with 2-(1-(2-tert-butoxyethyl)piperidin-4-yl)ethanol (916 mg, 4.4 mmol) in the presence of triphenylphosphine (1.2 g, 4.6 mmol) by slow addition of a solution of di-tert-butyl azodicarboxylate (1.058 g, 4.6 mmol) in dichloromethane (5 ml). The mixture was stirred for 2 hours at ambient temperature and purified by chromatography. Elution with dichloromethane:ethyl acetate:methanol (5:4:1) yielded N′-(5-{2-[1-(2-tert-butoxyethyl)piperidin-4-yl]ethoxy}-2-cyano-4-methoxyphenyl)-N,N-dimethylimidoformamide (720 mg, 42% yield): 1H-NMR (DMSO d6, TFA): 8.54 (s, 1H), 7.50 (s, 1H), 7.29 (s, 1H), 4.14 (m, 2H), 3.85 (s, 3H), 3.64 (m, 2H), 3.53 (d, 2H), 3.37 (s, 3H), 3.33 (m, 1H), 3.27 (s, 3H), 3.21 (m, 2H), 2.98 (t, 2H), 1.80-2.00 (m, 2H), 1.60-1.80 (m, 2H), 1.30-1.60 (m, 2H), 1.18 (s, 9H): MS (+ve ESI): 431.28 (M+H)+. c) MV-(5-{2-[1-(2-tert-butoxyethyl)piperidin-4-yl]ethoxy}-2-cyano-4-methoxyphenyl)-N,N-dimethylimidoformamide (654 mg, 1.5 mmol) in acetic acid (1.35 ml) was heated with (3-amino-1H-pyrazol-5-yl)acetic acid (214 mg, 1.52 mmol) at reflux for 45 minutes. Acetic acid was evaporated and the residue taken up in a mixture of dichloromethane:methanol. Excess diisopropylethylamine was added, and the solvent evaporated in vacuo. Dichloromethane was added to the solid, which was filtered and dried to yield {3-[(7-{2-[1-(2-tert-butoxyethyl)piperidin-4-yl]ethoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetic acid as a white powder (530 mg, 66% yield): 1H-NMR (DMSO d6): 8.94 (s, 1H), 8.27 (s, 1H), 7.33 (s, 1H), 6.80 (s, 1H), 4.27 (m, 2H), 3.99 (s, 3H), 3.74 (s, 2H), 3.65 (m, 2H), 3.52 (d, 2H), 3.20-3.30 (m, 3H), 2.99 (t, 2H), 1.98 (d, 2H), 1.9-1.7 (m, 2H), 1.5 (m, 2H), 1.82 (s, 9H): MS (+ve ESI): 527.2 (M+H)+. d) {3-[(7-{2-[1-(2-tert-butoxyethyl)piperidin-4-yl]ethoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetic acid (210 mg, 0.4 mmol) in dimethylformamide (2.1 ml) was reacted with 3-fluoroaniline (58 mg, 0.52 mmol) in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (107 mg, 0.56 mmol) and 2-hydroxypyridine-1-oxide (53 mg, 0.48 mmol) at 55° C. for 1.5 hours. The reaction mixture was cooled, diluted with dichloromethane (7 ml) and purified by chromatography on silica gel. Elution with dichloromethane:methanol (9:1) and increased polarity to dichloromethane methanol:ammonia (9:1:0.1) yielded 2-{3-[(7-{2-[1-(2-tert-butoxyethyl)piperidin-4-yl]ethoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide (162 mg, 65% yield) as a light pink solid: 1H-NMR (DMSO d6, TFA): 8.94 (s, 1H), 8.27 (s, 1H), 7.63 (m, 1H), 7.32-7.40 (m, 3H), 6.89 (m, 1H), 6.82 (s, 1H), 4.25 (m, 2H), 3.99 (s, 3H), 3.84 (s, 2H), 3.64 (m, 2H), 3.51 (d, 2H), 3.10-3.30 (m, 3H), 2.99 (t, 2H), 1.97 (d, 2H), 1.60-1.95 (m, 2H), 1.78 (s, 9H), 1.51 (m, 2H): MS (+ve ESI): 620.3 (M+H)+. EXAMPLE 34 Preparation of Compound 34 in Table 3—N-(3-fluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(propyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 7, but starting with 2-(propylamino)ethanol (160 mg, 1.55 mmol) and carrying out the reaction in N-methyl pyrrolidinone (2.5 ml) in the presence of potassium iodide (103 mg, 0.62 mmol) at 60° C. for 8 hours yielded compound 34 in table 3 (21 mg, 12% yield): 1H-NMR (DMSO d6, TFA): 8.98 (s, 1H), 8.32 (s, 1H), 7.66 (d, 1H), 7.35-7.41 (m, 2H), 7.36 (s, 1H), 6.91 (t, 1H), 6.85 (s, 1H), 4.32 (t, 2H), 4.02 (s, 3H), 3.86 (s, 2H), 3.78 (t, 2H), 3.35 (m, 2H), 3.28 (m, 2H), 3.17 (m, 2H), 2.29 (m, 2H), 1.73 (m, 2H): MS (+ve ESI): 552.2 (M+H)+. EXAMPLE 35 Preparation of Compound 35 in Table 3—N-(3-fluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(isopropyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 34, but starting with 2-(isopropyl amino)ethanol (160 mg, 1.55 mmol) yielded compound 35 in table 3 (98 mg, 57% yield): 1H-NMR (DMSO d6, TFA): 8.98 (s, 1H), 8.31 (s, 1H), 7.66 (d, 1H), 7.32-7.41 (m, 2H), 7.37 (s, 1H), 6.92 (t, 1H), 6.85 (s, 1H), 4.33 (t, 2H), 4.02 (s, 3H), 3.86 (s, 2H), 3.79 (m, 2H), 3.33 (m, 4H), 3.17 (m, 1H), 2.33 (m, 2H), 1.31 (t, 6H): MS (+ve ESI): 552.2 (M+H)+. EXAMPLE 36 Preparation of Compound 36 in Table 3—N-(3-fluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(isobutyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 34, but starting with 2-(isobutyl amino)ethanol (181 mg, 1.55 mmol) yielded compound 36 in table 3 (101 mg, 57% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.63 (d, 1H), 7.32-7.41 (m, 2H), 7.34 (s, 1H), 6.90 (t, 1H), 6.83 (s, 1H), 4.30 (t, 2H), 4.00 (s, 3H), 3.84 (s, 2H), 3.80 (t, 2H), 3.37 (t, 2H), 3.28 (t, 2H), 3.00-3.15 (m, 2H), 2.29 (m, 2H), 2.12 (m, 2H), 1.00 (d, 6H): MS (+ve ESI): 566.3 (M+H)+. 2-(isobutylamino)ethanol used as starting material was obtained as follows: Ethylene oxide (5.28 g, 120 mmol) in methanol (14 ml), cooled to −60° C., was slowly added to a solution of isobutylamine (30.7 g, 420 mmol) in methanol (100 ml) at −65° C. under argon. The mixture was allowed to stir at ambient temperature for 14 hours, concentrated and the residual oil was purified by distillation (130° C. @ 0.5 mm Hg) to yield 2-(isobutylamino)ethanol (11 g, 78% yield): 1H-NMR (DMSO d6): 4.40 (m, 1H), 3.42 (m, 2H), 2.50 (m, 2H), 2.30 (d, 2H), 1.63 (m, 1H), 0.85 (d, 6H). EXAMPLE 37 Preparation of Compound 37 in Table 3—2-{3-[(7-{3-[(2,2-dimethylpropyl)(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide An analogous reaction to that described in example 34, but starting with 2-(2,2-dimethylpropyl)amino)ethanol (203 mg, 1.55 mmol) yielded compound 37 in table 3 (111 mg, 61% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.64 (d, 1H), 7.32-7.41 (m, 2H), 7.34 (s, 1H), 6.90 (t, 1H), 6.83 (s, 1H), 4.31 (t, 2H), 3.99 (s, 3H), 3.84 (s, 2H), 3.83 (t, 2H), 3.42 (t, 2H), 3.32 (t, 2H), 3.20 (dd, 2H), 2.35 (m, 2H), 1.07 (s, 9H): MS (+ve ESI): 580.3 (M+H)+. 2-((2,2-dimethylpropyl)amino)ethanol used as starting material was obtained as follows: Ethylene oxide (2.5 ml, 5.0 mmol) cooled to −20° C. was slowly added to a solution of (2,2-dimethylpropyl)amine (13 g, 150 mmol) in methanol (15 ml) at −30° C. under argon. The mixture was stirred at ambient temperature for 16 hours. The solvent was evaporated, and the residue purified by distillation (b.p. 132° C. @ 9 mmHg) to yield 2-((2,2-dimethylpropyl)amino)ethanol (6.4 g, 97% yield): 1H-NMR (DMSO d6, TFA): 3.70 (m, 2H), 3.02 (m, 2H), 2.81 (m, 2H), 0.98 (s, 9H). EXAMPLE 38 Preparation of Compound 38 in Table 3—2-{3-[(7-{3-[allyl(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide An analogous reaction to that described in example 34, but starting with 2-(allylamino)ethanol (156 mg, 1.55 mmol) yielded compound 38 in table 3 (33 mg, 19% yield): 1H-NMR (DMSO d6, TEA): 8.98 (s, 1H), 8.31 (s, 1H), 7.65 (d, 1H), 7.34-7.43 (m, 2H), 7.34 (s, 1H), 6.92 (t, 1H), 6.85 (s, 1H), 6.01 (m, 1H), 5.64 (d, 1H), 5.58 (d, 1H), 4.31 (t, 2H), 4.02 (s, 3H), 3.92 (t, 2H), 3.86 (s, 2H), 3.81 (t, 2H), 3.20-3.40 (m, 4H), 2.31 (m, 2H): MS (+ve ESI): 550.2 (M+H)+. 2-(allylamino)ethanol used as starting material was obtained as follows: Ethylene oxide (2.5 ml, 50 mmol) cooled to −20° C. was added to a solution of allylamine (14 g, 250 mmol) in methanol (20 ml) at −20° C. The mixture was stirred at ambient temperature for 14 hours, the solvent was evaporated, and the residual oil purified by distillation (b.p.140° C. @ 14 mmHg) to yield 2-(allylamino)ethanol (4.2 g, 84% yield): 1H-NMR (DMSO d6): 5.80-5.86 (m, 1H), 5.14 (m, 1H), 5.02 (m, 1H), 3.43 (m, 2H), 3.14 (m, 2H), 2.50 (m, 2H). EXAMPLE 39 Preparation of Compound 39 in Table 3—N-(3-fluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(prop-2-yn-1-yl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 34, but starting with 2-(prop-2-yn-1-ylamino)ethanol (153 mg, 1.55 mmol) yielded compound 39 in table 3 (48 mg, 28% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.29 (s, 1H), 7.64 (d, 1H), 7.32-7.41 (m, 2H), 7.32 (s, 1H), 6.90 (t, 1H), 6.90 (s, 1H), 4.31 (t, 2H), 4.29 (s, 2H), 4.00 (s, 3H), 3.90 (s, 1H), 3.84 (s, 2H), 3.79 (t, 2H), 3.43 (m, 2H), 3.34 (m, 2H), 2.30 (m, 2H): MS (+ve ESI): 548.2 (M+H)+. 2-(prop-2-yn-1-ylamino)ethanol used as starting material was obtained as follows: Ethylene oxide (3.3 g, 75 mmol) in methanol (10 ml) cooled to −40° C. was slowly added to a solution of propargylamine (16.5 g, 300 mmol) in methanol (60 ml) cooled to −6° C. under argon. The mixture was stirred at ambient temperature for 16 hours, the solvent was evaporated, and the residue purified by distillation to yield 2-(prop-2-yn-1-ylamino)ethanol (5 g, 67% yield): 1H-NMR (DMSO d6, TFA): 3.91 (m, 2H), 3.65 (m, 3H), 3.06 (m, 2H). EXAMPLE 40 Preparation of Compound 40 in Table 3—2-{3-[(7-{3-[cyclopropyl(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide An analogous reaction to that described in example 34, but starting with 2-(cyclopropylamino)ethanol (156 mg, 1.55 mmol, obtained as described by Morrow, D, F et al in J. Med. Chem. 1973, 16, 736-9) yielded compound 40 in table 3 (22 mg, 13% yield): 1H-NMR (DMSO d6, TFA): 8.97 (s, 1H), 8.31 (s, 1H), 7.65 (d, 1H), 7.33-7.42 (m, 2H), 7.37 (s, 1H), 6.92 (t, 1H), 6.85 (s, 1H), 4.33 (m, 2H), 4.02 (s, 3H), 3.86 (s, 2H), 3.79 (t, 2H), 3.48 (m, 2H), 3.42 (t, 2H), 2.97 (m, 1H), 2.36 (m, 2H), 1.04 (m, 2H), 0.94 (m, 2H): MS (+ve ESI): 550.2 (M+H)+. EXAMPLE 41 Preparation of Compound 41 in Table 3—2-{3-[(7-{3-[(cyclopropylmethyl)(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide An analogous reaction to that described in example 34, but starting with 2-((cyclopropylmethyl)amino)ethanol (178 mg, 1.55 mmol) yielded compound 41 in table 3 (19 mg, 11% yield): 1H-NMR (DMSO d6, TFA): 8.97 (s, 1H), 8.31 (s, 1H), 7.66 (d, 1H), 7.33-7.42 (m, 2H), 7.34 (s, 1H), 6.91 (t, 1H), 6.85 (s, 1H), 4.32 (t, 2H), 4.01 (s, 3H), 3.86 (s, 2H), 3.81 (t, 2H), 3.44 (m, 2H), 3.35 (m, 2H), 3.18 (t, 2H), 2.30 (m, 2H), 1.16 (m, 1H), 0.61 (m, 2H), 0.46 (m, 2H): MS (+ve ESI): 564.2 (M+H)+. 2-((cyclopropylmethyl)amino)ethanol used as starting material was obtained as follows: a) A solution of ethyl oxalyl chloride (4.2 ml, 37.6 mmol) in dichloromethane (35 ml) was added over 30 minutes to a solution of cyclopropylmethylamine (3 ml, 34.6 mmol) and triethylamine (7 ml) in dichloromethane (35 ml) at 0° C. The mixture was stirred at ambient temperature for 2 hours. Water (20 ml) was added and the pH adjusted to 3 using 2.0 N hydrochloric acid. The organic phase was separated, dried (magnesium sulphate) and concentrated to yield ethyl [(cyclopropylmethyl)amino](oxo)acetate (5.9 g, 100% yield): 1H-NMR (CDCl3): 7.24 (br s, 1H), 3.24 (m, 2H), 1.43 (t, 3H), 1.04 (m, 1H), 0.59 (m, 2H), 0.29 (m, 2H): MS (+ve ESI): 172 (M+H)*. b) A solution of ethyl [(cyclopropylmethyl)amino](oxo)acetate (5.9 g, 34.6 mmol) in tetrahydrofuran (30 ml) was added at ambient temperature to a mixture of borane-tetrahydrofuran complex (130 ml of a 1.0 N solution in THF, 130 mmol) and chlorotrimethylsilane (34 ml, 268 mmol). The reaction mixture was stirred at ambient temperature for 48 hours. Methanol (20 ml) was added and the reaction stirred for a further 30 minutes before dilution with dichloromethane followed by addition of a concentrated solution of hydrochloric acid (4 ml). The mixture was stirred for 30 minutes, basified with methanolic ammonia (7 N) and the resultant solid filtered and washed with dichloromethane. The organic phases were recovered, concentrated and purified by chromatography on silica gel. Elution with dichloromethane followed by increased polarity to dichloromethane:methanol (95:5), dichloromethane:methanolic ammonia (9:1) yielded 2-((cyclopropylmethyl)amino)ethanol as a pale yellow liquid (2.99 g, 75% yield): 1H-NMR (DMSO d6, TFA): 3.66 (t, 2H), 3.02 (t, 2H), 2.84 (d, 2H), 1.06 (m, 1H), 0.58 (m, 2H), 0.35 (m, 2H). EXAMPLE 42 Preparation of Compound 42 in Table 3—2-{3-[(7-{3-[cyclobutyl(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolino-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide An analogous reaction to that described in example 34, but starting with 2-(cyclobutylamino)ethanol (178 mg, 1.55 mmol—obtained as described by D. F. Morrow et al, J. Med. Chem. 1973, 16, 736-9) yielded compound 42 in table 3 (42 mg, 24% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.29 (s, 1H), 7.64 (d, 1H), 7.36 (m, 2H), 7.34 (s, 1H), 6.90 (t, 1H), 6.83 (s, 1H), 4.29 (t, 2H), 4.00 (s, 3H), 3.94 (m, 1H), 3.85 (s, 2H), 3.75 (m, 2H), 3.25 (m, 2H), 3.17 (m, 2H), 2.08-2.39 (m, 6H), 1.76 (m, 1H), 1.69 (m, 1H): MS (+ve ESI): 564.2 (M+H)+. EXAMPLE 43 Preparation of Compound 43 in Table 3—2-{3-[(7-{3-[cyclopentyl(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide An analogous reaction to that described in example 34, but starting with 2-(cyclopentylamino)ethanol (200 mg, 1.55 mmol—obtained as described by D. F. Morrow et al J. Med. Chem. 1973, 16, 736-9) yielded compound 43 in table 3 (30 mg, 17% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.64 (d, 1H), 7.34-7.42 (m, 2H), 7.33 (s, 1H), 6.90 (t, 1H), 6.84 (s, 1H), 4.31 (t, 2H), 4.00 (s, 3H), 3.85 (s, 2H), 3.65 (t, 2H), 3.48 (m, 1H), 3.37 (m, 2H), 3.28 (m, 2H), 2.30 (m, 2H), 2.08 (m, 2H), 1.72 (m, 3H), 1.58 (m, 3H): MS (+ve ESI): 578.3 (M+H)+. EXAMPLE 44 Preparation of Compound 44 in Table 3—2-{3-[(7-{3-[(2,2-dimethoxyethyl)(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin 4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide An analogous reaction to that described in example 34, but starting with 2-((2,2-dimethoxyethyl)amino)ethanol (231 mg, 1.55 mmol) yielded compound 44 in table 3 (89 mg, 48% yield): 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.29 (s, 1H), 7.63 (d, 1H), 7.31-7.40 (m, 2H), 7.33 (s, 1H), 6.89 (t, 1H), 6.83 (s, 1H), 4.85 (t, 1H), 4.28 (t, 2H), 4.00 (s, 3H), 3.84 (s, 2H), 3.80 (t, 2H), 3.41 (s, 6H), 3.37 (m, 6H), 2.29 (m, 2H): MS (+ve ESI): 598.2 (M+H)+. 2-((2,2-dimethoxyethyl)amino)ethanol used as starting material was obtained as follows. Ethanolamine (4 ml, 66.3 mmol) in dioxane (50 ml) in the presence of potassium carbonate (6.9 g, 50 mmol) was reacted with 2-bromo-1,1-dimethoxyethane (5 ml, 42.3 mmol) at 75° C. for 6 hours. The solid was filtered and washed with dioxane. The recovered organic phase was concentrated and purified by chromatography on silica gel. Elution with dichloromethane followed by increased polarity to dichloromethane:methanol (97:3), dichloromethane:methanolic ammonia (94:6) yielded 2-((2,2-dimethoxyethyl)amino)ethanol (2.4 g, 38% yield) as a pale yellow liquid: 1H-NMR (DMSO d6, AcOD): 4.64 (t, 1H), 3.61 (t, 2H), 3.34 (s, 6H), 2.99 (m, 2H), 2.93 (m, 2H). EXAMPLE 45 Preparation of Compound 45 in Table 3—2-{3-[(7-{3-[(2,2-difluoroethyl)(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide An analogous reaction to that described in example 34, but starting with 2-((2,2-difluoroethyl)amino)ethanol (194 mg, 1.55 mmol) yielded compound 45 in table 3 (27 mg, 15% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.64 (d, 1H), 7.33-7.40 (m, 2H), 7.33 (s, 1H), 6.89 (t, 1H), 6.84 (s, 1H), 6.61 (t, 1H), 4.30 (t, 2H), 4.01 (s, 3H), 3.90 (t, 2H), 3.85 (m, 4H), 3.48 (m, 2H), 3.42 (m, 2H), 2.34 (m, 2H): MS (+ve ESI): 574;3 (M+H)+. 2-((2,2-difluoroethyl)amino)ethanol used as starting material was obtained as follows: a) Methyl difluoroacetate (5 g, 45 mmol) in acetonitrile (50 ml) was reacted with ethanolamine (2.66 ml, 45.4 mmol) at ambient temperature for 24 hours. The solvent was evaporated and the residual oil was purified by chromatography on silica gel, eluting with dichloromethane:methanol (96:4) then dichloromethane:methanolic ammonia (94:6) to yield 2,2-difluoro-N-(2-hydroxyethyl)acetamide (6.18 g, 98% yield): 1H-NMR (DMSO d6): 8.76 (br s, 1H), 6.21 (t, 1H), 4.78 (t, 1H), 3.46 (t, 2H), 3.22 (t, 2H): MS (+ve ESI): 140 (M+H)+. b) Borane-tetrahydrofuran complex (40 ml of a 1.0 N solution in THF, 40 mmol) was added dropwise at 0° C. to a solution of 2,2-difluoro-N-(2-hydroxyethyl)acetamide (2.78 g, 20 mmol) in tetrahydrofuran (30 ml). The mixture was warmed to ambient temperature and then heated at reflux for 18 hours. The reaction mixture was cooled to ambient temperature and concentrated hydrochloric acid (6 ml) was added dropwise. The solvent was evaporated and the crude product was purified by chromatography on silica gel. Elution with dichloromethane methanolic ammonia (96:4) then dichloromethane:methanolic ammonia (94:6) yielded 2-((2,2-difluoroethyl)amino)ethanol (0.97 g, 39% yield): 1H-NMR (DMSO d6, TFA): 6.40 (m, 1H), 3.69 (t, 2H), 3.56 (m, 2H), 3.11 (t, 2H). EXAMPLE 46 Preparation of compound 46 in table 3—N-(3-fluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(3,3,3-trifluoropropyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 34, but starting with 2-((3,3,3-trifluoropropyl)amino)ethanol (221 mg, 1.55 mmol) yielded compound 46 in table 3 (77 mg, 41% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.29 (s, 1H), 7.63 (d, 1H), 7.31-7.40 (m, 2H), 7.33 (s, 1H), 6.89 (t, 1H), 6.83 (s, 1H), 4.29 (t, 2H), 3.99 (s, 3H), 3.84 (s, 2H), 3.79 (t, 2H), 3.51 (m, 2H), 3.38 (m, 2H), 2.91 (m, 2H), 2.29 (m, 2H): MS (+ve ESI): 606.2 (M+H)+. 2-((3,3,3-trifluoropropyl)amino)ethanol used as starting material was obtained as follows: 3-bromo-1,1,1-trifluoropropane (5.5 ml, 51.65 mmol) in dioxane (50 ml) in the presence of potassium carbonate (14.15 g, 102.5 mmol) was reacted with ethanolamine (3.0 ml, 51 mmol) at 60° C. for 36 hours. The solvent was evaporated and the residue purified by chromatography on silica gel. Elution with dichloromethane:methanol (95:5) then increased polarity to dichloromethane:methanolic ammonia (95:5) yielded 2-((3,3,3-trifluoropropyl)amino)ethanol (4.47 g, 55% yield): 1H-NMR (DMSO d6, TFA): 3.56 (t, 2H), 2.97 (t, 2H), 2.82 (t, 2H), 2.57 (m, 2H). EXAMPLE 47 Preparation of Compound 47 in Table 3—2-{3-[(7-{3-[(cyclobutylmethyl)(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide An analogous reaction to that described in example 34, but starting with 2-((cyclobutylmethyl)amino)ethanol (200 mg, 1.55 mmol) yielded compound 47 in table 3 (87 mg, 49% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.64 (d, 1H), 7.32-7.43 (m, 2H), 7.32 (s, 1H), 6.89 (t, 1H), 6.83 (s, 1H), 4.29 (t, 2H), 4.00 (s, 3H), 3.85 (s, 2H), 3.77 (t, 2H), 3.19-3.34 (m, 6H), 2.75-3.03 (m, 1H), 2.27 (m, 2H), 2.11 (m, 2H), 1.85 (m, 6H): MS (+ve ESI): 578.3 (M+H)+. 2-((cyclobutylmethyl)amino)ethanol used as starting material was obtained as follows: a) Cyclobutane carbonyl chloride (5 ml, 43.8 mmol) was slowly added to a solution of ethyl glycinate (5.86 g, 42 mmol) in dichloromethane (100 ml) and triethylamine (14.6 ml, 105 mmol) at 0° C. The mixture was then stirred at ambient temperature for 14 hours. The reaction mixture was washed with 1.0 N hydrochloric acid and the organic phase separated, dried (magnesium sulphate) and evaporated in vacuo to yield a yellow solid. Recrystallisation from dichloromethane:petroleum ether, yielded ethyl N-(cyclobutylcarbonyl)glycinate as a white solid (7.78 g, 100% yield): 1H-NMR (DMSO d6): 8.08 (t, 1H), 4.09 (q, 2H), 3.79 (s, 2H), 3.07 (m, 1H), 2.00-2.18 (m, 4H), 1.89 (m, 1H), 1.78 (m, 1H), 1.20 (t, 3H). b) Ethyl N-(cyclobutylcarbonyl)glycinate (7.6 g, 41 mmol) in tetrahydrofuran (40 ml) was added to borane-tetrahydrofuran complex (100 ml of a 1.0 N solution in tetrahydrofuran, 100 mol) and heated at 60° C. for 24 hours. Additional borane-tetrahydrofuran complex (20 ml) was added to the mixture and heating continued for a further 8 hours. The reaction mixture was then diluted slowly with methanol (20 ml) and stirred at ambient temperature for 0.5 hour. A concentrated solution of hydrochloric acid (6 ml) was slowly added following dilution with dichloromethane. The solid which precipitated was removed by filtration and washed with dichloromethane. The organic phase was dried (magnesium sulphate), concentrated and purified by chromatography on silica gel. Elution with dichloromethane:methanol (96:4) then dichloromethane:methanolic ammonia (94:6) yielded 2-((cyclobutylmethyl)amino)ethanol (4.16 g, 78% yield): 1H-NMR (DMSO d6, TFA): 8.38 (br s, 1H), 3.65 (t, 2H), 2.98 (m, 4H), 2.62 (m, 2H), 2.06 (m, 2H), 1.72-1.94 (m, 4H). EXAMPLE 48 Preparation of Compound 48 in Table 3—N-(3-fluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(2-methoxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 34, but starting with 2-((2-methoxy ethyl)amino)ethanol (184 mg, 1.55 mmol—obtained according to A. A. Santilli at al, J. Heterocycl. Chem. 1972, 9, 309-13) yielded compound 48 in table 3 (37 mg, 21% yield): 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.29 (s, 1H), 7.64 (d, 1H), 7.31-7.42 (m, 2H), 7.32 (s, 1H), 6.89 (t, 1H), 6.83 (s, 1H), 4.29 (t, 2H), 4.00 (s, 3H), 3.84 (s, 2H), 3.78 (t, 1H), 3.71 (t, 1H), 3.65 (t, 1H), 3.59 (t, 1H), 3.35-3.53 (m, 4H), 3.14 (t, 1H), 3.02 (t, 1H), 2.29 (m, 2H): MS (+ve ESI): 568.2 (M+H)+. EXAMPLE 49 Preparation of Compound 49 in Table 3—2-{3-[(7-{3-[(1,3-dioxolan-2-ylmethyl)(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide An analogous reaction to that described in example 34, but starting with 2-((1,3-dioxolan-2-ylmethyl)amino)ethanol (227 mg, 1.55 mmol) yielded compound 49 in table 3 (105 mg, 57% yield): 1H-NMR (DMSO d6, TA): 8.95 (s, 1H), 8.29 (s, 1H), 7.64 (d, 1H), 7.31-7.41 (m, 2H), 6.88 (t, 1H), 6.83 (s, 1H), 5.31 (t, 1H), 4.29 (t, 2H), 4.00 (s, 3H), 4.00 (t, 2H), 3.89 (t, 2H), 3.84 (s, 2H), 3.81 (t, 2H), 3.34-3.55 (m, 6H), 2.31 (m, 2H): MS (+ve ESI): 596.3 (M+H)+. 2-((1,3-dioxolan-2-ylmethyl)amino)ethanol used as starting material was obtained as follows: 2-(bromomethyl)-1,3-dioxolane (4.4 ml, 42.5 mmol) in dioxane (60 ml) was reacted with ethanolamine (4 ml, 66.3 mmol) in the presence of potassium carbonate (6.9 g, 50 mmol) at 75° C. for 7 hours. The mixture was concentrated and purified by chromatography on silica gel, eluting with dichloromethane:methanol (97:3) then dichloromethane:methanolic ammonia (94:6), to yield 2-((1,3-dioxolan-2-ylmethyl)amino)ethanol (1.90 g, 24% yield): 1H-NMR (DMSO d6, TFA): 5.17 (t, 1H), 3.86-4.04 (m, 4H), 3.67 (t, 2H), 3.20 (m, 2H), 3.06 (m, 2H). EXAMPLE 50 Preparation of Compound 50 in Table 3—2-(3-{[7-(4-chlorobutoxy)-6-methoxyquinazolin-4-yl]amino}-1H-pyrazol-5-yl)-N-(3-fluorophenyl)acetamide An analogous reaction to that described in example 3, but starting with (3-{[7-(4-chlorobutoxy)-6-methoxyquinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetic acid (2.05 g, 5 mmol) yielded compound 50 in table 3 as an off-white solid (1.45 g, 58% yield): 1H-NMR (DMSO d6, TFA): 8.94 (s, 1H), 8.27 (s, 1H), 7.64 (m, 1H), 7.33-7.40 (m, 2H), 7.29 (s, 1H), 6.72-6.88 (m, 1H), 6.83 (s, 1H), 4.27 (m, 2H), 4.01 (s, 3H), 3.85 (s, 2H), 3.76 (m, 2H), 1.92-1.99 (m, 4H): MS (+ve ESI): 499.1 (M+H)+. (3-{[7-(4-chlorobutoxy)-6-methoxyquinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetic acid used as starting material was obtained as follows: a) A solution of N′-(2-cyano-5-hydroxy-4-methoxyphenyl)-N,N-dimethylimidoformamide (3.29 g, 1.5 mmol) in dimethylformamide (33 ml) and potassium carbonate (4.14 g, 30 mmol) was reacted with 1-bromo 4-chorobutane (3.86 g, 2.5 mmol) at 60° C. for 2 hours. Water was added to the reaction mixture which was then extracted with ethyl acetate. The organic phase was dried (magnesium sulphate), concentrated and the residue was purified by chromatography on silica gel. Elution with dichloromethane:ethyl acetate (8:2) then increased polarity to (6:4) yielded N′-[5-(4-chlorobutoxy)-2-cyano-4-methoxyphenyl]-N,N-dimethylimidoformamide as a white solid (3.7 g, 80% yield): 1H-NMR (DMSO d6): 7.97 (s, 1H), 7.09 (s, 1H), 6.74 (s, 1H), 4.07 (m, 2H), 3.73 (m, 5H), 3.06 (s, 3H), 2.96 (s, 3H), 1.87 (m, 4H). b) N′-[5-(4-chlorobutoxy)-2-cyano-4-methoxyphenyl]-N,N-dimethylimidoformamide (464 g, 15 mmol) in acetic acid (13.5 ml, 225 mmol) was reacted with (3-amino-1H-pyrazol-5-yl)acetic acid (2.22 g, 15.8 mmol) at reflux for 1 hour. The mixture was cooled, diluted with ethanol (25 ml) and the resultant precipitate recovered by suction filtration. The solid was stirred in water for 1 hour, collected by suction filtration and dried to yield (3-([7-(4-chlorobutoxy)-6-methoxyquinazolin-4-yl]amino)-1H-pyrazol-5-yl)acetic acid (4.5 g, 74% yield): 1H-NMR (DMSO d6, TFA): 8.47 (s, 1H), 7.97 (s, 1H), 7.15 (s, 1H), 6.69 (s, 1H), 4.18. (m, 2H), 3.94 (s, 3H), 3.76 (m, 2H), 3.65 (s, 2H), 1.93 (m, 4H): MS (+ve ESI): 406.14 (M+H)+. EXAMPLE 51 Preparation of Compound 51 in Table 3—N-(3-fluorophenyl)-2-{3-[(7-{4-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]butoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 7, but starting with 2-(3-{[7-(4-chlorobutoxy)-6-methoxyquinazolin-4-yl]amino}-1H-pyrazol-5-yl)-N-(3-fluorophenyl)acetamide (125 mg, 0.25 mmol) and D-prolinol (76 mg, 0.75 mmol) in the presence of potassium iodide (83 mg, 0.5 mmol) and heating for 3 hours, yielded compound 51 in table 3 as a pale yellow solid (68 mg, 48% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.29 (s, 1H), 7.64 (m, 1H), 7.34-7;40 (m, 2H), 7.33 (s, 1H), 6.90 (m, 1H), 6.84 (s, 1H), 4.25 (m, 2H), 4.01 (s, 3H), 3.79 (s, 2H), 3.77 (m, 1H), 3.58-3.65 (m, 3H), 3.40-3.50 (m, 1H), 3.14 (m, 2H), 2.10 (m, 1H), 2.00 (m, 1H), 1.80-1.95 (m, 5H), 1.75 (m, 1H): MS (+ve ESI): 564.3 (M+H)+. EXAMPLE 52 Preparation of Compound 52 in Table 3—N-(3-fluorophenyl)-2-{3-[(7-{4-[(2-hydroxyethyl)(isobutyl)amino]butoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 51, but starting with 2-(isobutyl amino)ethanol (117 mg, 0.75 mmol) yielded compound 52 in table 3 as a yellow solid (88 mg, 60% yield): 1H-NMR (DMSO d6, TEA): 8.96 (s, 1H), 8.30 (s, 1H), 7.65 (m, 1H), 7.33-7.38 (m, 3H), 6.89 (m, 1H), 6.85 (s, 1H), 4.26 (m, 2H), 4.01 (s, 3H), 3.86 (s, 2H), 3.79 (m, 2H), 3.23-3.29 (m, 2H), 3.09 (m, 1H), 2.98 (m, 1H), 2.10 (m, 1H), 1.91 (m, 4H), 0.99 (d, 6H): MS (+ve ESI): 580.2 (M+H)+. EXAMPLE 53 Preparation of Compound 53 in Table 3—2-{3-[(7-{[(2R)-1-(2-tert-butoxyethyl)pyrrolidin-2-yl]methoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide An analogous reaction to that described in example 3, but starting with 3-[(7-{[(2R)-1-(2-tert-butoxyethyl)pyrrolidin-2-yl]methoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetic acid (450 mg, 0.9 mmol) yielded compound 53 in table 3 (130 mg, 24% yield): 1H-NMR (DMSO d6): 10.45 (s, 1H), 10.18 (s, 1H), 8.45 (s, 1H), 7.95 (s, 1H), 7.62 (d, 1H), 7.36 (m, 2H), 7.14 (s, 1H), 6.90 (m, 1H), 6.73 (s, 1H), 4.06 (m, 1H), 3.93 (m, 4H), 3.73 (s, 2H), 3.40 (m, 2H), 3.00 (m, 4H), 2.36 (m, 2H), 1.75 (m, 3H), 1.11 (s, 9H): MS (+ve ESI): 592.2 (M+H)+. 3-[(7-{[(2R)-1-(2-tert-butoxyethyl)pyrrolidin-2-yl]methoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl)acetic acid used as starting material was obtained as follows: a) A solution of N′-(2-cyano-5-hydroxy-4-methoxyphenyl)-N,N-dimethyl-imidoformamide (3.00 g, 13.7 mmol) in dichloromethane (30 ml) was reacted with tert-butyl (2R)-2-(hydroxymethyl)pyrrolidine-1-carboxylate (3.03 g, 15 mmol) in the presence of triphenylphosphine (5.38 g, 20.5 mmol) and diethyl azodicarboxylate (3.23 ml, 20.5 mmol). The mixture was stirred at ambient temperature for 2 hours, the solvent was evaporated, and the residue purified by chromatography on silica gel. Elution with ethyl acetate:petroleum ether (2:8) then (1:1) yielded tert-butyl(2R)-2-[(4-cyano-5-{[(1E)-(dimethylamino)methylene]amino}-2-methoxyphenoxy)methyl]pyrrolidine-1-carboxylate (5.4 g, 99% yield): 1H-NMR (DMSO d6): 7.88-8.00 (m, 1H), 6.92-7.10 (m, 1H), 6.73 (s, 1H), 4.08 (m, 2H), 3.98 (m, 1H), 3.73 (s, 3H), 3.26 (m, 2H), 3.05 (s, 3H), 2.95 (s, 3H), 1.99 (m, 2H), 1.96 (m, 2H), 1.41 (s, 9H): MS (+ve ESI): 403.3 (M+H)+. b) tert-butyl(2R)-2-[(4-cyano-5-{[(1E)-(dimethylamino)methylene]amino}-2-methoxyphenoxy)methyl]pyrrolidine-1-carboxylate (5.4 g, 13 mmol) was reacted with a mixture of dichloromethane/trifluoroacetic acid (5:1) at ambient temperature for 14 hours. The solvent was evaporated, and the residue purified by chromatography on silica gel, eluting with dichloromethane:methanol (9:1) then dichloromethane:methanolic ammonia (9:1), to yield N′-{2-cyano-4-methoxy-5-[(2R)-pyrrolidin-2-ylmethoxy]phenyl}-N,N-dimethylimidoformamide (1.5 g, 35% yield): 1H-NMR (DMSO d6, TFA): 8.56 (s, 1H), 7.57 (s, 1H, 7.36 (s, 1H), 4.40 (m, 1H), 4.21 (m, 1H), 4.05 (m, 1H), 3.90 (s, 3H), 3.27 (m, 2H), 3.39 (s, 3H), 3.29 (s, 3H), 2.20 (m, 1H), 2.02 (m, 1H), 1.95 (m, 1H), 1.75 (m, 1H): MS (+ve ESI): 330.2 (M+H)+. c) N′-(2-cyano-4-methoxy-5-[(2R)-pyrrolidin-2-ylmethoxy]phenyl)-N,N-dimethylimidoformamide (1.23 g, 4.06 mmol) in dimethylformamide (13 ml) was reacted with 2-(2-bromoethoxy)-2-methylpropane (809 mg, 4.47 mmol) in the presence of potassium carbonate (842 mg, 6.1 mmol) at 50° C. for 5 hours. The solvent was then evaporated, and the residue purified by chromatography on silica gel, eluting with dichloromethane:methanol (98:2) then (95:5), to yield N′-(5-{[(2R)-1-(2-tert-butoxyethyl)pyrrolidin-2-yl]methoxy}-2-cyano-4-methoxyphenyl)-N,N-dimethylimidoformamide (908 mg, 56% yield): 1H-NMR (DMSO d6): 7.91 (s, 1H), 7.07 (s, 1H), 6.74 (s, 1H), 3.97 (m, 1H), 3.84 (m, 1H), 3.72 (s, 3H), 3.39 (m, 2H), 2.92 (m, 2H), 2.50 (m, 1H), 2.31 (m, 1H), 1.91 (m, 1H), 1.68 (m, 2H), 1.57 (m, 1H), 1.11 (s, 9H): MS (+ve ESI): 403.25 (M+H)+. d) N′-(5-{[(2R)-1-(2-tert-butoxyethyl)pyrrolidin-2-yl]methoxy}-2-cyano-4-methoxyphenyl)-N,N-dimethylimidoformamide (300 mg, 0.74 mmol) in acetic acid (0.64 ml) was reacted with (3-amino-1H-pyrazol-5-yl)acetic acid (110 mg, 0.78 mmol) at 120° C. for 20 minutes. The solvent was evaporated, and the residue triturated with dichloromethane to yield {3-[(7-{[(2R)-1-(2-tern-butoxyethyl)pyrrolidin-2-yl]methoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetic acid (183 mg, 47% yield): 1H-NMR (DMSO d6): 10.25 (s, 1H), 8.44 (s, 1H), 7.97 (s, 1H), 7.13 (s, 1H), 6.65 (s, 1H), 4.06 (m, 1H), 3.93 (m, 4H), 3.64 (s, 2H), 3.40 (m, 2H), 3.05 (m, 4H), 2.36 (m, 2H), 1.75 (m, 3H), 1.11 (s, 9H): MS (+ve ESI): 499.17 (M+H)+. EXAMPLE 54 Preparation of Compound 54 in Table 3—N-(3-fluorophenyl)-2-{3-[(7-{[(2R)-1-(2-hydroxyethyl)pyrrolidin-2-yl]methoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide 2-{3-[(7-{[(2R)-1-(2-tert-butoxyethyl)pyrrolidin-2-yl]methoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide (120 mg, 0.2 mmol) was reacted with a mixture of dichloromethane trifluoroacetic acid (5:2) at ambient temperature for 18 hours. The solvent was evaporated in vacuo and the residue purified by chromatography on silica gel, eluting with dichloromethane:methanol (9:1) then dichloromethane:methanolic ammonia (95:5), to yield compound 54 in table 3 (40 mg, 37% yield): 1H-NMR (DMSO d6): 11.00 (s, 1H), 10.33 (s, 1H), 8.45 (s, 1H), 7.99 (s, 1H), 7.62 (d, 1H), 7.34 (m, 2H), 7.15 (s, 1H), 6.89 (t, 1H), 6.83 (s, 1H), 4.40 (s, 1H), 4.07 (s, 1H), 3.93 (m, 4H), 3.76 (s, 2H), 3.50 (s, 2H), 3.09 (m, 1H), 2.97 (m, 2H), 2.31 (m, 1H), 1.94 (m, 1H), 1.73 (m, 2H), 1.65 (m, 1H): MS (+ve ESI): 536.2 (M+H)+. EXAMPLE 55 Preparation of Compound 55 in Table 3—N-(3,5-difluorophenyl)-2-(3-{[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetamide An analogous reaction to that described in example 7, but starting with 2-(5-[(7-(3-chloropropoxy)-6-methoxyquinazolin-4-yl)amino)-1H-pyrazol-3-yl)-N-(3,5-difluorophenyl)acetamide (130 mg, 0.26 mmol) and pyrrolidine (71 mg, 1 mmol) yielded compound 55 in table 3 (24 mg, 17% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.25-7.45 (m, 3H), 6.91 (m, 1H), 6.84 (s, 1H), 4.30 (m, 2H), 4.01 (s, 3H), 3.86 (s, 2H), 3.60-3.75 (m, 2H), 3.30-3.45 (m, 2H), 3.00-3.15 (m, 2H), 2.20-2.32 (m, 2H), 2.00-2.15 (m, 2H), 1.80-2.00 (m, 2H): MS (+ve ESI): 538.5 (M+H)+. EXAMPLE 56 Preparation of Compound 56 in Table 3—N-(3,5-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 55 but starting with ethanolamine (61 mg, 1 mmol) yielded compound 56 in table 3 (50 mg, 36% yield): 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.29 (s, 1H), 7.36 (d, 1H), 7.35 (d, 1H), 7.31 (s, 1H), 6.92 (t, 1H), 6.83 (s, 1H), 4.30 (t, 2H), 4.01 (s, 3H), 3.86 (s, 2H), 3.69 (t, 2H), 3.16 (m, 2H), 3.09 (m, 2H), 2.23 (m, 2H): MS (+ve ESI): 528.5 (M+H)+. EXAMPLE 57 Preparation of Compound 57 in Table 3—N-(3,5-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxy-1,1-dimethylethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 55, but starting with 2-amino-2-methyl-1-propanol (89 mg, 1 mmol) yielded compound 57 in table 3 (50 mg, 35% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.37 (d, 1H), 7.35 (d, 1H), 7.33 (s, 1H), 6.91 (t, 1H), 6.84 (s, 1H), 4.32 (t, 2H), 4.01 (s, 3H), 3.86 (s, 2H), 3.46 (s, 2H), 3.10 (m, 2H), 2.22 (m, 2H), 1.25 (s, 6H): MS (+ve ESI): 556.5 (M+H)+. EXAMPLE 58 Preparation of Compound 58 in Table 3—N-(3,5-difluorophenyl)-2-[3-({6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinazolin-4-yl}amino)-1H-pyrazol-5-yl]acetamide An analogous reaction to that described in example 55, but starting with 1-methylpiperazine (100 mg, 1 mmol) yielded compound 58 in table 3 (60 mg, 41% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.37 (d, 1H), 7.35 (s, 1H), 7.34 (d, 1H), 6.91 (t, 1H), 6.84 (s, 1H), 4.31 (t, 1H), 4.01 (s, 3H), 3.86 (s, 2H), 3.20-3.95 (m, 8H), 3.44 (t, 2H), 2.95 (s, 3H), 2.30 (m, 2H): MS (+ve ESI): 567.5 (M+H)+. EXAMPLE 59 Preparation of Compound 59 in Table 3—N-(3,5-difluorophenyl)-2-{3-[(7-{3-[ethyl(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 55, but starting with 2-(ethylamino)ethanol (89 mg, 1 mmol) yielded compound 59 in table 3 (124 mg, 86% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.35 (m, 2H), 7.33 (s, 1H), 6.90 (m, 1H), 6.84 (s, 1H), 4.30 (m, 2H), 4.01 (s, 3H), 3.86 (s, 2H), 3.78 (t, 2H), 3.30 (m, 6H), 2.29 (m, 2H), 1.27 (t, 3H): MS (+ve ESI): 556.5 (M+H)+. EXAMPLE 60 Preparation of Compound 60 in Table 3—N-(3,5-difluorophenyl)-2-{3-[(7-{3-[2-(2-hydroxyethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 55, but starting with 2-(2-hydroxyethyl)piperidine (129 mg, 1 mmol) yielded compound 60 in table 3 (58 mg, 37% yield): 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.29 (s, 1H), 7.36 (m, 3H), 6.95 (t, 1H), 6.90 (s, 1H), 4.30 (m, 2H), 4.00 (s, 3H), 3.85 (s, 2H), 3.10-3.70 (m, 7H), 2.25 (m, 2H), 1.80 (m, 6H), 1.50 (m, 2H): MS (+ve ESI): 596.6 (M+H)+. EXAMPLE 61 Preparation of Compound 61 in Table 3—N-(3,5-difluorophenyl)-2-{3-[(7-{3-4-(2-hydroxyethyl)piperazin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 55, but starting with 2-piperazin-1-ylethanol (130 mg, 1 mmol) yielded compound 61 in table 3 (80 mg, 52% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.36 (m, 3H), 6.95 (t, 1H), 6.83 (s, 1H), 4.31 (m, 2H), 4.00 (s, 3H), 3.86 (s, 2H), 3.30-3.90 (m, 14H), 2.30 (m, 2H): MS (+ve ESI): 597.5 (M+H)+. EXAMPLE 62 Preparation of Compound 62 in Table 3—N-(3,5-difluorophenyl)-2-{3-[(7-{3-[4-(2-hydroxyethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 55, but starting with 4-(2-hydroxyethyl)piperidine (129 mg, 1 mmol) yielded compound 62 in table 3 (67 mg, 43% yield): 1H-NMR (DMSO d6, TFA): 8.45 (s, 1H), 8.00 (s, 1H), 7.37 (m, 2H), 7.14 (s, 1H), 6.95 (m, 1H), 6.84 (s, 1H), 4.34 (t, 1H), 4.17 (m, 2H), 3.94 (s, 3H), 3.79 (s, 2H), 3.45 (m, 2H), 2.88 (m, 2H), 2.40 (t, 2H), 1.90 (m, 4H), 1.62 (d, 2H), 1.36 (m, 3H), 1.15 (m, 2H): MS (+ve ESI): 596.6 (M+H)+. EXAMPLE 63 Preparation of Compound 63 in Table 3—N-(3,5-difluorophenyl)-2-[3-({7-[3-(3-hydroxypiperidin-1-yl)propoxy]-6-methoxyquinazolin-4-yl}amino)-1H-pyrazol-5-yl]acetamide An analogous reaction to that described in example 55, but starting with piperidin-3-ol (101 mg, 1 mmol) yielded compound 63 in table 3 (105 mg, 71% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.29 (s, 1H), 7.97 (m, 3H), 6.92 (t, 1H), 6.86 (s, 1H), 4.30 (m, 2H), 4.00 (s, 3H), 3.86 (s, 2H), 2.80-3.60 (m, 6H), 1.70-2.30 (m, 2H): MS (+ve ESI): 568.5 (M+H)+. EXAMPLE 64 Preparation of Compound 64 in Table 3—N-(3,5-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxybutyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 55, but starting with 1-aminobutan-2-ol (89 mg, 1 mmol) yielded compound 64 in table 3 (80 mg, 55% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.29 (s, 1H), 7.37 (m, 3H), 6.90 (t, 1H), 6.83 (s, 1H), 4.30 (m, 2H), 4.00 (s, 3H), 3.85 (s, 2H), 3.70 (m, 1H), 2.80-3.20 (m, 4H), 2.25 (m, 2H), 1.45 (m, 2H), 0.90 (t, 3H): MS (+ve EST): 556.5 (M+H)+. EXAMPLE 65 Preparation of Compound 65 in Table 3—N-(3,5-difluorophenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 55, but starting with 4-(hydroxymethyl)piperidine (115 mg, 1 mmol) yielded compound 65 in table 3 (54 mg, 35% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.29 (s, 1H), 7.37 (m, 3H), 6.92 (t, 1H), 6.83 (s, 1H), 4.30 (t, 2H), 4.00 (s, 3H), 3.86 (s, 2H), 3.61 (d, 2H), 3.30 (m, 4H), 3.00 (t, 2H), 2.30 (m, 2H), 1.90 (d, 2H), 1.65 (m, 1H), 1.40 (m, 2H): MS (+ve ESI): 582.6 (M+H)+. EXAMPLE 66 Preparation of Compound 66 in Table 3—N-(3,5-difluorophenyl)-2-{3-[(7-{3-[(3-hydroxy-2,2-dimethylpropyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 55, but starting with 3-amino-2,2-dimethylpropan-1-ol (103 mg, 1 mmol) yielded compound 66 in table 3 (53 mg, 36% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.29 (s, 1H), 7.36 (m, 3H), 6.92 (t, 1H), 6.83 (s, 1H), 4.30 (t, 2H), 4.00 (s, 3H), 3.85 (s, 2H), 3.28 (s, 2H), 3.16 (m, 2H), 2.91 (s, 2H), 2.26 (m, 2H), 0.94 (s, 6H): MS (+ve ESI): 570.6 (M+H)+. EXAMPLE 67 Preparation of Compound 67 in Table 3—N-(3,5-difluorophenyl)-2-{3-[(7-{3-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 55, but starting with D-prolinol (101 mg, 1 mmol) yielded compound 67 in table 3 (83 mg, 56% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.30-7.40 (m, 3H), 6.85-6.95 (m, 1H), 6.84 (s, 1H), 4.30 (m, 2H), 4.01 (s, 3H), 3.86 (s, 2H), 3.72-3.82 (m, 1H), 3.50-3.70 (m, 4H), 3.15-3.30 (m, 2H), 2.25-2.40 (m, 2H), 1.95-2.20 (m, 2H), 1.85-1.95 (m, 1H), 1.70-1.85 (m, 1H): MS (+ve ESI): 568.5 (M+H)+. EXAMPLE 68 Preparation of Compound 68 in Table 3—N-(3,5-difluorophenyl)-2-{3-[(7-{3-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 55, but starting with L-prolinol (101 mg, 1 mmol) yielded compound 68 in table 3 (85 mg, 57% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.30-7.40 (m, 3H), 6.85-6.95 (m, 1H), 6.84 (s, 1H), 4.30 (m, 2H), 4.01 (s, 3H), 3.86 (s, 2H), 3.72-3.82 (m, 1H), 3.50-3.70 (m, 4H), 3.15-3.30 (m, 2H), 2.25-2.40 (m, 2H), 1.95-2.20 (m, 2H), 1.85-1.95 (m, 1H), 1.70-1.85 (m, 1H): MS (+ve ESI): 568.5 (M+H)+. EXAMPLE 69 Preparation of Compound 69 in Table 3—N-(3,5-difluorophenyl)-2-(3-{[7-(3-{[(2S)-2-hydroxypropyl]amino}propoxy)-6-methoxyquinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetamide An analogous reaction to that described in example 55, but starting with (S)-(+)-1-aminopropan-2-ol (75 mg, 1 mmol) yielded compound 69 in table 3 (67 mg, 48% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.29 (s, 1H), 7.36 (m, 3H), 6.90 (t, 1H), 6.84 (s, 1H), 4.31 (t, 2H), 4.01 (s, 3H), 3.95 (m, 1H), 3.86 (s, 2H), 3.16 (m, 2H), 3.07 (m, 1H), 2.85 (m, 1H), 2.25 (m, 2H), 1.15 (d, 3H): MS (+ve ESI): 542.5 (M+H)+. EXAMPLE 70 Preparation of Compound 70 in Table 3—N-(3,5-difluorophenyl)-2-{3-[7-(3-{[(2R)-2-hydroxypropyl]amino}propoxy)-6-methoxyquinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetamide An analogous reaction to that described in example 55, but starting with (R)-(−)-1-aminopropan-2-ol (75 mg, 1 mmol) yielded compound 70 in table 3 (52 mg, 37% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.29 (s, 1H), 7.36 (m, 3H), 6.91 (t, 1H), 6.83 (s, 1H), 4.29 (t, 2H), 4.00 (s, 3H), 3.95 (m, 1H), 3.85 (s, 2H), 3.15 (m, 2H), 3.07 (m, 1H), 2.85 (m, 1H), 2.25 (m, 2H), 1.15 (d, 3H): MS (+ve ESI): 542.5 (M+H)+. EXAMPLE 71 Preparation of Compound 71 in Table 3—N-(3,5-difluorophenyl)-2-{3-[(7-{3-[(3S)-3-hydroxypyrrolidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 55, but starting with (S)-(−)-3-hydroxypyrrolidine (87 mg, 1 mmol) yielded compound 71 in table 3 (76 mg, 53% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.29 (s, E1H), 7.34 (m, 3H), 6.91 (t, 1H), 6.83 (s, 1H), 4.45 (m, 1H), 4.30 (m, 2H), 4.00 (s, 3H), 3.86 (s, 2H), 3.00-3.80 (m, 6H), 2.25 (m, 2H), 1.95 (m, 2H): MS (+ve ESI): 554.5 (M+H)+. EXAMPLE 72 Preparation of Compound 72 in Table 3—N-(3,5-difluorophenyl)-2-{3-[(7-{3-[(3R)-3-hydroxypyrrolidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 55, but starting with (R)-(+)-3-hydroxypyrrolidine (87 mg, 1 mmol) yielded compound 72 in table 3 (76 mg, 53% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.29 (s, 1H), 7.35 (m, 3H), 6.90 (t, 1H), 6.84 (s, 1H), 4.45 (m, 1H), 4.30 (m, 2H), 4.01 (s, 3H), 3.86 (s, 2H), 3.00-3.80 (m, 6H), 2.25 (m, 2H), 1.95 (m, 2H): MS (+ve ESI): 554.5 (M+H)+. EXAMPLE 73 Preparation of Compound 73 in Table 3—N-(3,5-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(isobutyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide 2-(3-{[7-(3-chloropropoxy)-6-methoxyquinazolin-4-yl]amino}-1H-pyrazol-5-yl)-N-(3,5-difluorophenyl)acetamide (2 g, 4 mmol) in 1-methyl-2-pyrrolidinone (20 ml) was reacted with potassium iodide (1.33 g, 8 mmol) and 2-(isobutylamino)ethanol (1.88 g, 16 mmol) under argon, at 60° C. for 8 hours. The solvent was evaporated, and the residue purified by chromatography on silica gel, eluting with dichloromethane:methanol (95:5) then dichloromethane:methanolic ammonia (95:5), to yield compound 73 in table 3 (1.05 g, 45% yield): 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.29 (s, 1H), 7.35 (d, 2H), 7.34 (s, 1H), 6.92 (t, 1H), 6.83 (s, 1H), 4.30 (m, 2H), 4.00 (s, 3H), 3.86 (s, 2H), 3.82 (t, 2H), 3.89 (m, 2H), 3.29 (m, 2H), 2.17-2.98 (m, 2H), 2.30 (m, 2H), 2.13 (m, 1H), 1.01 (d, 6H): MS (+ve ESI): 584.3 (M+H)+. EXAMPLE 74 Preparation of Compound 74 in Table 3—N-(3,5-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(propyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 73, but starting with 2-(propylamino)ethanol (1.83 ml, 16 mmol) yielded compound 74 in table 3 (900 mg, 39% yield): 1H-NMR (DMSO d6): 10.63 (s, 1H), 10.17 (s, 1H), 8.46 (s, 1H), 8.00 (s, 1H), 7.36 (d, 2H), 7.14 (s, 1H), 6.94 (t, 1H), 6.85 (s, 1H), 4.35 (br s, 1H), 4.20 (t, 2H), 3.95 (s, 3H), 3.79 (s, 2H), 3.46 (m, 2H), 2.63 (m, 2H), 2.52 (m, 2H), 2.42 (m, 2H), 1.92 (m, 2H), 1.42 (m, 2H), 0.83 (t, 3H): MS (+ve ESI): 570.3 (M+H)+. EXAMPLE 75 Preparation of Compound 75 in Table 3—2-{3-[(7-{3-[allyl(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3,5-difluorophenyl)acetamide An analogous reaction to that described in example 73, but starting with 2-(allylamino)ethanol (101 mg, 1 mmol) in dimethylacetamide (1.4 ml) at 110° C. for 2.5 hours yielded compound 75 in table 3 (52 mg, 33% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.35 (m, 2H), 7.32 (s, 1H), 6.91 (m, 1H), 6.84 (s, 1H), 5.90-6.10 (m, 1H), 5.50-5.75 (m, 2H), 4.30 (m, 2H), 4.00 (s, 3H), 3.86-4.00 (m, 2H), 3.86 (s, 2H), 3.79 (m, 2H), 3.20-3.40 (m, 4H), 2.20-2.40 (m, 2H): MS (+ve ESI): 568.2 (M+H)+. EXAMPLE 76 Preparation of Compound 76 in Table 3—N-(3,5-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(prop-2-yn-1-yl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 73, but starting with 2-(prop-2-yn-1-ylamino)ethanol (99 mg, 1 mmol) and heating at 105° C. for 12 hours yielded compound 76 in table 3 (50 mg, 31% yield): 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.29 (s, 1H), 7.34 (m, 2H), 7.31 (s, 1H), 6.91 (m, 1H), 6.83 (s, 1H), 4.29 (m, 4H), 4.00 (s, 3H), 3.89 (m, 1H), 3.86 (s, 2H), 3.80 (m, 2H), 3.43 (m, 2H), 3.36 (m, 2H), 2.30 (m, 2H): MS (+ve ESI): 566.2 (M+H)+. EXAMPLE 77 Preparation of Compound 77 in Table 3—N-(3,5-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(isopropyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 73, but starting with 2-(isopropylamino)ethanol (130 mg, 1 mmol) and heating at 105° C. for 12 hours and 125° C. for 8 hours, yielded compound 77 in table 3 (40 mg, 25% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.30-7.40 (m, 3H), 6.89 (m, 1H), 6.84 (s, 1H), 4.30 (m, 2H), 4.00 (s, 3H), 3.86 (s, 2H), 3.76 (m, 2H), 3.35 (m, 4H), 3.18 (m, 1H), 2.30 (m, 2H), 1.30 (m, 6H): MS (+ve ESI): 570.3 (M+H)+. EXAMPLE 78 Preparation of Compound 78 in Table 3—N-(3,5-difluorophenyl)-2-{3-[(7-{3-[(2,2-dimethylpropyl)(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 73, but starting with 2-((2,2-dimethylpropyl)amino)ethanol (131 mg, 1 mmol) and heating at 130° C. for 2 hours, yielded compound 78 in table 3 (42 mg, 25% yield): 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.29 (s, 1H), 7.30-7.40 (m, 3H), 6.88 (m, 1H), 6.83 (s, 1H), 4.30 (m, 2H), 3.99 (s, 3H), 3.85 (s, 2H), 3.78-3.85 (m, 2H), 3.40 (m, 2H), 3.30 (m, 2H), 3.22 (m, 1H), 3.12 (m, 1H), 2.30 (m, 2H): MS (+ve ESI): 598.2 (M+H)+. EXAMPLE 79 Preparation of Compound 79 in Table 3—2-{3-[(7-{3-[cyclobutyl(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3,5-difluorophenyl)acetamide An analogous reaction to that described in example 73, but starting with 2-(cyclobutylamino)ethanol (115 mg, 1 mmol) and heating at 80° C. for 6 hours in the presence of potassium iodide (93 mg, 0.56 mmol), yielded compound 79 in table 3 (33 mg, 20% yield): 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.29 (s, 1H), 7.35 (m, 2H), 7.32 (s, 1H), 6.88 (m, 1H), 6.83 (s, 1H), 4.29 (m, 2H), 4.00 (s, 3H), 3.87-3.99 (m, 1H), 3.86 (s, 2H), 3.72 (m, 2H), 3.35 (m, 2H), 3.15 (m, 2H), 2.30 (m, 2H), 2.20 (m, 4H), 1.85 (m, 2H): MS (+ve ESI): 582.3 (M+H)+. EXAMPLE 80 Preparation of Compound 80 in Table 3—2-{3-[(7-{3-[(cyclopropylmethyl)(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3,5-difluorophenyl)acetamide An analogous reaction to that described in example 79, but starting with 2-((cyclopropylmethyl)amino)ethanol (115 mg, 1 mmol) yielded compound 80 in table 3 (33 mg, 20% yield): 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.30 (s, 1H), 7.35 (m, 2H), 7.33 (s, 1H), 6.88 (m, 1H), 6.84 (s, 1H), 4.30 (m, 2H), 4.00 (s, 3H), 3.86 (s, 2H), 3.80 (s, 2H), 3.20-3.45 (m, 4H), 3.15 (m, 2H), 2.30 (m, 2H), 1.12 (m, 1H), 0.68 (m, 2H), 0.42 (m, 2H): MS (+ve ESI): 582.3 (M+H)+. EXAMPLE 81 Preparation of Compound 81 in Table 3—N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 73, but starting with L-prolinol (1.3 ml, 13.17 mmol) and 2-(3-([7-(3-chloropropoxy)-6-methoxyquinazolin-4-yl]amino)-1H-pyrazol-5-yl)-N-(2,3-difluorophenyl)acetamide (1.63 g, 3.24 mmol) yielded compound 81 in table 3 (1.64 g, 89% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.74 (m, 1H), 7.33 (s, 1H), 7.19 (t, 2H), 6.84 (s, 1H), 4.31 (t, 2H), 4.01 (s, 3H), 3.94 (s, 2H), 3.77 (q, 1H), 3.64 (m, 4H), 3.22 (m, 2H), 2.30 (m, 2H), 2.14 (m, 1H), 2.03 (m, 1H), 1.90 (m, 1H), 1.78 (m, 1H): MS (+ve ESI): 568.3 (M+H)+. EXAMPLE 82 Preparation of Compound 82 in Table 3—N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2,2-dimethylpropyl)(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 81, but starting with 2-((2,2-dimethylpropyl)amino)ethanol (131 mg, 1 mmol) in dimethylacetamide at 70° C. for 10 hours yielded compound 82 in table 3 (64 mg, 33% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.74 (m, 1H), 7.35 (s, 1H), 7.19 (m, H), 6.84 (s, 1H), 4.31 (m, 2H), 3.99 (s, 3H), 3.94 (s, 2H), 3.84 (m, 2H), 3.42 (m, 2H), 3.3 (m, 2H), 3.22 (d, 1H), 3.15 (d, 1H), 3.13 (m, 2H), 2.35 (m, 2H), 1.09 (s, 9H) (+ve ESI): 598.3 (M+H)+. EXAMPLE 83 Preparation of Compound 83 in Table 3—N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(propyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 81, but starting with 2-(propylamino)ethanol (700 mg, 68 mmol) and heating at 85° C. for 5 hours, yielded compound 83 in table 3 as an off-white solid (650 mg, 67% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.75 (m, 1H), 7.33 (s, 1H), 7.18-7.22 (m, 2H), 6.84 (s, 1H), 4.30 (m, 2H), 4.00 (s, 3H), 3.94 (s, 2H), 3.78 (m, 2H), 3.30-3.45 (m, 2H), 3.28 (m, 2H), 3.15-3.20 (m, 2H), 2.28 (m, 2H), 1.73 (m, 2H), 0.95 (t, 3H): MS (+ve ESI): 570.3 (M+H)+. EXAMPLE 84 Preparation of Compound 84 in Table 3—N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(isobutyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 81, but starting with 2-(isobutylamino)ethanol (936 mg, 80 mmol) and heating at 90° C. for 3.5 hours, yielded compound 84 in table 3 as an off-white solid (810 mg, 69% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.45 (m, 1H), 7.34 (s, 1H), 7.21 (m, 2H), 6.84 (s, 1H), 4.31 (m, 2H), 4.00 (s, 3H), 3.95 (s, 2H), 3.81 (m, 2H), 3.36 (m, 2H), 3.30 (m, 2H), 3.12 (m, 1H), 3.06 (m, 1H), 2.31 (m, 2H), 2.13 (m, 1H), 1.01 (d, 6H): MS (+ve ESI): 584.3 (M+H)+. EXAMPLE 85 Preparation of Compound 85 in Table 3—2-{3-[(7-{3-[cyclobutyl(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(2,3-difluorophenyl)acetamide An analogous reaction to that described in example 81, but starting with 2-(cyclobutylamino)ethanol (117 mg, 1 mmol) and potassium iodide (103 mg, 0.62 mmol) in dimethylacetamide (2 ml) at 95° C. for 4 hours under argon yielded compound 85 in table 3 (97 mg, 56% yield): 1H-NMR (DMSO d6, TFA): 8.92 (s, 1H), 8.27 (s, 1H), 7.74 (m, 1H), 7.29 (s, 1H), 7.15-7.20 (m, 2H), 6.83 (s, 1H), 4.30 (m, 2H), 3.98 (s, 3H), 3.98 (m, 3H), 3.68-3.80 (m, 2H), 3.20-3.30 (m, 2H), 3.15 (m, 2H), 2.30 (m, 2H), 2.22 (m, 4H), 1.65-1.82 (m, 2H): MS (+ve ESI): 582.2 (M+H)+. EXAMPLE 86 Preparation of Compound 86 in Table 3—2-{3-[(7-{3-[cyclopentyl(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(2,3-difluorophenyl)acetamide An analogous reaction to that described in example 85, but starting with 2-(cyclopentylamino)ethanol (129 mg, 1 mmol) yielded compound 86 in table 3 (86 mg, 48% yield): 1H-NMR (DMSO d6, TFA): 8.93 (s, 1H), 8.28 (s, 1H), 7.73 (m, 1H), 7.30 (s, 1H), 7.14 (m, 2H), 6.83 (s, 1H), 4.29 (m, 2H), 3.98 (s, 3H), 3.93 (s, 2H), 3.78 (m, 3H), 3.37 (m, 2H), 3.26 (m, 2H), 2.30 (m, 2H), 2.09 (m, 2H), 1.74 (m, 4H), 1.72 (m, 2H): MS (+ve ESI): 596.2 (M+H)+. EXAMPLE 87 Preparation of Compound 87 in Table 3—N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 81, but starting with (2R)-pyrrolidin-2-ylmethanol (101 mg, 1 mmol) yielded compound 87 in table 3 (134 mg, 79% yield): 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.29 (s, 1H), 7.75 (m, 1H), 7.32 (s, 1H), 7.16 (m, 2H), 6.84 (s, 1H), 4.30 (m, 2H), 4.00 (s, 3H), 3.94 (s, 2H), 3.70-3.85 (m, 1H), 3.52-3.70 (m, 4H), 3.15-3.30 (m, 2H), 2.25 (m, 2H), 1.75-2.20 (m, 4H): MS (+ve ESI): 568.2 (M+H)+. EXAMPLE 88 Preparation of Compound 88 in Table 3—N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(prop-2-yn-1-yl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 81, but starting with 2-(prop-2-yn-1-ylamino)ethanol (99 mg, 1 mmol) yielded compound 88 in table 3 (128 mg, 75% yield): 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.29 (s, 1H), 7.74 (m, 1H), 7.31 (s, 1H), 7.18 (m, 2H), 6.83 (s, 1H), 4.30 (m, 4H), 4.00 (s, 3H), 3.94 (s, 2H), 3.87 (m, 1H), 3.80 (m, 2H), 3.44 (m, 2H), 3.35 (m, 2H), 2.30 (m, 2H): MS (+ve ESI): 566.2 (M+H)+. EXAMPLE 89 Preparation of Compound 89 in Table 3—2-{3-[(7-{3-[(cyclopropylmethyl)(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(2,3-difluorophenyl)acetamide An analogous reaction to that described in example 81, but starting with 2-(cyclopropylmethyl)amino)ethanol (115 mg, 1 mmol) yielded compound 89 in table 3 (6 mg, 3% yield): 1H-NMR (DMSO d6): 10.23 (s, 1H), 10.16 (s, 1H), 8.44 (s, 1H), 7.98 (s, 1H), 7.72 (m, 1H), 7.18 (m, 2H), 7.14 (s, 1H), 6.84 (s, 1H), 4.32 (s, 1H), 4.18 (t, 2H), 3.93 (s, 3H), 3.85 (s, 2H), 3.45 (m, 2H), 2.69 (t, 2H), 2.58 (t, 2H), 2.35 (d, 2H), 1.90 (m, 2H), 0.83 (m, 1H), 0.41 (m, 2H), 0.08 (m, 2H): MS (+ve ESI): 582.2 (M+H)+. EXAMPLE 90 Preparation of Compound 90 in Table 3—2-{3-[(7-{3-[(cyclobutylmethyl)(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(2,3-difluorophenyl)acetamide An analogous reaction to that described in example 81, but starting with 2-((cyclobutylmethyl)amino)ethanol (129 mg, 1 mmol) yielded compound 90 in table 3 (134 mg, 75% yield): 1H-NMR (DMSO d6): 8.49 (s, 1H), 8.00 (s, 1H), 7.70-7.78 (m, 1H), 7.15-7.30 (m, 3H), 6.75 (m, 1H), 4.25 (m, 2H), 3.96 (s, 3H), 3.86 (s, 2H), 3.60-3.80 (m, 2H), 3.00-3.40 (m, 4H), 2.50-2.80 (m, 4H), 1.61-2.40 (m, 7H): MS (+ve ESI): 596.2 (M+H)+. EXAMPLE 91 Preparation of Compound 91 in Table 3—N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2,2-dimethoxyethyl)(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 81, but starting with 2-((2,2-dimethoxyethyl)amino)ethanol (149 mg, 1 mmol) yielded compound 91 in table 3 (94 mg, 51% yield): 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.29 (s, 1H), 7.70-7.80 (m, 1H), 7.32 (s, 1H), 7.17 (m, 2H), 6.84 (s, 1H), 4.85 (t, 1H), 4.30 (m, 2H), 4.00 (s, 3H), 3.94 (s, 2H), 3.81 (m, 2H), 3.30-3.55 (m, 10H), 2.30 (m, 2H): MS (+ve ESI): 616.2 (M+H)+. EXAMPLE 92 Preparation of Compound 92 in Table 3—N-(2,3-difluorophenyl)-2-{3-[(7-{3-[4-(2-hydroxyethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 81, but starting with 4-(2-hydroxyethyl)piperidine (129 mg, 1 mmol) yielded compound 92 in table 3 (113 mg, 63.% yield): 1H-NMR (DMSO d6, TFA): 8.94 (s, 1H), 8.28 (s, 1H), 7.73 (m, 1H), 7.31 (s, 1H), 7.10-7.20 (m, 2H), 6.83 (s, 1H), 4.30 (m, 2H), 3.99 (s, 3H), 3.93 (s, 2H), 3.56 (d, 2H), 3.47 (m, 2H), 3.26 (m, 2H), 2.96 (m, 2H), 2.30 (m, 2H), 1.75-1.95 (m, 2H), 1.60-1.75 (m, 1H), 1.30-1.45 (m, 4H): MS (+ve ESI): 596.2 (M+H)+. EXAMPLE 93 Preparation of Compound 93 in Table 3—N-(2,3-difluorophenyl)-2-[3-({7-[3-(4-hydroxypiperidin-1-yl)propoxy]-6-methoxyquinazolin-4-yl}amino)-1H-pyrazol-5-yl]acetamide An analogous reaction to that described in example 81, but starting with piperidin-4-ol (101 mg, 1 mmol) yielded compound 93 in table 3 (146 mg, 86% yield): 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.29 (s, 1H), 7.73 (m, 1H), 7.32 (s, 1H), 7.19 (m, 2H), 6.84 (s, 1H), 4.30 (m, 2H), 4.00 (s, 3H), 3.94 (s, 2H), 3.70-3.80 (m, 1H), 3.55-3.70 (m, 2H), 3.35-3.45 (m, 1H), 3.25-3.35 (m, 2H), 2.95-3.10 (m, 1H), 2.30 (m, 2H), 1.95-2.05 (m, 1H), 1.75-1.95 (m, 2H), 1.55-1.70 (m, 1H): MS (+ve ESI): 568.2 (M+H)+. EXAMPLE 94 Preparation of Compound 94 in Table 3—N-(2,3-difluorophenyl)-2-{3-[(7-{3-[4-(2-hydroxyethyl)piperazin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 81, but starting with 2-piperazin-1-ylethanol (130 mg, 1 mmol) yielded compound 94 in table 3 (52 mg, 29% yield): 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.30 (s, 1H), 7.72 (m, 2H), 7.32 (s, 1H), 7.17 (m, 2H), 6.84 (s, 1H), 4.33 (m, 2H), 4.00 (s, 3H), 3.94 (s, 2H), 3.78 (m, 2H), 3.45-3.78 (m, 8H), 3.44 (m, 2H), 3.37 (m, 2H), 2.30 (m, 2H): MS (+ve ESI): 597.2 (M+H)+. EXAMPLE 95 Preparation of Compound 95 in Table 3—N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(2-methoxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 81, but starting with 2-((2-methoxyethyl)amino)ethanol (119 mg, 1 mmol) yielded compound 95 in table 3 (124 mg, 71% yield): 1H-NMR (DMSO d6, TFA): 8.97 (s, 1H), 8.31 (s, 1H), 7.76 (m, 1H), 7.33 (s, 1H), 7.19 (m, 2H), 6.85 (s, 1H), 4.31 (t, 2H), 4.02 (s, 3H), 3.95 (s, 2H), 3.80 (t, 2H), 3.73 (t, 2H), 3.45 (m, 4H), 3.36 (m, 5H), 2.31 (m, 2H): MS (+ve ESI): 586.2 (M+H)+. EXAMPLE 96 Preparation of Compound 96 in Table 3—2-{3-[(7-{3-[allyl(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(2,3-difluorophenyl)acetamide An analogous reaction to that described in example 81, but starting with 2-(allylamino)ethanol (101 mg, 1 mmol) yielded compound 96 in table 3 (99 mg, 58% yield): 1H-NMR (DMSO d6, TFA): 8.97 (s, 1H), 8.32 (s, 1H), 7.77 (m, 1H), 7.33 (s, 1H), 7.18 (m, 2H), 6.87 (s, 1H), 6.01 (m, 1H), 5.60 (m, 2H), 4.31 (t, 2H), 4.02 (s, 3H), 3.94 (m, 4H), 3.82 (t, 2H), 3.35 (m, 4H), 2.34 (m, 2H): MS (+ve ESI): 568.2 (M+H)+. EXAMPLE 97 Preparation of Compound 97 in Table 3—N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(1,3-dioxolan-2-ylmethyl)(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 81, but starting with 2-((1,3-dioxolan-2-ylmethyl)amino)ethanol (147 mg, 1 mmol) yielded compound 97 in table 3 (126 mg, 68% yield): 1H-NMR (DMSO d6, TFA): 8.94 (s, 1H), 8.29 (s, 1H), 7.75 (m, 1H), 7.31 (s, 1H), 7.16 (m, 2H), 6.83 (s, 1H), 5.30 (m, 1H), 4.30 (m, 2H), 4.01 (m, 5H), 3.99 (s, 2H), 3.93 (m, 2H), 3.89 (m, 2H), 3.45 (m, 6H), 2.30 (m, 2H): MS (+ve ESI): 614.2 (M+H)+. EXAMPLE 98 Preparation of Compound 98 in Table 3—N-(2,3-difluorophenyl)-2-{3-[(7-{3-[ethyl(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 81, but starting with 2-(ethylamino)ethanol (89 mg, 1 mmol) yielded compound 98 in table 3 (94 mg, 56% yield): 1H-NMR (DMSO d6, TFA): 8.94 (s, 1H), 8.29 (s, 1H), 7.75 (m, 1H), 7.31 (s, 1H), 7.15 (m, 2H), 6.83 (s, 1H), 4.31 (m, 2H), 3.99 (s, 3H), 3.93 (s, 2H), 3.76 (m, 2H), 3.30 (m, 6H), 2.26 (m, 2H), 1.25 (t, 3H): MS (+ve ESI): 556.2 (M+H)+. EXAMPLE 99 Preparation of Compound 99 in Table 3—N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(isopropyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 81, but starting with 2-(isopropylamino)ethanol (103 mg, 1 mmol) yielded compound 99 in table 3 (84 mg, 49% yield): 1H-NMR (DMSO d6, TFA): 8.97 (s, 1H), 8.33 (s, 1H), 7.79 (m, 1H), 7.35 (s, 1H), 7.18 (m, 2H), 6.88 (s, 1H), 4.34 (t, 2H), 4.03 (s, 3H), 3.98 (s, 2H), 3.81 (m, 3H), 3.40 (m, 3H), 3.20 (m, 1H), 2.35 (m, 2H), 1.33 (m, 6H): MS (+ve ESI): 570.2 (M+H)+. EXAMPLE 100 Preparation of Compound 100 in Table 3—N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxy-1,1-dimethylethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 81, but starting with 2-amino-2-methylpropan-1-ol (101 mg, 1 mmol) yielded compound 100 in table 3 (165 mg, 99% yield): 1H-NMR (DMSO d6): 8.48 (s, 1H), 7.99 (s, 1H), 7.72 (m, 1H), 7.22 (m, 4H), 4.25 (t, 2H), 3.95 (s, 3H), 3.85 (s, 2H), 3.35 (m, 2H), 2.95 (m, 2H), 2.10 (m, 2H), 1.16 (s, 6H): MS (+ve ESI): 556.2 (M+H)+. EXAMPLE 101 Preparation of Compound 101 in Table 3—N-(2,3-difluorophenyl)-2-{3-[(7-{[(2R)-1-(2-hydroxyethyl)pyrrolidin-2-yl]methoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 54, but starting with 2-{3-[(7-{[(2R)-1-(2-tert-butoxyethyl)pyrrolidin-2-yl]methoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(2,3-difluorophenyl)acetamide (67 mg, 0.11 mmol) yielded compound 101 in table 3 (36 mg, 59% yield): 1H-NMR (DMSO d6, TFA): 8.98 (s, 1H), 8.35 (s, 1H), 7.76 (m, 1H), 7.36 (s, 1H), 7.19 (m, 2H), 6.87 (s, 1H), 4.62 (m, 1H), 4.50 (m, 1H), 4.20 (m, 1H), 4.04 (s, 3H), 3.96 (s, 2H), 3.81 (m, 2H), 3.73 (m, 2H), 3.33 (m, 2H), 2.34 (m, 1H), 2.11 (m, 2H), 1.91 (m, 1H): MS (+ve ESI): 554.1 (M+H)+. 2-{3-[(7-{[(2R)-1-(2-tert-butoxyethyl)pyrrolidin-2-yl]methoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(2,3-difluorophenyl)acetamide use as starting material was obtained as follows: An analogous reaction to that described in example 5, but starting with {3-[(7-{[(2R)-1-(2-tert-butoxyethyl)pyrrolidin-2-yl]methoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetic acid (240 mg, 0.48 mmol) yielded 2-{3-[(7-{[(2R)-1-(2-tert-butoxyethyl)pyrrolidin-2-yl]methoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}N-(2,3-difluorophenyl)acetamide (72 mg, 25% yield): 1H-NMR (DMSO d6, TFA): 8.98 (s, 1H), 8.34 (s, 1H), 7.75 (m, 1H), 7.35 (s, 1H), 7.19 (m, 2H), 6.85 (s, 1H), 4.62 (m, 1H), 4.50 (m, 1H), 4.20 (m, 1H), 4.03 (s, 3H), 3.95 (s, 2H), 3.72 (m, 4H), 3.40 (m, 2H), 2.34 (m, 1H), 2.11 (m, 2H), 1.91 (m, 1H), 1.20 (s, 9H): MS (+ve ESI): 610.2 (M+H)+. EXAMPLE 102 Preparation of Compound 102 in Table 3—N-(3-chlorophenyl)-2-{3-[(7-{3-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 7, but starting with 2-(5-((7-(3-chloropropoxy)-6-methoxy-quinazolin-4-yl)amino)-1H-pyrazol-3-yl)-N-(3-chlorophenyl)acetamide (100 mg, 0.2 mmol) and L-prolinol (71 mg, 0.7 mmol) yielded compound 102 in table 3 (73 mg, 64% yield): 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.29 (s, 1H), 7.86 (m, 1H), 7.40-7.50 (m, 1H), 7.30-7.40 (m, 2H), 7.10-7.15 (m, 1H), 6.83 (s, 1H), 4.30 (m, 2H), 4.00 (s, 3H), 3.84 (s, 2H), 3.70-3.80 (m, 1H), 3.47-3.70 (m, 4H), 3.12-3.35 (m, 2H), 2.20-2.40 (m, 2H), 1.97-2.20 (m, 2H), 1.85-1.97 (m, 1H), 1.70-1.85 (m, 1H): MS (+ve ESI): 566.5 (M+H)+. EXAMPLE 103 Preparation of Compound 103 in Table 3—N-(3-chlorophenyl)-2-{3-[(7-{3-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 102, but starting with D-prolinol (71 mg, 0.7 mmol) yielded compound 103 in table 3 (75 mg, 66% yield): 1H-NMR (DMSO d6, TFA): 8.94 (s, 1H), 8.29 (s, 1H), 7.86 (s, 1H), 7.48 (m, 1H), 7.34 (m, 2H), 7.12 (m, 1H), 6.82 (s, 1H), 4.30 (m, 2H), 3.99 (s, 3H), 3.83 (s, 2H), 3.76 (m, 1H), 3.60 (m, 4H), 3.20 (m, 2H), 2.30 (m, 2H), 1.95 (m, 4H): MS (+ve ESI): 566.5 (M+H)+. EXAMPLE 104 Preparation of Compound 104 in Table 3—N-(3-chlorophenyl)-2-[3-({7-[3-(3-hydroxypiperidin-1-yl)propoxy]-6-methoxyquinazolin-4-yl}amino)-1H-pyrazol-5-yl]acetamide An analogous reaction to that described in example 102, but starting with piperidin-3-ol (71 mg, 0.7 mmol) yielded compound 104 in table 3 (82 mg, 72% yield): 1H-NMR (DMSO d6, TFA): 8.94 (s, 1H), 8.29 (s, 1H), 7.86 (s, 1H), 7.47 (m, 1H), 7.34 (m, 2H), 7.12 (m, 1H), 6.82 (s, 1H), 4.28 (m, 2H), 4.09 (m, 0.5H), 3.99 (s, 3H), 3.83 (s, 2H), 3.70 (m, 0.5H), 2.60-3.55 (m, 6H), 1.15-3.40 (m, 6H): MS (+ve ESI): 566.5 (M+H)+. EXAMPLE 105 Preparation of Compound 105 in Table 3—N-(3-chlorophenyl)-2-{3-[(7-{3-[ethyl(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 102, but starting with 2-(ethyl-amino)ethanol (78 mg, 0.87 mmol) yielded compound 105 in table 3 (72 mg, 52% yield): 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.29 (s, 1H), 7.86 (m, 1H), 7.45-7.52 (m, 1H), 7.25-7.30 (m, 2H), 7.08-7.15 (m, 1H), 6.83 (s, 1H), 4.29 (m, 2H), 4.00 (s, 3H), 3.84 (s, 2H), 3.70-3.82 (m, 2H), 3.20-3.45 (m, 6H), 2.20-2.35 (m, 2H), 1.26 (t, 3H): MS (+ve ESI): 554.5 (M+H)+. EXAMPLE 106 Preparation of Compound 106 in Table 4—2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-methoxyphenyl)acetamide {3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetic acid (118 mg, 0.25 mmol) in dimethylformamide (1.2 ml) was reacted with 3-methoxyaniline (46 mg, 0.37 mmol) in the presence of 1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride (81 mg, 0.42 mmol), 2-hydroxypyridin-1-oxide (42 mg, 0.37 mmol) at 55° C. for 2 hours. The solvent was evaporated, and the residue purified by preparative LCMS to yield compound 106 in table 4 (50 mg, 35% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.35 (m, 2H), 7.23 (t, 1H), 7.16 (d, 1H), 6.83 (s, 1H), 6.66 (m, 1H), 4.30 (t, 2H), 4.01 (s, 3H), 3.82 (s, 2H), 3.74 (s, 3H), 3.60 (d, 2H), 3.30 (m, 4H), 2.98 (t, 2H), 2.28 (m, 2H), 1.87 (d, 2H), 1.65 (m, 1H), 1.44 (m, 2H): MS (+ve ESI): 576.6 (M+H)+. (3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl)acetic acid used as starting material was obtained as follows: (3-([7-(3-chloropropoxy)-6-methoxyquinazolin-4-yl]amino)-1H-pyrazol-5-yl)acetic acid (7.83 g, 20 mmol) in dimethylacetamide (30 ml) was reacted with 4-(hydroxymethyl)piperidine (8.05 g, 70 mmol) at 100° C. for 2 hours. The solvent was evaporated, and the residue triturated with a mixture of dichloromethane:ethyl acetate (1:1). The paste was recovered, and dissolved in a mixture of dichloromethane:methanol. Ethanolic HCl (7.0 N) (10 ml, 70 mmol) was added to the mixture and the solvents were evaporated. Methanol (200 ml) was added to the solid and the mixture was stirred for 0.5 hour. The reaction mixture was reduced in volume and dichloromethane added. The resultant solid was recovered by filtration and dried to yield {3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetic acid (6.5 g, 60% yield) as a yellow solid: 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.31 (s, 1H), 7.37 (s, 1H), 6.80 (s, 1H), 4.31 (m, 2H), 4.00 (s, 3H), 3.75 (s, 2H), 3.59 (d, 2H), 3.24-3.30 (m, 4H), 2.97 (t, 2H), 2.35 (m, 2H), 1.86-1.91 (m, 2H), 1.68 (m, 1H), 1.47 (m, 2H). EXAMPLE 107 Preparation of Compound 107 in Table 4—2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl)-N-phenyl}acetamide An analogous reaction to that described in example 106, but starting with aniline (35 mg, 0.37 mmol) yielded compound 107 in table 4 (106 mg, 75% yield): 1H-NMR (DMSO d6, TFA): 8.94 (s, 1H), 8.29 (s, 1H), 7.63 (d, 2H), 7.31 (t, 3H), 7.05 (t, 1H), 6.83 (s, 1H), 4.27 (t, 2H), 3.99 (s, 3H), 3.82 (s, 2H), 3.60 (d, 2H), 3.30 (m, 4H), 2.97 (t, 2H), 2.27 (m, 2H), 1.89 (d, 2H), 1.65 (m, 1H), 1.44 (m, 2H): MS (+ve ESI): 546.5 (M+H)+. EXAMPLE 108 Preparation of Compound 108 in Table 4—N-(4-fluorophenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 106, but starting with 4-fluoroaniline (42 mg, 0.37 mmol) yielded compound 108 in table 4 (127 mg, 88% yield): 1H-NMR (DMSO d6, TFA): 8.94 (s, 1H), 8.29 (s, 1H), 7.65 (m, 2H), 7.31 (s, 1H), 7.14 (t, 2H), 6.82 (s, 1H), 4.27 (t, 2H), 3.99 (s, 3H), 3.82 (s, 2H), 3.60 (d, 2H), 3.30 (m, 4H), 2.97 (t, 2H), 2.27 (m, 2H), 1.89 (d, 2H), 1.65 (m, 1H), 1.44 (m, 2H): MS (+ve ESI): 564.5 (M+H)+. EXAMPLE 109 Preparation of Compound 109 in Table 4—N-(3,5-dichlorophenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 106, but starting with 3,5-dichloroaniline (62 mg, 0.37 mmol) yielded compound 109 in table 4 (46 mg, 28% yield): 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.30 (s, 1H), 7.70 (m, 2H), 7.33 (s, 1H), 7.27 (s, 1H), 6.84 (s, 1H), 4.27 (t, 2H), 3.99 (s, 3H), 3.82 (s, 2H), 3.60 (d, 2H), 3.30 (m, 4H), 2.97 (t, 2H), 2.27 (m, 2H), 1.89 (d, 2H), 1.65 (m, 1H), 1.44 (m, 2H): MS (+ve ESI): 614.4 (M+H)+. EXAMPLE 110 Preparation of Compound 110 in Table 4—N-(5-chloro-2-methoxyphenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 106, but starting with 5-chloro-2-methoxyaniline (60 mg, 0.37 mmol) yielded compound 110 in table 4 (65 mg, 41% yield): 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.29 (s, 1H), 8.15 (s, 1H), 7.32 (s, 1H), 7.08 (m, 2H), 6.81 (s, 1H), 4.27 (t, 2H), 3.99 (s, 3H), 3.82 (s, 2H), 3.60 (d, 2H), 3.30 (m, 4H), 2.97 (t, 2H), 2.27 (m, 2H), 1.69 (d, 2H), 1.65 (m, 1H), 1.44 (m, 2H): MS (+ve ESI): 610.5 (M+H)+. EXAMPLE 111 Preparation of Compound 111 in Table 4—2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-[3-(trifluoromethyl)phenyl]acetamide An analogous reaction to that described in example 106, but starting with 3-trifluoro-methylaniline (61 mg, 0.37 mmol) yielded compound 111 in table 4 (75 mg, 47% yield): 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.29 (s, 1H), 8.14 (s, 1H), 7.80 (d, 1H), 7.52 (t, 1H), 7.40 (d, 1H), 7.31 (s, 1H), 6.85 (s, 1H), 4.29 (t, 2H), 4.00 (s, 3H), 3.87 (s, 2H), 3.60 (d, 2H), 3.30 (m, 4H), 2.97 (t, 2H), 2.27 (m, 2H), 1.89 (d, 2H), 1.65 (m, 1H), 1.44 (m, 2H): MS (+ve ESI): 614.5 (M+H)+. EXAMPLE 112 Preparation or Compound 112 in Table 4—2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-hydroxyphenyl)acetamide An analogous reaction to that described in example 106, but starting with 3-hydroxyaniline (41 mg, 0.37 mmol) yielded compound 112 in table 4 (118 mg, 82% yield): 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.29 (s, 1H), 7.31 (s, 1H), 7.21 (s, 1H), 7.07 (t, 1H), 7.01 (d, 1H), 6.81 (s, 1H), 6.45 (d, 1H), 4.28 (t, 2H), 3.99 (s, 3H), 3.79 (s, 2H), 3.58 (d, 2H), 3.30 (m, 4H), 2.97 (t, 2H), 2.27 (m, 2H), 1.89 (d, 2H), 1.65 (m, 1H), 1.44 (m, 2H): MS (+ve ESI): 562.5 (M+H)+. EXAMPLE 113 Preparation of Compound 113 in Table 4—2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-nitrophenyl)acetamide An analogous reaction to that described in example 106, but starting with 3-nitroaniline (52 mg, 0.37 mmol) yielded compound 113 in table 4 (62 mg, 40% yield): 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.70 (s, 1H), 8.30 (s, 1H), 7.94 (d, 2H), 7.62 (t, 1H), 7.32 (s, 1H), 6.86 (s, 1H), 4.29 (t, 2H), 4.00 (s, 3H), 3.79 (s, 2H), 3.58 (d, 2H), 3.30 (d, 2H), 2.97 (t, 2H), 2.27 (m, 2H), 1.89 (d, 2H), 1.65 (m, 1H), 1.44 (m, 2H): MS (+ve ESI): 591.5 (M+H)+. EXAMPLE 114 Preparation of Compound 114 in Table 4—2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-1H-indazol-5-ylacetamide An analogous reaction to that described in example 106, but starting with 1H-indazol-5-amine (51 mg, 0.37 mmol) yielded compound 114 in table 4 (95 mg, 63% yield): 1H-NMR (DMSO d6, TFA): 8.94 (s, 1H), 8.29 (s, 1H), 8.18 (s, 1H), 8.03 (s, 1H), 7.50 (m, 2H), 7.35 (s, 1H), 6.84 (s, 1H), 4.28 (t, 2H), 3.99 (s, 3H), 3.83 (s, 2H), 3.60 (d, 2H), 3.30 (m, 4H), 2.97 (t, 2H), 2.27 (m, 2H), 1.89 (d, 2H), 1.65 (m, 1H), 1.44 (m, 2H): MS (+ve ESI): 586.5 (M+H)+. EXAMPLE 115 Preparation of Compound 115 in Table 4—N-(4-bromo-2-fluorophenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 106, but starting with 4-bromo-2-fluoroaniline (72 mg, 0.37 mmol) yielded compound 115 in table 4 (28 mg, 16% yield): 1H-NMR (DMSO d6, TFA): 8.94 (s, 1H), 8.28 (s, 1H), 7.95 (t, 1H), 7.53 (m, 1H), 7.35 (d, 1H), 7.31 (s, 1H), 6.82 (s, 1H), 4.28 (t, 2H), 3.99 (s, 3H), 3.92 (s, 2H), 3.60 (d, 2H), 3.30 (m, 4H), 2.97 (t, 2H), 2.27 (m, 2H), 1.89 (d, 2H), 1.65 (m, 1H), 1.44 (m, 2H): MS (+ve ESI): 644.4 (M+H)+. EXAMPLE 116 Preparation of compound 116 in table 4—N-(3-chlorophenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 106, but starting with 3-chloroaniline (48 mg, 0.37 mmol) yielded compound 116 in table 4 (96 mg, 64% yield): 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.30 (s, 1H), 7.86 (s, 1H), 7.48 (d, 1H), 7.34 (m, 2H), 7.13 (d, 1H), 6.84 (s, 1H), 4.28 (t, 2H), 4.00 (s, 3H), 3.84 (s, 2H), 3.60 (d, 2H), 3.30 (m, 4H), 2.97 (t, 2H), 2.27 (in, 2H), 1.89 (d, 2H), 1.65 (m, 1H), 1.44 (m, 2H): MS (+ve ESI): 580.5 (M+H)+. EXAMPLE 117 Preparation of Compound 117 in Table 4—N-(2-fluorophenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 106, but starting with 2-fluoroaniline (42 mg, 0.37 mmol) yielded compound 117 in table 4 (74 mg, 50% yield): 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.29 (s, 1H), 7.94 (m, 1H), 7.33 (s, 1H), 7.26 (m, 1H), 7.16 (m, 2H), 6.83 (s, 1H), 4.28 (t, 2H), 4.00 (s, 3H), 3.92 (s, 2H), 3.60 (d, 2H), 3.30 (m, 4H), 2.97 (t, 2H), 2.27 (m, 2H), 1.89 (d, 2H), 1.65 (m, 1H), 1.44 (m, 2H): MS (+ve ESI): 564.5 (M+H)+. EXAMPLE 118 Preparation of compound 118 in table 4—N-(3,5-dimethoxyphenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin 4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 106, but starting with 3,5-dimethoxyaniline (58 mg, 0.37 mmol) yielded compound 118 in table 4 (89 mg, 57% yield): 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.29 (s, 1H), 7.31 (s, 1H), 6.89 (m, 2H), 6.82 (s, 1H), 6.24 (m, 1H), 4.29 (t, 2H), 4.00 (s, 3H), 3.80 (s, 2H), 3.71 (s, 6H), 3.60 (m, 2H), 3.30 (m, 4H), 3.00 (t, 2H), 2.30 (m, 2H), 1.90 (m, 2H), 1.65 (m, 1H), 1.40 (m, 2H): MS (+ve ESI): 606.5 (M+H)+. EXAMPLE 119 Preparation of Compound 119 in Table 4—2-{3-[(7-{3-[4-(hydroxymethyl)Piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(5-methylpyridin-2-yl)acetamide An analogous reaction to that described in example 106, but starting with 2-amino-5-picoline (41 mg, 0.37 mmol) yielded compound 119 in table 4 (89 mg, 62% yield): 1H-NMR (DMSO d6, TFA): 8.94 (s, 1H), 8.29 (s, 1H), 8.26 (s, 1H), 8.05 (m, 1H), 7.75 (m, 1H), 7.35 (s, 1H), 6.87 (s, 1H), 4.29 (t, 2H), 4.00 (m, 5H), 3.60 (d, 2H), 3.30 (m, 4H), 3.00 (t, 2H), 2.34 (s, 3H), 2.30 (m, 2H), 1.90 (m, 2H), 1.65 (m, 1H), 1.40 (m, 2H): MS (+ve ESI): 561.6 (M+H)+. EXAMPLE 120 Preparation of Compound 120 in Table 4—N-(2,3-difluorophenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 81, but starting with 4-(hydroxymethyl)piperidine (115 mg, 1 mmol) yielded compound 120 in table 4 (138 mg, 79% yield): 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.29 (s, 1H), 7.75 (m, 1H), 7.32 (s, 1H), 7.17 (m, 2H), 6.83 (s, 1H), 4.29 (m, 2H), 4.00 (s, 3H), 3.93 (s, 2H), 3.60 (d, 2H), 3.30 (m, 4H), 3.00 (t, 2H), 2.30 (m, 2H), 1.90 (m, 2H), 1.70 (m, 1H), 1.40 (m, 2H): MS (+ve ESI): 582.2 (M+H)+. EXAMPLE 121 Preparation of Compound 121 in Table 4—N-(3-chloro-2-fluorophenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 106, but starting with 3-chloro-2-fluoroaniline (55 mg, 0.37 mmol) yielded compound 121 in table 4 (16 mg, 9% yield): 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.29 (s, 1H), 7.89 (m, 1H), 7.32 (m, 2H), 7.21 (m, 1H), 6.83 (s, 1H), 4.29 (m, 2H), 4.00 (s, 3H), 3.93 (s, 2H), 3.59 (d, 2H), 3.30 (m, 4H), 2.97 (m, 2H), 2.30 (m, 2H), 1.86 (m, 2H), 1.68 (m, 1H), 1.40 (m, 2H): MS (+ve ESI): 598.5 (M+H)+. EXAMPLE 122 Preparation of Compound 122 in Table 4—N-(2,5-difluorophenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 106, but starting with 2,5-difluoroaniline (49 mg, 0.37 mmol) yielded compound 122 in table 4 (15 mg, 8% yield): 1H-NMR (DMSO ds, TFA): 8.94 (s, 1H), 8.29 (s, 1H), 7.95 (m, 1H), 7.25-7.40 (m, 1H), 7.32 (s, 1H), 6.95 (m, 1H), 4.31 (m, 2H), 4.00 (s, 3H), 3.93 (s, 2H), 3.59 (d, 2H), 3.30 (m, 4H), 2.97 (t, 2H), 2.30 (m, 2H), 1.86 (m, 2H), 1.65 (m, 1H), 1.43 (m, 2H): MS (+ve ESI): 582.5 (M+H)+. EXAMPLE 123 Preparation of Compound 123 in Table 4—N-[2-fluoro-5-(trifluoromethyl)phenyl]-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 106, but starting with 2-fluoro-5-trifluoromethylaniline (68 mg, 0.37 mmol) yielded compound 123 in table 4 (6 mg, 1% yield): 1H-NMR (DMSO d6, TFA): 8.94 (s, 1H), 8.48 (d, 1H), 8.30 (s, 1H), 7.52 (s, 1H), 7.50 (m, 1H), 7.31 (s, 1H), 6.84 (s, 1H), 4.30 (m, 2H), 3.99 (s, 3H), 3.98 (s, 2H), 3.60 (m, 2H), 3.20-3.35 (m, 4H), 2.98 (m, 2H), 2.30 (m, 2H), 1.88 (m, 2H), 1.67 (m, 1H), 1.42 (m, 2H): MS (+ve ESI): 632.5 (M+H)+. EXAMPLE 124 Preparation of Compound 124 in Table 4—N-(3,4-difluorophenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 106, but starting with 3,4-difluoroaniline (49 mg, 0.37 mmol) yielded compound 124 in table 4 (85 mg, 56% yield): 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.30 (s, 1H), 7.83 (m, 1H), 7.35 (m, 2H), 7.33 (s, 1H), 6.84 (s, 1H), 4.30 (m, 2H), 4.00 (s, 3H), 3.84 (s, 2H), 3.60 (d, 2H), 3.30 (m, 4H), 2.98 (t, 2H), 2.31 (m, 2H), 1.87 (m, 2H), 1.68 (m, 1H), 1.44 (m, 2H): MS (+ve ESI): 582.5 (M+H)+. EXAMPLE 125 Preparation of Compound 125 in Table 4—N-(2,4-difluorophenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 106, but starting with 2,4-difluoroaniline (49 mg, 0.37 mmol) yielded compound 125 in table 4 (62 mg, 41% yield): 1H-NMR (DMSO d6, TFA): 8.96 (s, 1H), 8.30 (s, 1H), 7.88 (m, 1H), 7.33 (s, 1H), 7.29 (m, 1H), 7.06 (m, 1H), 6.84 (s, 1H), 4.30 (m, 2H), 4.00 (s, 3H), 3.90 (s, 2H), 3.61 (d, 2H), 3.31 (m, 2H), 3.28 (m, 2H), 3.00 (t, 2H), 2.31 (m, 2H), 1.87 (m, 2H), 1.65 (m, 1H), 1.42 (m, 2H): MS (+ve ESI): 582.5 (M+H)+. EXAMPLE 126 Preparation of Compound 126 in Table 4—N-(3-chloro-4-fluorophenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 106, but starting with 3-chloro-4-fluoroaniline (55 mg, 0.37 mmol) yielded compound 126 in table 4 (84 mg, 54% yield): 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.30 (s, 1H), 7.97 (m, 1H), 7.49 (m, 1H), 7.35 (t, 1H), 7.32 (s, 1H), 6.84 (s, 1H), 4.30 (m, 2H), 4.00 (s, 3H), 3.84 (s, 2H), 3.61 (d, 2H), 3.30 (m, 2H), 3.27 (m, 2H), 2.98 (t, 2H), 2.30 (m, 2H), 1.87 (m, 2H), 1.68 (m, 1H), 1.45 (m, 2H): MS (+ve ESI): 598.5 (M+H)+. EXAMPLE 127 Preparation of Compound 127 in Table 4—N-[2-(difluoromethoxy)phenyl]-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 106, but starting with 2-difluoro-methoxyaniline (60 mg, 0.37 mmol) yielded compound 127 in table 4 (49 mg, 30% yield): 1H-NMR (DMSO d6, TFA): 8.93 (s, 1H), 8.29 (s, 1H), 7.95 (m, 1H), 7.31 (s, 1H), 7.10-7.30 (m, 3H), 6.84 (s, 1H), 4.3 (m, 2H), 3.99 (s, 3H), 3.92 (s, 2H), 3.59 (d, 2H), 3.20-3.30 (m, 4H), 2.97 (t, 2H), 2.26 (m, 2H), 1.86 (m, 2H), 1.65 (m, 1H), 1.42 (m, 2H): MS (+ve ESI): 612.5 (M+H)+. EXAMPLE 128 Preparation of Compound 128 in Table 4—N-(3-cyanophenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 106, but starting with 3-cyanoaniline (45 mg, 0.37 mmol) yielded compound 128 in table 4 (65 mg, 43% yield): 1H-NMR (DMSO d6, TFA): 8.93 (s, 1H), 8.28 (s, 1H), 8.14 (s, 1H), 7.81 (d, 1H), 7.51 (m, 2H), 7.30 (s, 1H), 6.84 (s, 1H), 4.28 (m, 2H), 3.99 (s, 3H), 3.86 (s, 2H), 3.59 (d, 2H), 3.20-3.35 (m, 4H), 2.96 (t, 2H), 2.30 (m, 2H), 1.88 (m, 2H), 1.68 (m, 1H), 1.44 (m, 2H): MS (+ve ESI): 571.6 (M+H)+. EXAMPLE 129 Preparation of Compound 129 in Table 4—N-(3-bromophenyl)-2-{3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 106, but starting with 3-bromoaniline (65 mg, 0.37 mmol) yielded compound 129 in table 4 (62 mg, 32% yield): 1H-NMR (DMSO d6, TFA): 8.95 (s, 1H), 8.30 (s, 1H), 8.00 (s, 1H), 7.52 (d, 1H), 7.32 (s, 1H), 7.26-7.31 (m, 2H), 6.84 (s, 1H), 4.29 (m, 2H), 4.00 (s, 3H), 3.84 (s, 2H), 3.60 (m, 2H), 3.20-3.35 (m, 4H), 2.98 (t, 2H), 2.30 (m, 2H), 1.87 (m, 2H), 1.65 (m, 1H), 1.44 (m, 2H): MS (+ve ESI): 626.4 (M+H)+. EXAMPLE 130 Preparation of Compound 130 in Table 5—N-(2,3-difluorophenyl)-2-{3-[(7-{3-[ethyl(2-hydroxyethyl)amino]propoxy}quinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide 2-(3-([7-(3-chloropropoxy)quinazolin-4-yl]amino)-1H-pyrazol-5-yl)-N-(2,3-difluorophenyl)acetamide (300 mg, 0.634 mmol), potassium iodide (210 mg, 1.27 mmol), dimethylamine (2 ml) and 2-(ethylamino)ethanol (226 mg, 2.54 mmol) were combined and heated to 50° C. for 72 hours. The reaction was diluted with dichloromethane (20 ml) and loaded onto a 40S silica biotage column. Elution with dichloromethane followed by increased polarity to dichloromethane:methanol (9:1), then dichloromethane:methanol:ammonia (9:1:0.8) yielded compound 130 in table 5 as a pale pink solid (181 mg, 54% yield): 1H-NMR (DMSO d6): 12.35 (s, 1H), 10.25 (s, 2H), 8.52 (s, 2H), 7.71 (m, 1H), 7.16 (m, 4H), 6.78 (s, 1H), 4.33 (t, 1H), 4.17 (t, 2H), 3.84 (s, 2H), 3.43 (m, 2H), 2.60 (t, 2H), 2.49 (m, 4H), 1.88 (m, 2H), 0.96 (t, 3H): MS (−ve ESI): 524 (M−H)−, MS (+ve ESI): 526 (M+H)+. 2-{3-[7-(3-chloropropoxy)quinazolin-4-yl]amino)-1H-pyrazol-5-yl)-N-(2,3-difluorophenyl)acetamide, used as the starting material was obtained as follows: a) 2-Amino-4-fluorobenzoic acid (15 g, 96 mmol) was dissolved in 2-methoxyethanol (97 ml). Formamidine acetate (20.13 g, 193.4 mmol) was added and the mixture heated to reflux for 18 hours. The reaction was cooled, concentrated and the residue stirred in aqueous ammonium hydroxide (0.01 N, 250 ml) for 1 hour. The suspension was filtered, washed with water and dried over phosphorus pentoxide to yield 7-fluoroquinazolin-4(3H)-one as an off-white solid (10.35 g, 65% yield): 1H-NMR (DMSO d6): 12.32 (br s, 1H), 8.19 (dd, 1H), 8.14 (s, 1H), 7.45 (dd, 1H), 7.39 (m, 1H): MS (−ve ESI): 163 (M−H)−, MS (+ve EST): 165 (M+H)+. b) Sodium hydride (14.6 g, 365 mmol) was added at 0° C. to a solution of 1,3-propanediol (27.8 g, 365 mmol) in dimethylformamide (70 ml). 7-Fluoroquinazolin-4(3H)-one (10 g, 60.9 mmol) was added portionwise and the reaction mixture heated at 60° C., then at 110° C. for 3 hours. The reaction was cooled to 0° C., quenched with water (280 ml) and adjusted to pH 5.9. The resulting suspension was filtered, washed with water then ether and dried over phosphorus pentoxide to afford 7-(3-hydroxypropoxy)quinazolin-4(3H)-one as a white powder (12.41 g, 92% yield): 1H-NMR (DMSO d6): 11.90 (br s, 1H), 8.04 (s, 1H), 8.00 (d, 1H), 7.10 (m, 2H), 4.17 (t, 2H), 3.58 (t, 2H), 1.92 (m, 2H): MS (+ve ESI): 221 (M+H)+. c) 7-(3-hydroxypropoxy)quinazolin-4(3H)-one (10.5 g, 47.7 mmol) and thionyl chloride (100 ml, 137 mmol) were combined. Dimethylformamide (1 ml) was added and the reaction mixture heated to 85° C. for 1 hour. The mixture was cooled to room temperature, diluted with toluene and evaporated to dryness. This was repeated until all thionyl chloride was removed. The residue was dissolved in dichloromethane and washed with a saturated sodium bicarbonate solution. The aqueous layer was extracted with dichloromethane. The organics were combined, dried (magnesium sulphate) and concentrated to leave a yellow solid. Trituration with ether removed a less soluble impurity and the ether filtrate was concentrated to leave 4-chloro-7-(3-chloropropoxy)quinazoline as an off-white solid (8.5 g, 70% yield): 1H-NMR (DMSO d6): 13.25 (br s, 1H), 8.34 (s, 1H), 8.06 (d, 1H), 7.17 (m, 2H), 4.21 (t, 2H), 3.83 (t, 2H), 2.23 (m, 2H): MS (+ve ESI): 257, 259 (M+H)+. d) 4-chloro-7-(3-chloropropoxy)quinazoline (2.5 g, 9.72 mmol) and (3-amino-1H-pyrazol-5-yl)acetic acid (1.37 g, 9.72 mmol) were combined in dimethylformamide (25 ml). A solution of 4M HCl in dioxane (1.25 ml, 4.8 mmol) was added and the reaction heated to 90° C. for 40 minutes. The solution was cooled to room temperature, diluted with water (250 ml) and filtered through celite. The acidic solution was basified to pH 4.9 and the yellow powder filtered. (At pH 3, a red solid precipitated which was isolated, suspended in water and basified to pH 12. Careful adjustment back to pH 4.8 resulted in the precipitation of a yellow powder, which was combined with the first crop). The solid was washed with diethyl ether and dried over phosphorus pentoxide to yield (3-{[7-(3-chloropropoxy)quinazolin-4-yl]amino)-1H-pyrazol-5-yl)acetic acid as a pale orange solid (2.88 g, 82% yield): 1H-NMR (DMSO d6): 12.60 (br s, 2H), 10.78 (br s, 1H), 8.65 (s, 1H), 8.60 (d, 1H), 7.26 (d, 1H), 7.22 (s, 1H), 6.67 (s, 1H), 4.28 (t, 2H), 3.83 (t, 2H), 3.67 (s, 2H), 2.24 (m, 2H): MS (−ve ESI): 360, 362 (M−H)−, MS (+ve ESI): 362, 364 (M+H)+. e) 2,3-difluoroaniline (1.15 g, 8.95 mmol) was added to a suspension of (3-([7-(3-chloropropoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetic acid (2.70 g, 7.46 mmol) in pyridine (30 ml) and the reaction cooled to 0° C. Phosphorous oxychloride (1.14 g, 7.46 mmol) was added dropwise and the reaction stirred at 0° C. for 1 hour. The reaction was warmed to ambient temperature and more phosphorous oxychloride (0.5 ml) added. The reaction was stirred for 4.5 hours. The reaction mixture was diluted with ethyl acetate:ether (100 ml: 37 ml) and stirred for 18 hours. The precipitate was filtered, suspended in water and neutralised with ammonium hydroxide (7%, 15 ml). The resultant yellow suspension was filtered, washed with water and dried (phosphorous pentoxide) to yield 2-(3-([7-(3-chloropropoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)-N-(2,3-difluorophenyl)acetamide as an orange powder (3.15 g, 89% yield): 1H-NMR (DMSO d6): 10.64 (br s, 1H), 10.27 (s, 1H), 8.60 (s, 1H), 8.55 (d, 1H), 7.70 (m, 1H), 7.20 (m, 6H), 6.68 (s, 1H), 4.27 (t, 2H), 3.83 (m, 4H), 2.25 (m, 2H): MS (−ve ESI): 471, 473 (M−H)−, MS (+ve ESI): 473, 475 (M+H)+. EXAMPLE 131 Preparation of Compound 131 in Table 5—N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(isopropyl)amino]propoxy}quinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 130, but starting with 2-(isopropylamino)ethanol (262 mg, 2.54 mmol) yielded compound 131 in table 5 as a pink solid (182 mg, 53% yield): 1H-NMR (DMSO d6): 12.35 (s, 1H), 10.20 (s, 1H), 8.50 (s, 2H), 7.71 (m, 1H), 7.20 (m, 4H), 6.78 (s, 1H), 4.29 (br s, 1H), 4.19 (t, 2H), 3.85 (s, 2H), 3.38 (dt, 2H), 2.88 (m, 1H), 2.55 (t, 2H), 2.45 (t, 2H), 1.82 (m, 2H), 0.93 (d, 6H): MS (−ve ESI): 538 (M−H)−, MS (+ve ESI): 540 (M+H)+. EXAMPLE 132 Preparation of Compound 132 in Table 5—N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]propoxy}quinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 130, but starting with D-prolinol (257 mg, 2.54 mmol) yielded compound 132 in table 5 as a pink solid (206 mg, 60% yield): 1H-NMR (DMSO d6, AcOD): 11.60 (br s, 7H), 10.25 (s, 1H), 8.52 (m, 2H), 7.75 (m, 1H), 7.16 (m, 4H), 6.67 (s, 1H), 4.22 (t, 2H), 3.84 (s, 2H), 3.50 (d, 2H), 3.35 (m, 1H), 3.28 (m, 1H), 3.07 (m, 1H), 2.86 (m, 1H), 2.72 (m, 1H), 2.05 (m, 2H), 1.95 (m, 1H), 1.60-1.90 (m, 4H): MS (−ve ESI): 536 (M−H)−, MS (+ve ESI): 538 (M+H)+. EXAMPLE 133 Preparation of Compound 133 in Table 5—N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(propyl)amino]propoxy}quinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 130, but starting with 2-(n-propylamino)ethanol (262 mg, 2.54 mmol) yielded compound 133 in table 5 as a pink solid (168 mg, 49% yield): 1H-NMR (DMSO d6): 12.35 (s, 1H), 10.22 (s, 2H), 8.51 (s, 2H), 7.71 (m, 1H), 7.20 (m, 4H), 6.78 (s, 1H), 4.30 (t, 1H), 4.17 (t, 2H), 3.85 (s, 2H), 3.43 (m, 2H), 2.59 (t, 2H), 2.49 (m, 2H), 2.39 (t, 2H), 1.87 (m, 2H), 1.39 (m, 2H), 0.82 (t, 3H): MS (−ve ESI): 538 (M−H)−, MS (+ve ESI): 540 (M+H)+. EXAMPLE 134 Preparation of Compound 134 in Table 5—N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(prop-2-yn-1-yl)amino]propoxy}quinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 130, but starting with 2-(prop-2-yn-1-ylamino)ethanol (220 mg, 2.22 mmol) yielded compound 134 in table 5 as a beige solid (162 mg, 48% yield): 1H-NMR (DMSO d6): 12.40 (s, 1H), 10.22 (br s, 1H), 8.50 (s, 2H), 7.73 (m, 1H), 7.17 (m, 4H), 6.78 (br s, 1H), 4.52 (br s, 1H), 4.17 (t, 2H), 3.84 (s, 2H), 3.49 (s, 4H), 3.17 (s, 1H), 2.70 (s, 2H), 2.60. (s, 2H), 1.93 (m, 2H): MS (−ve ESI): 534 (M−H)−, MS (+ve ESI): 536 (M+H)+. EXAMPLE 135 Preparation of Compound 135 in Table 5—N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2-hydroxyethyl)(isobutyl)amino]propoxy}quinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 130, but starting with 2-(isobutylamino)ethanol (260 mg, 2.22 mmol) yielded compound 135 in table 5 as a beige solid (168 mg, 48% yield): 1H-NMR (DMSO d6): 12.35 (s, 1H), 10.28 (br s, 2H), 8.50 (s, 2H), 7.72 (m, 1H), 7.16 (m, 4H), 6.78 (s, 1H), 4.32 (s, 1H), 4.20 (t, 2H), 3.85 (s, 2H), 3.45 (m, 2H), 2.57 (br s, 2H), 2.48 (m, 2H), 2.16 (d, 2H), 1.89 (m, 2H), 1.66 (m, 1H), 0.83 (d, 6H): MS (−ve ESI): 552 (M−H)−, MS (+ve ESI): 554 (M+H)+. EXAMPLE 136 Preparation of Compound 136 in Table 5—N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2,2-dimethylpropyl)(2-hydroxyethyl)amino]propoxy}quinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 130, but starting with 2-[(2,2-dimethylpropyl)amino]ethanol (291 mg, 2.22 mmol) yielded compound 136 in table 5 as a beige solid (93 mg, 26% yield): 1H-NMR (DMSO d6): 12.36 (s, 1H), 10.22 (s, 1H), 8.52 (s, 2H), 7.72 (m, 1H), 7.19 (m, 4H), 6.77 (s, 1H), 4.34 (s, 1H), 4.19 (m, 2H), 3.83 (s, 2H), 3.45 (m, 2H), 2.64 (m, 2H), 2.54 (m, 2H), 2.21 (s, 2H), 1.89 (m, 2H), 0.83 (s, 9H): MS (−ve ESI): 566 (M−H)−, MS (+ve ESI): 568 (M+H)+. EXAMPLE 137 Preparation of Compound 137 in Table 6—N-(3-fluorophenyl)-2-[3-({5-{[1-(2-hydroxyethyl)piperidin-4-yl]oxy}-7-[3-(4-methylpiperazin-1-yl)propoxy]quinazolin-4-yl}amino)-1H-pyrazol-5-yl]acetamide 2-[3-({5-{[1-(2-tert-butoxyethyl)piperidin-4-yl]oxy}-7-[3-(4-methylpiperazin-1-yl)propoxy]quinazolin-4-yl}amino)-1H-pyrazol-5-yl]-N-(3-fluorophenyl)acetamide (102 mg, 0.117 mmol) was treated with a mixture of dichloromethane:trifluoroacetic acid (5:1) at ambient temperature for 16 hours. The solvent was evaporated, and the residue purified by preparative LCMS to yield compound 137 in table 6 (55 mg, 71% yield): 1H-NMR (DMSO d6): 10.44 (s, 1H), 10.28 (s, 1H), 8.44 (s, 1H), 7.61 (d, 1H), 7.31-7.39 (m, 1H), 7.33 (s, 1H), 6.91 (t, 1H), 6.87 (s, 1H), 6.77 (s, 1H), 6.75 (s, 1H), 4.87 (br s, 1H), 4.40 (t, 1H), 4.13 (t, 2H), 3.76 (s, 2H), 3.50 (s, 2H), 2.78 (m, 2H), 2.19-2.47 (m, 14H), 2.14 (s, 3H), 2.09 (m, 2H), 1.91 (m, 2H), 1.84 (m, 2H): MS (+ve ESI): 662.3 (M+H)+. 2-[3-({5-{[1-(2-tert-butoxyethyl)piperidin-4-yl]oxy}-7-[3-(4-methylpiperazin-1-yl)propoxy]quinazolin-4-yl}amino)-1H-pyrazol-5-yl]-N-(3-fluorophenyl)acetamide used as starting material was obtained as follows: a) A solution of 5,7-difluoroquinazolin-4(3H)-one (1.82 g, 10 mmol) and 1-(2-tert-butoxyethyl)piperidin-4-ol (1.91 g, 9.5 mmol) in tetrahydrofuran (40 ml) was treated with potassium tert-butoxide (3.36 g, 30 mmol). The mixture was heated at 70° C. for 5 hours. The solvent was evaporated and the residue purified by chromatography on silica gel. Elution with dichloromethane:methanolic ammonia (95:5) yielded 5-([1-(2-ten-butoxyethyl)piperidin-4-yl]oxy)-7-fluoroquinazolin-4(3H)-one (2.88 g, 83% yield): 1H-NMR (DMSO d6): 7.98 (s, 1H), 7.01 (d, 1H), 6.90 (d, 1H), 4.58 (br s, 1H), 3.43 (t, 2H), 2.74 (m, 2H), 2.43 (t, 2H), 2.34 (m, 2H), 1.90 (m, 2H), 1.71 (m, 2H), 1.13 (s, 9H): MS (+ve ESI): 364.3 (M+H)+. b) 5-{[1-(2-tert-butoxyethyl)piperidin-4-yl]oxy}-7-fluoroquinazolin-4(3H)-one (5.45 mg, 1.5 mmol) in anhydrous diglyme (15 ml) was reacted with 3-(4-methylpiperazin-1-yl)propan-1-ol (474 mg, 3 mmol) in the presence of potassium tert-butoxide (11.77 g, 10 mmol) at 100° C. for 4 hours. The reaction mixture was diluted with dichloromethane (10 ml) and water (10 ml) and the pH adjusted to 7.7. The mixture was extracted several times with dichloromethane and the organic phase dried (magnesium sulphate), evaporated and the residue purified by chromatography on silica gel. Elution with dichloromethane:methanolic ammonia (9:1) yielded 5-{[1-(2-tert-butoxyethyl)piperidin-4-yl]oxy}-7-[3-(4-methylpiperazin-1-yl)propoxy]quinazolin-4(3H)-one (411 mg, 55% yield): 1H-NMR (DMSO d6): 7.89 (s, 1H), 6.63 (s, 1H), 6.55 (s, 1H), 4.49 (br s, 1H), 4.09 (t, 2H), 3.40 (t, 2H), 2.75 (m, 2H), 2.52 (m, 2H), 2.22-2.43 (m, 12H), 2.14 (s, 3H), 1.88 (m, 4H), 1.69 (m, 2H), 1.12 (s, 9H): MS (+ve ESI): 502.4 (M+H)+. c) 5-{[1-(2-ten-butoxyethyl)piperidin-4-yl]oxy}-7-[3-(4-methylpiperazin-1-yl)propoxy]quinazolin-4(3H)-one (400 mg, 0.8 mmol) in dichloroethane (8 ml) was reacted with triphenylphosphine (420 mg, 1.6 mmol)and carbon tetrachloride (0.78 ml, 8 mmol) at 70° C. for 1.5 hours. The solvent was evaporated, the residue dissolved in isopropanol (8 ml) and reacted with (3-amino-1H-pyrazol-5-yl)acetic acid (124 mg, 0.88 mmol) at 80° C. under argon for 2 hours. The solvent was evaporated, and the residue purified by preparative LCMS to yield [3-({5-{[1-(2-tert-butoxyethyl)piperidin-4-yl]oxy}-7-[3-(4-methylpiperazin-1-yl)propoxy]quinazolin-4-yl}amino)-1H-pyrazol-5-yl]acetic acid (270 mg, 54% yield): 1H-NMR (DMSO d6): 8.99 (s, 1H), 7.09-7.15 (m, 1H), 6.96 (m, 1H), 6.88 (m, 1H), 5.08-5.38 (m, 1H), 4.30 (t, 2H), 3.29-3.95 (m, 21H), 3.22 (t, 1H), 2.74 (s, 3H), 2.08-2.39 (m, 6H), 1.20 (m, 9H): MS (+ve ESI): 625.3 (M+H)*. d) [3-({5-{[1-(2-tert-butoxyethyl)piperidin-4-yl]oxy}-7-[3-(4-methylpiperazin-1-yl)propoxy]quinazolin-4-yl}amino)-1H-pyrazol-5-yl]acetic acid (140 mg, 0.22 mmol) in dimethylformamide (1 ml) was reacted with 3-fluoroaniline (24 μl, 0.25 mmol) in the presence of 1-(3-dimethylamino-propyl)-3-ethylcarbodiimide hydrochloride (48 mg, 0.25 mmol) and 2-hydroxypyridin-1-oxide (27 mg, 0.24 mmol) at 50° C. for 45 minutes. The solvent was evaporated and the residue purified by chromatography on silica gel. Elution with dichloromethane:methanol (97:3) then dichloromethane:methanolic ammonia (95:5) yielded 2-[3-({5-{[1-(2-tert-butoxyethyl)piperidin-4-yl]oxy}-7-[3-(4-methylpiperazin-1-yl)propoxy]quinazolin-4-yl}amino)-1H-pyrazol-5-yl]-N-(3-fluorophenyl)acetamide (109 mg, 58% yield): 1H-NMR (DMSO d6): 10.44 (s, 1H), 10.27 (s, 1H), 8.44 (s, 1H), 7.61 (d, 1H), 7.30-7.38 (m, 1H), 7.33 (s, 1H), 6.88 (t, 1H), 6.87 (s, 1H), 6.76 (s, 1H), 6.75 (s, 1H), 4.86 (br s, 1H), 4.13 (t, 2H), 3.75 (s, 2H), 3.41 (t, 2H), 2.78 (m, 2H), 2.20-2.48 (m, 12H), 2.17 (t, 2H), 2.14 (s, 3H), 2.07 (m, 2H), 1.90 (t, 2H), 1.82 (m, 2H), 1.11 (s, 9H): MS (+ve ESI): 718.1 (M+H)+. EXAMPLE 138 Preparation of Compound 138 in Table 6—N-(3-fluorophenyl)-2-[5-({7-methoxy-5-[(1-methylpiperidin-4-yl)oxy]quinazolin-4-yl}amino)-1H-pyrazol-3-yl]acetamide [5-({7-methoxy-5-[(1-methylpiperidin-4-yl)oxy]quinazolin-4-yl}amino)-1H-pyrazol-3-yl]acetic acid (95 mg, 0.2 mmol) in dimethylformamide (1 ml) was reacted with 3-fluoroaniline (21 μl, 0.22 mmol) in the presence of 1-(3-dimethylamino-propyl)-3-ethylcarbodiimide hydrochloride (46 mg, 0.24 mmol) and 2-hydroxypyridin-1-oxide (24 mg, 0.22 mmol) at 60° C. for 2.5 hours. The solvent was evaporated, and the residue purified by chromatography on silica gel. Elution with dichloromethane then increased polarity to dichloromethane:methanolic ammonia (9:1) yielded compound 138 in table 6 (30 mg, 30% yield): 1H-NMR (DMSO d6): 8.47 (s, 1H), 7.63 (d, 1H), 7.35 (m, 2H), 6.90 (m, 2H), 6.80 (m, 2H), 4.88 (m, 1H), 3.90 (s, 3H), 3.77 (s, 2H), 2.68 (m, 2H), 2.39 (m, 2H), 2.23 (s, 3H), 2.12 (m, 2H), 1.90 (m, 2H): MS (+ve ESI): 506.2 (M+H)+. [5-({7-methoxy-5-[(1-methylpiperidin-4-yl)oxy]quinazolin-4-yl}amino)-1H-pyrazol-3-yl]acetic acid used as starting material was obtained as follows: a) 3,5-Dimethoxyaniline hydrochloride (80.21 g, 0.424 mol) was added cautiously to oxalyl chloride (136 ml, 1.56 mol) and the solution heated at reflux for 3 hours. The solution was cooled and concentrated in vacuo. Methanol (300 ml) was added to the residue and the mixture heated at reflux for 1 hour. The reaction was allowed to cool, and the resulting precipitate filtered and washed with methanol to yield 4,6-dimethoxyisatin (40.4 g, 46%) as a yellow solid. 1H-NMR (DMSO d6): 10.86 (br s, 1H), 6.17 (d, 1H), 6.00 (d, 1H), 3.86 (s, 3H), 3.83 (s, 3H). b) 4,6-Dimethoxyisatin (5.00 g, 24.0 mmol) was dissolved in 33% (w/v) aqueous sodium hydroxide solution (42 ml) at 75° C. To this solution was added hydrogen peroxide (30%, 8 ml) dropwise over 30 minutes. The reaction was stirred for an hour at 75° C. and then cooled to room temperature. Ice was added, and the reaction mixture acidified to pH 1 with concentrated hydrochloric acid. The resulting precipitate was filtered, washed with water and dried in vacuo to yield 2-amino-4,6-dimethoxybenzoic acid hydrochloride salt (3.3 g, 59% yield) acid as a pale yellow solid: 1H-NMR (DMSO d6): 5.92 (d, 1H), 5.77 (d, 1H), 3.75 (s, 3H), 3.69 (s, 3H): MS (+ve ESI): 198 (M+H)+. c) Dimethyl sulfate (1.04 ml, 11.0 mmol) was added dropwise to a mixture of potassium carbonate (3.34 g, 24.2 mmol) and 2-amino-4,6-dimethoxybenzoic acid (2.56 g, 11.0 mmol) in dimethylformamide (70 ml) at 0° C. The reaction was stirred for 1 hour, then poured into water. The resulting precipitate was filtered, washed with water and dried in vacuo. The filtrate was extracted with ethyl acetate, and the combined organic extracts were dried (magnesium sulphate) and concentrated in vacuo. The combined solids were dried in vacuo to yield methyl 2-amino-4,6-dimethoxybenzoate (1.8 g, 77% yield) as a yellow crystalline solid: 1H-NMR (DMSO d6): 6.13 (s, 2H), 5.90 (d, 1H), 5.75 (d, 1H), 3.68 (s, 3H), 3.67 (s, 3H), 3.66 (s, 3H). d) A solution of methyl 2-amino-4,6-dimethoxybenzoate (600 mg, 2.8 mmol) and formamidine acetate (650 mg, 6.3 mmol) in 2-methoxyethanol (7 ml) was heated at 120° C. for 16 hours. The reaction was cooled, concentrated in vacuo, and the residue triturated with methanol to give 5,7-dimethoxy-3,4-dihydroquinazolin-4(3H)-one as a beige solid (290 mg, 58% yield): 1H-NMR (DMSO d6): 11.62 (br s, 1H), 7.88 (s, 1H), 6.63 (d, 1H), 6.51 (d, 1H), 3.84 (s, 3H), 3.80 (s, 3H): MS (+ve ESI): 207 (M+H)+. e) Magnesium bromide (3.83 g, 20.8 mmol) was added cautiously to 5,7-dimethoxy-3,4-dihydroquinazolin-4(3H)-one (4.29 g, 20.8 mmol) in pyridine (60 ml) and the solution heated at reflux for 1 hour. The reaction mixture was cooled, concentrated in vacuo and the residue triturated with water and filtered to yield 7-methoxyquinazoline-4,5-diol (3.72 g, 93% yield): as an off-white solid: MS (+ve ESI): 193 (M+H)+. f) Sodium hydride (60 mg, 1.49 mmol) was added portionwise over 5 minutes to 7-methoxyquinazoline-4,5-diol (260 mg, 1.35 mmol) in dimethylformamide (2 ml) at 0° C. Chloromethyl pivalate (200 μl, 1.36 mmol) was added dropwise over 15 minutes to give a clear orange solution. The reaction mixture was allowed to warm to ambient temperature and stirred for a further 18 hours. Incomplete reaction was seen by tic, therefore the reaction was cooled to 0° C. and sodium hydride (10 mg, 0.25 mmol) was added followed by chloromethyl pivalate (26 μl, 6.18 mmol). The reaction was complete after stirring for 1 hour at ambient temperature. The reaction mixture was concentrated in vacuo and purified by chromatography on silica gel, eluting with 2-10% methanol in dichloromethane, to yield (5-hydroxy-7-methoxy-4-oxoquinazolin-3(4H)-yl)methyl pivalate (170 mg, 41% yield) as a cream solid: 1H-NMR (DMSO d6): 11.42 (s, 1H), 8.37 (s, 1H), 6.66 (d, 1H), 6.51 (d, 1H), 5.86 (s, 2H), 3.85 (s, 3H), 1.11 (s, 9H): MS (+ve ESI): 305 (M+H)+. g) (5-hydroxy-7-methoxy-4-oxoquinazolin-3(4H)-yl)methyl pivalate (500 mg, 1.63 mmol), 4-hydroxy-N-methylpiperidine (280 mg, 2.45 mmol) and triphenylphosphine (640 mg, 2.45 mmol) were dissolved in anhydrous dichloromethane (8 ml), under a nitrogen atmosphere at 0° C. A solution of di-tert-butyl azodicarboxylate (560 mg, 2.45 mmol) in dichloromethane (1 ml) was added dropwise over 5 minutes and the resulting yellow solution was allowed to warm to ambient temperature and stirred for 18 hours. A further 1 equivalent of all reagents was added in the same sequence as above under the same reaction conditions and was left to stir for a further 12 hours at ambient temperature. The reaction mixture was concentrated in vacuo and the residue purified by chromatography on silica gel, eluting with 2-8% methanol in dichloromethane, to yield (7-methoxy-5-((1-methylpiperidin 4-yl)oxy)-4-oxoquinazolin-3(4H)-yl)methyl pivalate (370 mg, 56% yield) as a cream solid: 1H-NMR (DMSO d6): 8.16 (s, 1H), 6.67 (d, 1H), 6.61 (d, 1H), 5.79 (s, 2H), 4.52 (m, 1H), 3.84 (s, 3H), 2.57 (m, 2H), 2.18 (m, 2H), 2.13 (s, 3H), 1.87 (m, 2H), 1.71 (m, 2H), 1.11 (s, 9H): MS (+ve ESI): 405 (M+H)+. h) 7.0 N ammonia in methanol (25 ml) was added to (7-methoxy-5-((1-methylpiperidin-4-yl)oxy)-4-oxoquinazolin-3(4H)-yl)methyl pivalate (370 mg, 0.92 mmol) and the solution stirred at ambient temperature for 18 hours. The reaction mixture was concentrated in vacuo to give an oil which was triturated with diethyl ether to give an orange solid which was collected by suction filtration and dried in vacuo to yield 7-methoxy-5-((1-methylpiperidin-4-yl)oxy)quinazolin-4(3H)-one (200 mg, 75% yield): 1H-NMR (DMSO d6): 11.60 (br s, 1H), 7.86 (s, 1H), 6.64 (d, 2H), 6.53 (d, 2H), 4.45 (m, 1H), 3.82 (s, 3H), 2.61 (m, 2H), 2.18 (m, 2H), 2.11 (s, 3H), 1.84 (m, 2H), 1.68 (m, 2H): MS (+ve ESI): 290 (M+H)+. i) A solution of 7-methoxy-5-((1-methylpiperidin-4-yl)oxy)quinazolin-4(3H)-one (3.00 g, 10.4 mmol) and diisopropyl ethylamine (5 ml) in dichloromethane (300 ml) was stirred at ambient temperature under an atmosphere of nitrogen. Phosphoryl chloride (10 ml) was added, and the resultant orange solution was heated at reflux for 20 hours. The reaction mixture was then cooled to ambient temperature and concentrated in vacuo. Residual phosphoryl chloride was then removed by azeotrope with toluene to give the crude product as an orange oil. Purification by chromatography on silica gel, eluting with 5% triethylamine in dichloromethane, gave an orange solid, which was further purified by trituration under acetonitrile, and then dried in vacuo to yield 4-chloro-5-(N-methylpiperidin-4-yloxy)-7-methoxyquinazoline (2.4 g, 75% yield) as a pale yellow amorphous solid: 1H-NMR (CDCl3) 8.80 (s, 1H), 6.94 (d, 1H), 6.60 (d, 1H), 4.58 (s, 1H), 3.95 (s, 3H), 2.74 (m, 2H), 2.44 (m, 2H), 2.35 (s, 3H), 2.10 (m, 4H): MS (+ve ESI): 308, 310 (M+H)+. j) 4-chloro-7-methoxy-5-[(1-methylpiperidin-4-yl)oxy]quinazoline (307 mg, 0.85 mmol) was condensed with (3-amino-1H-pyrazol-5-yl)acetic acid (132 mg, 0.93 mmol) in dimethylacetamide (3 ml) and hydrochloric acid in dioxane (4.0 N solution, 467 μl) at 90° C. for 1 hour. The solvent was evaporated, and the residual oil was triturated with ethanol:diethyl ether to yield [5-({7-methoxy-5-[(1-methylpiperidin-4-yl)oxy]quinazolin-4-yl}amino)-1H-pyrazol-3-yl]acetic acid as a beige solid (320 mg, 78% yield): 1H-NMR (DMSO d6): 8.88 (m, 1H), 7.12 (m, 1H), 6.88 (m, 1H), 6.82 (m, 1H), 5.05-5.45 (m, 1H), 3.96 (m, 3H), 3.73 (s, 2H), 3.10-3.60 (m, 4H), 2.80 (m, 3H), 2.00-2.50 (m, 4H): MS (+ve ESI): 413.2 (M+H)+. EXAMPLE 139 Preparation of Compound 139 in Table 6—N-(2,3-difluorophenyl)-2-{3-[(5,7-dimethoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 137d but starting with (3-[(5,7-dimethoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl acetic acid (165 mg, 0.5 mmol) and 2,3-difluoroaniline (70 μl, 0.6 mmol) at 50° C. for 10 hours yielded compound 139 in table 6 (30 mg, 14% yield): 1H-NMR (DMSO d6, TFA): 8.82 (s, 1H), 7.65 (m, 1H), 7.09-7.16 (m, 1H), 7.12 (s, 1H), 6.92 (s, 1H), 6.79 (d, 1H), 6.66 (d, 1H), 4.10 (s, 3H), 3.92 (s, 3H), 3.85 (s, 2H): MS (+ve ESI): 441.0 (M+H)+. {3-[(5,7-dimethoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl acetic acid used as starting material was obtained as follows: a) An anlogous reaction to that described in example 137c, but starting with 5,7-dimethoxyquinazolin-4(3H)-one (618 mg, 3 mmol—see patent WO 0194341) yielded (3-[(5,7-dimethoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetic acid (913 mg, 92% yield): 1H-NMR (DMSO d6): 10.72 (s, 1H), 8.85 (s, 1H), 7.00 (s, 1H), 6.96 (s, 1H), 6.67 (s, 1H), 4.16 (s, 3H), 3.97 (s, 3H), 3.72 (s, 2H): MS (+ve ESI): 330.1 (M+H)+. EXAMPLE 140 Preparation of Compound 140 in Table 6—2-(3-{[5,7-bis(2-methoxyethoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)-N-(2,3-difluorophenyl)acetamide A solution of phosphoryl chloride (51 μl, 0.55 mmol) in dichloromethane (0.5 ml) was added slowly at 0° C. to a solution of (3-([5,7-bis(2-methoxyethoxy)quinazolin-4-yl]amino)-1H-pyrazol-5-yl)acetic acid (209 mg, 0.5 mmol) and 2,3-difluoroaniline (61 μl, 0.6 mmol) in pyridine (2 ml. The mixture was stirred at ambient temperature for 6 hours. Ice was then added to the reaction mixture at 0° C., and the solvent was evaporated. The crude product was purified by preparative LCMS to yield compound 140 in table 6 (26 mg, 10% yield): 1H-NMR (DMSO d6): 10.22 (s, 1H), 10.15 (s, 1H), 8.45 (s, 1H), 7.71 (t, 1H), 7.14-7.23 (m, 1H), 7.18 (s, 1H), 6.86 (s, 1H), 6.79 (s, 1H), 6.74 (s, 1H), 4.40 (s, 2H), 4.24 (t, 2H), 3.84 (s, 4H), 3.71 (t, 2H), 3.42 (s, 3H), 3.33 (s, 3H): MS (+ve ESI): 529.1 (M+H)+. (3-{[5,7-bis(2-methoxyethoxy)quinazolin-4-yl]amino)-1H-pyrazol-5-yl)acetic acid used as starting material was obtained as follows a) 5,7-difluoroquinazolin-4(3H)one (728 mg, 4 mmol) in diglyme (15 ml) and potassium tert-butoxide (4.48 g, 32 mmol) were reacted with 2-methoxyethanol (2.52 ml, 32 mmol) at 110° C. for 1 hour. The mixture was cooled and purified by chromatography on silica gel. Elution with dichloromethane:methanol (96:4) then increased polarity to dichloromethane:methanolic ammonia (95:5) yielded 5,7-bis(2-methoxyethoxy)quinazolin-4(3H)-one (982 mg, 99% yield): 1H-NMR (DMSO d6): 11.71 (br s, 1H), 7.90 (s, 1H), 6.66 (d, 1H), 6.56 (d, 1H), 4.20 (t, 2H), 4.15 (t, 2H), 3.69 (m, 4H), 3.36 (s, 3H), 3.32 (s, 3H): MS (+ve ESI): 295.1 (M+H)+. b) An analogous reaction to that described in example 137c, but starting with 5,7-bis(2-methoxyethoxy)quinazolin-4(3H)-one (648 mg, 2.2 mmol) yielded (3-([5,7-bis(2-methoxyethoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetic acid (632 mg, 68% yield) as a beige solid: 1H-NMR (DMSO d6): 10.90 (s, 1H), 8.86 (s, 1H), 7.02 (s, 1H), 6.96 (s, 1H), 6.78 (s, 1H), 4.52 (t, 2H), 4.31 (t, 2H), 3.85 (t, 2H), 3.74 (t, 2H), 3.71 (s, 2H), 3.42 (s, 3H), 3.33 (s, 3H): MS (+ve ESI): 418.1 (M+H)+. EXAMPLE 141 Preparation of Compound 141 in Table 6—N-(2,3-difluorophenyl)-2-(3-{[5-isopropoxy-7-(2-methoxyethoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetamide An analogous reaction to that described in example 140, but starting with (3-([5-isopropoxy-7-(2-methoxyethoxy)quinazolin-4-yl]amino)-1H-pyrazol-5-yl)acetic acid (230 mg, 0.5 mmol) yielded compound 141 in table 6 (68 mg, 31% yield) as a beige solid: 1H-NMR (DMSO d6, TFA): 8.92 (s, 1H), 7.73 (m, 1H), 7.17-7.23 (m, 2H), 7.07 (s, 1H), 6.88 (s, 1H), 6.85 (s, 1H), 5.19 (m, 1H), 4.33 (t, 2H), 3.93 (s, 2H), 3.75 (t, 2H), 3.54 (s, 3H), 1.52 (s, 3H), 1.51 (s, 3H): MS (+ve ESI): 513.16 (M+H)+. (3-{[5-isopropoxy-7-(2-methoxyethoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetic acid used as starting material was obtained as follows. a) 5,7-Difluoroquinazolin-4(3H)one (2.73 g, 15 mmol) in dimethylformamide (20 ml) was reacted with isopropanol (1.26 ml, 16.4 mmol) and sodium hydride (1.8 g, 45 mmol) at 0° C. under argon. The mixture was stirred at ambient temperature for 14 hours, acidified with acetic acid and concentrated. The residue was washed with water and dried to yield 7-fluoro-5-isopropoxyquinazolin-4(3H)-one (3.17 g, 95% yield) as a beige solid: 1H-NMR (DMSO d6): 11.92 (br s, 1H), 7.97 (s, 1H), 6.95 (dd, 1H), 6.89 (dd, 1H), 4.73 (m, 1H), 1.32 (s, 3H), 1.31 (s, 3H): MS (+ve ESI): 223.1 (M+H)+. b) An analogous reaction to that described in example 137b, but starting with 7-fluoro-5-isopropoxyquinazolin-4(3H)-one (444 mg, 2 mmol) and 2-methoxyethanol (0.32 ml, 4.06 mmol) and heating at 120° C. for 1.5 hours yielded 5-isopropoxy-7-(2-methoxyethoxy)quinazolin-4(3H)-one (155 mg, 28% yield) as a beige solid: 1H-NMR (DMSO d6): 11.62 (m, 1H), 7.88 (s, 1H), 6.64 (d, 1H), 6.54 (d, 1H), 4.66 (m, 1H), 4.66 (m, 2H), 4.20 (m, 2H), 1.30 (s, 3H), 1.29 (s, 3H): MS (+ve ESI): 279.2 (M+H)+. c) An analogous reaction to that described in example 137c, but starting with 5-isopropoxy-7-(2-methoxyethoxy)quinazolin-4(3H)-one (935 mg, 3.36 mmol) yielded (3-{[5-isopropoxy-7-(2-methoxyethoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetic acid as a beige solid (1.0 g, 74% yield): 1H-NMR (DMSO ds): 11.06 (s, 1H), 8.87 (s, 1H), 7.03 (s, 1H), 6.94 (s, 1H), 6.82 (s, 1H), 5.17 (m, 1H), 4.31 (t, 2H), 3.74 (t, 2H), 3.72 (s, 2H), 3.34 (s, 3H), 1.51 (s, 3H), 1.49 (s, 3H): MS (+ve ESI): 402.1 (M+H)+. EXAMPLE 142 Preparation of Compound 142 in Table 6—N-(3-fluorophenyl)-2-(3-{[5-isopropoxy-7-(2-methoxyethoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetamide An analogous reaction to that described in example 140, but starting with (3-{[5-isopropoxy-7-(2-methoxyethoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetic acid (308 mg, 0.7 mmol) and 3-fluoroaniline (81 μl, 0.84 mmol) yielded compound 142 in table 6 as a white solid (62 mg, 18% yield): 1H-NMR (DMSO ds): 10.44 (s, 1H), 10.33 (s, 1H), 8.44 (s, 1H), 7.61 (d, 1H), 7.30-7.39 (m, 1H), 7.32 (s, 1H), 6.89 (t, 1H), 6.85 (s, 1H), 6.77 (s, 1H), 6.76 (s, 1H), 5.01 (m, 1H), 4.24 (t, 2H), 3.75 (s, 2H), 3.71 (t, 2H), 3.33 (s, 3H), 1.47 (s, 3H), 1.46 (s, 3H): MS (+ve ESI): 495.1 (M+H)+. EXAMPLE 143 Preparation of Compound 143 in Table 6—N-(3-fluorophenyl)-2-{3-[(5-{[1-(2-hydroxyethyl)piperidin-4-yl]oxy}-7-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide An analogous reaction to that described in example 137, but starting with 2-{3-[(5-([1-(2-tert-butoxyethyl)piperidin-4-yl]oxy}-7-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl)-N-(3-fluorophenyl)acetamide (39 mg, 0.066 mmol) yielded compound 143 in table 6 as a beige solid (26 mg, 74% yield): 1H-NMR (DMSO d6, TFA): 8.94 (s, 1H), 7.61 (d, 1H), 7.29-7.37 (m, 2H), 7.12-7.18 (m, 1H), 6.91-6.85 (m, 3H), 5.10-5.35 (s, 0.5H), 3.97 (s, 3H), 3.83 (s, 2H), 3.79 (t, 1H), 3.76 (t, 1H), 3.71 (d, 1H), 3.60 (d, 1H), 3.41 (t, 1H), 3.32 (s, 1H), 3.23 (m, 1H), 3.19 (t, 1H), 2.52 (m, 1H), 2.30 (m, 2H), 2.14 (m, 1H): MS (+ve ESI): 536.1 (M+H)+. 2-{3-[(5-{[1-(2-tert-butoxyethyl)piperidin-4-yl]oxy}-7-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide used as starting material was obtained as follows. a) An analogous reaction to that described in example 137b, but starting with 5-{[1-(2-tert-butoxyethyl)piperidin-4-yl]oxy}-7-fluoroquinazolin-4(3H)-one (363 mg, 1 mmol) and methanol (162 μl, 4 mmol) at 110° C. for 2 hours yielded 5-{[1-(2-tert-butoxyethyl)piperidin-4-yl]oxy)-7-methoxyquinazolin-4(3H)-one (237 mg, 63% yield): 1H-NMR (DMSO d6): 11.64 (br s, 1H), 7.91 (s, 1H), 6.65 (d, 1H), 6.56 (d, 1H), 4.48 (m, 1H), 3.84 (s, 3H), 3.40 (t, 2H), 2.74 (m, 2H), 2.41 (t, 2H), 2.29 (m, 2H), 1.87 (m, 2H), 1.69 (m, 2H), 1.12 (s, 9H): MS (+ve ESI): 376.2 (M+H)+. b) An analogous reaction to that described in example 137c, but starting with 5-([1-(2-tert-butoxyethyl)piperidin-4-yl]oxy)-7-methoxyquinazolin-4(3H)-one (458 mg, 1.22 mmol) and heating for 4 hours yielded (3-[(5-t [1-(2-tert-butoxyethyl)piperidin-4-yl]oxy}-7-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl)acetic acid as a beige solid (386 mg, 63% yield): 1H-NMR (DMSO d6): 8.97 (s, 1H), 7.14-7.20 (m, 1H), 6.98 (s, 1H), 6.86 (m, 1H), 5.10-5.35 (m, 1H), 3.99 (s, 3H), 3.67-3.80 (m, 3H), 3.75 (s, 2H), 3.60 (m, 1H), 3.27-3.46 (m, 3H), 3.22 (t, 1H), 2.52 (m, 1H), 2.34 (br s, 2H), 2.15 (m, 1H), 1.21 (s, 3H), 1.16 (s, 3H): MS (+ve ESI): 499.1 (M+H)+. c) An analogous reaction to that described in example 137d, but starting with {3-[(5-{[1-(2-tert-butoxyethyl)piperidin-4-yl]oxy}-7-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetic acid (250 mg, 0.5 mmol) and heating for 4 hours yielded 2-{3-[(5-{[1-(2-tert-butoxyethyl)piperidin-4-yl]oxy}-7-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide as a yellow solid (44 mg, 15% yield): 1H-NMR (DMSO d6): 12.36 (s, 1H), 10.44 (s, 1H), 10.28 (s, 1H), 8.45 (s, 1H), 7.61 (d, 1H), 7.31-7.37 (m, 2H), 6.89 (t, 1H), 6.87 (s, 1H), 6.79 (s, 1H), 6.78 (s, 1H), 4.85 (br s, 1H), 3.89 (s, 3H), 3.75 (s, 2H), 3.41 (t, 2H), 2.79 (m, 2H), 2.46 (m, 4H), 2.07 (m, 2H), 1.83 (m, 2H), 1.11 (s, 9H): MS (+ve ESI): 592.2 (M+H)+. EXAMPLE 144 Preparation of Compound 144 in Table 6—2-{3-[(5,7-dimethoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide An analogous reaction to that described in example 140, but starting with (3-[(5,7-dimethoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl)acetic acid (230 mg, 0.70 mmol) and 3-fluoroaniline (81 μl, 0.84 mmol) yielded compound 144 in table 6 as a pale orange solid (43 mg, 15% yield): 1H-NMR (DMSO d6): 12.39 (s, 1H), 10.44 (s, 1H), 9.88 (s, 1H), 8.45 (s, 1H), 7.61 (d, 1H), 7.30-7.39 (m, 1H), 7.33 (s, 1H), 6.89 (t, 1H), 6.82 (s, 1H), 6.80 (s, 1H), 6.72 (s, 1H), 4.08 (s, 3H), 3.90 (s, 3H), 3.76 (s, 2H): MS (+ve ESI): 423 (M+H)+. EXAMPLE 145 Preparation or Compound 145 in Table 6—2-(3-{[5,7-bis(2-methoxyethoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)-N-(3-fluorophenyl)acetamide An analogous reaction to that described in example 140, but starting with (3-{[5,7-bis(2-methoxyethoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetic acid (222 mg, 0.70 mmol) and 3-fluoroaniline (81 μl, 0.84 mmol) yielded compound 145 in table 6 as a beige solid (108 mg, 30% yield): 1H-NMR (DMSO d6): 8.90 (s, 1H), 7.61 (d, 1H), 7.30-7.38 (m, 2H), 7.32 (s, 1H), 7.05 (s, 1H), 6.88 (t, 1H), 6.85 (s, 1H), 6.82 (s, 1H), 4.53 (t, 2H), 4.32 (t, 2H), 3.85 (t, 2H), 3.81 (s, 2H), 3.73 (t, 2H), 3.42 (s, 3H), 3.33 (s, 3H): MS (+ve ESI): 511.1 (M+H)+. EXAMPLE 146 Preparation of Compound 146 in Table 7—N-(3-fluorophenyl)-3-[(7-{3-[(2-hydroxyethyl)(isobutyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazole-5-carboxamide An analogous reaction to that described in example 7, but starting with 2-(isobutylamino)ethanol (110 mg, 0.94 mmol) and 3-{[7-(3-chloropropoxy)-6-methoxyquinazolin-4-yl]amino)-N-(3-fluorophenyl)-1H-pyrazole-5-carboxamide (120 mg, 0.23 mmol) in the presence of potassium iodide (78 mg, 0.47 mmol) and heating for 3 hours yielded compound 146 in table 7 (96 mg, 73% yield): 1H-NMR (DMSO d6, TFA): 9.04 (s, 1H), 8.34 (s, 1H), 7.81 (m, 1H), 7.74 (s, 1H), 7.62 (m, 1H), 7.43 (m, 2H), 6.96 (m, 1H), 4.34 (s, 2H), 4.04 (s, 3H), 3.84 (t, 2H), 3.38 (m, 2H), 3.32 (m, 2H), 3.11 (m, 2H), 2.36 (m, 2H), 2.16 (m, 1H), 1.04 (d, 6H): MS (+ve ESI): 552.2 (M+H)+. 3-{[7-(3-chloropropoxy)-6-methoxyquinazolin-4-yl]amino}-N-(3-fluorophenyl)-1H-pyrazole-5-carboxamide used as starting material was obtained as follows: a) 3-nitro-1H-pyrazole-5-carboxylic acid (1 g, 6.36 mmol) in dimethylformamide (10 ml) was reacted with 3-fluoroaniline (673 μl, 7 mmol) in the presence of 1-(3-dimethylamino-propyl)-3-ethylcarbodiimide hydrochloride (1.34 g, 7 mmol) and 2-hydroxy-pyridin-1-oxide (778 mg, 7 mmol) at 40° C. for 1.5 hour. The solvent was evaporated, and the residue purified by chromatography on silica gel. Elution with dichloromethane:methanol (99:1) then (97:3) yielded N-(3-fluorophenyl)-3-nitro-1H-pyrazole-5-carboxamide (668 mg, 42% yield): 1H-NMR (DMSO d6): 7.86 (s, 1H), 7.71 (m, 1H), 7.51 (m, 1H), 7.44 (m, 1H), 7.01 (m, 1H). b) N-(3-fluorophenyl)-3-nitro-1H-pyrazole-5-carboxamide (100 mg, 0.4 mmol) in ethyl acetate:ethanol (10:4) was stirred with platinum dioxide (10 mg) under an atmosphere of hydrogen (70 psi) for 3 hours. The catalyst was filtered off and the solvent was evaporated in vacuo to yield 3-amino-N-(3-fluorophenyl)-1H-pyrazole-5-carboxamide (65 mg, 73% yield): 1H-NMR (DMSO d6): 7.76 (m, 1H), 7.60 (s, 1H), 7.33 (m, 1H), 6.86 (s, 1H), 5.71 (s, 1H), 5.22 (s, 2H): MS (+ve ESI): 221.2 (M+H)+. c) 3-Amino-N-(3-fluorophenyl)-1H-pyrazole-5-carboxamide (153 mg, 0.69 mmol) in dimethylacetamide (1.8 ml) and HCl in dioxane (4 M solution in dioxane, 174 μl, 0.69 mmol) was reacted with 4-chloro-7-(3-chloropropoxy)-6-methoxyquinazoline (200 mg, 0.69 mmol) at 90° C. for 1.5 hour. Dichloromethane (35 ml) was added to the cooled reaction mixture, and the solid recovered by filtration, washed with dichloromethane and dried to yield 3-1 [7-(3-chloropropoxy)-6-methoxyquinazolin-4-yl]amino}-N-(3-fluorophenyl)-1H-pyrazole-5-carboxamide (286 mg, 81% yield): 1H-NMR (DMSO d6, TFA): 9.03 (s, 1H), 8.33 (s, 1H), 7.80 (m, 1H), 7.73 (s, 1H), 7.62 (m, 1H), 7.44 (m, 2H), 6.96 (m, 1H), 4.36 (t, 2H), 4.04 (s, 3H), 3.85 (t, 2H), 2.33 (t, 2H): MS (+ve ESI): 471.0 (M+H)+. 4-chloro-7-(3-chloropropoxy)-6-methoxyquinazoline was itself made as follows: d) A mixture of 2-amino-4-benzyloxy-5-methoxybenzamide (10 g, 0.04 mol), (prepared according to J. Med. Chem. 1977, 20, 146-149), and Gold's reagent (7.4 g, 0.05 mol) in dioxane (100 ml) was stirred and heated at reflux for 24 hours. Sodium acetate (3.02 g, 0.037 mol) and acetic acid (1.65 ml, 0.029 mol) were added to the reaction mixture and it was heated for a further 3 hours. The volatiles were removed by evaporation, water was added to the residue, the solid was collected by filtration, washed with water and dried. Recrystallisation from acetic acid yielded. 7-benzyloxy-6-methoxy-3,4-dihydroquinazolin-4-one (8.7 g, 84% yield) as a white solid. e) Chloromethyl pivalate (225 ml, 1.56 mol) was added dropwise to a stirred mixture of 6-methoxy-7-benzyloxyquinazol-4-one (400 g, 1.42 mol) and potassium carbonate (783 g, 5.67 mol) in dimethylacetamide (5500 ml). The reaction was heated to 90° C. for 4 hours. The reaction was cooled and filtered to remove inorganic salts. The filtrate was concentrated in vacuo to yield, crude tert-butyl 2-[7-(benzyloxy)-6-methoxy-4-oxo-3(4H)-quinazolin-4-yl]acetate (562 g, 100% yield): 1H-NMR (DMSO d6): 8.33 (s, 1H), 7.30-7.50 (m, 6H), 7.25 (s, 1H), 5.90 (s, 2H), 5.25 (s, 2H), 3.88 (s, 3H), 1.10 (s, 9H): MS (+ve ESI): 397 (M+H)+. f) 10% palladium on carbon (56 g, 53 mmol) was added to a solution of tert-butyl 2-[7-(benzyloxy)-6-methoxy-4-oxo-3(4H)-quinazolin-4-yl]acetate (562 g, 1.42 mmol) in dimethylacetamide (3500 ml) at ambient temperature and stirred for 3 hours under an atmosphere of hydrogen (1 bar). The reaction was filtered through a pad of celite and the solvent evaporated in vacuo. The residual solid was dissolved in 20% methanol in dichloromethane and passed through a pad of silica gel. Evaporation of the solvent in vacuo followed by trituration with methanol yielded, tert-butyl 2-[7-hydroxy-6-methoxy-4-oxo-3(4H)-quinazolin-4-yl]acetate (188 g, 43% yield): 1H-NMR (DMSO d6): 8.25 (s, 1H), 7.45 (s, 1H), 6.97 (s, 1H), 5.85 (s, 2H), 4.04 (s, 1H), 3.87 (s, 3H), 1.10 (s, 9H): MS (+ve ESI): 307 (M+H)+. g) A mixture of tert-butyl 2-[7-hydroxy-6-methoxy-4-oxo-3(4H)-quinazolin-4-yl]-acetate (100 g, 0.327 mol), 3-bromopropanol (49.3 g, 0.355 mol) and potassium carbonate (133 g, 0.967 mol) in dimethylformamide (500 ml) was stirred at 80° C. for 20 hours. The reaction was cooled and concentrated to quarter volume in vacuo. The residue was poured into ice/water (1500 ml) and the resulting solid collected by suction filtration. Purification by crystallisation from ethanol, yielded crude tert-butyl 2-[7-(3-hydroxypropoxy)-6-methoxy-4-oxo-3(4H)-quinazolin-4-yl]acetate (33.8 g, 41% yield) as a beige solid: 1H-NMR (DMSO d6): 7.95 (s, 1H), 7.43 (s, 1H), 7.10 (s, 1H), 4.16 (t, 2H), 3.86 (m, 5H), 2.08 (t, 2H), 1.12 (s, 9H): MS (+ve ESI): 365 (M+H)+. h) Aqueous sodium hydroxide solution (100 ml, 0.2 mol) was added to a solution of tert-butyl 2-[7-(3-hydroxypropoxy)-6-methoxy-4-oxo-3(4H)-quinazolin-4-yl]acetate (33.8 g, 93 mmol) in methanol (300 ml) and the solution heated to reflux for 1 hour. The methanol was evaporated in vacuo, the residue was acidified with aqueous hydrochloric acid, sodium bicarbonate was added and the solid was collected by suction filtration. Washing with water and drying yielded 7-(3-hydroxypropoxy)-6-methoxy-4-quinazolone (26 g, 95% yield): 1H-NMR (DMSO d6): 7.96 (s, 1H), 7.41 (s, 1H), 7.07 (s, 1H), 4.14 (t, 2H), 3.84 (s, 3H), 3.55 (t, 2H), 1.90 (t, 2H): MS (+ve ESI): 251 (M+H)+. i) 7-(3-hydroxypropoxy)-6-methoxy-4-quinazolone (25 g, 100 mmol) was added slowly to a solution of dimethylforamide (1 ml) in thionyl chloride (250 ml). The mixture was heated to reflux for 4 hours then cooled and the solvents evaporated in vacuo. The residue was dissolved in dichloromethane and washed with aqueous sodium bicarbonate, brine, dried over magnesium sulphate and evaporated. Trituration and collection of the solid by suction filtration yielded, 4-chloro-6-methoxy-7-(3-chloroxypropoxy)quinazoline (19.5 g, 68% yield): as a yellow solid: 1H-NMR (CDCl3): 8.85 (s, 1H), 7.40 (s, 1H), 7.38 (s, 1H), 4.38 (t, 2H), 4.03 (s, 3H), 3.80 (t, 2H), 2.40 (m, 2H): MS (+ve ESI): 287 (M+H)+. EXAMPLE 147 Preparation of Compound 147 in Table 7—N-(2,3-difluorophenyl)-3-[(7-{3-[(2-hydroxyethyl)(isobutyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazole-5-carboxamide An analogous reaction to that described in example 146, but starting with 3-{[7-(3-chloropropoxy)-6-methoxyquinazolin-4-yl]amino}-N-(2,3-difluorophenyl)-1H-pyrazole-5-carboxamide (120 mg, 0.23 mmol) yielded compound 147 in table 7 (59 mg, 45% yield): 1H-NMR (DMSO d6, TFA): 9.03 (s, 1H), 8.32 (s, 1H), 7.69 (s, 1H), 7.50 (m, 1H), 7.41 (s, 1H), 7.30 (m, 3H), 4.33 (m, 2H), 4.03 (s, 3H), 3.82 (m, 2H), 3.40 (m, 2H), 3.31 (m, 2H), 3.13 (m, 2H), 2.33 (m, 2H), 2.15 (m, 1H), 1.03 (d, 6H): MS (+ve ESI): 570.2 (M+H)+. 3-{[7-(3-chloropropoxy)-6-methoxyquinazolin-4-yl]amino}-N-(2,3-difluorophenyl)-1H-pyrazole-5-carboxamide used as starting material was obtained as follows: a) An analogous reaction to that described in 146a, but starting with 2,3-difluoroaniline (212 μl, 2.1 mmol) yielded N-(2,3-difluorophenyl)-3-nitro-1H-pyrazole-5-carboxamide (200 mg, 0.74 mmol) (230 mg, 45% yield): 1H-NMR (DMSO d6): 7.86 (s, 1H), 7.43 (m, 1H), 7.37 (m, 1H), 7.29 (m, 1H). b) An analogous reaction to that described in 146b, but starting with N-(2,3-difluorophenyl)-3-nitro-1H-pyrazole-5-carboxamide (200 mg, 0.74 mmol) yielded 3-amino-N-(2,3-difluorophenyl)-1H-pyrazole-5-carboxamide (161 mg, 91% yield): 1H-NMR (DMSO d6): 9.50 (s, 1H), 7.72 (s, 1H), 7.20 (m, 2H), 5.72 (s, 1H), 5.28 (s, 2H). c) An analogous reaction to that described in 146c, but starting with 3-amino-N-(2,3-difluorophenyl)-1H-pyrazole-5-carboxamide (124 mg, 0.52 mmol) yielded 3-{[7-(3-chloropropoxy)-6-methoxyquinazolin-4-yl]amino}-N-(2,3-difluorophenyl)-1H-pyrazole-5-carboxamide (246 mg, 89% yield): 1H-NMR (DMSO d6, TFA): 9.02 (s, 1H), 8.32 (s, 1H), 7.69 (s, 1H), 7.52 (m, 1H), 7.43 (s, 1H), 7.27 (m, 2H), 4.36 (t, 2H), 4.04 (s, 3H), 3.85 (t, 2H), 2.33 (m, 2H): MS (+ve ESI): 489.0 (M+H)+.

20041117

20080722

20050331

94734.0

TRUONG, TAMTHOM NGO

SUBSTITUTED QUINAZOLINE DERIVATIVES AS INHIBITORS OF AURORA KINASES

UNDISCOUNTED

ACCEPTED

ACCEPTED

Method and device for the production of a trimmed metal strip

The invention relates to a method for production of a metal strip from a strip (6), cast directly from molten metal (4), whereby a trimming of the strip edges (9, 9′) of the strip (6) is carried out, characterised in that the strip edges (9, 9′) are cooled before the trimming in such way as to render said edges more brittle than the rest of the strip (6). The invention further relates to a unit for processing a thin metal strip (6), arising from the casting of thin strips directly from molten metal, characterised in comprising a unit for the controlled, exclusive or preferential cooling of the strip edges (9, 9′) of the strip (6).

1. A process for producing a metal strip from a strip (6) which is cast directly from liquid metal (4) and the strip edges (9, 9′) of which are trimmed, characterized in that the strip edges (9, 9′) are cooled in a controlled way, in order to make them more brittle than the remainder of the strip (6), before being trimmed. 2. The process as claimed in claim 1, characterized in that the metal is steel and the cooling of the strip edges (9, 9′) begins at a temperature of from 950 to 1100° C. 3. The process as claimed in claim 1, characterized in that the strip edges (9, 9′) are trimmed immediately after the controlled cooling thereof. 4. The process as claimed in claim 1, characterized in that the strip edges (9, 9′) are trimmed before the strip (6) is coiled. 5. The process as claimed in claim 1, characterized in that the controlled cooling of the strip edges (9, 9′) is carried out after hot-rolling of the strip (6), which is preceded by reheating of the strip (6) by inductive heating. 6. The process as claimed in claim 1, characterized in that the controlled cooling of the strip edges (9, 9′) is carried out in-line with the casting of the strip (6). 7. An installation for processing a thin metal strip (6) which comes from an installation for casting thin strips directly from liquid metal, and which comprises an installation (15, 15′) for trimming the strip edges (9, 9′), characterized in that an installation for the exclusive or preferential controlled cooling of the strip edges (9, 9′) of the strip (6) precedes an installation (15, 15′) for trimming the strip edges (9, 9′). 8. The installation as claimed in claim 7, characterized in that the installation for the controlled cooling of the strip edges (9, 9′) of the strip (6) is arranged on the same processing line as the casting installation for thin strips. 9. The installation as claimed in claim 7, characterized in that the installation for the controlled cooling of the strip edges (9, 9′) comprises ramps (10, 10′, 10″) with spray nozzles which each direct a jet (11) of a cooling fluid onto one side of a strip edge (9, 9′) of the strip (6). 10. The installation as claimed in claim 9, characterized in that the ramps (10, 10′, 10″) are arranged above and below the strip (6), and in that the spray nozzles direct the jets (11) onto the outer side of the strip (6). 11. The installation as claimed in claim 9, characterized in that the ramps (10, 10′, 10″) are arranged at the sides of the strip (6), in that the spray nozzles direct the jets (11) onto the narrow sides of the strip (6), and in that the installation for the controlled cooling of the strip edges (9, 9′) also comprises barriers (13, 13′) which are in sliding contact with the surface of the strip (6) and each delimit a section (14, 14′) of the width of the strip edges (9, 9′) of the strip (6) which constitutes the area of action of the cooling fluid.

The invention relates to the continuous casting of metals, more specifically the casting of strips of small thickness directly from liquid metal. The continuous casting of metal strips, in particular of strips made from carbon steel or stainless steel, with a thickness of a few mm, preferably thicknesses of less than 10 mm, directly from liquid metal is nowadays well-known in the literature. The casting of a metal strip is generally carried out on an installation for what is known as twin-roll casting. Installations of this type comprise as their main components, which form the permanent mold and in which the strip solidifies, two rolls with substantially horizontal axes which are arranged opposite one another and are driven in rotation in opposite directions about their respective axes. These rolls are strongly cooled on the inside, and their lateral surfaces define a casting mold with moveable walls, at which solidification of the strip in the form of two strand shells commences; these strand shells develop further starting from the roll surfaces. These stand shells converge so as to meet substantially at the “kissing point”, i.e. the zone in which the surfaces of the rolls are closest together, with a distance between them which corresponds to the thickness of the desired strip, in order to form the strip which is drawn continuously out of the casting mold. The casting space is laterally delimited by two refractory walls which are placed against the flat ends of the rolls or are held at a very short distance therefrom, in order to avoid leakage of metal. This process is described in more detail, for example, in document EP-A 0 698 433. It is also conceivable to produce thin metal strips by the liquid metal being applied to the rotating lateral surface of a single cooled casting roll on which the metal solidifies. This makes it possible to obtain a strip with a thickness which is generally less than that produced by casting between two rolls. The strips cast using these processes are generally intended for cold-rolling in order to obtain metal sheets with standard thicknesses. They may previously also be subjected to hot-rolling, which is intended to alter microstructures and close up porosities which may form in the core of the strip as it solidifies. From an economic point of view, it is-particularly advantageous for this hot-rolling to be carried out using a rolling stand which is positioned along the conveying path for the strip which has just been cast. The strips cast in this way generally have to be subjected to strip-edge trimming to a width of approximately 15 mm before they are cold-rolled or also preferably before they are first coiled after casting. This is because these strip edges are formed from strand shell sections which have solidified under different conditions than those which have led to solidification of the more central parts of the strip, in particular on account of the proximity of the lateral closure walls, which have a tendency to cool the metal more quickly than normal. Possible differences between the cooling actions effected by the rolls between their edges and their more central parts may also occur. The cooling may be greater at the edges than in the center and vice versa, depending on the design of the rolls. These differences, which are often difficult to control during the solidification and cooling process between the edges and the remainder of the strip, often cause differences in the mechanical properties of the strip along its width. The metal sheets produced under these conditions may therefore have inhomogeneous properties, which needs to be avoided. The strip edges may also be irregular in shape, which leads to inhomogeneities in the mechanical properties of the metal sheets during the subsequent rolling operations, in particular on account of the local differences in the degree of reduction obtained. On the other hand, if leaks of liquid metal occur between the casting rolls and the lateral closure walls, the strip edges become uneven, and this unevenness needs to be eliminated before the cold-rolling in order not to adversely affect the surface of the roll cylinders. For all these reasons, the strip edges are trimmed at a given time during the processing of the strips, with the aid of trimming shears or any other tool which is conventionally used in installations for processing strips which have been produced by standard processes. In principle, it is advantageous for the strip edges to be trimmed as early as possible, for example before the strip is coiled following its casting. If at this stage the edges are significantly warmer than the remainder of the strip, however, there is a risk of them having mechanical properties which make it more difficult for them to be completely separated from the strip by the shears, in particular if the width of the hot zone does not precisely correspond to the width of the edges which are to be cut. This problem may be exacerbated if hot-rolling of the strip prior to trimming of its edges is performed in one line. This is because this hot-rolling is often preceded by a step of reheating the strip in an induction furnace. During this reheating, the field lines tend to concentrate at the edges of the strips, which leads to temperatures at the edges which are higher than the temperatures prevailing at the remainder of the strip. This homogeneity persists after the hot-rolling and makes subsequent correct trimming of the strip edges difficult. It is an object of the invention to propose a process and a device which allow satisfactory trimming of the strip edges to be carried out even if the strip edges are initially at a higher temperature than desirable. For this purpose, the invention relates to a process for producing a metal strip from a strip which is cast directly from liquid metal and the strip edges of which are trimmed, characterized in that the strip edges are cooled in a controlled way, in order to make them more brittle than the remainder of the strip, before being trimmed. This metal may be steel, and in this case the cooling of the strip edges begins at a temperature of from 950 to 1100° C. The strip edges are preferably cut immediately after the controlled cooling thereof. The strip edges may be trimmed before the strip is coiled. The controlled cooling of the strip edges may be carried out after hot-rolling of the strip, which is itself preceded by reheating of the strip by inductive heating. The controlled cooling of the strip edges is preferably carried out in-line with the casting of the strip. The invention also relates to an installation for processing thin metal strips which come from an installation for casting thin strips directly from liquid metal, characterized in that it comprises an installation for the exclusive or preferential controlled cooling of the strip edges of the strip. This installation for the controlled cooling of the strip edges of the strip may be arranged upstream of an installation for trimming the strip edges. The installation for the controlled cooling of the strip edges of the strip may be arranged on the same processing line as the casting installation for thin strips. The installation for the controlled cooling of the edges may comprise ramps with spray nozzles which each direct a jet of cooling fluid onto one side of a strip edge. The ramps may be arranged above and below the strip, and the spray nozzles direct the jets onto the outer side of the strip. The ramps may be arranged at the sides of the strip, with the spray nozzles directing the jets onto the narrow side of the strip, and the installation for the controlled cooling of the edges also comprises barriers which are in sliding contact with the strip surface and each delimit a section of the width of the strip edges which constitutes the area of action of the cooling fluid. As has been explained, the invention consists in strong cooling of the edges of the strip before they are cut. This cooling is carried out by spraying a fluid onto a width which corresponds to the width of the region to be cut. The invention is made easier to understand by studying the following description, which does not restrict the invention and relates to the following appended figures, in which: FIG. 1 diagrammatically depicts a perspective view (FIG. 1a) of a continuous casting installation for thin strips, which is provided with a device for trimming the strip edges, upstream of which there is an installation for cooling the strip edges (FIG. 1b); FIG. 2 shows a variant of the installation for cooling the strip edges. The example of a casting installation for strips made from metal, in particular from steel, which is illustrated in FIG. 1a, conventionally comprises two casting rolls 1, 1′, which are internally cooled and are driven in rotation in opposite directions about their axes in a horizontal position. Lateral closure walls 2, 2′, which are fitted between the flat end sides 3, 3′ of the rolls 1, 1′, together with the side walls of the rolls 1, 1′, delimit a casting space into which liquid steel is cast continuously by means (not shown) such as for example a refractory pipe which is connected to a tundish. In this way, a strip 6 is solidified and removed in the direction indicated by the arrow 5, with a thickness of generally 1 to 10 mm. In the example illustrated, the strip 6 passes through an induction furnace 7 in a known way; the induction furnace is intended to reheat the strip before it enters a hot-rolling stand 8, which reduces the thickness of the strip 6 by, for example, 10% or more. According to the invention, the strip edges 9, 9′ of the strip 6 are then subjected to strong, controlled cooling, while the remainder of the strip 6 continues to cool naturally or under the effect of a significantly more moderate, controlled cooling. The term “strip edges” 9, 9′ of the strip 6 is to be understood as meaning sections which each extend from one of the lateral boundaries of the strip 6 over a width which may be up to 25 mm and are then cut off or trimmed in a step which precedes the cold-rolling of the strip 6. In the example illustrated, this trimming is carried out immediately after the controlled cooling and prior to coiling of the strip 6. In the example illustrated in FIG. 1, the installation for the controlled cooling is formed by ramps 10, 10′, 10″ which comprise spray nozzles that each direct a jet 11 of a cooling fluid onto the strip 6. This fluid may, in a known way, be water, a water-air mixture, air, liquid nitrogen, etc., provided that it is sprayed on in sufficient quantity to obtain the desired cooling action at the strip edges 9, 9′ of the strip 6. The ramps 10, 10′, 10″ are preferably present above and below each strip edge 9, 9′, in order to cool both sides of each edge. Strictly speaking, to obtain identical cooling on both sides of each strip edge, it should be taken into account that the cooling fluid may run off the top side over the impingement region of the jet 11 which comes from a given spray nozzle, whereas runoff of this type is much more limited on the underside of the strip 6. If precisely symmetrical cooling of the strip edges 9, 9′ is to be achieved on both sides of the strip 6, therefore, this phenomenon has to be compensated for, for example by more cooling fluid being sprayed onto the underside of the strip. This phenomenon is known from conventional continuous casting, and the person skilled in the art can use his standard knowledge and the mathematical models available for cooling of the strip, which he has available to him for the specific case of his casting installation, in order to remedy the problem. In the example illustrated in FIG. 1, the ramps 10, 10′, 10″ spray fluid jets 11 which are directed onto the outside of the strip 6. This means that the fluid does not run off toward the central region of the strip 6, and consequently the cooling of the central region continues naturally. In this way, the action of the cooling is restricted to the strip edges 9, 9′, which are indicated by dashed lines 12, 12′. This restricting of the location of the cooling action can be supplemented by all or part of the central region of the strip 6 which is not to be cooled being covered with one or more caps, this or these cap(s) being held at a short distance from the surface of the strip 6. In the variant illustrated in FIG. 2, the ramps 10, 10′ are arranged at the side rather than above or below the strip 6 and spray their jets 11 of the cooling fluid onto the narrow side of the strip 6. The fluid is prevented from running off toward the central region of the strip by virtue of a barrier 13, 13′ which strictly limits the area of action of the cooling fluid to a section 14, 14′ of the length of the strip edges 9, 9′, being arranged in sliding contact with the surface of the strip. This solution offers the advantage over the solution described above that the surface of the central region continues to remain clear, so that it can be observed more easily. Furthermore, the ramps 10, 10′ are therefore located at a distance from the radiation emanating from the strip 6, and there is therefore no need for complex means for protecting or cooling them in order to prevent them from being adversely affected. Following the installation for cooling the edges which has just been described, the strip passes through an installation for trimming the strip edges, which is formed by circular saws 15, 15′ and preferably by circular blade shears, although it is, of course, possible to use any known device which is able to ensure this function at the outgoing strip 6. Devices of this type are generally known and are used in particular in rolling mill trains. Then, the strip 6 is wound up to form a coil 16 about a rotating coiler drum 17. The wound coil can then be conveyed to the installation which is responsible for further treatment of the strip 6, for example cold-rolling, annealing and pickling which precedes cold rolling, etc. The accelerated cooling of the strip edges 9, 9, is intended to provide the strip edges with a metallurgical structure which represents a significant change compared to the structure of the remainder of the strip 6, this change being toward greater cohesion of the metal. The installation for trimming the strip edges requires a higher level of outlay for cutting to be carried out at this level than if the mechanical properties of the strip 6 were to be substantially homogeneous over its entire width. However, this increased outlay leads to a cleaner cut which does not require any subsequent deburring. The installation according to the invention for cooling the strip edges of a thin strip which has been produced by continuous casting is not necessarily arranged in-line with the casting installation. It may be arranged at any location in the production line at which the temperature of the strip is greater than 950° C., so that the desired metallurgical action for this cooling is obtained. Moreover, it is not always necessary for the installation 15, 15′ for cutting the strip edges 9, 9′ to immediately follow the cooling installation in accordance with the invention, except if this cooling would be ineffective as a result of there being a risk of the strip edges 9, 9′ fracturing spontaneously during processing of the strip 6 before the strip edges 9, 9′ are cut off. An uncontrollable, spontaneous fracture may cause danger to the operating staff and equipment if it occurs at a location which is not intended to receive the cut strip edges 9, 9′. A further advantage of the cooling and cutting directly following one another is that the strip edges 9, 9′ therefore do not have time to heat up again under the action of the heat emanating from the remainder of the strip 6. Renewed heating of this nature could return the edges 9, 9′ to a metallurgical structure and mechanical properties which are closer to those of the remainder of the strip 6, which would reduce the effect of the cooling of the edges and also the cut quality. As a variant, the step of cooling the strip edges 9, 9′ may coincide with a step of controlled cooling of the entire strip 6 for metallurgical reasons. In this case, during this step significantly greater cooling is to be performed at the strip edges 9, 9′ than at the remainder of the strip 6 in order for the invention to be deployed. Therefore, this variant no longer represents exclusive cooling, but rather just preferential cooling of the strip edges 9, 9′. The situation which has just been described arises in the case of a strip 6 which is cast between rolls, but it will be understood that the invention can also be employed if the thin strip 6 has been cast by means of a different process. The process according to the invention can also be applied to metals other than steel, provided that they are able to be cast directly to form a thin strip, such as for example aluminum, copper and alloys thereof.

20040924

20080506

20050526

71818.0

TAOUSAKIS, ALEXANDER P

METHOD AND DEVICE FOR THE PRODUCTION OF A TRIMMED METAL STRIP

UNDISCOUNTED

ACCEPTED

ACCEPTED

Method for continuously filtering raw brine for use in chlor-alkali electrolysis

Disclosed is a method for continuously filtering raw brine (A) for use in chlor-alkali electrolysis by means of an all-automatic, backwashing pressure filter (5). In a first step, raw brine (A) is separated into a partial flux with a low solids content as clear brine (B) and a partial flux (C) with a high solids content via a decanter (1). In a second step, one portion of the partial flux (C) of the clear brine (B), which has a high solids content, is added to the pressure filter (5) as an auxiliary filtering means.

1. Method for continuously filtering raw brine (A) for use in chlor-alkali electrolysis, by means of a backwashing pressure filter (5), characterised in that in a first stage, the raw brine (A) is separated into a partial flux with a low solids content as clear brine (B) and a partial flux (C) with a high solids content via a decanter (1), and in a second stage, some of the partial flux (C) of the clear brine (B), which has a high solids content, is added to the pressure filter (5) as an auxiliary filtering means. 2. Method according to claim 1, characterised in that the dosage of the partial flux (C) with a high solids content is added directly to the clear brine (B) in a controlled manner. 3. Method according to claim 1, characterised in that a backwashing pressure filter (5) is used as a pressure filter.

The invention relates to a method for continuously filtering raw brine for use in chlor-alkali electrolysis by means of a backwashing pressure filter. During conversion to membrane cell technology in chlor-alkali electrolysis the demands on the brine qualities have increased considerably. In order to protect downstream plant components and electrolysis cells, inter alia solid, suspended impurities have to be removed down to a very low level. This solid/liquid separating task is frequently carried out nowadays by multi-stage and correspondingly expensive separating methods, high demands being placed on the reliability primarily in the last separating stage. Owing to the high investment and operating costs for such plant, alternative concepts which allow method simplification are becoming increasingly important. In addition, the fact plays a part that many installations are conversion operations replacing available obsolete electrolyses by the more efficient and environmentally friendly membrane plant. In these cases an extensive use of available separating apparatus is aimed for. The local conditions, such as infrastructure, space limitations; etc. also have to be considered here. The shutdown or disassembly of available separating apparatus (primarily large-volume thickeners) is often also not desirable at all or is-connected with very high expenditure. Raw brine contains insoluble suspended solids originating from dissolving basins or precipitation reactions. Typical components of raw brine are barium sulphate, calcium sulphate, calcium carbonate, metal hydroxides and gangue. The concentration and composition of the impurities depends primarily on the salt source and can vary sharply depending on location. Typical concentrations for brines made of rock salt of European origin are in the region of 300 to 1,500 ppm suspended solids. Owing to the decanting primarily fine particles or small agglomerates arrive in the overflow while primarily larger particles or agglomerates are to be found in the underflow. For this reason the direct filtration of the overflow is difficult on backwashing pressure filters or is sometimes even impossible. The fine particles quickly tend to form a thin and impermeable layer on the filter medium. An immediate increase in pressure and low filtration rates result. In addition it is difficult to remove the particle layer and this leads to a sharply limited backwashing capacity (capacity to regenerate) of the filter medium. A method for purifying a backwashing pressure filter is known from U.S. Pat. No. 4,443,346 of the type which is suitable, for example, for use in the method according to the invention. U.S. Pat. No. 3,497,452 describes a method using auxiliary filtering means, some of the filtrate being reprocessed for further filtration, in the removal of solids from solvents in the chemical industry. Although the formation and removal of a filter cake is described in known methods, it is not described how or in what form the auxiliary filtering means is used. As is known, substances extraneous to the process of mineral (for example perlite, diatomite) or organic (for example cellulose) origin are added as auxiliary filtering means in suspended form to the prefilt prior to the filter. The drawback is that in known applications new auxiliary filtering means have to be added and accumulate as an additional residue during disposal. It is the object of the invention to provide an improved method for filtering brines in chlor-alkali chemistry, a stream of material accumulating during the process itself being used as the filtering aid. It is the object of the invention to provide an improved fully-automatic method for filtering brine that is suitable for chlor-alkali electrolysis. This object is achieved according to the invention in that, in a first stage, the raw brine is separated into a partial flux with a low solids content as clear brine and a partial flux with a high solids content via a decanter, and in a second stage, some of the partial flux of the clear brine, which has a high solids content, is added to the pressure filter as an auxiliary filtering means. During filtration, the coarser particles of the partial flux with a high solids content forms a porous and highly permeable filter cake. Problematical fine particles are intercalated and reliably retained. The coarse grain of the partial flux with a high solid content is thus assigned the function of an auxiliary filtering means. This results in a slow pressure increase and high filtration rates. The particle layer reaches a thickness of about 1 to 2 mm and can be easily removed and this leads to a good backwashing capacity (capacity to regenerate) of the filter medium. High solids retention is ensured by the use of suitable, fine-pore filter media. The dosage of the partial flux with a high solids content is a substantially freely selectable parameter and increases the flexibility of the filtration with respect to variations in the solids composition. Because the clear brine to be filtered has a partial flux of the decanter underflow added prior to entry into the pressure filter, there is a displacement of the particle size distribution into the coarser range. The displacement of the particle size distribution in cooperation with backwashing pressure filters offers substantial technical and economical advantages: Increase in the filtration output, i.e. saving in filter area Improved separation of the solids from the filter medium Reduced risk of clogging of the filter medium Insensitivity to varying solids composition Increased flexibility and reliability of the filtration stage. The method is to be described in more detail with the aid of a diagrammatic view as the single FIG. 1. In FIG. 1 a container with raw brine A to be purified is designated by the reference numeral 1. The container 1 is connected via a line containing a clear brine B as overflow and connected to a second container 2. Leading from a lower part of the container 1 is the line containing slurry C with a high solids content leading partially to a disposal site, not shown. The other part of the slurry with a high solids content leads to a metering pump 3. The lower part of the container 2 is connected to a pump 4 via a line. The pressure line of the pump 4 contains a mixed brine D and leads to a backwashing pressure filter 5 with a line E for the pure brine and a line F for the elutriation. During operation the raw brine A is initially subjected in the container 1 to a preliminary clarification, thickeners, so-called static decanters, generally being used. Owing to the large buffer. volume (frequently several thousand cubic metres) and the long dwell time resulting therefrom, these decanters contribute to the operating safety of electrolysis plant. To improve the sedimentation properties of the solids a flocculation aid (for example polyelectrolyte) is generally added to the raw brine. The raw brine A is separated in the container 1 into a raw brine B with a low solids content and an underflow C with a high solids content. The clear brine B typically also contains solids in the range of 30 to 100 ppm. Some of the underflow C with a high solids content is added to the clear brine B and thus generates a mixed brine D which is fed to the filter 5 via the pump 4. The addition of the underflow may take place at various points, either on the suction or pressure side of the pump 4 or also into the container 2 if a mixing device is available. The pressure filter 5 generates a virtually solid-free filtrate E, the required discharge values generally being fallen below without further post-treatment (0.5 to 1 ppm). The retained solids are intermittently discharged as thickened slurry F and fed together with the underflow of the thickener, for example to a downstream dehydration process. The invention will now be described in more detail with the aid of an embodiment and a comparison example. In both cases treatment of 100 m3/h raw brine with a solids content of 1,000 ppm is assumed. Embodiment 1 Brine flux Raw brine Clear brine Thick slurry Mixed brine Pure brine Elutriation Designation A B C D E F Concentration (ppm) 1000 50 150000 250 0.5 150000 Ratio of the solids concentration (flux D/B) 5 Specific filter output pressure (l/m2 × h) 1000 filter 5 Required filter area pressure (m2) 100 filter 5 Result: After the start of operation with feeding, a permanent increase in the filtration output by the factor 5 to 6 could be found. The decanter underflow was added in the process in different ratios. Stable and reliable operations could be observed at ratios of 5 to 10:1, based on the solids loading, i.e. the solids concentration in the inlet D to the filter 5 was 5 to 10 times higher than that of the clear brine B. The filtrate quality was clearly below 1 ppm, a value of 0.5 ppm was mainly achieved. COMPARISON EXAMPLE (Without Feeding of Decanter Underflow) Brine flux Raw brine Clear brine Thick slurry Mixed brine Pure brine Elutriation Designation A B C — E F Concentration (ppm) 1000 50 150000 — 0.5 150000 Ratio of the solids concentration (flux D/B) — Specific filter output pressure (l/m2 × h) 200 filter 5 Required filter area pressure (m2) 500 filter 5 Result: It has been found that owing to the low output, filtration is impossible from the point of view of economy. A clear tendency to clog was also established, which was shown by continuously decreasing filtration output.

20040622

20060718

20050224

66563.0

POPOVICS, ROBERT J

METHOD FOR CONTINUOUSLY FILTERING RAW BRINE FOR USE IN CHLOR-ALKALI ELECTROLYSIS

SMALL

ACCEPTED

ACCEPTED

Brush seal

A brush seal assembly is provided for sealing components which move relative to one another. One of the components includes a recess or groove for accommodating a clamping sleeve which supports bristles. A support plate which is formed separately from the component and the clamping sleeve is pressed into the recess and abuts the recess wall surfaces and the clamping sleeve to hold the same in a predetermined working position.

1. A brush seal for sealing components which move relative to one another, having a sealing part, of which the bristles, which are held by a bristle backing with their free ends aligned with the sealing surface, are held in their predetermined working position by a support plate, wherein the support plate is designed as an independent clamping member for the sealing part, which support plate is held by being pressed into a recess, of a component which bears the brush seal (11), which recess includes a bearing surface (21) for the support plate. 2. The brush seal as claimed in claim 1, wherein the support plate has a knurling which extends into a region of the recess and of which one knurling section which faces an undercut in the recess engages into the undercut, whereas an opposite knurling section bears against a bristle backing clamping sleeve of the sealing part so as to clamp it in a form and force locking manner in the recess. 3. The brush seal as claimed in claim 1, wherein the support plate, which has a bearing surface which corresponds with the bearing surface of the recess and acts as a clamping member, has projections which project into a region of the recess, are bent off alternately in a wavy manner and on the one hand engage in an undercut surface of the recess and on the other hand bear against a bristle backing clamping sleeve in such a manner as to clamp it in a form and force locking manner in the recess. 4. The brush seal as claimed in claim 1, wherein the support plate, which bears against the bearing surface of the recess and serves as a clamping member, has a collar, which partially surrounds the bristle backing, and projects into the recess in the component and engages in an undercut (43) of the recess (groove 20), in such a manner as to surround the bristle backing by means of a flanged edge (41), located opposite the bearing surface (21), such that the bristle backing is held in a form and force locking manner in the recess. 5. A brush seal according to claim 1, wherein the support plate has a collar which engages in a recess, that includes two undercuts located opposite one another, in the component bearing the sealing part and partially surrounds the bristle backing and whose base surface, remote from the bristle ends, is provided with a central bead which can be permanently deformed by the sealing part being pressed into the recess, in such a manner that the collar (50) moves onto the walls of the recess in order to hold the sealing part in a form and force locking manner. 6. The brush seal as claimed in claim 5, wherein the recess is designed as a groove with a dovetail-like cross section, the opposite walls of which form the undercuts. 7. A brush seal assembly comprising: a component having a recess, sealing bristles, a clamping sleeve operatively clamping the sealing bristles, and a support plate separate from the component and clamping sleeve, said support plate being configured to be pressable into the recess to clamp the clamping sleeve in the recess and thereby clamp the sealing bristles in a predetermined desired working position. 8. A brush seal assembly according to claim 7, wherein the support plate is configured as a replaceable part which is press fit in said recess when in an in-use position and which is removable and replaceable to accommodate replacement of a respective clamping sleeve and sealing bristles clamped thereby. 9. A brush seal assembly according to claim 7, wherein the support plate has knurled surface sections which engage at least one of the clamping sleeve and a bearing surface of the recess when in an in-use position clamping the clamping sleeve. 10. A brush seal assembly according to claim 9, wherein said knurled surface sections are located to engage the bearing surface. 11. A brush seal assembly according to claim 9, wherein said knurled surface sections are located to engage the clamping sleeve. 12. A brush seal assembly according to claim 9, wherein said knurled surface sections are located to engage both the bearing surface and the clamping sleeve. 13. A brush seal assembly according to claim 7, wherein said support plate is configured to partially surround the clamping sleeve when in an in-use position clamping the clamping sleeve. 14. A brush seal assembly according to claim 14, wherein the recess has a dove-tail shape, and wherein the support plate is plastically deformable to engage sloped surfaces of the dove-tail shape when in said in-use position. 15. A method of holding a brush seal clamping sleeve in a recess of a component, comprising: placing the clamping seal in said recess and press fitting a support plate between bearing surface sections of the recess and the clamping sleeve to thereby clamp the clamping sleeve in the recess to the component. 16. A method according to claim 15, wherein the support plate is configured as a replaceable part which is press fit in said recess when in an in-use position and which is removable and replaceable to accommodate replacement of a respective clamping sleeve and sealing bristles clamped thereby. 17. A method according to claim 15, wherein the support plate has knurled surface sections which engage at least one of the clamping sleeve and a bearing surface of the recess when in an in-use position clamping the clamping sleeve. 18. A method according to claim 17, wherein said knurled surface sections are located to engage both the bearing surface and the clamping sleeve. 19. A method according to claim 15, wherein said support plate is configured to partially surround the clamping sleeve when in an in-use position clamping the clamping sleeve. 20. A method according to claim 19, wherein said support plate is configured to partially surround the clamping sleeve when in an in-use position clamping the clamping sleeve. 21. A method of making a brush seal assembly comprising: providing a component having a recess, providing sealing bristles, providing a clamping sleeve operatively clamping the sealing bristles, and pressing a support plate which is separate from the component and clamping sleeve into the recess to clamp the clamping sleeve in the recess and thereby clamp the sealing bristles in a predetermined desired working position. 22. A method according to claim 21, wherein the support plate is configured as a replaceable part which is press fit in said recess when in an in-use position and which is removable and replaceable to accommodate replacement of a respective clamping sleeve and sealing bristles clamped thereby. 23. A method according to claim 21, wherein the support plate has knurled surface sections which engage at least one of the clamping sleeve and a bearing surface of the recess when in an in-use position clamping the clamping sleeve. 24. A method according to claim 23, wherein said knurled surface sections are located to engage both the bearing surface and the clamping sleeve. 25. A method according to claim 23, wherein said support plate is configured to partially surround the clamping sleeve when in an in-use position clamping the clamping sleeve. 26. A method according to claim 25, wherein the recess has a dove-tail shape, and wherein the support plate is plastically deformable to engage sloped surfaces of the dove-tail shape when in said in-use position.

BACKGROUND AND SUMMARY OF THE INVENTION The invention relates to a brush seal for sealing components which move relative to one another, having a sealing part, of which the bristles, which are held by a bristle backing with their free ends aligned with the sealing surface, are held in their predetermined working position by a support plate. In known brush seals of this type, the sealing part which bears the bristles is clamped in a rotationally symmetrical bristle housing, which includes a cover plate and a support plate, in such a manner that the free ends of the bristles are directed radially inward onto the surface which is to be sealed off; cf. DE 100 18 273 A1. Brush seals of this type, which are used to seal off a rotor with respect to a stator and the cover and support plates of which are welded together or connected to one another by other joining processes (e.g. flanging), and which, moreover, have to have positioning means on the bristle housing, so as to prevent incorrect installation and twisting of the brush seal, with assigned corresponding positioning means on a bearing surface of the component which bears the brush seal, are of complex structure and are only suitable for sealing off rotationally symmetrical bodies. The invention is based on the object of widening the application area for brush seals of this type, simplifying their structure and developing them further in such a manner that they are suitable for sealing any desired sealing surfaces, i.e. including three-dimensionally curved sealing surfaces. Working on the basis of a brush seal of the type described in the introduction, this object is achieved, according to the invention, by the fact that the support plate is designed as an independent clamping member for the sealing part, which is held by being pressed into a recess of a component which bears the brush seal, which recess includes a bearing surface for the support plate. The design in accordance with the invention comprises only a sealing part and the support plate, which holds the bristles of the sealing part in their predetermined working position. The support plate is designed as a clamping part for the sealing part and can be pressed into recesses of any desired curvature, in the form of grooves in the component which bears the brush seal, so as to form a form and force locking securing means for the sealing part. There is therefore no need to construct the welded or flanged bristle housing which has hitherto been customary and to form special positioning means. Should the sealing part need to be replaced, the support plate can be removed from the groove. To insert a new sealing part, a new support plate is required, since the previous support plate becomes unusable when it is removed from the groove. This amazingly simple design of the parts of the brush seal, which are held by being pressed into place, results in simple and inexpensive assembly and dismantling even for complicated applications which encompass sealing surfaces of any desired curvature, which has not been possible with the brush seals which have been disclosed hitherto. According to a preferred exemplary embodiment of the invention, the clamping member, which is designed as a support plate, has a knurling, which extends into the region of the recess and clamps the bristle backing of the sealing element in the recess, and also a bearing surface which corresponds with the bearing surface of the recess. According to a further feature of the invention, the clamping member, which serves as a support plate, has a bearing surface, which corresponds with the bearing surface of the recess, and alternating wavy projections which extend into the region of the recess and on the one hand engage in an undercut surface of the recess and on the other hand bear against the bristle backing of the sealing member. According to the invention, the clamping member, which serves as a support plate, may also have a collar, which partially surrounds the bristle backing of the sealing member, projects into the recess in the component which bears the brush seal and is assigned an undercut, located opposite the bearing surface, in the recess, while the bristle backing of the sealing element is at least partially surrounded by means of a flange lip of the collar. Finally, according to a preferred embodiment of the invention, the collar of the support plate which is to be pressed into the recess is provided, at the base surface remote from the bristle ends, with a central bead, which can be permanently deformed by the sealing part being pressed into the recess, in such a manner that the collar comes to bear against the walls of the recess, which is preferably designed as a groove with a dovetail-like cross section. The invention is described below on the basis of four exemplary embodiments illustrated in the drawing, in which, in detail: BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 shows a cross-sectional view through a first exemplary embodiment of a brush seal in accordance with the invention, FIG. 2 shows a cross-sectional view through a second exemplary embodiment of a brush seal in accordance with the invention, FIG. 3 shows a cross-sectional view through a third exemplary embodiment of a brush seal in accordance with the invention, FIG. 4 shows a cross-sectional view through a fourth embodiment of a brush seal in accordance with the invention before it is pressed into the recess which holds it, and FIG. 5 shows the exemplary embodiment shown in FIG. 4 after it has been pressed into the recess. DETAILED DESCRIPTION OF THE DRAWINGS The foregoing disclosure has been set forth merely to illustrate the invention and is not intended to be limiting. Since modifications of the disclosed embodiments incorporating the spirit and substance of the invention may occur to persons skilled in the art, the invention should be construed to include everything within the scope of the appended claims and equivalents thereof. All that is shown in FIG. 1 of the components which move relative to one another and are to be sealed with respect to one another by means of the brush seal to be described below is part of the component 10 which accommodates the brush seal, denoted overall by reference numeral 11. The brush seal comprises a sealing part 12, which is formed by bristles 16, which are wrapped around a core wire 14 and are held in an aligned position by a clamping sleeve 15 which supports the free bristle ends 17 and a support plate 18. All these components together are fixed in a groove 20 in the component 10 by being pressed in and are held in a form and force locking manner. The core wire 14 and the clamping sleeve 15 form what is known as the bristle backing of the sealing part 12. The sealing part may also be produced by clamping, welding, soldering or adhesive bonding as alternatives to the clamped version shown by reference numeral 12. The groove 20, which has a bearing surface 21 and an undercut 22, has a profile which corresponds to the sealing surface (not shown) and determines a defined, unambiguous positioning of the sealing part with respect to the component to be sealed (not shown), which its bristle ends face. To produce a form and force locking connection of sealing part and support plate in the groove, the support plate 18, which is supported against the bearing surface 21, has, at its end projecting into the groove 20, knurlings 25 and 26 which are oriented longitudinally on both sides, with the knurling 25 engaging into the undercut 22 of the groove 20 and, in the position illustrated, the knurling 26 clamping against the clamping sleeve 15 of the sealing part 12. After the bristle backing of the sealing part and the support plate have been pressed into the groove—as illustrated in FIG. 1—the sealing part 12 is fixedly connected in a form and force locking manner to the component 10 and the free ends 17 of the bristles 16 are held supported in a predetermined position corresponding to the required sealing action. The groove 20 in the component 10 therefore forms a bristle housing. The further exemplary embodiment illustrated in FIG. 2 likewise shows only a part of the component 10 which includes the groove 20 and accommodates the brush seal, which is denoted overall by reference numeral 11. In this case too, the brush seal comprises the sealing part 12 and a support plate 28, which after they have been pressed into the groove 20 form a form and force locking, fixed connection to the component 10. For this purpose, that end of the support plate 28, supported against the bearing surface 21 of the groove 20, which projects into the groove 20 has alternating projections 31 and 32 which are bent off so as to form a wave-like structure and of which the projections 31 facing away from the sealing part engage in an undercut 29 of the groove 20, whereas the projections 32 engage on the clamping sleeve 15, i.e. on the bristle backing of the sealing part 12, so as to partially surround it. In the exemplary embodiment of a brush seal illustrated in FIG. 3, there is once again a sealing part 12, which is constructed in the same way as has been described for the exemplary embodiment illustrated in FIG. 1. In this case once again, therefore, the brush seal is held in a form and force locking manner in a groove 20 in a component 10 bearing the brush seal 11 by being pressed in. This purpose is once again served by a support plate 38, which supports the bristles 16, bears flat against the bearing surface 21 of the groove 20 and, in its region which projects into the groove 20, has a collar 40 which, by means of a flanged edge 41, partially surrounds the clamping sleeve 15 of the bristle backing. In the pressed-in position illustrated in FIG. 3, the collar 40 engages in an associated undercut 43 of the groove 20, so that in this embodiment too the sealing element is held in a form and force locking manner in the groove 20 by means of the support plate 38. The preferred exemplary embodiment shown in FIGS. 4 and 5 likewise has a sealing part 12, which is constructed in the same way as has been described for the exemplary embodiment illustrated in FIG. 1. However, the recess in the component 10 which accommodates the sealing part is now designed in the form of a groove 23 with a dovetail-like cross section, i.e.—compared to the previous exemplary embodiments—has two opposite undercuts 44 and 45 which correspond to one another in mirror-image fashion. The support plate, which is denoted by reference numeral 48, likewise has a collar 50, which faces the groove 23, partially surrounds the bristle backing, i.e. core wire 14 and clamping sleeve 15, and the base surface of which, remote from the bristle end 17, bears a central bead 51; cf. FIG. 4. When the support plate and sealing part are pressed into the groove 23 in the direction indicated by arrows 52, 53, the bead 51 is permanently deformed in such a manner that the collar 50 comes to bear against the walls 44, 45 of the groove 23 so as to form the form and force locking connection, as shown in FIG. 5. The long limb of the support plate 48 adopts the position illustrated in FIG. 5, and the support plate thereby holds the bristles 16 in a predetermined position corresponding to the required sealing action. The sheet-metal thickness of the support plate 48 serving as a clamping member is preferably 0.5 mm. A common feature of all the exemplary embodiments described above is that the sealing part is held, by means of a suitably shaped support plate, in the groove, which serves as a bristle housing and follows any desired three-dimensionally curved sealing surface, in the component bearing the brush seal in a form and force locking manner by being pressed in during assembly, and that the seal is only formed as a result of the sealing part and the support plate being inserted.

<SOH> BACKGROUND AND SUMMARY OF THE INVENTION <EOH>The invention relates to a brush seal for sealing components which move relative to one another, having a sealing part, of which the bristles, which are held by a bristle backing with their free ends aligned with the sealing surface, are held in their predetermined working position by a support plate. In known brush seals of this type, the sealing part which bears the bristles is clamped in a rotationally symmetrical bristle housing, which includes a cover plate and a support plate, in such a manner that the free ends of the bristles are directed radially inward onto the surface which is to be sealed off; cf. DE 100 18 273 A1. Brush seals of this type, which are used to seal off a rotor with respect to a stator and the cover and support plates of which are welded together or connected to one another by other joining processes (e.g. flanging), and which, moreover, have to have positioning means on the bristle housing, so as to prevent incorrect installation and twisting of the brush seal, with assigned corresponding positioning means on a bearing surface of the component which bears the brush seal, are of complex structure and are only suitable for sealing off rotationally symmetrical bodies. The invention is based on the object of widening the application area for brush seals of this type, simplifying their structure and developing them further in such a manner that they are suitable for sealing any desired sealing surfaces, i.e. including three-dimensionally curved sealing surfaces. Working on the basis of a brush seal of the type described in the introduction, this object is achieved, according to the invention, by the fact that the support plate is designed as an independent clamping member for the sealing part, which is held by being pressed into a recess of a component which bears the brush seal, which recess includes a bearing surface for the support plate. The design in accordance with the invention comprises only a sealing part and the support plate, which holds the bristles of the sealing part in their predetermined working position. The support plate is designed as a clamping part for the sealing part and can be pressed into recesses of any desired curvature, in the form of grooves in the component which bears the brush seal, so as to form a form and force locking securing means for the sealing part. There is therefore no need to construct the welded or flanged bristle housing which has hitherto been customary and to form special positioning means. Should the sealing part need to be replaced, the support plate can be removed from the groove. To insert a new sealing part, a new support plate is required, since the previous support plate becomes unusable when it is removed from the groove. This amazingly simple design of the parts of the brush seal, which are held by being pressed into place, results in simple and inexpensive assembly and dismantling even for complicated applications which encompass sealing surfaces of any desired curvature, which has not been possible with the brush seals which have been disclosed hitherto. According to a preferred exemplary embodiment of the invention, the clamping member, which is designed as a support plate, has a knurling, which extends into the region of the recess and clamps the bristle backing of the sealing element in the recess, and also a bearing surface which corresponds with the bearing surface of the recess. According to a further feature of the invention, the clamping member, which serves as a support plate, has a bearing surface, which corresponds with the bearing surface of the recess, and alternating wavy projections which extend into the region of the recess and on the one hand engage in an undercut surface of the recess and on the other hand bear against the bristle backing of the sealing member. According to the invention, the clamping member, which serves as a support plate, may also have a collar, which partially surrounds the bristle backing of the sealing member, projects into the recess in the component which bears the brush seal and is assigned an undercut, located opposite the bearing surface, in the recess, while the bristle backing of the sealing element is at least partially surrounded by means of a flange lip of the collar. Finally, according to a preferred embodiment of the invention, the collar of the support plate which is to be pressed into the recess is provided, at the base surface remote from the bristle ends, with a central bead, which can be permanently deformed by the sealing part being pressed into the recess, in such a manner that the collar comes to bear against the walls of the recess, which is preferably designed as a groove with a dovetail-like cross section. The invention is described below on the basis of four exemplary embodiments illustrated in the drawing, in which, in detail:

<SOH> BACKGROUND AND SUMMARY OF THE INVENTION <EOH>The invention relates to a brush seal for sealing components which move relative to one another, having a sealing part, of which the bristles, which are held by a bristle backing with their free ends aligned with the sealing surface, are held in their predetermined working position by a support plate. In known brush seals of this type, the sealing part which bears the bristles is clamped in a rotationally symmetrical bristle housing, which includes a cover plate and a support plate, in such a manner that the free ends of the bristles are directed radially inward onto the surface which is to be sealed off; cf. DE 100 18 273 A1. Brush seals of this type, which are used to seal off a rotor with respect to a stator and the cover and support plates of which are welded together or connected to one another by other joining processes (e.g. flanging), and which, moreover, have to have positioning means on the bristle housing, so as to prevent incorrect installation and twisting of the brush seal, with assigned corresponding positioning means on a bearing surface of the component which bears the brush seal, are of complex structure and are only suitable for sealing off rotationally symmetrical bodies. The invention is based on the object of widening the application area for brush seals of this type, simplifying their structure and developing them further in such a manner that they are suitable for sealing any desired sealing surfaces, i.e. including three-dimensionally curved sealing surfaces. Working on the basis of a brush seal of the type described in the introduction, this object is achieved, according to the invention, by the fact that the support plate is designed as an independent clamping member for the sealing part, which is held by being pressed into a recess of a component which bears the brush seal, which recess includes a bearing surface for the support plate. The design in accordance with the invention comprises only a sealing part and the support plate, which holds the bristles of the sealing part in their predetermined working position. The support plate is designed as a clamping part for the sealing part and can be pressed into recesses of any desired curvature, in the form of grooves in the component which bears the brush seal, so as to form a form and force locking securing means for the sealing part. There is therefore no need to construct the welded or flanged bristle housing which has hitherto been customary and to form special positioning means. Should the sealing part need to be replaced, the support plate can be removed from the groove. To insert a new sealing part, a new support plate is required, since the previous support plate becomes unusable when it is removed from the groove. This amazingly simple design of the parts of the brush seal, which are held by being pressed into place, results in simple and inexpensive assembly and dismantling even for complicated applications which encompass sealing surfaces of any desired curvature, which has not been possible with the brush seals which have been disclosed hitherto. According to a preferred exemplary embodiment of the invention, the clamping member, which is designed as a support plate, has a knurling, which extends into the region of the recess and clamps the bristle backing of the sealing element in the recess, and also a bearing surface which corresponds with the bearing surface of the recess. According to a further feature of the invention, the clamping member, which serves as a support plate, has a bearing surface, which corresponds with the bearing surface of the recess, and alternating wavy projections which extend into the region of the recess and on the one hand engage in an undercut surface of the recess and on the other hand bear against the bristle backing of the sealing member. According to the invention, the clamping member, which serves as a support plate, may also have a collar, which partially surrounds the bristle backing of the sealing member, projects into the recess in the component which bears the brush seal and is assigned an undercut, located opposite the bearing surface, in the recess, while the bristle backing of the sealing element is at least partially surrounded by means of a flange lip of the collar. Finally, according to a preferred embodiment of the invention, the collar of the support plate which is to be pressed into the recess is provided, at the base surface remote from the bristle ends, with a central bead, which can be permanently deformed by the sealing part being pressed into the recess, in such a manner that the collar comes to bear against the walls of the recess, which is preferably designed as a groove with a dovetail-like cross section. The invention is described below on the basis of four exemplary embodiments illustrated in the drawing, in which, in detail:

20050207

20070123

20050602

67635.0

LEE, GILBERT Y

BRUSH SEAL AND METHOD OF USING AND MAKING SAME

UNDISCOUNTED

ACCEPTED

ACCEPTED

Gastric ring for treatment of obesity

This gastric ring comprises a band which is able to surround the wall of the stomach, and means with which it is possible, after implantation, to modify the cross section of the opening delimited by the ring. According to the invention, the band comprises at least one zone made of a material which is elastically deformable in the longitudinal direction of this band; said zone has at least two bearing points formed on it at two locations separated in the longitudinal direction of the band, and the ring comprises at least one rigid element made of a bioabsorbable material and bearing against said zone in the area of said bearing points, this rigid element, before absorption, making it possible to maintain said bearing points at a distance from one another different than the distance separating these two bearing points in the absence of elastic deformation of said zone of the bands, and, after absorption, no longer forming an obstacle to the return of said zone of the band to its nondeformed state.

1. A gastric ring for treatment of obesity, comprising: a band which is able to surround the wall of the stomach; means for maintaining the band in the form of a ring able to surround the stomach, and means with which it is possible, after implantation, to modify the cross section of the opening delimited by the ring; said gastric ring being characterized in that: the band comprises at least one zone made of a material which is elastically deformable in the longitudinal direction of this band; said zone has at least two bearing points formed on it at two locations separated in the longitudinal direction of the band, and the ring comprises at least one rigid element made of a bioabsorbable or biodegradable material and bearing against said zone in the area of said bearing points, this rigid element, before absorption, making it possible to maintain said bearing points at a distance from one another different than the distance separating these two bearing points in the absence of elastic deformation of said zone of the band, and, after absorption, no longer forming an obstacle to the return of said zone of the band to its nondeformed state. 2. The gastric ring as claimed in claim 1, characterized in that each element made of bioabsorbable material is designed in such a way as to maintain the zone of the band, along which it extends, in a stretched state. 3. The gastric ring as claimed in claim 1, characterized in that each element made of bioabsorbable material is designed in such a way as to maintain the zone of the band, along which it extends, in a contracted state. 4. The gastric ring as claimed claim 1, characterized in that the band forms, at one end, an eyelet delimiting a shoulder, and in that it has, at its other end, a tapered shape facilitating its insertion into the eyelet, this other end comprising at least one snap-fit catch intended to be snap-fitted into the eyelet and to cooperate with the shoulder in order to maintain the band in the form of a ring. 5. The gastric ring as claimed in claim 4, characterized in that said other end comprises several successive catches, making it possible to close the band at several diameters adapted to the specific circumstances of the patient to be treated. 6. The gastric ring as claimed in claim 1 characterized in that: each pair of bearing points is formed by two opposite zones of an opening formed radially and through said deformable zone of the band, this opening being of circular shape when the deformable zone is in a nondeformed state, but being able to assume an oblong shape when this deformable zone is stretched longitudinally; and each rigid element has an oblong tubular shape and is dimensioned so as to be able to be introduced with force into the aforementioned opening in order to confer on this opening a corresponding oblong shape, this oblong shape producing a correlated longitudinal stretching of said deformable zone. 7. The gastric ring as claimed in claim 6, characterized in that each insert has a slightly flared shape and is intended to be placed on said deformable zone in such a way that its end of greater cross section is disposed on the outside of the ring. 8. The gastric ring as claimed in claim 1 characterized in that: each pair of bearing points is formed by two holes formed in said deformable zone of the band, and each rigid element has a staple shape, that is to say comprises a body having two stubs, these stubs being intended to be received in the holes; the distance separating the stubs is greater than the distance separating the two holes when said zone is in the unstretched state, so that the portion of this zone situated between these holes is stretched when these stubs are engaged in these holes. 9. The gastric ring as claimed in claim 8, characterized in that the body has a curved shape permitting adaptation of this element to the curvature of the ring. 10. The gastric ring as claimed in claim 7, characterized in that the stubs have a length which is such that they traverse said deformable zone, and in that these stubs receive a small plate engaged on them and connecting them to one another. 11. The gastric ring as claimed in claim 10, characterized in that the stubs and said small plate are designed in such a way as to form an assembly, in particular by snap-fitting, between these stubs and this small plate. 12. The gastric ring as claimed in claim 8, characterized in that the holes of the deformable zone which are intended to receive said stubs are formed substantially perpendicular to this deformable zone, in such a way as to be located substantially parallel to the axis of the ring after formation of the latter. 13. The gastric ring as claimed in claim 1 characterized in that: each pair of bearing points is formed by two shoulders delimited by a portion with a cross section smaller than that of said deformable zone, and each rigid element has a tubular shape and is intended to be engaged on this portion of smaller cross section, in such a way as to bear against the shoulders, the length of this element being greater than the distance separating said shoulders when said deformable zone in is the unstretched state, in such a way that, when the ends of the tubular element are placed against these shoulders, said portion of smaller cross section is stretched. 14. The gastric ring as claimed in claim 13, characterized in that the element has a curved shape corresponding to the curvature of the ring. 15. The gastric ring as claimed in claim 1, characterized in that at least said deformable zone, if not the whole of the band, is made of silicone. 16. The gastric ring as claimed in claim 1, characterized in that each rigid element is made of a lactic acid or polyglycolic acid polymer, or of a lactic acid or polyglycolic acid copolymer.

The present invention concerns a gastric ring for treatment of obesity. Such a ring is also presently known as a “gastroplasty ring”. It is known to treat a patient with pathological obesity by fitting a ring round the patient's stomach in such a way as to create, in the upper part of the stomach, a pouch of small dimensions, and an opening for flow of food, also of small dimensions. The principle of such rings is well known, and the documents WO-A-86/04498 and EP-A-0 611 561 may be cited as documents illustrating existing gastric rings. An existing gastric ring comprises an inflatable pouch situated on its inner face, making it possible to adjust the cross section of the opening delimited by the ring. This is because implantation of such a ring, which involves prior dissection, causes a greater or lesser degree of trauma to the stomach wall, and it is best not to immediately tighten this ring round this wall, so as to ensure that the latter can heal by scar formation. The pouch is inflated by means of a fluid which is delivered percutaneously from an implantable chamber and by means of a conduit connecting this chamber to the pouch. Some of the gastric rings according to the prior art have the disadvantage of being relatively aggressive with regard to the wall of the stomach, to the point of causing inflammation of this wall, or, in extreme cases, perforations of this wall. This aggressiveness is the result in particular of the pressure exerted by the inflatable pouch and of a lumen which is not perfectly continuous. Moreover, said implantable chamber and said tube connecting this chamber and the pouch have the disadvantage of posing risks of leakage, migration and infection. The chamber may be more or less visible beneath the skin, which is unfavorable from the esthetic point of view. It is an object of the present invention to overcome all these disadvantages of the existing rings. The ring to which the invention relates comprises in a manner known per se: a band which is able to surround the wall of the stomach; means for maintaining the band in the form of a ring able to surround the stomach, and means with which it is possible, after implantation, to modify the cross section of the opening delimited by the ring. According to the invention: the band comprises at least one zone made of a material which is elastically deformable in the longitudinal direction of this band; said zone has at least two bearing points formed on it at two locations separated in the longitudinal direction of the band, and the ring comprises at least one rigid element made of a bioabsorbable or biodegradable material and bearing against said zone in the area of said bearing points, this rigid element, before absorption, making it possible to maintain said bearing points at a distance from one another different than the distance separating these two bearing points in the absence of elastic deformation of said zone of the band, and, after absorption, no longer forming an obstacle to the return of said zone of the band to its nondeformed state. “Biodegradable” or “bioabsorbable” signifies the property by which a material degrades in vivo by a cellular, enzymatic or microbial mechanism (cf. for example degradation of collagen by collagenase) or by a physical-chemical mechanism (cf. for example hydrolysis of a lactic acid polymer). Such a bioabsorbable material is preferably chosen from the group consisting of polymers of p-dioxanone, polyglycolides, polyorthoesters, polymers of trimethylene carbonate, stereocopolymers of L and D lactic acid, homopolymers of L lactic acid, copolymers of lactic acid and a compatible comonomer, such as alphahydroxy acid derivatives. Still more preferred, the bioabsorbable material has a polydispersity of less than 2. By way of a preferred example, the biodegradable or bioabsorbable material is a lactic acid polymer (PLA) or polyglycolic acid polymer (PGA), or a copolymer of lactic acid or polyglycolic acid (PLA-PGA). The ring according to the invention is placed round the stomach, after which the absorption of the element or elements made of bioabsorbable material which the ring comprises allows said deformable zone or zones of the band to recover their neutral form of nondeformation. The circumference of the ring, and thus the cross section of the opening delimited by this ring, can thus be adapted to the treatment needs of the patient. This ring does not therefore comprise a pouch on its inner face, nor an implantable chamber and tube connecting this chamber to this pouch. The result of this is that the ring is largely nonaggressive with respect to the wall of the stomach and makes it possible to eliminate all the aforementioned disadvantages of using an inflatable pouch, implantable chamber and tube. Each element made of bioabsorbable material is principally intended to maintain the zone of the band, along which it extends, in a stretched state; the ring can thus be put in place in a state of relative distension in order to permit cicatrization of the stomach wall, then, after absorption of its element or elements made of bioabsorbable materal, undergo contraction as a result of the resilience of the material constituting said deformable zone. The principles of the invention could however be applied inversely, in order to obtain a distension after absorption, in which case each element made of bioabsorbable material is intended to maintain the zone of the band, along which it extends, in a contracted state. Preferably, the band forms, at one end, an eyelet delimiting a shoulder, and it has, at its other end, a tapered shape facilitating its insertion into the eyelet; this other end comprises at least one snap-fit catch intended to be snap-fitted into the eyelet and to cooperate with the shoulder in order to maintain the band in the form of a ring. Said other end can comprise several successive catches, making it possible to close the band at several diameters adapted to the specific circumstances of the patient to be treated. According to one possible embodiment of the invention each pair of bearing points is formed by two opposite zones of an opening formed radially and through said deformable zone of the band, this opening being of circular shape when the deformable zone is in a nondeformed state, but being able to assume an oblong shape when this deformable zone is stretched longitudinally; and each rigid element has an oblong tubular shape and is dimensioned so as to be able to be introduced with force into the aforementioned opening in order to confer on this opening a corresponding oblong shape, this oblong shape producing a correlated longitudinal stretching of said deformable zone. Each insert can have a slightly flared shape and can be placed on said deformable zone in such a way that its end of greater cross section is disposed on the outside of the ring. This slightly flared shape permits adaptation of the insert to the curvature of the ring and thus avoids any risk of this insert being expelled when the band is curved to form the ring. According to another possible embodiment of the invention: each pair of bearing points is formed by two holes formed in said deformable zone of the band, and each rigid element has a staple shape, that is to say comprises a body having two stubs, these stubs being intended to be received in said holes; the distance separating the stubs is greater than the distance separating the two holes when said zone is in the unstretched state, so that the portion of this zone situated between these holes is stretched when these stubs are engaged in these holes. The body of each element according to this other embodiment can have a curved shape permitting adaptation of this element to the curvature of the ring. According to yet another possible embodiment of the invention: each pair of bearing points is formed by two shoulders delimited by a portion with a cross section smaller than that of said deformable zone, and each rigid element has a tubular shape and is intended to be engaged on this portion of smaller cross section, in such a way as to bear against the shoulders, the length of this element being greater than the distance separating said shoulders when said deformable zone in is the unstretched state, in such a way that, when the ends of the tubular element are placed against these shoulders, said portion of smaller cross section is stretched. The element can have a curved shape corresponding to the curvature of the ring, again to permit adaptation of this element to the curvature of the ring. The invention will be clearly understood from the following description in which reference is made to the attached diagrammatic drawing which shows, by way of nonlimiting examples, three possible embodiments of the gastric ring in question. FIGS. 1, 3 and 4 are views of this ring according to these three embodiments, respectively, shown in a cross section passing through the median plane of the thickness of this ring, and FIG. 2 is a partial view of the ring shown in FIG. 1, from the direction of the arrow A in said figure. To simplify matters, the elements or parts of elements found from one embodiment to another are designated by the same reference numbers. FIG. 1 shows a gastric ring 1 used for treatment of pathological obesity of a patient and presently referred to as a “gastroplasty ring”. The ring 1 comprises a band 2 which is able to surround the stomach wall, and three rigid inserts 3. The band 2 is made of a material which is elastically deformable in the longitudinal direction of this band and is in particular made of silicone. At one end 2a, it forms an eyelet 4 delimiting a shoulder 5. At its other end 2b, it has a tapered shape facilitating its insertion into the eyelet 4 and comprises a snap-fit catch 6 intended to be snap-fitted into the eyelet 4 and to cooperate with the shoulder 5 in order to maintain the band 2 in the form of a ring. This end 2b can comprise several successive catches 6, making it possible to close the band 2 at several diameters adapted to the specific circumstances of the patient to be treated. At its end 2b, the band 2 has a zone 2c in which three radial through-openings 7 are formed. Each opening 7 is circular when the band 2 is in a nondeformed state, but can assume an oblong shape when this zone 2c is stretched longitudinally. Each insert 3 is made of a bioabsorbable or biodegradable material such as a lactic acid polymer (PLA) or polyglycolic acid polymer (PGA), or a copolymer of lactic acid or polyglycolic acid (PLA-PGA). As is shown in FIG. 2, it has an oblong tubular shape and is dimensioned in such a way as to be able to be introduced with force into an opening 7. It thus confers on this opening 7 a corresponding oblong shape which produces a correlated longitudinal stretching of the zone 2c. To adapt to the curvature of the band 2 when the ends 2a and 2b are in engagement, the inserts 3 have a slightly flared shape, their ends of greater cross section being disposed on the outside of the ring 1. In practice, the band 2 is introduced into the patient's body and placed round the stomach using a minimally invasive technique such as laparoscopy, after which the end 2b is engaged through the eyelet 4 until the catch 6 snap-fits behind the eyelet 4 and this catch 6 bears against the shoulder 5. The respective locations of this catch 6 and of this shoulder 5 have been predetermined in such a way that the ring 1 thus formed has a relative distension in relation to the desired tightening of the stomach wall, so as to permit cicatrization of the stomach wall before exerting a tightening stress on this wall. The thickness of the inserts 3 is calculated, as a function of the material used, to ensure mechanical rupture of these inserts 3 about one to two months after implantation, this rupture taking place under the combined effect of the absorption of the inserts 3 and the tension exerted by the band 2. The rupture of these inserts 3 allows the zone 2c to recover its neutral, unstretched state. The ring 1 then undergoes contraction resulting from the resilience of the material constituting said zone 2c, which gives to the circumference of the ring 1, and thus to the cross section of the opening delimited by this ring 1, dimensions adapted to the treatment needs of the patient. In the case of the ring 1 shown in FIG. 3, the zone 2c comprises two holes 7 which receive the stubs 3a of an inserted staple-shaped element 3. The distance separating the stubs 3a is greater than the distance separating the two holes 7 when the zone 2c is in the unstretched state, so that the portion of this zone 2c situated between these holes 7 is stretched when these stubs 3a are engaged in these holes 7. The body 3b of the element 3 which comprises the stubs 3a has a curved shape permitting adaptation of this element 3 to the curvature of the ring 1. In the case of the ring 1 shown in FIG. 4, the zone 2c has a portion of smaller cross section forming two shoulders 7. A tubular element 3 is engaged on this portion of smaller cross section and bears against these shoulders 7. The length of the element 3 is greater than the distance separating the shoulders 7 when the zone 2c is in the unstretched state, so that, when the ends of the element 3 are placed against the shoulders 7, said portion of smaller cross section is stretched. Here too, the element 3 has a curved shape corresponding to the curvature of the ring 1. This gastric ring 1 affords a decisive improvement to the prior art, given that it does not comprise an inflatable pouch on its inner face, nor an implantable chamber and tube connecting this chamber to this pouch. The result is that this ring is largely nonaggressive with respect to the wall of the stomach and eliminates all the disadvantages associated with the use of an inflatable pouch, implantable chamber and tube. It goes without saying that the invention is not limited to the embodiment described above by way of example, and that on the contrary it encompasses all variant embodiments falling within the scope of protection defined by the attached claims. Thus, the ring can comprise several deformable zones 2c; the band 2 can be of a monobloc structure, as shown, or can have, outside the zone or zones 2c, a structure different than that of this zone or these zones 2c; each element 3 is principally intended to maintain the corresponding zone 2c in a stretched state, but each zone 2c could be maintained in a contracted state by one or more of these elements 3 in order to obtain a distension of the ring after absorption of these elements 3; the element 3 can be in the form of a “staple” as shown in FIG. 3, but with stubs 3a having a length such that they traverse said deformable zone 2c and receive a small plate engaged on them and connecting them to one another, this small plate making it possible to distribute the forces exerted on these stubs 3a; these stubs 3a and this small plate can be designed in such a way as to form an assembly, in particular by snap-fitting, between these stubs 3a and this small plate; so as not to form an excessive thickness on the inner face of the ring, the holes of the deformable zone 2c which are intended to receive said stubs 3a can be formed substantially perpendicular to the zone 2c, so as to be situated substantially parallel to the axis of the ring 1 after formation of the latter, such that the body 3b connecting these stubs 3a is situated on one axial side of the ring 1 and said small plate on the other axial side of this ring 1.

20040811

20071120

20050714

75517.0

MATTHEWS, CHRISTINE HOPKINS

GASTRIC RING FOR TREATMENT OF OBESITY

UNDISCOUNTED

ACCEPTED

ACCEPTED

Light-beam switching/adjusting apparatus and manufacturing method thereof

The light guide substrate 2 has mirror receiving grooves 24 and light guides. The light guides conduct light that is input into the input ports to selected output ports in accordance with the advance and retraction of the mirrors 31 with respect to the grooves 24. The actuator substrate 4 has mirrors 31 and actuators which place the mirrors 31 in a state in which the mirrors are drawn in toward the substrate 4, or a state in which the mirrors protrude from the substrate 4. The light guide substrate 2 and actuator substrate 4 are aligned using alignment marks and joined with a spacer 3 interposed so that the mirrors 31 retract from the grooves 24 when the mirrors 31 are drawn in toward the substrate 4, and so that the mirrors 31 advance into the grooves 24 when the mirrors 31 protrude from the substrate 4. This alignment is performed in a state in which all of the mirrors 31 are drawn in toward the substrate 4.

1. A light beam switching and adjustment device comprising: a light guide substrate which has one or more input ports, a plurality of output ports, one or more mirror receiving recesses that are formed in one surface of the light guide substrate, and light guides that conduct the light that is input into the one or more input ports to selected output ports among the plurality of output ports in accordance with the advance and retraction of the one or more mirrors with respect to one or more mirror receiving recesses; and an actuator substrate which has the one or more mirrors and one or more actuators which are disposed in positions corresponding to the one or more mirrors so that these actuators support the corresponding mirrors, and which position these corresponding mirrors on the side of one surface of the actuator substrate in a first position that is relatively far from this surface or in a second position that is relatively close to this surface, in accordance with signals; which is characterized in that the light guide substrate and the actuator substrate are aligned and joined so that the first positions of the one or more mirrors are advanced positions with respect to the one or more mirror receiving recesses, and so that the second positions of the one or more mirrors are retracted positions with respect to the one or more mirror receiving recesses, first alignment marks which are used to align the light guide substrate and the actuator substrate are formed on the light guide substrate, and second alignment marks which are used to align the light guide substrate and the actuator substrate are formed on the actuator substrate. 2. The light beam switching and adjustment device according to claim 1, which is characterized in that the first and second alignment marks can be observed by means of infrared light. 3. The light beam switching and adjustment device according to claim 1, which is characterized in that the first alignment marks are formed on the first surface of the light guide substrate, the second alignment marks are formed on the first surface of the actuator substrate, and the actuator substrate has characteristics that allow the transmission of infrared light. 4. A light beam switching and adjustment device comprising: a light guide substrate which has one or more input ports, a plurality of output ports, one or more mirror receiving recesses that are formed in one surface of the light guide substrate, and light guides that conduct the light that is input into the one or more input ports to selected output ports among the plurality of output ports in accordance with the advance and retraction of the one or more mirrors with respect to the one or more mirror receiving recesses; and an actuator substrate which has the one or more mirrors and one or more actuators which are disposed in positions corresponding to the one or more mirrors so that these actuators support the corresponding mirrors, and which position these corresponding mirrors on the side of one surface of the actuator substrate in a first position that is relatively far from this surface or in a second position that is relatively close to this surface, in accordance with signals; in which the light guide substrate and the actuator substrate are aligned and joined so that the first positions of the one or more mirrors are advanced positions with respect to the one or more mirror receiving recesses, and so that the second positions of the one or more mirrors are retracted positions with respect to the one or more mirror receiving recesses; which is characterized in that the supply of electric power to the actuator substrate is performed directly to the actuator substrate from the outside. 5. A light beam switching and adjustment device comprising: a light guide substrate which has one or more input ports, a plurality of output ports, one or more mirror receiving recesses that are formed in one surface of the light guide substrate, and light guides that conduct the light that is input into the one or more input ports to selected output ports among the plurality of output ports in accordance with the advance and retraction of the one or more mirrors with respect to the one or more mirror receiving recesses; and an actuator substrate which has one or more mirrors and one or more actuators which are disposed in positions corresponding to the one or more mirrors so that these actuators support the corresponding mirrors, and which position these corresponding mirrors on the side of one surface of the actuator substrate in a first position that is relatively far from this surface or in a second position that is relatively close to this surface, in accordance with signals; in which the light guide substrate and the actuator substrate are aligned and joined so that the first positions of the one or more mirrors are advanced positions with respect to the one or more mirror receiving recesses, and so that the second positions of the one or more mirrors are retracted positions with respect to the one or more mirror receiving recesses; which is characterized in that the device comprises a relay substrate which is used to relay electrical connections with respect to the actuator substrate, the relay substrate is joined to the other surface of the actuator substrate so that a portion of this relay substrate protrudes from the actuator substrate, and the relay substrate does not cover the regions on this other surface of the actuator substrate corresponding to the second alignment marks. 6. The light beam switching and adjustment device according to claim 5, which is characterized in that a plurality of first pads used for electrical connections are formed on the first surface of the actuator substrate, a plurality of second pads used for electrical connections are formed on the surface of the relay substrate located on the side of the actuator substrate in the portion of the relay substrate that protrudes from the actuator substrate, the plurality of first pads and plurality of second pads are respectively electrically connected to each other by bonding wires, a plurality of third pads used for electrical connections, each of which is electrically connected to one of the plurality of second pads, are formed on the relay substrate, a plurality of conductive parts which are respectively electrically connected to some of the second pads among the plurality of second pads are formed on the relay substrate, and the mutual disposition pitch of at least portions of the plurality of conductive parts is wider than the disposition pitch of the plurality of second pads and the disposition pitch of the plurality of third pads. 7. The light beam switching and adjustment device according to claim 6, which is characterized in that the plurality of conductive parts are formed on the surface of the relay substrate located on the side of the actuator substrate in the protruding portion of the relay substrate, and the plurality of third pads are formed on the surface of the relay substrate located on the opposite side from the actuator substrate. 8. The light beam switching and adjustment device according to claim 6, which is characterized in that the device comprises a substrate which has a plurality of lead terminals used for external connections, and the plurality of third pads and plurality of lead terminals used for external connections are respectively electrically connected to each other by bonding wires. 9. A light beam switching and adjustment device comprising: a light guide substrate which has one or more input ports, a plurality of output ports, one or more mirror receiving recesses that are formed in one surface of the light guide substrate, and light guides that conduct the light that is input into the one or more input ports to selected output ports among the plurality of output ports in accordance with the advance and retraction of the one or more mirrors with respect to the one or more mirror receiving recesses; and an actuator substrate which has the one or more mirrors and one or more actuators which are disposed in positions corresponding to the one or more mirrors so that these actuators support the corresponding mirrors, and which position these corresponding mirrors on the side of one surface of the actuator substrate in a first position that is relatively far from this surface or in a second position that is relatively close to this surface, in accordance with signals; in which the light guide substrate and the actuator substrate are aligned and joined so that the first positions of the one or more mirrors are advanced positions with respect to the one or more mirror receiving recesses, and so that the second positions of the one or more mirrors are retracted positions with respect to the one or more mirror receiving recesses; which is characterized in that the actuator substrate comprises a plurality of feed terminals used for the electrical driving of the actuators, and one or more terminals of a first type used to perform feeding for the purpose of individually driving the actuators, and one or more terminals of a second type used to perform feeding for the purpose of collectively driving all of the actuators so that all of the one or more mirrors are positioned in the second positions, are included in the plurality of feed terminals. 10. The light beam switching and adjustment device according to claim 9, which is characterized in that a driving circuit which drives the one or more actuators so that when signals that are used to cause respective desired optical switching operations are supplied to the terminals of the first type, these optical switching operations are performed, and so that when specified signals are supplied to the terminals of the second type, all of the one or more mirrors are positioned in the second positions, is mounted on the actuator substrate. 11. The light beam switching and adjustment device according to claim 9, which is characterized in that at least one concavo-convex portion is provided in each mirror, and the insertion depth of the mirrors in the mirror receiving recesses can be observed by using these concavo-convex portions as a focusing reference for the microscopic observation. 12. The light beam switching and adjustment device according to any one of claims 1 through 11, which is characterized in that the light guide substrate and the actuator substrate are joined with a spacer interposed so that the second positions of the one or more mirrors are positions in which the mirrors are completely retracted from the one or more mirror receiving recesses. 13. The light beam switching and adjustment device according to claim 12, which is characterized in that the spacer is disposed so that this spacer surrounds the region in which the one or more mirrors are distributed on the actuator substrate. 14. The light beam switching and adjustment device according to claim 13, which is characterized in that the space between the light guide substrate and actuator substrate is filled with a refractive index adjusting liquid which has a refractive index that is substantially the same as the refractive index of the core layers of the light guides so that this liquid enters the mirror receiving recesses, and the spacer forms a part of a sealing structure that seals the refractive index adjusting liquid. 15. A light beam switching and adjustment device comprising: a light guide substrate which has one or more input ports, a plurality of output ports, one or more mirror receiving recesses that are formed in one surface of the light guide substrate, and light guides that conduct the light that is input into the one or more input ports to selected output ports among the plurality of output ports in accordance with the advance and retraction of one or more mirrors with respect to the one or more mirror receiving recesses; an actuator substrate which has the one or more mirrors and one or more actuators which are disposed in positions corresponding to the one or more mirrors so that these actuators support the corresponding mirrors, and which position these corresponding mirrors on the side of one surface of the actuator substrate in a first position that is relatively far from this surface or in a second position that is relatively close to this surface, in accordance with signals; and a relay substrate which is used to relay electrical connections to the actuator substrate; which is characterized in that the light guide substrate and the actuator substrate are aligned and joined so that the first positions of the one or more mirrors are advanced positions with respect to the one or more mirror receiving recesses, and so that the second positions of the one or more mirrors are retracted positions with respect to the one or more mirror receiving recesses, and the relay substrate is joined to the other surface of the actuator substrate so that a portion of this relay substrate protrudes from the actuator substrate. 16. The light beam switching and adjustment device according to claim 15, which is characterized in that a plurality of first pads used for electrical connections are formed on the first surface of the actuator substrate, a plurality of second pads used for electrical connections are formed on the surface of the relay substrate located on the side of the actuator substrate in the portion of the relay substrate that protrudes from the actuator substrate, the plurality of first pads and plurality of second pads are respectively electrically connected to each other by bonding wires, and a plurality of third pads used for electrical connections, each of which is electrically connected to one of the plurality of second pads, are formed on the relay substrate. 17. The light beam switching and adjustment device according to claim 15 or claim 16, which is characterized in that the device comprises a substrate which has a plurality of lead terminals used for external connections, and the plurality of third pads and plurality of lead terminals used for external connections are respectively electrically connected to each other by bonding wires. 18. The light beam switching and adjustment device according to claim 16, which is characterized in that a plurality of conductive parts which are respectively electrically connected to some of the second pads among the plurality of second pads are formed on the relay substrate, and the mutual disposition pitch of at least portions of the plurality of conductive parts is wider than the disposition pitch of the plurality of second pads and the disposition pitch of the plurality of third pads. 19. The light beam switching and adjustment device according to claim 18, which is characterized in that the plurality of conductive parts are formed on the surface of the relay substrate located on the side of the actuator substrate in the protruding portion of the relay substrate, and the plurality of third pads are formed on the surface of the relay substrate located on the opposite side from the actuator substrate. 20. The light beam switching and adjustment device according to claim 18, which is characterized in that all of the one or more mirrors are positioned in the second positions when specified signals are respectively supplied to the plurality of conductive parts. 21. The light beam switching and adjustment device according to claim 18, which is characterized in that a driving circuit which drives the one or more actuators so that when signals that are used to cause respective desired optical switching operations are supplied to the plurality of third pads, these optical switching operations are performed, and so that when specified signals are respectively supplied to the plurality of conductive parts, all of the one or more mirrors are positioned in the second positions, is mounted on the actuator substrate. 22. A light beam switching and adjustment device comprising: a light guide substrate which has one or more input ports, a plurality of output ports, one or more mirror receiving recesses that are formed in one surface of the light guide substrate, and light guides that conduct the light that is input into the one or more input ports to selected output ports among the plurality of output ports in accordance with the advance and retraction of one or more mirrors with respect to the one or more mirror receiving recesses; and an actuator substrate which has the one or more mirrors and one or more actuators which are disposed in positions corresponding to the one or more mirrors so that these actuators support the corresponding mirrors, and which position these corresponding mirrors on the side of one surface of the actuator substrate in a first position that is relatively far from this surface or in a second position that is relatively close to this surface, in accordance with signals; which is characterized in that the light guide substrate and the actuator substrate are aligned and joined so that the first positions of the one or more mirrors are advanced positions with respect to the one or more mirror receiving recesses, and so that the second positions of the one or more mirrors are retracted positions with respect to the one or more mirror receiving recesses, and the light guide substrate and the actuator substrate are joined with a spacer interposed so that the second positions of the one or more mirrors are positions in which the mirrors are completely retracted from the one or more mirror receiving recesses. 23. The light beam switching and adjustment device according to claim 22, which is characterized in that the spacer is disposed so that this spacer surrounds the region in which the one or more mirrors are distributed on the actuator substrate. 24. The light beam switching and adjustment device according to claim 23, which is characterized in that the space between the light guide substrate and actuator substrate is filled with a refractive index adjusting liquid which has a refractive index that is substantially the same as the refractive index of the core layers of the light guides so that this liquid enters the mirror receiving recesses, and the spacer forms a part of a sealing structure that seals the refractive index adjusting liquid. 25. A method for manufacturing a light beam switching and adjustment device comprising: a step of preparing a light guide substrate [i] which has one or more input ports, a plurality of output ports, one or more mirror receiving recesses that are formed in one surface of the light guide substrate, and light guides that conduct the light that is input into the one or more input ports to selected output ports among the plurality of output ports in accordance with the advance and retraction of the one or more mirrors with respect to the one or more mirror receiving recesses, and [ii] on which first alignment marks are formed; a step of preparing an actuator substrate [i] which has the one or more mirrors and one or more actuators which are disposed in positions corresponding to the one or more mirrors so that these actuators support the corresponding mirrors, and which position these corresponding mirrors on the side of one surface of the actuator substrate in a first position that is relatively far from this surface or in a second position that is relatively close to this surface, in accordance with signals, and [ii] on which second alignment marks are formed; and a step of aligning and joining the light guide substrate and the actuator substrate using the first and second alignment marks so that the first positions of the one or more mirrors are advanced positions with respect to the one or more mirror receiving recesses, and so that the second positions of the one or more mirrors are retracted positions with respect to the one or more mirror receiving recesses. 26. A method for manufacturing a light beam switching and adjustment device comprising: a step of preparing a light guide substrate which has one or more input ports, a plurality of output ports, one or more mirror receiving recesses that are formed in one surface of the light guide substrate, and light guides that conduct the light that is input into the one or more input ports to selected output ports among the plurality of output ports in accordance with the advance and retraction of one or more mirrors with respect to the one or more mirror receiving recesses; a step of preparing an actuator substrate which has the one or more mirrors and one or more actuators which are disposed in positions corresponding to the one or more mirrors so that these actuators support the corresponding mirrors, and which position these corresponding mirrors on the side of one surface of the actuator substrate in a first position that is relatively far from this surface or in a second position that is relatively close to this surface, in accordance with signals; a step of preparing a spacer that is joined between the light guide substrate and the actuator substrate; a spacer joining step in which the spacer is joined to either the light guide substrate or the actuator substrate; and a step which is performed following the spacer joining step, and in which the light guide substrate and actuator substrate are aligned, and the spacer is joined to the other of the two substrates, i.e., either the light guide substrate or actuator substrate, so that the first positions of the one or more mirrors are advanced positions with respect to the one or more mirror receiving recesses, and so that the second positions of the one or more mirrors are retracted positions with respect to the one or more mirror receiving recesses; which is characterized in that when the spacer is joined between the light guide substrate and actuator substrate, the second positions of the one or more mirrors are positions in which the mirrors are completely retracted from the one or more mirror receiving recesses. 27. The method for manufacturing a light beam switching and adjustment device according to claim 26, which is characterized in that first alignment marks are formed on the light guide substrate, second alignment marks are formed on the actuator substrate, and the alignment of the light guide substrate and the actuator substrate is performed utilizing the first and second alignment marks. 28. The method for manufacturing a light beam switching and adjustment device according to any one of claims 25 through 27, which is characterized in that the actuators are constructed so that when absolutely no signals are supplied, the mirrors supported on these actuators return to specified positions that are farther from the actuator substrate on the first surface of this substrate than the second positions, and when the light guide substrate and the actuator substrate are aligned, specified signals are applied to the actuator substrate, so that all of the one or more mirrors are positioned in the second positions. 29. A method for manufacturing a light beam switching and adjustment device comprising: a step of preparing a light guide substrate which has one or more input ports, a plurality of output ports, one or more mirror receiving recesses that are formed in one surface of the light guide substrate, and light guides that conduct the light that is input into the one or more input ports to selected output ports among the plurality of output ports in accordance with the advance and retraction of the one or more mirrors with respect to the one or more mirror receiving recesses; a step of preparing an actuator substrate which has the one or more mirrors and one or more actuators which are disposed in positions corresponding to the one or more mirrors so that these actuators support the corresponding mirrors, and which position these corresponding mirrors on the side of one surface of the actuator substrate in a first position that is relatively far from this surface or in a second position that is relatively close to this surface, in accordance with signals; and a step of aligning and joining the light guide substrate and the actuator substrate so that the first positions of the one or more mirrors are advanced positions with respect to the one or more mirror receiving recesses, and so that the second positions of the one or more mirrors are retracted positions with respect to the one or more mirror receiving recesses; which is characterized in that the actuators are constructed so that when absolutely no signals are supplied, the mirrors supported on these actuators return to specified positions that are farther from the actuator substrate on the first surface of this substrate than the second positions, and when the light guide substrate and the actuator substrate are aligned, specified signals are applied to the actuator substrate, so that all of the one or more mirrors are positioned in the second positions. 30. The method for manufacturing a light beam switching and adjustment device according to claim 28, which is characterized in that signals are supplied to the actuator substrate so that all of the one or more mirrors gradually return to the specified positions described above following the completion of the alignment between the light guide substrate and the actuator substrate. 31. The method for manufacturing a light beam switching and adjustment device according to claim 29, which is characterized in that signals are supplied to the actuator substrate so that all of the one or more mirrors gradually return to the specified positions described above following the completion of the alignment between the light guide substrate and the actuator substrate. 32. A light beam switching and adjustment device used for the switching of the light paths of light beams or adjustment of the amount of transmitted light of light beams that are propagated through light guides by inserting and removing insertion plates into and from slits formed in these light guides, which is characterized in that the light guides and slits are disposed on a first substrate, the insertion plates are held by insertion plate driving means disposed on a second substrate, the first and second substrates are disposed so that the insertion plates can be inserted into and removed from the slits, a first region of the first substrate which contains the slits and a second region of the second substrate which is provided with the insertion plates are constructed so that these regions can transmit light of a specified wavelength, this light of a specified wavelength is caused to be incident from either the first region or second region, and the transmitted light is emitted from either the second region or first region, so that the insertion positions of the insertion plates inside the slits can be observed by microscopic observation. 33. A light beam switching and adjustment device used for the switching of the light paths of light beams or adjustment of the amount of transmitted light of light beams that are propagated through light guides by inserting and removing insertion plates into and from slits formed in these light guides, which is characterized in that the light guides and slits are disposed on a first substrate, the insertion plates are held by insertion plate driving means disposed on a second substrate, the first and second substrates are disposed so that the insertion plates can be inserted into and removed from the slits, either a first region of the first substrate which contains the slits or a second region of the second substrate which is provided with the insertion plates is constructed so that this region can transmit light of a specified wavelength, this light of a specified wavelength is caused to be incident from either the first region or second region, and the reflected light is emitted from the first region or second region, so that the insertion positions of the insertion plates inside the slits can be observed by microscopic observation. 34. The light beam switching and adjustment device according to claim 32 or claim 33, which is characterized in that at least one concavo-convex portion is provided in each insertion plate, and the insertion depth of the insertion plates in the slits can be observed by using these concavo-convex portions as a focusing reference for the microscopic observation.

TECHNICAL FIELD The present invention relates to a light beam switching and adjustment device used to perform light beam light path conversion and adjustment of the amount of transmission in (for example) optical communications networks, optical switching systems or the like, and a method for manufacturing the same. BACKGROUND ART Light beam switching and adjustment devices used for light path conversion are necessary in optical communications systems, and in recent years, matrix light beam switching and adjustment devices used to perform light path switching among a plurality of inputs and outputs have become especially important. For example, such matrix light beam switching and adjustment devices perform actions such as the transmission of light signals from one of numerous parallel input optical fibers to one of numerous parallel output optical fibers; a light beam switching and adjustment device such as that disclosed in Japanese Patent Application Kokai No. 2001-142008 is known as a concrete example of such a device. In such a light beam switching and adjustment device, light from optical fibers is conducted to light guides in which light paths are formed in a matrix. Micromirrors using MEMS technology (MEMS: micro-electro-mechanical systems) are disposed at the intersection points of the light paths, and light path conversion and adjustment of the amount of transmission of the light beams are performed by moving these micro-mirrors into and out of slits disposed in the light paths. FIG. 17 shows diagrams used to illustrate an example of the construction of a conventional light beam switching and adjustment device using MEMS technology. FIG. 17(a) is a plan view of this light beam switching and adjustment device, and FIG. 17(b) is a sectional view along line A-A′ in FIG. 17(a). As is shown in FIG. 17(a), this light beam switching and adjustment device comprises first through third light guide cores 302a, 302b and 302c on a core supporting substrate 301. These light guide cores are connected to incident-side optical fibers 308 or transmission-side optical fibers 309, and slits 303 are disposed in the intersection parts of the light guide cores so that these slits cut across the light guides that intersect with each other. Furthermore, an insertion plate supporting substrate 304 is disposed as shown in FIG. 17(b) on the upper surface region of the core supporting substrate 301 indicated by a dotted line in FIG. 17(a), and a structure is formed in which insertion plates 305 disposed on this insertion plate supporting substrate 304 are driven by an insertion plate driving mechanism 307. Furthermore, 306 indicates electrical wiring used for the electrical driving of the insertion plate driving mechanism. The insertion plates 305 are disposed facing the upper portions of the slits 303. The insertion plates 305 are driven upward and downward by the insertion plate driving mechanism 307 so that these insertion plates 305 are inserted into or removed from the slits 303. As a result, a switching action based on the switching of the light paths of the light beams that enter the slits 303 from the optical fiber core parts 310 of the incident-side optical fibers 308, and an attenuation action based on the adjustment of the amount of transmitted light, can be accomplished. Specifically, in a state in which the corresponding insertion plate 305 is inserted into the corresponding slit 303, the light beam that enters this slit 303 from the first light guide core 302a is reflected by the insertion plate 305, and is therefore coupled with the end surface of the second light guide core 302b. On the other hand, in a state in which this insertion plate 305 is withdrawn from the slit 303, the light beam that enters the slit 303 from the first light guide core 302a is coupled “as is” with the end surface of the facing third light guide core 302c. In this way, switching of the light paths of the light beams is performed, so that a switching action is realized. Furthermore, if the insertion position (insertion depth) of the insertion plate 303 in the slit 303 is adjusted, an attenuation action that attenuates the intensity of the transmitted light can be realized by blocking a portion of the light beam that enters the slit 303 from the first light guide core 302a in accordance with this insertion position, and allowing the remaining light beam component to pass through so that this component is coupled with the end surface of the third light guide core 302c. In order to realize a light beam switching and adjustment device based on the system described above, it is necessary to attach MEMS actuators and micro-mirrors manufactured on the surface of a silicon substrate or the like by a MEMS process using a silicon semiconductor process or the like to a light guide substrate manufactured by a separate process. Specifically, in the manufacture of this light beam switching and adjustment device, it is necessary to join a light guide substrate which has mirror receiving recesses and an actuator substrate which has mirrors and actuators that support and move these mirrors, after aligning the mirrors and the mirror receiving recesses. However, in the actual performance of such alignment, it has been ascertained that this alignment is extremely difficult. Specifically, since the mirror receiving recesses are disposed at intermediate points in the light guides, it is desirable that the width of the mirror receiving recesses be set as narrow as possible in order to suppress light loss. Accordingly, an extremely high degree of precision is required in the alignment of the mirrors and mirror receiving recesses. Furthermore, if the mirrors collide with parts other than the mirror receiving recesses in the process of this alignment of the mirrors relative to the mirror receiving recesses, the mirrors are easily damaged. Accordingly, the alignment of the light guide substrate and actuator substrate is extremely difficult. Especially in cases where the number of mirrors is large, all of the mirrors must be aligned with the corresponding mirror receiving recesses; accordingly, this alignment is extremely difficult. Furthermore, the actuators are driven in accordance with signals. In the light beam switching and adjustment device of the present invention, the device has the following special characteristic: namely, the actuator substrate is joined with the light guide substrate in the assembly process. With this as a prerequisite, in order to reduce the size of the device and to facilitate inspections and the like during the manufacturing process, it is necessary to devise the structure of the wiring and the like that is used to supply signals to the actuator substrate so that this wiring, etc., does not interfere with the assembly, and so that inspections can easily be performed by connecting temporary wiring during such inspections. Furthermore, in such a light beam switching and adjustment device, the relative positional relationship between the insertion plates and the slits formed in the light guide cores needs to be set so that the reflection loss is minimized when the insertion plates are caused to function as reflective plates. Furthermore, in order to reduce the loss of reflected light, it is desirable that the positions of the insertion plates with respect to the slits be aligned with a precision of 1 μm or better. Moreover, in cases where the amount of attenuation of the light beams is adjusted, the insertion plates must be smoothly driven by the insertion plate driving mechanism. In order to observe the state of high-precision alignment of the insertion plates and slits in such a light beam adjustment device, it is important to accurately monitor these relative positions and the insertion depth of the insertion plates inside the slits from the outside. Generally, a method is used in which microscopic observation by an optical method is used to monitor the relative positional relationship between the insertion plates and the slits following the bonding of the core supporting substrate and insertion plate supporting substrate, with observation being performed using an infrared microscope in cases where the device is constructed using silicon substrates, and using a common optical microscope equipped with a visible-light light source in cases where glass substrates are used. However, in addition to the insertion plate driving mechanism being attached to the insertion plate supporting substrate, wiring used to operate the insertion plate driving mechanism is also disposed. Accordingly, the following problem arises: namely, the presence of such constituent elements is a major obstacle to observation of the relative positional relationship between the insertion plates and the slits. Furthermore, the following problem is also encountered: specifically, the observational magnification during microscopic observation inevitably increases according to the width of the slits and the size of the insertion plates that are the objects of observation; accordingly, the depth of field is shallow, so that it is difficult to discriminate the insertion positions of the insertion plates inside the slits. DISCLOSURE OF THE INVENTION The present invention was devised in order to solve the problems described above. The first object of the present invention is to provide a light beam switching and adjustment device which can be manufactured easily and with a good yield as a result of the alignment of the mirrors and mirror receiving recesses being facilitated, and a method for manufacturing this light beam switching and adjustment device. Furthermore, the second object of the present invention is to provide a light beam switching and adjustment device in which discrimination of the positional relationship between the insertion plates and the slits formed in the light guide cores, and the discrimination of the insertion positions of the insertion plates inside the slits, are easy. The inventions used to achieve the first object described above are the following first through thirtieth inventions. The first invention is a light beam switching and adjustment device comprising: a light guide substrate which has one or more input ports, a plurality of output ports, one or more mirror receiving recesses that are formed in one surface of the light guide substrate, and light guides that conduct the light that is input into the one or more input ports to selected output ports among the plurality of output ports in accordance with the advance and retraction of the one or more mirrors with respect to the one or more mirror receiving recesses; and an actuator substrate which has the one or more mirrors described above]and one or more actuators which are disposed in positions corresponding to the one or more mirrors so that these actuators support the corresponding mirrors, and which position these corresponding mirrors on the side of one surface of the actuator substrate in a first position that is relatively far from this surface or in a second position that is relatively close to this surface, in accordance with signals; which is characterized in that the light guide substrate and the actuator substrate are aligned and joined so that the first positions of the one or more mirrors are advanced positions with respect to the one or more mirror receiving recesses, and so that the second positions of the one or more mirrors are retracted positions with respect to the one or more mirror receiving recesses, first alignment marks which are used to align the light guide substrate and the actuator substrate are formed on the light guide substrate, and second alignment marks which are used to align the light guide substrate and the actuator substrate are formed on the actuator substrate. The second invention is the first invention, which is characterized in that the first and second alignment marks can be observed by means of infrared light. The third invention is the first or second invention, which is characterized in that the first alignment marks are formed on the first surface of the light guide substrate, the second alignment marks are formed on the first surface of the actuator substrate, and the actuator substrate has characteristics that allow the transmission of infrared light. The fourth invention is a light beam switching and adjustment device comprising: a light guide substrate which has one or more input ports, a plurality of output ports, one or more mirror receiving recesses that are formed in one surface of the light guide substrate, and light guides that conduct the light that is input into the one or more input ports to selected output ports among the plurality of output ports in accordance with the advance and retraction of the one or more mirrors with respect to the one or more mirror receiving recesses; and an actuator substrate which has the one or more mirrors and one or more actuators which are disposed in positions corresponding to the one or more mirrors so that these actuators support the corresponding mirrors, and which position these corresponding mirrors on the side of one surface of the actuator substrate in a first position that is relatively far from this surface or in a second position that is relatively close to this surface, in accordance with signals; in which the light guide substrate and the actuator substrate are aligned and joined so that the first positions of the one or more mirrors are advanced positions with respect to the one or more mirror receiving recesses, and so that the second positions of the one or more mirrors are retracted positions with respect to the one or more mirror receiving recesses; which is characterized in that the supply of electric power to the actuator substrate is performed directly to the actuator substrate from the outside. The fifth invention is a light beam switching and adjustment device comprising: a light guide substrate which has one or more input ports, a plurality of output ports, one or more mirror receiving recesses that are formed in one surface of the light guide substrate, and light guides that conduct the light that is input into the one or more input ports to selected output ports among the plurality of output ports in accordance with the advance and retraction of the one or more mirrors with respect to the one or more mirror receiving recesses; and an actuator substrate which has the one or more mirrors and one or more actuators which are disposed in positions corresponding to the one or more mirrors so that these actuators support the corresponding mirrors, and which position these corresponding mirrors on the side of one surface of the actuator substrate in a first position that is relatively far from this surface or in a second position that is relatively close to this surface, in accordance with signals; in which the light guide substrate and the actuator substrate are aligned and joined so that the first positions of the one or more mirrors are advanced positions with respect to the one or more mirror receiving recesses, and so that the second positions of the one or more mirrors are retracted positions with respect to the one or more mirror receiving recesses; which is characterized in that the device comprises a relay substrate which is used to relay electrical connections to the actuator substrate, the relay substrate is joined to the other surface of the actuator substrate so that a portion of this relay substrate protrudes from the actuator substrate, and the relay substrate does not cover the regions on this other surface of the actuator substrate corresponding to the second alignment marks. The sixth invention is the fifth invention, which is characterized in that a plurality of first pads used for electrical connections are formed on the first surface of the actuator substrate, a plurality of second pads used for electrical connections are formed on the surface of the relay substrate located on the side of the actuator substrate in the portion of the relay substrate that protrudes from the actuator substrate, the plurality of first pads and plurality of second pads are respectively electrically connected to each other by bonding wires, a plurality of third pads used for electrical connections, each of which is electrically connected to one of the plurality of second pads, are formed on the relay substrate, a plurality of conductive parts which are respectively electrically connected to some of the second pads among the plurality of second pads are formed on the relay substrate, and the mutual disposition pitch of at least portions of the plurality of conductive parts is wider than the disposition pitch of the plurality of second pads and the disposition pitch of the plurality of third pads. The seventh invention is the sixth invention, which is characterized in that the plurality of conductive parts are formed on the surface of the relay substrate located on the side of the actuator substrate in the protruding portion of the relay substrate, and the plurality of third pads are formed on the surface of the relay substrate located on the opposite side from the actuator substrate. The eighth invention is the sixth or seventh invention, which is characterized in that the device comprises a substrate which has a plurality of lead terminals used for external connections, and the plurality of third pads and plurality of lead terminals used for external connections are respectively electrically connected to each other by bonding wires. The ninth invention is a light beam switching and adjustment device comprising: a light guide substrate which has one or more input ports, a plurality of output ports, one or more mirror receiving recesses that are formed in one surface of the light guide substrate, and light guides that conduct the light that is input into the one or more input ports to selected output ports among the plurality of output ports in accordance with the advance and retraction of the one or more mirrors with respect to the one or more mirror receiving recesses; and an actuator substrate which has the one or more mirrors and one or more actuators which are disposed in positions corresponding to the one or more mirrors so that these actuators support the corresponding mirrors, and which position these corresponding mirrors on the side of one surface of the actuator substrate in a first position that is relatively far from this surface or in a second position that is relatively close to this surface, in accordance with signals; in which the light guide substrate and the actuator substrate are aligned and joined so that the first positions of the one or more mirrors are advanced positions with respect to the one or more mirror receiving recesses, and so that the second positions of the one or more mirrors are retracted positions with respect to the one or more mirror receiving recesses; which is characterized in that the actuator substrate comprises a plurality of feed terminals used for the electrical driving of the actuators, and one or more terminals of a first type used to perform feeding for the purpose of individually driving the actuators, and one or more terminals of a second type used to perform feeding for the purpose of collectively driving all of the actuators so that all of the one or more mirrors are positioned in the second positions, are included in the plurality of feed terminals. The tenth invention is the ninth invention, which is characterized in that a driving circuit which drives the one or more actuators so that when signals that are used to cause respective desired optical switching operations are supplied to the terminals of the first type, these optical switching operations are performed, and so that when specified signals are supplied to the terminals of the second type, all of the one or more mirrors are positioned in the second positions, is mounted on the actuator substrate. The eleventh invention is the ninth invention or tenth invention, which is characterized in that at least one concavo-convex portion is provided in each mirror, and the insertion depth of the mirrors in the mirror receiving recesses can be observed by using these concavo-convex portions as a focusing reference for the microscopic observation. The twelfth invention is any of the first through eleventh inventions, which is characterized in that the light guide substrate and the actuator substrate are joined with a spacer interposed so that the second positions of the one or more mirrors are positions in which the mirrors are completely retracted from the one or more mirror receiving recesses. The thirteenth invention is the twelfth invention, which is characterized in that the spacer is disposed so that this spacer surrounds the region in which the one or more mirrors are distributed on the actuator substrate. The fourteenth invention is the thirteenth invention, which is characterized in that the space between the light guide substrate and actuator substrate is filled with a refractive index adjusting liquid which has a refractive index that is substantially the same as the refractive index of the core layers of the light guides so that this liquid enters the mirror receiving recesses, and the spacer forms a part of a sealing structure that seals the refractive index adjusting liquid. The fifteenth invention is a light beam switching and adjustment device comprising: a light guide substrate which has one or more input ports, a plurality of output ports, one or more mirror receiving recesses that are formed in one surface of the light guide substrate, and light guides that conduct the light that is input into the one or more input ports to selected output ports among the plurality of output ports in accordance with the advance and retraction of the one or more mirrors with respect to the one or more mirror receiving recesses; an actuator substrate which has the one or more mirrors and one or more actuators which are disposed in positions corresponding to the one or more mirrors so that these actuators support the corresponding mirrors, and which position these corresponding mirrors on the side of one surface of the actuator substrate in a first position that is relatively far from this surface or in a second position that is relatively close to this surface, in accordance with signals; and a relay substrate which is used to relay electrical connections to the actuator substrate; which is characterized in that the light guide substrate and the actuator substrate are aligned and joined so that the first positions of the one or more mirrors are advanced positions with respect to the one or more mirror receiving recesses, and so that the second positions of the one or more mirrors are retracted positions with respect to the one or more mirror receiving recesses, and the relay substrate is joined to the other surface of the actuator substrate so that a portion of this relay substrate protrudes from the actuator substrate. The sixteenth invention is the fifteenth invention, which is characterized in that a plurality of first pads used for electrical connections are formed on the first surface of the actuator substrate, a plurality of second pads used for electrical connections are formed on the surface of the relay substrate located on the side of the actuator substrate in the portion of the relay substrate that protrudes from the actuator substrate, the plurality of first pads and plurality of second pads are respectively electrically connected to each other by bonding wires, and a plurality of third pads used for electrical connections, each of which is electrically connected to one of the plurality of second pads, are formed on the relay substrate. The seventeenth invention is the fifteenth or sixteenth invention, which is characterized in that the device comprises a substrate which has a plurality of lead terminals used for external connections, and the plurality of third pads and plurality of lead terminals used for external connections are respectively electrically connected to each other by bonding wires. The eighteenth invention is the sixteenth or seventeenth invention, which is characterized in that a plurality of conductive parts which are respectively electrically connected to some of the second pads among the plurality of second pads are formed on the relay substrate, and the mutual disposition pitch of at least portions of the plurality of conductive parts is wider than the disposition pitch of the plurality of second pads and the disposition pitch of the plurality of third pads. The nineteenth invention is the eighteenth invention, which is characterized in that the plurality of conductive parts are formed on the surface of the relay substrate located on the side of the actuator substrate in the protruding portion of the relay substrate, and the plurality of third pads are formed on the surface of the relay substrate located on the opposite side from the actuator substrate. The twentieth invention is the eighteenth or nineteenth invention, which is characterized in that all of the one or more mirrors are positioned in the second positions when specified signals are respectively supplied to the plurality of conductive parts. The twenty-first invention is any of the eighteenth through twentieth inventions, which is characterized in that a driving circuit which drives the one or more actuators so that when signals that are used to cause respective desired optical switching operations are supplied to the plurality of third pads, these optical switching operations are performed, and so that when specified signals are respectively supplied to the plurality of conductive parts, all of the one or more mirrors are positioned in the second positions, is mounted on the actuator substrate. The twenty-second invention is a light beam switching and adjustment device comprising: a light guide substrate which has one or more input ports, a plurality of output ports, one or more mirror receiving recesses that are formed in one surface of the light guide substrate, and light guides that conduct the light that is input into the one or more input ports to selected output ports among the plurality of output ports in accordance with the advance and retraction of theone or more mirrors with respect to the one or more mirror receiving recesses; and an actuator substrate which has the one or more mirrors and one or more actuators which are disposed in positions corresponding to the one or more mirrors so that these actuators support the corresponding mirrors, and which position these corresponding mirrors on the side of one surface of the actuator substrate in a first position that is relatively far from this surface or in a second position that is relatively close to this surface, in accordance with signals; which is characterized in that the light guide substrate and the actuator substrate are aligned and joined so that the first positions of the one or more mirrors are advanced positions with respect to the one or more mirror receiving recesses, and so that the second positions of the one or more mirrors are retracted positions with respect to the one or more mirror receiving recesses, and the light guide substrate and the actuator substrate are joined with a spacer interposed so that the second positions of the one or more mirrors are positions in which the mirrors are completely retracted from the one or more mirror receiving recesses. The twenty-third invention is the twenty-second invention, which is characterized in that the spacer is disposed so that this spacer surrounds the region in which the one or more mirrors are distributed on the actuator substrate. The twenty-fourth invention is the twenty-third invention, which is characterized in that the space between the light guide substrate and actuator substrate is filled with a refractive index adjusting liquid which has a refractive index that is substantially the same as the refractive index of the core layers of the light guides so that this liquid enters the mirror receiving recesses, and the spacer forms a part of a sealing structure that seals the refractive index adjusting liquid. The twenty-fifth invention is a method for manufacturing a light beam switching and adjustment device comprising: a step of preparing a light guide substrate [i] which has one or more input ports, a plurality of output ports, one or more mirror receiving recesses that are formed in one surface of the light guide substrate, and light guides that conduct the light that is input into the one or more input ports to selected output ports among the plurality of output ports in accordance with the advance and retraction of the one or more mirrors with respect to the one or more mirror receiving recesses, and [ii] on which first alignment marks are formed; a step of preparing an actuator substrate [i] which has the one or more mirrors and one or more actuators which are disposed in positions corresponding to the one or more mirrors so that these actuators support the corresponding mirrors, and which position these corresponding mirrors on the side of one surface of the actuator substrate in a first position that is relatively far from this surface or in a second position that is relatively close to this surface, in accordance with signals, and [ii] on which second alignment marks are formed; and a step of aligning and joining the light guide substrate and the actuator substrate using the first and second alignment marks so that the first positions of the one or more mirrors are advanced positions with respect to the one or more mirror receiving recesses, and so that the second positions of the one or more mirrors are retracted positions with respect to the one or more mirror receiving recesses. The twenty-sixth invention is a method for manufacturing a light beam switching and adjustment device comprising: a step of preparing a light guide substrate which has one or more input ports, a plurality of output ports, one or more mirror receiving recesses that are formed in one surface of the light guide substrate, and light guides that conduct the light that is input into the one or more input ports to selected output ports among the plurality of output ports in accordance with the advance and retraction of the one or more mirrors with respect to the one or more mirror receiving recesses; a step of preparing an actuator substrate which has the one or more mirrors and one or more actuators which are disposed in positions corresponding to the one or more mirrors so that these actuators support the corresponding mirrors, and which position these corresponding mirrors on the side of one surface of the actuator substrate in a first position that is relatively far from this surface or in a second position that is relatively close to this surface, in accordance with signals; a step of preparing a spacer that is joined between the light guide substrate and actuator substrate; a spacer joining step in which the spacer is joined to either the light guide substrate or the actuator substrate; and a step which is performed following the spacer joining step, and in which the light guide substrate and the actuator substrate are aligned, and the spacer is joined to the other of the two substrates, i.e., either the light guide substrate or actuator substrate, so that the first positions of the one or more mirrors are advanced positions with respect to the one or more mirror receiving recesses, and so that the second positions of the one or more mirrors are retracted positions with respect to the one or more mirror receiving recesses; which is characterized in that when the spacer is joined between the light guide substrate and actuator substrate, the second positions of the one or more mirrors are positions in which the mirrors are completely retracted from the one or more mirror receiving recesses. The twenty-seventh invention is the twenty-sixth invention, which is characterized in that first alignment marks are formed on the light guide substrate, second alignment marks are formed on the actuator substrate, and the alignment of the light guide substrate and the actuator substrate is performed utilizing the first and second alignment marks. The twenty-eighth invention is any of the twenty-fifth through twenty-seventh inventions, which is characterized in that the actuators are constructed so that when absolutely no signals are supplied, the mirrors supported on these actuators return to specified positions that are farther from the actuator substrate on the first surface of this substrate than the second positions, and when the light guide substrate and the actuator substrate are aligned, specified signals are applied to the actuator substrate, so that all of the one or more mirrors are positioned in the second positions. The twenty-ninth invention is a method for manufacturing a light beam switching and adjustment device comprising: a step of preparing a light guide substrate which has one or more input ports, a plurality of output ports, one or more mirror receiving recesses that are formed in one surface of the light guide substrate, and light guides that conduct the light that is input into the one or more input ports to selected output ports among the plurality of output ports in accordance with the advance and retraction of the one or more mirrors with respect to the one or more mirror receiving recesses; a step of preparing an actuator substrate which has the one or more mirrors and one or more actuators which are disposed in positions corresponding to the one or more mirrors so that these actuators support the corresponding mirrors, and which position these corresponding mirrors on the side of one surface of the actuator substrate in a first position that is relatively far from this surface or in a second position that is relatively close to this surface, in accordance with signals; and a step of aligning and joining the light guide substrate and the actuator substrate so that the first positions of the one or more mirrors are advanced positions with respect to the one or more mirror receiving recesses, and so that the second positions of the one or more mirrors are retracted positions with respect to the one or more mirror receiving recesses; which is characterized in that the actuators are constructed so that when absolutely no signals are supplied, the mirrors supported on these actuators return to specified positions that are farther from the actuator substrate on the first surface of this substrate than the second positions, and when the light guide substrate and the actuator substrate are aligned, specified signals are applied to the actuator substrate, so that all of the one or more mirrors are positioned in the second positions. The thirtieth invention is the twenty-eighth or twenty-ninth invention, which is characterized in that signals are supplied to the actuator substrate so that all of the one or more mirrors gradually return to the specified positions described above following the completion of the alignment between the light guide substrate and the actuator substrate. In these first through twenty-eighth inventions, the light guides may be disposed in the form of a two-dimensional matrix, the mirror receiving recesses may be disposed so that these recesses include the positions of the intersection parts of the light guides, and the respective mirrors may be disposed so that these mirrors can advance into the respective intersection parts. These first through thirtieth inventions make it possible to provide light beam switching and adjustment devices that can be manufactured easily and with a good yield, and manufacturing methods for the same, in accordance with the respective inventions. Furthermore, these inventions can provide light beam switching and adjustment devices that allow a reduction in the size of the device and facilitate inspections and the like in the manufacturing process. Furthermore, the matter of which of these effects is obtained by which invention will be clear from the constructions of the inventions described above and the embodiments described later. The inventions used to achieve the second object are the following thirty-first through thirty-third inventions. The thirty-first invention is a light beam switching and adjustment device used for the switching of the light paths of light beams or adjustment of the amount of transmitted light of light beams that are propagated through light guides by inserting and removing insertion plates into and from slits formed in these light guides, which is characterized in that the light guides and slits are disposed on a first substrate, the insertion plates are held by insertion plate driving means disposed on a second substrate, the first and second substrates are disposed so that the insertion plates can be inserted into and removed from the slits, a first region of the first substrate which contains the slits and a second region of the second substrate which is provided with the insertion plates are constructed so that these regions can transmit light of a specified wavelength, this light of a specified wavelength is caused to be incident from either the first region or second region, and the transmitted light is emitted from either the second region or first region, so that the insertion positions of the insertion plates inside the slits can be observed by microscopic observation. The thirty-second invention is a light beam switching and adjustment device used for the switching of the light paths of light beams or adjustment of the amount of transmitted light of light beams that are propagated through light guides by inserting and removing insertion plates into and from slits formed in these light guides, which is characterized in that the light guides and slits are disposed on a first substrate, the insertion plates are held by insertion plate driving means disposed on a second substrate, the first and second substrates are disposed so that the insertion plates can be inserted into and removed from the slits, either a first region of the first substrate which contains the slits or a second region of the second substrate which is provided with the insertion plates is constructed so that this region can transmit light of a specified wavelength, this light of a specified wavelength is caused to be incident from either the first region or second region, and the reflected light is emitted from the first region or second region, so that the insertion positions of the insertion plates inside the slits can be observed by microscopic observation. The thirty-third invention is the thirty-first or thirty-second invention, which is characterized in that at least one concavo-convex portion is provided in each of the insertion plates, and the insertion depth of the insertion plates in the slits can be observed by using these concavo-convex portions as a focusing reference for the microscopic observation. These twenty-ninth and thirtieth inventions make it possible to provide a light beam switching and adjustment device in which discrimination of the positional relationship between the insertion plates and the slits disposed in the light guide cores is easy. Furthermore, in addition to this, the thirty-first invention makes it possible to provide a light beam switching and adjustment device in which discrimination of the insertion positions of the insertion plates inside the slits is easy. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a schematic plan view which shows in model form a light beam switching and adjustment device according to one embodiment of the present invention. FIG. 2 is a schematic sectional view along line A-B in FIG. 1, and shows a state in which all of the mirrors have advanced into the grooves of the light guide substrate. FIG. 3 is a schematic sectional view along line A-B in FIG. 1, and shows a state in which all of the mirrors have withdrawn from the grooves of the light guide substrate. FIG. 4 is a schematic plan view which shows in model form the assembly of the substrate, light guide substrate, light input optical fibers, and light output optical fibers in the manufacturing process of the light beam switching and adjustment device shown in FIG. 1. FIG. 5 is a schematic plan view which shows the actuator substrate in model form. FIG. 6 is a schematic enlarged plan view which shows one of the mirrors and one of the actuators that supports and drives this mirror in model form. FIG. 7 is a schematic sectional view along line X1-X2 in FIG. 6. FIG. 8 is a schematic sectional view along line Y1-Y2 in FIG. 6. FIG. 9 is a schematic sectional view corresponding to FIG. 7 and showing a state in which the mirror is drawn in toward the substrate. FIG. 10 is an electrical circuit diagram which shows the circuit mounted on the actuator substrate. FIG. 11 is a diagram which shows the spacer. FIG. 12 is a diagram which shows in model form the assembly of the actuator substrate and relay substrate in the manufacturing process of the light beam switching and adjustment device shown in FIG. 1. FIG. 13 is a diagram which shows the conditions of voltage application to the assembly shown in FIG. 12. FIG. 14 is a schematic sectional view which illustrates the alignment of the actuator substrate and light guide substrate in model form. FIG. 15 shows diagrams which are used to illustrate an example of the construction of the light beam switching and adjustment device of the present invention; FIG. 15(a) is a plan view of this device, and FIG. 15(b) is a sectional view along line A-A′ in FIG. 15(a). FIG. 16 is a diagram which is used to illustrate the conditions in the vicinity of the slits and insertion plates in the light beam switching and adjustment device of the present invention with a construction in which depth detection markers are disposed on the insertion plates. FIG. 17 shows diagrams which are used to illustrate an example of construction of a conventional light beam switching and adjustment device using MEMS technology; FIG. 17(a) is a plan view of this light beam switching and adjustment device, and FIG. 17(b) is a sectional view along line A-A′ in FIG. 17(a). BEST MODE FOR CARRYING OUT THE INVENTION The light beam switching and adjustment device of the present invention, and method for manufacturing the same, will be described below with reference to the figures. FIG. 1 is a schematic plan view which shows in model form a light beam switching and adjustment device according to one embodiment of the present invention. For convenience of description, mutually perpendicular X, Y and Z axes are defined as shown in FIG. 1 (these axes are the same in figures described later). Furthermore, in FIGS. 1 through 14, the same constituent elements are labeled with the same symbols, and a description for each figure may be omitted. The surface of the light guide substrate 2 and the surface of the actuator substrate 4 are parallel to the XY plane. Furthermore, for convenience of description, the + side in the direction of the Z axis (i.e., the side toward which the arrow is oriented) will be referred to as the +Z side, and the − side in the direction of the Z axis will be referred to as the −Z side. The same is true in regard to the direction of the X axis and the direction of the Y axis. FIG. 2 is a schematic sectional view along line A-B in FIG. 1, and shows a state in which all of the mirrors 31 have advanced into the grooves 24 of the light guide substrate 2. FIG. 3 is a schematic sectional view along line A-B in FIG. 1, and shows a state in which all of the mirrors 31 have withdrawn from the grooves 24 of the light guide substrate 2. FIG. 4 is a schematic plan view which shows in model form the assembly of the substrate 1, light guide substrate 2, light input optical fibers 11, and light output optical fibers 12 and 13 in the manufacturing process of the light beam switching and adjustment device shown in FIG. 1. As is shown in FIGS. 1 through 4, the light beam switching and adjustment device of the present embodiment comprises a substrate 1 such as a base disposed on the bottom surface part of a package main body (not shown in the figures) or inside a package main body, a light guide substrate 2 which is joined to the surface of the substrate 1, an actuator substrate 4 which is joined to the surface of the light guide substrate 2 with a spacer 3 interposed, and a relay substrate 5 which is joined to the surface of the actuator substrate 4. As is shown in FIGS. 1 and 4, ten lead terminals 6 used for external connections are disposed on the substrate 1. As is shown in FIGS. 2 through 4, the light guide substrate 2 has three input ports 21 in the left end surface in FIG. 4, three output ports 22 in the right end surface in FIG. 4, three output ports 23 in the lower end surface in FIG. 4, 3×3 grooves 24 used as mirror receiving recesses which are formed in the −Z-side surface of the light guide substrate 2, and light guides 25. Three light input optical fibers 11 are optically coupled to the three input ports 21, three light output optical fibers 12 are optically coupled to the three output ports 22, and three light output optical fibers 13 are optically coupled to the three output ports 23. The light guides 25 are formed so that these light guides conduct the light that is input into the three input ports 21 to selected output ports in accordance with the advance (see FIG. 2) and retraction (see FIG. 3) of 3×3 individual mirrors 31 (described later) corresponding to the 3×3 individual grooves 24. In the present embodiment, the light guides 25 are formed in the form of a 3×3 matrix, and the grooves 24 are respectively formed at the 3×3 intersection points of this matrix. The number of 3×3 described above is merely an example; the present invention is not limited to this number. In cases where a construction with the form of a two-dimensional matrix is used, this number may be set in general terms at M×N (M and N are integers of 2 or greater) instead of 3×3. For example, a case in which this number is 100×100 is the same in principle. Of course, in the present invention, it is not always necessary to use a two-dimensional matrix-form construction. The respective ports 21, 22 and 33 constitute the end portions of the light guides 25 appearing at the end surfaces of the light guide substrate 2. Furthermore, the light guides 25 are constructed from core layers, cladding layers and the like; the construction of these light guides 25 is universally known. In order to suppress light loss, it is desirable that the width of the grooves 24 be set as narrow as possible. Furthermore, the respective grooves 24 that are lined up side by side in rectilinear form in FIG. 4 may also be connected so that these grooves are constructed as a single integral groove overall. It goes without saying that such a light guide substrate 2 can be manufactured by a publicly known manufacturing method using a silicon substrate, glass substrate, or the like. Unlike the case of a conventional light guide substrate, alignment marks 26 which are used for the alignment of the light guide substrate 2 and actuator substrate 4 are formed on the −Z-side surface of the light guide substrate 2 as shown in FIG. 4. For example, these alignment marks 26 can be formed by etching the light guide substrate 2 to a depth of approximately 1 μm using an ordinary photolithographic/etching technique, and these alignment marks 26 can be observed by means of infrared light. In the present embodiment, as is shown in FIG. 4, the alignment marks 26 are formed in two places with a cruciform pattern. However, the pattern and number, etc., of the alignment marks 26 may be appropriately set as desired. However, as will be described later, it is necessary that the alignment marks 26 be set so that these marks can be observed using infrared light in order to perform alignment by means of infrared light with alignment marks 39 formed on the actuator substrate 4. Next, the actuator substrate 4 will be described with reference to FIGS. 5 through 10. FIG. 5 is a schematic plan view which shows the actuator substrate 4 in model form. Furthermore, in FIG. 5, the actuators 32, wiring patterns, driving circuit and the like are omitted. FIG. 6 is a schematic enlarged plan view which shows one of the mirrors 31 and one of the actuators 32 that supports and drives this mirror 31 in model form. FIG. 7 is a schematic sectional view along line X1-X2 in FIG. 6. FIG. 8 is a schematic sectional view along line Y1-Y2 in FIG. 6. FIG. 9 is a schematic sectional view corresponding to FIG. 7, and shows a state in which the mirror 31 is held in a position that is relatively close to the +Z-side surface of the actuator substrate 4 (second position, which is a position on the +Z-side surface of the actuator substrate 4 in the present embodiment; this will be referred to below as a “state in which the mirror 31 is drawn in toward the substrate 4”). Incidentally, FIG. 7 shows a state in which the mirror 31 has returned to a position (first position) that is relatively distant from the +Z-side surface of the actuator substrate 4 (this will be referred to below as a “state in which the mirror 31 protrudes from the substrate 4”). FIG. 10 is an electrical circuit diagram which shows the circuit mounted on the actuator substrate 4. The actuator substrate 4 has 3×3 micromirrors 31 and one or more actuators 32 which are disposed in positions corresponding to these mirrors 31 so that these actuators support the corresponding mirrors 31, and which position these corresponding mirrors 31 on the side of the +Z surface of the actuator substrate 4 (i.e., on the +Z side of the substrate 4) in a first position (see FIG. 7) that is relatively far from this surface or in a second position (see FIG. 9) that is relatively close to this surface, in accordance with signals. As is shown in FIG. 5, the 3×3 mirrors 31 are disposed in positions corresponding to the 3×3 grooves 24 in the light guide 25. As is shown in FIGS. 6 through 9, each actuator 32 comprises a movable plate 33 and flexure parts 34a and 34b that are disposed on either side of the movable plate 33 in the direction of the X axis. Recessed parts 38 which form regions into which the movable plates 33 advance are formed in the actuator substrate. In the present embodiment, a semiconductor substrate such as a silicon substrate is used as the actuator substrate 4, and the portions that face the movable plates 33 on the substrate 4 constitute first electrode parts. Of course, it would also be possible to form the first electrode parts separately from the substrate 4 by means of metal films or the like on the surface of the substrate 4. Each movable plate 33 is formed by a thin film, and is constructed from a lower-side insulating film 36 consisting of an SiN film or SiO2 film, and a metal film 37 such as an Al film used as a second electrode part, which is formed on top of the lower side insulating film 36. The metal film 37 can generate an electrostatic force between this metal film 37 and the substrate 4 that constitutes the first electrode part by means of a voltage that is applied across this metal film 37 and the substrate 4. In the present embodiment, both end portions of each movable plate 33 in the direction of the X axis are mechanically connected to the peripheral portions of the recessed part 38 in the substrate 4 via the respective flexure parts 34a and 34b (acting as spring parts that possess springiness) and anchor parts 35a and 35b in that order. The flexure parts 34a and 34b and anchor parts 35a and 35b are each constructed from a lower-side insulating film 36 and an upper-side metal film 37 that extend “as is” as continuations of the movable plate 33. In the anchor parts 35a and 35b, the upper-side metal films 37 are respectively electrically connected to specified locations on the substrate 4 via holes (not shown in the figures) formed in the lower-side insulating films 36. As is shown in FIG. 6, the flexure parts 34a and 34b have a sinuous shape (as seen in a plan view). As a result, the corresponding movable plate 33 can move upward and downward (i.e., in the direction of the Z axis). Specifically, in the present embodiment, the system is devised so that each movable plate 33 can move between an upper-side position (first position) (see FIGS. 7 and 8) to which the movable plate 33 is caused to return by the spring force (returning force) of the flexure parts 34a and 34b when no electrostatic force is acting on the movable plate 33 (i.e., when absolutely no signal is applied), and a lower-side position.(second position) (see FIG. 9) where the movable plate 33 advances into the recessed part 38 of the substrate 4 and contacts the bottom part of this recessed part 38 when an electrostatic force acts on the movable plate 33 (i.e., when a signal is applied). The mirrors 31 are fastened to the upper surfaces of the movable plates 33 in an upright attitude. The orientation of the reflective surfaces of the mirrors 31 is set so that the normal of each mirror 31 forms an angle of 45° with the X axis in a plane parallel to the XY plane. Of course, this orientation may be appropriately altered in accordance with the disposition of the light guides 25. In a state in which the mirrors 31 have returned to the first positions on the side of the substrate 4 (i.e., a state in which the mirrors 31 protrude from the substrate 4), as is shown in FIG. 7, the incident light advancing in the direction of the X axis is reflected by the mirrors 31 and advances toward the front with respect to the plane of the page in FIG. 7. In a state in which the mirrors 31 are positioned in the second positions (i.e., a state in which the mirrors 31 are drawn in toward the substrate 4), as is shown in FIG. 9, the incident light advancing in the direction of the X axis is not reflected by the mirrors 31, and passes through “as is” to form emitted light. In FIGS. 7 and 9, the incident light that reaches the positions of the mirrors 31 is shown as though this light were propagated through space. However, as a result of the light guide substrate 2 and actuator substrate 4 being aligned and joined with a spacer 3 interposed as shown in FIGS. 2 and 3, this incident light, after being guided by the light guides 25 of the light guide substrate 2 so that this light reaches the interiors of the grooves 24 in the light guide substrate 2, is guided to the light guide 25 in the direction in question after being either reflected or allowed to pass through “as is” by the mirrors 31 according to whether the mirrors 31 are positioned in the first or second positions. Specifically, the light guide substrate 2 and actuator substrate 4 are aligned and joined with a spacer 3 interposed so that the first positions of the respective mirrors 31 are positions in which the mirrors 31 are advanced relative to the respective grooves 24 in the light guide substrate 2, and so that the second positions of the respective mirrors 31 are positions in which the mirrors 31 are retracted relative to the respective grooves 24. In the present embodiment, as is shown in FIG. 3, the thickness of the spacer 3 is set so that the second positions of the respective mirrors 31 are positions in which the mirrors are completely retracted from the grooves 24. As is shown in FIG. 11, the spacer 3 is constructed in the form of a frame and disposed so that this spacer 3 surrounds the area in which all of the mirrors 31 are distributed. FIG. 11 shows the spacer 3; FIG. 11(a) is a plan view, and FIG. 11(b) is an arrow view along line X3-X4 in FIG. 11(a). As is shown in FIGS. 2 and 3, the space between the light guide substrate 2 and actuator substrate 4 is filled with a refractive index adjusting liquid 30 which has substantially the same refractive index as the refractive index of the core layers of the light guides 25 of the light guide substrate 2, so that this liquid enters the interiors of the grooves 24. The spacer 3 forms one portion of a sealing structure that seals the refractive index adjusting liquid 30. The spacer 3 plays a large role in preventing damage to the mirrors 31 during the alignment of the light guide substrate 2 and actuator substrate 4 (as will be described later). This spacer 3 also has the function of allowing easy sealing of the refractive index adjusting liquid 30. As a result of the spacer 3 thus being endowed with the function of sealing the refractive index adjusting liquid 30, there is no need for the separate installation of a special sealing member. Furthermore, from the standpoint of reducing the amount of light loss, it is desirable to fill the space described above with a refractive index adjusting liquid 30; however, it is not absolutely necessary to fill this space with such a refractive index adjusting liquid 30. As is shown in FIG. 5, alignment marks 39 which are used for the alignment of the light guide substrate 2 and actuator substrate 4 are formed on the +Z-side surface of the actuator substrate 4. These alignment marks 39 are disposed so that these marks 39 are precisely superimposed on the alignment marks 26 (see FIG. 4) formed on light guide substrate 2 as shown in FIG. 1 when the two substrates are accurately aligned as described above. For example, these alignment marks 39 can also be formed by etching the actuator substrate 4 to a depth of approximately 1 μm using an ordinary photolithographic/etching technique, and these alignment marks 39 can be observed by means of infrared light. The actuator substrate 4 is constructed from a silicon substrate or the like, and has the characteristic of blocking visible light, but transmitting infrared light. By thus forming the alignment marks 39 as marks that can be observed using infrared light, and observing these marks 39 via an actuator substrate 4 made of a material that allows the transmission of infrared light, it is possible to recognize the positions of the alignment marks 39 even in cases where the alignment marks 39 are disposed on the back side of the actuator substrate 4. In the present embodiment, the driving circuit shown in FIG. 10 is mounted on the actuator substrate 4. However, the voltage VC in FIG. 10 is supplied from the outside. In electrical-circuit terms, the single actuator 32 that drives the single mirror 31 shown in FIGS. 6 through 9 may be viewed as a single capacitor (a capacitor formed by the first electrode part (substrate 4) and second electrode part (metal film 37 which constitutes the movable plate 21)). In FIG. 10, the capacitors of the actuators 32 in m rows and n columns are respectively indicated as Cmn. For example, the capacitor of the actuator 32 at the upper left (row 1, column 1) in FIG. 10 is indicated as C11. When voltages are applied to the capacitors Cmn, an electrostatic force that causes mutual attraction is generated between the movable plates 21 of the corresponding actuators and the substrate 4, so that the mirrors 31 assume a state in which these mirrors are drawn in toward the substrate 4 as shown in FIGS. 3 and 9. When the capacitors Cmn are discharged, the electrostatic force between the movable plates 21 of the corresponding actuators and the substrate 4 disappears, so that the mirrors 31 are caused by the spring force to assume a state in which the mirrors 31 protrude from the substrate 4 as shown in FIGS. 2 and 7. Specifically, the corresponding mirrors 31 can be moved by applying a voltage to the capacitors Cmn and discharging this voltage. In the circuit shown in FIG. 10, column selection switches Mmnb and row selection switches Mmna are disposed for the capacitors Cmn. One end of each capacitor Cmn is connected to one end of the corresponding row selection switch Mmna, the other end of this row selection switch Mmna is connected to one end of the corresponding column selection switch Mmnb, and the other end of this column selection switch Mmnb is connected to one end of a voltage control switch MC1 and one end of a voltage control switch MC2. The other end of each capacitor Cmn is connected to ground. The other end of the voltage control switch MC1 is connected to a clamping voltage VC, and the other end of the voltage control switch MC2 is connected to ground. The gates of the voltage control switches MC1 and MC2 are respectively connected to terminals C1 and C2. For example, in cases where a silicon substrate is used as the actuator substrate 4, the column selection switches Mmnb, row selection switches Mmna, and voltage control switches MC1 and MC2 used as switching elements can be constructed from N-type MOS transistors formed on the substrate 4. Here, it is assumed that these switches are constructed from N-type MOS transistors. The gates of the row selection switches M11a, M12a and M13a of the first row are connected in common by wiring OV1, and are connected to the output terminal of a NOR gate NV1 (furthermore, in the figure, the NOR gates are indicated by the symbol commonly used for AND gates; however, these gates are all NOR gates). Similarly, the gates of the row selection switches of the second row are connected to the output terminal of a NOR gate NV2 by wiring OV2, and the gates of the row selection switches of the third row are connected to the output terminal of a NOR gate NV3 by wiring OV3. One of the input terminals of each of the NOR gates NV1 through NV3 is connected to a terminal V1, and the other input terminals of these NOR gates are respectively connected to the respective output terminals of a decoder DV via respective sets of wiring DV1 through DV3. The decoder DV supplies row selection signals corresponding to the states of address terminals VA1 and VA2 to the wiring DV1 through DV3. The gates of the column selection switches M11b, M12b and M13b of the first column are connected in common by wiring OH1, and are connected to the output terminal of a NOR gate NH1. Similarly, the gates of the column selection switches of the second column are connected to the output terminal of a NOR gate NH2 by wiring OH2, and the gates of the column selection switches of the third column are connected to the output terminal of a NOR gate NH3 by wiring OH3. One of the input terminals of each of the NOR gates NH1 through NH3 is connected to a terminal H1, and the other input terminals of these NOR gates are respectively connected to the respective output terminals of a decoder DH via respective sets of wiring DH1 through DH3. The decoder DH supplies column selection signals corresponding to the states of address terminals HA1 and HA2 to the wiring DH1 through DH3. In the use state of an ordinary light beam switching and adjustment device, it is necessary to move specified mirrors 31 as required. For example, in a case where only the mirror 31 corresponding to the capacitor C11 is to be placed in a state in which this mirror 31 protrudes from the substrate 4 as shown in FIGS. 7 and 8 from a state in which all of the mirrors 31 are drawn in toward the substrate 4 as shown in FIGS. 3 and 9, i.e., a state in which a voltage is applied to all of the capacitors, the switches M11a, M11b and MC2 are switched ON, so that the capacitor C11 is discharged. In this case, if the respective switches are N-type MOS transistors, the sets of wiring OH1 and OV1 are placed at a high level of approximately 5 V, and the sets of wiring OH2, OH3, OV2 and OV3 are placed at a low level of approximately 0 V. If the terminal C2 is then placed at a high level, a discharge of the capacitor C11 occurs. The wiring OH1 can be placed at a high level by placing either of the input terminals of the NOR gate NH1 at a low level. The terminal H1 is constantly maintained at a high level, and the wiring DH1 is controlled by the states of the address terminals HA1 and HA2 of the decoder DH. For example, the logic of the decoder DH is constructed so that when HA1 is at a high level and HA2 is at a low level, DH1 is at a low level, and DH2 and DH3 are at a high level. Similarly, the wiring OV1 can be placed at a high level by placing either of the input terminals of the NOR gate NV1 at a low level. The terminal V1 is constantly maintained at a high level, and the wiring DV1 is controlled by the states of the address terminals VA1 and VA2 of the decoder DV. For example, the logic of the decoder DV is constructed so that when VA1 is at a high level and VA2 is at a low level, DV1 is at a low level, and DV2 and DV3 are at a high level. Where N is the number of address terminals, a decoder circuit with a maximum of 2N outputs can be constructed by ordinary methods. The operation of such an ordinary light beam switching and adjustment device in the use state can be realized by removing the NOR gates NV1 through NV3 and NH1 through NH3 and the terminals V1 and H1, making a direct connection between the wiring OV1 and DV1, and also making direct connections between the corresponding sets of wiring. Such a driving circuit construction is a circuit construction that is formed in accordance with conventional technical common sense. In the present embodiment, on the other hand, all of the switches Mnma and Mnmb can be switched ON independently of the outputs of the decoders DH and DV by adding the NOR gates NV1 through NV3 and NH1 through NH3 and terminals V1 and H1 and wiring these parts as described above, so that the control terminals H1 and V1 are placed at a low level. In this case, if the terminals H1 and V1 are placed at a low level and the terminal C1 is placed at a high level, all of the capacitors Cmn are charged. As a result, a state is created in which all of the mirrors 31 are drawn in toward the substrate 4. Accordingly, in the present embodiment, a state can be created in which all of the mirrors 31 are drawn in toward the substrate 4 merely by supplying the respective specified signals described above to a total of six terminals, i.e., the terminals H1, V1, C1 and C2, the clamping voltage VC terminal (not shown in the figure), and the ground terminal (not shown in the figure), without supplying signals to the address terminals VA1, VA2, HA1 and HA2 (i.e., by placing these address terminals in an electrically floating state). Furthermore, since the signals that are to be applied to the terminals H1 and V1 are always the same, both of these terminals can be connected in common. In this case, the number of terminals that is to be used can be further reduced by 1. Of course, even if the circuit construction described above in which the NOR gates NV1 through NV3 and NH1 through NH3 and the terminals V1 and H1 are excluded is used, a state can be created in which all of the mirrors 31 are drawn in toward the substrate 4 by supplying respective specified signals to a total of eight terminals, i.e., the terminals C1, C2, VA1, VA2, HA1 and HA2, the clamping voltage VC terminal, and the ground terminal. In this case, however, an increase in the number of terminals that must be used cannot be avoided. In particular, when the number of mirrors 31 increases, there is also a corresponding increase in the number of address terminals; as a result, there is a great increase in the number of terminals that must be used in order to place all of the mirrors 31 in a state in which the mirrors are drawn in toward the substrate 4. For example, in cases where the number of light input optical fibers 11, the number of light output optical fibers 12, and the number of light output optical fibers 13 are all 64, the number of mirrors 31 is 64×64. Since 64=26, the total number of address terminals required is 12, i.e., 6 horizontal and 6 vertical. In this case, in order to place all of the mirrors 31 in the state shown in FIG. 9 using the circuit construction in which the NOR gates NV1 through NV3 and NH1 through NH3 and the terminals V1 and H1 are removed, it is necessary to supply signals to 12 address terminals in addition to the terminals C1 and C2, the clamping voltage VC terminal and the ground terminal, so that signals must be supplied to a total of 16 terminals. On the other hand, if a circuit construction which uses the NOR gates NV1 through NV3 and NH1 through NH3 and the terminals V1 and H1 is employed as in the present embodiment, even if the number of mirrors 31 is 64×64, all of the mirrors 31 can be placed in a state in which the mirrors are drawn in toward the substrate 4 merely by supplying signals to 6 terminals regardless of the number of mirrors 31. Significant advantages can be obtained in the manufacture of the light beam switching and adjustment device of the present embodiment as a result of the fact that all of the mirrors 31 are placed in a state in which the mirrors are drawn in toward the substrate 4, and the fact that only a small number of terminals need be used in order to create this state; however, these points will be described later. In the present embodiment, as is shown in FIG. 5, 10 pads (first pads) 40 used for electrical connections, which respectively correspond to the terminals H1, V1, C1, C2, VA1, VA2, HA1 and HA2, the clamping voltage VC terminal, and the ground terminal, are formed on the +Z-side surface of the actuator substrate 4. For example, the actuator substrate 4 constructed as described above can be manufactured using semiconductor manufacturing techniques such as film formation, patterning and etching besides a MOS transistor manufacturing process. Here, the relationship between the actuator substrate 4 and the relay substrate 5 will be described not only with reference to FIGS. 1 through 3, but also with reference to FIG. 12. FIG. 12 comprises diagrams which show (in model form) the assembly of the actuator substrate 4 and relay substrate 5 in the manufacturing process of the light beam switching and adjustment device shown in FIG. 1. FIG. 12(a) is a schematic plan view as seen from the +Z side, FIG. 12(b) is an arrow view along line Y3-Y4 in FIG. 12(a), and FIG. 12(c) is a schematic plan view as seen from the −Z side. As is shown in these figures, the relay substrate 5 is a substrate which is used to relay electrical connections to the actuator substrate 4. For example, this substrate is constructed from a ceramic substrate, and has characteristics that substantially prevent the transmission of infrared light. The relay substrate 5 is joined to the −Z-side surface of the actuator substrate 4 so that a portion of this substrate 5 protrudes from the actuator substrate 4. An opening part 41 is formed in the central portion of the relay substrate 5 so that the relay substrate 5 does not cover the −Z-side surface regions of the actuator substrate 4 corresponding to the alignment marks 39 formed on the +Z-side surface of the actuator substrate 4. Even if the relay substrate 5 is a substrate that allows the transmission of infrared light, it is desirable to form such an opening part 41 in order to minimize the attenuation of infrared light so that the alignment marks 39 can be clearly recognized. As is shown in FIG. 12, 10 pads (second pads) 42 used for electrical connections, which correspond to the pads (first pads) 40 on the actuator substrate 4 on a one-to-one basis, are formed on the +Z-side surface of the portion of the relay substrate 5 that protrudes from the actuator substrate 4. The respective pads 40 and respective pads 42 are electrically connected by bonding wires 43 consisting of metal wires, etc. Thus, as a result of a portion that protrudes from the actuator substrate 4 being formed on the relay substrate 5, the pads (second pads) 42 used for electrical connections can be disposed on this protruding portion, so that the electrical connection of these pads 42 with the pads (first pads) 40 on the actuator substrate 4 is facilitated. If wire bonding is used for such electrical connections as described above, the work is facilitated. Six wiring patterns 44 that are respectively electrically connected to six of the pads 42 among the 10 pads 42 are formed on the +Z-side surface of the protruding portion of the relay substrate 5. These six wiring patterns 44 respectively extend to the end edge of the protruding portion, and the disposition pitch of the parts in the vicinity of this end edge is wider than the disposition pitch of the pads 40 and the disposition pitch of pads 46 (described later). In the state shown in FIG. 12, the root portions of six temporary lead terminals 45 are connected to portions of the six wiring patterns 44 located in the vicinity of the end edge, and the disposition pitch of these lead terminals 45 is also wide. As a result of the disposition pitch of the portions of the six wiring patterns 44 located in the vicinity of the end edge thus being set at a pitch that is wider than the disposition pitch of the pads 40 and the disposition pitch of the pads 46 (described later), the attachment of the lead wires is facilitated when such lead wires are connected to the temporary lead terminals 45 so that the actuator substrate 4 and light guide substrate 2 are aligned in a state in which all of the mirrors 31 are drawn in toward the substrate 4 by supplying electric power from a temporary voltage application circuit and actuating the microactuators (as will be described later). The six pads 42 respectively correspond to the terminals H1, V1, C1 and C2, the clamping voltage VC terminal and the ground terminal that are used in order to place all of the mirrors 31 in a state in which the mirrors are drawn in toward the substrate 4. Accordingly, these six terminals are respectively electrically connected to the lead terminals 45. Consequently, when the specified signals described above are supplied from the six lead terminals 45, all of the mirrors 31 can be placed in a state in which the mirrors are drawn in toward the substrate 4. In the state shown in FIG. 12, since absolutely no signals are supplied, all of the mirrors 31 are in a state in which the mirrors protrude from the actuator substrate 4 as shown in FIG. 12(b). As will be described later, the lead terminals 45 are used when the light guide substrate 2 and actuator substrate 4 are aligned. Following this alignment, the lead terminals 45 are cut along the end edge of the actuator substrate 4, so that only the root portions of the lead terminals 45 remain on the wiring patterns 44. Accordingly, the lead terminals 45 do not appear in FIG. 1. In the present embodiment, the six wiring patterns 44 and the remaining root portions of the lead terminals 45 form six conductive parts that are respectively electrically connected to the six pads 40. As will be seen from the description above, the disposition pitch of these conductive parts toward the end edge is wider than the disposition pitch of the pads 40 and the disposition pitch of the pads 46 (described later). As is shown in FIGS. 1 and 12, ten pads (third pads) 46 used for electrical connections are formed on the −Z-side surface of the relay substrate 5. The ten third pads 46 are respectively electrically connected to the ten second pads 42 via through-holes not shown in the figures. As a result of the surface of the relay substrate 5 on which the second pads 42 are disposed and the surface of the relay substrate 5 on which the pads (third pads) 46 used for electrical connections are disposed thus being made opposite surfaces, positional interference between the second pads 42 and third pads 46 can be prevented. Furthermore, as a result of this, external wiring can be connected to the third pads 46 which are positioned on the outside of the assembly in a state in which the light guide substrate 2 and actuator substrate 4 are assembled, so that external wiring work is facilitated. As is shown in FIG. 1, the ten pads 46 are respectively electrically connected by means of bonding wires 47 consisting of metal wires, etc., to ten lead terminals 6 used for external connections disposed on the substrate 1. It is not absolutely necessary to use bonding wires for such connections; however, the work can be made more efficient by employing a connection method using bonding wires. Accordingly, the ten lead terminals 6 used for external connections are respectively electrically connected to the terminals H1, V1, C1, C2, VA1, VA2, HA1 and HA2, the clamping voltage VC terminal, and the ground terminal. Consequently, signals for performing desired optical switching operations can be supplied from the lead terminals 6 used for external connections. As a result of the electrical connections described above being made, the driving circuit shown in FIG. 10 that is mounted on the actuator substrate 4 drives the actuators 31 so that desired optical switching operations are performed when signals that cause these optical switching operations to be performed are respectively supplied to the ten pads 46, and so that all of the mirrors 31 are placed in a state in which the mirrors are drawn in toward the substrate 4 when specified signals are respectively supplied to the six conductive parts. Furthermore, in a case where the relay substrate 5 shown in FIG. 13 is used, unlike the example shown in FIG. 1, electric power can be directly supplied to the actuator substrate 4 without using the external connection lead terminals 6 disposed on the substrate 1. Furthermore, it is not absolutely necessary to use the relay substrate shown in FIG. 13 to supply electric power directly to the actuator substrate 4. For example, in FIG. 13, it would also be possible to remove the relay substrate 5 and the second pads 42, wiring patterns 44, lead terminals 45 and third pads 46 belonging to this substrate, to connect outside lead wiring directly to the pads 40 beforehand, and to supply electric power via this lead wiring. If this is done, electric power can be supplied directly to the actuator substrate 4 without using a relay substrate 5 and without using external connection lead terminals 6 disposed on the substrate 1; accordingly, the structure is simplified. Next, one example of the method for manufacturing the light beam switching and adjustment device of the present embodiment will be described. First, the substrate 1, light guide substrate 2, external connection lead terminals 6 and optical fibers 11, 12 and 13 are respectively prepared, and these parts are assembled into the state of the assembly shown in FIG. 4. Specifically, the lead terminals 6 are attached to the substrate 1, the light guide substrate 2 is joined to the substrate 1 by means of a bonding agent, etc., and the optical fibers 11 through 13 are respectively coupled with the respective ports 21 through 23 of the light guide substrate 2. Of course, as will be described later, the joining of the light guide substrate 2 to the substrate 1 and the coupling of the optical fibers 11 through 13 may also be performed after the light guide substrate 2 and actuator substrate 4 have been aligned and joined with the spacer 3 interposed. Meanwhile, the actuator substrate 4 and relay substrate 5 are respectively prepared, and these parts are assembled into the state of the assembly shown in FIG. 12. Specifically, the actuator substrate 4 and relay substrate 5 are joined by means of a bonding agent, etc., the pads 40 and 42 are connected to each other by bonding wires 43 consisting of metal wires, etc., using a wire bonding method, and the temporary lead terminals 45 are connected to the wiring patterns 44. In the state of the assembly shown in FIG. 12, signals are supplied to the actuator substrate 4 via the relay substrate 5, the operation of the actuator substrate 4 is checked, and the actuator substrate 4 is inspected. In this case, if the actuator substrate 4 is defective, this actuator substrate 4 can be discarded without being attached to the light guide substrate 2. It is also possible to employ a construction in which the pads on the actuator substrate 4 are directly connected to the external connection lead terminals 6 on the substrate 1 without installing a relay substrate 5. In such a case, however, since it is difficult to inspect the actuator substrate 4 alone, the pass/fail status of the actuator substrate can only be checked in the stage in which the light beam switching and adjustment device has finally been completed. In this case, if the actuator substrate 4 is defective, the entire light beam switching and adjustment device must be discarded; this results in increased waste both in terms of parts and in terms of the effort required in manufacture, so that an increase in cost is inevitable. Next, the spacer 3 is joined to the light guide substrate 2 in an airtight manner by means of a bonding agent or soldering, etc. Instead, it would also be possible to join the spacer 3 to the actuator substrate 4. Subsequently, the actuator substrate 4 in the assembly shown in FIG. 12 is aligned with the light guide substrate 2, and the actuator substrate 4 and spacer 3 are joined in an airtight manner by means of a bonding agent or soldering, etc. In cases where the spacer 3 is joined to the actuator substrate 4 beforehand, the spacer 3 and light guide substrate 2 may simply be joined. The conditions of this alignment are shown in FIG. 14. FIG. 14 is a schematic sectional view which shows (in model form) the conditions of the alignment of the actuator substrate 4 and the light guide substrate 2; this figure corresponds to FIGS. 2 and 3. This alignment is performed in a state in which all of the mirrors 31 are drawn in toward the substrate 4 as a result of the specified signals described above being supplied to the lead terminals 45 in the assembly shown in FIG. 12 from a voltage application circuit 51 via lead wires 52 as shown in FIG. 13. FIG. 13 shows diagrams which illustrate the conditions of voltage application to the assembly shown in FIG. 12; FIG. 13(a) is a schematic plan view as seen from the +Z side, and FIG. 13(b) is an arrow view along line Y5-Y6 in FIG. 13(a). Since alignment is performed in a state in which all of the mirrors 31 are drawn in toward the substrate 4, even if the actuator substrate 4 is lowered downward in FIG. 4 in a state in which the position of the actuator substrate 4 in the left-right direction in FIG. 4 is shifted, the system will be regulated in a state in which the actuator substrate 4 contacts the spacer 3 before the mirrors 31 strike portions other than the grooves 24 in the light guide substrate 2 (this is also seen from FIG. 3). In particular, this effect is ensured by the disposition of the spacer 3 so that this spacer 3 surrounds the region in which the mirrors 31 are distributed on the actuator substrate 4 as shown in FIG. 11. As a result, a situation can be prevented in which the mirrors 31 collide with other locations and are damaged; therefore, the manufacturing yield is improved. Such a complete damage preventing effect that prevents damage to the mirrors 31 during this alignment is obtained both as a result of the fact that all of the mirrors 31 are in a state in which the mirrors are drawn in toward the substrate 4 during alignment, and as a result of the fact that the spacer 3 is interposed. However, even if only one of these two means is used, damage to the mirrors 31 is far less likely than in cases where neither of these means is used. Since the number of terminals used in order to place all of the mirrors 31 in a state in which the mirrors are drawn in toward the substrate 4 is only six terminals (as was described above), the number of temporary lead terminals 45 required is also only six terminals; accordingly, the size of the relay substrate 5 can be reduced while maintaining the disposition pitch of the lead terminals 45 at a pitch that allows easy electrical wiring with respect to the voltage application circuit 21. The size and cost of the light beam switching and adjustment device can therefore be reduced. For example, in cases where the circuit construction described above in which the NOR gates NV1 through NV3 and NH1 through NH3 and the terminals V1 and H1 are removed is employed, 16 lead terminals 45 must be lined up side by side in the example described above in which the number of mirrors 31 is 64×64. As a result, the relay substrate 5 must be made fairly large, so that an increase in the size and cost of the light beam switching and adjustment device is unavoidable. Furthermore, the pads 42 can generally be manufactured with a narrower pitch than the lead terminals 45. Furthermore, the alignment of the actuator substrate 4 and light guide substrate 2 is performed while the alignment marks 26 and 39 respectively formed on the light guide substrate 2 and actuator substrate 4 are observed by means of infrared light. For example, the alignment marks 26 and 39 are observed through the actuator substrate 4 using an infrared microscope, and the movement of the actuator substrate 4 in the lateral direction to a position where the marks 26 and 39 are completely superimposed, and the movement of the actuator substrate 4 toward the light guide substrate 2, are simultaneously or alternately repeated so that the alignment marks 26 and 29 are aligned. Then, the actuator substrate 4 is caused to contact the spacer 3, and the actuator substrate 4 is joined to the spacer 3 by means of a bonding agent, etc. Thus, since this alignment is performed using the alignment marks 26 and 29, the alignment is easy, and this alignment can be performed with good precision. Furthermore, in the present embodiment, since the alignment marks 26 and 39 are formed on the mutually facing surfaces of the light guide substrate 2 and actuator substrate 4, the distance between the alignment marks 26 and 39 is reduced compared to a case in which one or both sets of alignment marks are formed on the surfaces located on the opposite sides. Accordingly, alignment can be performed with higher precision. Even if such a disposition of the alignment marks 26 and 39 is used, there is no obstacle to the observation of the alignment marks since the actuator substrate 4 has the characteristic of transmitting infrared light, and since the relay substrate 5 that does not transmit infrared light is disposed so that this relay substrate 5 does not cover the locations of the alignment marks 39. After the actuator substrate 4 and spacer 3 have thus been joined with all of the mirrors 31 placed in a state in which the mirrors are drawn in toward the substrate 4, the output voltage of the voltage application circuit 51 is varied so that all of the mirrors 31 are placed in a state in which the mirrors protrude from the substrate 4. If the terminal C1 in FIG. 10 is set at a low level, and the terminal C2 is then set at a high level via the corresponding lead terminals 45, the voltages of all of the capacitors Cmn are discharged, so that the electrostatic force is eliminated; accordingly, a state results in which all of the mirrors 31 are caused to protrude from the substrate 4 by the spring force of the actuators 32. As a result, all of the mirrors 31 are accommodated in the grooves 24 of the light guide substrate 2. When the mirrors 31 are thus caused to return to a state in which the mirrors protrude from the substrate 4, it is desirable that the mirrors 31 be gradually returned from a state in which the mirrors are drawn in toward the substrate 4. The reason for that is as follows: specifically, in cases where the alignment described above is incomplete so that the mirrors 31 are shifted from the grooves 24, there is a danger that the mirrors 31 will be damaged if the mirrors 31 are abruptly returned to a state in which the mirrors protrude from the substrate 4, i.e.,if the discharge of the voltages of the capacitors Cmn is abruptly performed. The mirrors 31 can be gradually returned from a state in which the mirrors are drawn in toward the substrate 4 to a state in which the mirrors protrude from the substrate 4, for example, by gradually lowering the clamping voltage VC that is supplied by the voltage application circuit 51. Subsequently, all of the lead terminals 45 are cut along the end edge of the actuator substrate 4 using a cutting tool or the like. The reason for this is that it is no longer necessary to supply signals from the voltage application circuit 51. Next, a refractive index adjusting liquid 30 is injected into the space between the light guide substrate 2 and actuator substrate 4 via an injection port (not shown in the figures) formed beforehand in the light guide substrate 2, actuator substrate 4 or spacer 3. Following this injection, the injection port is sealed. When this refractive index adjusting liquid 30 is injected, the fluid pressure created by the injection pressure acts on the mirrors 31. However, since the injection of the refractive index adjusting liquid 30 is performed in a state in which the mirrors 31 have protruded from the substrate 4 and advanced into the grooves 24, the fluid pressure to which the mirrors 31 are subjected is small, so that there is no danger that the mirrors 31 will be damaged. If the refractive index adjusting liquid 30 is injected in a state in which the mirrors 31 are drawn in toward the substrate 4 and retracted from the grooves 24, the fluid pressure to which the mirrors 31 are subjected is large, so that there is a danger that the mirrors 31 will be damaged unless the injection pressure of the refractive index adjusting liquid 30 is lowered. Next, the pads 46 on the relay substrate 5 and the external connection lead terminals 6 on the substrate 1 are connected by bonding wires 47 consisting of metal wires, etc., using a wire bonding method. As a result, the assembly in the state shown in FIG. 1 is completed. Subsequently, processes which complete the package and the like are performed as required, thus completing the light beam switching and adjustment device of the present embodiment. A light beam switching and adjustment device and a method for manufacturing the same constituting embodiments of the present invention were described above. However, the present invention is not limited to these embodiments. For example, in the embodiment described above, a structure in which both sides of each movable plate 33 were supported by flexure parts 34a and 34b was used as the structure of the actuators 32; however, for example, it would also be possible to employ a structure utilizing a cantilever. FIG. 15 shows diagrams which are used to illustrate an example of the construction of the light beam switching and adjustment device of the present invention; FIG. 15(a) is a plan view of this device, and FIG. 15(b) is a sectional view along line A-A′ in FIG. 15(a). Furthermore, in FIGS. 15 through 17, the same constituent elements are labeled with the same symbols, and a description in each figure may be omitted. As is shown in FIG. 15(a), this light beam switching and adjustment device comprises first and second light guide cores 101 (101a and 101b) on a core supporting substrate 112. The end portions of the first light guide cores 101a are connected to incident-side optical fibers 105 and transmission-side optical fibers 106, and one end of the second light guide core 101b is connected to a reflection-side optical fiber 107. Furthermore, slits 102 (102a and 102b) are formed so that these slits cut across the light guides in the intersection parts of the light guide cores. Furthermore, in FIG. 15(a), the insertion plate driving mechanism accommodating part 113 and insertion plate driving mechanism supporting substrate 114 are omitted. Furthermore, as is shown in FIG. 15(b), an insertion plate driving mechanism supporting substrate 114 is disposed on the upper surface region of the core supporting substrate 112 with an insertion plate driving mechanism accommodating part 113 interposed. The insertion plates 103 (103a and 103b) are supported by insertion plate driving mechanisms 111 which are supported on this insertion plate driving mechanism supporting substrate 114. Insertion plate driving wiring 110 which is connected to wiring terminals 109 disposed on the side surface part of the core supporting substrate 112 is formed on the insertion plate driving mechanism supporting substrate 114, and the insertion plates 103 that are disposed facing the upper parts of the slits 102 are driven upward and downward by the insertion plate driving mechanisms 111 (which are operated by an electromagnetic force or electrostatic force) so that these insertion plates 103 are inserted into or withdrawn from the slits 102, thus making it possible to perform a switching operation by switching the light paths of the light beams that are incident from the optical fiber core parts 108, or an attenuation operation by adjusting the amount of light that is transmitted. Specifically, as is shown in FIG. 15(a), in a state in which the insertion plate 103b is withdrawn from the slit 102b, for example, the incident light beam 104a that enters the slit 102b from the first light guide core 101a coupled to the incident-side optical fiber 105 is coupled “as is” with the end surface of the facing light guide core 101a to form a transmitted light beam 104c. On the other hand, in a state in which the insertion plate 103a is inserted into the slit 102a, the incident light beam 104a is reflected by the insertion plate 103a, thus forming a reflected light beam 104b; this light beam is coupled with the end surface of the light guide core 101b, so that the light path of the light beam is switched, thus realizing a switching operation. Furthermore, an attenuation operation that attenuates the intensity of the transmitted light can also be realized by adjusting the insertion positions (insertion depths) of the insertion plates 103 inside the slits 102. Ordinarily, in a light beam switching and adjustment device, the insertion plate driving wiring is formed as metal wiring, and this metal wiring presents an obstacle to microscopic observation of the insertion positions (insertion depths) of the insertion plates inside the slits. In particular, observation is extremely difficult in cases where the metal wiring is disposed in the vicinity of the slits and insertion plates. Accordingly, in the light beam switching and adjustment device of the present invention, the system is devised with the insertion plate driving wiring 110 disposed around the peripheries of the insertion plates 103 instead of in the vicinity of the insertion plates 103, so that observation of the in-plane positional relationship between the slits 102 and insertion plates 103 in the plane parallel to the plane of the core holding substrate 112 is facilitated. Specifically, as is shown in FIG. 15(a), the insertion plate driving wiring 110 is wired so that the positions of the slits 102 and insertion plates 103 are avoided, thus devising the system so that there is no obstacle to observation of the in-plane positional relationship between the slits 102 and insertion plates 103 from the normal direction of the surface of the core supporting substrate 112, which is the ordinary direction of observation. Furthermore, in this light beam switching and adjustment device, the region 115 that includes the slits 102 and insertion plates 103 shown in FIG. 15(b) is formed from a material that transmits the light used in microscopic observation, and the shape of this region 115 is also formed as a shape that does not block observation, in order to allow observation from the normal direction of the surface of the core supporting substrate 112. The device construction shown in FIG. 15 is an example of the construction used in a case in which observation is performed with the observation light transmitted through the core supporting substrate 112 and insertion plate driving mechanism supporting substrate 114. However, in the case of a device in which light is caused to be incident from the side of the core supporting substrate 112, and observation of the positions is performed from the reflected images of this light, a material and a shape that are transparent to the observation light may be used for the region that includes the slits 102 of the core supporting substrate 112. Furthermore, in cases where light is caused to be incident from the side of the insertion plate driving mechanism supporting substrate 114, and the reflected light is observed, a construction may be used in which the region in the vicinity of the insertion plates 103 of the insertion plate driving mechanism supporting substrate 114 is transparent to the observation light. An outline of the manufacturing process of the light beam switching and adjustment device of the present invention is as follows: In such a light beam switching and adjustment device, it is necessary to suppress the light loss of the transmitted light beams and reflected light beams in the slits with respect to the incident light beams to an extremely small value. For example, in order to lower the light loss in the slits to approximately 0.5 dB or less, it is desirable to set the slit width at 10 μm or less. Accordingly, in the light beam switching and adjustment device of the present invention as well, in cases where light guide cores and slits that have a width of 10 μm or less are formed, a so-called “PLC (planar light wave circuit)” technique is employed in which quartz is deposited on the surface of a silicon substrate, and this quartz is then etched. Furthermore, besides a silicon substrate, a glass substrate or the like may also be used as the core supporting substrate of the light beam switching and adjustment device of the present invention. In cases where the light beam switching and adjustment device of the present invention is used only as a variable attenuation device which varies the intensity of the transmitted light beams by controlling the positions of the insertion plates inside the slits, it is not necessary to endow the device with the switching operation function (among the functions describe above). In this case, the formation of mutually crossing light guide cores as shown in FIG. 15 is unnecessary, and it is also unnecessary to use a PLC technique for the formation of the light guide cores. In such a case, a glass substrate in which the positions of the optical fibers can be designated by the formation of V grooves or the like may be used, and the optical fiber core parts may be used as light guide cores, and a glass substrate as the core supporting substrate, by forming slits in the optical fibers that are bonded and fastened to this substrate. Meanwhile, the insertion plates are formed on a silicon substrate using MEMS technology, this silicon substrate is used as the insertion plate driving mechanism supporting substrate, and the device is completed as a light beam switching device by bonding these parts after optimizing the in-plane positional relationship between the slits and the insertion plates by means of alignment marks disposed beforehand. Furthermore, the present invention, which allows monitoring from the outside, is also effective in cases where the state of alignment between the insertion plates and the slits is finely adjusted before bonding is completed. In order to confirm the effects of the construction used in this light beam switching device of the present invention, a light beam switching and adjustment device was manufactured by respectively forming light guide cores and insertion plates on a core supporting substrate and an insertion plate driving mechanism supporting substrate consisting of silicon substrates, and forming aluminum insertion plate driving wiring on the surface of the insertion plate driving mechanism supporting substrate in a pattern that avoided wiring in the vicinity of the insertion plates and slits. Infrared light was transmitted from the core supporting substrate side of this light beam switching and adjustment device, and the transmitted light was observed by means of an infrared microscope from the side of the insertion plate driving mechanism supporting substrate. As a result, the in-plane positional relationship between the insertion plates and slits was clearly observed without any blocking of the infrared light by the insertion plate driving wiring or the like. Furthermore, the in-plane positional relationship between the insertion plates and the slits was clearly observed both in a case in which infrared light was caused to be incident from the side of the insertion plate driving mechanism supporting substrate and the reflected images of this light were observed, and a case in which infrared light was caused to be incident from the side of the core supporting substrate and the reflected images of this light were observed from the side of the core supporting substrate. Furthermore, the in-plane positional relationship between the insertion plates and the slits was clearly observed from the side of the core supporting substrate in a variable attenuation device in which a glass substrate was used as the core supporting substrate, and the light guide cores of optical fiber core parts were formed on top of this substrate. The positional observations described above relate to the relative positions of the insertion plates and slits in the plane parallel to the surface of the core supporting substrate. In the case of such planar observations, even if it is assumed that the focal point of the microscope is successfully adjusted to the insertion plates, the depth of field is shallow when the magnification of the microscope is high; as a result, the positions of the insertion plates in the direction of depth inside the slits is usually unclear, so that the positions of the insertion plates in the direction of depth inside the slits is difficult to ascertain. In order to simultaneously obtain positional information for the insertion plates in the direction of depth inside the slits in addition to in-plane positional relationship information, it is effective to provide depth detection markers on the insertion plates of the light beam switching and adjustment device of the present invention. The depth positions of the insertion plate can be observed by adjusting the focal point of the microscope to these markers. FIG. 16 is a diagram which is used to illustrate the conditions in the vicinity of the slits 102 and insertion plates 103 of the light beam switching device of the present invention with a construction in which projection-form depth detection markers 116 are disposed in appropriate positions on the insertion plates 103. A total of six depth detection markers 116, i.e., three markers each on the left and right, are disposed on the insertion plate 103 shown in this figure. Furthermore, the construction shown in this figure is such that the depth detection markers 116 are disposed on the insertion plates 103; however, it would also be possible to use a construction in which markers are formed on both the insertion plates 103 and the light guide cores 101. If such a construction is used, the relationship of the positions of the insertion plates 103 and slits 102 in the direction of depth can be more easily observed; furthermore, the degree of tilting of the insertion plates 103 inside the slits 102 can be determined from the overlapping of the markers by setting the observation conditions so that the direction of extension of the insertion plates 103 coincides with the direction of position observation. Furthermore, the shape of the markers is not limited to projections; these markers may be indented or projecting parts (varying parts) such as indentations, and it is sufficient if at least one such marker is disposed on each insertion plate 103. Furthermore, if the projecting parts of the depth detection markers are attached to the tip end portions of the insertion plates 103 as shown (for example) by 116a, this is convenient for observing the positional relationship of the slits 102 and insertion plates 103 from the side of the core supporting substrate 112 following bonding, and is also effective in the fine adjustment of bonding. In order to confirm the effect of disposing such markers, the conditions of insertion of the insertion plates 103 into the slits 102 were observed using a light beam switching and adjustment device with a construction in which the projections shown in FIG. 16 were used as markers. As a result, when the positions of the projections were read from the depth scale of the microscope using the depths of the cores 101 as a reference, it was possible to detect the positions of the insertion plates 103 with a precision of 3 μm or better. Furthermore, when observations were performed with the projections overlapping each other, it was confirmed that there was almost no tilting of the insertion plates in the direction of observation. Moreover, when observations were not performed with the projections overlapping each other, it was possible to determine the tilting of the insertion plates by calculation from the shift in the positions of the respective projections in the horizontal direction and the distance between the projections at the time of manufacture of the insertion plates. INDUSTRIAL APPLICABILITY For example, the light beam switching and adjustment device of the present invention can be utilized to perform the light path switching of light beams and adjustment of the amount of transmitted light in optical communication systems.

<SOH> BACKGROUND ART <EOH>Light beam switching and adjustment devices used for light path conversion are necessary in optical communications systems, and in recent years, matrix light beam switching and adjustment devices used to perform light path switching among a plurality of inputs and outputs have become especially important. For example, such matrix light beam switching and adjustment devices perform actions such as the transmission of light signals from one of numerous parallel input optical fibers to one of numerous parallel output optical fibers; a light beam switching and adjustment device such as that disclosed in Japanese Patent Application Kokai No. 2001-142008 is known as a concrete example of such a device. In such a light beam switching and adjustment device, light from optical fibers is conducted to light guides in which light paths are formed in a matrix. Micromirrors using MEMS technology (MEMS: micro-electro-mechanical systems) are disposed at the intersection points of the light paths, and light path conversion and adjustment of the amount of transmission of the light beams are performed by moving these micro-mirrors into and out of slits disposed in the light paths. FIG. 17 shows diagrams used to illustrate an example of the construction of a conventional light beam switching and adjustment device using MEMS technology. FIG. 17 ( a ) is a plan view of this light beam switching and adjustment device, and FIG. 17 ( b ) is a sectional view along line A-A′ in FIG. 17 ( a ). As is shown in FIG. 17 ( a ), this light beam switching and adjustment device comprises first through third light guide cores 302 a , 302 b and 302 c on a core supporting substrate 301 . These light guide cores are connected to incident-side optical fibers 308 or transmission-side optical fibers 309 , and slits 303 are disposed in the intersection parts of the light guide cores so that these slits cut across the light guides that intersect with each other. Furthermore, an insertion plate supporting substrate 304 is disposed as shown in FIG. 17 ( b ) on the upper surface region of the core supporting substrate 301 indicated by a dotted line in FIG. 17 ( a ), and a structure is formed in which insertion plates 305 disposed on this insertion plate supporting substrate 304 are driven by an insertion plate driving mechanism 307 . Furthermore, 306 indicates electrical wiring used for the electrical driving of the insertion plate driving mechanism. The insertion plates 305 are disposed facing the upper portions of the slits 303 . The insertion plates 305 are driven upward and downward by the insertion plate driving mechanism 307 so that these insertion plates 305 are inserted into or removed from the slits 303 . As a result, a switching action based on the switching of the light paths of the light beams that enter the slits 303 from the optical fiber core parts 310 of the incident-side optical fibers 308 , and an attenuation action based on the adjustment of the amount of transmitted light, can be accomplished. Specifically, in a state in which the corresponding insertion plate 305 is inserted into the corresponding slit 303 , the light beam that enters this slit 303 from the first light guide core 302 a is reflected by the insertion plate 305 , and is therefore coupled with the end surface of the second light guide core 302 b . On the other hand, in a state in which this insertion plate 305 is withdrawn from the slit 303 , the light beam that enters the slit 303 from the first light guide core 302 a is coupled “as is” with the end surface of the facing third light guide core 302 c . In this way, switching of the light paths of the light beams is performed, so that a switching action is realized. Furthermore, if the insertion position (insertion depth) of the insertion plate 303 in the slit 303 is adjusted, an attenuation action that attenuates the intensity of the transmitted light can be realized by blocking a portion of the light beam that enters the slit 303 from the first light guide core 302 a in accordance with this insertion position, and allowing the remaining light beam component to pass through so that this component is coupled with the end surface of the third light guide core 302 c. In order to realize a light beam switching and adjustment device based on the system described above, it is necessary to attach MEMS actuators and micro-mirrors manufactured on the surface of a silicon substrate or the like by a MEMS process using a silicon semiconductor process or the like to a light guide substrate manufactured by a separate process. Specifically, in the manufacture of this light beam switching and adjustment device, it is necessary to join a light guide substrate which has mirror receiving recesses and an actuator substrate which has mirrors and actuators that support and move these mirrors, after aligning the mirrors and the mirror receiving recesses. However, in the actual performance of such alignment, it has been ascertained that this alignment is extremely difficult. Specifically, since the mirror receiving recesses are disposed at intermediate points in the light guides, it is desirable that the width of the mirror receiving recesses be set as narrow as possible in order to suppress light loss. Accordingly, an extremely high degree of precision is required in the alignment of the mirrors and mirror receiving recesses. Furthermore, if the mirrors collide with parts other than the mirror receiving recesses in the process of this alignment of the mirrors relative to the mirror receiving recesses, the mirrors are easily damaged. Accordingly, the alignment of the light guide substrate and actuator substrate is extremely difficult. Especially in cases where the number of mirrors is large, all of the mirrors must be aligned with the corresponding mirror receiving recesses; accordingly, this alignment is extremely difficult. Furthermore, the actuators are driven in accordance with signals. In the light beam switching and adjustment device of the present invention, the device has the following special characteristic: namely, the actuator substrate is joined with the light guide substrate in the assembly process. With this as a prerequisite, in order to reduce the size of the device and to facilitate inspections and the like during the manufacturing process, it is necessary to devise the structure of the wiring and the like that is used to supply signals to the actuator substrate so that this wiring, etc., does not interfere with the assembly, and so that inspections can easily be performed by connecting temporary wiring during such inspections. Furthermore, in such a light beam switching and adjustment device, the relative positional relationship between the insertion plates and the slits formed in the light guide cores needs to be set so that the reflection loss is minimized when the insertion plates are caused to function as reflective plates. Furthermore, in order to reduce the loss of reflected light, it is desirable that the positions of the insertion plates with respect to the slits be aligned with a precision of 1 μm or better. Moreover, in cases where the amount of attenuation of the light beams is adjusted, the insertion plates must be smoothly driven by the insertion plate driving mechanism. In order to observe the state of high-precision alignment of the insertion plates and slits in such a light beam adjustment device, it is important to accurately monitor these relative positions and the insertion depth of the insertion plates inside the slits from the outside. Generally, a method is used in which microscopic observation by an optical method is used to monitor the relative positional relationship between the insertion plates and the slits following the bonding of the core supporting substrate and insertion plate supporting substrate, with observation being performed using an infrared microscope in cases where the device is constructed using silicon substrates, and using a common optical microscope equipped with a visible-light light source in cases where glass substrates are used. However, in addition to the insertion plate driving mechanism being attached to the insertion plate supporting substrate, wiring used to operate the insertion plate driving mechanism is also disposed. Accordingly, the following problem arises: namely, the presence of such constituent elements is a major obstacle to observation of the relative positional relationship between the insertion plates and the slits. Furthermore, the following problem is also encountered: specifically, the observational magnification during microscopic observation inevitably increases according to the width of the slits and the size of the insertion plates that are the objects of observation; accordingly, the depth of field is shallow, so that it is difficult to discriminate the insertion positions of the insertion plates inside the slits.

<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>FIG. 1 is a schematic plan view which shows in model form a light beam switching and adjustment device according to one embodiment of the present invention. FIG. 2 is a schematic sectional view along line A-B in FIG. 1 , and shows a state in which all of the mirrors have advanced into the grooves of the light guide substrate. FIG. 3 is a schematic sectional view along line A-B in FIG. 1 , and shows a state in which all of the mirrors have withdrawn from the grooves of the light guide substrate. FIG. 4 is a schematic plan view which shows in model form the assembly of the substrate, light guide substrate, light input optical fibers, and light output optical fibers in the manufacturing process of the light beam switching and adjustment device shown in FIG. 1 . FIG. 5 is a schematic plan view which shows the actuator substrate in model form. FIG. 6 is a schematic enlarged plan view which shows one of the mirrors and one of the actuators that supports and drives this mirror in model form. FIG. 7 is a schematic sectional view along line X 1 -X 2 in FIG. 6 . FIG. 8 is a schematic sectional view along line Y 1 -Y 2 in FIG. 6 . FIG. 9 is a schematic sectional view corresponding to FIG. 7 and showing a state in which the mirror is drawn in toward the substrate. FIG. 10 is an electrical circuit diagram which shows the circuit mounted on the actuator substrate. FIG. 11 is a diagram which shows the spacer. FIG. 12 is a diagram which shows in model form the assembly of the actuator substrate and relay substrate in the manufacturing process of the light beam switching and adjustment device shown in FIG. 1 . FIG. 13 is a diagram which shows the conditions of voltage application to the assembly shown in FIG. 12 . FIG. 14 is a schematic sectional view which illustrates the alignment of the actuator substrate and light guide substrate in model form. FIG. 15 shows diagrams which are used to illustrate an example of the construction of the light beam switching and adjustment device of the present invention; FIG. 15 ( a ) is a plan view of this device, and FIG. 15 ( b ) is a sectional view along line A-A′ in FIG. 15 ( a ). FIG. 16 is a diagram which is used to illustrate the conditions in the vicinity of the slits and insertion plates in the light beam switching and adjustment device of the present invention with a construction in which depth detection markers are disposed on the insertion plates. FIG. 17 shows diagrams which are used to illustrate an example of construction of a conventional light beam switching and adjustment device using MEMS technology; FIG. 17 ( a ) is a plan view of this light beam switching and adjustment device, and FIG. 17 ( b ) is a sectional view along line A-A′ in FIG. 17 ( a ). detailed-description description="Detailed Description" end="lead"?

20040624

20060307

20050127

69212.0

KIANNI, KAVEH C

LIGHT-BEAM SWITCHING/ADJUSTING APPARATUS AND MANUFACTURING METHOD THEREOF

UNDISCOUNTED

ACCEPTED

ACCEPTED

Cvd method and device for forming silicon-containing insulation film

A CVD apparatus (2) forms an insulating film, which is a silicon oxide film, silicon nitride film, or silicon oxynitride film. The CVD apparatus includes a process chamber (8) to accommodate a target substrate (W), a support member (20) to support the target substrate in the process chamber, a heater (12) to heat the target substrate supported by the support member, an exhaust section (39) to vacuum-exhaust the process chamber, and a supply section (40) to supply a gas into the process chamber. The supply section includes a first circuit (42) to supply a first gas of a silane family gas, a second circuit (44) to supply a second gas, which is an oxidizing gas, nitriding gas, or oxynitriding gas, and a third circuit (46) to supply a third gas of a carbon hydride gas, and can supply the first, second, and third gases together.

1. A CVD method of forming a silicon-containing insulating film, comprising: supplying a film-formation gas into a process chamber that accommodates a target substrate, while exhausting an interior of the process chamber, thereby forming the insulating film on the target substrate by deposition, wherein a carbon hydride gas is supplied together with the film-formation gas. 2. The method according to claim 1, wherein the carbon hydride gas is at least one gas selected from the group consisting of acetylene, ethylene, methane, ethane, propane, and butane. 3. The method according to claim 2, wherein the carbon hydride gas consists essentially of ethylene, and supplied into the process chamber without pre-heating. 4. The method according to claim 1, further comprising pre-heating the carbon hydride gas to a predetermined temperature immediately before supplying the carbon hydride gas into the process chamber. 5. The method according to claim 4, wherein a temperature of the pre-heating is set to fall within a range of from 500 to 1000° C. 6. The method according to claim 1, wherein a flow rate ratio of the carbon hydride gas relative to the film-formation gas is set to fall within a range of from 0.3 to 3.2. 7. The method according to claim 1, wherein the insulating film consists essentially of a film selected from the group consisting of a silicon oxide film, silicon nitride film, and silicon oxynitride film. 8. The method according to claim 7, wherein the film-formation gas comprises a first gas consisting essentially of a silane family gas, and a second gas consisting essentially of a gas selected from the group consisting of an oxidizing gas, nitriding gas, and oxynitriding gas. 9. The method according to claim 8, wherein the first gas consists essentially of a gas selected from the group consisting of hexachlorodisilane, hexaethylaminodisilane, bistertialbutylaminosilane, and dichlorosilane, the second gas consists essentially of a nitriding gas, and the insulating film is formed by deposition at a process temperature set to fall within a range of from 450 to 600° C. 10. A CVD method of forming an insulating film, consisting essentially of a film selected from the group consisting of a silicon oxide film, silicon nitride film, and silicon oxynitride film, the method comprising: supplying first, second, and third gases into a process chamber that accommodates a target substrate, while heating and exhausting an interior of the process chamber, thereby forming the insulating film on the target substrate by deposition, wherein the first gas consists essentially of a silane family gas, a second gas consists essentially of a gas selected from the group consisting of an oxidizing gas, nitriding gas, and oxynitriding gas, the third gas consists essentially of a carbon hydride gas, and a flow rate ratio of the third gas relative to the first gas is set to fall within a range of from 10 to 100. 11. A CVD apparatus for forming an insulating film, consisting essentially of a film selected from the group consisting of a silicon oxide film, silicon nitride film, and silicon oxynitride film, the apparatus comprising: a process chamber configured to accommodate a target substrate; a support member configured to support the target substrate in the process chamber; a heater configured to heat the target substrate supported by the support member; an exhaust section configured to vacuum-exhaust an interior of the process chamber; and a supply section configured to supply a gas into the process chamber, wherein the supply section comprises a first circuit configured to supply a first gas consisting essentially of a silane family gas, a second circuit configured to supply a second gas consisting essentially of a gas selected from the group consisting of an oxidizing gas, nitriding gas, and oxynitriding gas, and a third circuit configured to supply a third gas consisting essentially of a carbon hydride gas, and is capable of supplying the first, second, and third gases at the same time. 12. The apparatus according to claim 11, wherein the supply section includes a pre-heating unit configured to pre-heat the third gas to a predetermined temperature immediately before supplying the third gas into the process chamber.

TECHNICAL FIELD The present invention relates to a CVD method and apparatus for forming a silicon-containing insulating film on a target substrate. BACKGROUND ART Semiconductor devices include insulating films made of SiO2, PSG (Phospho Silicate Glass), P-SiO (“P” stands for formation by plasma CVD), P-SiN (“P” stands for formation by plasma CVD), SOG (Spin On Glass), Si3N4 (silicon nitride), etc. As a method of forming such a silicon oxide film or silicon nitride film on the surface of a semiconductor wafer, there is known a method of forming a film by thermal CVD (Chemical Vapor Deposition), which employs a silane family gas, such as monosilane (SiH4), dichlorosilane (DCS: SiH2Cl2), hexa-chlorodisilane (HCD: Si2Cl6), bistertialbutylamino-silane (BTBAS: SiH2(NH(C4H9)2), as a silicon source gas. Specifically, for example, where a silicon oxide film is deposited, the thermal CVD for forming the silicon oxide film is performed, using a gas combination, such as SiH4+N2O, SiH2Cl2+N2O, or TEOS (tetraethyl-orthosilicate)+O2. Where a silicon nitride film is deposited, the thermal CVD for forming the silicon nitride film is performed, using a gas combination, such as SiH2Cl2+NH3, or Si2Cl6+NH3. Owing to the demands of increased miniaturization and integration of semiconductor devices, insulating films such as those described above need to be made thinner. Furthermore, in order to maintain the electric properties of the various films that lay below insulating films, the temperature used in thermal CVD in forming the insulating films needs to be lowered. In this respect, for example, where a silicon nitride film is deposited, thermal CVD for forming the silicon nitiride film is conventionally performed at a high temperature of about 760° C. In recent years, thermal CVD for forming the silicon nitiride film is performed at a lower temperature of about 600° C., as the case may be. When semiconductor devices are fabricated, a conductive film and an insulating film as described above are stacked and pattern-etched to form a multi-layer structure. Where an insulating film is formed and another thin film is then formed thereon, contaminants such as organic substances and particles may have stuck to the surface of the insulating film. In order to remove the contaminants, a cleaning process is performed, as needed. In this case, the semiconductor wafer is immersed in a cleaning solution, such as dilute hydrofluoric acid, to etch the surface of the insulating film. By doing so, the surface of the insulating film is etched by a very small amount, thereby removing the contaminants. Where an insulating film is formed by CVD at a high temperature of, e.g., about 760° C., the etching rate of the insulating film during cleaning is very small. Accordingly, the insulating film is not excessively etched by cleaning, and thus the cleaning process is performed with a high controllability in the film thickness. On the other hand, where an insulating film is formed by CVD at a low temperature of, e.g., about 600° C., the etching rate of the insulating film during cleaning is relatively large. Accordingly, the insulating film may be excessively etched by cleaning, and thus the cleaning process entails less controllability in the film thickness. DISCLOSURE OF INVENTION An object of the present invention is to provide a method and apparatus for forming a silicon-containing insulating film, which allows the etching rate of the film during cleaning to be relatively small even if the film has been formed at a relatively low temperature, thereby improving the controllability in the film thickness during cleaning. According to a first aspect of the present invention, there is provided a CVD method of forming a silicon-containing insulating film, comprising: supplying a film-formation gas into a process chamber that accommodates a target substrate, while exhausting an interior of the process chamber, thereby forming the insulating film on the target substrate by deposition, wherein a carbon hydride gas is supplied together with the film-formation gas. According to a second aspect of the present invention, there is provided a CVD method of forming an insulating film, consisting essentially of a film selected from the group consisting of a silicon oxide film, silicon nitride film, and silicon oxynitride film, the method comprising: supplying first, second, and third gases into a process chamber that accommodates a target substrate, while heating and exhausting an interior of the process chamber, thereby forming the insulating film on the target substrate by deposition, wherein the first gas consists essentially of a silane family gas, a second gas consists essentially of a gas selected from the group consisting of an oxidizing gas, nitriding gas, and oxynitriding gas, the third gas consists essentially of a carbon hydride gas, and a flow rate ratio of the third gas relative to the first gas is set to fall within a range of from 10 to 100. According to a third aspect of the present invention, there is provided a CVD apparatus for forming an insulating film, consisting essentially of a film selected from the group consisting of a silicon oxide film, silicon nitride film, and silicon oxynitride film, the apparatus comprising: a process chamber configured to accommodate a target substrate; a support member configured to support the target substrate in the process chamber; a heater configured to heat the target substrate supported by the support member; an exhaust section configured to vacuum-exhaust an interior of the process chamber; and a supply section configured to supply a gas into the process chamber, wherein the supply section comprises a first circuit configured to supply a first gas consisting essentially of a silane family gas, a second circuit configured to supply a second gas consisting essentially of a gas selected from the group consisting of an oxidizing gas, nitriding gas, and oxynitriding gas, and a third circuit configured to supply a third gas consisting essentially of a carbon hydride gas, and is capable of supplying the first, second, and third gases at the same time. BRIEF DESCRIPTION OF DRAWINGS FIG. 1 is a sectional view showing a CVD apparatus according to a first embodiment of the present invention; FIG. 2 is a graph obtained by experiment 1 and showing the relationship between the C2H6 gas flow rate and the carbon component concentration in a silicon nitride film; FIG. 3 is a graph obtained by experiment 2 and showing the relationship between the C2H6 gas pre-heating temperature and the carbon component concentration in a silicon nitride film; FIG. 4 is a graph obtained by experiment 3 and showing the relationship between the carbon component concentration in a silicon nitride film and the normalized etching rate thereof relative to dilute hydrofluoric acid (49%-HF: H2O=1:100); FIG. 5 is a graph obtained by experiment 4 and showing the relationship between the C2H6 gas pre-heating temperature and the normalized etching rate of a silicon nitride film relative to dilute hydrofluoric acid (49%-HF:H2O=1:100); FIG. 6 is a graph obtained by experiment 5 and showing the relationship between the C2H6 gas flow rate (with/without pre-heating) and the normalized etching rate of a silicon nitride film relative to dilute hydrofluoric acid (49%-HF:H2O=1:100); FIG. 7 is a sectional view showing a CVD apparatus according to a second embodiment of the present invention; FIG. 8 is a graph obtained by experiment 6 and showing the relationship between the carbon hydride gas flow rate and the normalized etching rate of a silicon nitride film relative to dilute hydrofluoric acid (49%-HF:H2O=1:100); and FIG. 9 is a graph obtained by experiment 7 and showing the relationship between the ethylene gas flow rate and the normalized etching rate of a silicon nitride film relative to dilute hydrofluoric acid (49%-HF:H2O=1:100). BEST MODE FOR CARRYING OUT THE INVENTION In the process of developing the present invention, the inventors studied etching rates of silicon-containing insulating films, such as a silicon oxide film, silicon nitride film, and silicon oxynitride film, during cleaning. As a result, the inventors have arrived at the finding that the etching rates during cleaning are reduced if the insulating films are prepared to positively contain carbon components. Embodiments of the present invention will now be described with reference to the accompanying drawings. In the following description, the constituent elements having substantially the same function and arrangement are denoted by the same reference numerals, and a repetitive description will be made only when necessary. <First Embodiment> FIG. 1 is a sectional view showing a CVD apparatus according to a first embodiment of the present invention. The CVD apparatus 2 is arranged to supply a first gas consisting essentially of a silane family gas (silicon source gas), a second gas consisting essentially of a gas selected from the group consisting of an oxidizing gas, nitriding gas, and oxynitriding gas, and a third gas consisting essentially of a carbon hydride gas, at the same time, so as to form an insulating film consisting essentially of a film selected from the group consisting of a silicon oxide film, silicon nitride film, and silicon oxynitride film. For example, where Si2Cl6 and NH3 gases are used to deposit a silicon nitride film, a carbon hydride gas is supplied to cause carbon components to be contained in the film. As shown in FIG. 1, the CVD apparatus 2 includes a process chamber 8 having a double tube structure, which is formed of a cylindrical inner tube 4 made of quartz, and an outer tube 6 made of quartz and disposed concentrically with the inner tube 4 with a predetermined gap 10 therebetween. The process chamber 8 is surrounded by a heating cover 16, which includes a heater or heating means 12 and a thermal insulator 14. The heating means 12 is disposed over the entire inner surface of the thermal insulator 14. In this embodiment, the inner tube 4 of the process chamber 8 has an inner diameter of about 240 mm, and a height of about 1300 mm. The process chamber 8 has a volume of about 110 liters. The bottom of the process chamber 8 is supported by a cylindrical manifold 18 made of, e.g., stainless steel. A ring support plate 18A extends inward from the inner wall of the manifold 18 and supports the bottom of the inner tube 4. A number of target substrates or semiconductor wafers W are stacked on a wafer boat 20 made of quartz. The wafer boat 20 is loaded/unloaded into and from the process chamber 8 through the bottom of the manifold 18. In this embodiment, the wafer boat 20 can support 150 product wafers having a diameter of 200 mm and 13 or 20 dummy wafers at substantially regular intervals in the vertical direction. In other words, the wafer boat 20 can accommodate 170 wafers in total. The wafer boat 20 is placed on a rotary table 24 through a heat-insulating cylinder 22 made of quartz. The rotary table 24 is supported by a rotary shaft 28, which penetrates a lid 26 used for opening/closing the bottom port of the manifold 18. The portion of the lid 26 where the rotary shaft 28 penetrates is provided with, e.g., a magnetic-fluid seal 30, so that the rotary shaft 28 is rotatably supported in an airtightly sealed state. A seal member 32, such as an O-ring is interposed between the periphery of the lid 26 and the bottom of the manifold 18, so that the interior of the process chamber 8 can be kept sealed. The rotary shaft 28 is attached at the distal end of an arm 36 supported by an elevating mechanism 34, such as a boat elevator. The elevating mechanism 34 moves up and down the wafer boat 20 and lid 26 integratedly. An exhaust port 38 is formed in the side of the manifold 18 to exhaust the atmosphere in the process chamber 8 through the bottom of the gap 10 between the inner tube 4 and outer tube 6. The exhaust port 38 is connected to a vacuum exhaust section 39 including a vacuum pump and so forth. A gas supply section 40 is connected to the side of the manifold 18 to supply predetermined process gases into the inner tube 4. More specifically, the gas supply section 40 includes a silane family gas circuit 42, an oxidizing and/or nitriding gas circuit 44, and a carbon hydride gas circuit 46. The gas circuits 42, 44, and 46 respectively include linear gas nozzles 48, 50, and 52, which penetrate the sidewall of the manifold 18. The gas nozzles 48, 50, and 52 are respectively connected to gas passages 60, 62, and 64 provided with flow rate controllers 54, 56, and 58, such as mass-flow controllers. The gas passages 60, 62, and 64 are arranged to respectively supply a silane family gas, an oxidizing and/or nitriding gas, and a carbon hydride gas at controlled flow rates. For example, the silane family gas (silicon source gas) is hexachlorodisilane (Si2Cl6) gas, the nitriding gas is NH3 gas, and the carbon hydride gas is ethane (C2H6) gas. N2O gas or O2 gas may be used as an oxidizing gas. The carbon hydride gas passage 64 is provided with a pre-heating unit 66. For example, the pre-heating unit 66 is formed of a quartz container wound with a heater outside and filled with quartz grains. The pre-heating unit 6 pre-heats a carbon hydride gas, such as ethane gas, flowing therethrough, to a predetermined temperature. As a consequence, the ethane gas flowing through the pre-heating unit 66 is activated. Next, an explanation will be given of a CVD method according to an embodiment of the present invention, performed in the apparatus described above. At first, when the CVD apparatus is in a waiting state with no wafers loaded therein, the interior of the process chamber 8 is kept at a process temperature of, e.g., about 50° C. On the other hand, a number of wafers, e.g. 150 product wafers W and 20 dummy wafers, are transferred into the wafer boat 20. After the wafers are transferred, the wafer boat 20, which is at a normal temperature, is moved up from below the process chamber 8 and loaded into the process chamber 8. Then, the lid 26 closes the bottom port of the manifold 18 to airtightly seal the interior of the process chamber 8. Then, the interior of the process chamber 8 is vacuum exhausted to a predetermined process pressure of, e.g., about 27 Pa. The wafer temperature is increased to a process temperature for film formation of, e.g., about 600° C. After the temperature becomes stable, Si2Cl6 gas used as a silane family gas, NH3 gas used as a nitriding gas, and C2H6 gas used as a carbon hydride gas are supplied from the respective nozzles 48, 50, and 52 of the gas supply section 40 at controlled flow rates, in accordance with a predetermined manner. The C2H6 gas is heated to a predetermined temperature of, e.g., from 500 to 1000° C. in the pre-heating unit 66, which is disposed on the carbon hydride gas passage 64 immediately before the nozzle 52, so that it is activated immediately before the supply. The C2H6 gas, however, may be supplied without pre-heating. The C2H6 gas thus activated by pre-heating, or with no pre-heating, is supplied into the bottom of the process chamber 8 and mixed with the Si2Cl6 gas and NH3 gas. The gases thus mixed react with each other while flowing upward in the process space S, and cause a silicon nitride thin film to be deposited on the surface of each wafer W. The process gases thus flowing upward in the process space S bounce off the ceiling of the process chamber 8, and flow through the gap 10 between the inner tube 4 and outer tube 6, and then are exhausted through the exhaust port 38. The lower limit of the heating temperature of C2H6 gas in the pre-heating unit 66 is set at about 500° C. The upper limit of the pre-heating is not restricted, but it is preferably set at a temperature at which the etching rate of a silicon nitride film becomes saturated, as described later, at about 1000° C. for example. The upper limit of the C2H6 gas flow rate is not restricted, but it is preferably set at a flow rate at which the etching rate of a silicon nitride film becomes saturated, as described later, at about 200 sccm for example. In this embodiment, the Si2Cl6 gas flow rate is set at about 30 sccm, and the NH3 gas flow rate is set at about 900 sccm. As described above, C2H6 gas is supplied into the process chamber 8, and carbon components are thereby contained in a silicon nitride film formed on a wafer surface. This brings about a low etching rate of the silicon nitride film surface relative to the dilute hydrofluoric acid used in a cleaning process, even though the film-formation temperature is lower than the conventional film-formation temperature of, e.g., about 760° C. As a consequence, it is possible to prevent the silicon nitride film from being excessively etched during the cleaning process, thereby improving the controllability in the film thickness. Particularly, the pre-heating of C2H6 gas activates this gas and causes more carbon components to be contained in the silicon nitride film by that much. As a consequence, the etching rate of the silicon nitride film is reduced still further. In this case, as described later, the carbon component concentration in the silicon nitride film can be controlled to attain a predetermined etching rate. Next, an explanation will be given of experiments conducted using the CVD apparatus 2 shown in FIG. 1. In these experiments, a process was performed in a state corresponding to conditions with 150 product wafers and 20 dummy wafers placed on the wafer boat 20. As shown also in FIG. 1, the process chamber 8 (and wafer boat 20) was divided in terms of wafer position into three zones in the vertical direction, i.e., TOP (top), CTR (center), and BTM (bottom). From the top of the wafer boat 20, 1st to 60th wafers belonged to the top zone, 61st to 111th wafers belonged to the center zone, and 112th to 170th wafers belonged to the bottom zone. Etching rate values obtained by the experiments were converted into comparative values relative to a reference value “1”, and were used as normalized etching rates. The reference value “1” was set to be the etching rate of a silicon nitride film, which was formed at a process temperature of 760° C. (conventional film-formation temperature), using dichlorosilane (SiH2Cl2) gas and NH3 gas, without any carbon hydride gas. [Experiment 1] An experiment was conducted to examine the relationship between the C2H6 gas flow rate and the carbon component concentration in a silicon nitride film. This experiment employed the following conditions as constants, i.e., a process temperature of 600° C., process pressure of 27 Pa, Si2Cl6 gas flow rate of 30 sccm, NH3 gas flow rate of 900 sccm, and C2H6 gas pre-heating temperature of 1000° C. On the other hand, this experiment employed different C2H6 gas flow rates falling within a range of from 0 to 200 sccm. FIG. 2 is a graph obtained by experiment 1 and showing the relationship between the C2H6 gas flow rate and the carbon component concentration in a silicon nitride film. As shown in FIG. 2, the carbon component concentration in a silicon nitride film almost linearly increased with increase in the C2H6 gas flow rate within a range of from 0 to 200 sccm, without reference to the wafer positions from the top to bottom. Accordingly, it has been found that the carbon component concentration in a silicon nitride film increases as the C2H6 gas flow rate increases. [Experiment 2] An experiment was conducted to examine the relationship between the C2H6 gas pre-heating temperature and the carbon component concentration in a silicon nitride film. This experiment employed the following conditions as constants, i.e., a process temperature of 600° C., process pressure of 27 Pa, Si2Cl6 gas flow rate of 30 sccm, NH3 gas flow rate of 900 sccm, and C2H6 gas flow rate of 200 sccm. On the other hand, this experiment employed different C2H6 gas pre-heating temperatures within a range of from 500 to 1000° C. FIG. 3 is a graph obtained by experiment 2 and showing the relationship between the C2H6 gas pre-heating temperature and the carbon component concentration in a silicon nitride film. As shown in FIG. 3, where the C2H6 gas pre-heating temperature was within a range of from 500 to 700° C., the carbon content concentration in a silicon nitride film gradually increased in principle, although there was a partly downward trend, which seems to be in the range of error. Where the pre-heating temperature was within a range of from 700 to 900° C., the carbon content concentration drastically increased with increase in the temperature. Where the pre-heating temperature was within a range of from 900 to 1000° C., the carbon content concentration gradually increased with increase in the temperature, to be almost saturated. Accordingly, it has been found that, where the C2H6 gas pre-heating is performed, the carbon component concentration increases as the temperature increases. In this case, in order to increase the carbon component concentration in a silicon nitride film to a certain extent or more, it is preferable to pre-heat the C2H6 to a temperature of about 500° C. or more. Since the carbon component concentration is almost saturated at about 1000° C., the upper limit of pre-heating is preferably set at about 1000° C. [Experiment 3] With reference to the results of experiments 1 and 2, an experiment was conducted to examine the relationship between the carbon component concentration in a silicon nitride film and the etching rate thereof relative to dilute hydrofluoric acid. This experiment employed the following conditions as constants, i.e., a process temperature of 600° C., process pressure of 27 Pa, Si2Cl6 gas flow rate of 30 sccm, NH3 gas flow rate of 900 sccm, and C2H6 gas flow rate of 200 sccm. On the other hand, this experiment employed different pre-heating temperatures to vary the carbon component concentration in a silicon nitride film within a range of from 1×1018 to 1×1022 atms/cm3. FIG. 4 is a graph obtained by experiment 3 and showing the relationship between the carbon component concentration in a silicon nitride film and the normalized etching rate thereof relative to dilute hydrofluoric acid (49%-HF:H2O=1:100). A shown in FIG. 4, the etching rate linearly decreased with increase in the carbon component concentration in a silicon nitride film within a range of from 1×1018 to 1×1022 atms/cm3, without reference to the wafer positions from the top to bottom. Accordingly, it has been found that the normalized etching rate can be controlled by adjusting the carbon content concentration. Particularly, where the carbon content concentration was 1×1022 atms/cm3, the normalized etching rate was about “1”. It means that a film formed at a process temperature as low as 600° C. showed almost the same etching rate as conventional silicon nitride film formed at 760° C. [Experiment 4] In order to supplement the result of experiment 3, an experiment was conducted to examine the relationship between the C2H6 gas pre-heating temperature and the etching rate of a silicon nitride film relative to dilute hydrofluoric acid. This experiment employed the following conditions as constants, i.e., a process temperature of 600° C., process pressure of 27 Pa, Si2Cl6 gas flow rate of 30 sccm, NH3 gas flow rate of 900 sccm, and C2H6 gas flow rate of 200 sccm. On the other hand, this experiment employed different C2H6 gas pre-heating temperatures within a range of from 500 to 1000° C. FIG. 5 is a graph obtained by experiment 4 and showing the relationship between the C2H6 gas pre-heating temperature and the normalized etching rate of a silicon nitride film relative to dilute hydrofluoric acid (49%-HF:H2O=1:100). A shown in FIG. 5, the normalized etching rate gradually decreased with increase in the pre-heating temperature within a range of from 500 to 700° C., without reference to the wafer positions from the top to bottom. Where the pre-heating temperature was within a range of from 700 to 900° C., the normalized etching rate sharply decreased with increase in the temperature. Where the pre-heating temperature was within a range of from 900 to 1000° C., the normalized etching rate gradually decreased again with increase in the temperature. Where the pre-heating temperature was at about 1000° C., the normalized etching rate was about “1” and the decrease was saturated. Accordingly, it has been found that the normalized etching rate can be arbitrarily set at a vale within a range of from about 1 to 8, by adjusting the C2H6 gas pre-heating temperature within a range of from 500 to 1000° C. [Experiment 5] In order to supplement the result of experiment 3, an experiment was conducted to examine the relationship between the C2H6 gas flow rate (with/without pre-heating) and the etching rate of a silicon nitride film relative to dilute hydrofluoric acid. This experiment employed the following conditions as constants, i.e., a process temperature of 600° C., process pressure of 27 Pa, Si2Cl6 gas flow rate of 30 sccm, and NH3 gas flow rate of 900 sccm. On the other hand, this experiment employed different C2H6 gas flow rates within a range of from 0 to 200 sccm. Furthermore, at each selected flow rate, two kinds of conditions were set, i.e., without C2H6 pre-heating (normal temperature) and with pre-heating at 1000° C. FIG. 6 is a graph obtained by experiment 5 and showing the relationship between the C2H6 gas flow rate (with/without pre-heating) and the normalized etching rate of a silicon nitride film relative to dilute hydrofluoric acid (49%-HF:H2O=1:100). A shown in FIG. 6, in a case where the C2H6 gas was supplied at a normal temperature without pre-heating, the normalized etching rate decreased only slightly from “6 to 7.5” to “5.5 to 7.0” with increase in the C2H6 gas flow rate within a range of from 0 to 200 sccm, without reference to the wafer positions from the top to bottom. Accordingly, it has been found that, where no pre-heating is performed, the etching rate tends to decrease with increase in the C2H6 gas flow rate, but the degree of the decrease is very small. On the other hand, in a case where the C2H6 gas was pre-heated at 1000° C., the normalized etching rate remarkably changed with increase in the C2H6 gas flow rate within a range of from 0 to 200 sccm, without reference to the wafer positions from the top to bottom. Specifically, where the C2H6 gas flow rate was within a range of from 0 to 100 sccm, the normalized etching rate sharply decreased from “6 to 8” to about “2”. Where the flow rate was within a range of from 100 to 200 sccm, the normalized etching rate gradually decreased with increase in the flow rate. Where the flow rate was at 200 sccm, the etching rate was about “1” and the decrease was saturated. Accordingly, it has been found that the normalized etching rate can be arbitrarily set at a vale within a range of from about 1 to 8, by adjusting the C2H6 gas flow rate within a range of from 0 to 200 sccm, while maintaining the C2H6 gas pre-heating temperature at 1000° C. <Second Embodiment> In the first embodiment described above, ethane (C2H6), which belongs to the paraffin series carbon hydrides, is used as a carbon hydride gas. Instead, another paraffin series carbon hydride, such as methane, propane, or butane, may be used as a carbon hydride gas. Furthermore, in place of a paraffin series carbon hydride, an acetylene series carbon hydride, such as acetylene or ethylene, may be used. In the second embodiment, ethylene (C2H4) gas is used as a carbon hydride gas. Using ethylene gas as a carbon hydride gas is advantageous in that, even where it is supplied into the process chamber 8 without pre-heating, the same effect as described above can be obtained, i.e., a silicon-containing film showing a sufficiently small etching rate can be formed. Also in this case, ethylene gas may be pre-heated. FIG. 7 is a sectional view showing a CVD apparatus according to a second embodiment of the present invention. The CVD apparatus 2X show in FIG. 7 differs from the CVD apparatus 2 shown in FIG. 1, in that a gas supply section 40 includes a carbon hydride gas circuit 46, which is connected to an ethylene (C2H4) gas source and is provided with no pre-heating unit 66. The other parts of the CVD apparatus 2X show in FIG. 7 are basically the same as those of the CVD apparatus 2 shown in FIG. 1. Specifically, in the CVD apparatus 2X according to the second embodiment, hexachlorodisilane (Si2Cl6) gas is used as a silane family gas (silicon source gas), NH3 gas is used as a nitriding gas, and ethylene (C2H4) gas is used as a carbon hydride gas. The ethylene gas used as a carbon hydride gas is fed into the process chamber 8 at about a room temperature without pre-heating. Where a silicon nitride film is formed in the CVD apparatus 2X according to the second embodiment, carbon components can be sufficiently contained in the silicon nitride film, even though the ethylene is not pre-heated. This allows the etching rate of the film during cleaning to be relatively small even if the film has been formed at a relatively low temperature, thereby improving the controllability in the film thickness during cleaning. The reason why pre-heating is unnecessary where ethylene gas is used as a carbon hydride gas is thought to be that the bond dissociation energy (about 63 kcal/mol) of C═C (double bond) in ethylene is smaller than the bond dissociation energy (about 83 kcal/mol) of C—C in ethane, and thus ethylene has a higher reactivity (the difference is about 20 kcal/mol). Next, an explanation will be given of experiments conducted using the CVD apparatus 2X shown in FIG. 7. Also in these experiments, a process was performed in a state corresponding to conditions with 150 product wafers and 20 dummy wafers placed on the wafer boat 20. As shown also in FIG. 7, the process chamber 8 (and wafer boat 20) was divided in terms of wafer position into three zones in the vertical direction, i.e., TOP (top), CTR (center), and BTM (bottom). From the top of the wafer boat 20, 1st to 60th wafers belonged to the top zone, 61st to 111th wafers belonged to the center zone, and 112th to 170th wafers belonged to the bottom zone. Etching rate values obtained by the experiments were converted into comparative values relative to a reference value “1”, and were used as normalized etching rates. The reference value “1” was set to be the etching rate of a silicon nitride film, which was formed at a process temperature of 760° C. (conventional film-formation temperature), using dichlorosilane (SiH2Cl2) gas and NH3 gas, without any carbon hydride gas. [Experiment 6] An experiment was conducted to examine the effect in a case where ethylene (C2H4) gas was used in place of ethane (C2H6) gas, as a carbon hydride gas. This experiment employed the following conditions as constants, i.e., a process temperature of 600° C., process pressure of 27 Pa, Si2Cl6 gas flow rate of 30 sccm, and NH3 gas flow rate of 900 sccm. On the other hand, this experiment employed different C2H4 gas flow rates falling within a range of from 0 to 150 sccm. FIG. 8 is a graph obtained by experiment 6 and showing the relationship between the carbon hydride gas flow rate and the normalized etching rate of a silicon nitride film relative to dilute hydrofluoric acid (49%-HF:H2O=1:100). This graph also includes the result where ethane was used without pre-heating, for comparison. As shown in FIG. 8, where ethane (C2H6) was used without pre-heating, the normalized etching rate did not become smaller than a range of from about 6 to 8, with increase in the gas flow rate within a range of from 0 to 150 sccm, although the were some differences depending on the wafer positions from the top to bottom. In other words, the normalized etching rate in this case was almost constant or only slightly decreased with increase in the gas flow rate. On the other hand, where ethylene was used as a carbon hydride gas without pre-heating, the normalized etching rate decreased from about “5 to 6” to about “3.2 to 4” with increase in the gas flow rate within a range of from 0 to 150 sccm, in all the wafer positions from the top to bottom. [Experiment 7] Furthermore, an experiment was conducted to examine the relationship between the ethylene (C2H4) gas flow rate and the etching rate of a silicon nitride film relative to dilute hydrofluoric acid. This experiment employed the following conditions as constants, i.e., a process temperature of 600° C., process pressure of 27 Pa, Si2Cl6 gas flow rate of 30 sccm, and NH3 gas flow rate of 900 sccm. On the other hand, this experiment employed different C2H4 gas flow rates within a range of from 0 to 900 sccm. FIG. 9 is a graph obtained by experiment 7 and showing the relationship between the ethylene gas flow rate and the normalized etching rate of a silicon nitride film relative to dilute hydrofluoric acid (49%-HF:H2O=1:100). This graph shows the etching rate by means of average values among the wafer positions from the top to bottom A shown in FIG. 9, the normalized etching rate gradually decreased from about 6.45 to about 1.80 with increase in the ethylene gas flow rate within a range of from 0 to 900 sccm. The decrease in the normalized etching rate was almost saturated where the ethylene gas flow rate was near 900 sccm. Judging from the results of experiments 6 and 7, it has been found that, where ethylene is used as a carbon hydride gas even without pre-heating, the etching rate of a silicon nitride film can be sufficiently low (i.e., carbon components are sufficiently contained in the silicon nitride film). [Experiment 8] In order to supplement the results of experiments 6 and 7, an experiment was conducted, employing the same conditions as experiment 6 (i.e., without pre-heating), except a process temperature of 450° C., and ethylene gas flow rate of 300 sccm. As a consequence, it has been found that the normalized etching rate decreases to about a half, compared to the case where no ethylene gas is supplied. The first and second embodiments have been explained such that a carbon hydride gas and film-formation gases (a combination of a first gas consisting essentially of a silane family gas (silicon source gas), with a second gas selected from the group consisting of an oxidizing gas, nitriding gas, and oxynitriding gas) are supplied into the process chamber 8 separately from each other though different routes. However, a carbon hydride gas may be supplied while being mixed into one of film-formation gases (Si2Cl6 gas or NH3 gas). In any case, the flow rate ratio of a carbon hydride gas relative to film-formation gases is set to fall within a range of from 0.3 to 3.2, preferably of from 0.4 to 2.8. The flow rate ratio of a carbon hydride gas relative to a silane family gas is set to fall within a range of from 10 to 100, preferably of from 15 to 85. Where the flow rate ratio of a carbon hydride gas is lower than the range described above, the etching rate of a silicon-containing insulating film becomes too high. In this case, the insulating film is excessively etched during cleaning, thereby deteriorating the controllability in the film thickness. On the other hand, where the flow rate ratio of a carbon hydride gas is higher than the range described above, the etching rate of a silicon-containing insulating film becomes too low, which is not practical. The first and second embodiments have also been explained in the case of hexachlorodisilane (HCD: Si2Cl6) and NH3 being used to form a silicon nitride film, wherein a carbon hydride gas is supplied at the same time. However, also in the case of another process gas being used to form a silicon nitride film, supply of a carbon hydride gas together therewith brings about the same effect as described above. An example of another process gas for forming a silicon nitride film is a combination of one of dichlorosilane (DCS: SiH2Cl2), tetrachlorosilane (SiCl4), bistertialbutylaminosilane (BTBAS: SiH2(NH(C4H9)2), and hexaethylaminodisilane (HEAD), which belong to the silane family gases (silicon source gas), with NH3, which belong to the nitriding gases. Furthermore, in the case of a silicon oxide film being formed by thermal CVD instead of a silicon nitride film, supply of a carbon hydride gas together therewith brings about the same effect as described above. An example of a process gas for forming a silicon oxide film by thermal CVD is a combination of monosilane (SiH4) with N2O, a combination of dichlorosilane (DCS: SiH2Cl2) with N2O, a combination of TEOS (tetraethylorthosilicate) with O2, or a. combination of hexachlorodisilane (HCD:Si2Cl6) with N2O. In this case, N2O gas or O2 gas described above is used as an oxidizing gas. Furthermore, in the case of a silicon oxynitride film being formed, supply of a carbon hydride gas together with a film-formation gas brings about the same effect as described above. An example of a process gas for forming a silicon oxynitride film by thermal CVD is a combination of dichlorosilane (DCS: SiH2Cl2) with N2O and NH3. In this case, as indicated with a broken line in FIG. 1, the CVD apparatus is preferably provided with an N2O gas circuit 45 (in FIG. 1, reference characters 57 and 63 denote a flow rate controller and a gas passage, respectively) as an oxynitriding gas circuit, in addition to the NH3 gas circuit 44, so that N2O and NH3 are individually supplied into the process chamber 8. The above embodiments have also been explained in the case of the CVD apparatus being formed of a batch type vertical apparatus. The present invention, however, may be applied to a batch type lateral apparatus, or a single-substrate type CVD apparatus in which target substrates are processed one by one. As regards a target substrate, the present invention may be applied to a glass substrate or LCD substrate other than a semiconductor wafer. A CVD method and apparatus for forming a silicon-containing insulating film according to the embodiments provides the following advantages. Specifically, a carbon hydride gas is supplied together during film-formation of a silicon-containing insulating film to cause carbon components to be contained in the film. This allows the etching rate of the silicon-containing insulating film during cleaning to be relatively small even if the film has been formed at a relatively low temperature, thereby improving the controllability in the film thickness during cleaning. In addition, the carbon hydride gas thus supplied may be pre-heated and activated to cause more carbon components to be contained in the silicon-containing insulating film.

<SOH> BACKGROUND ART <EOH>Semiconductor devices include insulating films made of SiO 2 , PSG (Phospho Silicate Glass), P-SiO (“P” stands for formation by plasma CVD), P-SiN (“P” stands for formation by plasma CVD), SOG (Spin On Glass), Si 3 N 4 (silicon nitride), etc. As a method of forming such a silicon oxide film or silicon nitride film on the surface of a semiconductor wafer, there is known a method of forming a film by thermal CVD (Chemical Vapor Deposition), which employs a silane family gas, such as monosilane (SiH 4 ), dichlorosilane (DCS: SiH 2 Cl 2 ), hexa-chlorodisilane (HCD: Si 2 Cl 6 ), bistertialbutylamino-silane (BTBAS: SiH 2 (NH(C 4 H 9 ) 2 ), as a silicon source gas. Specifically, for example, where a silicon oxide film is deposited, the thermal CVD for forming the silicon oxide film is performed, using a gas combination, such as SiH 4 +N 2 O, SiH 2 Cl 2 +N 2 O, or TEOS (tetraethyl-orthosilicate)+O 2 . Where a silicon nitride film is deposited, the thermal CVD for forming the silicon nitride film is performed, using a gas combination, such as SiH 2 Cl 2 +NH 3 , or Si 2 Cl 6 +NH 3 . Owing to the demands of increased miniaturization and integration of semiconductor devices, insulating films such as those described above need to be made thinner. Furthermore, in order to maintain the electric properties of the various films that lay below insulating films, the temperature used in thermal CVD in forming the insulating films needs to be lowered. In this respect, for example, where a silicon nitride film is deposited, thermal CVD for forming the silicon nitiride film is conventionally performed at a high temperature of about 760° C. In recent years, thermal CVD for forming the silicon nitiride film is performed at a lower temperature of about 600° C., as the case may be. When semiconductor devices are fabricated, a conductive film and an insulating film as described above are stacked and pattern-etched to form a multi-layer structure. Where an insulating film is formed and another thin film is then formed thereon, contaminants such as organic substances and particles may have stuck to the surface of the insulating film. In order to remove the contaminants, a cleaning process is performed, as needed. In this case, the semiconductor wafer is immersed in a cleaning solution, such as dilute hydrofluoric acid, to etch the surface of the insulating film. By doing so, the surface of the insulating film is etched by a very small amount, thereby removing the contaminants. Where an insulating film is formed by CVD at a high temperature of, e.g., about 760° C., the etching rate of the insulating film during cleaning is very small. Accordingly, the insulating film is not excessively etched by cleaning, and thus the cleaning process is performed with a high controllability in the film thickness. On the other hand, where an insulating film is formed by CVD at a low temperature of, e.g., about 600° C., the etching rate of the insulating film during cleaning is relatively large. Accordingly, the insulating film may be excessively etched by cleaning, and thus the cleaning process entails less controllability in the film thickness.

<SOH> BRIEF DESCRIPTION OF DRAWINGS <EOH>FIG. 1 is a sectional view showing a CVD apparatus according to a first embodiment of the present invention; FIG. 2 is a graph obtained by experiment 1 and showing the relationship between the C 2 H 6 gas flow rate and the carbon component concentration in a silicon nitride film; FIG. 3 is a graph obtained by experiment 2 and showing the relationship between the C 2 H 6 gas pre-heating temperature and the carbon component concentration in a silicon nitride film; FIG. 4 is a graph obtained by experiment 3 and showing the relationship between the carbon component concentration in a silicon nitride film and the normalized etching rate thereof relative to dilute hydrofluoric acid (49%-HF: H 2 O=1:100); FIG. 5 is a graph obtained by experiment 4 and showing the relationship between the C 2 H 6 gas pre-heating temperature and the normalized etching rate of a silicon nitride film relative to dilute hydrofluoric acid (49%-HF:H 2 O=1:100); FIG. 6 is a graph obtained by experiment 5 and showing the relationship between the C 2 H 6 gas flow rate (with/without pre-heating) and the normalized etching rate of a silicon nitride film relative to dilute hydrofluoric acid (49%-HF:H 2 O=1:100); FIG. 7 is a sectional view showing a CVD apparatus according to a second embodiment of the present invention; FIG. 8 is a graph obtained by experiment 6 and showing the relationship between the carbon hydride gas flow rate and the normalized etching rate of a silicon nitride film relative to dilute hydrofluoric acid (49%-HF:H 2 O=1:100); and FIG. 9 is a graph obtained by experiment 7 and showing the relationship between the ethylene gas flow rate and the normalized etching rate of a silicon nitride film relative to dilute hydrofluoric acid (49%-HF:H 2 O=1:100). detailed-description description="Detailed Description" end="lead"?

20040712

20061024

20050505

57520.0

LE, THAO P

CVD METHOD AND DEVICE FOR FORMING SILICON-CONTAINING INSULATION FILM

UNDISCOUNTED

ACCEPTED

ACCEPTED

Mould for continuous casting of metal strips

A mould for continuously casting metal strips comprises a pair of side walls (11) on opposite sides of an open-ended mould cavity (C) having an entrance end (E) for continuously receiving molten metal and an exit end (D) for continuously discharging a moving solidified strip (D) formed from the molten metal. Each mould side wall (11) includes a graphite block (13) formed of a stack of a multiplicity of elongate graphite laminae (16) having opposite faces (16A) and inner edges (16B), said inner edges (16B) jointly forming a surface (16A) directed toward the mould cavity (C). The mould further comprises a cooling system associated with each graphite block (13) and including coolant tubes (15) extending through the stack transversely to said opposite faces (16A) of the graphite laminae (16) forming the stack.

1. A mould for continuously casting metal strips, comprising a pair of mould side walls on opposite sides of an open-ended mould cavity having an entrance end for continuously receiving molten metal and an exit end for continuously discharging a moving solidified strip formed from the molten metal, each said mould side wall including a graphite block (13), and further comprising a cooling system associated with each graphite block and including coolant tubes contacting the graphite block, the graphite block of each of said mould side walls formed of a stack of a multiplicity of elongate graphite laminae having opposite faces and inner edges, said inner edges jointly forming a surface directed toward the mould cavity, and in that the coolant tubes extending through the stack transversely to said opposite faces of the graphite laminae forming the stack. 2. A continuous-casting mould as claimed in claim 1, including a pair of metal end members in face-to-face engagement with the outer face of respective ones of the two outermost graphite laminae of the stack, the coolant tubes being received in said end members. 3. A continuous-casting mould as claimed in claim 1, wherein the graphite laminae of each stack are oriented such that their inner edges extend between the entrance and exit ends of the mould cavity, the coolant tubes extending transversely of the direction of movement of the strip discharging through the exit end of the mould cavity during operation of the mould. 4. A continuous-casting mould as claimed in claim 1 wherein a pair of opposed end walls of the mould cavity are formed by a pair of graphite bars bridging the gap between said side walls along the ends of the stacks of graphite laminae. 5. A continuous-casting mould as claimed in claim 1 including for each of said mould side walls a mould cavity lining member formed of a thin graphite plate supported by said stack of laminae. 6. A continuous-casting mould as claimed in claim 1 including for each stack of graphite laminae a stack-supporting plate substantially coextensive with the stack. 7. A continuous-casting mould as claimed in claim 1 wherein said graphite laminae are made of compacted graphite flakes oriented so as to be generally parallel to said opposite faces of the graphite laminae. 8. A cooling device comprising a stack of a multiplicity of elongate graphite laminae having opposed faces and inner edges, said inner edges jointly forming a surface for receiving heat from an object to be cooled, and further comprising coolant tubes extending through the stack transversely to said opposite faces of the laminae forming the stack.

This invention relates to a mould for continuous casting of metal strips and more particularly to a continuous-casting mould of the kind comprising a pair of mould side walls on opposite sides of an open-ended mould cavity having an entrance end for continuously receiving molten metal and an exit end for continuously discharging a moving solidified strip formed from the molten metal, each said mould side wall including a graphite block, and further comprising a cooling system associated with each graphite block and including coolant tubes contacting the graphite block. In the art of continuous casting of metals, especially in the continuous casting of non-ferrous metals or alloys, such as copper or copper base alloys, it is common practice to use a casting mould in which the walls of the open-ended mould cavity are formed by graphite lining plates, because graphite has advantageous lubricating properties and a fairly high thermal conductivity. These properties are highly desirable, firstly because low friction between the mould cavity walls and the moving solidified strip is essential and secondly because high thermal conductivity is required to permit efficient cooling of the mould and thus rapid solidification of the molten metal continuously fed into the mould cavity. U.S. Pat. No. 3,519,062 and U.S. Pat. No. 3,809,148 A show examples of moulds for continuous casting of metal strips in which the inner faces of the side walls of the mould cavity are covered by thin lining plates of graphite. On the side directed away from the mould cavity, the graphite lining plates engage and are supported by backing and cooling members of metal. These backing and cooling members not only support and protect the graphite lining plate but also serve as cooling jackets through which a liquid coolant is passed to carry away heat from the mould cavity via the graphite lining plates. It is also known, although not common practice, to form the inner faces of the mould side walls from thick graphite blocks or slabs and essentially dispensing with the conventional backing and cooling members. Thus, GB 2 034 218 A discloses a continuous-casting mould of the kind initially indicated, in which the horizontal mould cavity is defined by a pair of heavy solid graphite blocks which are placed one on top of the other and provided with mould cavity defining recesses in their confronting inner faces. An array of flattened coolant tubes of metal are urged against the outer faces of the blocks to be held in close contact with the blocks to carry off heat transmitted from the mould cavity across the thickness of the graphite blocks. An object of the invention is to provide an improved continuous-casting mould of the kind indicated initially which can be produced economically and is capable of efficiently cooling the molten metal in the mould cavity. In accordance with the invention there is provided a mould for continuously casting metal strips, comprising a pair of mould side walls on opposite sides of an open-ended mould cavity having an entrance end for continuously receiving molten metal and an exit end for continuously discharging a moving solidified strip formed from the molten metal, each said mould side wall including a graphite block, and further comprising a cooling system associated with each graphite block and including coolant tubes contacting the graphite block, characterised in that the graphite block of each of said mould side walls is formed of a stack of a multiplicity of elongate graphite laminae having opposite faces and inner edges, said inner edges jointly forming a surface directed toward the mould cavity, and in that the coolant tubes extend through the stack transversely to said opposite faces of the graphite laminae forming the stack. The laminated construction of the graphite block lends itself to a simple and economical production. Before the graphite laminae are stacked they are formed with apertures for receiving the coolant tubes, e.g. by punching. Then they are stacked by sliding them over the tubes. When the stacking is completed, the stack, which thus encloses the tubes, is compacted by the application of opposing forces to the ends of the stack to force the laminae into close face-to-face contact with one another and at the same time bring about a close contact between the laminae and the coolant tubes. Preferably, a pair of metal end members are applied to the ends of the stack in face-to-face engagement with the outer face of respective ones of the outermost graphite laminae of the stack. The coolant tubes are preferably received on the end members. In this manner, the laminae forming the stack are securely held together by the tubes and the end members so that the assembly formed by the stack, the coolant tubes and the end members can be easily handled as a unit and the faces of the stack can be machined to become smooth. A particularly efficient heat transfer from the mould cavity to the coolant passing through the coolant tubes is obtained by forming the stack from laminae made from compacted graphite flakes oriented so as to be generally parallel to the opposite faces of the graphite laminae. With graphite laminae so made, the heat conductivity in planes parallel to the faces of the laminae is considerably higher than the heat conductivity in the direction perpendicular thereto. The invention will be described in greater detail below with reference to the accompanying drawings in which an embodiment of the continuous-casting mould according to the invention is diagrammatically illustrated. FIG. 1 is a view in vertical section along line I-I of FIG. 1 illustrating an example of a continuous-casting mould embodying the invention, the mould being shown with a tundish and strip that is being cast; FIG. 2 is a plan view of the mould shown in FIG. 1, the tundish shown in FIG. 1 being omitted; and FIG. 3 is a fractional elevational view of one of the two graphite blocks which form essential parts of the mould shown in FIG. 1. In the embodiment of the invention shown by way of example in the drawings, the continuous-casting mould 10 according to the invention is used for continuous vertical casting of metal strips. As will be appreciated, however, the invention is not limited to vertical casting; the inventive concept is equally well applicable to horizontal casting. As best shown in FIG. 1, and as is well known in the art, molten metal is continuously poured from a tundish T into a generally parallelepipedal mould cavity C which extends vertically through the mould 10 and is open at the top and at the bottom of the mould. The molten metal in the tundish T is poured through a nozzle N into the upper or entrance end E of the mould cavity C where it forms a relatively stationary meniscus covered by a liquid flux. During its passage from the entrance end E to the lower or exit end D of the mould cavity C the molten metal is cooled by the mould to form a solidified strand S, which is in this case a strip and thus of a width that is a large multiple of the thickness. In operation, the mould 10 is mounted between a pair of mounting blocks M of a casting machine, which may be of conventional design. The mould proper comprises a pair of spaced-apart side walls, generally designated by 11, and a pair of end walls 12 formed of a pair of graphite bars and bridging the gap between the confronting inner sides of the side walls 11 so that the side and end walls 11, 12 jointly define the mould cavity C. FIG. 2 clearly shows the rectangular shape of the mould cavity C as viewed in the direction the cast metal moves through the passage formed by the mould cavity. The side walls 11 are substantially identical in design. Each side wall comprises two main parts, namely a graphite slab or block 13 one face of which, the inner face 13A, is directed toward the mould cavity C and the opposite or outer face is directed away from the mould cavity, and a backing plate 14 which is secured to the mounting blocks M and supports and protects the graphite block 13. The backing plate 14 covers the entire outer face of the graphite block 13 and also engages the ends thereof. The graphite block 13 and its construction is unique and will be described in detail below, whereas the backing plate 14 may be of a substantially conventional design and need not be further described. Associated with each side wall 11 is a cooling system which is largely conventional except for a part thereof. That part is included in the graphite block 13 and comprises an array of parallel, coolant tubes 15 of metal, such as copper. Other parts (not shown) of the system include means incorporated in the backing plates 14 for passing a liquid coolant through the graphite block 13. As shown in the drawings, the tubes extend horizontally—that is, transversely to the direction in which the cast metal moves through the mould cavity C—between opposite ends of the graphite block 15 along a vertical plane approximately centrally between the vertical large faces 13A, 13B of the graphite block 13. The graphite block 13 of each side wall 11 is formed of a large number of thin strip-like rectangular elongate thin (thickness e.g. about 1 mm) graphite sheets or laminae 16 which are stacked with their broad surfaces or faces 16A in engagement with one another and their narrow longitudinal surfaces or edges 16B jointly forming the broad sides or faces 13A, 13B of the parallelepipedal slab-like straight stack or graphite block 13 so formed. The inner face 13A of the graphite block 13 mounted in the mould 10 forms one of the sides of the mould cavity C. Preferably, the laminae 16 are made from flaky graphite, that is, graphite made up essentially of compacted flakes which are oriented such that they extend in planes substantially parallel to the faces of the graphite sheets from which the laminae are cut. Graphite sheets (foils and plates) that kind are readily available as commercial products. A particular attraction of such graphite sheets in the context of the present invention is that their thermal conductivity in directions parallel to the faces is considerably better than their thermal conductivity perpendicular to the faces. Examples of commercially available graphite sheet products that are suitable for the graphite block according to the invention are marketed by Sigri Elektrografit GmbH, Meitingen bei Augsburg, Germany, under the designations SIGRAFLEX-F (foils) and SIGRAFLEX-L (plates). For the purpose of the present invention, namely to achieve as favourable heat conducting properties as possible, it is desirable that the density of the graphite making up the laminae be as high as possible. It may be advantageous, therefore, to increase the density of the commercially available sheets of flaky graphite by subjecting the sheets, or the laminae cut from them, to a densifying treatment, such as by rolling, before the stacks are formed. Before the graphite block 13 is formed by stacking the laminae 16, apertures are formed, e.g. punched in the laminae to allow for reception of the coolant tubes 15. The size of the apertures should be accurately matched with the size of the coolant tubes 15 so that a snug fit of the tubes in the apertures is achieved. Such a fit is essential to obtain an efficient heat transfer from the graphite to the liquid coolant flowing in the coolant tubes. A convenient procedure for forming the stack from the apertured laminae 16 is to secure one end of the coolant tubes 15 to an end member 17, preferably a rectangular plate of approximately the length and width of the laminae 16 (see FIG. 3 where the thickness of the lamina is exaggerated in the interest of clarity), such that the tubes extend in accurately parallel relation, and then sliding the laminae 16 over the opposite ends of the tubes and pushing them along the tubes until they are in face-to face engagement with one another. When all laminae 16 required to form the stack have been added, a similar end member 17 is applied to the stack and pressure is applied in opposite directions through the end members to compact the stack and the laminae 16 forming the stack. Such compaction enhances the contact of the lamina with the coolant tubes 15 and thereby promotes the heat transfer from the lamina 16 to the coolant flowing in the tubes. Following the above-described assembly of the graphite block 13 with the coolant tubes 15 accommodated in it, the large faces 13A, 13B of the graphite block are machined, such as by milling, so that the graphite block is reduced to the proper accurate dimensions and will have smooth surfaces. The so finished block is then mounted to its backing plate and installed in the casting machine. The plate-like end members 17 shown in the drawings, which engage the outer faces of the end or outermost laminae 16C (FIG. 3) of the stack, may form parts of or be joined with housings (not shown) in which the ends of the coolant tubes 15 received in the end members are connected to suitable means for passing the coolant through the coolant tubes. As described above, the confronting faces 13A of the graphite blocks 13 form parts of the walls of the mould cavity C. It is within the scope of the invention, although not preferred, to line the graphite blocks 13 with thin, e.g. 3 mm thick lining plates of graphite. Although the graphite block 13 is illustrated and described as a component of a continuous-casting mould, its applicability as a cooling device extends to other applications. Accordingly, the cooling device formed by the graphite block 13 is within the scope of the invention as claimed independently of its use in a particular application, whether in the metal-processing field or otherwise.

20050613

20070626

20060126

68087.0

B22D1100

LIN, KUANG Y

MOULD FOR CONTINUOUS CASTING OF METAL STRIPS

UNDISCOUNTED

ACCEPTED

B22D

ACCEPTED

Arrangement for fastening heating elements to a furnace

The invention relates to an arrangement for mounting electric heating elements in a furnace in which objects are intended to be heated, wherein the furnace wall includes a furnace insulation (4) comprised of high grade brick, and wherein the heating zones (6) of respective electric heating the inner surface of the furnace wall in operation. The invention is characterised in that the electric leads or conductors (7, 8) of each element (2) are mounted in a cassette (9) and extend in channels (10, 11) therein; in that the heating zone (6) of the heating element projects outwards and defines an angle with the longitudinal axis of the cassette (9); in that the furnace insulation (4) includes for each cassette a hole (12) which is larger at its outer end than at its inner end, therewith enabling the cassette (9) to be rotated in a vertical plane as the heating zone (6) of the element (2) is inserted through the hole (12) and into said operating position parallel with the furnace wall; and in that a wedge-like body (13) is provided, whose shape corresponds to the shape of the empty space created by the shape of the hole (12) and located between the hole (12) and the cassette (9) when the cassette is placed in operating position in the hole, said body (13) being placed in said empty space during operation.

1. An arrangement for fastening electric heating elements in a furnace in which objects are to be heated, wherein the furnace wall includes a layer of furnace insulation, and wherein heating zones of respective electrical heating elements are positioned substantially vertically and parallel with an inner surface of the furnace wall, said arrangement comprising: a heating element cassette including channels for receiving electric leads of a heating element having a heating zone that projects out from and defines an angle with a longitudinal axis of the cassette; the furnace insulation including for each cassette a hole which is larger at its outer end than at its inner end, to enable the cassette to be rotated in a vertical plane as the heating zone of the element is inserted through the hole and into an operating position substantially parallel with the furnace wall; and a wedge body having a shape that corresponds to the shape of an empty space created by the shape of the hole (12) and located between the hole and the cassette when the cassette is placed in said operating position in the hole; wherein the body is located in said empty space during operation of the furnace. 2. An arrangement according to claim 1, wherein said angle is between about 30 and about 60 degrees. 3. An arrangement according to claim 1, wherein the cassette is elongate and has a generally rectangular cross-section. 4. An arrangement according to claim 1, wherein the furnace insulation and the cassettes are comprised of high grade brick. 5. An arrangement according to claim 4, wherein said body is comprised of high grade brick. 6. An arrangement according to claim 1, wherein said hole has a generally rectangular cross-section. 7. An arrangement according to claim 6, wherein the hole has a horizontal underside, parallel vertical side edges, and an upper side that defines an angle with the a horizontal plane. 8. An arrangement according to claim 7, wherein the cassette is in abutment with the upper side of the hole when in an operating position; and wherein the body is inserted beneath the cassette. 9. An arrangement according to claim 1, wherein the furnace includes a process tube in which objects are heated, wherein a space is formed between the process tube and the furnace insulation, and wherein the heating zones of respective electric heating elements are located in said space substantially parallel with the outer surface of the tube during operation of the furnace. 10. An arrangement according to claim 4, wherein the brick is aluminum oxide brick. 11. An arrangement according to claim 5, wherein the brick is aluminum oxide brick.

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an arrangement for mounting an electric heating element in a furnace. 2. Description of the Related Art Electrically heated furnaces or ovens that include a process tube in which objects are heated are known to the art. Furnace insulation comprised of high grade brick, such as aluminum oxide brick, is provided externally of the process tube and in spaced relationship therewith. Such a furnace, or oven, will normally have a generally circular cross-section and will typically operate at a temperature of around 1700° C. The heating elements used are placed equidistantly around the furnace, and heating zones are positioned in the space defined between the outer surface of the process tube and the inner surface of the brick insulation. The contacts of the elements are placed outside the brick insulation, i.e., externally of the furnace. The electrical conductors of the elements extend through holes in the brick insulation. The aforesaid space has a narrow dimension in the radial direction of the furnace and, hence, the heating zone of the elements is disposed parallel with the outer surface of the process tube. The length of the heating zone is significantly greater than the width of said space. A serious problem with this solution is that the elements cannot be replaced from outside the furnace. It is therefore necessary to first cool down the furnace and then remove the process tube, in order to be able to reach and to exchange the elements. The elements are therewith removed by withdrawing them inwardly into the furnace. It will be obvious from this that the exchange of the elements is both laborious and complicated. This problem is solved by the present invention, which provides an arrangement by means of which the elements can be replaced from outside the furnace and without removing the process tube. SUMMARY OF THE INVENTION Accordingly, the present invention relates to an arrangement for mounting electric heating elements in a furnace in which objects are to be heated, wherein the furnace wall furnace insulation comprised of high grade brick. The heating zones of respective electric heating elements are placed vertically and parallel with the inner surface of the furnace wall in operation. The electrical leads or conductors of each heating element are mounted in a cassette and extend in channels provided therein, and the heating zone of respective heating elements project out and define an angle with the longitudinal axis of the cassette. The furnace insulation includes for each cassette a hole which is larger at its outer end than at its inner end, therewith enabling the cassette to be rotated in a vertical plane as the heating zone of the element is inserted through the hole and into said operating position parallel with the furnace wall. A wedge-like body is provided whose shape corresponds to the shape of the empty space created by the shape of the hole and is located between the hole and the cassette when the cassette is placed in operating position in the hole. The body is placed in the empty space during operation. BRIEF DESCRIPTION OF THE DRAWINGS The invention will now be described in more detail partly with reference to an exemplifying embodiment thereof illustrated in the accompanying drawings, in which: FIG. 1 is an outside view of part of a furnace equipped with heating elements; FIG. 2 is a cross-sectional view of part of the furnace; FIG. 3 is a perspective view of a heating element cassette; FIG. 4 is a head-on view of the heating element cassette; and FIG. 5 is a cross-sectional view of the heating element cassette taken from one side. DESCRIPTION OF THE PREFERRED EMBODIMENTS FIG. 1 shows part of a furnace 1 equipped with heating elements 2. The type of furnace shown is one that includes a process tube 3 within which objects are intended to be heated. Although the invention is described below with reference to a furnace that includes a process tube, it will be understood that the invention can be applied equally as well to a furnace without a process tube. Located externally of the process tube 3 and in spaced relationship therewith is furnace insulation 4 comprised of high grade brick. The process tube 3 and the furnace insulation 4 are normally cylindrical and have their longitudinal axes placed vertically. As will be seen from FIG. 2, a space 5 is defined between the process tube and the furnace insulation. As will also be seen from FIG. 2, the heating zones 6 of respective electrical heating elements 2 are located within said space 5 vertically and parallel with the inner surface of the furnace wall, in operation. The heating elements must hang vertically during operation, because of the high temperatures involved. The aforesaid space is only slightly wider than said heating zones. According to the invention, the electric leads, or conductors, 7, 8 of each heating element 2 are mounted in a cassette 9 and extend in channels 10, 11 therein, as shown in FIG. 3. The heating zones 6 of respective heating elements project out and define an angle with the longitudinal axis of the cassette 9. The channels may have the form of cylindrical holes or may be upwardly open, as in FIG. 3. The elements suitably rest in the channels on ceramic supports 18, to prevent the elements sticking to the cassettes. The elements are of a suitable kind and are supplied by the Applicants of this Patent. As shown in FIG. 1, the furnace insulation 4 includes a hole 12 for each cassette 9. The hole 12 is larger at its outer end than at its inner end. This enables the cassette 9 to be rotated in the vertical plane as the heating zone 6 is inserted through the hole 12 and into the operating position parallel with the process tube 3. This is illustrated in FIG. 2, where the cassette, referenced 9a, is moved to a position 9b and finally to a position 9c. For the sake of clarity, the position 9c is illustrated by an overlying cassette. The arrangement also includes a wedge-like body 13 whose shape corresponds to the shape of the empty space created by the shape of the hole 12 and located between the hole 12 and the cassette 9 when the cassette is placed in its operating position in said hole. As will be best seen from FIG. 5, the body 13 is placed in said empty space during operation. An element is removed by first removing the wedge-shaped body and then the cassette. In this case, the cassette has the design shown in FIG. 3. The contact shoes 14, 15 of the element are loosened, the element holder 16 is removed and the element is taken away by moving it obliquely downwards as viewed in FIG. 3. A new element can then be fitted in the reverse order of the above steps. Thus, it is possible to remove and to fit elements as the furnace is in operation, which affords a significant advantage over known techniques. According to one preferred embodiment of the invention, the element is at an angle of between 30 and 60 degrees, although said angle may, of course, be adapted to the design of the hole and to the width of the space 5 between the process tube and the insulation 4, so that the element can be inserted and withdrawn in the aforesaid manner. According to one preferred embodiment, each cassette 9 is elongate and has a generally rectangular cross-section. It is preferred that the furnace insulation 4 and the cassettes 9 are made from high grade brick, such as from aluminum oxide brick. It is also preferred that the body 13 is made from high grade brick, such as aluminum oxide brick. The aforesaid hole will preferably have a generally rectangular cross-section. It is also preferred that the hole 12 has a horizontal undersurface, parallel vertical side edges and an upper side that defines an angle with the horizontal plane. In case of such a design of the hole, it is preferred that the cassette 9 will abut the upper side of the hole 12 when in its operating position. Assuming that the cassette 9 has the same width as the hole 12 and that the cassette 9 abuts the upper side of said hole when fitted, a wedge shaped open space will be formed beneath the cassette 9, as shown in FIG. 1 at the hole 12. In this case, the body 13 is shaped to fit in the wedge shaped space. Assembly is thus terminated by pushing the body in beneath the cassette. As a result, the furnace insulation is sealed essentially against heat leakage at the heating elements. It will be obvious that the present invention solves the problem mentioned in the introduction. It will also be obvious that the invention can be varied with regard to the design of the cassettes, the configuration of the holes and said body without departing from the function of achieving a seal essentially against the leakage of heat at said elements. The present invention shall not therefore be considered as restricted to the embodiments indicated above, since variations and modifications can be made within the scope of the accompanying claims.

<SOH> BACKGROUND OF THE INVENTION <EOH>1. Field of the Invention The present invention relates to an arrangement for mounting an electric heating element in a furnace. 2. Description of the Related Art Electrically heated furnaces or ovens that include a process tube in which objects are heated are known to the art. Furnace insulation comprised of high grade brick, such as aluminum oxide brick, is provided externally of the process tube and in spaced relationship therewith. Such a furnace, or oven, will normally have a generally circular cross-section and will typically operate at a temperature of around 1700° C. The heating elements used are placed equidistantly around the furnace, and heating zones are positioned in the space defined between the outer surface of the process tube and the inner surface of the brick insulation. The contacts of the elements are placed outside the brick insulation, i.e., externally of the furnace. The electrical conductors of the elements extend through holes in the brick insulation. The aforesaid space has a narrow dimension in the radial direction of the furnace and, hence, the heating zone of the elements is disposed parallel with the outer surface of the process tube. The length of the heating zone is significantly greater than the width of said space. A serious problem with this solution is that the elements cannot be replaced from outside the furnace. It is therefore necessary to first cool down the furnace and then remove the process tube, in order to be able to reach and to exchange the elements. The elements are therewith removed by withdrawing them inwardly into the furnace. It will be obvious from this that the exchange of the elements is both laborious and complicated. This problem is solved by the present invention, which provides an arrangement by means of which the elements can be replaced from outside the furnace and without removing the process tube.

<SOH> SUMMARY OF THE INVENTION <EOH>Accordingly, the present invention relates to an arrangement for mounting electric heating elements in a furnace in which objects are to be heated, wherein the furnace wall furnace insulation comprised of high grade brick. The heating zones of respective electric heating elements are placed vertically and parallel with the inner surface of the furnace wall in operation. The electrical leads or conductors of each heating element are mounted in a cassette and extend in channels provided therein, and the heating zone of respective heating elements project out and define an angle with the longitudinal axis of the cassette. The furnace insulation includes for each cassette a hole which is larger at its outer end than at its inner end, therewith enabling the cassette to be rotated in a vertical plane as the heating zone of the element is inserted through the hole and into said operating position parallel with the furnace wall. A wedge-like body is provided whose shape corresponds to the shape of the empty space created by the shape of the hole and is located between the hole and the cassette when the cassette is placed in operating position in the hole. The body is placed in the empty space during operation.

20050124

20060314

20050616

60499.0

HOANG, TU BA

ARRANGEMENT FOR FASTENING HEATING ELEMENTS TO A FURNACE

UNDISCOUNTED

ACCEPTED

ACCEPTED

Automated centerline detection algorithm for colon-like 3d surfaces

A three dimensional image of the colon like surface is processed to determine at least its ring structure. The image is composed of vertex points, each vertex point having a discrete point identifier and three dimensional position information. The three dimensional position information is averaged in a shrinking procedure to contract the three dimensional image proximate to a major axis of the colon-like surface. Evenly spaced points are taken through the shrunken colon like surface and connected to form a curve. Planes are generated at intervals normal to the curve to split the shrunken colon like surface into image segments. By mapping these image segments back to the original image through their discrete point identifiers, an accurate ring profile of the colon like surface can be generated.

1. An automated detection algorithm to compute the ring profile of colon like surfaces comprising the steps of: providing an original image of a colon like surface disposed along a major axis in a scan having vertex points, each vertex point having a discrete point identifier and three dimensional position information; generating a thin version of the colon like surface utilizing neighbors averaging of the three dimensional position information for every vertex point in the original colon view; modeling the thin version of the colon like surface with an ordered set of 3-D points to produce a curve proximate to the major axis of the colon like surface; isolating segments of vertex points (along) between planes normal to the curve proximate to the major axis of the colon from the thin version of the colon like surface; mapping the isolated segments of vertex points from the thin version of the colon like surface back to the original image of the colon like surface to generate a ring profile of the colon like surface. 2. The automated detection algorithm to compute the ring profile of colon like surfaces according to claim 1 comprising the steps of: decimating the vertex points of the provided original image. 3. The automated detection algorithm to compute the ring profile of colon like surfaces according to claim 1 comprising the steps of: computing a centerline of the colon utilizing the ring profile of the colon like surface. 4. The automated detection algorithm to compute the ring profile of colon like surfaces according to claim 3 comprising the steps of: measuring along the computed centerline of the colon like surface to determine positional information relative to the colon like surface. 5. The automated detection algorithm to compute the ring profile of colon like surfaces according to claim 3 comprising the steps of: computing a smoothed version of the centerline of the colon to approximate centerlines obtained by invasive colonoscopy. 6. The automated detection algorithm to compute the ring profile of colon like surfaces according to claim 3 comprising the steps of: utilizing the ring profile along a preselected length of the computed colon centerline to determine the local colon volume and local colon distension along the preselected length of the colon. 7. The automated detection algorithm to compute the ring profile of colon like surfaces according to claim 3 comprising the steps of: mapping the vertices distance to the computed centerline; and, building an image of vertices distances to centerline to map the colon. 8. The automated detection algorithm to compute the ring profile of colon like surfaces according to claim 3 comprising the steps of: mapping the vertices distance to the computed centerline to obtain a mapped centerline view of the colon; rotating the mapped centerline view of the colon to spatially reorient the mapped centerline view of the colon; and, reconstructing a spatially reoriented image of the colon from the rotated centerline view by expanding the vertices distances to map the colon. 9. An automated detection algorithm to compute the ring profile of colon like surfaces comprising the steps of: providing an original image of the colon like surfaces disposed along a major axis in a scan having the colon like surface identified by vertex points, each of vertex point having a discrete point identifier and three-dimensional positional information; generating a thinned image of the colon like surface utilizing a neighbors averaging of the three-dimensional positional information for vertex points in the original colon view; randomly designating a first vertex modeling point at a vertex point along the thinned the colon image; identifying and marking neighboring vertex points to the randomly selected first vertex modeling point; designating a second vertex modeling point located at a predetermined distance from the first of vertex modeling point; sequentially repeating the identifying and marking, and designating steps to designate vertex modeling points from the randomly selected first vertex modeling point to an end of the colon; connecting the designated vertex modeling points to produce a curve proximate to the major axis of the colon like surface; isolating groups of vertex points between planes normal to the curve from the thin image of the colon like surface; and, mapping the isolated groups of a vertex points from the thinned image of the colon like surface back to the original image of the colon like surface to generate a ring profile of the colon like surface. 10. An automated detection algorithm to compute an approximate centerline profile of colon like surfaces comprising the steps of: providing an original image of the colon like surfaces disposed along a major axis in a scan having the colon like surface identified by vertex points, each of vertex point having a discrete point identifier and three-dimensional positional information; generating a thinned image of the colon like surface utilizing a neighbors averaging of the three-dimensional positional information for vertex points in the original colon view; randomly designating a first vertex modeling point at a vertex point along the thinned the colon image; identifying and marking neighboring vertex points to the randomly selected first vertex modeling point; designating a second vertex modeling point located at a predetermined distance from the first of vertex modeling point; sequentially repeating the identifying and marking, and designating steps to designate vertex modeling points from the randomly selected first vertex modeling point to an end of the colon; connecting the designated vertex modeling points to produce a curve proximate to the major axis of the colon like surface. 11. An automated detection algorithm to compute the ring profile of colon like surfaces comprising the steps of: providing an original image of the colon like surfaces disposed along a major axis in a scan having the colon like surface identified by vertex points, each of vertex point having a discrete point identifier and three-dimensional positional information; generating a thinned image of the colon like surface utilizing a neighbors averaging of the three-dimensional positional information for vertex points in the original colon view; randomly designating a first vertex modeling point at a vertex point along the thinned the colon image; identifying and marking neighboring vertex points to the randomly selected first vertex modeling point; designating a second vertex modeling point located at a predetermined distance from the first of vertex modeling point; sequentially repeating the identifying and marking, and designating steps to designate vertex modeling points from the randomly selected first vertex modeling point to an end of the colon; connecting the designated vertex modeling points to produce a curve proximate to the major axis of the colon like surface; isolating groups of vertex points between planes normal to the curve from the thin image of the colon like surface; and, mapping the isolated groups of a vertex points from the thinned image of the colon like surface back to the original image of the colon like surface to generate a ring profile of the colon like surface. 12. An automated detection algorithm to compute an approximate centerline profile of colon like surfaces comprising the steps of: providing an original image of the colon like surfaces disposed along a major axis in a scan having the colon like surface identified by vertex points, each of vertex point having a discrete point identifier and three-dimensional positional information; generating a thinned image of the colon like surface utilizing a neighbors averaging of the three-dimensional positional information for vertex points in the original colon view; randomly designating a first vertex modeling point at a vertex point along the thinned the colon image; identifying and marking neighboring vertex points to the randomly selected first vertex modeling point; designating a second vertex modeling point located at a predetermined distance from the first of vertex modeling point; sequentially repeating the identifying and marking, and designating steps to designate vertex modeling points from the randomly selected first vertex modeling point to an end of the colon; connecting the designated vertex modeling points to produce a curve proximate to the major axis of the colon like surface.

This invention relates to virtual colonoscopy and includes processing computer tomographic image slices of the patient. The disclosure assumes the procurement of a three dimensional image of the colon like surface of vertex points distributed along an elongate major axis, each vertex point having a discrete point identifier and three dimensional position information. In this disclosure, an accurate ring profile of the colon like surface can be generated. Utilizing the accurate ring profile, reconstruct the 3D surface of the colon, serially view the colon cross-section for anomalies such as polyps and thus provide both non-invasive colon screening together with the positional information needed for follow up conventional colonoscopy. BACKGROUND OF THE INVENTION Virtual Colonoscopy is a relatively new field in medicine and consists in processing the computer tomographic (CT) image planes or “slices” of the patient rather than the traditional and invasive colonoscopic inspection. By segmenting the original parallel CT slices, it is possible to reconstruct the 3D surface of the colon and thus provide the information needed for Colonoscopy. Such a process is disclosed in Summers et al. U.S. Pat. No. 6,246,748 issued Jun. 12, 2001 and entitled Method for Segmenting Medical Images and Detecting Surface Anomalies in Anatomical Structures. This disclosure assumes as a starting point that an image similar to that produced by Summers et al '748 is produced. Assuming the presence of such an image, further processing of the image such as detecting the centerline of the colon is still a challenging problem. The following articles are representative of relevant image processing techniques that can be used to address this problem: Gabriel Taubin, “Curve and Surface Smoothing without Shrinkage”, IEEE (1995); Ingmar Bitter, et al., “Penalized-Distance Volumetric Skeleton Algorithm”, IEEE Transactions on Visualization and Computer Graphics, Vol.7, No. 3, July—September 2001; Ge, Y., D. R. Stelts, et al., “Computing the centerline of a colon; a robust and efficient method based on 3D skeletons”, J Comput Assist Tomogr, 23(5): 786-94 (1999); Jie Wang, Yaorong Ge, “An Optimization problem in Virtual Colonoscopy”, Theoretical Computer Science, Elsevier Science B. V., pp 203-216 (1998); Yaorong Ge, et al., “Computing the Centerline of a Colon: a Robust and Efficient Method Based on 3D Skeletons”, Journal of Computer Assisted Tomography, 23(5):786-794 (1999); Rui Chiou, et al., “An Interactive Fly-Path Planning Using Potential Fields and Cell Decomposition for Virtual Endoscopy”, IEEE Transactions on Nuclear Science, Vol 46, No. 4, August 1999; David Paik, et al., “Automated flight path planning for virtual endoscopy”, American Assoc Of Physicists in Medicine (1998); C. L. Wyatt, et al., “Automatic Segmentation of the Colon for Virtual Colonoscopy”, Elsevier Science (2000); Elisabeth McFarland, et al., “Spiral Computed Tomographic Colonography: Determination of the Central Axis and Digital Unravelling of the Colon”, Technical Report, Acad. Radiology, 4:367-373 (1997); Roel Truyen, et al., “Efficacy of automatic path tracking in Virtual colonoscopy”, Cars 2001—H. U Lemke, et al. (Editors), Elsevier Science (2001). C. E. Shannon, “A Mathematical Theory of Communication”, Bell System Tech. J, 379-423 (1948); and W. J. Schroeder, et al., “Decimation of Triangle Meshes”, Computer Graphics, 26:26 (1992). The reader will understand that the colonoscope is the usual instrument used both for inspection and surgery of the colon. The measurements of the colon must be all related to the path of the colonoscope, always from the rectum. In making its penetration of the colon, the colon “gathers” the invading colonoscope into the serpentine path of the major axis of the colon while the colonoscope “hunts” this path within the confines of the colon. As a consequence of this well known and understood technique of using a colonoscope, relevant measurements taken with respect to the colon by non-invasive CT scans must all be related to penetration of a colonoscope. Further, scans taken by a colonoscope must be able to be compared to non-invasive scans taken by computer tomography to establish the efficacy of the non-invasive scans. Likewise, and assuming efficacy of the non-invasive scans, the findings of the non-invasive scans must be directly translatable to the doctor using colonoscope to be of practical value. BRIEF SUMMARY OF THE INVENTION A virtual non-invasive colonoscopy of a colon like surface includes processing computer tomographic image slices of the patient. The procurement of a three dimensional image of the colon like surface of vertex points, each vertex point having a discrete point identifier and three dimensional position information is presumed. The three dimensional position information of all vertex's neighbors is averaged in a shrinking procedure to contract the three dimensional image proximate to a major axis of the colon-like surface, with the overall length of the colon along the major axis remaining substantially unchanged. Evenly spaced points are taken through the shrunken colon like surface and connected to form a curve. Planes are generated at intervals normal to the curve to split the shrunken colon like surface into image segments. By mapping these image segments back to the original image through their discrete vertex point identifiers, an accurate ring profile of the colon like surface can be generated. Utilizing the accurate ring profile, it is possible to compute an accurate colon centerline, serially view the colon cross-section for anomalies such as polyps and thus provide both non-invasive colon screening together with the positional information needed for follow up conventional colonoscopy. As of the filing of this Patent Cooperation Treaty application, an improved technique for modeling of the centerline of the colon includes taking the image of the shrunken colon and choosing and marking a first random vertex. The reader will understand that all vertices on the shrunken image of the colon are by definition very close to the colon centerline by virtue of the fact of the image being a shrunken image. Once this first random vertex is choosen, all unmarked neighbors of the random vertex of the shrunken image of the colon are identified and marked. The identification and marking process is sequentially repeated from each marked neighbor to all unmarked neighbors. When the identification and marking process propagates a predetermined distance (preferably a multiple of the maximum diameter of the shrunken colon, plus or minus a chosen tolerance), a second random vertex is designated. A third random vertex is chosen at substantially the same interval from the first random vertex, but in the opposite direction. Thus, starting with the first random vertex, marking of the vertices propagates from the first random vertex to both ends of the shrunken colon image. In this process, all unmarked neighbors of each random vertex are identified and marked until the process propagates the predetermined distance, a new random vertex is designated, and marking process continued. The marking of vertices thus proceeds from the first random vertex, located centrally of the colon, to spaced random vertices extending along the colon to the respective ends of the colon at the anal verge and the cecum. The reader will understand that since we are working on an image of a shrunken colon, all vertices on the surface of the shrunken image must by definition be very close to the colon centerline. Thus, the shrunken colon surface, the centerline of the shrunken colon, and the centerline taken along the length of the colon are all essentially the same. They have the essentially the same (serpentine) three dimensional position in space along the length of the colon. An advantage of this marking system is that it eliminates the use of vectors in determining the centerline of the colon. The simple process of vertex identification and marking followed by designating vertices systematically tracks the length of the shrunken image of the colon from the first random vertex to both colon ends. In the following disclosure, it is necessary to define terms. These terms are: Colon like surface: This term obviously includes the colon. It includes other surfaces within the human body that are elongate about what can be generally termed a major axis or axes. Such surfaces can also include blood vessels, biliary ducts, airways, small intestine, spinal canal and cord. Major axis or axes: When one views a body structure, such as the colon, an irregular enclosed but generally cylindrical elongate structure is shown. Elongation can be said to occur generally proximate to a major axis of the structure. This major axis is not the same as the ultimately computed centerline. Further, this term is used in this disclosure to express an intuitive concept perceived by observing the elongate colon structure. Vertex point: This is the discrete informational image point that together with many other similar image points makes up the initial image processed by this invention. Such vertex points each have a discrete identifier. Further, the vertex points have three dimensional image information, commonly in Cartesian coordinates. As will be apparent in what follows, this disclosure alters the positional information in a shrinking process. The shrinking process leaves the colon like surface length substantially unchanged along the major axis but drastically shrinks the width of the colon like surface. Once shrinking has occurred, the shrunken image is parsed and mapped back to the original image utilizing the discrete identifiers. Shrunken colon like surface: This is a 3D surface, obtained from the originally supplied 3D-colon like surface. The shrunken colon is very thin and almost as long as the original colon. The shrunken colon like surface has the same number of vertices as the original colon and the same “structure.” The vertices neighborhood relation is the same, indexed (triangle) strip sets are the same. Stated in theoretical terms, this means that, for every integer “i” and “k”, if vertex Vi (vertex number i) has vertex Vk (vertex number k) as a neighbor in the original colon, there will be a vertex Vi in the shrunken colon that will have a neighbor Vk. The only difference will be in the three dimensional image information. In the “shrunken colon like surfaces”, the distances from the major axis to the vertex points will be almost 10 to 100 times smaller in the shrunken colon as in original colon image. Rings: It will be understood that slices of the (original or shrunken) colon like surfaces generally are normal to the major axis of the elongate surface. These slices are deformed cylinders. These cylinders will be large in the original image and small in the shrunken image and composed of vertex points. We also want the axis of these cylinders to be parallel to (if not included in) the centerline of the original or shrunken colon. When this happens we also refer to such slices as “perpendicular rings.” Centerline: This is the most useful output of our image manipulation. It approximates the gathered path of a colonoscope as it hunts centrally of the colon. It is close to the more mathematically elaborated concept of skeletons. We want the centerline to closely model the inserted profile of the colonoscope, which is semi-rigid and cannot make sharp bends. Intuitively the centerline of a colon-like surface should be the curve that stays inside the colon and never goes “too close” to the walls. We use the computed centerline to discriminate various colon areas that are polyp candidates in order to be able to evaluate the accuracy of the polyp detection software module, such as that set forth in Summers et al. U.S. Pat. No. 6,246,748 issued Jun. 12, 2001 entitled Method for Segmenting Medical Images and Detecting Surface Anomalies in Anatomical Structures. Utilizing centerline information realized from the processed original image of the colon like surface, the software-detected polyps are compared with the human detected polyps to both establish efficacy of the disclosed technique and to render the disclosed non-invasive colonoscopy a useful tool for further colonoscope inspection and surgery. In most cases, comparison is based on the distance to and from the anal verge. These provided values are actually based on the length of the colonoscope at the moment of polyp detection. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a perspective view of a typical human colon omitting related anatomy illustrating the exterior profile obtained by the disclosure of Summers et al. U.S. Pat. No. 6,246,748 issued Jun. 12, 2001 and entitled Method for Segmenting Medical Images and Detecting Surface Anomalies in Anatomical Structures; FIG. 2A is a two dimension plot of vertex points illustrated along a circular path illustrating shrinkage of the circle by the averaging technique of this invention; FIG. 2B is a two dimensional plot of vertex points illustrated along a linear path illustrating no shrinkage of the linear path by the averaging technique of this invention; FIG. 3 is the colon of FIG. 1 having been shrunken by “neighbors averaging” with about 250 iterations; FIG. 4 is a schematic of a three dimensional “neighbors averaging” illustrating the alteration of three dimensional position of the vertex points along a length of a colon having its local major axis oriented horizontally; FIG. 5 is a schematic of a three dimensional “neighbors averaging” illustrating the alteration of three dimensional position along a length of a colon having its local major axis undertaking relatively large curvature; FIG. 6 is a schematic of vertex points taken along a shrunken colon illustrating how previous selected random vertex points generate both a position or origination of a vector and a search volume defined about the vector to enable selection of the next random vertex point along the length of the shrunken colon; FIG. 7A is a schematic of a search sphere segment taken along a solid angle generated from a vector defined by two previously located random vertex points; FIG. 7B is a schematic on a reduced scale illustrating the location of the random vertex points along the length of the shrunken colon; FIG. 8 is a schematic detail illustrating the difficulty of tracking random vertex points where the colon-like surface being tracked undertakes a sharp bend; FIG. 9 is a schematic diagram illustrating the construction of planes normal to model curve, and passing through points in the curve constructed from randomly determined data points along the length of the shrunken colon to separate out those vertex points local to a ring segment of the colon; FIG. 10 is a schematic illustrating vertex points from between two planes taken in FIG. 9 being mapped to the original image of the colon; FIG. 11A display a ideal ring when the colon is ideal—a twisted cylinder and 11B illustrates the real situation when the rings are not small cylinders. We also suggest another technique, simpler but different than averaging technique that is used in our implementation, for determining the centerline of the colon in the real situation: we can compute the centerline point using the center of the bounding box of the rings; FIG. 12 illustrates a coordinate Cartesian coordinate convention superimposed upon a typical human colon; and, FIG. 13 is a schematic illustrating a colon stretched along a linear path. FIG. 14 is a schematic of a thinned colon image illustrating the selection of a random vertex point VO illustrating successive identification and marking of the neighboring vertex points with propagation occurring generally from the left to the right of the illustration; and, FIG. 15 is a schematic of a thinned colon image illustrating designation of a random vertex points from an initially selected first random of vertex to both colon ends. DETAILED DESCRIPTION OF THE INVENTION Referring to FIG. 1, we assume the acquisition of a 3-D image of the colon like surface such as that disclosed in Summers et al. U.S. Pat. No. 6,246,748 issued Jun. 12, 2001 and entitled Method for Segmenting Medical Images and Detecting Surface Anomalies in Anatomical Structures. We are using the results of the module which process the CT slices and computes the 3D surface of the colon in accordance with that disclosure. In this view, the anal verge 14 and the cecum 16 can be seen at either end of the colon. Having acquired such an image, our problem is: given the 3D surface of the colon we want to find an (ordered) set of 3D points which define the colon 's centerline. The method involves basic steps: 1) Compute a shrunken version of the colon. Basically the distances between vertices are iteratively averaged, the result being a shrunken colon. The shrunken colon is very thin and almost as long as the original colon. 2) Model the shrunken colon by an ordered group of 3D points along the major axis of the colon. We take equally distanced arbitrary vertices from the shrunken colon to form a curve consisting of an ordered group of 3D points. This curve is generally similar to but may or may not coincide with the major axes, or the ultimately computed centerline. 3) Using the curve of the connected 3D points, we generate equally distanced planes perpendicular to the curve to define equal length segments along the shrunken colon We map vertex points between these planes back to the original image of the colon to compute ring-like areas in the original colon. 4) Using the ring-like areas from the original colon, a centerline can be computed. The indices of the vertices from the same segment are used to get a ring-like area “slice” from the original colon image. Any such ring-like area slice is processed to compute the local centerline point. It can be understood that the resulting points could be further used for computing better slices (“more” perpendicular on the centerline and more straight edged, smoothed or filtered centerline, etc). The original (not shrunken) colon is thus sliced. Our method could be used to process any similar shape (twisted cylinder). The method does not need the original CT slices and it uses only the reconstructed 3D surface. The results are based on colon versions with reduced-number of vertices. This permits us not only to reduce the total processing time but also to improve the algorithm performances. The shrunken colon model is accurate if the distances between points are much bigger (2-5 times) than the shrunken colon diameter. To perform the shrinking step, the distances between vertices are iteratively averaged, the result being a shrunken colon. For the purposes of this disclosure,, the two terms are equivalent; colon shrinking is the same as colon averaging. As will be explained later in this disclosure the “averaging” technique takes place in a three-dimensional basis. Referring to FIGS. 2A and 2B, a simplified explanation of the iterative averaging technique is offered in two dimensions utilizing for each averaging only two adjacent vertex points. While the reader will understand that the iterative averaging is three-dimensional and includes always more than two vertex points, the following examples are believed to be helpful. Referring to FIG. 2A, a circle 19 having vertex points 20 through 24 is illustrated. So-called “averaging” of the two-dimensional positions of the vertex points 20 through 24 is disclosed. By way of example, the averaging position of vertex point 21 can be considered. Specifically, the actual two-dimensional position of vertex point 21 is ignored. Instead, in accordance with the averaging technique here disclosed, the new two-dimensional position of vertex point 21′ is the average of the respective positions of vertex point 20 and vertex point 22. This results in the position of averaged vertex point 21′ being on a chord midway between vertex point 20 and vertex point 22. Proceeding further with the two-dimensional analogy illustrated in FIG. 2A, this procedure is repeated for all vertex points located around circle 19. The result will be a new set of vertex points 20′ through 24′. When these points are all connected with a smooth curve, a new, smaller and concentric circle 19′ will be generated. It can further be seen that what has been described constitutes only one iteration. By conducting many iterations, circle 19 can effectively be shrunken to a point. Thus, using this simplistic example, one can understand how the essentially cylindrical section of a human colon can be “shrunk.” Referring to FIG. 2B, a straight line 29 is shown having vertex points 30 through 34 along its length. The same averaging technique is applied. For example vertex point 31 has as its new position the average position of its vertex neighbors 30 and 32; this “new” position is labeled as vertex point 31′. It is immediately seen that the position of vertex point 31 and vertex point 31′ is identical. Thus the reader will appreciate that line 29 does not shrink. In what follows, we will apply this illustrated two-dimensional technique to the three-dimensional image. Further, it will be understood that “average” positions will constitute three-dimensional average positions selected from many more than just two neighbors. Remembering that the serpentine colon is elongate along a major axis but generally irregularly cylindrical in shape, the reader can be given an intuitive understanding of why the iterative averaging process of this invention results in the shrunken colon having the same length but considerably reduced in diameter. It further will be remembered that each vertex point has at least two information sets. One of these information sets is a discrete identifier for each vertex point. This discrete identifier for each vertex point is not altered as a result of the shrinking process. The other of these information sets is the three-dimensional position of the vertex point. This information set is altered as a result of the averaging process. The disclosed “shrinking” causes all of the vertex points to move to and towards the major axis of the colon. Having given an oversimplified example of the averaging technique, a more technical description will be offered. The pseudo-code for one iteration is: TABLE 1 STEP Description 1) Take neighbors of Vi 2) Average their coordinates. Get averageX, averageY, averageZ 3) Assign Vi the above computed Vi. X = averageX; Vi.Y = coordinates: averageY; Vi.Z averageZ All the operations from Table 1 are repeated for all the vertices of the surface for a certain number of times. FIG. 1 presents a 3D surface of the human colon. FIG. 3 presents the same surface shrunken 250 times. There are two important side effects of averaging: 1) Thinning of the whole shape; and, 2) Compression of the whole shape (its bounding box is smaller than the original shape). It is important to note the effect of thinning is more important than that of compression. Attention is directed to FIG. 4. In this example, the position information of a vertex point is altered utilizing the average positional information of its “neighbors.” Thus, the alteration of the positional information of the vertex points can be referred to as “neighbors averaging.” As shown in FIG. 4, the contribution of round neighbors 40, 41 (which are “at the same level” as the current vertex) to the vertex 47 movement is less significant than that of the other two vertices (displayed as squares 42, 43 and which are lower than current vertex). Observing FIG. 4, the section of the colon C illustrated is elongate (has its major axis 46) in the horizontal. The horizontal change in position due to neighbors averaging is not significant; a larger change of position is obtained perpendicular to the major axis, here on the vertical axis. If the iteration process is extremely long it is possible to obtain a straight line. The size of the movement depends actually on the curvature of the surface; points with greater curvature tend to move more. This is helpful because by shrinking we actually want to obtain a thin and twisted surface not a collapsed shape. The reader should understand that the shrunken colon is not used as the centerline of the normal colon. Referring to FIGS. 5A and 5B, it will be seen that the averaging technique of this invention does result in some shortening of the length of the colon. Points on the tight loops of the colon relative to the major axis present big curvatures. Thus points 53, 54, will tend to cause point 50 to move away from and even outside of the original surface of colon C. Points 51, 52 will tend to cause point 50 to move toward the inside of the colon C. Other points on the outside of the curvature of colon C will move toward the inside of the colon. Table 2 shows some values of the colon bounding-box (normal and shrunken version): TABLE 2 Colon type Xmin(cm) Ymin(cm) Zmin(cm) Xmax(cm) Ymax(cm) Zmax(cm) 1 normal 9.94 11.91 4.00 36.88 32.59 47.40 thinned 10.43 13.86 5.20 35.89 30.89 44.22 2 normal 8.81 11.26 3.98 33.67 34.16 45.90 thinned 12.19 14.43 8.09 30.16 31.43 41.94 We can see that the variation of the bounding box is not as important as the thinning effect. For example, for colon 1, the “X” variation is: (35.89−10.43)/(36.88−9.94)=25.46/26.94=94.5% The second step is to get a model of the shrunken colon. Our aim is to obtain a set of 3D points that should approximate the shrunken colon. These points will be used in the next step, when we want to get ring-like areas of the colon surface and use them to compute the centerline. We use this ordered set of 3D points to reduce the number of vertices processed. The ordered set of 3D points is spline interpolated and the control points are used to compute rings. We define a ring as a cylinder-like portion of the shrunken colon whose axis is more or less parallel with the colon model or colon centerline. A fundamental assumption for our algorithm can be stated: the shrunken colon centerline and its model are almost the same. This is true if the shrunken colon is thin and the distance between model points is bigger (2-5 times) than the shrunken colon diameter. We now model the shrunken colon by an ordered group of 3D points along the major axis of the colon in accordance with the second step of our procedure. Referring to FIG. 6, the algorithm to extract the points is quite simple: We start with some random vertex point 60 located at the beginning of the shrunken colon. An easy area to select a random vertex point is the rectum because of its uniform location and more or less uniform direction with respect to any image of the colon. We select a first random vertex point on the rectum. The next random vertex point 61 selected is a vertex point that is located at a preselected distance D from the first random vertex point. This second vertex point and the first vertex point define a three dimensional direction or vector V. We use this vector from the second vertex to choose the new (third) vertex point 62. From now on, every time we want to choose a new vertex we do the following: compute the new direction or vector (direction=current vertex−previous vertex); define a search volume VC (see FIG. 6). This volume is the intersection between (see FIG. 7A): the sphere 65 centered in last chosen vertex and having a radius equal to the largest preselected distance allowed between two consecutive vertices; the sphere 66 centered in last chosen vertex and having a radius equal to the smallest preselected distance allowed between two consecutive vertices; and, the solid angle 67 central to the vector defined by the previous and current vertex. The solid angle could be even more than half a sphere. We use a large solid angle only to ensure the vertices are following the shrunken colon. If we do not use the vector V to define the spherical segment for search, it is possible to return back and select one of the previous vertex's close neighbors (or even the previous vertex itself). In such case it is possible to enter an infinite loop and never be able to end the colon processing. It will be understood that the solid angle should be as big as possible (even bigger than half a sphere) to ensure the proper track. Vertex choosing is random but nevertheless confined to a path generally along the major axis of the colon. The first vertex that happens to “be” within the correct search volume (VC) is chosen to be the next vertex. Our implementation uses typically a two dimensional search angle whose cosine minimum value is between (−0.2; 0.2). This means we are considering angle ranges from (−102°, +102°) to (−78°, +78°). See Table 3: min(cosine)>−1 is the lowest possible value →maximum angle range: −180° to 180°. TABLE 3 Search Angle Values min(cosine) Range (degrees) Maximum range −1 (−180°, +180°). Range 1 −0.2 (−102°, +102°) Range 2 0.2 (−78°, +78°) Minimum range 1 (−00, +0°) The low limit value depends also on the shrunken colon diameter. In order to be able to follow every colon bend, we need the solid angle to be as large as possible (see FIG. 8). If we take the maximum angle range, we risk tracking the colon incorrectly (and/or enter a infinite loop so that we'll never be able to finish data processing). In FIG. 7A, we displayed a situation when the value of 102° is not good (it is too big). The solid angle delimited spherical segment complies with our search conditions but is obviously not desired. Usually this situation doesn't happen because the ratio (distance between two vertices)/(shrunken colon diameter) is much larger. Ideally this ratio should be very large (in the range of 5-100), as we want the shrunken colon to be very thin. We have had success with the user selecting the value of the solid angle. For most colons, an angle of 102° was sufficient. The last step is to use the shrunken colon model to compute the centerline of the real (not shrunken) colon. Reviewing the disclosure thus far, we have the original colon, its shrunken version and a model of it (an ordered set of 3D points or a curve). We need to determine an ordered set of points that should stay inside the colon. This set of ordered points should model the centerline of the colon like surface. For our purposes (polyps candidates discrimination in terms of their distance from origin), it is not necessary that the centerline be really “central” (provided this could be accurately defined). In general (for example to generate a “fly” path through virtual colon) if the centerline stays inside the surface of the colon, this is enough. With reference to FIG. 9, the main steps are: For each Pi of the model Take point Pi and Pi+1 of the model; Compute the two planes 91, 92 perpendicular on the shrunken colon model (which model is actually a curve). The two planes are computed so that each of them passes through one of the corresponding points Pi and Pi+1. (see FIG. 9); Select all the vertices between these two planes 91, 92 that belong to the shrunken colon; Map these vertices to the original colon C. Thus and referring to FIG. 11A, we get vertices that are grouped in ring-like areas R ring that are perpendicular on the major axis 100 of the shrunken colon; and, Process these vertices (for example average them or compute the center of their bounding box 101) (FIGS. 10 and 11). As a primary matter, it can be seen that we have developed a new method to “segment” cylindrical shapes of an irregular cylindrical surface, here the human colon. It can be used in general in image segmentation (2D, 3D, etc) and provides an easy and efficient way to process the colon. To get the centerline we can use any method to process the resulting slices. Further, we can obtain a point or a segment of line 102 to uniquely identify that slice. The resulting points or line segments define the desired centerline. Our needs require mapping distances determined back to the actual use of the colonoscope (polyps discrimination in terms of their distance from the rectum for example). We have run a software program based on the technique here displayed. This program was run on a Dell Optiplex GX 1p PC with the features described in table 4: TABLE 4 Operating Bus Memory Processor Frequency System frequency (RAM) Intel Pentium III 550 MHz Windows 100 MHz 255 MB NT 4.00 4.1 Shrinking Shrinking the colon is vital for the whole algorithm. Typically a colon surface has 300000-500000 vertices. Averaging such a great number of vertices for 1000 times is very time consuming. For example if the number of vertices is 350000 and number of iterations is 1000 we have 11 seconds/iteration*11000 iterations=11000 seconds (almost 180 minutes=3 hours) only to shrink the colon. Also, due to the huge number of vertices, after 200-300 iterations, vertices are very close one to another. Further averaging does not generate appreciable three dimensional movement. This means that the effect of colon thinning is reduced (especially in the rectum and cecum—which are usually thick). The differences between 1000 iterations and 2000 iterations are small. It will be appreciated that we do not need all the vertices supplied from an image of the colon shown in FIG. 1 to compute the shrunken colon. Therefore, before shrinking we preprocess the 3D colon surface by decimating the vertex points comprising the image of the colon. For example, we prefer to reduce the number of vertices composing the surface by as much as 80%. Using a decimated colon image (65000 vertices instead on 350000), the average time per iteration is under 0.5 seconds (typically between 0.1-0.3 seconds), which leads to an average total time of 3 minutes per 1000 iterations. This time can be further improved by increasing the number of decimated vertices. If we are using ⅕ of the total number of points even the colon looks nice. 4.2 Interpolation Since the shrunken colon is smooth, we are using spline functions to interpolate the first approximation. The interpolated points are then used to get the get the slices in the shrunken colon and in the original colon. Final points are again interpolated (using splines) in order to provide a smooth curve inside the colon. This last step (interpolation in normal colon) is not necessary—it was implemented only to provide “nicer” (smoother) curves. This could be useful, however, in virtual navigation—allowing a small image variation between two navigation points. 4.3 Shrunken Colon Approximation The main parameters that control this stage of processing are (see FIG. 7B): vector of the solid angle for the next vertex; segment of the searched sphere delimited within the solid angle; and, radius of the searched sphere. Typical values are summarized in table 5. TABLE 5 Radius Width Angle (min value of cosine) 0.7 * Az/20 0.4 of radius −0.2 < min cos < 0.2 where: Az=Zmax−Zmin=amplitude of the whole colon on z axis (see FIG. 11 and table 2); and, Radius is expressed as a fraction of Az/20 where 20 is an empirical value. The above value (Az/20) is chosen for the following reasons. In order to minimize data processing, we implemented a “locality” mechanism. We sort our vertices based on their Z coordinate (see FIG. 12). The total number of classes is 20 and each i-th class contain vertices whose Z coordinate is between i*Az/20 and (i+1)*Az/20 (+Z mm) where i=0 . . . 19 (see FIG. 12). 20 is an empirical value and is based on the general features of the colon. If the processed shape is more twisted this value can be increased. Actually what matters is how tight are the loops of the shrunken shape: the tighter the loops are, bigger the number of classes. Referring to FIG. 12, classes are used to minimize the number of searches. For every vertex in class i we search the vertices in class i, i-1, i+1. If the total number of classes is 20 we reduce our searches by almost 85% ((20-3)/20=17/20=0.85—provided each class has the same number of points). Of course the classes have different number of vertices (for example class 0 includes only a fraction of rectum vertices) but the principle is good and it could even be increased on the X axis (defining a rectangular grid). The shrunken colon is limited to a k*20 maximum number, where k is again 20 (and again empirical), which means no more than 400 points. These points are interpolated, introducing 3 new points between each 2 old points, and we obtain (400−1)*3+1 total numbers for the shrunken colon. These (almost) 1200 points generate 1200 points in the original colon, which in turn are again interpolated. Finally we have a centerline composed of maximum (1200−1)*3+1 values=cca 3600. We never obtain such big values, typically the centerlines are modeled by less than 1000 points (500-900). The colon thickness (diameter) is also important. If this is not small the approximating line will be twisted and the slices will not be processed accurately. One solution is to increase the shrinking (either the number of iterations or the number of decimated vertices). Another solution would be to provide an adaptive sphere radius, function of the colon diameter. This could be made either automatically (compute somehow the colon diameter) or using some a priori known information about colon shape (radius bigger at the beginning for the rectum and at the end for cecum, since these are usually the biggest segments of the colon). We are using the first solution in our algorithm. If, at the beginning, we were using 500 iterations to shrink, finally the value of 1000 proved to be enough for our needs. Another solution would be to increase the volume/surface averaged (considering not only the corresponding ring but also a part of the previous and next ring) in the original colon again on some a priori known areas where the colon diameter is usually big. We are using this actually on the whole colon in order to obtain a smoother centerline that models the colonoscope. 4.4 Computing Slices in the Original Colon Using the points that approximate the shrunken colon is easy to determine slices (rings) as thick as we wish which are perpendicular on the shrunken colon centerline. Actually the main idea behind the shrunken colon is that the shrunken colon model and its centerline are almost the same. This is true because the shrunken colon is very thin and smooth, unlike the normal colon. Importantly, our method enables us to determine the vertices of the shrunken colon that belong to a certain slice (or ring) and then find their matching vertices in the original colon. These new vertices (from the original colon) form a ring that is more or less perpendicular on the colon centerline. The edges of this new ring (on the original colon) are not sharp (see FIGS. 11A and 11B) but we can take this ring as thick as we wish. All the values that right now are manually adjusted for each colon can be fully determined function of the local features of the colon (diameter). The whole process described above (excluding shrinking) takes less than 3 minutes (almost 2 minutes for a 65000 vertices colon). The computed slices can be further processed if we want an even more accurate centerline. Provided the slices are thin, a possible projection on a plane perpendicular on the above computed centerline can be used as illustrated in FIG. 13. In order to obtain an individual shape, we will need to re-index all the vertices. However such a 2D image can be processed easier to obtain a better approximation of the centerline. For example in FIG. 11B, we suggest taking the center of the bounding box while in our algorithm we use the average of all vertices (which may not always be inside the colon). In our program, using averaged thick cross-sections of the shrunken colon, we were able to obtain centerlines that reside completely inside the normal (not shrunken) colon. It will be understood that our algorithm uses only the 3D surface, it does not need the original CT images. Also it uses the coordinates as they are, as float numbers. The data does not need to be presented as a 3D rectilinear grid. This is one of the big differences comparing with other techniques. We are using vertices connectivity (vertex neighbors) and local vicinity. The resulting centerline is continuous and is interpolated using spline functions. The algorithm is “open” which means it can be improved using different techniques. The algorithm has basic steps and each one (or at least parts of them) could be changed and re-implemented using better approaches. For example, at some point we manage to get a cross-section of the colon. For each cross-section, a number of vertices form a “cylinder” whose axis is on the colon centerline. We average all these vertices to compute one point on the centerline. It will be understood that we could use here any other method to compute the center line point: center of the bounding box, axis of the approximating cylinder computed using minimum of total square error, skeletons and so on. The technique is fully automated. All the parameters have empirically defined values and for normal colons user interaction is not necessary. However if the colons are collapsed (sometimes the CT segmentation module fails to determine the colon boundaries), or data acquisition has gaps, sometimes the shrunken colon modeling stops before the colon end (before the cecum). In such cases we need user interaction (modifying search sphere radius and solid angle) in order to be able to cover the whole colon. The technique is relatively quick. Total average processing time is 5 minutes, from the original decimated surface to the ordered set of 3D points of the center-line, all the processing being done on a modest machine—Intel Pentium III PC, 550 MHz (see table 4). It can be further improved increasing the decimation degree for example. Another important advantage of our technique is that it already provides virtual fly-path elements (actually these elements are obtained before computing the centerline). The rings computed (slices in the original colon) are used to determine the centerline points but their projection on a plane perpendicular on their axis actually defines what the user wants to see during virtual navigation. FIG. 11B shows also that, for virtual navigation purposes, the errors involved in centerline computation (if it stays or not inside the colon) don't affect the navigation accuracy. Using the slice's bounding box, we can provide an accurate and helpful image sequence (which is actually equivalent to considering the bounding box center as the centerline point). Our method is simple. All the steps presented above are only logically separated. Their implementation is quite simple. Although the complete program (written in C/C++) takes more than 1000 lines, the most important parts (shrunken colon modeling, vertices re-mapping etc) are simple functions. Referring to FIG. 13, given a colon-like surface, we developed a method to obtain its centerline and to split the surface in slices perpendicular on its centerline. In FIG. 13 we show the colon centerline linearly disposed and how the parameters should be adapted to local conditions (in this case—local diameter) in order to increase the degree of automation of the whole process. Centerline is a vital parameter for any CAD (Computer Assisted Diagnostic) tool. For example, a navigation path to display a 2D map of vertices' distances to the centerline could be generated. Observing asymmetries in the continuum of successive ring structures could improve polyp detection. Another application of out method is computing whole colon volume and local colon volume: the simplest way to do this would be to consider very thin slices, compute their area and compute local volume by multiplying each ring area by its height. Adding all these volumes (of all the colon rings) gives us the whole colon volume. Referring to FIG. 14, a random chosen selected modeling vertex point VO is designated along the colon length, the point here being adjacent one end of the shrunken colon image. The reader will understand that this image point could be chosen anywhere along the length of the shrunken colon image—it does not have to necessarily be adjacent one end of the colon (for example toward the cecum) or the other end of the colon (toward the rectum). (See FIG. 15) A process of neighbor identification and marking occurs. In the example here shown neighbors Nvo0 through Nvo5 are all identified and marked. Next, from each marked neighbor, identification and marking of previously unmarked neighbors occurs. Taking the example of neighbor vertex Nvo2, three neighboring and are marked vertices Nvo2_2, Nvo2_1, and Nvo2_0 are all marked. This process continues along the colon segment here illustrated. As the reader can understand, in the example here illustrated propagation of neighbor vertex identification and marking happens to proceed from the left of FIG. 14 to the right of FIG. 14. It could have just as well occurred in an opposite direction. It will be understood that once directionality of neighbor identification and marking of vertices is established, this directionality will occur from the arbitrarily selected random vertex point VO to an end of the colon. Referring to FIG. 15, the neighbor vertex identification and marking process continues until a located vertices exceeds a predetermined distance from the random vertex point VO initially designated. When this predetermined distance plus or minus a tolerance) is reached, that vertex becomes a second designated modeling vertex V1-1. At this point, neighbor identification and marking will occur as illustrated in FIG. 14 until a third selected modeling vertex V1-2 is designated. This two-step process of neighbor identification and marking followed by designation of a modeling vertex will continue until an end of the colon is reached. Again referring to FIG. 15, the reader will understand that it is necessary to have the process of neighbor identification and marking followed by designation of a modeling vertex in an opposite direction. This opposite direction will be from randomly designated modeling vertex point VO (see FIGS. 14 and 15) to the opposite end of the colon. To begin this process, once second selected modeling vertex V1-1 is designated, an opposite modeling vertex V2-1 is designated in a direction opposite to second selected modeling vertex V1-1 at the predetermined distance. Once this choice is made, the two-step process of neighbor identification and marking followed by designation of modeling of vertices continues to the opposite end of the colon. Thus, it can be seen that the designation of modeling vertex points along the length of the colon effectively establishes a point trace of the shrunken colon image. This has the advantage of avoiding searches through solid angles of view for vertices as set forth in FIG. 6 and is capable of following colon images having relatively sharp curvature. Further, the disclosed process is simple, iterative, and ideal for digital processing.

<SOH> BACKGROUND OF THE INVENTION <EOH>Virtual Colonoscopy is a relatively new field in medicine and consists in processing the computer tomographic (CT) image planes or “slices” of the patient rather than the traditional and invasive colonoscopic inspection. By segmenting the original parallel CT slices, it is possible to reconstruct the 3D surface of the colon and thus provide the information needed for Colonoscopy. Such a process is disclosed in Summers et al. U.S. Pat. No. 6,246,748 issued Jun. 12, 2001 and entitled Method for Segmenting Medical Images and Detecting Surface Anomalies in Anatomical Structures. This disclosure assumes as a starting point that an image similar to that produced by Summers et al '748 is produced. Assuming the presence of such an image, further processing of the image such as detecting the centerline of the colon is still a challenging problem. The following articles are representative of relevant image processing techniques that can be used to address this problem: Gabriel Taubin, “Curve and Surface Smoothing without Shrinkage”, IEEE (1995); Ingmar Bitter, et al., “Penalized-Distance Volumetric Skeleton Algorithm”, IEEE Transactions on Visualization and Computer Graphics, Vol.7, No. 3, July—September 2001; Ge, Y., D. R. Stelts, et al., “Computing the centerline of a colon; a robust and efficient method based on 3D skeletons”, J Comput Assist Tomogr, 23(5): 786-94 (1999); Jie Wang, Yaorong Ge, “An Optimization problem in Virtual Colonoscopy”, Theoretical Computer Science, Elsevier Science B. V., pp 203-216 (1998); Yaorong Ge, et al., “Computing the Centerline of a Colon: a Robust and Efficient Method Based on 3D Skeletons”, Journal of Computer Assisted Tomography, 23(5):786-794 (1999); Rui Chiou, et al., “An Interactive Fly-Path Planning Using Potential Fields and Cell Decomposition for Virtual Endoscopy”, IEEE Transactions on Nuclear Science, Vol 46, No. 4, August 1999; David Paik, et al., “Automated flight path planning for virtual endoscopy”, American Assoc Of Physicists in Medicine (1998); C. L. Wyatt, et al., “Automatic Segmentation of the Colon for Virtual Colonoscopy”, Elsevier Science (2000); Elisabeth McFarland, et al., “Spiral Computed Tomographic Colonography: Determination of the Central Axis and Digital Unravelling of the Colon”, Technical Report, Acad. Radiology, 4:367-373 (1997); Roel Truyen, et al., “Efficacy of automatic path tracking in Virtual colonoscopy”, Cars 2001—H. U Lemke, et al. (Editors), Elsevier Science (2001). C. E. Shannon, “A Mathematical Theory of Communication”, Bell System Tech. J, 379-423 (1948); and W. J. Schroeder, et al., “Decimation of Triangle Meshes”, Computer Graphics, 26:26 (1992). The reader will understand that the colonoscope is the usual instrument used both for inspection and surgery of the colon. The measurements of the colon must be all related to the path of the colonoscope, always from the rectum. In making its penetration of the colon, the colon “gathers” the invading colonoscope into the serpentine path of the major axis of the colon while the colonoscope “hunts” this path within the confines of the colon. As a consequence of this well known and understood technique of using a colonoscope, relevant measurements taken with respect to the colon by non-invasive CT scans must all be related to penetration of a colonoscope. Further, scans taken by a colonoscope must be able to be compared to non-invasive scans taken by computer tomography to establish the efficacy of the non-invasive scans. Likewise, and assuming efficacy of the non-invasive scans, the findings of the non-invasive scans must be directly translatable to the doctor using colonoscope to be of practical value.

<SOH> BRIEF SUMMARY OF THE INVENTION <EOH>A virtual non-invasive colonoscopy of a colon like surface includes processing computer tomographic image slices of the patient. The procurement of a three dimensional image of the colon like surface of vertex points, each vertex point having a discrete point identifier and three dimensional position information is presumed. The three dimensional position information of all vertex's neighbors is averaged in a shrinking procedure to contract the three dimensional image proximate to a major axis of the colon-like surface, with the overall length of the colon along the major axis remaining substantially unchanged. Evenly spaced points are taken through the shrunken colon like surface and connected to form a curve. Planes are generated at intervals normal to the curve to split the shrunken colon like surface into image segments. By mapping these image segments back to the original image through their discrete vertex point identifiers, an accurate ring profile of the colon like surface can be generated. Utilizing the accurate ring profile, it is possible to compute an accurate colon centerline, serially view the colon cross-section for anomalies such as polyps and thus provide both non-invasive colon screening together with the positional information needed for follow up conventional colonoscopy. As of the filing of this Patent Cooperation Treaty application, an improved technique for modeling of the centerline of the colon includes taking the image of the shrunken colon and choosing and marking a first random vertex. The reader will understand that all vertices on the shrunken image of the colon are by definition very close to the colon centerline by virtue of the fact of the image being a shrunken image. Once this first random vertex is choosen, all unmarked neighbors of the random vertex of the shrunken image of the colon are identified and marked. The identification and marking process is sequentially repeated from each marked neighbor to all unmarked neighbors. When the identification and marking process propagates a predetermined distance (preferably a multiple of the maximum diameter of the shrunken colon, plus or minus a chosen tolerance), a second random vertex is designated. A third random vertex is chosen at substantially the same interval from the first random vertex, but in the opposite direction. Thus, starting with the first random vertex, marking of the vertices propagates from the first random vertex to both ends of the shrunken colon image. In this process, all unmarked neighbors of each random vertex are identified and marked until the process propagates the predetermined distance, a new random vertex is designated, and marking process continued. The marking of vertices thus proceeds from the first random vertex, located centrally of the colon, to spaced random vertices extending along the colon to the respective ends of the colon at the anal verge and the cecum. The reader will understand that since we are working on an image of a shrunken colon, all vertices on the surface of the shrunken image must by definition be very close to the colon centerline. Thus, the shrunken colon surface, the centerline of the shrunken colon, and the centerline taken along the length of the colon are all essentially the same. They have the essentially the same (serpentine) three dimensional position in space along the length of the colon. An advantage of this marking system is that it eliminates the use of vectors in determining the centerline of the colon. The simple process of vertex identification and marking followed by designating vertices systematically tracks the length of the shrunken image of the colon from the first random vertex to both colon ends. In the following disclosure, it is necessary to define terms. These terms are: Colon like surface: This term obviously includes the colon. It includes other surfaces within the human body that are elongate about what can be generally termed a major axis or axes. Such surfaces can also include blood vessels, biliary ducts, airways, small intestine, spinal canal and cord. Major axis or axes: When one views a body structure, such as the colon, an irregular enclosed but generally cylindrical elongate structure is shown. Elongation can be said to occur generally proximate to a major axis of the structure. This major axis is not the same as the ultimately computed centerline. Further, this term is used in this disclosure to express an intuitive concept perceived by observing the elongate colon structure. Vertex point: This is the discrete informational image point that together with many other similar image points makes up the initial image processed by this invention. Such vertex points each have a discrete identifier. Further, the vertex points have three dimensional image information, commonly in Cartesian coordinates. As will be apparent in what follows, this disclosure alters the positional information in a shrinking process. The shrinking process leaves the colon like surface length substantially unchanged along the major axis but drastically shrinks the width of the colon like surface. Once shrinking has occurred, the shrunken image is parsed and mapped back to the original image utilizing the discrete identifiers. Shrunken colon like surface: This is a 3D surface, obtained from the originally supplied 3D-colon like surface. The shrunken colon is very thin and almost as long as the original colon. The shrunken colon like surface has the same number of vertices as the original colon and the same “structure.” The vertices neighborhood relation is the same, indexed (triangle) strip sets are the same. Stated in theoretical terms, this means that, for every integer “i” and “k”, if vertex Vi (vertex number i) has vertex Vk (vertex number k) as a neighbor in the original colon, there will be a vertex Vi in the shrunken colon that will have a neighbor Vk. The only difference will be in the three dimensional image information. In the “shrunken colon like surfaces”, the distances from the major axis to the vertex points will be almost 10 to 100 times smaller in the shrunken colon as in original colon image. Rings: It will be understood that slices of the (original or shrunken) colon like surfaces generally are normal to the major axis of the elongate surface. These slices are deformed cylinders. These cylinders will be large in the original image and small in the shrunken image and composed of vertex points. We also want the axis of these cylinders to be parallel to (if not included in) the centerline of the original or shrunken colon. When this happens we also refer to such slices as “perpendicular rings.” Centerline: This is the most useful output of our image manipulation. It approximates the gathered path of a colonoscope as it hunts centrally of the colon. It is close to the more mathematically elaborated concept of skeletons. We want the centerline to closely model the inserted profile of the colonoscope, which is semi-rigid and cannot make sharp bends. Intuitively the centerline of a colon-like surface should be the curve that stays inside the colon and never goes “too close” to the walls. We use the computed centerline to discriminate various colon areas that are polyp candidates in order to be able to evaluate the accuracy of the polyp detection software module, such as that set forth in Summers et al. U.S. Pat. No. 6,246,748 issued Jun. 12, 2001 entitled Method for Segmenting Medical Images and Detecting Surface Anomalies in Anatomical Structures. Utilizing centerline information realized from the processed original image of the colon like surface, the software-detected polyps are compared with the human detected polyps to both establish efficacy of the disclosed technique and to render the disclosed non-invasive colonoscopy a useful tool for further colonoscope inspection and surgery. In most cases, comparison is based on the distance to and from the anal verge. These provided values are actually based on the length of the colonoscope at the moment of polyp detection.

20041230

20090804

20050602

73444.0

PARK, EDWARD

AUTOMATED CENTERLINE DETECTION ALGORITHM FOR COLON-LIKE 3D SURFACES

UNDISCOUNTED

ACCEPTED

ACCEPTED

Aqueous liquid preparations and light-stabilized aqueous liquid preparations

An aqueous liquid preparation containing (+)-(S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid or a pharmacologically acceptable acid addition salt thereof, which is stabilized with a water-soluble metal chloride, is provided.

1. An aqueous liquid preparation comprising (+)-(S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid or a pharmacologically acceptable acid addition salt thereof, and a water-soluble metal chloride. 2. The aqueous liquid preparation of claim 1, wherein the metal chloride has a concentration selected from the range of a lower limit concentration of 0.15 w/v % and an upper limit concentration of 1.5 w/v %. 3. The aqueous liquid preparation of claim 1, wherein the metal chloride is at least one kind selected from sodium chloride, potassium chloride and calcium chloride. 4. The aqueous liquid preparation of claim 1, wherein the (+)-(S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid or the pharmacologically acceptable acid addition salt thereof has a concentration selected from the range of a lower limit concentration of 0.1 w/v % and an upper limit concentration of 2.0 w/v %. 5. The aqueous liquid preparation of claim 1, which is an acid addition salt of (+)-(S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid. 6. The aqueous liquid preparation of claim 5, wherein the acid addition salt is monobenzenesulfonate. 7. The aqueous liquid preparation of claim 1, wherein the aqueous liquid preparation has a pH in the range of 4-8.5. 8. The aqueous liquid preparation of claim 1, which is an eye drop. 9. The aqueous liquid preparation of claim 1, which is a nasal drop. 10. An aqueous eye drop comprising (+)-(S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid monobenzenesulfonate and sodium chloride at not less than 0.2 w/v % and not more than 0.8 w/v %. 11. A method of light-stabilizing (+)-(S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid in an aqueous solution, which comprises adding a water-soluble metal chloride to an aqueous solution comprising (+)-(S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid or a pharmacologically acceptable acid addition salt thereof.

TECHNICAL FIELD The present invention relates to an aqueous liquid preparation comprising (+)-(S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid or a pharmacologically acceptable acid addition salt thereof, and a water-soluble metal chloride. The present invention also relates to a method of light-stabilizing (+)-(S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid and a pharmacologically acceptable acid addition salt thereof, which comprises adding a water-soluble metal chloride. BACKGROUND ART (+)-(S)-4-[4-[(4-Chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid and a pharmacologically acceptable acid addition salt thereof have an antihistaminic action and an antiallergic action. They are also characterized in that secondary effects such as stimulation or suppression of the central nerve often seen in the case of conventional antihistaminic agents can be minimized, and can be used as effective pharmaceutical agents for the treatment of human and animals (JP-B-5-33953, JP-A-2000-198784). Particularly, a tablet comprising (+)-(S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid monobenzenesulfonate (general name: bepotastine besilate) has been already marketed as a therapeutic agent for allergic rhinitis and itching associated with hives and dermatoses. On the other hand, (+)-(S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid and a pharmacologically acceptable acid addition salt thereof are unstable to light in an aqueous solution, and colored or precipitated with the lapse of time, which has made the use thereof as an aqueous liquid preparation difficult. In the case of an aqueous liquid preparation such as an eye drop and a nasal drop, a method comprising blocking light by preserving in a light-shielding container and the like can be used, but complete light-shielding is practically difficult. Thus, stabilization of an aqueous liquid preparation itself as a preparation is desirable. As a method of light-stabilizing an eye drop, a U.S. Pat. No. 2,929,274 discloses a method comprising adding boric acid and/or borax and glycerin, but according to this method, stabilization of (+)-(S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid and a pharmacologically acceptable acid addition salt thereof to light was not observed. As a general stabilization method, a method comprising placing in the coexistence of an antioxidant such as BHT etc., and the like are known (JP-A-7-304670). DISCLOSURE OF THE INVENTION The present invention aims at providing an aqueous liquid preparation comprising stabilized (+)-(S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid or a pharmacologically acceptable acid addition salt thereof. Another object of the present invention is to provide a method of light-stabilizing (+)-(S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid and a pharmacologically acceptable acid addition salt thereof in an aqueous solution. Under the above-mentioned situation, the present inventor has conducted various studies and, as a result, found that (+)-(S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid and a pharmacologically acceptable acid addition salt thereof can be light-stabilized in water by adding a water-soluble metal chloride, and further studied to complete the present invention. Accordingly, the present invention relates to (1) an aqueous liquid preparation comprising (+)-(S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid or a pharmacologically acceptable acid addition salt thereof, and a water-soluble metal chloride, (2) the aqueous liquid preparation of the above-mentioned (1), wherein the metal chloride has a concentration selected from the range of a lower limit concentration of 0.15 w/v % and an upper limit concentration of 1.5 w/v %, (3) the aqueous liquid preparation of the above-mentioned (1) or (2), wherein the metal chloride is at least one kind selected from sodium chloride, potassium chloride and calcium chloride, (4) the aqueous liquid preparation of any of the above-mentioned (1) to (3), wherein the (+)-(S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid or the pharmacologically acceptable acid addition salt thereof has a concentration selected from the range of a lower limit concentration of 0.1 w/v % and an upper limit concentration of 2.0 w/v %, (5) the aqueous liquid preparation of any of the above-mentioned (1) to (4), which is an acid addition salt of (+)-(S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid, (6) the aqueous liquid preparation of the above-mentioned (5), wherein the acid addition salt is monobenzenesulfonate, (7) the aqueous liquid preparation of any of the above-mentioned (1) to (6), wherein the aqueous liquid preparation has a pH in the range of 4-8.5, (8) the aqueous liquid preparation of any of the above-mentioned (1) to (7), which is an eye drop, (9) the aqueous liquid preparation of any of the above-mentioned (1) to (7), which is a nasal drop, (10) an aqueous eye drop comprising (+)-(S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid monobenzenesulfonate and sodium chloride at not less than 0.2 w/v % and not more than 0.8 w/v %, and (11) a method of light-stabilizing (+)-(S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid in an aqueous solution, which comprises adding a water-soluble metal chloride to an aqueous solution comprising (+)-(S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid or a pharmacologically acceptable acid addition salt thereof. In the present invention, as a pharmacologically acceptable acid addition salt of (+)-(S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid, for example, salts with hydrohalic acid such as hydrochloride, hydrobromide and the like; salts with inorganic acid such as sulfate, nitrate, phosphate and the like; salts with organic acid such as acetate, propionate, hydroxyacetate, 2-hydroxypropionate, pyruvate, malonate, succinate, maleate, fumarate, dihydroxyfumarate, oxalate, benzoate, cinnamate, salicylate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, cyclohexylsulfamate, 4-aminosalicylate and the like; and the like can be mentioned. The above-mentioned compound to be used in the present invention is generally preferably an acid addition salt, and of these acid addition salts, benzenesulfonate and benzoate are more preferable, and monobenzenesulfonate is particularly preferable. (+)-(S)-4-[4-[(4-Chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid and a pharmacologically acceptable acid addition salt thereof can be produced by, for example, the methods described in JP-B-5-33953 and JP-A-2000-198784. In the aqueous liquid preparation of the present invention, the content of (+)-(S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid or a pharmacologically acceptable salt thereof as monobenzenesulfonate is generally shown by a lower limit of about 0.1 w/v %, preferably about 0.3 w/v %, more preferably about 0.5 w/v %, and an upper limit of about 2.0 w/v %, preferably about 1.5 w/v %, which are increased or decreased appropriately depending on the object of use and the degree of symptoms. In the present invention, as a preferable water-soluble metal chloride, alkali metal chlorides such as sodium chloride, potassium chloride and the like, and alkaline earth metal chlorides such as calcium chloride and the like can be mentioned, which may be used alone, or in combination of two or more kinds thereof. Particularly preferred is sodium chloride. In the aqueous liquid preparation of the present invention, the content of the water-soluble metal chloride is generally shown by a lower limit of about 0.15 w/v % and an upper limit of about 1.5 w/v %, preferably a lower limit of about 0.2 w/v % and an upper limit of about 1.2 w/v %. Particularly, as sodium chloride, it is not less than about 0.15 w/v %, about 0.2 w/v %, about 0.3 w/v %, and not more than about 1.0 w/v %, about 0.8 w/v %, about 0.6 w/v %. As potassium chloride, it is not less than about 0.15 w/v %, about 0.2 w/v %, about 0.3 w/v %, and not more than about 1.0 w/v %, about 0.9 w/v %, about 0.8 w/v %. As calcium chloride and as dihydrate, it is not less than about 0.2 w/v %, about 0.3 w/v %, and not more than about 1.5 w/v %, about 1.2 w/v %. Moreover, the concentration of these water-soluble metal chlorides is preferably determined as appropriate within the above-mentioned concentration range, such that the osmotic pressure is generally about 230 mOsm-about 350 mOsm, in consideration of the amount of other isotonic agents to be added, such as boric acid and the like, that do not influence stabilization. Various additives that are generally used such as buffer, preservative, chelating agent, flavor and the like may be appropriately added to the aqueous liquid preparation of the present invention. As the buffer, for example, phosphate buffer, borate buffer, citrate buffer, tartrate buffer, acetate buffer, amino acid and the like can be mentioned. As the preservative, for example, quaternary ammonium salts such as benzalkonium chloride, chlorhexidine gluconate and the like, parahydroxybenzoic acid esters such as methyl parahydroxybenzoate, propyl parahydroxybenzoate and the like, sorbic acid and a salt thereof and the like can be mentioned. As the chelating agent, disodium edetate, citric acid and the like can be mentioned. As the flavor, 1-menthol, borneol, camphor, oil of eucalyptus and the like can be mentioned. The pH of the aqueous liquid preparation of the present invention is adjusted to not less than about 4, 5, 6, and not more than about 8.5, 8. In the aqueous liquid preparation of the present invention, other same or different kinds of efficacious ingredients may be added appropriately as long as the object of the present invention is not impaired. As the aqueous liquid preparation of the present invention, an eye drop, a nasal drop, an ear drop and the like can be mentioned. When the aqueous liquid preparation of the present invention is used as a nasal drop, it may be prepared into a propellant. The aqueous liquid preparation of the present invention can be produced by a production method known per se, such as a method described in the liquid preparation or eye drop of the General Rules for Preparations in the Japanese Pharmacopoeia 14th Edition. The aqueous liquid preparation of the present invention can be used for warm-blooded animals (e.g., human, rat, mouse, rabbit, bovine, pig, dog, cat and the like). When the aqueous liquid preparation of the present invention is used as, for example, an eye drop, it can be used for allergic conjunctivitis, spring catarrh, pollinosis and the like. The dose thereof when, for example, an eye drop of the present invention comprising 1.0 w/v % of (+)-(S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid monobenzenesulfonate (hereinafter to be referred to as bepotastine besilate) is instilled into the eye of an adult, is 1-2 drops per instillation, which is given 3-6 times a day by instillation into the eye. The frequency can be increased or decreased appropriately depending on the degree of symptom. BEST MODE FOR EMBODYING THE INVENTION The present invention is explained in more detail by referring to Experimental Examples and Examples, which are not to be construed as limitative. EXPERIMENTAL EXAMPLE 1 Effect of Water-Soluble Metal Chloride on Light-Stability of Bepotastine Besilate Test Method The aqueous liquid preparations (Formulations 1-6) shown in the following [Table 1], which contained bepotastine besilate, were prepared according to conventional methods and filled in glass ampoules by 5 mL each. Using a xenon long-life fade meter (FAL-25AX-Ec manufactured by SUGA TEST INSTRUMENTS Co., Ltd.), a light corresponding to not less than 200 W·h/m2 in a total near-ultraviolet radiation energy was irradiated (irradiation time: 23-34 hr), and appearance of each formulated liquid preparation was observed. The amount of light exposure was measured by a quinine chemical actinometry system described in the Drug Approval and Licensing Procedures in Japan 2001. TABLE 1 Formulation 1 2 3 4 5 6 bepotastine 1.5 g 1.5 g 1.5 g 1.5 g 1.5 g 1.5 g besilate sodium — 0.1 g 0.2 g 0.3 g — — chloride potassium — — — — 0.79 g — chloride calcium — — — — — 1.18 g chloride 2H2O sodium suitable suitable suitable suitable suitable suitable hydroxide amount amount amount amount amount amount total 100 mL 100 mL 100 mL 100 mL 100 mL 100 mL amount pH 7.0 7.0 6.7 6.9 6.7 6.8 Test Results The appearance after light irradiation was black green in Formulation 1, and a precipitate was observed. It was slightly dark green-pale yellow in Formulation 2, and a precipitate was slightly observed. Formulations 3-6 did not change from immediately after preparation and were pale yellow and clear. The results indicate that addition of a water-soluble metal chloride in not less than 0.2 w/v % improves stability of bepotastine besilate under light irradiation conditions. EXPERIMENTAL EXAMPLE 2 Effect of Boric Acid and Glycerin on Light-Stability of Bepotastine Besilate Test Method The aqueous liquid preparations (Formulations 7-9) shown in the following [Table 2], which contained bepotastine besilate, were prepared according to conventional methods and processed in the same manner as in Experimental Example 1, and appearance of each formulated liquid preparation was observed. TABLE 2 Formulation 7 8 9 bepotastine besilate 1.5 g 1.5 g 1.5 g sodium dihydrogen 0.1 g — — phosphate dihydrate boric acid — 1.0 g 0.5 g sodium chloride 0.6 g — — glycerin — 0.5 g 2.0 g benzalkonium chloride 0.005 g 0.005 g 0.005 g sodium hydroxide suitable suitable suitable amount amount amount total amount 100 mL 100 mL 100 mL pH 6.8 6.8 6.8 Test Results The appearance after light irradiation did not change from immediately after preparation and was pale yellow and clear for Formulation 7 comprising sodium chloride, but black green for Formulations 8 and 9 comprising boric acid and glycerin and a precipitate was observed. The results indicate that addition of boric acid and glycerin fails to improve stability of bepotastine besilate under light irradiation conditions. EXPERIMENTAL EXAMPLE 3 Effect of pH and Bepotastine Besilate Concentration on Light-Stability of Bepotastine Besilate Test Method The aqueous liquid preparations (Formulations 10-12) shown in the following [Table 3], which contained bepotastine besilate, were prepared according to conventional methods and processed in the same manner as in Experimental Example 1, and appearance of each formulated liquid preparation was observed. TABLE 3 Formulation 10 11 12 Bepotastine besilate 1.5 g 1.5 g 0.1 g sodium dihydrogen 0.1 g 0.1 g 0.1 g phosphate dihydrate sodium chloride 0.6 g 0.6 g 0.82 g benzalkonium 0.005 g 0.005 g 0.005 g chloride sodium hydroxide suitable suitable suitable amount amount amount total amount 100 mL 100 mL 100 mL pH 4.0 8.5 6.8 Test Results The appearance after light irradiation did not change from immediately after preparation and was pale yellow and clear for Formulation 10 (pH 4) and Formulation 11 (pH 8.5) comprising sodium chloride. In addition, the appearance did not change from immediately after preparation and was colorless and clear for Formulation 12 having a bepotastine besilate concentration of 0.1 w/v %. These results and the results of Formulation 7 (pH 6.8) in Experimental Example 2 indicate that addition of sodium chloride, which is a water-soluble metal chloride, improves light stability of bepotastine besilate at pH 4-8.5. In addition, they indicate that the light-stability of bepotastine besilate is improved in the concentration range of 0.1 w/v %-1.5 w/v %. EXPERIMENTAL EXAMPLE 4 Effect of Bepotastine Besilate Concentration and pH on Light-Stability of Bepotastine Besilate in Aqueous Preparation Comprising Glycerin Test Method The aqueous liquid preparations (Formulations 13-17) shown in the following [Table 4], which contained bepotastine besilate, were prepared according to conventional methods and processed in the same manner as in Experimental Example 1, and appearance of each formulated liquid preparation was observed. TABLE 4 Formulation 13 14 15 16 17 bepotastine 0.5 g 1.0 g 1.5 g 1.5 g 1.5 g besilate sodium 0.1 g 0.1 g 0.1 g 0.1 g 0.1 g dihydrogen phosphate dihydrate glycerin 2.2 g 2.0 g 1.7 g 1.7 g 1.7 g benzalkonium 0.005 g 0.005 g 0.005 g 0.005 g 0.005 g chloride sodium hydroxide suitable suitable suitable suitable suitable amount amount amount amount amount total amount 100 mL 100 mL 100 mL 100 mL 100 mL pH 6.8 6.8 4.0 6.8 8.5 Test Results The appearance after light irradiation was pale black green for Formulation 13 and black green for Formulation 14, and a precipitate was observed in both Formulations. The results indicate that addition of glycerin results in coloration of bepotastine besilate into black green even at a low concentration. Formulation 15 (pH 4) turned blue and a precipitate was observed. Formulation 16 (pH 6.8) turned black green and a precipitate was observed. Formulation 17 (pH 8.5) turned yellow brown but no precipitation was observed. The results indicate that bepotastine besilate is extremely unstable at a pH near neutral. The results also indicate that glycerin does not improve light-stability of bepotastine besilate in the range of pH 4-8.5. When 3.3 w/v % of glucose or mannitol was added instead of glycerin of Formulation 16, black green was developed and a precipitate was observed. These results indicate that a water-soluble metal chloride improves light-stability of bepotastine besilate, and isotonic agents such as glycerin, saccharides and the like do not improve light-stability of bepotastine besilate. EXAMPLE 1 Eye Drop bepotastine besilate 0.3 g Sodium dihydrogenphosphate dihydrate 0.1 g sodium chloride 0.79 g benzalkonium chloride 0.005 g sodium hydroxide suitable amount sterile purified water total amount 100 mL pH 6.8 Using the above-mentioned ingredients, an eye drop is prepared by a conventional method. EXAMPLE 2 Eye Drop bepotastine besilate 0.5 g Sodium dihydrogenphosphate dihydrate 0.1 g sodium chloride 0.76 g benzalkonium chloride 0.005 g sodium hydroxide suitable amount sterile purified water total amount 100 mL pH 6.8 Using the above-mentioned ingredients, an eye drop is prepared by a conventional method. EXAMPLE 3 Eye Drop bepotastine besilate 1.0 g Sodium dihydrogenphosphate dihydrate 0.1 g sodium chloride 0.68 g benzalkonium chloride 0.005 g sodium hydroxide suitable amount sterile purified water total amount 100 mL pH 6.8 Using the above-mentioned ingredients, an eye drop is prepared by a conventional method. EXAMPLE 4 Eye Drop bepotastine besilate 1.5 g Sodium acetate trihydrate 0.1 g sodium chloride 0.6 g benzalkonium chloride 0.005 g sodium hydroxide suitable amount sterile purified water total amount 100 mL pH 4.0 Using the above-mentioned ingredients, an eye drop is prepared by a conventional method. EXAMPLE 5 Eye Drop bepotastine besilate 1.5 g epsilon-aminocaproic acid 0.1 g sodium chloride 0.6 g benzalkonium chloride 0.005 g sodium hydroxide suitable amount sterile purified water total amount 100 mL pH 4.0 Using the above-mentioned ingredients, an eye drop is prepared by a conventional method. EXAMPLE 6 Eye Drop bepotastine besilate 1.5 g citric acid 0.1 g sodium chloride 0.6 g benzalkonium chloride 0.005 g sodium hydroxide suitable amount sterile purified water total amount 100 mL pH 6.8 Using the above-mentioned ingredients, an eye drop is prepared by a conventional method. EXAMPLE 7 Eye Drop bepotastine besilate 1.5 g taurine 0.1 g sodium chloride 0.6 g benzalkonium chloride 0.005 g sodium hydroxide suitable amount sterile purified water total amount 100 mL pH 8.5 Using the above-mentioned ingredients, an eye drop is prepared by a conventional method. EXAMPLE 8 Eye Drop bepotastine besilate 1.5 g sodium dihydrogenphosphate dihydrate 0.1 g sodium chloride 0.6 g methyl parahydroxybenzoate 0.026 g propyl parahydroxybenzoate 0.014 g sodium hydroxide suitable amount sterile purified water total amount 100 mL pH 6.8 Using the above-mentioned ingredients, an eye drop is prepared by a conventional method. EXAMPLE 9 Eye Drop bepotastine besilate 1.5 g sodium dihydrogenphosphate dihydrate 0.1 g sodium chloride 0.6 g potassium sorbate 0.27 g sodium hydroxide suitable amount sterile purified water total amount 100 mL pH 6.8 Using the above-mentioned ingredients, an eye drop is prepared by a conventional method. EXAMPLE 10 Eye Drop bepotastine besilate 1.5 g sodium dihydrogenphosphate dihydrate 0.1 g sodium chloride 0.6 g chlorhexidine gluconate 0.005 g sodium hydroxide suitable amount sterile purified water total amount 100 mL pH 6.8 Using the above-mentioned ingredients, an eye drop is prepared by a conventional method. EXAMPLE 11 Eye Drop bepotastine besilate 1.5 g sodium dihydrogenphosphate dihydrate 0.1 g sodium chloride 0.6 g benzalkonium chloride 0.005 g sodium hydroxide suitable amount sterile purified water total amount 100 mL pH 6.8 Using the above-mentioned ingredients, an eye drop is prepared by a conventional method. EXAMPLE 12 Nasal Drop bepotastine besilate 1.0 g sodium dihydrogenphosphate dihydrate 0.1 g sodium chloride 0.68 g benzalkonium chloride 0.005 g sodium hydroxide suitable amount sterile purified water total amount 100 mL pH 6.8 Using the above-mentioned ingredients, a nasal drop is prepared by a conventional method. INDUSTRIAL APPLICABILITY In the present invention, the light-stability of (+)-(S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid or a pharmacologically acceptable acid addition salt thereof, particularly bepotastine besilate, which is monobenzenesulfonate, can be improved by adding a water-soluble metal chloride to an aqueous liquid preparation comprising (+)-(S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid or a pharmacologically acceptable acid addition salt thereof, and a stable aqueous liquid preparation can be produced. Since an aqueous liquid preparation stable to light can be obtained by the light-stabilizing method of the present invention, the aqueous liquid preparation of the present invention is advantageously used for the treatment of allergic conjunctivitis, spring catarrh, pollinosis, allergic rhinitis and the like. While some of the embodiments of this invention have been described in detail in the foregoing, it will be possible for those of ordinary skill in the art to variously modify and change the embodiments specifically shown herein, within the scope not substantially deviating from the novel teaching and benefit of the invention. Accordingly, this invention encompasses all such modifications and changes within the spirit and scope of the invention as defined by the following claims. This application is based on a patent application No. 223804/2002 filed in Japan, the contents of which are hereby incorporated by reference.

<SOH> BACKGROUND ART <EOH>(+)-(S)-4-[4-[(4-Chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid and a pharmacologically acceptable acid addition salt thereof have an antihistaminic action and an antiallergic action. They are also characterized in that secondary effects such as stimulation or suppression of the central nerve often seen in the case of conventional antihistaminic agents can be minimized, and can be used as effective pharmaceutical agents for the treatment of human and animals (JP-B-5-33953, JP-A-2000-198784). Particularly, a tablet comprising (+)-(S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid monobenzenesulfonate (general name: bepotastine besilate) has been already marketed as a therapeutic agent for allergic rhinitis and itching associated with hives and dermatoses. On the other hand, (+)-(S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid and a pharmacologically acceptable acid addition salt thereof are unstable to light in an aqueous solution, and colored or precipitated with the lapse of time, which has made the use thereof as an aqueous liquid preparation difficult. In the case of an aqueous liquid preparation such as an eye drop and a nasal drop, a method comprising blocking light by preserving in a light-shielding container and the like can be used, but complete light-shielding is practically difficult. Thus, stabilization of an aqueous liquid preparation itself as a preparation is desirable. As a method of light-stabilizing an eye drop, a U.S. Pat. No. 2,929,274 discloses a method comprising adding boric acid and/or borax and glycerin, but according to this method, stabilization of (+)-(S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid and a pharmacologically acceptable acid addition salt thereof to light was not observed. As a general stabilization method, a method comprising placing in the coexistence of an antioxidant such as BHT etc., and the like are known (JP-A-7-304670).

20040630

20140722

20050519

74700.0

FRAZIER, BARBARA S

AQUEOUS LIQUID PREPARATIONS AND LIGHT-STABILIZED AQUEOUS LIQUID PREPARATIONS

UNDISCOUNTED

ACCEPTED

ACCEPTED

Device for controlling the opening and closing of a trunk hood

A device designed to control opening and closing of a trunk hood comprises a jack whereof the cylinder is pivotably linked to the vehicle body and the free end of the piston rod sliding in the cylinder is linked to the hood in articulation. The device further has a control member arranged between the hood and the free end of the piston rod and designed to detect a force in the direction closing the hood and to control actuation of the jack in the direction for closing the hood.

1-7. (canceled) 8. A device for controlling the opening and closing of a trunk hood comprising a jack having a cylinder linked to vehicle bodywork in a manner free to pivot, and a rod sliding in the cylinder and linked to the hood in an articulated manner at a free end, a control member placed between the hood and the free end of the rod, for detecting a force in a hood closing direction and controlling activation of the jack in the hood closing direction. 9. The device according to claim 8, wherein the control member is linked to the free end of the rod deformably in translation substantially along a longitudinal direction of the rod between a remote position and a close position, and to the hood, said control member being free to pivot about a pivot pin. 10. The device according to claim 9, wherein the control member comprises a sliding element that slides with respect to the free end of the rod between a retracted position in which the hood is in a close position with respect to the free end, and an extended position in which the hood is in a remote position from the free end. 11. The device according to claim 10, further comprising an element for continuously applying a force on the hood pulling it towards said remote position, so as to substantially compensate for the weight of the hood. 12. The device according to claim 11, wherein the element is a compression element placed between a sliding element and the rod. 13. The device according to claim 10, further comprising a contact switch for detecting a close position of the hood and controlling activation of the jack in the closing direction of the hood. 14. The device according to claim 13, wherein the sliding element comprises a pin for activating the contact switch when the sliding element is in a retracted position.

BACKGROUND OF THE INVENTION This invention relates to a device for controlling the opening and closing of a motor vehicle trunk hood, particularly a luggage compartment. A device is known for controlling the opening and closing of a trunk hood of the type comprising a jack for which the cylinder is linked to the vehicle bodywork in a manner free to pivot, and in which the rod sliding in the cylinder is linked to the hood in an articulated manner at its free end. One disadvantage of a device suitable for controlling automatic closing of a hood is that a person who wants to quickly put down luggage or pick it up in the trunk can get trapped. The same is true if a person accidentally puts his hands in the immediate vicinity of the trunk. Another disadvantage of such a device for controlling the automatic closing of a hood is that a piece of luggage badly positioned in the trunk can hinder closing of the hood and either damage the device or damage the luggage. Some users need to be reassured that automatic closing of the hood will not cause any deterioration to the closing device or to badly positioned luggage, even if the hood is equipped with a device for preventing the closing movement from continuing if luggage hinders closing of the hood. SUMMARY OF THE INVENTION The purpose of the invention is a device for controlling the opening and closing of a hood in a safe manner, so that the user has the impression of closing the hood manually, even though closing is done automatically. According to the invention, the device of the type mentioned above comprises a control member placed between the hood and the free end of the rod, for detecting a force in the hood closing direction and controlling activation of the jack in the hood closing direction. Thus, a user who wants to close the hood on the trunk applies a force to the trunk in the closing direction. The control member detects this force and in response to this detection, orders activation of the jack in the hood closing direction. In this way, the user directly controls closing of the hood, accompanying the closing movement generated by the jack, and he has the impression of closing the hood himself. Other special features of this invention will become clear from the following description. BRIEF DESCRIPTION OF THE DRAWINGS In the appended drawings, given as non-limitative examples: FIG. 1 shows a diagrammatic sectional view of a device according to one embodiment of this invention, and FIG. 2 shows an enlargement of region II illustrated in FIG. 1 representing an embodiment of a control member for the device in FIG. 1. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT(S) A hood 1 is linked in an articulated manner about a rotation hinge pin 2 to a motor vehicle bodywork shown diagrammatically at 3 between an open position shown in FIG. 1 and a closed position. The vehicle includes a device 4 for controlling opening and closing of the hood 1 and that includes a jack 5. The jack 5 is a double acting jack of an arbitrary known type. As is known and illustrated in FIG. 1, the jack 5 comprises a cylinder 6 that is linked to the bodywork 3 in a manner free to pivot, about a pivot pin 7, and a rod 8 that is installed free to slide in the cylinder 6 and that is linked at its free end 9 to the hood 1 in an articulated manner about a second pivot pin 10. According to this invention, the device 4 for controlling the opening and closing of the hood 1 comprises a control member 11. As illustrated in FIG. 2, the control member 11 is placed between the hood 1 and the free end 9 of the rod 8. The member 11 is capable of detecting a force 12 applied on the hood 1 in the closing direction of the hood 1 and controlling activation of the jack 5 in the hood 1 closing direction. In the example illustrated in FIG. 2, the control member 11 is linked firstly to the free end 9 of the rod 8 deformably in translation (represented by double arrow 13) substantially along the longitudinal direction of the rod 8 between a remote position and a close position, and secondly to the hood 1 free to pivot about the second pivot pin 10. The control member 11 includes an element 14 for continuously applying a force on the hood 1 pulling it towards its remote position from the free end 9 of the rod 8, so as to substantially compensate the weight of the hood 1. Consequently, the only means of making the hood 1 move into a close position is to apply a force 12 onto the hood 1. The control member 11 also comprises a contact switch 15 for detecting a close position of the hood 1 and controlling activation of the jack 5 in the closing direction of the hood 1. The control member 11 comprises a sliding element 16 that slides with respect to the rod 8 of the jack 5. More precisely, the sliding element 16 slides in a chamber 17 made at the free end 9 of the rod 8 between a retracted position in the rod 8, shown in FIG. 2, in which the hood 1 is in a close position to the free end 9, and an extended position in which the hood 1 is in its remote position from the free end 9. In the example illustrated in FIG. 2, the elastic element 14 is a compression spring 14 placed in a housing 22 and continuously applying a force to the sliding element 16 in its deployed position outside the chamber 17. The housing 22 is separated from the chamber 17 by a partition 23 through which the sliding element 16 passes and with which the spring 14 comes into contact through one of its ends (the other end being in contact with the sliding element 16). The sliding element 16 comprises a pin 18 for activating the contact switch 15 when the sliding element 16 is in a retracted position, so as to activate the contact switch 15. The contact switch 15 comprises a straight edge 19 sliding in a housing 20 that is fixed to the free end 9 of the rod 8. The contact switch 15 is electrically linked by a cable 21 to actuation means of the jack 5 in the closing direction of the hood 1, these actuation means of the mechanism being any known type of means, for example a hydraulic control unit. If the user wants to close the hood 1, he applies a force 12 onto the hood in the closing direction that moves against the force applied by the spring 14. The hood 1 reaches a position close to the free end 9 of the rod 8, and at the same time the sliding element 16 reaches a retracted position in which the pin 18 causes sliding of the straight edge 19. After the contact switch 15 is actuated, the movement of the jack 5 in the closing direction of the hood 1 is generated. Every time that the user stops applying the force 12 in the closing direction of the hood 1, the spring 14 directs the sliding element 16 into its extended position, which deactivates the contact switch 15 and stops the closing movement of the jack 5. Every new force 12 reactivates the contact switch 15 and recloses the hood 1. Thus, the result is a device for assisted closing of the luggage compartment hood 1. Obviously, this invention is not limited to the embodiment that has just been described, and many changes and modifications could be made to it without going outside the framework of the invention. For example, the control member 11 could be linked firstly to the hood 1 free to move in translation between a remote position and a close position, and secondly to the free end 9 of the rod 8 in an articulated manner about the second hinge pin 10. Any control member 11 placed between the hood 1 and the free end 9 of the rod 8 for detecting a force 12 applied to the hood 1 in the hood closing direction and controlling activation of the jack 5 in the closing direction of the hood 1 would be suitable for carrying out this invention, and for example it could be composed of a piezo-electric element or a hydraulic element or an electromagnetic element.

<SOH> BACKGROUND OF THE INVENTION <EOH>This invention relates to a device for controlling the opening and closing of a motor vehicle trunk hood, particularly a luggage compartment. A device is known for controlling the opening and closing of a trunk hood of the type comprising a jack for which the cylinder is linked to the vehicle bodywork in a manner free to pivot, and in which the rod sliding in the cylinder is linked to the hood in an articulated manner at its free end. One disadvantage of a device suitable for controlling automatic closing of a hood is that a person who wants to quickly put down luggage or pick it up in the trunk can get trapped. The same is true if a person accidentally puts his hands in the immediate vicinity of the trunk. Another disadvantage of such a device for controlling the automatic closing of a hood is that a piece of luggage badly positioned in the trunk can hinder closing of the hood and either damage the device or damage the luggage. Some users need to be reassured that automatic closing of the hood will not cause any deterioration to the closing device or to badly positioned luggage, even if the hood is equipped with a device for preventing the closing movement from continuing if luggage hinders closing of the hood.

<SOH> SUMMARY OF THE INVENTION <EOH>The purpose of the invention is a device for controlling the opening and closing of a hood in a safe manner, so that the user has the impression of closing the hood manually, even though closing is done automatically. According to the invention, the device of the type mentioned above comprises a control member placed between the hood and the free end of the rod, for detecting a force in the hood closing direction and controlling activation of the jack in the hood closing direction. Thus, a user who wants to close the hood on the trunk applies a force to the trunk in the closing direction. The control member detects this force and in response to this detection, orders activation of the jack in the hood closing direction. In this way, the user directly controls closing of the hood, accompanying the closing movement generated by the jack, and he has the impression of closing the hood himself. Other special features of this invention will become clear from the following description.

20050318

20080701

20050721

70588.0

PEDDER, DENNIS H

DEVICE FOR CONTROLLING THE OPENING AND CLOSING OF A TRUNK HOOD

UNDISCOUNTED

ACCEPTED

ACCEPTED

Apparatus and method for flexible data rate matching

This invention relates to a flexible rate matching method, comprising the steps of: a) receiving a continuous stream of data items at a prespecified rate of a clock signal in a configurable data shift register; b) storing, for each data item stored in the data shirt register, an associated indication of validity in a configurable validity shift register and shifting the indications of validity at said prespecified rate; c) modifying the contents of the data shift register and the validity shift register through puncture/repetition operations so as to achieve a rate matching, and d) outputting valid data items at said prespecified rate using said indications of validity stored in the validity shift register. The invention also relates to a corresponding flexible rate matching apparatus as well as to a computer program product and a processor program product.

1. A flexible rate matching apparatus, comprising: a dual shift register having a configurable data shift register adapted to receive a continuous stream of data items at a prespecified rate of a clock signal; and a configurable validity shift register adapted to store, for each data item stored in the data shift register, an associated indication of validity, and adapted to shift the indications of validity at said prespecified rate; a control unit adapted to modify the contents of the data shift register and the validity shift register through puncturing/repetition operations so as to achieve a rate matching; and an output handler adapted to output valid data items at said prespecified rate using the indications of validity stored in the validity shift register. 2. The flexible rate matching apparatus according to claim 1, wherein said data shift register is adapted to receive a plurality of data items in each cycle of said clock signal. 3. The flexible rate matching apparatus according to claim 1, wherein the control unit comprises: an input and rate matching (RM) control unit adapted to control said dual shift register; an output control unit adapted to control said output handler; and a flexible RM control unit adapted to coordinate and synchronize the operations of said input and RM control unit and said output control unit. 4. The flexible rate matching apparatus according to claim 3, wherein the control unit further comprises a computation unit adapted to determine positions where data items have to be rate-matched according to a rate matching scheme. 5. The flexible rate matching apparatus according to claim 1, wherein said puncturing operations include assigning a value indicating non-validity to those indications of validity associated with data items to be punctured. 6. The flexible rate matching apparatus according to claim 1, wherein said repetition operations include shifting the data items to be repeated as well as their associated indications of validity to at least two memory locations of the data shift register and the validity shift register, respectively. 7. The flexible rate matching apparatus according to claim 1, wherein the output handler is adapted to output data items, where the associated indications of validity stored in the validity shift register have a value indicating validity. 8. The flexible rate matching apparatus according to claim 1, characterized in that the apparatus has a cascade structure. 9. A flexible rate matching method, comprising the steps of: a) receiving a continuous stream of data items at a prespecified rate of a clock signal in a configurable data shift register; b) storing, for each data item stored in the data shift register, an associated indication of validity in a configurable validity shift register and shifting the indications of validity at said prespecified rate; c) modifying the contents of the data shift register and the validity shift register through puncture/repetition operations so as to achieve a rate matching; and d) outputting valid data items at said prespecified rate using said indications of validity stored in the validity shift register. 10. The flexible rate matching method according to claim 9, wherein the step of receiving the continuous stream of data items includes receiving a plurality of data items in the data shift register in each cycle of said clock signal. 11. The flexible rate matching method according to claim 9, further comprising determining positions where data items have to be rate-matched according to a rate matching scheme. 12. The flexible rate matching method according to claim 9, wherein said puncturing operations include assigning a value indicating non-validity to those indications of validity associated with data items to be punctured. 13. The flexible rate matching method according to claim 9, wherein said repetition operations include shifting the data items to be repeated as well as their associated indications of validity to at least two memory locations of the data shift register and the validity shift register, respectively. 14. The flexible rate matching method according to claim 9, wherein said step of outputting valid data items comprises continuously outputting data items where the associated indications of validity stored in the validity shift register have a value indicating validity. 15. A computer program product directly loadable into the internal memory of a mobile communication unit, said computer program product comprising software code portions that run on a processor of the mobile communication unit and perform the steps of: receiving a continuous stream of data items at a prespecified rate of a clock signal in a configurable data shift register; storing, for each data item stored in the data shift register, an associated indication of validity in a configurable validity shift register and shifting the indications of validity at said prespecified rate; modifying the contents of the data shift register and the validity shift register through puncture/repetition operations so as to achieve a rate matching; and outputting valid data items at said prespecified rate using said indications of validity stored in the validity shift register. 16. A processor program product stored on a processor usable medium and provided for flexible rate matching, comprising: a processor readable program means for causing a processor to control reception of a continuous stream of data items at a prespecified rate by a configurable data shift register; a processor readable program means for causing the processor to store, for each data item stored in the data shift register, an associated indication of validity in a configurable validity shift register; a processor readable program means for causing a processor to modify the contents of the data shift register and the validity shift register through puncture/repetition operations so as to achieve a rate matching; and a processor readable program means for causing a processor to output valid data items at the prespecified clock rate using the indications of validity stored in the validity shift register. 17. The flexible rate matching apparatus according to claim 1, wherein said puncturing operations include shifting the data items to be punctured as well as their associated indications of validity to no memory location of the data shift register and the validity shift register, respectively. 18-19. (canceled) 20. The flexible rate matching apparatus according to claim 1, wherein said dual shift register includes at least two pipeline stages, each having a different number of memory locations. 21. (canceled) 22. The flexible rate matching method according to claim 9, wherein said puncturing operations include shifting the data items to be punctured as well as their associated indications of validity to no memory location of the data shift register and the validity shift register, respectively. 23-26. (canceled)

FIELD OF THE INVENTION The present invention relates to rate matching in the baseband part of a transmitter or a transceiver of a telecommunication system, and in particular to a flexible rate matching implementation. DESCRIPTION OF THE PRIOR ART A transmitter for use in a digital telecommunication system is known, for instance, from 3GPP TS 25.212 V3.4.0 (2000-09) “3rd Generation Partnership Project; Technical Specification Group Radio Access Network; Multiplexing and channel coding (FDD) (Release 1999)”, section 4.2. In FIG. 1a of the present application, a block diagramme of parts of such a transmitter is given. As shown, the transmitter includes a channel encoder, a rate matcher, an interleaver, and a modulator. Further components (for frequency up-conversion, amplification etc.) are omitted for reasons of conciseness. Channel Encoder: The channel encoder (also referred to as forward error control encoder) adds redundant information to each incoming data block. Thereby, the size (length) of the data block increases from K “uncoded” bits, at the encoder input, to C>K “coded” bits at its output. Herein, the size C of the coded data block depends on, at least, the number K of uncoded bits (in the uncoded data block) and a parameter r commonly referred to as the coding rate. With values in the range of 0<r<1, the coding rate r provides an indication of the degree (extent, scope) of redundancy introduced by the channel encoder: the smaller the value of r, the more redundant information is added. The way, in which redundant information is generated, depends on the channel coding scheme employed and, more particularly, on functions such as generator polynomials (with parameters such as constraint lengths, e.g.). Typical examples for channel coding schemes are convolutional coding, concatenated convolutional coding such as “turbo” coding, and block coding. The skilled person will readily appreciate that according to some channel coding schemes such as turbo coding, the coded data block may also include a number of so-called “systematic bits”, i.e. bits which are identical to the uncoded bits and therefore do not carry any redundant information. In this case, the other bits of the coded data block, i.e. those actually carrying redundant information, are referred to as “parity bits”. The coded data block output by the channel encoder may (or may not) include a certain number of (coded) “tail bits” also referred to as terminating bits. Tail bits are widely used in order to ensure that the encoding process terminates in a pre-defined state, e.g. in the zero state, thus providing the same degree of protection for the last uncoded bits in the incoming data block (compared with other uncoded bits). Similarly, tail bits ensure that the decoder in the receiver reaches a predetermined final state. In other words, tail bits ensure a proper termination of the decoder trellis. The size C of the coded data block-generated by the channel encoder of FIG. 1a can be described for instance by the equation C=K/r+TC=(K+TU)/r with TU≧0, TC≧0, (1) wherein K and r denote the number of uncoded bits (i.e. the size of the incoming data block) and the coding rate, respectively. In equation (1), TC denotes the number of coded tail bits while TU refers to the number of uncoded tail bits. Equation (1) states that, out of the C bits contained in the coded data block, K/r bits result from the encoding of the incoming data block (consisting of K uncoded bits and not including tail bits) while a total of TC output bits was derived from a given number of tail bits introduced inside the channel encoder of FIG. 1a. In case of convolutional coding, a number TU of uncoded tail bits is typically encoded into a total of TC=TU/r coded tail bits so that the first and second parts of equation (1) apply to this case. With turbo coding, e.g., an internal feedback of the last encoder state ensures that the encoding process terminates in the pre-defined state. In the coded data block output by the turbo encoder, this results in a number TC of coded tail bits so that the first part of equation (1) applies. In most applications, the coding rates can be described by expressions of the form r=1/x, wherein x can assume integer values greater than or equal to two. In these cases, eq. (1) always delivers integer output values for C, as one would expect for a number of bits in a block. For coding rates of the general form r=y/z with positive integer parameters y and z, however, eq. (1) could in principal deliver non-integer output values. However, this is a rather theoretical case, because the skilled person in the field of channel coding is aware of this problem as well as of solutions to it, such as choosing the number of bits input into the channel encoder and/or the number of (uncoded/coded) tail bits appropriately. For example, in case of a convolutional channel encoder with a coding rate of r=4/9, the skilled person would select the number K of uncoded bits and the number TU of uncoded tail bits so that their total number is an integer multiple of 4. This exemplary measure would ensure that C assumes a value equal to an integer multiple of 9. In the sequel, references to the size C of the coded data block (and in particular to eq. (1)) assume such obvious measures for obtaining an integer number of coded output bits to have been taken. In applications where for the same channel coding scheme several coding modes with different coding rates r have to be supported (such as r=1/2 and r=1/3, e.g.), it is rather common, in order to decrease implementational complexity and thus cost of the transmitter, to only implement a single channel encoder hardware capable of encoding at the smallest coding rate (r=1/3 in the above example). This ensures that enough redundant information is generated in a first step, no matter what coding mode actually has to be used. If (and whenever) a coding mode with a higher coding rate (r=1/2, e.g.) is to be performed, the excessive part of the redundant information is simply removed (“punctured”) from the output of the channel encoder hardware, in a subsequent step. In the sequel, such puncturing, i.e. puncturing performed (a) after channel coding as such, i.e. after redundant information has been generated, and (b) for the purpose of achieving a desired (higher) coding rate, is considered part of the rate matcher (as described below) rather than part of the channel encoder, because a coded data block (coded at a coding rate of r=1/3 in the above example) is adjusted in size. Interleaver, Modulator etc.: The purpose of the interleaver is to change the order of data bits inside each coded data block in order to ensure that a temporary disturbance during transmission of the data block (over the physical channel) does not lead to a loss of many adjacent coded data bits, since such a loss in many cases would be unrecoverable at the receiver side. Then, the modulator converts the interleaved data bits into symbols which, in general, are complex-valued. Further components, such as digital-to-analog conversion, frequency up-conversion and amplification are not shown in FIG. 1a for conciseness reasons. Finally, a signal is transmitted over the physical channel (the air interface, a wireline etc.). The channel encoding scheme, the interleaving scheme, and the modulation scheme are specified in detail by the communication standard according to which the telecommunication system is to be operated. For example, in third generation (3G) mobile communication standards such as WCDMA (wideband code division multiple access), two channel coding schemes are specified apart from the “no coding” case: convolutional coding and turbo coding. With these coding schemes, several coding rates are to be used (r=1/2, r=1/3, and others). Also, the uncoded data blocks supplied to the channel encoder may have different sizes K. For these reasons, 3G systems will have to support many different coded data block sizes C_i, i=1,2, . . . also referred to as different “transport channel types”, wherein the block sizes may vary over a wide range (from a few bits to more than 10000 bits, e.g.). On the other hand, due to different physical channel sizes, several interleaving schemes with different interleaver sizes M_j, j=1,2, . . . may have to be supported. For example, the WCDMA standard specifies seven different interleaver sizes in the uplink and 17 in the downlink. In order to match the channel encoder output to a given time slot and/or frame structure, several transport channel types with different (but maybe similar) coded data block sizes C_i should use the same physical channel type (having a given size referred to as target block size in the following). Rate Matcher: For this to become possible, a rate matcher is typically introduced between the channel encoder and the interleaver, as shown in FIG. 1a. Although it is clear from the above, that a single communication system may have to support several or even many combinations of coded block-sizes C_i and target block sizes M_j, the following generic description is based, for simplicity and clarity reasons, on a single combination of a coded data block size C and a target block size M. The rate matcher shown in FIG. 1a either adds (inserts) to each coded data block or deletes (removes, “punctures”) from each coded data block a certain number of bits in order to obtain a rate-matched data block having a given target block size of M bits (which is, e.g., the size of an interleaver or a particular block length required for transmission). For this purpose, the rate matcher has to add M−C bits to the coded data block, if C is inferior to M, or to remove (puncture) C−M bits therefrom, if C is superior to M, so as to adapt the block size C to said target block size M. In cases where M is equal to C, no adjustment in size is necessary, of course. With the definition A=M−C (2) the functionality of the rate matcher can be described as adjusting the size of the coded data block by a number |A| of bits with |A| denoting the magnitude of A, wherein for A>0 (i.e. C<M) the rate matcher adds A bits to the coded data block, while for A<0 (i.e. C>M), it removes |A|=−A=C−M bits therefrom. In case of A=0 (i.e. M=C), obviously, no adjustment in size is required. Although in principle, the bits to be added (inserted) in case of A>0 could have any value, the receiver performance can be improved if bits of the coded data block are repeated instead of, e.g., adding bits with fixed values. For this reason, typically, the expression “adding A bits” is equivalent in meaning to “repeating” said number of bits so that in the rate-matched data block, A bits represent copies of A “original” bits contained in the coded data block. As long as not all C bits of the coded data block are repeated, these repetition schemes are referred to as “unequal repetition” schemes. The positions inside each coded data block (together with the number of repetitions, if applicable), where bits are to be repeated or deleted, are also specified in detail by the communication standard according to which the telecommunication system is operated. Herein, the positions can either be specified directly (by listing bit indices, e.g.) or by an algorithm to be executed in order to determine said bit indices, as will be explained below in more detail. It should be noted that, depending on the application under consideration, the parameter |A| can assume rather high values (in the hundreds or even thousands of bits). This can lead to a considerable implementational complexity, because for each bit to be repeated or deleted, its position inside the coded data block, along with the number of repetitions (if applicable), has to be determined or stored both in the transmitter and in the receiver, as will be seen below. With the knowledge of the positions inside each coded (or rate-matched) data block, where bits were repeated or deleted by the rate matcher in the transmitter, the receiver is able to reconstruct a decoded data block (corresponding to the uncoded data block) comprising K bits from the received data block. GSM Example for a Rate Matcher: As an example for a rate matcher according to the prior art, FIG. 1b shows a block diagramme of a puncturing unit 100 adapted to the GSM standard. In case of the GSM traffic channel “F96”, the coded data blocks supplied to the puncturing unit comprise C=488 bits, while the rate-matched data blocks to be output by the puncturing unit must have a target block size of M=456 bits, so that |A|=|M−C|=|456−488|=32 bits must be punctured according to equation (2). For this purpose, the puncturing unit 100 shown in FIG. 1b comprises a shift enable unit 101 having a counter 102, a comparison unit 103, and a position memory 104. Further, the puncturing unit 100 comprises a shift register 105 and a memory 106. Operatively, the coded data block (input data block) comprising C coded bits (input bits) is shifted into the shift register 105 in a bit-serial manner at the respective input bit rate. In this example, the shift register 105 has a width of 8 bits. When the shift register is filled up, its contents (i.e. 8 input bits) will be stored, in a single step (i.e. parallely), in the memory 106 having a width of 8 bits. Thereafter, the serial supply of input bits to the shift register 105 is resumed (continued). Further, the counter 102 in the shift enable unit 101 counts the input bits in each input data block. The comparison unit 103 of the shift enable unit 101 compares the counter value with the (in this example: 32) puncturing positions stored in the position memory 104 of the shift enable unit 101. In case the comparison unit 103 determines a coincidence of the counter value and one of the puncturing positions, the respective shift operation in the shift register 105 is suppressed (not enabled) thus achieving the puncturing. In other words, an input bit to be punctured will not be shifted into the shift register 105 (or alternatively: will be overwritten in the shift register by the subsequent input bit), and therefore will not be written into the memory 106 at a later stage. A rate matcher according to FIG. 1b may only be used for a single puncturing scheme according to, e.g., the GSM standard. However, in view of 3G mobile communication standards such as WCDMA, several problems arise. Rate Matching Requirements: In existing implementations according to, e.g., the GSM standard, the input data blocks (coded data blocks, e.g.) are input bit-serially, at the respective input bit rate, to the rate matcher. In view of the high input bit rates specified by 3G standards such as WCDMA, it is not possible to serially process the input bits at these high input bit rates. In other words, existing rate matching implementations do not support a parallel input and processing of input bits (coded bits, e.g.) which is a prerequisite to meeting future throughput and delay requirements, as the following example will show. Consider, e.g., the rate matching of 1024 channels, each being a voice channel with 320 coded bits supplied serially within a time period of 2.5 ms so that the associated input bit rate (clock rate) equals to 131 MHz. At this clock rate, it would be very difficult to implement the rate matcher according to FIG. 1b in FPGA (field programmable gate array) or ASIC (application specific integrated circuit) technology. If, however, a 4 bit parallel processing was possible, the clock rate could be reduced to 32 MHz. The skilled person will readily appreciate that, at this clock rate, the rate matcher could very well be implemented in FPGA or ASIC technology. As already outlined above, according to 3G mobile communication standards such as WCDMA, rate matchers will have to be implemented for many different transport channel types and data rates. A straightforward solution to this problem would consist in implementing several rate matchers according to the prior art and operate them in a parallel manner (different rate matchers for different transport channel types and/or data rates). However, such an implementation would lead to a large and complex control logic (using a plurality of counters, memories, etc.) for controlling which data block has to be input into which rate matcher and for assembling the outputs of the rate matchers into a single stream of data. In other words, the implementational effort in terms of the required hardware would exceed typical limitations given for FPGA/ASIC circuits or defined printed circuit board sizes for 3G transmitters. As stated above, the positions inside each input data block, where bits are to be rate-matched (repeated or deleted), are specified in detail by the communication standard according to which the telecommunication system is operated. Herein, the positions can be specified in a variety of different ways, referred to as “rate matching schemes” in the following. For small values of |A|, the positions can simply be identified by explicitly listing the indices of the bits to be rate-matched, as described above with respect to the GSM rate matcher. This will be referred to as rate matching scheme RMS1. To achieve a reduction of at least the required memory hardware in cases where |A| assumes higher values, it has been proposed to not explicitly store all positions of bits to be rate-matched. For example, a 3G standard proposal by the Japanese standardization body ARIB, referred to as rate matching scheme RMS2 herein, does not explicitly list the positions of all bits to be rate-matched but rather defines the distance therebetween, e.g., the information that each 15th bit has to be rate-matched. As this distance is always the same within one input data block only one parameter must be stored (assuming that the position of the first bit to be rate-matched is known). Nevertheless, in order to achieve any desired value for the target block size M, it may become necessary to further modify the result after the first pass of puncturing/repetition of bits in the initially supplied input data block, i.e. it may be necessary to apply puncturing or repetition recursively. One such example would be the processing of an input data block where, in a first pass, each 16th input bit is punctured, then, in a second pass, each 26th bit, then, in a third pass, each 98th bit, and finally, in a fourth pass, each 156th bit, in order to obtain the desired value for the target block size M. In order to avoid such recursive rate matching schemes, another 3G standard proposal presented by the European standardization body ETSI, referred to as scheme RMS3 herein, defines two different distances between bits to be rate-matched in a non-recursive manner. According to this proposal, there could be a distance of, e.g., 8 bits between the first two bits to be rate-matched and then there could be a distance of, e.g., 9 bits between the 2nd and 3rd bits to be rate-matched, and then, for instance, again a distance of 8 bits between the 3rd and 4th bits to be rate-matched etc. Of course, more than two different distances could be specified as well. The positions where bits are to be rate-matched can also be specified by more complex algorithms which require more or less complex calculations to be executed in order to determine said positions. Examples for such rate matching schemes, referred to as RMS4 herein, can be found in the WCDMA standard (UMTS). In view of the above, a rate matching implementation should meet the following requirements: a) it must be capable of coping with high input bit rates; for example, 3G standard proposals (ARIB, ETSI) specify a maximum input bit rate of 1024000 bits/s; b) it must be capable of coping with a large variety of transport channel types, or equivalently, sizes C of input data blocks, e.g., for ARIB and ETSI: C=160 . . . 10240 bits; c) it must be capable of coping with a large variety of numbers |A| of bits to be rate-matched; for example, |A| may range from 0 to 1000 bits to be rate-matched in a single input data block; d) it must be capable of supporting many different rate matching schemes (such as the schemes RMS1, RMS2, . . . described above); e) it should minimize the delay as measured for instance in terms of the time difference between “first input bit in” and “first output bit out” or “last output bit out”, respectively; f) it should minimize hardware complexity; e) ideally, a single hardware structure should be able to meet the above requirements (e.g. to implement rate matching no matter how the positions of the bits to be repeated or punctured are specified). SUMMARY OF THE INVENTION In view of the above, the object of the invention is to develop a flexible rate matching implementation at minimal costs (low complexity). According to the present invention, this object is achieved through a flexible rate matching apparatus having the features of claim 1 and also through a flexible rate matching method having the features of claim 9. Therefore, the flexible rate matching apparatus and method according to the present invention rely on the provision of a dual shift register comprising a configurable data shift register (DSR) and a configurable validity shift register (VSR). In particular, the VSR enables to use validity information (VI), also referred to as indications of validity, as masking information, wherein bits (or data items comprising one or several bits) to be punctured are invalidated without further modification of the contents of the DSR. In case of repetition, the necessary memory space in the DSR may easily be provided through appropriate shifting of subsequent data items in the DSR and appropriate setting of the indications of validity (validity bits) in the VSR. This enables the output of valid data items using the validity information stored in the VSR. Therefore, the proposed flexible rate matching implementation is highly flexible in the way that a multitude of transport channel types, i.e. sizes C of input data blocks (coded data blocks), may be supported according to, e.g., 3G requirements. Further, the provision of the VSR allows to support, for each input data block, various kinds of rate matching schemes (RMS1, RMS2, etc.) as described above with respect to the prior art. Further, the proposed solution supports repetition and puncturing in one functional block which minimizes hardware complexity while ensuring the above-mentioned capabilities and flexibility. A further benefit of the proposed solution is that a flexible rate matching can be achieved on a continuous stream of data items (and also resulting in a continuous output data stream) without temporarily storing a complete input data block so that only a small memory is necessary and the overall delay is minimized. According to a preferred embodiment of the present invention it is proposed that a plurality of data items are handled as subblocks during each cycle of the (common) clock signal. In other words, the inventive flexible rate matching approach allows to process a plurality of data items in parallel (i.e. concurrently, simultaneously) during each cycle of the (common) clock signal. Therefore, the inventive flexible rate matching can cope with extremely high data rates required for, e.g. 3G standards. Therefore, these standards may be supported by still using fast turnaround and easily available FPGA and ASIC technologies. Also with this processing of data items it is possible to work on a continuous data stream without storage of a complete input data block. Again, only a small dual shift register for buffering some of the data items is sufficient, the length of the dual shift register being related to the total number |A| of data items to be rate-matched in an input data block. According to a further preferred embodiment, the dual shift register and the output handler are controlled by an input and RM (rate matching) control unit and an output control unit, respectively. These control (sub) units are controlled by a flexible RM control unit which coordinates and synchronizes the operations of said two (sub)units. Preferably, the positions of data items which need to be rate-matched (puntured or repeated) according to the rate matching scheme to be employed, can be determined (calculated) in a separate computation unit/step. This allows to achieve flexible rate matching in a fully programmable way so that changes in a standard can be incorporated with extremely low efforts. According to another preferred embodiment, in order to perform puncturing operations, the indications of validity (validity bits) associated with data items to be punctured are set to a value indicating non-validity. For example, they can be reset to zero to indicate that the corresponding data item is to be considered invalid (and thus is not to be output). In order to perform repetition operations, both the data items to be repeated and their associated indications of validity (i.e. the associated set validity bits) are each shifted to at least two memory locations (registers) of the data shift register and the validity shift register, respectively. These features lead to a simplified implementation of the flexible rate matching approach with a single hardware structure being able to meet all requirements. According to another preferred embodiment, rate-matched data items are continuously output. Herein, only valid data items are output, i.e. the data items having an associated indication of validity (validity bit) indicating validity (by a set validity bit, e.g.). With a continuous stream of output data items, the delay of the flexible rate matching approach can be minimized (thus maximizing the throughput). According to another preferred embodiment, in order to perform puncturing operations, both the data items to be punctured and their associated indications of validity (i.e. the associated set validity bits) are shifted to no memory location (register) of the data shift register and the validity shift register, respectively. In order to perform repetition operations, both the data items to be repeated and their associated indications of validity (i.e. the associated set validity bits) are each shifted to two memory locations (registers) of the data shift register and the validity shift register, respectively. These features lead to a further simplified implementation of the flexible rate matching approach while still meeting the other requirements. According to another preferred embodiment, rate-matched data items are output on a not fully continuous basis, i.e. no output may be generated at some points in time, although the output rate still is equal to the rate of the common clock. With a stream of output data items which is not entirely continuous, the requirements of subsequent functional blocks such as interleavers can be met. According to another preferred embodiment, said dual shift register includes at least two pipeline stages each having a different number of memory locations. By providing the dual shift register with pipeline stages comprising, from stage to stage, a different number of memory locations (registers), complexity can be further reduced because the rate-matching can be done for a single data item (and associated validity bit) at a given time (in a given pipeline stage). According to a preferred embodiment of the present invention it is proposed to carry out the flexible rate matching using a cascade structure. By cascading the flexible rate matching apparatus according to the present invention it is possible to realize a recursive rate matching algorithm hardware. In particular, a complex recursive rate matching algorithm may be implemented using a plurality of. flexible rate matching apparatuses according to the present invention. It is possible to calculate parameters in a separate computation device and to then write them into a storage of each of the flexible rate matching apparatuses. Also, it should be noted that the cascade structure of flexible rate matching apparatuses is suitable both for the serial and parallel implementation. According to another preferred embodiment of the present invention there is provided a computer program product directly loadable into the internal memory of a mobile communication unit comprising software code portions for performing the inventive flexible rate matching process when the product is run on a processor of the mobile communication unit. Therefore, the present invention is also provided to achieve an implementation of the inventive method steps on computer or processor systems. In conclusion, such implementation leads to the provision of computer program products for use with a computer system or more specifically a processor comprised in e.g., a mobile communication unit. This program defining the functions of the present invention can be delivered to a computer/processor in many forms, including, but not limited to information permanently stored on non-writable storage media, e.g., read only memory devices such as ROM or CD ROM discs readable by processors or computer I/O attachments; information stored on writable storage media, i.e. floppy discs and harddrives; or information convey to a computer/processor through communication media such as network and/or telephone networks via modems or other interface devices. It should be understood that such media, when carrying processor readable instructions implementing the inventive concept represent alternate embodiments of the present invention. DESCRIPTION OF THE DRAWINGS Preferred embodiments of the present invention will, by way of example, be described in the sequel with reference to the following drawings. FIG. 1: Block diagram of a transmitter (a) and a rate matcher (b) according to the prior art; FIG. 2: Block diagram of a radio communication system according to the present invention; FIG. 3: Block diagramme of a transceiver in a radio communication system according to the present invention; FIG. 4: Principle of flexible rate matching (data item repetition) according to the present invention; FIG. 5: Principle of flexible rate matching (data item puncturing) according to the present invention; FIG. 6: Temporal relation between (sub)processes of the flexible rate matching method according to the present invention; FIG. 7: Flow chart of the (sub)process “subblock input” according to the present invention; FIG. 8: Flow chart of the (sub)process “subblock rate-matching” according to the present invention; FIG. 9: Flow chart of the (sub)process “subblock output” according to the present invention; FIG. 10: Block diagram of a first flexible rate matching apparatus according to the present invention; FIG. 11: Block diagram of a second flexible rate matching apparatus according to the present invention; FIG. 12: Block diagram of an exemplary configurable dual shift register illustrating shift, repetition, and puncturing operations according to the present invention; FIG. 13: Block diagram of an exemplary implementation of a part of a configurable shift register capable of performing higher order shift operations according to the present invention; FIG. 14: Block diagram of an output handler according to the present invention; FIG. 15: Cascaded structure of flexible rate matching apparats according to the present invention; FIG. 16: Block diagram of another exemplary configurable dual shift register together with parts of an exemplary control unit according to the present invention; FIG. 17: Illustration of repetition, puncturing and shift operations performed in an exemplary configurable dual shift register according to FIG. 16; FIG. 18: Block diagram of another exemplary output handler according to the present invention. DETAILED DESCRIPTION OF THE INVENTION FIG. 2 shows a digital radio telecommunication system according to the invention. A typical application of such a system is to connect a mobile station or mobile terminal (MT) 1 to a core network such as the public switched telephone network (PSTN) 4. For this purpose, the mobile terminal 1 is connected to a base station (BS) 3 via a radio link 2. The radio telecommunication system provides a plurality of base stations which, through other network nodes such as controllers, switches and/or gateways (not shown) are connected to the PSTN 4. Each base station typically supports, at any one time, many radio links 2 towards different mobile terminals 1. The radio telecommunication system shown in FIG. 2 could for instance be operated according to cellular mobile communication standards such as GSM, PDC, TDMA, IS-95, WCDMA. It should however be mentioned that the invention generally applies to digital telecommunication systems no matter whether they are radio (i.e. wireless) or wireline telecommunication systems. Moreover, the invention also applies to uni-directional (“one-way”) communication systems such as broadcasting systems. FIG. 3 shows a block diagramme of a transceiver used in mobile terminals and base stations. Both the mobile terminal 1 and the base station 3 are equipped with one (or several) antenna(s) 5, an antenna duplex filter 6, a radio frequency receiver part 7, a radio frequency transmitter part 8, a baseband processing unit 9 and an interface 10. In case of a base station, the interface 10 is an interface towards a controller controlling the operation of the base station, while in case of a mobile terminal, the interface 10 includes a microphone, a loudspeaker, a display etc., i.e. components necessary for the user interface. The present invention relates to the baseband processing unit 9, parts of which have already been described above with respect to FIG. 1a. The skilled person will readily appreciate that instead of transceivers each having a common baseband processing unit for both the transmission and the reception branches, in uni-directional (broadcasting) communication systems, there are transmitters each including a first baseband processing unit for the transmission branch only and separate receivers each including a second baseband processing unit for the reception branch only. The invention applies to baseband processing units for at least the transmission branch. The person skilled in the art will also appreciate that such baseband processing units can be implemented in different technologies such as FPGA (field programmable gate array), ASIC (application specific integrated circuit) or DSP (digital signal processor) technology. In these cases, the functionality of such baseband processing units is described (and thus determined) by a computer program written in a given programming language such as VHDL, C or Assembler which is then converted into a file suitable for the respective technology. The concept underlying the flexible rate matching approach according to the invention is explained in the following with respect to FIGS. 4 and 5. It is assumed that the input data block (typically output by the channel encoder) comprises C bits, or in more general terms, C “data items”, wherein a data item may consist of a single bit or a plurality of bits. Given a desired number M (target block size) of data items in the rate-matched (output) data block, a total of A=M−C data items has to be rate-matched according to equation (2). For reasons of clarity and conciseness, only a part of the input data block (and thus the rate-matched data block) is considered in FIGS. 4 and 5. This part of the input data block is denoted data block DB. It is further assumed in both Figures that the data block DB includes 12 data items as defined above. Also, in both Figures, it is assumed that in the data block DB, two data items have to be rate-matched, wherein FIG. 4 relates to the repetition of these two data items while FIG. 5 is devoted to the puncturing of the two data items. Note that according to the present invention there is no particular restriction on the way in which the data items to be rate-matched are selected, i.e. on the rate matching scheme as described above with respect to the prior art (RMS1, RMS2, etc.). The resulting modified data block, denoted DB′, will, when output from the rate matcher, represent a part of the rate-matched data block. FIG. 4 shows the basic principles underlying the flexible rate matching approach as far as the repetition case is concerned (M>C, A=M−C>0). An exemplary data block DB comprising 12 data items b1, b2, . . . , b12 is shown in the upper part. The modified data block DB′ resulting from the repetition of two data items is shown in the middle part of FIG. 4. As also shown in the upper part of FIG. 4, according to a preferred implementation of the present invention, each data block DB is organized into a plurality of subblocks SB1, SB2, SB3, SB4, . . . , each including a number p of data items, wherein p will be referred to as the order of “parallelization” in the following and p=1 refers to the case of a non-parallelized input handling. As an example, the upper part of FIG. 4 shows subblocks SB1 . . . SB4 with p=3 data items each. The impact of the organization of the data block DB into a plurality of subblocks comprising p>1 data items is that for each subblock, a plurality of data items (p data items) may be considered simultaneously. In other words, the present invention preferably relies on a parallelized approach to rate matching. In the repetition case, it is necessary to achieve a duplication/multiplication of certain data items. For example, the data item b2 (in subblock SB1 of data block DB) is duplicated into the data items b2-1 and b2-2 in the modified data block DB′ and the data item b11 (in subblock SB4) is duplicated into the data items b11-1 and b11-2 in the modified data block DB′. In addition to the data blocks DB and DB′, FIG. 4 shows in its bottom part validity information (VI) associated to the modified data block DB′. More particularly, according to the present invention, it is proposed to provide, for each data item, an indication of validity referred to as “validity bit” in the following. This allows to indicate whether a certain data item is to be considered valid or invalid or, in other words, whether or not it is to be considered a data item to be output by the rate-matcher at a later stage. Apart from parallelization of rate matching, the present invention thus also relies on the provision of validity information for each data item. In its bottom part, FIG. 4 shows that all data items of the data block DB′, i.e. both the original and the repeated (duplicated) data items, are considered valid. This is indicated by the validity bits all having a value of one (while non-validity would be indicated by a value of zero). The skilled person will readily appreciate that any value can be used to indicate validity and non-validity, respectively, of the associated data item. In the following, a validity bit will be referred to as a “set validity bit” (in the sense of ‘set to a value corresponding to validity’, e.g. one) in order to indicate validity, or as a “reset validity bit” (in the sense of ‘reset to a value corresponding to non-validity’, e.g. zero) in order to indicate non-validity of the associated data item. For example, the data blocks DB and DB′ shown in FIG. 4 can be stored in a first shift register referred to as “data shift register” (DSR), while the validity information VI can be stored in a second shift register referred to as “validity shift register” (VSR). The skilled person will readily appreciate that a shift register includes a plurality of registers (memory locations), wherein data is shifted from registers to other registers at a given clock rate. In order to enable the one-to-one relation between the data items stored in the registers of the DSR and the associated validity bits stored in the registers of the VSR, it is clear that both shift registers will have the same number of registers. In order to maintain said one-to-one relation during shift operations, the skilled person will readily appreciate that both shift registers will have to use the same (common) clock rate (e.g. by applying the same clock signal). A pair of shift registers having these properties will be referred to as a “dual shift register” in the following. The common clock rate mentioned above will have to correspond to the rate at which the subblocks (comprising p>0 data items) are input into the DSR. For p=1 (no parallelization), it will thus correspond to the rate of the data items, while it will be p times slower for p>1 (with parallelization). In the latter case (p>1), the DSR and VSR must however be adapted to receive subblocks of p data items (DSR) and subblocks of p validity bits (VSR), respectively, within a single period of the common clock signal instead of receiving only a single data item/validity bit for p=1. Also, the skilled person will readily appreciate that each register of the DSR must be able to store a data item (i.e. one or several bits) while the registers of the VSR have to store a single bit, only. FIG. 5 shows the basic principles underlying the flexible rate matching approach as far as the puncturing case is concerned (M<C, A=M−C<0). The upper part of FIG. 5 again shows the exemplary data block DB composed of a plurality of subblocks SB1, SB2, . . . each including p=3 data items, as described above with respect to FIG. 4. In contrast to FIG. 4, FIG. 5 relates to the puncturing case, where the data items b2 (in subblock SB1) and b11 (in subblock SB4) are to be removed. Typically, one would expect that due to the puncturing of the data items b2 and b11, the other data items b3-b10 and b12 are shifted such that no “gaps” remain in the DSR between the data items considered for output, as shown by the upper data block DB′ in FIG. 5. In contrast, the present invention uses the concept of validity information (VI) as explained above with respect to FIG. 4 for the repetition case. In the puncturing case, the data items in the data block DB remain unchanged, as can be seen from the bottom data block DB′ in FIG. 5, while the validity bits associated with the data items to be punctured are reset, e.g., to a value of zero, as explained above. For this reason, the validity bits associated with the data items b2 and b11 are reset in the example of FIG. 5. Thus, by the addition of validity information, unnecessary shift operations in the DSR may be avoided so that the overall complexity of the rate matching process and related hardware is reduced. In conclusion, the important aspects underlying the present invention and illustrated with respect to FIGS. 4 and 5 may be summarized as follows: a) It is proposed to add validity information (in the form of validity bits, e.g.) to each data item stored in the data shift register (DSR). Each validity bit indicates whether or not the associated data item is to form part of the output of the rate matching process. For data items to be punctured (removed), the validity bits are reset, while they are set for data items not to be rate-matched as well as for those representing copies or original data items in case of repetition. Finally, only valid data items (i.e. those with set validity bits) are output by the rate matching process. b) For the implementation of the rate matching process, not only a single shift register is proposed but a dual shift register divided into a data shift register (DSR) and a validity shift register (VSR) for storing the data items and the validity information, respectively. Both shift registers have the same number of memory locations (registers) and use the same (common) clock rate/signal. c) Further, the input of data items is organized into subblocks each comprising a number p>0 of data items. For p=1, the data items are input serially, while for p>1, a plurality of data items may be considered simultaneously to achieve a parallelization for the rate matching process and implementation. With these aspects in mind, the flexible rate matching process according to the present invention can be decomposed into several (sub)processes. In a first subprocess, data items are input into the data shift register (DSR) in the form of subblocks input at a prespecified rate of a common clock signal. Simultaneous to the input of each subblock (comprising p>0 data items) into the DSR, another subblock comprising p set validity bits is preferably input into the validity shift register (VSR) in order to indicate that the p data items being input are considered valid for a start. This subprocess, referred to as “subblock input” process in the following, continues as long as subblocks are available for input, i.e. until all subblocks of an input data block to be rate-matched have been input. In a second subprocess, referred to as “subblock rate matching” process in the following, the data items part of the current subblock, i.e. the subblock which has been input into the DSR during the last cycle of the common clock signal, are considered for rate-matching. For this to become possible, it must be clear which data items in the current subblock have to be rate-matched. Here, it may be assumed that the positions of the data items to be rate-matched, i.e. the result of an evaluation of the rate matching scheme to be employed, is either known in advance or generated concurrently during the flexible rate matching process. If, according to these positions, it is necessary to puncture one or several data items of the current subblock, the associated validity bits are reset in order to indicate that the corresponding data items are not to be considered for output. On the other hand, if one or several data items of the current subblock have to be repeated, these data items are duplicated together with the associated validity bits while making sure that no information relating to the preceding subblocks is lost. In any case (even if no rate-matching is to be executed at all in the current subblock), the current subblock is shifted together with the associated validity bits in order to make it possible for this subprocess to consider the next subblock during the next cycle of the common clock signal. In a third subprocess, as soon as a predetermined number of data items (or equivalently, subblocks) has been input into the DSR, the output of data items, preferably again in a blockwise manner, may start. According to this subprocess, referred to as “subblock output” process in the following, a subblock of p>0 valid data items is output at the prespecified rate of the common clock signal while the associated validity bits are reset in order to indicate that the corresponding data items have been output. This subprocess continues as long as set validity bits are present in the VSR. From the above, the skilled person will readily appreciate that both shift registers (DSR/VSR) must be configurable/programmable in the sense that a given register can receive data from one of several possible other registers in a configurable/programmable way. Also, it is clear that the DSR must not be adapted to store complete input data blocks (comprising C data items) but only some subblocks of data items to achieve the overall flexible rate matching. For these reasons, the present invention achieves the decisive advantage of a significantly reduced hardware effort while still being able to implement all kinds of rate matching schemes (RMS1, RMS2 etc.). From the above description of the three subprocesses, it is also clear that their execution periods overlap in time. In particular, the continuous input of data items (or subblocks thereof) and the continuous output of rate-matched data items (or subblocks thereof) are carried out concurrently, i.e. simultaneously for a significant period of the execution time of the overall flexible rate matching process. Also, data items (or subblocks thereof) are continuously input and output at the same rate, i.e. at the rate of the common clock signal. FIG. 6 illustrates the overlapping execution periods of the processes “subblock input”, “subblock rate-matching” and “subblock output” as described above. For a detailed description of the duration of these processes as well as of the instants in time, when these processes start and finish their operations, respectively, a number of parameters is needed. Note that the following definitions and equations will be adhered to throughout this document. Assuming that the overall input data block to be rate-matched comprises C data items and the overall output data block (i.e. the rate-matched data block) is to comprise M data items, it can be stated that, according to equation (2), a total of |A|=|M−C| data items has to be rate-matched by repetition or puncturing of data items. Subdividing said input and output data blocks into subblocks each comprising p>0 data items, wherein p is referred to as the order of parallelization, the following parameters can be defined: CSub=ceil{C/p} (3) MSub=ceil{M/p} (4) ASub=MSub−CSub (5) wherein “ceil” denotes the ceiling operation delivering the smallest integer value equal to or superior to its argument. In equations (3) and (4), CSub and MSub denote the number of subblocks in the input and output data blocks, respectively, wherein due to the ceiling operations, it may be necessary in case of p>1 to pad the last (input and/or output) subblock of data items with dummy data items (with zero values, e.g.) in order to obtain a full subblock comprising p items. According to equation (5), ASub indicates the difference between the numbers of subblocks in the output and input data blocks, respectively. Note that for p>1, in the subblock notation according to equations (3)-(5), the repetition case is characterized by Msub≧CSub (and thus ASub≧0) and the puncturing case is characterized by MSub≦CSub (and thus ASub≦0) while on the level of data items (or equivalently, for p=1), the equal sign (“=”) cannot apply (M>C and A>0 for the repetition case and M<C and A<0 for the puncturing case). In order to simplify the temporal description of processes and the temporal relations between operations performed by said processes, let “[clk i]” denote the i-th event (falling or rising edge, e.g.) of the common clock signal applied to both DSR and VSR “[clk i]”: i-th event of common clock signal. (6) For example the fifth event of said common clock signal will be denoted by “[clk 5]”. FIG. 6 will now be described with the help of the parameters and definitions according to equations (3) to (6). On the horizontal axis shown in FIG. 6, time is indicated in terms of the index i of the clock event [clk i] as defined above with respect to equation (6). For example, the fifth event of said common clock signal is identified by i=5 on the horizontal axis of FIG. 6. As can be seen from FIG. 6, the process “subblock input” starts to input subblocks of data items at the time of the first event (i=1) of the common clock signal (wherein, of course, any arbitrary offset can be added to the values of i). This process terminates its operations once all CSub subblocks according to equation (3) have been input. This will be the case just after the i=CSub-th event of the common clock signal. The process “subblock rate-matching” starts its operations with the second event (i=2) of said common clock signal, as shown in FIG. 6, i.e. one clock cycle later than the “subblock input” process. Subsequently, it operates in parallel (simultaneously) to the “subblock input” process until it terminates its operations one cycle after the process “subblock input”, i.e. just after the event i=CSub+1 of said common clock signal. As far as the process “subblock output” is concerned, it can be stated that this process will terminate its operations when MSub subblocks according to eq. (4) have been output. For this to be achieved, a total of MSub cycles of said common clock signal will be required. When, however, it comes to the point in time where this process can begin with its operations, the two cases of repetition and puncturing have to be distinguished, as indicated in FIG. 6 by the two different execution periods relating to this process. In case of repetition (MSub≧CSub), the “subblock output” process can begin to output subblocks of data items one clock cycle after the start of the process “subblock rate-matching”, or equivalently, two cycles after the start of the “subblock input” process, i.e. with the third event (i=3) of said common clock signal. With a duration of MSub cycles, this process will finish its operations with i=MSub+2≧CSub+2, i.e. a number of ASub+2 cycles later than the “subblock input” process. In case of puncturing (MSub≦CSub), however, the “subblock output” process can only begin with its operations once a sufficient number of subblocks in the DSR is ready for output so that an underflow of subblocks and thus an interruption in the otherwise continuous output stream of subblocks can be avoided. The “sufficient” number of output subblocks is given by |ASub| according to equation (5). Compared with the repetition case, in case of puncturing, the process “subblock output” can therefore only start with a delay of |ASub| cycles, i.e. at i=3−Asub=3−(MSub−CSub)=3+CSub−MSub≧3, as shown in FIG. 6. With a duration of MSub cycles, it will finish its operations with i=CSub+2, i.e. two cycles later than the “subblock input” process. From the above, it becomes clear that the flexible rate matching process minimizes the delay as measured for instance in terms of the time difference between the input of the first subblock and the output of the last (or first) subblock. The skilled person will also appreciate that the input, the rate-matching, and the output rely on concurrent software processes and/or independently operating hardware. In the following, the processes “subblock input”, “subblock rate-matching”, and “subblock output” will be explained in more detail with respect to FIGS. 7-9. These explanations also refer to the parameters and definitions as described above with respect to equations (3) to (6). In particular, any reference to a clock event, such as for example “[clk 5]” or “[clk i]”, in any of the FIGS. 6 to 9, does refer to the same clock event of the common clock signal, namely the fifth and the i-th, respectively. In order to distinguish between operations and/or steps which are executed at a particular clock event and those which may be executed at any point in time (for example in between clock events), clocked operations are marked with expressions such as “[clk i]” in the flow charts of FIGS. 7 to 9. For the description of FIGS. 7-9, an assumption and a definition relating to shift registers must be given. As stated above with respect to FIG. 4, a shift register includes a plurality of memory locations (registers), wherein data is shifted from registers to other registers at a given clock rate. In a programmable/configurable shift register, it can be programmed/configured, which output (i.e. the output of which register among a plurality of possible registers) is to be connected to the input of a given other register. In this way, it is possible, for example, that an output of a given register is connected to the inputs of several other registers. In the following, it is assumed that the registers (memory locations) are ordered in some way, for example by assigning an index j=1, 2, 3, . . . to each register so that the first, second, . . . , and j-th register can be denoted r1, r2, . . . , and rj, respectively. On this assumption, the expression of a higher order shift (operation), also referred to as a shift (operation) “of order s” or “of width s” can be defined as a shift from register rj to the register rj+s. A first order shift (i.e. a shift of order/width one) thus corresponds to a shift from register rj to the next/subsequent (in terms of its index) register rj+1. In the following, it is assumed that both the data shift register (DSR) and the validity shift register (VSR) are capable of performing such higher order shift operations in a single period of the common clock signal and in a configurable/programmable way as described above. FIG. 7 shows a flow chart of the “subblock input” process. In a first step 71, a clock event counter i is initialized to an initialization value such as zero. Furthermore, the data shift register (DSR) and the validity shift register (VSR) are reset (not shown in step 71). Then, in step 72, the clock event counter i is incremented by one. In step 73, executed with the i-th clock event (“[clk i]”), the i-th subblock (denoted SB(i) in the following) of p>0 data items and another subblock of p set validity bits are input simultaneously into the first p registers (memory locations) of the DSR and VSR, respectively. Then, in step 74, the value of the clock event counter i is compared with CSub as defined in equation (3). If the value of i is equal to CSub, i.e. when a total of CSub subblocks has been input into the DSR, the “subblock input” process terminates (“step” 75). Otherwise, the sequence of steps 72, 73 and 74 is repeated, i.e. the clock event counter is further incremented in step 72 in order to input, with the next clock event, the next subblock of data items in step 73, and then to again compare the increased value of i with CSub. This sequence of steps is repeated until it is determined in step 74, that the clock event counter has reached the value of CSub. For the following description of the FIGS. 8 and 9, it is assumed that at subsequent clock events [clk i] with i>CSub, i.e. after termination of the “subblock input” process, dummy subblocks with arbitrary or dummy data items are input together with reset validity bits. FIG. 8 shows a flow chart of the “subblock rate-matching” process. As this process starts its operations one clock event after the “subblock input” process has started its operations (cf. FIG. 6), the clock event counter i is initialized to a value of one, here, in step 81. Upon incrementing the clock event counter i by one in step 82, it is determined in step 83, how many data items of the (i−1)-th subblock, denoted SB(i−1) and stored in the first p>0 registers of the DSR, have to be rate-matched according to the rate matching scheme to be employed (RMS1, RMS2 etc.). Let a denote the number of data items to be rate-matched in said subblock SB(i−1). Note that a is in the range 0≦a≦p. In step 84, the value of a is compared with zero. If a=0, i.e. in case no rate-matching has to be applied to the subblock SB(i−1) stored in the first p registers of the DSR, only shift operations are executed with the i-th clock event (“[clk i]”), as shown in step 87, wherein a shift of order p as defined above is applied to all registers of the DSR and VSR. As the skilled person will appreciate, this implies that the contents of the last p registers of the DSR (and also of the VSR) will be lost upon execution of this operation. However, the process “subblock output” will ensure that valid data items are output before this can happen, as will be described with respect to FIG. 9. If it was determined in step 84, that a is not equal to zero, i.e. at least one data item has to be rate-matched in subblock SB(i−1), it can be stated that there are a positions in subblock SB(i−1) where data items have to be rate-matched. These a positions, denoted φ(1),φ(2), . . . ,φ(a) and depending on the rate matching scheme to be employed, are determined in step 85. Then, it is determined in step 86 whether the data items stored at said positions φ(1), . . . , φ(a) of subblock SB(i−1) have to be punctured or repeated. In case of puncturing, shift and puncturing operations will be performed in step 88, while in the repetition case, shift and repetition operations will be performed in step 89. In case of puncturing (step 88), the validity bits associated to those data items of SB(i−1) which need to be punctured, i.e. the validity bits stored at said positions φ(1), . . . , φ(a) of the subblock of validity bits associated to the subblock SB(i−1) of data items, are reset. At a later stage, these reset validity bits will indicate to the process “subblock output” that the corresponding data items are not to be output, as will be seen from the description with respect to FIG. 9 below. Upon resetting said validity bits, a shift of order p will be applied, with the i-th clock event (“[clk i]”), to all registers of the DSR and VSR, just as in step 87. In the repetition case (step 89), with the i-th clock event (“[clk i]”), a shift of order p+a will be applied to a second part of the dual shift register (both DSR and VSR) in order to prevent the contents stored in said second part to be overwritten by the shift and repetition operations applied at the same time (“[clk i]”) to a first part of the dual shift register (both DSR and VSR). More precisely, said first part of the dual shift register comprises the first p registers of the DSR, where subblock SB(i−1) is stored, and also the first p registers of the VSR, where the associated validity bits are stored, cf. step 73 of FIG. 7. Said second part of the dual shift register comprises the remaining registers of both DSR and VSR, where preceeding subblocks of data items which have already been rate-matched, and associated validity bits are stored. In order to achieve a repetition of the a data items stored at the positions φ(1), . . . , φ(a) of subblock SB(i−1), the p data items of subblock SB(i−1) and the associated p validity bits, i.e. the 2p items stored in said first part of the dual shift register, are shifted, with the i-th clock event (“[clk i]”), to the first 2(p+a) registers of said second part of the dual shift register while repeating, i.e. shifting to two registers each, those a data items and those a associated validity bits stored at said positions φ(1), . . . , φ(a) in the first parts of the DSR and VSR, respectively. Upon execution of one of the steps 87-89, the value of the clock event counter i is compared with CSub+1 in step 90, wherein the “+1” in the latter expression is due to the init value of one assigned to the clock event counter in step 81. If i is equal to CSub+1, all CSub subblocks input by the “subblock input” process described above with respect to FIG. 7 have been processed in one of the steps 87-89 and are thus ready for output, so that the “subblock rate-matching” process can be terminated. Otherwise, if i is inferior to CSub+1, the process continues with step 82 etc. As the skilled person will readily appreciate, steps other than the steps 83-86 described above can easily be conceived in order to perform step 87 when neither repetition nor puncturing operations are required for the subblock under consideration (SB(i−1)), or to perform step 88 or 89 when puncturing and repetition operations are required, respectively, for said subblock. For example, instead of the steps 83-86 as described above, it could be attempted in a first step to directly determine positions where data items in subblock SB(i−1) have to be rate-matched. In a second step, it would then have to be branched into step 87, if no such positions were found, and into step 88 or 89, if at least one position was found in said first step, where a data item needs to be punctured or repeated, respectively. From the above description of the steps 87-89, it can be concluded that shift operations of order p are applied to all registers of the dual shift register, whenever no data item of the subblock under consideration (SB(i−1)) needs to be repeated, i.e. whenever one of the steps 87 and 88 is executed. In contrast, shift operations of order p+a are applied to the second part of the dual shift register and shift operations of an order in between p and p+a are applied to the first part thereof, whenever said subblock SB(i−1) does require a number a>0 of its data items to be repeated in step 89. Given the fact that, in step 89, a lies in the range of 1≦a≦p, this implies that the dual shift register must be capable of performing shift operations of orders ranging from p (minimum order) to 2p (maximum order) in a programmable/configurable manner. As the value of a and the positions φ(1), . . . , φ(a) may (and will in general) change from subblock to subblock, it may be necessary to reconfigure/reprogram the dual shift register from clock event to clock event. This will also be seen from the detailed description of the steps 87-89 provided below with respect to FIG. 12. FIG. 9 shows a flow chart of the “subblock output” process. In a first step 91, a clock event counter i is initialized to an initialization value iinit. This initialization value is equal to 2 in the repetition case and equal to 2+CSub−MSub in the case of puncturing, if it is desired to start the output of subblocks at the earliest possible clock event which is [clk iinit+1], as can be seen from FIG. 6. Thereafter, in step 92, the clock event counter i is incremented by one. Then, in step 93, the validity information stored in the VSR is evaluated. In particular, the number v of set validity bits in all but the first p registers of the VSR is determined. In step 94, said number v is compared with p, the order of parallelization, or equivalently, the number of data items per subblock. If it is determined that said number v is superior or equal to p, the positions ψ(1), ψ(2), . . . , ψ(p) of the p rightmost (i.e. last) set validity bits stored in the VSR are determined in step 95. Note that due to puncturing not necessarily said positions will refer to adjacent registers of the VSR. In step 96, executed with the i-th clock event (“[clk i]”), the p (valid) data items corresponding to said p rightmost set validity bits, i.e. the p data items stored at the positions ψ(1), . . . , ψ(p) of the DSR, are output as a (full) subblock while the associated validity bits are reset as an indication that the corresponding data items have been output. Then, the sequence of said steps 92-96, i.e. incrementing the clock event counter (step 92), determining the number v of set validity bits (step 93), comparing v with p (step 94) and, if v≧p, determining the positions of the p rightmost (last) set validity bits (step 95) and outputting the corresponding valid data items while resetting the associated validity bits (step 96), is repeated until it is determined in step 94 that v is inferior to p. In this case, it is no longer possible to output a full subblock of valid data items. Then, in step 97, v is compared with zero. If v is equal to zero, the “subblock output” process terminates. Otherwise, i.e. if v is in the range 1≦v≦p−1, the process continues with step 98, where the positions ψ(1), ψ(2), . . . , ψ(v) of the final v set validity bits stored in the VSR are determined. In step 99, executed with the i-th clock event (“[clk i]”), the v (valid) data items corresponding to said v set validity bits, i.e. the v data items stored at the positions ψ(1), . . . , ψ(v) of the DSR, are output as a partial subblock, possibly together with p−v dummy data items in order to form a full subblock comprising p items, while the associated validity bits may be reset. Thereafter, the “subblock output” process terminates. As the skilled person will readily appreciate, steps other than the steps 93, 94, 95, 97, 98 described above can easily be conceived in order to perform step 96 as long as p set validity bits can be found, or to perform step 99 if 1≦v≦p−1 set validity bits are found. For example, instead of the steps 93, 94, 95, 97, and 98 as described above, it could be attempted in a first step to directly determine the positions of the p rightmost set validity bits. In a second step, it would then have to be branched into step 96, if p positions could be determined in the first step, and into step 99, if at least one position was found in said first step, respectively. Moreover, steps 96 and 99 could be merged into a combined step capable of outputting a number of valid data items equal to the number (≦p) of positions determined in said first step. In this case, instead of the two comparisons in steps 94 and 97, a single check whether at least one position was found, would suffice. Furthermore, as the skilled person will readily appreciate, other loop structures and/or criteria for terminating the “subblock output” process can easily be conceived. For example, the “subblock output” process could be terminated once a total of MSub subblocks according to eq. (4) has been output. This will be the case just after the clock event [clk iinit+MSub]. According to the above description with respect to FIGS. 6 to 9, both the input of subblocks to the DSR and the output of possibly modified (rate-matched) subblocks therefrom are executed at the same (common) clock rate. The “subblock output” process operates continuously and concurrently (simultaneously) to the “subblock input” process as soon as the respective start condition [clk iinit+1] is met and as long as valid data items are found in the DSR. It is this interleaved input and output processing that allows for a minimization of hardware complexity, where only a small set of subblocks must be maintained in the DSR. Also, through the parallelized input and output processing, extremely high data rates necessary for future 3G applications can be dealt with using, e.g., FPGA or ASIC technology. Another important advantage of the present invention is the significantly improved flexibility with regard to different rate matching schemes. This is achieved by using only a single hardware structure (to be detailed below) irrespective of the question how the positions of the data items to be rate-matched are specified (and thus determined) and irrespective of the variety of transport channel types and sizes C of coded data blocks. While in the above, with respect to FIGS. 4 to 9, concepts and principles of the invention have been illustrated with respect to an algorithmic representation thereof, in the following, options to implement the invention in hardware (and/or software) will be discussed with respect to FIGS. 10 to 18. FIG. 10 shows a block diagram of a flexible rate matching apparatus according to the present invention. It includes a dual shift register 14, an output handler 16, and a control unit 12. The dual shift register 14 is composed of a configurable data shift register (DSR) 26 and a configurable validity shift register (VSR) 28. Operatively, in the flexible rate matching apparatus, the dual shift register 14 and the output handler 16 are operated by the control unit 12 such that data items of an input data block are input into the DSR 26, shifted and modified (rate-matched, i.e. repeated or punctured) therein (together with the associated validity bits in the VSR) and finally output as a part of a rate-matched data block, wherein all these operations are performed according to the flexible rate matching approach as described above. Heretofore, the DSR 26 is adapted to receive a continuous stream of data items (or subblocks thereof each comprising p≧1 data items) at a prespecified clock rate. To each data item there is assigned a validity bit as described above. The validity bits (or subblocks thereof each comprising p≧1 validity bits) are stored in the VSR 28 and shifted (moved) therein at the same prespecified clock rate. Further, the output handler 16 is adapted to continuously output valid data items (or subblocks thereof each comprising p≧1 valid data items) at the same prespecified clock rate using the validity information stored in the VSR 28 as masking information. The control signals applied by the control unit 12 to the dual shift register 14 and the output handler 16 include configuration parameters/data required for an appropriate configuration/programming of the dual shift register 14 and/or the output handler 16 as well as clock/shift enable signals, set and/or reset signals, timing signals etc. For example, as shown in FIG. 10, the control unit 12 includes an “input and RM control unit” 22 (RM: rate matching), an “output control unit” 23, and a “flexible RM control unit” 24. Herein, the execution of the “subblock input” and “subblock rate-matching” processes described above with respect to FIGS. 7 and 8 could be controlled by the input and RM control unit 22 while the execution of the “subblock output” process described above with respect to FIG. 9 could be controlled by the output control unit 23. The flexible RM control unit 24 can take over the coordination of the control (sub)units 22 and 23. This implies a synchronization of their operations, i.e. of the steps of said three processes in the sense of the above description with respect to FIGS. 6-9, as well as a coordination of the exchange of information therebetween. For example, the rate matching scheme(s) specified by the standard(s) according to which the telecommunication system is to operate (cf. the example schemes RMS1, RMS2 etc. described above with respect to the prior art) could be evaluated by the flexible RM control unit 24 or in a separate computation unit (not shown) under control of the flexible RM control unit 24 in dependence of one or several parameters supplied to said flexible RM control unit 24 (said parameters identifying for example a particular rate matching scheme to be used). The resulting positions, where data items have to be rate-matched could then be supplied to the input and RM control unit 22 for use in, e.g., steps 83 and 85 of FIG. 8, or alternatively stored in a position memory (not shown) to be accessed by the input and RM control unit 22. Note that the determination of said positions (as well as their storage, if applicable) can be done data block wise (i.e. once for all subblocks part of the input data block) prior to the flexible rate matching process itself or subblock-wise (i.e. from subblock to subblock) concurrently to the flexible rate matching process itself. The arrangement of components of the control unit 12 shown in FIG. 10 can easily be modified. For example, the input and RM control unit 22 could be split into two control (sub)units, one input control (sub)unit for controlling the “subblock input” process only, and one RM control (sub)unit for controlling the “subblock rate-matching” process only. In this case, the flexible RM control unit 24 would have to coordinate a total of three control (sub)units. On the other hand, the output control unit 23 could be part of the output handler 16 and/or said input control (sub)unit could be part of the dual shift register 14. In this case, the flexible RM control unit 24 would directly control the dual shift register 14 and/or the output handler 16 with respect to the input and output of data items which said RM control (sub)unit would control the rate-matching operations themselves. Also, the computation unit mentioned above as well as the position memory (both not shown in FIG. 10) could be combined into the input and RM control unit 22 or said RM control (sub)unit. Further, while the different functional subunits of the control unit 12 are shown as dedicated and separated units, the implementation thereof may as well be based on a standard controller, microcomputer, microprocessor or digital signal processor suitably programmed so as to execute the described steps. Another option would be to use FPGA or ASIC hardware designed through VHDL code, e.g. FIG. 11 shows a block diagram of a second flexible rate matching apparatus according to the present invention. Elements identical to those discussed above with respect to FIG. 10 are identified by the same reference numerals and the explanation thereof will be omitted. According to the second embodiment of the present invention, the control unit 12 comprises a parameter memory 29, a data item counter 31 and a repeat/puncture module 30. Operatively, the parameter memory 29 stores at least one parameter associated with the rate matching scheme(s) to be employed. Examples for such parameters include positions of data items to be rate-matched or distances therebetween, as described above with respect to the prior art (RMS1, RMS2, . . . ). The data item counter 31 counts all incoming data items. In case the counter value reaches a trigger value derived from the stored parameter(s), this is an indication to repeat/puncture the data item. Typically, the determination of the trigger value as well as the comparison of the counter value with the trigger value is carried out by the repeat/puncture module 30, wherein for p>1, a total of p comparisons has to be performed simultaneously. In case the compared values are identical, the repeat/puncture module 30 either resets the validity bits of the corresponding data items in case of puncturing or initiates double shifts in the dual shift register 14 together with the repetitions themselves in case of repetition. The repeat/puncture module 30 may coordinate the operations of the other components of the control unit 12 and further of the dual shift register 14 and the output handler 16. In the following, shift, repeat and puncture operations in the dual shift register will be explained in more detail with respect to FIG. 12, wherein an exemplary configurable data shift register (DSR) and an exemplary configurable validity shift register (VSR), each comprising Nreg=15 memory locations (registers), are shown. Herein, small square boxes bearing an index j=1, 2, 3, . . . represent the j-th register (register rj) of the DSR and the VSR, respectively, as can be seen from the legend of FIG. 12. The parallelization order p, i.e. the number of data items per subblock, is assumed to be p=3 while of course other values p≧1 are possible. It is assumed in FIG. 12 that the subblock under consideration, denoted SB(i) and comprising p=3 data items, is stored in the first p=3 registers r1, r2, r3 of the DSR with the associated validity bits stored in the first p=3 registers of the VSR, while previously input subblocks of data items and their associated validity bits are stored in the other registers of the DSR and VSR, respectively. Arrows are used in FIG. 12 to indicate the shift operations to be executed at the next event of the common clock signal ([clk i+1]). It should be noted that in FIG. 12, the registers are arranged in the DSR and the VSR such that the shift operations can easily be indicated by straight arrows. Other than that there is no meaning to the placement of a particular register in the DSR/VSR. While FIG. 12a relates to the case in which only shift operations need to be executed (cf. step 87 of FIG. 8), FIGS. 12b and 12c are devoted to the situation wherein a number a of data items of the subblock SB(i) need to be repeated (cf. step 89 of FIG. 8) with a=1 for FIG. 12b and a=p=3 for FIG. 12c. In FIG. 12a, it is assumed that no rate-matching is necessary for the subblock SB(i) so that only shift operations are to be executed. It can be seen that a shift of order p=3 is to be applied to all registers of the DSR and the VSR at the next clock event, as described above with respect to step 87 of FIG. 8. All data items stored in the DSR as well as all validity bits stored in the VSR will then be shifted p=3 registers “to the right” (wherein expressions such as “to the right” and “to the left” are intended to mean “to higher register indices j” and “to lower register indices j”, respectively). For example, the subblock SB(i) and its associated validity bits will then be stored in the registers r4, r5, r6 of the DSR and VSR, respectively. Simultaneously, the next subblock SB(i+1) of p=3 data items and an associated subblock of p=3 set validity bits is input into the first p=3 registers r1, r2, r3 of the DSR and VSR, respectively, as indicated in FIG. 12a (cf. step 73 of FIG. 7). Note that in principle, FIG. 12a also applies to the case in which a number a of data items has to be punctured from the subblock SB(i). If, for example, the data item stored in register r2 of the DSR is to be punctured, its associated validity bit, i.e. the validity bit stored in the register r2 of the VSR must be reset prior to the illustrated shift operations executed at the next clock event, as described above with respect to step 88 of FIG. 8. Alternatively, if resetting is done after said next clock event, the (same) validity bit (then) stored in r5 of the VSR has to be reset. FIG. 12b relates to the case in which a single (a=1) data item of the subblock SB(i) has to be repeated, namely the second data item stored in the register r2 of the DSR. As noted above, the registers are arranged in a different manner (compared with FIG. 12a) in order to facilitate the illustration of the shift operations. As can be seen from FIG. 12b, at the next clock event, the data item stored in the register r1 of the DSR will be shifted to register r4 (just as in FIG. 12a) while the data item stored in r2 will be shifted to r5 and r6 and thus will be repeated. The data item stored in r3 will be shifted to r7 while shifts of order p+a=4 are to be applied to the remaining registers r4, r5, . . . . Since the shift operations applied to the VSR are always the same as those applied to the DSR, the illustration of the VSR is omitted in FIG. 12b (and also in FIG. 12c). The validity bits are thus shifted and repeated in an analoguous manner. In FIG. 12c, it is assumed that all p data items of the subblock SB(i) have to be repeated (a=p=3). At the next clock event, the data items stored in registers r1, r2, and r3 will therefore be shifted (and repeated) to the registers r4 & r5, r6 & r7, and r8 & r9, respectively, while shifts of order p+a=6 are to be applied to the registers r4, r5, . . . . Again, an analoguous picture applies to the VSR. A note on the total number Nreg of registers appears to be in order, here. The DSR must be able to store |ASub| subblocks [see eq. (5)], i.e. p*|ASub| data items, in order to prevent both an underflow in case of puncturing (leading to an interruption of the otherwise continuous stream of output subblocks) and an overflow in case of repetition (leading to a loss of valid data items). In addition, a further p registers must be provided for storing the newly incoming (and not yet rate-matched) subblock. The minimum total number of registers required for each shift register (DSR and VSR) thus amounts to Nreg=p*|ASub|+p=p*(|ASub|+1). (8) Given the values of p=3 and Nreg=15, the exemplary shift registers shown in FIG. 12 would thus be sufficient for a flexible rate matching apparatus with |ASub|=|MSub−CSub|=4. From the above description with respect to FIG. 12, it is obvious that the connections between registers must be configurable/programmable in both the DSR and the VSR. For an implementation of such configurable/programmable shift registers, it is necessary to determine which minimum shift order and which maximum shift order needs to be supported for each register under consideration. Such limits for the orders of shift operations will be derived in the following. From FIGS. 12b and 12c, it can be generalized that when 1≦a≦p data items of the subblock SB(i) have to be repeated, shift operations of order p+a are to be applied to the registers rp+1, rp+2, . . . , and one or two different shift operations (with orders in between p and p+a) have to be applied to the first p registers r1, r2, . . . , rp. This confirms the above description with respect to step 89 of FIG. 8. Since at most a=p data items have to be repeated, the maximum order of shift operations necessary to be implemented amounts to 2p for the registers rp+1, rp+2, . . . , and p+j for the first p registers rj with j=1, 2, . . . , p. The minimum order of shift operations can be determined from the shift-only and shift&puncture cases described above with respect to FIG. 12a. Accordingly, the minimum order of shift operations necessary to be implemented amounts to p for all registers. It can therefore be concluded that the registers of both the DSR and the VSR must be able to perform, in each cycle of the common clock signal and in a configurable/programmable manner, higher order shift operations with shift orders in the following ranges: rj with j≦p: shift orders in the range p, . . . , p+j (7a) rj with j>p: shift orders in the range p, . . . , 2p. (7b) FIG. 13 provides an exemplary implementation of a part of a configurable/programmable shift register capable of performing such higher order shift operations. Herein, a single register rj with reference numeral 42 is considered, wherein j>2p is assumed for the moment. In contrast to the description of FIG. 12 where an output view was given for each register (i.e. where to is the register contents shifted with the next clock event?), for FIG. 13 an input view is chosen for the register rj in the sense of the question “where from does the register rj possibly receive data with the next clock event?”. According to equations (7a) and (7b), in general, the shift operations necessary to be supported can have orders ranging from p to 2p. For this reason, in general, the “destination” register rj must be adapted to receive data, in a configurable manner, from the p+1 “source” registers rj−2p, rj−(2p−1), . . . , rj−(p+1), rj−p. According to FIG. 13, this can for example be achieved by providing a multiplexer MUX-J (46) adapted to selectively connect the output of one of said source registers rj−2p (45), rj−(2p−1) (44) . . . , rj−p (43) to the input of said destination register rj (42). In this arrangement, a configuration parameter sj is used in order to control said multiplexer MUX-j (46) so as to select the output of the appropriate source register (depending on the desired shift order at the input of said destination register rj). For an entire configurable shift register comprising Nreg registers, an arrangement such as the one shown in FIG. 13 (with a multiplexer MUX-j) is necessary for all registers rj with j=p+2, p+3, . . . , Nreg while the first p+1 registers r1, r2, . . . , rp+1 do not require such an arrangement, because their inputs can be hard-wired either to the p inputs of the shift register (this holds for the destination registers r1, . . . , rp) or to the output of the register r1 (this holds for rp+1). In summary, a total of Nreg−(p+1) multiplexers (and thus configuration parameters sj) is thus required for the entire configurable shift register. Herein, the destination registers rj with j=p+2, . . . , 2p will have to be connected to fewer than p+1 (but at least two) source registers, as the skilled person will readily appreciate. From the above description with respect to FIGS. 6 to 9, 12 and 13, it is clear that the multiplexers MUX-j of the shift registers (DSR and VSR) must be reconfigured/reprogrammed (by applying different sets of configuration parameters sj under the control of the control unit 12 of FIGS. 10 and 11) in each cycle of the common clock signal in order to allow for the appropriate shift operations to be performed. FIG. 14 provides an exemplary implementation of the output handler 16 as described above with respect to FIGS. 9 to 11. As shown, the output handler includes a validity information evaluation unit 32, p multiplexers (MUX-1, MUX-2, . . . , MUX-p) 33, 34, 35, and p output registers (REG-1, REG-2, . . . , REG-p) 36, 37, 38, wherein p>0 denotes the order of parallelization. Each multiplexer is connected to the outputs of all but the first p registers of the DSR, while the validity information evaluation unit 32 is connected to the outputs of the corresponding registers of the VSR. Each multiplexer MUX-m with m=1, 2, . . . , p is adapted to selectively connect an output of one of said DSR registers to the input of its associated output register REG-m which, with the next event of the common clock signal, will output the data item stored in the selected DSR register. The selective connection established by each multiplexer MUX-m with m=1, 2, . . . , p is controlled by a configuration parameters om supplied by the validity information evaluation unit 32. Operatively, the validity information evaluation unit 32 evaluates, under the control of the control unit 12 of FIGS. 10 and 11, the validity information stored in said registers of the VSR (cf. step 93 of FIG. 9). In particular, it determines the positions of the p rightmost (last) set validity bits (cf. step 95) and derives p control parameters om, m=1, 2, . . . , p therefrom. When applied to said multiplexers, these control parameters ensure that the p valid data items stored at said positions in the DSR are forwarded to the p output registers, wherefrom they are output in the form of a subblock with the next event of the common clock signal (step 96). In addition, the validity information evaluation unit 32 controls the multiplexers so as to append dummy data items if less than p positions were found (not shown, cf. step 99) and resets the validity bits associated with output data items (not shown, cf. steps 96 and 99). As the skilled person will readily appreciate, the validity information evaluation unit 32 can also be part of the control unit 12 shown in FIGS. 10 and 11. From the above description with respect to FIGS. 6 to 9 and 14, it is clear that the multiplexers MUX-m of the output handler must be reconfigured/reprogrammed (by applying different sets of configuration parameters om) in each cycle of the common clock signal in order to allow for the output of the appropriate data items. It is to be noted that according to the description with respect to FIGS. 6, 9-11, and 14, the output handler is capable of delivering a continuous (uninterrupted) stream of subblocks at the rate of the common clock signal, wherein each subblock comprises p rate-matched data items (the last subblock possibly being padded with dummy data items). FIG. 15 shows a further embodiment of the flexible rate matching apparatus according to the present invention. This embodiment is characterized by a cascade structure. Herein, a plurality of flexible rate matching blocks 51, 52, 53 is connected in cascade. Each such block may have any structure as previously described with respect to any of the. FIGS. 4 to 14. The cascading of flexible rate matching blocks allows to realize complex recursive rate matching schemes (as described above with respect to the prior art) through recursively applying any of the flexible rate matching concepts according to the present invention. A further embodiment of the flexible rate matching apparatus according to the present invention will be described below with respect to FIGS. 16 to 18. This embodiment allows to further reduce implementational complexity while still meeting the other requirements. In fact, the operating speed (clock frequency) can even be increased as a consequence of the reduced complexity. FIG. 16 shows a block diagram of an exemplary configurable dual shift register together with parts of an exemplary control unit. Herein, FIG. 16a shows an overview block diagram that can be decomposed into an input section and a certain number of pipeline stages, while FIGS. 16b and c provide detailed views of two exemplary interfaces between adjacent pipeline stages. In its bottom part, FIG. 16a shows a configurable data shift register (DSR) in accordance with reference numeral 26 of FIGS. 10 or 11. As described above with respect to FIGS. 7 and 12a, a subblock comprising p data items is input into the first p registers (164) of the DSR in each cycle of a common clock signal. In general, p can assume any positive integer value, while typical values are 4, 8, 12, 16 etc. The configurable validity shift register (VSR, see ref. numeral 28 of FIG. 10 or 11) is not shown in FIG. 16a for conciseness reasons. It is assumed to have a structure identical to the one of the DSR. However, rather than data items, a subblock comprising p set validity bits is input into the first p registers of the VSR in each cycle of the common clock signal, as described above with respect to FIGS. 7 and 12a. In its upper part, FIG. 16a shows parts of an exemplary control unit in accordance with reference numeral 12 of FIGS. 10 or 11. These parts, which could for instance be included in the input and RM control unit 22 of FIG. 10 or the repeat/puncture module 30 of FIG. 11, are adapted to generate control signals (indicated by dashed arrows in FIG. 16) suitable for modifying the contents of the DSR and the VSR so as to achieve a rate matching. In each cycle of the common clock signal, a subblock comprising p rate matching flags (RM flags) is input into p registers (165) of said exemplary control unit. Herein, each RM flag is associated with one of the p data items input into the DSR (and thus also with one of the p validity bits input into the VSR); it indicates whether or not the corresponding data item (and validity bit) is to be rate-matched, i.e. repeated or punctured. As illustrated by the vertical dashed lines in the top part, the block diagram of FIG. 16a can be decomposed into an input section and p pipeline stages. The input section includes p registers 165 (part of the control unit) for storing RM flags, p registers 164 (part of the DSR) for storing data items and p registers (part of the VSR; not shown) for storing validity bits. Each pipeline stage is dedicated to the rate-matching of a particular one of the p data items contained in the subblock input into the DSR as well as to the rate-matching of its associated validity bits. Viewed from the right side to the left side, let the different pipeline stages have the indices 1, 2, . . . , p−1, p, as shown in the top part of FIG. 16a. Using this numbering convention (of course, other conventions are possible just as well), it can be stated that the jth pipeline stage is dedicated to the rate-matching of the j data item (of said subblock) stored in the j th register (from the bottom) of the p registers 164, wherein j=1, 2, . . . , p. Looking now in the direction of the signal flow, i.e. from left to right, it can thus be stated that first the pth (last) data item of said subblock is rate-matched in stage p (provided it needs to be rate-matched at all), then the (p−1)st data item in stage p−1, if applicable, and so on, until the 1st data item is rate-matched in stage 1, if applicable. As shown in FIG. 16a, each pipeline stage j (wherein j=1,2, . . . , p) includes a set of registers 161-j and a set of multiplexers 162-j connected to said set of registers, wherein both sets are part of the DSR. Each pipeline stage j further includes additional (such) sets of registers and multiplexers as part of the VSR (not shown). From stage 2 onwards, each stage j=2,3, . . . , p further includes an additional set of registers 163-j which is part of the control unit. In the DSR, the outputs of the p registers 164 of the input section are connected either directly or via the set of multiplexers 162-p (of stage p) to the inputs of the set of registers 161-p of stage p. Likewise, the outputs of the set of registers 161-j of stage j (wherein j=p, p−1, . . . , 2) are connected either directly or via the set of multiplexers 162-(j−1) (of stage j—1) to the inputs of the set of registers 161-(j−1) of the “subsequent” stage j−1, as will be shown below in more detail with respect to FIGS. 16b and 16c. Also, the sizes of the sets of registers 161-j in the DSR (and thus in the VSR) increase by one when the stage index j is decreased by one. While stage p contains p+1 DSR registers 161-p, stage p−1 contains p+2 DSR registers 161-(p−1), and so on, down to stage 1 which contains p+p=2*p DSR registers 161-1. In the control unit, the inputs of the set of registers 163-p of stage p are connected to outputs of the registers 165 of the input section, while the inputs of the set of registers 163-j of stage j (wherein j=p−1, p−2, . . . , 2) are connected to outputs of the set of registers 163-(j+1) of the “preceding” stage j+1, as will be shown below in more detail with respect to FIG. 17. Also, the sizes of the sets of registers 163-j in the control unit decrease by one when the pipeline stage index j is decreased by one. While stage p contains p−1 registers 163-p, stage p−1 contains p−2 registers 163-(p−1), and so on, down to stage 2 containing a single register 163-2. It is interesting to note that each stage comprises the same total number of registers in the control unit and the DSR, namely 2*p registers. In particular, in stage j=1,2, . . . , p, the control unit comprises j−1 registers in the set 163-j while the DSR comprises the remaining 2*p−(j−1) registers in the set 161-j. Of course, the VSR adds another 2*p−(j−1) registers in stage j. Each set of multiplexers 162-j with j=1, 2, . . . , p (of both DSR and VSR) is controlled by two control signals (dashed arrows) generated by the control unit. The first control signal, denoted “RM mode” in FIG. 16a, indicates whether repetition or puncturing operations are to be performed for a given data block if applicable for a given data item of said data block. The RM mode signal therefore is applied to all sets of multi-plexers 162-1,162-2, . . . ,162-p, including those of the VSR. The second control signal is derived from the RM flags indicating, for each of the p data items, whether or not the respective data item (and the associated validity bit) needs to be rate-matched. For this purpose, a second control input of the set of multiplexers 162-p of stage p is connected with one of the p registers 165 of the control unit's input section, while a second control input of the set of multiplexers 162-j of stage j (wherein j=p−1, p−2, . . . , 1) is connected with one register of the set of registers 163-(j+1) of the preceding stage j+1, as will be described below in more detail with respect to FIG. 17. It is to be noted that, in each stage, the control inputs of the DSR and VSR multiplexers are connected to the same pair of control signals. FIG. 16b provides a detailed view of the left dashed frame depicted in FIG. 16a. In other words, FIG. 16b shows the interface between the pipeline stages p and p−1 of the DSR, although it also applies to the respective interface of the VSR. On the left side of FIG. 16b, the set 161-p of p+1 registers part of pipeline stage p can be seen, while on the right side, the set 161-(p−1) of p+2 registers part of stage p−1 are shown. Herein, each register is marked with its index. The block diagram of FIG. 16b will be used in the following in order to illustrate the connections between the registers of stages p and p−1 necessary for the rate matching of the data item stored in the register p−1 of stage p, i.e. in register 166. Herein, the first (lower) p−2 registers of both stages are directly connected with each other, i.e. register 1,2, . . . , p−2 of pipeline stage p with register 1,2, . . . , p−2, respectively, of stage p−1. However, this does not apply to the remaining (upper) registers. With the help of four multiplexers 162-(p−1), which are all controlled by the same control signals, the input of each of the registers p−1, p, p+1, p+2 of stage p−1 can be connected to one of the outputs of the registers p−1, p, and p+1 of stage p, and ‘0’, depending on the values of the two control signals supplied by the control unit according to FIG. 16a. Thereby, it is determined whether, at the next clock event, the data item stored in register 166 will be copied to two (repetition), one (no rate matching) or zero (puncturing) destination registers of the subsequent stage p−1. For example, if the associated RM flag indicates that no rate matching is required for the data item stored in register 166, the multiplexers 162-(p−1) connect their outputs with the inputs designated with “N” (standing for NO rate matching), independent from the value of the RM mode signal. This is to say that the registers p−1, p, and p+1 of stage p−1 will be connected to the registers of stage p having the same indices, while register p+2 of stage p−1 will be connected with the value of ‘0’. More precisely, the register p+2 of stage p−1 of the VSR(!) will be reset (to zero, e.g.) so as to indicate invalidity of the corresponding data item, while the value of the data item stored in register p+2 of stage p−1 of the DSR(!) does not matter (“don't care” value) and will therefore be denoted “dummy data item”. For this reason, it can also be reset to zero, for instance, as indicated in FIG. 16b. In summary, it can thus be stated that with the multiplexers 162-(p−1) set to their “N” positions, the complete contents of the p+1 registers of stage p (161-p) will be copied to the first (bottom) p+1 registers of the subsequent stage p−1 (161-(p−1)) at the next clock event, while a dummy data item is appended and stored in the additional register p+2 of stage p−1. If, however, the associated RM flag indicates that the data item stored in register 166 needs to be repeated or punctured, the multiplexers 162-(p−1) connect their outputs with the inputs designated with “R” (for repetition) or “P” (for puncturing), depending on the value of the RM mode signal. If the RM mode signal is set so as to indicate repetition (“R”), both the registers p−1 and p of stage p−1 are connected with register 166 so that the data item stored therein will be repeated at the next event of the common clock signal. The registers p+1 and p+2 of stage p−1 are connected to the registers p and p+1, respectively, of stage p. If the RM mode signal is set so as to indicate puncturing (“P”), the registers p−1 and p of stage p−1are connected to the registers p and p+1, respectively, of stage p, while registers p+1 and p+2 of stage p−1 are connected to ‘0’ in order to receive dummy data items. In other words, the register 166 is not connected to any register of stage p−1 so that the data item contained therein will be punctured at the next clock event. FIG. 16c provides a detailed view of the right dashed frame depicted in FIG. 16a, i.e. of the interface between the pipeline stages 2 and 1 of the DSR.(and thus of the VSR, too). On the left side of FIG. 16c, the 2*p−1 registers 161-2 part of stage 2 can be seen, while on the right side, the 2*p registers 161-1 of stage 1 are shown. Since the block diagram of FIG. 16c is devoted to the rate matching of the data item stored in the first (bottom) register of stage 2, i.e. in register 167, multiplexers 162-1 are connected to the inputs of all registers of stage 1 (161-1). If no rate matching (“N”) is required for this data item, the registers of stage 2 will be connected with the registers of stage 1 having the same indices., while the (top) register 2*p of stage 1 will be connected to ‘0’ (dummy data item). In case of repetition, register 167 will be connected to the two (bottom) registers 1 and 2 of stage 1, while register j=2, 3, . . . , 2*p−1 of stage 2 will be connected to the respective register j+1=3, 4, . . . , 2*p of stage 1. If the data item stored in register 167 needs to be punctured, this register will not be connected to any register of stage 1, while the register j=2, 3, . . . , 2*p−1 of stage 2 will be connected to the respective register j−1=1, 2, . . . , 2*p−2 of stage 1 and the registers 2*p−1 and 2*p of stage 1 will be connected to ‘0’. Note that in stage 1, the valid items, i.e. the rate-matched data items, will be collected in the bottom registers of the set 161-1 of DSR registers with no gaps in between, while the invalid items, i.e. the dummy data items, are collected in the top registers thereof. This will be explained in more detail with respect to FIG. 17. FIGS. 17a and 17b show repetition, puncturing and shift operations performed in an exemplary configurable dual shift register according to FIG. 16. Using the arrangement of registers in the control unit and the DSR as shown in FIG. 16 and also the reference numerals of FIG. 16, FIGS. 17a and 17b illustrate how an exemplary subblock of p=6 data items I1,I2, . . . ,I6 stored in the registers 164 and an exemplary subblock of p=6 associated RM flags stored in the registers 165 successively propagate through the p=6 pipeline stages as a consequence of p=6 subsequent clock events. For this purpose, the registers shown in FIGS. 17a and b are marked with the contents stored therein in a particular period of the common clock signal rather than with their indices, as was the case in FIGS. 16b and 16c. The subblock of RM flags is assumed to have the value “101001” meaning that the 1st, 3rd and 6th data items in the subblock of data items need to be rate-matched while no rate-matching is to be performed for the 2nd, 4th and 5th data items (the same applies to the subblock of associated validity bits). The RM mode signal is set so as to indicate a mode of repetition (“R”) in FIG. 17a and a mode of puncturing (“P”) in FIG. 17b. Fixed (“hardwired”) connections are marked with thin arrows in FIGS. 17a and b, while switched connections are indicated by thick arrows. This is, instead of displaying the multiplexers of FIG. 16, FIGS. 17a and 17b show the connections established by the multiplexers as a consequence of the control signals resulting from the assumed values of the RM flags and RM mode signals. Hence, the control signals determine the origins (and thus the directions) of the thick arrows. They are marked with dashed lines in FIGS. 17a and 17b. Referring to the repetition case considered in FIG. 17a, the subblocks of data items I1, . . . ,I6 and RM flags “101001” are stored in the sets of registers 164 and 165, respectively, in a first period of the common clock signal. Herein, the RM flag associated with the last data item is stored in the top (hatched) register of the set 165. Having a value of one, this RM flag indicates that the data item 16 stored in the top (hatched) register of the set 164 is to be rate-matched. Together with the RM mode signal (set to “R”), the two multiplexers between the input section and the 6th pipeline stage of the DSR are controlled so as to establish the connections indicated by the two thick arrows in FIG. 17a. Given these two switched connections and the other five fixed connections between the input section and the 6th stage of the DSR, it becomes clear that data item I6 will be copied twice to the 6th stage at the next clock event while the other data items will be copied only once. After this clock event, the 6th stage of the DSR thus contains the p+1=7 items I1,I2,I3,I4,I5,I6,I6 so that I6 has been repeated, while the 6th stage of the control unit contains just those RM flags associated with the first five data items (the RM flag associated with the 6th data item has already been used and is therefore discarded). Now, the RM flag stored in the top (hatched) register of the set 163-6 and associated with the second last (5th) data item I5 stored in the 5th (hatched) register of the set 161-6, has a value of zero so that all four multiplexers between the 6th and 5th stages of the DSR establish horizontal connections (see FIG. 17a). After the next clock event, the 5th stage of the DSR therefore will contain the contents of the preceding (6th) stage with an appended dummy data item: I1,I2,I3,I4,I5, I6,I6, ‘0’. As the RM flag stored in the top (hatched) register of 163-5 and associated with I4 stored in the 4th (hatched) register of 161-5 also has a zero value, the six multiplexers between the 5th and 4th stages of the DSR will be controlled so as to append, at the next clock event, another dummy data item. Thus, after this clock event, the fourth stage of the DSR will contain the p+3=9 items I1,I2,I3,I4,I5,I6,I6, ‘0’,‘0’. With the RM flag associated with I3 and stored in the top (hatched) register of 163-4 having a value of one, the eight multiplexers between the 4th and 3rd stages of the DSR are controlled so as to establish the connection indicated by the corresponding eight thick arrows in FIG. 17a. As a result,I3 (stored in the 3rd (hatched) register of 161-4) will be repeated at the next clock event so that the third stage will store the p+4=10 items I1,I2,I3,I3,I4,I5,I6,I6,‘0’,‘0’. At the next clock event, another dummy data item will be appended by establishing 10 horizontal connections between the 3rd and 2nd stages of the DSR as a consequence of the zero value of the RM flag associated with I2 and stored in the top (hatched) register of 163-3. Finally, at the next clock event,I1 (stored in the 1st (hatched) register of 161-2) will be copied twice and thus repeated by establishing the 12 connections shown in FIG. 17a between the 2nd and 1st stages of the DSR as a consequence of the one value of the RM flag associated with I1 and stored in 163-2. The first stage of the DSR will therefore contain the 2*p=12 items I1,I1,I2,I3,I3,I4,I5,I6,I6,‘0’,‘0’,‘0’, thereby confirming that the first, third, and sixth data items (I1,I3,I6) have been repeated in response to the p=6. RM flags “101001” while appending a total of three dummy data items to the nine rate-matched data items. From the above description with respect to FIG. 17a, it can be concluded that the number of multiplexers and thus the number of switched connections begins with a value of two in stage p=6 and thereafter increases by two from stage to stage (left to right in FIG. 17a) until a value of 2*p is reached in stage 1. The total number of multiplexers thus amounts to p*(p+1)=42 in this example. Also, it can be concluded that a zero value of the RM flag associated with the jth data item (wherein j=1,2, . . . , p) controls the multiplexers of stage j so as to establish horizontal connections thereby appending a dummy data item at the next clock event. In contrast, a “1” value of the RM flag associated with the j data item controls the multiplexers of stage j so as to establish a single1 horizontal connection towards the j register of stage j, while diagonal connections pointing to the top right corner are established towards the registers j+1,j+2, . . . ,2*p+1−j of stage j. 1 Not counting the fixed horizontal connections. With the RM mode signal set to “P”, FIG. 17b refers to the puncturing case. Since the same subblock of RM flags is applied here (“101001”), the control signals derived from the RM flags are identical to those of FIG. 17a. For those RM flags having a value of zero, the value of RM mode does not matter, as no rate-matching is to be performed anyway. This applies to the RM flags associated with the 2nd, 4th, and 5th data items (I2,I4,I5) which control the multiplexers of the stages 5, 4, and 2 so as to establish horizontal connections between the stages 6-5, 5-4, and 3-2 identical to the ones shown in FIG. 17a. However, for the RM flags having a value of one, i.e. for those associated with I1,I3,I6, different connections are established by the multiplexers of the stages 1, 3 and 6 (compared with FIG. 17a) due to the RM mode signal indicating that puncturing rather than repetition operations are to be performed. Consider for instance the RM flag associated with the last data item (I6) and stored in the top (hatched) register of the set 165. Having a value of one, this RM flag indicates that the data item I6 (stored in the top (hatched) register of the set 164) is to be rate-matched. Together with the RM mode signal (set to “P”), the two multiplexers between the input section and the 6th pipe-line stage of the DSR are controlled so as to establish the connections indicated by the two thick arrows in FIG. 17b. Given these two switched connections and the other five fixed connections between the input section and the 6th stage of the DSR, it becomes clear that data item I6 will not be copied to the 6th stage at the next clock event. Instead, it will be replaced with a dummy data item (‘0’) and an additional dummy data item will be appended. After this clock event, the 6th stage of the DSR thus contains the p+1=7 items I1,I2,I3,I4,I5,‘0’,‘0’ so that I6 has been punctured. Similar operations are performed for the RM flags associated with I3 and I1. Instead of the data item to be punctured (say I3, stored in the 3rd (hatched) register of 161-4), the value in the register above it (I4, stored in the 4th register of 161-4) is forwarded to the subsequent stage (161-3) without generating a gap (3rd register of 161-3). Also, the contents of the further registers above said data item to be punctured (5th, 6th, etc. registers of 161-4) are forwarded to the subsequent stage without generating a gap (4th, 5th, etc. registers of 161-3). As a consequence, two dummy data items must be appended in order to take into account that the subsequent stage comprises one register more than the preceding one. Finally, the first stage of the DSR contains the 2*p=12 items I2,I4,I5,‘0’,‘0’,‘0’,‘0’,‘0’,‘0’,‘0’,‘0’,‘0’, thereby confirming that the first, third, and sixth data items (I1,I3,I6) have been punctured in response to the p=6 RM flags “101001” while appending a total of nine dummy data items to the three rate-matched data items. It can be concluded from FIG. 17b that a “1” value of the RM flag associated with the jth data item controls the multiplexers of stage j so as to establish a single2 horizontal connection towards the last (top) register of stage j, while diagonal connections pointing to the bottom right corner are established towards the registers j,j+1, . . . ,2*p−j of stage j. 2Not counting the fixed horizontal connections. From the above description with respect to FIGS. 17a and 17b, it can be seen that in both the repetition and the puncturing case, a subblock comprising 2*p items is available at the output of stage 1 of the DSR. It contains rate-matched data items as well as appended dummy data items. Herein, the number of rate-matched data items can range from 0 (all data items punctured) to 2*p (all data items repeated). Due to the fact that the VSR has exactly the same structure as the DSR and receives the same control signals, precisely the same operations are performed in the VSR and the DSR. The only difference is that validity bits having a value of one propagate through the pipeline stages of the VSR. Therefore, stage 1 of the VSR will contain values of one (indicating validity) in those (bottom) registers, where stage 1 of the DSR contains rate-matched data items, while it will contain values of zero (indicating invalidity) in those (top) registers, where stage 1 of the DSR contains dummy data items. Comparing the configurable dual shift register described above with respect to FIGS. 16 and 17 with the embodiment according to FIGS. 4-14, the following can be stated. According to FIGS. 16 and 17, repetition operations are performed by repeating a single data item (and its associated validity bit) at a time, i.e. in a given pipeline stage. This allows to limit the number of source registers to three for each destination register in a given stage. This is in contrast to the embodiment described above with respect to FIGS. 4, 8, 12, where the number of source registers, which must be connectable to a destination register, amounts to p+1 in order to implement variable shift orders between p and 2p. Moreover, according to FIGS. 16 and 17, puncturing operations are performed by removing the respective data item together with its associated validity bit. This is in contrast to the embodiment described above with respect to FIGS. 5, 8, where puncturing operations are performed by resetting the associated validity bit while leaving untouched the data item to be punctured. Concerning the requirements on rate matching implementations as formulated in the above section relating to the prior art, the following can be stated. According to FIG. 16a, the DSR comprises a total of p+1 stages (p pipeline stages plus an input section) consisting of (p+2*p)/2=1.5*p registers on average. The total number of registers in the DSR thus amounts to Nreg=1.5*p*(p+1). (9) With p having a value of 12 in exemplary rate matching apparati implemented by the applicant, merely Nreg=234 registers are required for the DSR. The same modest number of registers applies to the VSR, of course. It is important to note that the number of registers according to equation (9) does not depend on the maximum number |A| of data items to be rate-matched in a coded data block (for a definition of A, see equation (2) and the related description). This is in contrast to the embodiment described above with respect to FIG. 12, where the total number of registers in the DSR amounts to Nreg=p*(|ASub|+1)≈|A|+p, (10) as can be seen from equations (8) and equations (3)-(5). Given the fact that |A| can assume values as high as 1000 or even 10000, it becomes clear that the configurable dual shift register described above with respect to FIG. 12 requires many more registers when compared with the embodiment according to FIG. 16. When comparing the dual shift register embodiments according to FIGS. 12 and 16, a further reduction in hardware complexity is associated with the multiplexers. According to the embodiment of FIG. 12, multiplexers are required at the input of almost all registers of the DSR and VSR. More precisely, a total number of about |A| multiplexers is required in the DSR and also in the VSR. In contrast, the embodiment of FIG. 16 only requires (p+1)*p multiplexers in the DSR and also in the VSR, i.e. 156 for p=12. In addition, the complexity of each multiplexer is reduced in the embodiment of FIG. 16. While relatively complex multiplexers with p+1 inputs are needed in accordance with FIG. 13 so as to implement variable order shift operations in the dual shift register of FIG. 12, relatively simple multiplexers with three inputs are sufficient according to FIG. 16b and c. As the skilled person will appreciate, less complex multiplexers between the register stages imply that the common clock frequency of the configurable dual shift register can be increased significantly, thereby allowing for higher input bit rates and/or lower delay values. In addition, the hardware effort necessary to generate the control signals for the multiplexers is less complex in case of the embodiment described above with respect to FIG. 16. In summary, it can be stated that the embodiment described above with respect to FIG. 16 (and 17) requires fewer registers, fewer and less complex multiplexers and a simpler control unit, thereby allowing for less complex rate matching apparati capable of coping with very high input rates and revealing low delay values while still meeting the other requirements formulated above in the section relating to the prior art. FIG. 18a shows a block diagram of an exemplary output handler adapted to the configurable dual shift register described above with respect to FIG. 16. It includes a data collection register (DCR) 181, a validity collection register (VCR) 182, and a validity information evaluation unit 183 connected to both the DCR 181 and the VCR 182. The DCR 181 and the VCR 182 include 4*p−1 registers each. The DCR 181 is connected to the set of 2*p registers 161-1 in stage 1 of the DSR as described above with respect to FIGS. 16a and c. Likewise, the VCR 182 is connected to the 2*p registers in stage 1 of the VSR. The DCR 181 and the VCR 182 are adapted to receive, at the rate of the common clock signal, subblocks comprising 2*p items from the DSR and the VSR, respectively. In each cycle of the common clock signal, the validity information evaluation unit 183 evaluates the validity bits stored in the VCR 182 and determines a value of a variable insertion point therefrom. This variable insertion point is then applied as a starting address to both DCR and VCR. This is, the next subblocks from the DSR and VSR will be written into the DCR and VCR, respectively, from said starting address onwards. This is indicated in FIG. 18a by the two sets 184 of arrows. From the contents of the DCR 181, output subblocks of rate-matched data items are generated, at the rate of the common clock signal, as follows. Whenever at least 2*p valid items are stored in the DCR 181, a subblock comprising 2*p rate-matched data items will be output. However, whenever less than 2*p valid items are stored in the DCR 181, the subblock size will be reduced to zero (i.e. no output will be generated) until the DCR 181 contains at least 2*p valid items. The operations performed in the exemplary output handler of FIG. 18a will be described in more detail with respect to FIGS. 18b to 18d. Herein, for ease of illustration, a value of p=3 is assumed so that the DCR and VCR comprise 4*p−1=11 registers each. FIGS. 18b to 18d display the contents of the DCR 181 and VCR 182 in three subsequent cycles of the common clock signal. The subblocks input from the DSR in three subsequent cycles are denoted SB1, SB2, SB3 etc. Herein, each subblock comprises 2*p=6 items which can either be valid items (rate-matched data items) or invalid items (dummy data items), as described above with respect to FIG. 17. In FIGS. 18b to 18d, validity and invalidity is indicated by marking the corresponding register of the VCR with a value of one and zero, respectively. In FIG. 18b, it is assumed that subblock SB1 has been stored already in the bottom 2*p=6 registers of the DCR 181. As can be seen from the contents of the VCR 182, it is further assumed that SB1 contains 5 valid items (rate-matched data items) and a single invalid item (appended dummy data item). Given this scenario, when scanning the contents of the VCR “from bottom to top”, the validity information evaluation unit 183 would determine that the first zero value is stored in the sixth register of the VCR designated with reference numeral 185. Therefore, the starting address (variable insertion point) would be set to 6, as indicated by two horizontal arrows in FIG. 18b. As a consequence, the next subblocks from the DSR (SB2) and VSR will be applied to the top six registers, i.e. registers 6,7, . . . ,11, of the DCR and VCR, respectively, as indicated in FIG. 18b by the two parentheses. As a further consequence, the validity information evaluation unit 183 would prevent the DCR from generating an output at the next clock event, because less than 2*p=6 valid items, namely 5, are stored in the DCR. FIG. 18c displays the contents of the DCR and VCR after said next clock event. Subblock SB2 has been written into the top six registers of the DCR, thereby overwriting the final invalid item of subblock SB1. As can be seen from the top six registers of the VCR, it is assumed in FIG. 18c that SB2 contains three valid and three invalid items. Again, the validity information evaluation unit 183 would scan the contents of the VCR and determine that the first zero value now is stored in the 9th register of the VCR (register 186). Consequently, 2*p=6 valid items can be output from the bottom 2*p=6 registers of the DCR at the next clock event, as indicated in the bottom right part of FIG. 18c. In order to take into account the fact that the valid items which will have been output will need to be shifted “off” the DCR, the starting address is not set to 9 here, but to 9−2*p=3, as indicated by the horizontal arrows in FIG. 18c. Therefore, the next subblocks are applied to the registers 3,4, . . . ,8 of the DCR and VCR, respectively, as shown by the two left parentheses in FIG. 18c. Upon shifting down the contents of both the DCR and VCR by 2*p=6 register locations at said next clock event, they will enter the DCR and VCR. FIG. 18d displays the contents of the DCR and VCR after said next clock event. Due to the shifting down, all valid data items of SB1 and the first valid data item of SB2 have disappeared from the DCR. Also, the associated validity bits from the VCR have disappeared. On the other hand, the final two valid items of SB2 and their validity bits now occupy the bottom two registers of the DCR and VCR, respectively. Also, subblock SB3 and its associated validity bits are now stored in registers three to eight of the DCR and VCR, respectively. Assuming that SB3 contains four valid items, a total of six valid items is thus available in the DCR again, so that another output subblock of 2*p=6 rate-matched data items will be generated at the next clock event. With the first zero value being stored in the 7th register (187) of the VCR, the starting address will be determined as 7−2*p=1 in analogy with the procedure described above with respect to FIG. 18c. As a result, SB4 and its associated validity bits will be applied to the bottom six registers of the DCR and the VCR, respectively, as indicated in FIG. 18d. They will enter the DCR and VCR once their contents has been shifted down by 2*p=6 register locations. In summary, it can thus be stated that subblocks comprising 2*p rate-matched data items are output at the next clock event (followed by a down-shift of order 2*p) whenever at least 2*p valid items are present in the DCR beforehand. The starting address is set to the address of the register where the first (from bottom to top) zero validity bit is stored in the VCR, provided that this register is part of the bottom 2*p registers of the VCR. Otherwise, the starting address is set to the address of this register minus 2*p in order to make sure that sufficient space is available for the subsequent subblocks (hence the total number 4*p−1 of registers). From this, it can be seen that the variable insertion point, i.e. the starting address, may vary in a range of 1, 2, . . . , 2*p. It is to be noted that according to the description with respect to FIG. 18, the output handler is capable of delivering a stream of subblocks at the rate of the common clock signal, wherein (in contrast to the description with respect to FIGS. 9 and 14) each subblock comprises either 2p or zero rate-matched data items (the last subblock possibly being padded with dummy data items). In so far, the stream of subblocks output by the output handler is not fully continuous. Concerning the requirements on rate matching implementations as formulated in the above section relating to the prior art, the following can be stated. In accordance with FIG. 18a, the output handler includes a total of 2*(4*p−1) registers in the collection registers 181 and 182. In addition, the same number of multiplexers is used at the inputs of these registers so that the subblocks can be input at a variable insertion point (starting address). Herein, each multiplexer must have 2*p inputs connected to the 2*p registers of stage 1 of the DSR/VSR. The validity information evaluation unit 183 is required to search, in each cycle of the common clock signal, for a single zero in a total of 4*p−1 registers of the VCR. In contrast, the output handler according to FIG. 14 includes p registers and p multiplexers, only. However, each multiplexer is required to have a very high number of inputs, namely |A|≈Nreg−p. In addition, the validity information evaluation unit is required to search, in each clock cycle, for p ones in a very high number of registers in the VSR, namely in |A| registers thereof. Given typical values of 1000 or even 10000 for |A|, it is clear from the above that the output handler of FIG. 18a further reduces complexity due to the less complex multiplexers and validity information evaluation unit. As the skilled person will readily appreciate, a cascade structure according to FIG. 15 is also possible for the apparatus described above with respect to FIG. 16-18. Further, from the description given above with respect to the present invention it is clear that the present invention also relates to a computer program product directly loadable into the internal memory of a telecommunication unit (such as a transceiver or transmitter of a base station or a mobile phone etc.) for performing the steps of the inventive flexible rate matching process in case the product is run on a processor of the communication unit. Also, the invention relates to a processor program product stored on a processor usable medium and provided for flexible rate matching comprising processable readable program means to carry out any of the steps of the inventive flexible rate matching process. Therefore, this further aspect of the present invention covers the use of the inventive concepts and principles for flexible rate matching within, e.g., mobile phones adapted to future applications. The provision of the computer program products allows for easy portability of the inventive concepts and principles as well as for a flexible implementation in case of re-specifications of the rate matching scheme(s). The foregoing description of preferred embodiments has been presented for the purpose of illustration and description. It is not intended to be exhaustive or to limit the invention to the precise form disclosed. Obvious modifications or variations are possible in the light of the above technical teachings. The embodiments have been chosen and described to provide the best illustration of the principles underlying the present invention as well as its practical application and further to enable one of ordinary skill in the art to utilize the present invention in various embodiments and with various modifications as are suited to the particular use contemplated. All such modifications and variations are within the scope of the invention as determined by the appended claims. List of Abbreviations 3G: third generation 3GPP: third generation partnership project ARIB: Japanese standardization body ASIC: Application specific integrated circuit BS: Base station DB: Data block DSP: Digital signal processor DSR: Data shift register ETSI: European Telecomm. Standardization Institute FDD: Frequency division duplex FPGA: Field programmable gate array GSM: Global system for mobile communications MT: Mobile terminal/station PSTN: Public switched telephone network RMS: Rate matching scheme SB: Subblock TS: Technical specification VI: Validity information VSR: Validity shift register WCDMA: Wideband code division multiple access List of Symbols A: the number of data items (bits, e.g.) to be repeated or removed (“punctured”) by the rate matching apparatus/method is denoted |A|, a: number of data items (bits, e.g.) to be repeated or removed (“punctured”) in the subblock under consideration by the rate matching apparatus/method, C: number of data items (bits, e.g.) in the coded data block, i.e. the size (length) of the coded data block (input data block), CSub: number of subblocks in the coded data block (input data block), [clk i]: i-th clock event of the (common) clock signal, K: number of bits in the uncoded data block, i.e. size (length) of the uncoded data block, M: target block size (length), i.e. the number of data items (bits, e.g.) in the rate-matched data block (output data block), MSub: number of subblocks in the rate-matched data block (output data block), Nreg: total number of memory locations (registers) in each shift register (DSR/VSR), om: configuration parameter for the multiplexer MUX-m of the output handler, p: order of parallelization, number of data items (bits, e.g.) in each subblock, rj: j-th register of a shift register (DSR/VSR), s: order/width of a shift (operation), sj: configuration parameter for the multiplexer MUX-j of the configurable shift register (DSR/VSR), SB(i): i-th (input) subblock, v: number of set validity bits stored in the VSR.

<SOH> FIELD OF THE INVENTION <EOH>The present invention relates to rate matching in the baseband part of a transmitter or a transceiver of a telecommunication system, and in particular to a flexible rate matching implementation.

<SOH> SUMMARY OF THE INVENTION <EOH>In view of the above, the object of the invention is to develop a flexible rate matching implementation at minimal costs (low complexity). According to the present invention, this object is achieved through a flexible rate matching apparatus having the features of claim 1 and also through a flexible rate matching method having the features of claim 9 . Therefore, the flexible rate matching apparatus and method according to the present invention rely on the provision of a dual shift register comprising a configurable data shift register (DSR) and a configurable validity shift register (VSR). In particular, the VSR enables to use validity information (VI), also referred to as indications of validity, as masking information, wherein bits (or data items comprising one or several bits) to be punctured are invalidated without further modification of the contents of the DSR. In case of repetition, the necessary memory space in the DSR may easily be provided through appropriate shifting of subsequent data items in the DSR and appropriate setting of the indications of validity (validity bits) in the VSR. This enables the output of valid data items using the validity information stored in the VSR. Therefore, the proposed flexible rate matching implementation is highly flexible in the way that a multitude of transport channel types, i.e. sizes C of input data blocks (coded data blocks), may be supported according to, e.g., 3G requirements. Further, the provision of the VSR allows to support, for each input data block, various kinds of rate matching schemes (RMS 1 , RMS 2 , etc.) as described above with respect to the prior art. Further, the proposed solution supports repetition and puncturing in one functional block which minimizes hardware complexity while ensuring the above-mentioned capabilities and flexibility. A further benefit of the proposed solution is that a flexible rate matching can be achieved on a continuous stream of data items (and also resulting in a continuous output data stream) without temporarily storing a complete input data block so that only a small memory is necessary and the overall delay is minimized. According to a preferred embodiment of the present invention it is proposed that a plurality of data items are handled as subblocks during each cycle of the (common) clock signal. In other words, the inventive flexible rate matching approach allows to process a plurality of data items in parallel (i.e. concurrently, simultaneously) during each cycle of the (common) clock signal. Therefore, the inventive flexible rate matching can cope with extremely high data rates required for, e.g. 3G standards. Therefore, these standards may be supported by still using fast turnaround and easily available FPGA and ASIC technologies. Also with this processing of data items it is possible to work on a continuous data stream without storage of a complete input data block. Again, only a small dual shift register for buffering some of the data items is sufficient, the length of the dual shift register being related to the total number |A| of data items to be rate-matched in an input data block. According to a further preferred embodiment, the dual shift register and the output handler are controlled by an input and RM (rate matching) control unit and an output control unit, respectively. These control (sub) units are controlled by a flexible RM control unit which coordinates and synchronizes the operations of said two (sub)units. Preferably, the positions of data items which need to be rate-matched (puntured or repeated) according to the rate matching scheme to be employed, can be determined (calculated) in a separate computation unit/step. This allows to achieve flexible rate matching in a fully programmable way so that changes in a standard can be incorporated with extremely low efforts. According to another preferred embodiment, in order to perform puncturing operations, the indications of validity (validity bits) associated with data items to be punctured are set to a value indicating non-validity. For example, they can be reset to zero to indicate that the corresponding data item is to be considered invalid (and thus is not to be output). In order to perform repetition operations, both the data items to be repeated and their associated indications of validity (i.e. the associated set validity bits) are each shifted to at least two memory locations (registers) of the data shift register and the validity shift register, respectively. These features lead to a simplified implementation of the flexible rate matching approach with a single hardware structure being able to meet all requirements. According to another preferred embodiment, rate-matched data items are continuously output. Herein, only valid data items are output, i.e. the data items having an associated indication of validity (validity bit) indicating validity (by a set validity bit, e.g.). With a continuous stream of output data items, the delay of the flexible rate matching approach can be minimized (thus maximizing the throughput). According to another preferred embodiment, in order to perform puncturing operations, both the data items to be punctured and their associated indications of validity (i.e. the associated set validity bits) are shifted to no memory location (register) of the data shift register and the validity shift register, respectively. In order to perform repetition operations, both the data items to be repeated and their associated indications of validity (i.e. the associated set validity bits) are each shifted to two memory locations (registers) of the data shift register and the validity shift register, respectively. These features lead to a further simplified implementation of the flexible rate matching approach while still meeting the other requirements. According to another preferred embodiment, rate-matched data items are output on a not fully continuous basis, i.e. no output may be generated at some points in time, although the output rate still is equal to the rate of the common clock. With a stream of output data items which is not entirely continuous, the requirements of subsequent functional blocks such as interleavers can be met. According to another preferred embodiment, said dual shift register includes at least two pipeline stages each having a different number of memory locations. By providing the dual shift register with pipeline stages comprising, from stage to stage, a different number of memory locations (registers), complexity can be further reduced because the rate-matching can be done for a single data item (and associated validity bit) at a given time (in a given pipeline stage). According to a preferred embodiment of the present invention it is proposed to carry out the flexible rate matching using a cascade structure. By cascading the flexible rate matching apparatus according to the present invention it is possible to realize a recursive rate matching algorithm hardware. In particular, a complex recursive rate matching algorithm may be implemented using a plurality of. flexible rate matching apparatuses according to the present invention. It is possible to calculate parameters in a separate computation device and to then write them into a storage of each of the flexible rate matching apparatuses. Also, it should be noted that the cascade structure of flexible rate matching apparatuses is suitable both for the serial and parallel implementation. According to another preferred embodiment of the present invention there is provided a computer program product directly loadable into the internal memory of a mobile communication unit comprising software code portions for performing the inventive flexible rate matching process when the product is run on a processor of the mobile communication unit. Therefore, the present invention is also provided to achieve an implementation of the inventive method steps on computer or processor systems. In conclusion, such implementation leads to the provision of computer program products for use with a computer system or more specifically a processor comprised in e.g., a mobile communication unit. This program defining the functions of the present invention can be delivered to a computer/processor in many forms, including, but not limited to information permanently stored on non-writable storage media, e.g., read only memory devices such as ROM or CD ROM discs readable by processors or computer I/O attachments; information stored on writable storage media, i.e. floppy discs and harddrives; or information convey to a computer/processor through communication media such as network and/or telephone networks via modems or other interface devices. It should be understood that such media, when carrying processor readable instructions implementing the inventive concept represent alternate embodiments of the present invention.

20041216

20081014

20050519

61543.0

CHASE, SHELLY A

APPARATUS AND METHOD FOR FLEXIBLE DATA RATE MATCHING

UNDISCOUNTED

ACCEPTED

ACCEPTED

Radio communication system, radio communication device, radio communication method, and computer program

It is necessary to solve problems caused when constituting a communication system such as a radio LAN using an independent distributed type network without the controlling-controllable relationship of a master station and a slave station. In the radio communication system consisting of a plurality of communication stations having no relationship of a controlling station and a controllable station, each communication station transmits a beacon describing information on the network, thereby constituting a network. Through this beacon, it is possible to make a sophisticated judgment on the communication state in the other communication station.

1. A wireless communication system composed of a plurality of communication stations without a relationship of a control station and controlled stations, wherein respective communication stations transmit beacons with information concerning a network described thereon with each other to configure said network. 2. A wireless communication system according to claim 1, wherein said information concerning the network is information indicating whether the local station is aware of the presence of beacons the respective stations transmitted. 3. A wireless communication system according to claim 1, wherein each of said communication stations configure said network transmits a beacon signal at a predetermined time period. 4. A wireless communication system according to claim 3, wherein each of said communication stations performs reception continuously over a time period longer than its own beacon transmission interval at least once at a predetermined time. 5. A wireless communication system according to claim 2, wherein said communication station, which became aware of approach of a time at which other station plans to transmit a beacon with reference to a clock value memorized in the local station, transmits information for prohibiting a neighboring station from transmitting data over a predetermined time period. 6. A wireless communication system according to claim 2, wherein said information indicating whether the local station is aware of the presence of a beacon signal the respective stations transmitted is information indicated by a relative time at which the local station transmits a beacon signal. 7. A wireless communication system according to claim 2, wherein each of said communication station determines a beacon transmission timing of the local station based on information obtained from a beacon signal which the local station can receive from other station. 8. A wireless communication system according to claim 7, wherein each of said communication stations continues to receive a beacon from other station over a predetermined time period before starting transmitting a new beacon, it memorize reception time information of a received beacon transmitted from other station as first information, and it shifts said information described in said received beacon indicating whether the local station is aware of a presence of beacon based upon said first information, and it memorize the shifted information as second information. 9. A wireless communication system according to claim 8, wherein said communication station extracts a reception timing of a beacon, which the local station or other station can receive, from said second information, and it determines a target interval, which an interval in which a beacon reception time space becomes a maximum beacon space, and it sets a beacon transmission timing of the local station to a central time of said target interval. 10. A wireless communication system according to claim 9, wherein each of said communication stations attempts to receive a signal transmitted from other station during a predetermined time period and it memorize a time zone a beacon and other signal are received with a low frequency as third information. 11. A wireless communication system according to claim 10, wherein said communication station extracts each beacon space information, it determines a target interval, which an interval corresponding to a time zone with a low frequency at which a signal obtained from said third information, and it sets a beacon transmission timing of the local station to a central time of said target interval. 12. A wireless communication system according to claim 7, wherein said communication station which received alteration request message of a beacon transmission timing from other station determines a new beacon transmission timing. 13. A wireless communication system according to claim 1, wherein said information concerning the network is information indicating whether the local station is in reception state in which a timing beacon signals transmit. 14. A wireless communication system according to claim 13, wherein said information indicative of whether the local station is in reception state in which timing beacon signal transmit is information indicated by a relative time from a timing the local station transmit beacon. 15. A wireless communication system according to claim 13, wherein said specific time zone in which said beacon signal is transmitted is set to a transmission prohibit interval. 16. A wireless communication system according to claim 1, wherein said beacon transmission timing of said communication stations within said network is delayed a predetermined target beacon transmission timing by a random time, and describe information indicative of a delayed amount in said beacon. 17. A wireless communication system according to claim 16, wherein said communication station, which became aware of approach of a time at which other station plans to transmit a beacon with reference to a clock value memorized in the local station, transmits information for prohibiting a neighboring station from transmitting data over a predetermined time period. 18. A wireless communication system according to claim 16, wherein when each of said communication systems receives a beacon from other communication station, it calculates a target beacon transmission timing of said beacon transmission station from a beacon reception time in consideration of a time indicative of said delay amount. 19. A wireless communication system according to claim 18, wherein said communication station adjusts a clock of the local station in accordance with a timing of other station, when there is difference between a target beacon transmission timing of other station predicted from the clock value memorized in local station and a target beacon transmission timing which results from subtracting a timing at an intentionally delayed beacon transmission time described in a beacon from which a beacon was received in actual practice from. 20. A wireless communication system according to claim 19, wherein said communication station adjusts a clock of the local station to a timing of other station, when the target beacon transmission timing of the beacon transmission station is delayed from the target beacon transmission time predicted by the local station. 21. A wireless communication system according to claim 16, wherein each of said communication stations describes the effect thereof in said beacon if said beacon transmission time is delayed due to an external primary factor when it transmits a beacon. 22. A wireless communication system according to claim 16, wherein said random time with which the beacon transmission timing is delayed from the target beacon transmission timing is given in the form of a pseudorandom sequence and the value of said pseudorandom sequence is transmitted as information indicative of a delayed amount described in said beacon. 23. A wireless communication system according to claim 22, wherein each of said communication stations memorizes the value of said pseudorandom sequence described in said beacon and it calculates the next beacon transmission timing of said beacon transmission station by updating a pseudorandom sequence value of every predetermined period. 24. A wireless communication system according to claim 1, wherein it sets a predetermined time period in which a beacon transmission station can transmit a packet with a priority after has transmitted said beacon signal. 25. A wireless communication system according to claim 24, wherein it sets a time period in which each communication station transmit packet based upon predetermined contention control, after said predetermined time period in which said beacon transmission station can transmit a packet with a priority has expired. 26. A wireless communication system according to claim 25, wherein said communication station which communicates with said beacon transmission station can transmit a packet with a priority at said predetermined time period in which said beacon transmission station can transmit a packet with a priority. 27. A wireless communication system according to claim 24, wherein said communication station, which became aware of approach of a time at which other station plans to transmit a beacon with reference to a clock value memorized in the local station, transmits information for prohibiting a neighboring station from transmitting data over a predetermined time period. 28. A wireless communication system according to claim 24, wherein each of said communication stations recognizes the state in which it does not receive a signal from other station over a predetermined time period calculated by a predetermined procedure before the local station transmits a packet, and it sets said predetermined time period to be short during it can transmit a packet with a priority. 29. A wireless communication system according to claim 28, wherein each of said communication stations recognizes the state in which it does not receive a signal from other station over a predetermined time period calculated by a predetermined procedure before the local station transmits a packet, and it sets said predetermined time period to be long only during said predetermined time period immediately after it received a beacon from other station. 30. A wireless communication system according to claim 28, wherein each of said communication stations transmits a transmission request signal and recognizes reception of a response to said transmission request signal before the local station transmits a signal. 31. A wireless communication system according to claim 30, wherein each of said communication stations does not carry out virtual carrier sense when it received the transmission request signal correctly and it carries out virtual carrier sense when it received the response to said transmission request signal correctly. 32. A wireless communication system according to claim 28, wherein it is determined by said communication station whether or not a media is clear over a time period corresponding to a stipulated maximum signal length before transmission, when it attempts to transmit a beacon signal immediately after it is changed from the sleep state to the active state. 33. A wireless communication system according to claim 28, wherein said communication station adds a unique preamble word to the beginning of a packet, and it also adds a mid-amble of a similar unique word to every predetermined payload length. 34. A wireless communication system according to claim 24, wherein said communication station, which transmit a stream traffic extracts a plurality of time period in which a beacon is not transmitted, and it transmits a beacon or a signal similar to the beacon in the extracted time period. 35. A wireless communication system according to claim 34, wherein said communication station transmits said signal similar to the beacon continuously or intermittently. 36. A wireless communication system according to claim 34, wherein each of said communication stations recognizes the state in which it does not receive a signal from other station over a predetermined time period calculated by a predetermined procedure before the local station transmits a packet, and it sets said predetermined time period to be short during it can transmit a packet with a priority. 37. A wireless communication system composed of a plurality of communication stations without a relationship of a control station and controlled stations, wherein each of said communication stations performs reception operation during a predetermined time period after it has transmitted a signal, and it stops reception operations when a new signal is not transmitted during said predetermined time period until it receives a signal next or until a time at which transmission is planned. 38. A wireless communication system according to claim 37, wherein each of said communication stations configure said network transmits a beacon signal at substantially a predetermined time period. 39. A wireless communication system according to claim 38, wherein each of said communication stations performs reception continuously over a time period longer than its own beacon transmission interval at least once at a predetermined time. 40. A wireless communication system according to claim 37, wherein said communication station, which became aware of approach of a time at which other station plans to transmit a beacon with reference to a clock value memorized in the local station, transmits information for prohibiting a neighboring station from transmitting data over a predetermined time period. 41. A wireless communication system according to claim 37, wherein when each of said communication stations holds data for other specific station, it carries out reception processing at a time in which said specific other station transmits a beacon, and it attempts to transmit the data to said other specific station in accordance with a predetermined procedure after said other specific station has finished transmitting a beacon. 42. A wireless communication system according to claim 41, wherein said data transmitted after said other station has finished transmitting a beacon is data having a large emergency as compared with ordinary data. 43. A wireless communication system according to claim 37, wherein said communication station energizes a receiver over a predetermined time period before it transmits a signal to detect the presence or absence of a signal transmitted from other station to thereby execute access control for avoiding collision of packet communication timing with that of other station. 44. A wireless communication system according to claim 43, wherein it is determined by said communication station whether or not a media is clear over a time period corresponding to a stipulated maximum signal length before transmission, when it attempts to transmit a beacon signal immediately after it is changed from the sleep state to the active state. 45. A wireless communication system according to claim 43, wherein when each of said communication stations holds data for other specific station, it attempts to transmit memorized data to said other specific station at the timing before said other specific station transmit beacon in accordance with a predetermined procedure. 46. A wireless communication system according to claim 45, wherein said data transmitted just before a beacon transmission of said other station is data having a large emergency as compared with ordinary data. 47. A wireless communication system according to claim 37, wherein each of said communication stations attempts to transmit data to a station which is recognized as a destination station in receiving mode when it transmits data. 48. A wireless communication system according to claim 37, wherein each of said communication stations attempts to receive a beacon from other station recognized by the local station if it is determined that the local station is in the communication state. 49. A wireless communication system according to claim 48, wherein each of said communication stations describes information indicating that it has information to be transmitted to specific other station in a beacon transmitted from the local station and a communication station, which received said beacon, asks the beacon transmission station to transmit a signal informing that data can be transmitted to the beacon reception station if it is determined that said communication station holds data to be transmitted to the beacon reception station. 50. A wireless communication system according to claim 48, wherein said wireless communication system does not attempt to receive a beacon transmitted from a specific station if it is instructed that said communication station should not communicate with said specific station even when it is set to the environment in which it is able to receive a beacon from said specific station. 51. A wireless communication system according to claim 37, wherein each of said communication stations can continue to perform reception operation during a predetermined time period after it has transmitted some signal and it can stop reception operation until it receives a signal next or until a transmission reserve time when it does not receive a signal for the local station during said predetermined time period. 52. A wireless communication apparatus operating decentralized distributed type communication environment constructed such that respective communication stations transmit beacons indicative of information concerning a network with each other at a predetermined time space comprising: communication means for transmitting and receiving wireless data; beacon signal generating means for generating a beacon signal indicative of information concerning the local station; beacon signal analyzing means for analyzing a beacon signal received from a neighboring station by said communicating means; and timing control means for controlling a beacon transmission timing at which said communication means transmits beacons. 53. A wireless communication apparatus according to claim 52, wherein said information concerning the network written in the beacon generated from said beacon signal generating means is information indicating whether or not the local station is aware of a time at which a beacon signal is transmitted. 54. A wireless communication apparatus according to claim 52, wherein said timing control means transmits a beacon signal at a predetermined time space when a communication station joins a network. 55. A wireless communication apparatus according to claim 54, wherein said communication means performs reception continuously over a time period longer than its own beacon transmission interval at least once at a predetermined time. 56. A wireless communication apparatus according to claim 53, wherein said beacon signal generating means, which became aware of approach of a time at which other station plans to transmit a beacon with reference to a clock value memorized in the local station, transmits information for prohibiting a neighboring station from transmitting data over a predetermined period and it energizes said communication means to transmit said beacon. 57. A wireless communication apparatus according to claim 53, wherein said information indicating whether or not the local station is aware of a time at which a beacon signal is transmitted is information indicated by a relative time between said time and a time at which the local station transmits a beacon signal. 58. A wireless communication apparatus according to claim 53, wherein each of said timing control means determines a beacon transmission time based on information obtained from a beacon signal, analyzed by said beacon signal analyzing means, from other station. 59. A wireless communication apparatus according to claim 58, wherein said timing control means continues to receive a beacon from said communication means over a predetermined time period before starting transmitting a new beacon, it holds reception time information of a received beacon transmitted from other station as first information and it shifts information described in said received beacon indicating whether or not the local station is aware of a time at which a beacon signal is transmitted based upon said information and it holds the shifted information as second information. 60. A wireless communication apparatus according to claim 59, wherein said communication station extracts a reception time of a beacon, which the local station or the local station and other station can receive, from said second information, it determines an interval in which a beacon reception time space becomes a maximum beacon space as a target interval and it sets a beacon transmission time of the local station to a central time of said target interval. 61. A wireless communication apparatus according to claim 60, wherein said timing control means attempts to receive a signal transmitted from other station by said communication means during a predetermined time period and it holds a time zone with a small frequency at which a beacon and other signal are received as third information. 62. A wireless communication apparatus according to claim 61, wherein said timing control means extracts each beacon space information, it determines an interval corresponding to a time zone with a small frequency at which a signal obtained from said third information as a target interval and it sets a beacon transmission time of the local station to a central time of said target interval. 63. A wireless communication apparatus according to claim 58, wherein said timing control means determines a new beacon transmission time if said beacon signal analyzing means judges a beacon transmission time alteration request message from other station. 64. A wireless communication apparatus according to claim 52, wherein said information concerning the network described in a beacon generated from said beacon signal generating means is information indicating whether or not the local station is aware of a time at which a received beacon signal is transmitted. 65. A wireless communication apparatus according to claim 64, wherein said information indicative of whether or not the local station is aware of a time at which a received beacon signal is transmitted is information indicated by a relative time between said time and a transmission time of a beacon signal from the local station. 66. A wireless communication apparatus according to claim 64, wherein said specific time zone in which said beacon signal is transmitted is set to a transmission prohibit interval by information described in the beacon generated from said beacon signal generating means. 67. A wireless communication apparatus according to claim 52, wherein said timing control means delays said transmission time of a beacon signal transmitted from a communication station within said network from a predetermined target beacon transmission time by a random time and said beacon signal generating means describes information indicative of a delayed amount in said beacon. 68. A wireless communication apparatus according to claim 67, wherein said beacon signal generating means, which became aware of approach of a time at which other station plans to transmit a beacon with reference to a clock value memorized in the local station, adds information for prohibiting a neighboring station from transmitting data over a predetermined period to a beacon and it energizes said communication means to transmit said resultant information. 69. A wireless communication apparatus according to claim 67, wherein when said communication means receives a beacon from other communication station, said timing control means calculates a target beacon transmission time from a beacon reception time in consideration of a time indicative of said delay amount. 70. A wireless communication apparatus according to claim 69, wherein said communication station adjusts a clock of the local station in accordance with a timing of other station when a neighboring station target beacon transmission time predicted from the clock value memorized in the local station and a target beacon transmission time of a beacon transmission station which results from subtracting a time at which a beacon was received in actual practice and an intentionally delayed beacon transmission time described in a beacon are different from each other. 71. A wireless communication apparatus according to claim 70, wherein said communication station adjusts a clock of the local station in accordance with a timing of other station when the target beacon transmission time of the beacon transmission station is delayed from the target beacon transmission time predicted by the local station. 72. A wireless communication apparatus according to claim 67, wherein said beacon signal generating means describes a delay amount of a beacon transmission time in said beacon if said beacon transmission time is delayed due to an external primary factor when it transmits a beacon under control of said timing control means. 73. A wireless communication apparatus according to claim 67, wherein said random time with which the beacon transmission time is delayed from the target beacon transmission time is given in the form of a pseudorandom sequence and the state of said pseudorandom sequence is transmitted as information indicative of a delay amount described in said beacon. 74. A wireless communication apparatus according to claim 73, wherein said timing control means holds the state of said pseudorandom sequence described in said beacon and it calculates the next beacon transmission time of said beacon transmission station by updating a pseudorandom sequence value of every predetermined period. 75. A wireless communication apparatus according to claim 52, wherein said timing control means sets a predetermined time period in which a beacon transmission station can transmit a packet with a priority after said communication means has transmitted said beacon signal. 76. A wireless communication apparatus according to claim 75, wherein said communication station sets a time period in which each communication station performs transmission based upon predetermined contention control after said predetermined time period in which said beacon transmission station can transmit a packet with a priority has expired. 77. A wireless communication apparatus according to claim 76, wherein said communication station which communicates with said beacon transmission station can transmit a packet with a priority at said predetermined time period in which said beacon transmission station can transmit a packet with a priority. 78. A wireless communication apparatus according to claim 75, wherein said communication station, which became aware of approach of a time at which other station plans to transmit a beacon with reference to a clock value memorized in the local station, transmits information for prohibiting a neighboring station from transmitting data over a predetermined period. 79. A wireless communication apparatus according to claim 75, wherein said timing control means recognizes the state in which it does not receive a signal from other station over a predetermined period calculated by a predetermined procedure before the local station transmits a packet and it sets said predetermined period to be short during a predetermined time period in which it can transmit a packet with a priority. 80. A wireless communication apparatus according to claim 79, wherein said timing control means recognizes the state in which it does not receive a signal from other station over a predetermined period calculated by a predetermined procedure before the local station transmits a packet and it sets said predetermined period to be long only during said predetermined time period immediately after it received a beacon from other station. 81. A wireless communication apparatus according to claim 79, wherein each of said communication stations transmits a transmission request signal and recognizes reception of a response to said transmission request signal before said communication means transmits a signal. 82. A wireless communication apparatus according to claim 81, wherein each of said communication stations does not carry out virtual carrier sense when it received the transmission request signal correctly and it carries out virtual carrier sense when it received the response to said transmission request signal correctly. 83. A wireless communication apparatus according to claim 79, wherein it is determined by said communication station whether or not a media is clear over a time period corresponding to a stipulated maximum signal length before transmission when it attempts to transmit a beacon signal immediately after it is changed from the sleep state to the active state. 84. A wireless communication apparatus according to claim 79, wherein said communication station adds a preamble of a unique word to the beginning of a packet transmitted from said communication means and it also adds a mid-amble of a similar unique word to every constant payload length. 85. A wireless communication apparatus according to claim 75, wherein said timing control means, which received a stream traffic transmission request, extracts a plurality of intervals in which a beacon is not transmitted and it transmits a beacon or a signal similar to the beacon in said plurality of extracted intervals. 86. A wireless communication apparatus according to claim 85, wherein said communication station transmits said signal similar to said beacon continuously or intermittently. 87. A wireless communication apparatus according to claim 85, wherein each of said communication stations recognizes the state in which it does not receive a signal from other station over a predetermined period calculated by a predetermined procedure before the local station transmits a packet and it sets said predetermined period to be short during a predetermined time period in which it can transmit a packet with a priority. 88. A wireless communication apparatus comprising a communication station of a wireless communication system composed of a plurality of communication stations without a relationship of a control station and controlled stations further comprising: communication means for transmitting and receiving wireless data; and control means for performing reception operation during a predetermined time period after said communication means has transmitted a signal and stopping reception operation until a signal is received next or until a transmission planned time when said communication means does not transmit a new signal during said predetermined time period. 89. A wireless communication apparatus according to claim 88, wherein said communication means transmits a beacon signal periodically at substantially a constant space. 90. A wireless communication apparatus according to claim 89, wherein said communication means continuously performs reception over a time period longer than a beacon transmission space of the local station more than once in a decided time. 91. A wireless communication apparatus according to claim 88, wherein said communication means, which became aware of approach of a time at which other station plans to transmit a beacon with reference to a clock value memorized in the local station, transmits information for prohibiting a neighboring station from transmitting data over a predetermined period. 92. A wireless communication apparatus according to claim 88, wherein when said communication means holds information for other specific station, it carries out reception processing at a time in which said specific other station transmits a beacon and it attempts to transmit memorized information to said other specific station in accordance with a predetermined procedure after said other specific station has finished transmitting a beacon. 93. A wireless communication apparatus according to claim 92, wherein said information transmitted after said other station has finished transmitting a beacon is information having a large emergency as compared with ordinary data. 94. A wireless communication apparatus according to claim 88, wherein said communication means energizes a receiver over a predetermined time period before it transmits a signal to detect the presence or absence of a signal transmitted from other station to thereby execute access control for avoiding collision of packet communication timing with that of other station. 95. A wireless communication apparatus according to claim 94, wherein when said communication means attempts to transmit a signal after it has been changed from the sleep state to the active state, prior to transmission, it is determined by said control means during a time period corresponding to the stipulated maximum signal-length whether or not the media is clear. 96. A wireless communication apparatus according to claim 94, wherein when each of said communication stations holds information for other specific station, it attempts to transmit memorized information to said other specific station in accordance with a predetermined procedure immediately before said other specific station transmits a beacon. 97. A wireless communication apparatus according to claim 96, wherein said information transmitted just before a beacon transmission of said other station is information having a large emergency as compared with ordinary data. 98. A wireless communication apparatus according to claim 88, wherein each of said communication stations attempts to transmit information to a station which is recognized as a destination station operating to receive information when it transmits information. 99. A wireless communication apparatus according to claim 88, wherein said control means attempts to receive a beacon from other station recognized by the local station if it is determined that the local station is in the communication state. 100. A wireless communication apparatus according to claim 99, wherein each of said communication stations describes information indicating that it has information to be transmitted to specific other station in a beacon transmitted from said communication means and performs transmission after it received a signal informing that data can be transmitted from said other station. 101. A wireless communication apparatus according to claim 99, wherein said control means does not attempt to receive a beacon transmitted from a specific station if it is instructed by a signal received by said communication means that it should not communicate with said specific station even when it is set to the environment in which it is able to receive a beacon from said specific station. 102. A wireless communication apparatus according to claim 88, wherein said control means can continue to perform reception operation during a predetermined time period after it has transmitted some signal and it can stop reception operation until it receives a signal next or until a transmission planned time when it does not receive a signal for the local station during said predetermined time period. 103. A wireless communication method operating under a decentralized distributed communication environment constructed when respective communication station transmit beacons with information concerning a network written therein with each other at a predetermined time space comprising the steps of: a beacon signal generating step for generating a beacon signal in which information concerning the local station is written; a beacon signal analyzing step for analyzing a beacon signal received from the neighboring station by said communication means; and a timing control step for controlling beacon transmission timing at which said communication means transmits a beacon. 104. A wireless communication method according to claim 103, wherein said information concerning the network is information indicating whether or not the local station is aware of a time at which a beacon signal is transmitted. 105. A wireless communication method according to claim 103, wherein each of said communication stations joined said network transmits a beacon signal at a predetermined time space. 106. A wireless communication method according to claim 105, wherein each of said communication stations performs reception continuously over a time period longer than its own beacon transmission interval at least once at a predetermined time. 107. A wireless communication method according to claim 104, wherein said communication station, which became aware of approach of a time at which other station plans to transmit a beacon with reference to a clock value memorized in the local station, transmits information for prohibiting a neighboring station from transmitting data over a predetermined period. 108. A wireless communication method according to claim 104, wherein said information indicating whether or not the local station is aware of a time at which a beacon signal is transmitted is information indicated by a relative time between said time and a time at which the local station transmits a beacon signal. 109. A wireless communication method according to claim 104, wherein each of said communication station determines a beacon transmission time of the local station based on information obtained from a beacon signal which the local station can receive from other station. 110. A wireless communication method according to claim 58, wherein each of said communication stations continues to receive a beacon from other station over a predetermined time period before starting transmitting a new beacon, it holds reception time information of a received beacon transmitted from other station as first information and it shifts information described in said received beacon indicating whether or not the local station is aware of a time at which a beacon signal is transmitted based upon said information and it holds the shifted information as second information. 111. A wireless communication method according to claim 110, wherein said communication station extracts a reception time of a beacon, which the local station or the local station and other station can receive, from said second information, it determines an interval in which a beacon reception time space becomes a maximum beacon space as a target interval and it sets a beacon transmission time of the local station to a central time of said target interval. 112. A wireless communication method according to claim 111, wherein each of said communication stations attempts to receive a signal transmitted from other station during a predetermined time period and it holds a time zone with a small frequency at which a beacon and other signal are received as third information. 113. A wireless communication method according to claim 112, wherein said communication station extracts each beacon space information, it determines an interval corresponding to a time zone with a small frequency at which a signal obtained from said third information as a target interval and it sets a beacon transmission time of the local station to a central time of said target interval. 114. A wireless communication method according to claim 109, wherein said communication station which received a beacon transmission time alteration request message from other station determines a new beacon transmission time. 115. A wireless communication method according to claim 103, wherein said information concerning the network is information indicating whether or not the local station is aware of a time at which a received beacon signal is transmitted. 116. A wireless communication method according to claim 115, wherein said information indicative of whether or not the local station is aware of a time at which a received beacon signal is transmitted is information indicated by a relative time between said time and a transmission time of a beacon signal from the local station. 117. A wireless communication method according to claim 115, wherein said specific time zone in which said beacon signal is transmitted is set to a transmission prohibit interval. 118. A wireless communication method according to claim 103, wherein said transmission time of a beacon signal is delayed from a predetermined target beacon transmission time by a random time and information indicative of a delayed amount is described in said beacon. 119. A wireless communication method according to claim 118, wherein said communication station, which became aware of approach of a time at which other station plans to transmit a beacon with reference to a clock value memorized in the local station, transmits information for prohibiting a neighboring station from transmitting data over a predetermined period. 120. A wireless communication method according to claim 118, wherein when each of said communication systems receives a beacon from other communication station, it calculates a target beacon transmission time of said beacon transmission station from a beacon reception time in consideration of a time indicative of said delay amount. 121. A wireless communication method according to claim 120, wherein said communication station adjusts a clock of the local station in accordance with a timing of other station when a neighboring station target beacon transmission time predicted from the clock value memorized in the local station and a target beacon transmission time of a beacon transmission station which results from subtracting a time at which a beacon was received in actual practice and an intentionally delayed beacon transmission time described in a beacon are different from each other. 122. A wireless communication method according to claim 121, wherein said communication station adjusts a clock of the local station in accordance with a timing of other station when the target beacon transmission time of the beacon transmission station is delayed from the target beacon transmission time predicted by the local station. 123. A wireless communication method according to claim 118, wherein each of said communication stations describes a delay amount of a beacon transmission time in said beacon if said beacon transmission time is delayed due to an external primary factor when it transmits a beacon. 124. A wireless communication method according to claim 118, wherein said random time with which the beacon transmission time is delayed from the target beacon transmission time is given in the form of a pseudorandom sequence and the state of said pseudorandom sequence is transmitted as information indicative of a delay amount described in said beacon. 125. A wireless communication method according to claim 124, wherein each of said communication stations holds the state of said pseudorandom sequence described in said beacon and it calculates the next beacon transmission time of said beacon transmission station by updating a pseudorandom sequence value of every predetermined period. 126. A wireless communication method according to claim 103, wherein said communication station sets a predetermined time period in which a beacon transmission station can transmit a packet with a priority after said beacon transmission station has transmitted said beacon signal. 127. A wireless communication method according to claim 126, wherein said communication station sets a time period in which each communication station performs transmission based upon predetermined contention control after said predetermined time period in which said beacon transmission station can transmit a packet with a priority has expired. 128. A wireless communication method according to claim 127, wherein said communication station which communicates with said beacon transmission station can transmit a packet with a priority at said predetermined time period in which said beacon transmission station can transmit a packet with a priority. 129. A wireless communication method according to claim 126, wherein said communication station, which became aware of approach of a time at which other station plans to transmit a beacon with reference to a clock value memorized in the local station, transmits information for prohibiting a neighboring station from transmitting data over a predetermined period. 130. A wireless communication method according to claim 126, wherein each of said communication stations recognizes the state in which it does not receive a signal from other station over a predetermined period calculated by a predetermined procedure before the local station transmits a packet and it sets said predetermined period to be short during a predetermined time period in which it can transmit a packet with a priority. 131. A wireless communication method according to claim 130, wherein each of said communication stations recognizes the state in which it does not receive a signal from other station over a predetermined period calculated by a predetermined procedure before the local station transmits a packet and it sets said predetermined period to be long only during said predetermined time period immediately after it received a beacon from other station. 132. A wireless communication method according to claim 130, wherein each of said communication stations transmits a transmission request signal and recognizes reception of a response to said transmission request signal before the local station transmits a beacon signal. 133. A wireless communication method according to claim 132, wherein each of said communication stations does not carry out virtual carrier sense when it received the transmission request signal correctly and it carries out virtual carrier sense when it received the response to said transmission request signal correctly. 134. A wireless communication method according to claim 130, wherein it is determined by said communication station whether or not a media is clear over a time period corresponding to a stipulated maximum signal length before transmission when it attempts to transmit a beacon signal immediately after it is changed from the sleep state to the active state. 135. A wireless communication method according to claim 130, wherein said communication station adds a preamble of a unique word to the beginning of a packet and it also adds a mid-amble of a similar unique word to every constant payload length. 136. A wireless communication method according to claim 126, wherein said communication station, which received a stream traffic transmission request, extracts a plurality of intervals in which a beacon is not transmitted and it transmits a beacon or a signal similar to the beacon in said plurality of extracted intervals. 137. A wireless communication method according to claim 136, wherein said communication station transmits said signal similar to said beacon continuously or intermittently. 138. A wireless communication method according to claim 136, wherein each of said communication stations recognizes the state in which it does not receive a signal from other station over a predetermined period calculated by a predetermined procedure before the local station transmits a packet and it sets said predetermined period to be short during a predetermined time period in which it can transmit a packet with a priority. 139. A wireless communication method for performing wireless communication in a network composed of a plurality of communication stations without a relationship of a control station and controlled stations comprising the steps of: a transmission and reception step for performing reception operation during a predetermined time period after a signal was transmitted; and a reception timing control step for stopping reception operation until a signal is received next or until the transmission planned time when a new signal is not transmitted during said predetermined time period. 140. A wireless communication method according to claim 139, wherein each of said communication stations joined said network transmits a beacon signal periodically at substantially a constant space. 141. A wireless communication method according to claim 140, wherein each of said communication stations continuously performs reception over a time period longer than a beacon transmission space of the local station more than once in a decided time. 142. A wireless communication method according to claim 139, wherein said communication station, which became aware of approach of a time at which other station plans to transmit a beacon with reference to a clock value memorized in the local station, transmits information for prohibiting a neighboring station from transmitting data over a predetermined period. 143. A wireless communication method according to claim 139, wherein when each of said communication stations holds information for other specific station, it carries out reception processing at a time in which said specific other station transmits a beacon and it attempts to transmit memorized information to said other specific station in accordance with a predetermined procedure after said other specific station has finished transmitting a beacon. 144. A wireless communication method according to claim 143, wherein said information transmitted after said other station has finished transmitting a beacon is information having a large emergency as compared with ordinary data. 145. A wireless communication method according to claim 139, wherein said communication station energizes a receiver over a predetermined time period before it transmits a signal to detect the presence or absence of a signal transmitted from other station to thereby execute access control for avoiding collision of packet communication timing with that of other station. 146. A wireless communication method according to claim 145, wherein when said communication station attempts to transmit a signal after it has been changed from the sleep state to the active state, prior to transmission, it is determined by said communication station during a time period corresponding to the stipulated maximum signal length whether or not the media is clear. 147. A wireless communication method according to claim 145, wherein when each of said communication stations holds information for other specific station, it attempts to transmit memorized information to said other specific station in accordance with a predetermined procedure immediately before said other specific station transmits a beacon. 148. A wireless communication method according to claim 147, wherein said information transmitted just before a beacon transmission of said other station is information having a large emergency as compared with ordinary data. 149. A wireless communication method according to claim 139, wherein each of said communication stations attempts to transmit information to a station which is recognized as a destination station operating to receive information when it transmits information. 150. A wireless communication method according to claim 139, wherein each of said communication stations attempts to receive a beacon from other station recognized by the local station if it is determined that the local station is in the communication state. 151. A wireless communication method according to claim 150, wherein each of said communication stations describes information indicating that it has information to be transmitted to specific other station in a beacon transmitted from the local station and a communication station, which received said beacon, asks the beacon transmission station to transmit a signal informing that data can be transmitted to the beacon reception station if it is determined that said communication station holds data to be transmitted to the beacon reception station. 152. A wireless communication method according to claim 150, wherein said wireless communication system does not attempt to receive a beacon transmitted from a specific station if it is instructed that said communication station should not communicate with said specific station even when it is set to the environment in which it is able to receive a beacon from said specific station. 153. A wireless communication method according to claim 139, wherein each of said communication stations can continue to perform reception operation during a predetermined time period after it has transmitted some signal and it can stop reception operation until it receives a signal next or until a transmission reserve time when it does not receive a signal for the local station during said predetermined time period. 154. A computer program written in the form of a computer readable format such that processing for being operated under a decentralized distributed communication environment constructed when respective communication stations transmit beacons with information concerning a network written thereon transmit with each other at a predetermined time space is executed on a computer system comprising the steps of: a beacon signal generating step for generating a beacon signal in which information concerning the local station is written; a beacon signal analyzing step for analyzing a beacon signal received from a neighboring station by said communication means; and a timing control step for controlling beacon transmission timing by said communication means. 155. A computer program written in the form of a computer readable format such that processing for making wireless communication on a network composed of a plurality of communication stations without relationship between a control station and controlled stations is executed on a computer system comprising the steps of: a transmission and reception step for executing reception step during a predetermined time period after a signal has been transmitted; and a reception timing control step for stopping reception operation until a signal is received next or until a transmission planned time if said communication station does not transmit a new signal during said predetermined time period.

TECHNICAL FIELD The present invention relates to a wireless communication system, a wireless communication apparatus and a wireless communication method and a computer program suitable for use in configuring a wireless LAN (Local Area Network: local area network) for making data communication, for example, to construct a decentralized distributed type network without a relationship of control station and controlled station, such as a master station and slave stations. More specifically, the present invention relates to a wireless communication system, a wireless communication apparatus and a wireless communication method and a computer program for forming a decentralized distributed type wireless network formed when respective communication stations transmit their beacons with network information and the like written therein with each other at every predetermined frame period, and particularly relates to a wireless communication system, a wireless communication apparatus and a wireless communication method and a computer program for forming a decentralized distributed type wireless network while avoiding collision of beacons transmitted from the respective communication stations. BACKGROUND ART As media access control for wireless LAN system, access control standardized by IEEE (The Institute of Electrical and Electronics Engineers) 802.11 systems have been widely known so far. International Standard ISO/IEC 8802-11: 1999(E) ANSI/IEEE Std 802.11, 1999 Edition, Part II: Wireless LAN Medium Access Control (MAC) and Physical Layer (PHY) specifications or the like has described the details of the IEEE802.11. Networking in the IEEE802.11 is based on a concept of a BSS (Basic Service Set). Two kinds of BSS are available, that is, BBS defined by the infrastructure mode in which a master control station such as an access point (Access Point: AP) exists and IBSS (Independent BSS) defined by the ad hoc mode composed of only a plurality of mobile terminals (Mobile Terminal: MT). Operations of the IEEE802.11 in the infrastructure mode will be described with reference to FIG. 30. In the BSS in the infrastructure mode, an access point for performing coordination should be absolutely provided within a wireless communication system. In FIG. 30, assuming that a communication station SAT0, for example, is a communication station SA which functions as an access point, then BSSes within a range of radio waves near the local station are collected to construct a cell in the so-called cellular system. Mobile stations (SAT1, SAT2) existing neat the access point are accommodated into the access point and joined the network as a member of the BSS. The access point transmits a control signal called a beacon at a proper time space. A mobile terminal that can receive this beacon recognizes that the access points exists near it and establishes connection between it and the access point. The communication station SAT0, which is the access point, transmits a beacon (Beacon) at a predetermined period space as shown on the right-hand side of FIG. 30. The next beacon transmission time is sent into the beacon by a parameter called a target beacon transmit time (TBTT: Target Beacon Transmit Time). When a time reaches the TBTT field, the access point activates a beacon transmission procedure. Also, since a neighboring mobile terminal receives a beacon and is able to recognize the next beacon transmission time by decoding the inside TBTT field, depending on the cases (mobile terminal need not receive information), the receiver may be de-energized until the next TBTT field or a plurality of future target beacon transmission times and the mobile terminal may be placed in the sleep mode. This specification principally considers the gist of the present invention in which the network is operated without application of a master control station such as the access point, and hence the infrastructure mode will not be described any more. Next, communication operations according to the IEEE802.11 in the ad hoc mode will be described with reference to FIGS. 31 and 32. On the other hand, in the IBSS in the ad hoc mode, after each communication station (mobile terminal) has negotiated with a plurality of communication stations, each communication station defines the IBSS independently. When the IBSS is defined, the communication station group determines the TBTT at every constant interval after negotiations. When each communication station recognizes the TBTT with reference to a clock within the local station, if it recognizes that other communication station has not transmitted the beacon after a delay of a random time, then the communication station transmits the beacon. FIG. 31 shows an example of the case in which two communication stations SAT1, SAT2 constitute the IBSS. Accordingly, in this case, any one of communication stations belonging to the IBSS is able to transmit the beacon at each arrival of the TBTT field. Also, it is frequently observed that the beacons will conflict with each other. Further, also in the IBSS, according to the necessity, each communication station is placed in the sleep mode in which a power switch of its transmission and reception unit is turned off. A signal transmission and reception procedure in this case will be described with reference to FIG. 32. In the IEEE82.11, when the sleep mode is applied to the IBSS, a certain time period from the TBTT is defined as an ATIM (Announcement Traffic Indication Message) Window (hereinafter referred to as an. “ATIM window”). During the time period of the ATIM window, since all communication stations belonging to the IBSS are operating the reception units, even the communication station which is being operated in the sleep mode fundamentally is able to receive communication in this time period. When each communication station has its own information for other communication station, after a beacon has been transmitted in the time period of this ATIM window, the communication station lets the reception side know that the communication station has its own information for other communication station by transmitting the ATIM packet to other communication station. The communication station, which has received the ATIM packet, causes the reception unit to continue operating until the reception from the station that has transmitted the ATIM packet is ended. FIG. 32 shows the case in which three communication stations STA1, STA2, STA3 exist within the IBSS, by way of example. As shown in FIG. 32, at the time TBTT, the respective communication stations STA1, STA2, STA3 operate back-off timers while monitoring the media state over a random time. The example of FIG. 32 shows the case in which the communication station STA1 transmits the beacon after the timer of the communication station STA1 has ended counting in the earliest stage. Since the communication station STA1 transmits the beacon, other two communication stations STA2 and STA3 do not transmit the beacon. The example of FIG. 32 shows the case in which the communication station STA1 holds information for the communication station STA2, the communication station STA2 holding information for the communication station STA3. At that time, as shown in FIGS. 32B, 32C, after having transmitted/received the beacons, the communication stations STA1 and STA2 energize the back-off timers while monitoring the states of the media again over the random time, respectively. In the example of FIG. 32, since the timer of the communication station STA2 has ended counting earlier, first, the communication station STA2 transmits the ATIM message to the communication station STA3. As shown in FIG. 32A, when receiving the ATIM message, the communication station STA3 feeds the message of the reception back to the communication station STA2 by transmitting an ACK (Acknowledge) packet which is an acknowledge packet to the above communication station. After the communication station STA3 has finished transmitting the ACK packet, the communication station STA1 further energizes the back-off timer while monitoring the respective states of the media over the random time. When the timer finishes counting after a time set by the timer has passed, the communication station STA1 transmits the ATIM packet to the communication station STA2. The communication station STA2 feeds the message of the reception back to the communication station STA1 by returning the ACK packet to the above communication station. When the ATIM packet and the ACK packet are exchanged within the ATIM window, also during the following interval, the communication station STA3 energizes the receiver to receive information from the communication station STA2, and the communication station STA2 energizes the receiver to receive information from the communication station STA1. When the ATIM window is ended, the communication stations STA1 and STA2 which hold the transmission information energize the back-off timers while monitoring the respective states of the media over the random time. In the example of FIG. 32, since the timer of the communication station STA2 has finished counting first, the communication station STA2 first transmits the information to the communication station STA3. After this transmission of the information was ended, the communication station STA1 energizes the back-off timer while monitoring again the respective states of the media over the random time, and after the timer is ended, it transmits the packet to the communication station STA2. In the above-mentioned procedure, a communication station which has not received the ATIM packet within the ATIM window or which does not hold information de-energizes the transmitter and receiver until the next TBTT field and it becomes possible to decrease power consumption. Next, the access contention method of the IEEE802.11 system will be described with reference to FIG. 33. In the above explanation, while we have described “communication station energizes the back-off timer while monitoring the states of the media over the random time”, let us make additional explanation to this case. In the IEEE802.11 system, four kinds of IFS are defined as packet spaces (IFS: Inter Frame Space) extending from the end of the immediately-preceding packet to the transmission of the next packet. Of the four kinds of the inter frame spaces, three inter frame spaces will be described. As shown in FIG. 33, as the IFS, there are defined SIFS (Short IFS), PIFS (PCF IFS) and DIFS (DCF IFS) in the sequential order of short inter frame space. According to the IEEE802.11, a CSMA (Carrier Sense Multiple Access) is applied as the fundamental media access procedure. Accordingly, before the transmission unit transmits some information, the communication station energizes the backoff timer over the random time while monitoring the state of the media. If it is determined that the transmission signal does not exist during this time period, then the transmission unit is given a transmission right. When the communication station transmits the ordinary packet in accordance with the CSMA procedure (called a DCF: Distributed Coordination Function), after the transmission of some packet has been ended, the state of the media of only the DIFS is monitored. Unless the transmission signal exists during this time period, then the random backoff is made. Further, unless the transmission signal exists during this time period, the transmission unit is given a transmission right. On the other hand, when a packet such as ACK packet which has an exceptionally large emergency is transmitted, the transmission unit is allowed to transmit the packet after the SIFS packet space. Thus, it becomes possible to transmit the packet with the large emergency before the packet that is to be transmitted in accordance with the ordinary CSMA procedure. Different kinds of packet spaces IFS are defined for this reason. Packet transmission contention is prioritized depending upon whether the IFS is the SIFS or the PIFS or the DIFS. The purpose of using the PIFS will be described later on. Next, the RTS/CTS procedure in the IEEE802.11 will be described with reference to FIGS. 34 and 35. In network under the ad hoc environment, it is generally known that a problem of a hidden terminal arises. As a methodology for solving the most part of this problem, there is known a CSMA/CA based upon the RTS/CTS procedure. The IEEE802.11 also uses this methodology. An example of operation in the RTS/CTS procedure will be described with reference to FIG. 34. FIG. 34 shows an example of the case in which some information (DATA) is transmitted from a communication station STA0 to a communication station STA1. Before transmitting actual information, the communication station STA0 transmits an RTS (Request To Send) packet to the communication station STA1 which is an information destination station in accordance with the CSMA procedure. When the communication station STA1 received this packet, it transmits a CTS (Clear To Send) packet which feeds information indicative of the reception of the RTS packet back to the communication station STA0 to the communication station. When the communication station STA0 which is the transmission side receives the CTS packet without accident, the communication station regards that the media is clear and transmits an information (Data) packet immediately. After the communication station STA1 receives this information packet without accident, it returns the ACK packet and the transmission of one packet is ended. Actions that will occur in this procedure will be described with reference to FIG. 35. In FIG. 35, it is assumed that a communication station STA2 may transmit information to a communication station STA3. Having confirmed by the CSMA procedure that the media is clear during a predetermined period, the communication station STA2 transmits the RTS packet to the communication station STA3. This packet is also received by the neighbor communication station STA1 of the communication station STA2. Because the communication station STA1 receives the RTS packet and becomes aware that the station STA2 intends to transmit some information, it recognizes that the media is occupied by the station STA2 until the transmission of such information is ended, and it also becomes aware of the fact that the media is occupied without monitoring the media during this time period. This work is called an NAV (Network Allocation Vector). The RTS packet and the CTS packet have durations of time in which the media is occupied in the transaction written thereon. Returning to the description, having received the RTS packet transmitted from the communication station STA2 to the communication station STA3, the communication station STA1 becomes aware of the fact that the media is placed in the occupied state during a time period designated by the RTS packet, and hence it refrains from transmitting information. On the other hand, the communication station STA3 which received the RTS packet returns the CTS packet to the communication station to feed information indicative of the reception of the RTS packet back to the communication station STA2. This CTS packet is also received by a neighbor communication station STA4 of the communication station STA3. The communication station STA4 recognizes by decoding the content of the CTS packet that information is transmitted from the communication station STA2 to the communication station STA3, and it becomes aware of the fact that the media will be occupied during a time period designated by the CTS packet. Hence, it refrains from transmitting information. When the above-described RTS packet and CTS packet are transmitted and received, the transmission is prohibited between “neighboring station of the communication station STA2 which is the transmission station” which could receive the RTS packet and “neighboring station of the communication station STA3 which is the reception station” which could receive the CTS packet, whereby information can be transmitted from the communication station STA2 to the communication station STA3 and the ACK packet can be returned without being disturbed by the sudden transmission from the neighboring station. Next, a band reserve means in the IEEE802.11 system will be described with reference to FIG. 36. In the above-mentioned IEEE802.11 system access control, access contention based on the CSMA procedure is executed, and hence it is impossible to guarantee and maintain a constant band. In the IEEE802.11 system, a PCF (Point Coordination Function) exists as a mechanism for guaranteeing and maintaining the band. However, the basis of the PCF is polling and it does not operate in the ad hoc mode but it operates only in the infrastructure mode under control of the access point. Specifically, in order to execute the access control while the band is being guaranteed, a coordinator such as an access point is required and all controls are carried out by the access point. For reference, operations of the PCF will be described with reference to FIG. 36. In FIG. 36, it is assumed that the communication station STA0 is the access point and that the communication stations STA1 and STA2 joined in the BSS managed by the access point STA0. Also, it is assumed that the communication station STA1 transmits information while it guarantees the band. Having transmitted the beacon, for example, the communication station STA0 performs polling to the communication station STA1 at the SIFS space (CF-Poll in FIG. 36). The communication station STA1 which received the CF-Poll is given a right to transmit data and is thereby allowed to transmit data at the SIFS space. As a result, the communication station STA1 transmits the data after the SIFS space. When the communication station STA0 returns the ACK packet for the transmitted data and one transaction is ended, the communication station STA0 again performs polling to the communication station STA1. FIG. 36 shows also the case in which polling of this time is failed due to some reason, that is, the state in which the polling packet shown as the CF-Poll follows the SIFS space. Specifically, when the communication station STA0 becomes aware that no information is transmitted from the communication station STA1 after the SIFS space elapsed since it has performed polling, it regards that the polling is failed and performs polling again after the PIFS space. If this polling is successful, then data is transmitted from the communication station STA1 and the ACK packet is returned. Even when the communication station STA2 holds the transmitted packet during a series of this procedure, since the communication station STA0 or STA1 transmits information at the SIFS or PIFS space before the DIFS time space elapses, the right to transmit information is never moved to the communication station STA2 and hence the communication station STA1 to which the polling is performed is constantly given a priority. Official Gazette of Japanese laid-open patent application No. 8-98255 discloses an example of access control of such wireless communication. When access control of wireless communication is carried out without such master control station (access point), as compared with the case in which communication is carried out with the master control station, there were various restrictions. To be concrete, the following problems arise. Problem 1: Selection of Coordinator For example, as shown in FIG. 37, let it be assumed that a network is configured by the above-mentioned IEEE802.11 system when communication stations 10 to 17 are located in the scattered state and communication ranges 10a to 17a in which the communication stations 10 to 17 can directly communicate with each other. In such case, if the network is configured in the infrastructure mode, then there arises a problem of how to select a communication station that should be operated as the access point (coordinator). In the IEEE802.11 system, a communication station accommodated within the BSS may communicate with only a communication station which belongs to the same BSS, and the access point is operated as a gateway to other BSS. In order to efficiently make networking on the whole of the system, there are various arguments such as to select which location of the communication station as the access point or how to configure again the network when the access point is de-energized. Although it is desirable that the network could be configured without the coordinator, the infrastructure mode of the IEEE802.11 system cannot meet with such requirements. Problem 2: Disagreement of Achievable Area In the ad hoc mode of the IEEE802.11 system, although the network can be configured without the coordinator, it is assumed that the IBSS is constructed by a plurality of communication stations located at the surrounding areas. For example, as shown in FIG. 37, it is assumed that the communication stations 10, 11, 12, 13 (STA0, STA1, STA2, STA3) are accommodated within the same IBSS. Then, although the communication station 11 (STA1) can communicate with the communication stations 10, 12, 13 (STA0, STA2, STA3), the communication station 10 (STA0) cannot directly communicate with the communication station 12 (STA2). In such case, according to the beacon transmission procedure of the IEEE802.11 system, it is frequently observed that the communication station 10 (STA0) and the communication station 12 (STA2) transmit the beacons at the same time, and at that time, the communication station 11 (STA1) becomes unable to receive a beacon, which causes a problem. Further, as shown in FIG. 37, for example, let it be assumed that the communication stations 15, 16, 17 (STA5, STA6, STA7) constitute an IBSS (IBSS-A) and that the communication stations 10, 11, 12, 13 (STA0, STA1, STA3, STA3) constitute an IBSS (IBSS-B). At that time, since the two IBSSes are operating completely independently, an interference problem does not arise between the two IBSSes. Here, let it be considered the case in which a new communication station 14 (STA4) appears on the network. Then, the communication station 14 (STA4) is able to receive both signals from the IBSS-A and the IBSS-B. When the two IBSSes are coupled together, although the communication station STA4 can enter both of the IBSS-A and the IBSS-B, the IBSS-A is operated in accordance with the rule of the IBSS-A and the IBSS-B is operated in accordance with the rule of the IBSS-B. Then, there is a possibility that collision of the beacons and collision of the ATIM packets will occur, which also raises a problem. Problem 3: Method of Realizing Power Save Mode In the ad hoc mode, the power save mode can be realized by transmitting the ATIM packets with each other within the ATIM window according to the random access. When information to be transmitted is a small amount of information such as bits, an overhead required by the ATIM packets increases, and a methodology in which the ATIM packets are to be exchanged according to the random access is very inefficient. Problem 4: Band Reserve in Network Without Coordinator Also, according to the IEEE802.11 system, in the ad hoc mode, a mechanism for carrying out band reserve does not exist, and hence there is no method but to constantly follow the operation of the CSMA procedure. Problem 5: Incompleteness of RTS/CTS Procedure In the RTS/CTS procedure of the IEEE802.11 system, not only a communication station which received the CTS packet but also a communication station which received the RTS packet is prohibited from transmitting information. However, in the case shown in FIG. 35, the station that is prohibited from transmitting information is only the communication station STA4 and the communication station STA1 does not affect “transmission of DATA from the communication station STA2 to the communication station STA3”. In the RTS/CTS procedure, to prohibit the communication station which received the RTS packet from transmitting information requires a large margin to the safety side and this is one of the factors which degrade a system throughput. Problem 6: Considerations on Separation of BBSES by TDMA In the scenario described in the above-mentioned Problem 2 (in FIG. 37, the communication stations STA5, STA6, STA7 constitute the IBSS (IBSS-A) and the communication stations STA0, STA1, STA2, STA3 constitute the IBSS (IBSS-B)), as a method for solving the problem which arises when the communication station STA4 appears to couple both of the IBSSes, there exists a method for separating the IBSS-A and the IBSS-B by a TDMA (Time Division Multiple Access: time division multiple access) system. An example of this case is shown in FIG. 38. This is a method used in an ARIB STD-T70 (HiSWANa) system and the like. A time zone that is exclusively used for a sub-network is constructed in a frame of some BBS. However, according to this method, spatial recycling of resources is aborted and hence utilization ratio is decreased considerably, which also causes a problem. In view of the aforesaid aspects, it is an object of the present invention to provide excellent wireless communication system, wireless communication apparatus and wireless communication method and computer program in which the problems arising when a wireless system such as a wireless LAN is constructed as a decentralized distributed type network without control and controlled relationship such as a master station and slave stations can be solved. Other object of the present invention is to provide excellent wireless communication system, wireless communication apparatus and wireless communication method and computer program in which data can be transmitted while collisions are being avoided in a decentralized distributed type network. A further object of the present invention is to provide excellent wireless communication system, wireless communication apparatus and wireless communication method and computer program in which collisions of beacons can be suitably avoided among a plurality of communication stations in a network configured when communication stations transmit beacons with each other. Yet a further object of the present invention is to provide excellent wireless communication system, wireless communication apparatus and wireless communication method and computer program in which a decentralized distributed type wireless network can be suitably formed while collisions of beacons that communication stations transmitted with each other can be avoided. DISCLOSURE OF THE INVENTION The present invention is made in view of the aforesaid aspect. According to an aspect of the present invention, there is disclosed in connection with a wireless communication system composed of a plurality of communication stations without relationship of control station and controlled stations, wherein respective communication stations transmit beacons in which information concerning a network is written with each other to construct the network. However, “system” refers to something of logical set of a plurality of apparatus (or function modules that can realize specific function) regardless of whether each apparatus or function module is accommodated within a single housing or not. Under the decentralized distributed type communication environment, each communication station lets other neighbor (within a communication range) communication station become aware of its existence by transmitting beacon information to other neighbor communication station at a predetermined time space and also lets other communication station become aware of the network configuration. Also, the communication station executes scan operation on each channel and detects by receiving a beacon signal whether it joined the communication range of the adjacent station. Further, the communication station can recognize the network configuration by deciphering information written on the beacon. Also, each communication station transmits neighbor apparatus information concerning beacon transmission timing contained in the beacon signal. In such case, the communication station can obtain not only network information of the adjacent station from which the communication station can directly receive the beacon but also beacon information of the next station of the adjacent station from which the local station cannot receive the beacon but the adjacent station can receive the beacon, that is, a hidden terminal. In such decentralized distributed type network, a new communication station which joins the network attempts to execute scan operation, that is, to continuously receive a signal during a time period longer than a superframe length to confirm the presence of the beacon transmitted from the neighboring station. If the communication station cannot receive the beacon from the neighboring station in this process, then the communication station sets proper beacon transmission timing. On the other hand, if the communication station can receive the beacon transmitted from the neighboring station, then the communication station sets timing at which any one of existing stations does not transmit the beacon to the beacon transmission timing of the local station with reference to neighbor apparatus information described in each received beacon. Here, in the wireless communication network according to the present invention, each communication station obtains a traffic priority use period as it transmits the beacon. Then, each communication station may transmit a regular beacon only once at the above-described predetermined time space and may be allowed to transmit more than one auxiliary beacon composed of signals similar to the regular beacon. Also, according to a second aspect of the present invention, in a computer program written in the computer readable format such that processing for carrying out wireless communication operation under the decentralized distributed type communication environment configured when a specific control station is not located and respective communication stations transmit beacons with information concerning a network written thereon with each other at a predetermined time space may be executed, a computer program is comprised of a beacon signal generating step for generating a beacon signal with information concerning the local station written thereon, a beacon signal analyzing step for analyzing a beacon signal received from a neighboring station and a timing control step for controlling beacon transmission timing. The computer program according to the second aspect of the present invention is obtained by defining a computer program written in the computer readable format so that predetermined processing may be executed on the computer system. In other words, when the computer program according to the second aspect of the present invention is installed on the computer system, cooperative action is demonstrated on the computer system and thereby the computer system is operated as a wireless communication apparatus. A plurality of wireless communication apparatus may be activated to construct a wireless network with similar action and effects to those of the wireless communication system according to the first aspect of the present invention. According to the present invention, in a decentralized distributed type network having a control station/controlled station relationship such as a master station and slave stations, it is possible to provide excellent wireless communication system, wireless communication apparatus and wireless communication method and computer program in which data can be transmitted while collisions of beacons can be avoided. Also, according to the present invention, in a network configured when communication stations transmit beacons with each other, it is possible to provide excellent wireless communication system, wireless communication apparatus and wireless communication method and computer program in which collisions of beacons among a plurality of communication stations can be avoided suitably. Also, according to the present invention, it is possible to provide excellent wireless communication system, wireless communication apparatus and wireless communication method and computer program in which a decentralized distributed type wireless network can be suitably formed while collisions of beacons that respective communication stations transmit with each other can be avoided. BRIEF DESCRIPTION OF DRAWINGS FIG. 1 is an explanatory diagram showing an example in which communication apparatus are located according to an embodiment of the present invention; FIG. 2 is a block diagram showing an example of an arrangement of a communication apparatus according to an embodiment of the present invention; FIG. 3 is a timing chart showing an example of a wireless communication system according to an embodiment of the present invention; FIG. 4 is a timing chart showing an example of timing at which beacons are transmitted according to an embodiment of the present invention; FIG. 5 is an explanatory diagram showing part of beacon description information according to an embodiment of the present invention; FIG. 6 is an explanatory diagram showing an example of NOBI and NBAI processing procedures according to an embodiment of the present invention; FIG. 7 is an explanatory diagram showing an example of the manner in which a transmission prohibit interval is defined according to an embodiment of the present invention; FIG. 8 is an explanatory diagram showing a first example of a beacon collision scenario according to an embodiment of the present invention; FIG. 9 is an explanatory diagram showing a second example of a beacon collision scenario according to an embodiment of the present invention; FIG. 10 is an explanatory diagram showing a beacon transmission offset according to an embodiment of the present invention; FIG. 11 is an explanatory diagram showing part of beacon description information according to an embodiment of the present invention; FIG. 12 is a block diagram showing an example of an M-sequence generating circuit according to an embodiment of the present invention; FIG. 13 is a flowchart showing an example of timing control processing according to an embodiment of the present invention; FIG. 14 is an explanatory diagram showing an example of a manner of determining a packet space according to an embodiment of the present invention; FIG. 15 is an explanatory diagram showing an example of a transmission prioritized interval according to an embodiment of the present invention; FIG. 16 is an explanatory diagram showing the transmission prioritized interval and a conflict transmission interval according to an embodiment of the present invention; FIG. 17 is an explanatory diagram showing an example of a packet format according to an embodiment of the present invention; FIG. 18 is an explanatory diagram showing an example of a beacon signal format according to an embodiment of the present invention; FIG. 19 is a timing chart showing an example (example 1) of the communication state at a communication station according to an embodiment of the present invention; FIG. 20 is a timing chart showing an example (example 2) of the communication state at a communication station according to an embodiment of the present invention; FIG. 21 is an explanatory diagram showing an example of a manner of distributing a time-axis resource according to an embodiment of the present invention; FIG. 22 is an explanatory diagram showing an example of information which is used to determine beacon transmission timing according to an embodiment of the present invention; FIG. 23 is an explanatory diagram showing an example of band reserve processing according to an embodiment of the present invention; FIG. 24 is an explanatory diagram showing an example of the manner in which a quiet packet is used according to an embodiment of the present invention; FIG. 25 is an explanatory diagram showing an example of an arrangement of a quiet packet according to an embodiment of the present invention; FIG. 26 is an explanatory diagram showing an example of an arrangement of a PHY frame according to an embodiment of the present invention; FIG. 27 is an explanatory diagram showing an example (example 1) of media scan according to an embodiment of the present invention; FIG. 28 is an explanatory diagram showing an example of the manner in which data is transmitted a plurality of times according to an embodiment of the present invention; FIG. 29 is an explanatory diagram showing an example (example 2) of media scan according to an embodiment of the present invention; FIG. 30 is an explanatory diagram showing an example (infrastructure mode) of a conventional wireless communication system; FIG. 31 is an explanatory diagram showing an example (ad hoc mode) of a conventional wireless communication system; FIG. 32 is an explanatory diagram showing an example of a signal transmission procedure in the ad hoc mode according to the prior art; FIG. 33 is an explanatory diagram showing an example of a packet space in the conventional wireless communication system; FIG. 34 is an explanatory diagram showing an example of a CSMA/CA procedure in the conventional wireless communication system; FIG. 35 is an explanatory diagram showing an example of CSMA/CA operation in the conventional wireless communication system; FIG. 36 is an explanatory diagram showing an example of band reserve transmission in the conventional wireless communication system; FIG. 37 is an explanatory diagram showing an example of the communication state in the conventional wireless communication system; and FIG. 38 is an explanatory diagram showing an example of an arrangement of a sub-slot in the conventional wireless communication system. BEST MODE FOR CARRYING OUT THE INVENTION An embodiment according to the present invention will be described below with reference to FIGS. 1 to 29. A propagation line of communication assumed in this embodiment of the present invention is wireless and it is also assumed that a network is constructed among a plurality of devices by using a single transmission medium (when a link is not separated by a frequency channel). This will apply for the case in which a plurality of frequency channels exists as transmission mediums) as well. Communication assumed in this embodiment is a store and forward type traffic and hence information is transferred at the packet unit. Also, processing at each communication station which will be described below is fundamentally processing executed by all communication stations joined the network. However, depending on the cases, all communication stations comprising the network do not always execute the processing which will be described below. FIG. 1 shows an example of the manner in which communication apparatus comprising the wireless communication system according to an embodiment of the present invention are located. In this wireless communication system, a specific control station is not located and respective communication stations are operated in a decentralized distributed fashion to form a so-called ad hoc network. This sheet of drawing shows the manner in which communication apparatus #0 to #6 are distributed on the same space. Also, in this sheet of drawing, communication ranges of the respective communication apparatus are shown by broken lines. Communication apparatus can communicate with other communication apparatus located within such communication range and these communication ranges are defined as the ranges in which a signal transmitted from the local station interfere with signals transmitted from other communication apparatus. Specifically, the communication apparatus #0 is located within the range in which it can communicate with neighbor communication apparatus #1, #4, the communication apparatus #1 is located within the range in which it can communicate with the neighbor communication apparatus #0, #2, #4, the communication apparatus #2 is located within the range in which it can communicate with the neighbor communication apparatus #1, #3, #6, the communication apparatus #3 is located within the range in which it can communicate with the neighbor communication apparatus #2, the communication apparatus #4 is located within the range in which it can communicate with the neighbor communication apparatus #0, #1, #5, the communication apparatus #5 is located within the range in which it can communicate with the neighbor communication apparatus #4, and the communication apparatus #6 is located within the range in which it can communicate with the neighbor communication apparatus #2. When communication is made between certain specific communication apparatus, a communication apparatus which can receive information from one communication apparatus of the apparatus being called but which cannot receive information from other communication apparatus, that is, “hidden terminal” exists. FIG. 2 is a block diagram schematically showing function and arrangement of a wireless communication apparatus which is operated as a communication station in the wireless network according to the embodiment of the present invention. Under a decentralized distributed type communication environment in which a control station is not located, the illustrated wireless communication apparatus can form a network by effectively carrying out channel access within the same wireless system while collisions are being avoided. As illustrated, a wireless communication apparatus 100 is composed of an interface 101, a data buffer 102, a central control unit 103, a beacon generating unit 104, a wireless transmission unit 106, a timing control unit 107, an antenna 109, a wireless reception unit 110, a beacon analyzing unit 112 and an information storage unit 113. The interface 101 exchanges a variety of information between it and an external device (for example, a personal computer (not shown), etc.) connected to this wireless communication apparatus 100. The data buffer 102 is used to temporarily store data transmitted from a device connected through the interface 101 or data received through a wireless transmission line before such data is transmitted via the interface 101. The central control unit 103 controls transmission and reception of a series of information in the wireless communication apparatus 100 and performs access control of a transmission line in a centralized fashion. The central control unit 103 performs operation control such as collision avoidance when beacons collide with each other. The beacon generating unit 104 generates beacon signals that are periodically exchanged between it and the neighbor wireless communication apparatus. In order for the wireless communication apparatus 100 to use the wireless network, there should be stipulated the position at which its own beacon is transmitted and the position at which it receives a beacon from the neighboring station. This information is stored in the information storage unit 113 and is transmitted to neighboring wireless communication apparatus in the form in which it is written in the beacon signal. An arrangement of the beacon signal will be described later on. Since the wireless communication apparatus 100 transmits a beacon at the beginning of a transmission frame period, a transmission frame period in the channel used by the wireless communication apparatus 100 is defined by a beacon space. The wireless transmission unit 106 carries out predetermined modulation processing in order to transmit data temporarily stored in the data buffer 102 and a beacon signal via radio waves. Also, the wireless reception unit 110 receives information and a beacon signal transmitted from other wireless communication apparatus at a predetermined time. Various communication systems applicable to wireless LAN, for example, which is suitable for relatively short-distance communication, can be applied to the wireless transmission and reception system in the wireless transmission unit 106 and the wireless reception unit 110. To be concrete, it is possible to use a UWB (Ultra Wide Band) system, an OFDM (Orthogonal Frequency Division Multiplexing: orthogonal frequency division multiplexing) system, a CDMA (Code Division Multiple Access: code division multiple access) system and the like. The antenna 109 transmits a signal to other wireless communication apparatus through a predetermined frequency channel or collects signals transmitted from other wireless communication apparatus. In this embodiment, the communication apparatus includes a single antenna and is unable to receive and transmit signals concurrently. The timing control unit 107 controls timing at which a wireless signal should be transmitted and received. For example, the timing control unit controls its own beacon transmission timing at the beginning of the transmission frame period, timing at which it receives a beacon from other communication apparatus, timing at which it transmits and receives data between it and other communication apparatus and a scan operation period, etc. The beacon analyzing unit 112 analyzes the existence of the neighbor wireless communication apparatus by analyzing the beacon signal received from the adjacent station, For example, information such as the beacon reception timing of the adjacent station and the neighboring station beacon reception timing is stored in the information storage unit 113 as neighbor apparatus information. The information storage unit 113 stores therein an execution procedure command (program in which a collision avoidance processing procedure and the like are described) such as a series of access control operations executed by the central control unit 103 and neighbor apparatus information obtained from the analyzed result of the received beacon. In the decentralized distributed type network according to this embodiment, each communication station lets other neighbor (that is, within a communication range) station become aware of its existence by transmitting beacon information at a predetermined time space on a predetermined channel and also informs other communication station of the network arrangement. The beacon transmission period is defined as “superframe” (Super frame) of which duration is 80 milliseconds, for example. A new communication station that joins the network can recognize that it entered the communication range by receiving the beacon signal from the neighboring station through scan operation and it can recognize the network arrangement by deciphering information described in the beacon. Then, the new communication station sets its own beacon transmission timing to timing at which a beacon is not transmitted from the neighboring station in gentle synchronism with the beacon reception timing. Next, FIG. 17 shows an example of a packet format according to this embodiment. A preamble composed of a unique word is added to the beginning of the packet in order to demonstrate the existence of the packet. In a heading area transmitted immediately after the preamble, there are stored attribute of this packet, length, transmission power and a payload portion transmission rate if PHY is in the multi-transmission rate mode. The heading area decreases its transmission rate so that a predetermined SNR may decrease several [dB] as compared with that of the payload portion. This heading area is different from a so-called MAC header and the MAC header is contained in the Payload portion. The payload portion is the portion depicted as PSDU (PHY Service Data Unit) in FIG. 17 and in which there is stored a bearer bit string containing a control signal and information. The PSDU is composed of the MAC header and an MSDU (MAC Service Data Unit), and the MSDU portion stores therein a data string transferred from a high-order layer. In the following description, in order to describe the present invention concretely, it is assumed that duration of the preamble is 8 [μsec], a bit rate of the payload portion is 100 Mbps upon transmission and that the heading area is composed of 3 bytes and transmitted at 12 [Mbps]. Specifically, when one PSDU is transmitted and received, there occurs an overhead of 10 [μsec] (=preamble 8 [μsec]+heading 2 [μsec]). A fundamental access procedure in this embodiment is the same CSMA/CA as that of the prior art, and information is transmitted after it was confirmed that the media is clear before information is transmitted. Beacon Transmission Procedure: First, a beacon transmission procedure of each communication station according to this embodiment will be described with reference to FIG. 3. Each communication station that joined the network transmits a beacon periodically in order to let the neighboring station become aware of the existence of the communication station. Here, the period is assumed to be 80 [msec] and let us describe the present invention with reference to the case in which the beacon is transmitted at every 80 [msec]. However, the above period is not always limited to 80 [msec]. Assuming that information transmitted by the beacon is 100 bytes, then a time required by transmission becomes 18 [μsec]. Since the beacon is transmitted once at 80 [msec], a beacon media occupying rate of one communication station is as sufficiently small as 1/4444. Although it seem to be useless that a beacon is transmitted even when the transmission signal does not arrive at the station, the transmission time rate is as sufficiently small as 1/4444, and this problem does not become serious. The respective communication stations are gently synchronized with each other while receiving and confirming the beacons transmitted from the neighbor communication stations. When a new communication station joined the network, the new communication station sets beacon transmission timing of the local station to timing at which a beacon is not transmitted from the neighbor communication station. An example thereof will be described below. When the neighbor communication station does not exist, as shown in FIG. 3A, a communication station [number 01] can begin to transmit a beacon at proper timing. B01 shows transmission position (timing) of a beacon transmitted from the communication station [number 01]. The beacon transmission period is defined as superframe (Superframe) and a beacon space is 80 [msec]. Also in FIGS. 3B, 3C, 3D, positions depicted by communication station numbers added to B show communication timing. After that, the newly-joined communication station starts transmitting a beacon in substantially the center of a time zone with the longest beacon space in the range in which it can receive the beacon such that its beacon may not collide with beacons transmitted from other communication stations which were already located within the superframe. For example, when a new communication station [number 02] appears in the beacon transmission state shown in FIG. 3A, it starts transmitting a beacon at the middle timing of the beacon space of the communication station [number 01] while it is recognizing the existence of the communication station 01. After that, a new communication station which joined the communication range sets its own beacon transmission timing so that it may not collide with the layout of the existing beacons. At that time, since each communication station obtains a prioritized use area (TPP) immediately after it has transmitted the beacon (as will be described later on), it is preferable that beacon transmission timing of each communication station should be equally dispersed within the transmission frame period rather than crowded from a transmission efficiency standpoint. Accordingly, in this embodiment, the new communication station can start transmitting the beacon in substantially the middle of the time zone with the longest beacon space within the range in which it can receive the beacon from other communication station. Further, when a new communication station [number 03] appears in the state shown in FIG. 3B, it starts transmitting a beacon in the middle timing of the beacon space while it is confirming the existence of the communication state [number 01] and the communication station [number 02]. After that, according to a similar algorithm, as shown in FIGS. 3C and 3D, the beacon space is narrowed as a neighbor communication station occurs. However, as the beacon space is narrowed in this manner, the band (transmission frame period) is occupied by the beacons so that a minimum beacon space should be stipulated such that the band may not be filled with the beacons. For example, when the beacon space is stipulated as the minimum beacon space Bmin=625 [μsec], only 128 communications can be accommodated within the range in which radio waves can be received and transmitted at maximum. FIG. 4 shows an example of an arrangement of beacon transmission timing which can be located within the superframe. However, the illustrated example expresses the elapse of time in the superframe of 80 milliseconds as a clock of which hand is rotated in the clockwise direction on the circular ring. In the example shown in FIG. 4, 16 positions 0 to F from ranging 0 to F in total are constructed as times at which beacons can be transmitted, that is, “slots” in which beacon transmission timing can be located. As had already been described with reference to FIG. 3, let it be assumed that beacons are located in accordance with the algorithm in which the beacon transmission timing of the newly-joined station is sequentially set to at substantially the middle timing of the beacon space set by the existing communication station. When Bmin is stipulated as 5 milliseconds, only 16 beacons can be located at maximum per superframe. That is, more than 16 communication stations cannot join the network. Although not shown explicitly in FIGS. 3 and 4, each beacon is transmitted at a time which is intentionally displaced from a TBTT (Target Beacon Transmission Time) by a small time offset. This will be referred to as “TBTT offset”. In this embodiment, a TBTT offset value is determined by a pseudorandom number. This pseudorandom number is determined by a pseudorandom sequence TOIS (TBTT Offset Indication Sequence) that is uniquely determined and the TOIS is updated at every superframe period. With the TBTT offset, even when two communication stations have beacon transmission timings located at the same slot on the superframe, actual beacon transmission times can be displaced. Hence, even when the beacons collide with each other in a certain superframe period, the respective communication stations can transmit and receive their beacons in another superframe period (or the neighbor communication station can receive the beacons from both of the above communication stations) so that the communication station can recognize that the beacon of the local station collided with other beacons. The communication station includes the TOIS set at every superframe period in the beacon information and transmits this resultant beacon information to the neighboring station (which will be described later on). Also, according to this embodiment, each communication station is ought to carry out reception operation before and after the beacon transmitted from the local station when it does not transmit and receive data. Also, even when each communication station does not transmit and receive data, it is ought to carry out scan operation by continuously energizing the receiver over one superframe once per several seconds to thereby confirm whether or not the presence of the beacon from the neighboring station is changed or whether or not the TBTT of each neighboring station is displaced. Then, if it is determined that the TBTT is displaced, then a target beacon transmission time in which a displacement within −Bmin/2 milliseconds is stipulated as TBTT with reference to a TBTT group recognized by the local station is defined as “advanced target beacon transmission time” and a target beacon transmission time in which a displacement within +Bmin/2 milliseconds is stipulated as TBTT is defined as “delayed target beacon transmission time”, and a time is corrected in accordance with the most delayed TBTT. NBOI Field: As one of information transmitted by a beacon, FIG. 5 shows an example of the manner in which a Neighboring Beacon offset Information (NBOI) field is described. The position of the beacon that can be received by the local station (reception time) is written on the NBOI field by the relative position (relative time) from the position (transmission time) of the beacon of the local station in the form of a bit map. The example shown in FIG. 5 describes the case in which only 16 kinds of beacon transmission positions can exist at the minimum space Bmin=5 [msec], by way of example, and hence the NBOI field length is 16 bits but it may not always be limited to 16 bits. The example of FIG. 5 shows an example of the NBOI field indicative of the message that “the communication station (number 0) in FIG. 4 can receive the beacons from the communication station [number 1] and the communication station [number 9]”. With respect to the bits corresponding to the relative positions of the beacons that can be received, the relative position at which the beacon is received is depicted by a mark and the relative position at which the beacon is not received is depicted by a space. In the example of FIG. 5, 0th bit, first bit and ninth bit are depicted by the marks. The mark on the 0th bit indicates that the local station transmitted the beacon, and the mark on the first bit indicates that the beacon is received at timing delayed from the TBTT field of the beacon by a delay amount of Bmin*1. Similarly, the mark on the ninth bit indicates that the beacon is received at timing delayed from the TBTT field of the beacon by a delay amount of Bmin*9. Although the details will be described later on, bits corresponding to timing at which the beacon is not received may be depicted by a mark for other purpose such as when an auxiliary beacon is transmitted. NBAI Field: Also, similarly to the NBOI field, a Neighboring Beacon Activity Information (NBAI) field is defined as one of information similarly transmitted by the beacon. The NBAI field describes the position (reception time) of the beacon that is actually received by the local station based upon the relative position of the beacon from the local station in the form of a bit map. Specifically, the NBAI field indicates that the local station is set to the active state in which it is able to receive a beacon. Further, based upon the information of the NBOI field and the NBAI field, it is possible to provide information in which the local station receives a beacon at the beacon position within the superframe. Specifically, based on the NBOI field and the NBAI field contained in the beacon, the following two-bit information is transmitted to each communication station. NBAI NBOI Description 0 0 BEACON IS NOT RECOGNIZED AT CORRESPONDING TIME 0 1 BEACON IS RECOGNIZED AT CORRESPONDING TIME 1 0 COMMUNISCATION STATION IS SET TO ACTIVE STATE AT CORRESPONDING TIME 1 1 COMMUNICATION STATION IS RECEIVING BEACON AT CORRESPONDING TIME OR-Processing of NBOI/NBAI: FIG. 6 shows the manner in which a communication station A which joined the network sets the TBTT field of the local station based upon the NBOI field of each beacon obtained from the beacons received from the neighboring station by scan operation. Let it be assumed that the communication station could receive the beacons from the stations 0 to 2 during the superframe by scan operation. The beacon reception time of the neighboring station is treated as the relative position relative to the regular beacon of the local station and the NBOI field writes this beacon reception time in the bit map format (mentioned hereinbefore). Accordingly, the communication station A shifts the NBOI fields of the three beacons received from the neighboring stations and arranges the bit corresponding positions on the time axis, whereafter this communication station calculates a sum of NBOI bits of each timing to thereby synthesize the NBOI bits for reference. A procedure thereof will be described concretely. A beacon 1 is received with a delay of three slots with reference to the transmission timing of a beacon 0. The communication station stores this information in a memory and so on. Then, three slots of the NBOI field contained in the beacon 1 are shifted to the beginning and this information is stored in a suitable means such as a memory (second row in FIG. 6)). Similar processing is effected on the beacon 2 (third row in FIG. 6). A sequence obtained after the NBOI fields of the neighboring stations were synthesized and referred to is “1101, 0001, 0100, 1000” shown by “OR of NBOIs” in FIG. 6. “1” indicates the relative position of timing at which the TBTT field was already set within the superframe, and “0” indicates the relative position of timing at which the TBTT field is not yet set. In this sequence, the place in which the space (zero) becomes the longest run-length becomes a nominated place where a new beacon is located. In the example shown in FIG. 6, the longest run-length is 3 and two nominated places exist. Then, the communication station A determines 15th-bit timing as the TBTT field of the regular beacon of the local station. The communication station A sets the 15th-bit time as the TBTT field of the regular beacon of the local station (that is, the leading portion of the superframe of the local station) and starts transmitting the beacon. At that time, the NBOI field in which the communication station A transmits the beacon writes each reception time of the beacons of the communication stations 0 to 2 which can receive the beacons in the bit map format in which the bit positions corresponding to the relative positions from the transmission time of the regular beacon of the local station are marked. This is shown as “NBOI for TX (1 Beacon TX) in FIG. 10. When the communication station A transmits the auxiliary beacon for the purpose of obtaining a prioritized transmission right and the like, after that, this communication station searches the longest run-length of the space (zero) of the sequence shown by “OR of NBOIs” in which the NBOI field of the neighboring station is synthesized and sets a transmission time of the auxiliary beacon to the thus searched space. The example of FIG. 10 assumes the case in which the communication station transmits two auxiliary beacons, and the transmission timing of the auxiliary beacons is set to the times of 6th-bit and 11th-bit spaces. In this case, in the NBOI field during which the communication station A transmits the beacon, in addition to the relative positions of the regular beacon of the local station and the beacons received from the neighboring stations, the positions at which the local station transmits the auxiliary beacon (relative position to the regular beacon) also are marked and presented as shown by “NBOI for Tx (3 Beacon Tx)”. When each communication station sets the beacon transmission timing TBTT of the local station by the above-mentioned processing procedure and transmits the beacon, under the condition in which each communication station is in the stationary state and the range in which radio waves reach is not fluctuated, it is possible to avoid the beacons from colliding with each other. Also, the auxiliary beacon (or a plurality of signals similar to the beacon) is transmitted within the superframe in response to a degree of priority of transmission data, whereby resources can be assigned with a priority and Qos communication can be provided. Also, since each communication station can independently understand saturation of the system with reference to the number of beacons (NBOI fields) received from the neighboring station, the present invention, even though it is the distributed control system, can accommodate prioritized traffic while considering saturation of the system at every communication station. Further, since each communication station studies the NBOI field of the received beacon so that the beacon transmission times may not collide with each other, even when a plurality of communication stations accommodates the prioritized traffic, it is possible to avoid the beacon transmission times from frequently colliding with each other. As described above, when the new communication station joins the network, the sum of the NBOI fields obtained from the beacons received from the respective communication stations is calculated so that the center of the interval in which the run-length of the space becomes longest is determined as the beacon transmission timing. While the above description is the example in which the sum of the NBOI fields are calculated by OR, a sum (OR) of the NBAI fields is calculated by a similar procedure, whereby a beacon is not transmitted in the beacon transmission time of the marked timing under control. Specifically, when the communication station transmits some information, the beacon transmitted from the neighbor communication station is received and a sum (OR) of the NBAI fields obtained from the beacons received from the respective communication stations is calculated so that the beacon is not transmitted in the beacon transmission time of the marked timing. FIG. 7 shows the processing executed in that case in which the NBAI field is formed of 8 bits and in which 0th-bit, 4th-bit and 6th-bit are marked after a sum of NBAI fields of respective received beacons was calculated (OR), by way of example. The 0th-bit is the beacon of the local station and hence the addition processing is not carried out. Since the 4th-bit is marked, at the time T4 which is the beacon transmission time of the 4th-bit, the transmission permission flag of the local station is not raised. Also, this applies for the 6th-bit as well and hence at the corresponding time T6, the transmission permission flag of the local station is not raised and the transmission is not carried out. Thus, when a certain communication station wants to receive a beacon from a certain communication station, the transmission station can be prohibited from disturbing this reception and it becomes possible to transmit and receive information with high reliability. First Example of Beacon Collision Scenario: An example of the manner in which information obtained from the NBOI field is used will be described with reference to FIG. 8. The left-hand sides of FIGS. 8A to 8C show the states in which the communication stations are located, and the right-hand sides thereof show examples in which beacons are transmitted from the respective stations, respectively. FIG. 8A shows the case in which only a communication station 10 (STA0) exists to transmit a beacon B-0. At that time, since the communication station 10 attempts to receive a beacon but failed to receive the beacon, proper beacon transmission timing can be set and transmission of the beacon B0 can be started in response to the arrival of this timing. Here, the beacon is transmitted at the space of 80 [msec]. At that time, all bits of the NBOI field of the beacon transmitted from the communication station 10 are 0. FIG. 8B shows the case in which a communication station 11 (STA1) joined the communication range of the communication station 10 later on. When the communication station 11 attempts to receive a beacon, it receives the beacon B0 of the communication station 10. Further, since all bits of the NBOI field of the beacon B0 of the communication station 10 are all 0 except the bits indicating the transmission timing of the local station, the beacon transmission timing is set to substantially the center of the beacon space of the communication station 10 in accordance with the above-mentioned step 1. In the NBOI field of a beacon B1 transmitted from the communication station 11, the bit indicative of the transmission timing of the local station and the bit indicative of the reception timing of the beacon from the communication station 10 are set to 1 and other bits are set to 0. Also, when the communication station 10 also becomes aware of the beacon from the communication station 11, it sets the corresponding NBOI field to 1. Further, FIG. 8C shows the case in which a communication station 12 (STA2) joined the communication range of the communication station 11 later on. In the example of FIG. 8, the communication station 10 serves as a hidden terminal for the communication station 12. For this reason, since the communication station 12 cannot recognize that the communication station 11 is receiving the beacon from the communication station 10, there is a possibility that this communication station will transmit the beacon at the same timing as that of the communication station 10 so that their beacons will collide with each other. The NBOI field is used to avoid this phenomenon. When the communication station 12 attempts to receive the beacon, it receives the beacon B1 from the communication station 11. Further, in the NBOI field of the beacon B1 from the communication station 11, in addition to the bit indicative of the transmission timing of the local station, 1 is also set to the bit which indicates timing at which the communication station 10 is transmitting the beacon. For this reason, even when the communication station 12 cannot directly receive the beacon B0 transmitted from the communication station 10, it recognizes the timing at which the communication station 10 transmits the beacon B0 and will not transmit the beacon at this timing. Accordingly, at that time, the communication station 12 sets the beacon transmission timing to substantially the middle between the space of the beacon transmitted from the communication station 10 and the space of the beacon transmitted from the communication station 11. Of course, in the NBOI field of the beacon B2 transmitted from the communication station 12, bits indicative of the beacon transmission timings of the communication stations 12 and 11 are set to 1. The NBOI field in which the beacons are transmitted at the same timing as that of the communication station 10 to cause the beacons to collide with each other is used to avoid this phenomenon. That is, the NBOI field is used to avoid the occurrence of the beacon collision scenario (first example) shown on the right-hand side of FIG. 8C. As described above, in the wireless communication system according to this embodiment, each communication station transmits the beacon information to other communication station so that other communication station can recognize the existence of the local station and can also recognize the network arrangement. The new communication station, joined to the network, receives the beacon signal so that it can detect that it entered the communication range. At the same time, such new communication station deciphers the information written in the beacon and can transmit the beacon while avoiding its beacon signal from colliding with the existing beacon signal and thereby a new network can be configured. Second Example of Beacon Collision Scenario: In the case except the above-mentioned first example of the beacon collision scenario, the beacon collision case is assumed. This is assumed to be a second example of a beacon collision scenario and is shown in FIG. 9. The second example is the example in which the systems in which the networks were constructed already approach each other. As shown in FIG. 9A, the communication station 10 (STA0) and the communication station 11 (STA1) exist in the range in which they cannot receive radio waves from a communication station 12 (STA2) and a communication station 13 (STA3, and the communication station 10 and the communication station 11 communicate with each other. Quite independently of the relationship between the above communication stations, the communication stations 10 and 11 are communicating with each other. Let it be assumed that the beacon transmission timings of the respective stations which are not aware of them at that time unfortunately are overlapping with each other as shown on the right-hand side of FIG. 9A. Also, assuming that the respective stations are moved later and that they become able to transmit and receive information, then there occurs an accident in which the beacons of the respective stations collide with each other as shown in FIG. 9B. Such collision of the beacons can be avoided by the following processing. TBTT Offset Indicator (Offset Indicator): FIG. 10 shows the TBTT times and the transmission times at which the beacons are transmitted in actual practice. The beacon transmission timing is determined at every 80 [msec] in the step 1. The beacon transmission time determined at every 80 [msec] is defined as a TBTT (Target Beacon Transmit Time). In this embodiment, in order to prevent the beacons from colliding with each other continuously in the case like the above-mentioned second example of the beacon collision scenario, the beacon transmission timing is displaced from the TBTT time intentionally. For example, when the TBTT offset is defined such that the actual beacon transmission time is set to any one of TBTT, TBTT+20[μsec], TBTT+40[μsec], TBTT+60[μsec], TBTT+80[μsec], TBTT+100[μsec] TBTT+120[μsec] as shown in FIG. 10, the TBTT offset for transmitting a beacon is determined at every superframe period and a TOISS field (which will be described later on) contained in the beacon is updated. Before a beacon is transmitted, the offset amount from the TBTT may be selected randomly this time. While the beacon transmission time is defined at the unit of 20 [μsec] step, it is not limited to 20 [μsec] and may be defined by a smaller step. The amount displaced from the TBTT intentionally is referred to as a “TBTT offset”. Also, a TBTT Offset Indicator Sequence (TOISS) field shown in FIG. 15 is defined as one of information transmitted by the beacon. In the TOIS field, there is written a beacon transmission offset value indicating that the amount in which the beacon is intentionally displaced from the TBTT this time and transmitted. The example of FIG. 11 shows the case in which there are provided seven stages of the TBTT offset values and the TOIS field is expressed as 3 bits “2 {circumflex over ( )}3>=7”. When other packet is transmitted in the TBTT field, the beacon should be transmitted after the transmission of the above packet has been ended. It is frequently observed that the beacon will not be transmitted at the time as the transmission station intends to. In this case, a bit indicative of TBTT+X is set as the TOIS field and the fact that this time beacon transmission timing is not the intended time is transmitted to the neighboring station which can receive the beacon. As described above, since the beacon transmission time is displaced in accordance with the TBTT offset, in the worst cases like “the second example of beacon collision scenario”, it is possible to avoid the accident in which the beacon signals collide with each other continuously. The TBTT offset can be given by the pseudorandom sequence such as a PN sequence. FIG. 12 is a diagram showing an example of a circuit arrangement in which the TBTT offset is generated by a 16-bit pseudorandom sequence (M sequence) that can be obtained by a simple calculation. A bit string set to a register 80 is updated bit by bit to the value obtained by the addition of adders 81, 82, 83, values are obtained from predetermined positions of the register 80 and added by adders 84 to 92, 3 bits are inputted to a register 93 and the 3 bits are set to the TBTT offset. According to this arrangement, it is possible to effectively avoid the accident in which the beacon signals collide with each other continuously. While the definition of the TOIS field has been described so far as the information contained in the beacon, instead of the TOIS field, the content (TOI sequence) of the pseudorandom sequence register 80 shown in FIG. 12 will sometimes be transmitted as the information contained in the beacon. When the content of the register 80 is transmitted as the information contained in the beacon, the reception station which received that signal extracts information from the register 93 by the means shown in FIG. 12 and can obtain the TOI information. The TOIS field is calculated each time the station transmits the beacon that is to be transmitted periodically. As a result, the station which received the beacon once becomes able to calculate the TOIS information of the transmission station in a free-running fashion to thereby obtain the next offset and the next offset after the next TBTT offset before it receives the beacon. Also in this case, when the transmission station could not transmit the beacon at the time as it intends to, the transmission station informs the beacon reception station of the fact that the beacon transmission timing of this time is not the intended time by transmitting all zeroes as the TOI sequence (TOI Sequence). Beacon Transmission Timing Alteration Request: In the case of “the second example of beacon collision scenario”, there still remains a problem in which beacons will collide with each other once in several times. Accordingly, when each station recognizes that the TBTT fields are set substantially simultaneously at a plurality of stations, it can transmit a TBTT alteration request message to any one of the beacon transmission stations. The communication station which received such message scans the beacon of the neighboring station and sets a time at which the local station did not receive the beacon and at which 1 is not set by the NBOI field of the received beacon as a new TBTT (new TBTT). Before altering the TBTT field in actual practice after the new TBTT field was set, the communication station writes a message of “new TBTT field is set and the TBTT field is altered after XX [msec]” in the beacon that is transmitted from the existing TBTT field and alters the TBTT field. Countermeasure Against Difference of Clock Frequency: Next, a mechanism for removing a difference of a clock frequency occurred between the respective communication stations will be described. When the clock frequencies of the respective communication stations are different, drift of transmission and reception timings occurs among the respective stations. If a difference up to ±20 ppm is allowed as an accuracy of a clock frequency, a clock frequency is displaced 3.2 [μsec] at 80 [msec]. If such displacement is left as it is, then there occurs an accident in which the beacon transmission timings overlap with each other. Accordingly, each communication station continuously scans the beacons transmitted from the neighboring station more than once at about 4.0 [sec]. In that time period, it is desired that each communication station should receive over a time period longer than the beacon transmission space of the local station. Then, the communication station matches the beacon transmission timing to the most delayed beacon transmission timing (TBTT) of the communication station. Although the clock frequency is displaced approximately 160 [μsec] during a time period of 4.0 [μsec] at maximum, the communication station can make various countermeasures such as to control the timing within the local station after it has obtained displacement information. In addition to the above-described object, the beacon scan is carried out in order to confirm whether the state (presence) of a peripheral device is changed or not. Specifically, when the communication station receives a beacon from a new communication station during the beacon scan, the communication station transmits the message indicating that the new communication station appears to the high-order layer together with information transmitted by the above beacon. Conversely, when the communication station could not receive the beacon from the communication station of which beacon could be received so far, the communication station stores therein such information. When the communication station could not receive the beacon from the same communication station over a plurality of scanning, it becomes aware that the above communication station has left from the network and it informs the high-order layer of such information. Alternatively, when the communication station could not receive the beacon from the communication station of which beacon could be received son far, it regards that the presence of the neighboring station was changed and it informs the high-order layer of such information successively, whereafter it updates the list (Neighbor List) of the neighboring station. Next, details of an algorithm for countermeasure against difference of clock frequencies will be described with reference to a flowchart of FIG. 13. Clock frequency difference information is obtained by beacon scanning. When beacon scanning (countermeasure processing against difference of clock frequencies) is started, first, a timer is set to start counting 80 [msec] which is the beacon space. Then, it is determined whether or not this count is ended (step S1). When the count is ended, the beacon scanning and information collection required for clock frequency difference countermeasure is ended. The communication station continues to attempt to receive the beacon until the timer is ended. If the beacon is received (step S2), then the communication station compares the TBTT field calculated within the local station and the TBTT field of the received beacon with each other. The communication station can obtain the TBTT field of the received beacon by examining the time at which the beacon is received and the TOIS field. When the TOIS field is set as TBTT+X, that beacon received time is omitted from the total target. When the TIOS sequence is written in the beacon, all bits are set to 0 as the notation indicating TBTT+X. If the station which received this has the TIOS sequence in which all bits are 0, such beacon received time is omitted from the total target. The communication station calculates “delayed amount of the TBTT field of the received beacon from the TBTT field calculated within the local station” with respect to the beacon of the total target (step S3). Then, the beacon of which TBTT field is most delayed is judged from all the beacons received until the timer is ended (step S4), and this delayed amount is stored as a most delayed timing (Most Delayed Timing: MDT) (step S5). A value which results from subtracting a previously-set a [μsec] (for example, 2 [μsec]) from the MDT obtained at the time at which the timer is ended is set to α (step 6). Then, it is determined whether or not α is a positive number, that is, the value which results from subtracting a [sec] from the MDT is delayed from the clock frequency of the local station (step S7). If delayed, then the clock frequency of the local station is delayed a (step S8). According to the above processing, even when the clock frequency of each communication station is displaced, a time is fundamentally adjusted in accordance with the most delayed clock frequency of the communication station existing within the system and hence it is possible to avoid the accident in which transmission and reception timings will drift and overlap with each other. The above-described value a [μsec] is the value that should be set in accordance with the specification required for timing control and may not be limited herein. The scan space is first set to be a relatively short space of about 1 [sec]. When the above-described clock drift value is extracted, if it is determined that disagreement between the clock frequency of the local station and the clock frequency of the neighboring station is not so remarkable, then it is possible to further suppress the influence caused by the clock drift by using a method for setting a longer space stepwise. Stop Receiving Beacon of Specific Station: Although each communication station receives the beacon transmitted from the neighboring station in accordance with the above-described procedure, when it receives from the high-order layer an instruction message of “stop communication with this communication”, it does not perform reception operation at the beacon transmission time of the communication station. As a result, it becomes possible to decrease unnecessary reception processing between it and a communication station which is not relating to the local station. Hence, it becomes possible to contribute to decrease of power consumption. The instruction message of “stop communication with this communication station” is judged from attribute of devices of the communication station, it is issued when authentication was not made or it is instructed by users. Definition of Packet Space (Inter Frame Space): Similarly to the cases such as the IEEE802.11 system, a plurality of packet spaces is defined also in this example. The definition of this packet space will be described with reference to FIG. 14. As the packet space, there are defined an SIFS (Short Inter Frame Space) which is a short packet space and an LIFS (Long Inter Frame Space) which is a long packet space. Only a prioritized packet is allowed to be transmitted at the SIFS packet space, and other packets are allowed to be transmitted during the random backoff packet space in which the LIFS+ random value is obtained after it has been determined that the media is clear. To calculate the random-backoff value, there is used a method that is known in the existing technology. Further, in this embodiment, “LIFS” and “FIFS+backoff” (FIFS: Far Inter Frame Space) are defined in addition to the above-mentioned packet spaces “SIFS” and “LIFS+backoff”. Although it is customary to apply the packet spaces of “SIFS” and “LIFS+backoff”, in a time zone in which a certain communication station is given a prioritized transmission right, other communication station uses the packet space of “FIFS+backoff” and the communication station which is given the priority uses the packet space of SIFS or LIFS. The paragraph “time zone in which a certain communication station is given a prioritized transmission right” will be described below. Transmission Prioritized Interval TPP: While each communication station is transmitting a beacon at a constant space, according to this embodiment, during a proper time period after the transmission of the beacon, the communication station that has transmitted the beacon is given a prioritized transmission right. FIG. 15 shows an example of the manner in which the beacon transmission station is given a prioritized transmission right. FIG. 16 shows an example in which 480 [μsec] is given as this transmission prioritized interval. This prioritized interval is defined as TPP (Transmission Prioritized Period). The TPP is started immediately after the beacon was transmitted and ended at a time passed from the TBB field by T_TGP. Since each communication station transmits the beacon at every superframe, the TPP with the same time rate is fundamentally distributed to each communication station. A time period in which other communication station transmits the beacon after the TPP of one communication station elapsed is served as an FAP (Fairly Access Period). In the FAP (Fairly Access Period), there is carried out a fair media acquisition contention based upon the ordinary CSMA/CA system (or PSMA/CA system which will be described later on). FIG. 16 shows an arrangement of a superframe. As illustrated, after each communication station has transmitted the beacon, the TPP of the communication station which has transmitted such beacon is assigned, the FAP is assigned after a time corresponding to the duration of the TPP elapsed and the FAP is ended when the next communication station transmits the beacon. While the TPP is started immediately after the beacon was transmitted by way of example, the present invention is not limited thereto and the start time of the TPP may be set to a relative position (time) from the beacon transmission time. Also, the TPP may be defined in the form of 480 [μsec] from the TBTT field. Further, as shown in FIG. 15, since the TGP area is expired during the period T_TPP that is based on the TBTT field, when the beacon transmission time is delayed due to the TBTT offset, the TPP area is reduced. Here, a packet space in each field within the superframe will be described. During the FAP period, all communication stations can transmit the beacons at the “LIFS+backoff” space and hence the access right can be acquired by fair contention control. For example, in order to acquire the access right, the RTS packet and short commands are transmitted at the “LIFS+backoff” space and the CTS packet, data and the Ack packet which are to be transmitted later are transmitted at the “SIFS” space. IFS parameters in the FAP will be shown below. TABLE SETTING OF IFS PARAMETER IN FAP KIND OF COMMUNICATION ACCESS WAIT KIND OF TRANSMISSION STATION STATE FRAME SPACE TRIGGER ALL HAVING RTS LIFS + Backoff N/A COMMUNICATION TRANSMISSION COMMAND LIFS + Backoff N/A STATIONS DATA EXISTS N/A CTS SIFS SPACE AFTER RTS WAS RECEIVED HAVING DATA SIFS SPACE AFTER CTS WAS TRANSMISSION RECEIVED DATA EXISTS DATA RECEIVED ACK SIFS SPACE AFTER DATA WAS RECEIVED On the other hand, in the TPP area, the communication station which transmitted the beacon is given the access right and is allowed to transmit the frame after SIFS time passed. Also, the communication station which is designated by the communication station which transmitted the beacon is given a prioritized transmission right and is allowed to transmit the frame after the SIFS time elapsed. When an answer to the CTS packet is not received although the communication station which acquired the prioritized transmission right transmits the RTS packet to a specific communication station, the communication station which acquired the prioritized transmission right transmits again the RTS packet at the LIFS space. Also, when another communication station that holds data to be transmitted to the communication station which acquired the prioritized transmission right confirms the message “node does not have transmission data”, it allows the transmission at the SIFS+backoff (Backoff) frame space. However, it is frequently observed that the third communication station has no means to recognize that the communication station which acquired the prioritized transmission right has data. The communication station without the prioritized transmission right recognizes by receiving the beacon that other communication station starts the prioritized transmission, it sets the fundamental frame space to the FIFS during the period of T_TPP and it tries to acquire the access right at the FIFS+backoff frame space. By the above-described procedure, there is realized a mechanism in which when the communication station which acquired the prioritized transmission right in the TPP area by the above-described procedure has the data which the communication station is to transmit and receive, that communication station is given the access right while when the above communication station does not have the data to be transmitted and received, the access right of the communication station is discarded and other communication station acquires the access right. The following controls are required depending upon the kinds and states of the respective communication stations. TABLE SETTING OF IFS PARAMETER IN TPP KIND OF COMMUNICATION ACCESS WAIT KIND OF TRANSMISSION STATION STATE FRAME SPACE TRIGGER WITH ACCESS SET PRIORITY RTS SIFS SPACE AFTER BEACON RIGHT TRANSMISSION COMMAND WAS RIGHT TRANSMITTED WITH PRIORITY N/A CTS SIFS SPACE AFTER RTS WAS TRANSMISSION COMMAND RECEIVED RIGHT WITHOUT PRIORITY TRANSMIT BEACON RTS SIFS + Backoff AFTER COMPLETION TRANSMISSION TRANSMISSION DATA COMMAND OF TRANSMISSION RIGHT TO COMMUNICATION OF PRIORITY STATION EXISTS TRANSMISSION RIGHT COMMUNICATION STATION TRANSMIT BEACON RTS FIFS + backoff AFTER COMPLETION TRANSMISSION DATA COMMAND OF TRANSMISSION OF TO COMMUNICATION PRIORITY TRANSMISSION STATION DOES NOT RIGHT COMMUNICATION EXIST STATION ALL TRANSMISSION DATA SIFS SPACE AFTER CTS WAS COMMUNICATION DATA EXISTS RECEIVED STATIONS DATA RECEIVED ACK SIFS SPACE AFTER DATA WAS RECEIVED With respect to the packet transmission within the TPP of the local station, the communication station is also allowed to transmit the packet at the LIFS space. Further, with respect to the packet transmission within the TPP of other station, other station transmits the packet at the FIFS+backoff space. While the FIFS+backoff is constantly used as the packet space in the IEEE802.11 system, according to the arrangement of this embodiment, this space can be narrowed and hence more effective packet transmission becomes possible. Also, while each communication station fundamentally transmits one beacon at every superframe period, depending on the cases, it is allowed to transit a plurality of beacons or a signal similar to the beacon, and it can acquire the TPP each time it transmits these beacons. In other words, the communication station can maintain the prioritized transmission resources corresponding to the number of the beacons transmitted at every superframe. Here, the beacon that the communication station constantly transmits at the beginning of the superframe period is referred to as a “regular beacon” and the beacon following the second beacon that is transmitted at other timing in order to acquire the TPP or for other purposes is referred to as an “auxiliary beacon”. Application of Use of TPP: When the TPP is defined as 480 [μsec], 21 packets corresponding to 60 [Byte] or about one packet of 6000 [Byte] can be transmitted. Specifically, even when the media is crowded, transmission of approximately 21 ACK packets at 80 [msec] can be guaranteed. Alternatively, when only the TPP is used, a transmission line of 600 [kbps]=(6000 [Byte]/80 [msec]) can be maintained at the lowest. While the prioritized transmission right is given to the communication station in the TPP as described above, the prioritized transmission right is given to a communication station which is called by the communication station in the TPP. While transmission takes precedence in the TPP fundamentally, when the communication station does not have any information to be transmitted but it is clear that other station has information that is to be transmitted to the local station, a paging (Paging) message or a polling (Polling) message may be transmitted to such “other station”. Conversely, when the local station has no information to be transmitted although it has transmitted the beacon and the communication station is not aware of the fact that other station has information to be transmitted to the local station, the above communication station does nothing, it discards the transmission priority given thereto by the TPP and it does not transmit any information. Then, after the LIFS+backoff or the FIFS+backoff passed, other station starts transmission even in this time zone. Having considered the arrangement in which the TPP is followed immediately after the beacon was transmitted as shown in FIG. 16, it is preferable that the beacon transmission timing of each communication station should be equally dispersed within the transmission frame period rather than crowded. Accordingly, in this embodiment, fundamentally, the transmission of the beacon is started at substantially the center of the time zone in which the beacon space is longest within the range in which it can receive the beacon. Of course, there may be used a method in which the beacon transmission timing of each communication station is located intensively and reception operation is stopped during the remaining transmission frame period to decrease power consumption. Field of Beacon: Information described in the beacon transmitted in the decentralized distributed type wireless communication system according to this embodiment will be described. FIG. 18 shows an example of a beacon signal format. As was already been described with reference to FIG. 17, the preamble indicative of the existence of the packet is added to the beginning of the packet, the heading area in which attribute and length of the packet are described exists next to the preamble and the PSDU is coupled to the heading area. When the beacon is transmitted, information indicating a message in which the packet is the beacon is written in the heading area. Also, information that is transmitted by the beacon is written in the PSDU. In the illustrated example, the beacon contains a TA (Transmitter Address) field which is an address indicating the transmission station uniquely, a Type field indicative of the kind of the beacon, a TOI field indicative of a TBTT offset value in the superframe period during which the beacon is transmitted, an NBOI (Neighboring Beacon Offset Information) field which is reception time information that can be received from the neighboring station, an NBAI (Neighboring Beacon Activity Information) field which is information indicative of a transmitted time of a beacon signal received by the local station, an ALERT field which stores therein information for altering the TBTT field or other various kinds of information to be transmitted, a TxNum field indicative of an amount in which the communication station maintains resources with a priority, a Serial field indicative of an exclusive unique serial number assigned to the beacon when a plurality of beacons is transmitted during the superframe period, a TIM (Traffic Indication Map) field which is information indicating that the destination station to which information of this communication station is transmitted at present, a Page (Paging) field indicating that the reception station written in the TIM field plans to transmit information in the immediately-following TPP, a Sense Level field for storing therein information indicating the level (reception SINR) of the reception signal that the station detects as the reception signal, a TSF (Timing Synchronization Function) field for reporting time information included in the station and a NetID (Network Identifier) field that is an identifier such as an owner of the station and so on. The kind of the beacon is described in the Type field in the bit map format of 8-bit length. In this embodiment, information which determines whether the beacon is “regular beacon” that each communication station transmits once at the beginning of the superframe at every superframe or “auxiliary beacon” that is transmitted to acquire the prioritized transmission right is shown by using the values ranging from 0 to 255 which show a priority. To be concrete, 255 which show the maximum priority is assigned to the regular beacon that should be transmitted once at every superframe, and any one of 0 to 255 that corresponds to the priority of the traffic is assigned to the auxiliary beacon. The pseudorandom sequence that determines the above-mentioned TBTT offset is stored in the TOI field and it indicates the amount of the TBTT offset with which the beacon is transmitted. Since the TBTT offset is provided, even when two communication stations locate the beacon transmission timing at the same slot on the superframe, the actual beacon transmission timing can be displaced. Thus, even when the beacons collide with each other in a certain superframe period, the respective communication stations can listen to thief beacons (or neighbor communication stations can listen to their beacons) in another superframe period, that is, they can recognize the collision of the beacons. The NBOI field is the information in which the position (reception time) of the beacon of the neighboring station that the local station can receive in the superframe is described. In this embodiment, since one superframe has the slots into which 16 beacons can be located at maximum as shown in FIG. 4, information concerning the layout of the beacons that could be received is described in the bit map format of 16-bit length. That is, the leading bit (MSB) of the NBOI field is mapped with reference to the transmission time of the regular beacon of the local station, the position (reception time) of the beacon that can be received by the local station is mapped on the bit of the relative position from the transmission time of the regular beacon of the local station, 1 is written in the bit corresponding to the relative position (offset) of the regular or auxiliary beacon of the local station and the relative position (offset) of the beacon that can be received and the bit position corresponding to other relative position remains to be 0. For example, under the communication environment in which 16 communication stations 0 to F at maximum are accommodated as shown in FIG. 4, when the communication station 0 makes the NBOI field such as 1100, 0000, 0100, 0000”, this communication station can transmit a message “it is able to receive the beacons from the communication stations 1 to 9”. That is, “1” is assigned to the bit corresponding to the relative position of the beacon that can be received when the beacon can be received and “0”, that is, space is assigned thereto when the beacon is not received. Also, the reason that the MSB is “1” is that the local station transmits the beacon and hence “1” is assigned to the portion corresponding to the time at which the local station transmits the beacon. The position (reception time) of the beacon that the local station receives in actual practice is described in the NBAI field at its relative position from the beacon position of the local station by the bit map format. That is, the NBAI field indicates that the local station is set to the active state in which it can receive information. Information to be transmitted to the neighboring station is stored in the ALERT field in the abnormal state. For example, when it is planned to change the TBTT field of the regular beacon of the local station in order to avoid the collision of the beacons or when it is requested to stop the neighboring station from transmitting the auxiliary beacon, such message is described in the ALERT field. The manner in which the ALERT field is in actual use will be described later on. The number of the auxiliary beacons that the station is transmitting within the superframe period is described in the TxNum field. Since the communication station is given the TPP, that is, the prioritized transmission right after the transmission of the beacon, the number of the auxiliary beacons within the superframe period corresponds to a time rate in which the communication station maintains the resources with a priority to transmit information. A serial number assigned to the beacon when a plurality of beacons is transmitted within the superframe is written in the Serial field. As the serial number of the beacon, an exclusive and unique number is assigned to each beacon that is transmitted within the superframe. In this embodiment, a serial number indicative of the sequential order of the TBTT field in which the auxiliary beacon is transmitted based on the regular beacon of the local station is written in the Serial field. Report information indicating the destination station to which this communication station has information to be transmitted at present is stored in the TIM field. It is possible for the reception station to recognize that the local station should receive information with reference to the TIM field. Also, the Paging field is the field indicative of the reception station described in the TIM field to which the communication station intends to transmit information in the immediately-succeeding TPP. The station designated by this field should become ready to receive information in the TPP field, and other field (ETC field) is also prepared. A TSF field is a field in which time information included in the station is transmitted. This time is used for other uses than the media access and is mainly used to synchronize the applications. The transmission time of the signal that is calculated faithfully, in a free-running fashion, to the clock frequency of the transmission station independently of the access control such as the alteration of the transmission time of the beacon, the correction of the clock frequency to hold the TDMA structure and the TBTT offset is written in this field. The reception station supplies this value to the high-order layer together with the reception time and may hold it as the reference time of the information transmitted from the station. The NetID field is an identifier indicating the owner of the corresponding station. The reception station can recognize with reference to this field whether or not the local station and the corresponding station belong to the same network logically. Procedure of Transmtter and Receire in the Stationary State No. 1: A typical example of transmission and reception procedures of a communication station will be described with reference to FIG. 19. FIG. 19 shows a communication station STA0 and a communication station STA1 in the case in which the communication station STA0 transmits information to the communication station STA1. Each communication station does not always receive a beacon signal from other station every time. A frequency at which the communication station receives the beacon signal may be lowered by an instruction from the high-order layer and the like. FIG. 19A shows a sequence diagram of a packet transmitted and received between the communication stations STA0 and STA1, FIG. 19B shows the state of the transmission unit of the communication station STA0, and FIG. 19C shows the state of the reception unit of the communication station STA0. In the state of the transmission and reception unit, the high level state indicates the active state (state in which the transmission and reception unit attempts to receive or transmit information) and the low level state indicates the sleep state. First, having confirmed that the media is clear, the communication station STA0 transmits a beacon. Let it be assumed that the communication station STA1 is called in the TIM field and (or) PAGE field in this beacon. The communication station STA1 which received the beacon generates a response to paging information (0). Since this response corresponds to the TPP of the communication station STA0, it is given a priority and it is transmitted at the SIFS space. After that, transmission and reception between the communication stations STA1 and STA0 within the TPP is given a priority and hence this response is transmitted at the SIFS space. The communication station which received the response transmits a packet to the communication station STA1 after it has confirmed that the communication station STA1 is placed in the receivable state (1) Further, in FIG. 19, there exists another packet to the communication station STA1, and hence another packet is transmitted (2). The communication station STA1 which received the two packets transmits the ACK packet after it has confirmed that the two packets were received correctly (3). Thereafter, the communication station STA0 transmits the last packet (4). However, during the communication station is receiving the ACK packet, the TPP field of the communication station STA0 is ended and the communication station enters the FAP field when it transmits the last packet (4). Since the communication station does not have the prioritized transmission right in the FAP field and the communication station transmits the last packet (4) at the LIFS+backoff space. The communication station STA1 transmits the ACK packet corresponding to the last packet (4) (5). A time period from the last transmission is defined as a “listen period” (Listen Period) in which each communication station is ought to energize the receiver. FIG. 19 also shows this state. When the reception packet does not exist during the listen period, the communication station is changed to the sleep mode and it de-energizes the transmitter and receiver to decrease power consumption. However, when the communication station receives in advance some message indicating “DO NOT WISH TO CHANGE TO SLEEP MODE” from other station or when the communication station receives a similar message from the high-order layer, the communication station is not limited to the above operation but continues to operate the reception unit. The communication station, which was once placed in the sleep mode, releases the sleep mode in response to a time at which information is transmitted and received next time such as when the communication station receives a beacon from other station or it transmits the beacon of the local station and returned to the active state. In the example of FIG. 19, although the communication station is temporarily returned to the active mode in order to receive the beacon from the communication station STA1, after it was confirmed that the packet to be transmitted to the communication station STA1 does not exist in the TIM field and the PAGE field of the beacon transmitted from the communication station STA1, the communication station is again placed in the sleep mode. After that, before transmitting the beacon of the local station, the communication station energizes the reception unit for sensing the media and after it was confirmed that the media is clear, it transmits the beacon. Although the communication station does not access other communication station in the TIM field and the PAGE field when it transmits the beacon this time, since the communication station STA0 transmits the beacon, the communication station enters the listen period in accordance with the above-described procedure after it has transmitted the beacon and monitors for a while whether or not a signal to the local station is received. When the communication station does not receive any signal and the listen period is ended, it changes its mode to the sleep mode again. Summary of Example of Transmission and Reception No. 1: When the communication station transmits the signal, the transmission of the signal is started by the access of the beacon. Having transmitted and received the last packet, the communication station attempts to receive a signal for a while. When the packet does not arrive at the local station, the communication station enters the sleep mode (sleep state). Each time the communication station receives the beacon from other station or transmits the beacon of the local station, it is returned to the active mode (active state). That is, during a stipulated time period after the communication station has transmitted some signal, it energizes the reception unit (communication unit) constantly. Procedure of Transmtter and Receiver in the Stationary State No. 2 (Paging Transfer Sequence): Another typical example of the transmission and reception procedures of the communication station will be described with reference to FIG. 20. Each communication station does not always receive a beacon every time. It is frequently observed that a reception frequency may be lowered by an instruction from the high-order layer and the like. The transmission and reception procedures in this case will be described. FIG. 20 shows the communication stations STA0 and STA1 in which the communication station STA1 transmits a signal to the communication station STA0, by way of example. FIG. 20A shows a sequence diagram of a packet transmitted and received between the communication stations STA0 and STA1, FIG. 20B shows the state of the transmission unit of the communication station STA0, and FIG. 20C shows the state of the reception unit of the communication station STA0. In the state of the transmission and reception unit, the high level state indicates the active state (state in which the communication station is attempting to receive or transmit a signal) and the low level state indicates the sleep mode. Having confirmed that the media is clear, the communication station STA1 transmits a beacon. At that time, the communication station STA0 is placed in the sleep mode and is not in receipt of the beacon. Accordingly, even when the communication station STA0 is accessed in the TIM field and (or) PAGE field, the communication station STA0 does not respond to such accessing. Thereafter, the communication station STA0 transmits the beacon at the beacon transmission time of the local station. Each time the communication station STA1 receives the beacon from the communication station STA0, it transmits paging information to the communication station STA0 in accordance with the determined random backoff procedure. Having transmitted the beacon, the communication station STA0 is energizing the receiver during the listen period and hence it can receive this paging information. That is, when receiving the paging information, the communication station STA0 can recognize that the communication station STA1 has information for the local station. At that time point, the communication station STA0 may make a response to the paging information of the communication station STA1 and the communication station STA0 may start transmitting information to the communication station STA1 (although not shown). FIG. 20 shows an example of the case in which the communication station does not yet start transmitting information at that time. After that, at the beacon transmission time of the communication station STA1, the communication station STA0 is caused by the previous paging information to attempt to receive information from the communication station STA1 and it receives the beacon from the communication station STA1. Let it be assumed that the communication station STA0 is accessed in the TIM field and (or) PAGE field in the beacon. Then, the communication station STA0 which received this beacon makes a response to the paging information (0). This response corresponds to the TPP of the communication station STA1 and the communication station is given the prioritized transmission right and it transmits information at the SIFS space. After that, the transmission and reception between the communication stations STA1 and STA0 within the TPP field is given the prioritized transmission right and hence information is transmitted at the SIFS space. When the communication station STA1 which received the response recognizes that the communication station STA0 is placed in the receivable state, it transmits the packet to the communication station STA0 (1). The communication station STA0 which received this packet recognizes that the packet was received correctly and transmits the ACK packet (2). Thereafter, the communication station STA0 energizes the receiver during the listen period to confirm that the packet to the local station is not received, and it changes its state to the sleep mode. While the packet is transmitted to the beacon transmission station each time the communication station starts receiving the beacon on the assumption that the receiver is being operated during the listen period as described above, the present invention is not limited thereto. When media sense is performed before the beacon transmission time, it is clear that the receiver is being operated before the beacon transmission time. Thus, even when transmission processing is executed at this time zone, similar effects can be achieved. Summary of Example of the Above Transmission and Reception Procedure No. 2: When a signal is transmitted, paging information is transmitted immediately after the beacon has been transmitted from the reception side, whereby the reception side is changed into the active state to start transmission and reception processing. Alternatively, the transmission and reception processing is started in response to the access by the beacon from the transmission side. Then, after the last packet was transmitted and received, the reception unit attempts to receive information for a while. If the packet to the local station does not arrive at the communication station, the communication station is placed in the sleep move and each time it receives the beacon from other station or it transmits the beacon of the local station, the communication station is returned to the active mode. That is, the communication station transmits paging information during the listen period of the reception side or in the media sense interval prior to the transmission of the beacon. Although the message transmitted immediately before/immediately after the reception side transmits the beacon in the above-described reception procedure 2 is not limited to the paging information, since there is a possibility that contention of access of messages from a plurality of stations will occur, it is desired that only a message with a large emergency such as paging information and a beacon transmission timing alteration request should be transmitted. While the present invention has been described in the form in which the RTS/CTS procedure executed prior to the transmission of the packet for simplicity of description as described above, according to the necessity, the RTS packet and the CTS packet may be exchanged before the packet is transmitted. In that case, it is needless to say that the paging information in the beacon corresponds to the RTS packet and the page response corresponds to the CTS packet. Also, while the paging information and negotiation processing of its response are executed between the communication stations before transmission of data is started in the above-mentioned example, the present invention is not limited thereto and the source communication station which holds data to be transmitted to a certain communication station may start transmitting data without negotiation processing within the listen period of the reception communication station or an active timing in which such communication station is performing the reception operation (Active Transfer sequence). In this case, processing for establishing connection can be omitted and communication becomes highly efficient. Application of Process for Determining Beacon Transmission Timing: The beacon transmission timing will be described. First, the beacon transmission timing will be described with reference to FIGS. 21 and 22. For example, let it be assumed that two communication stations of communication stations STA-0 and STA-1 exist within the beacon radio wave reaching range. In this case, beacons B0, B1 are located substantially alternately and they are located at a timing relationship of approximately 40 [msec] space as shown in FIG. 21. When an amount of transmission data of the communication stations STA-0 and STA-1 is not so large, the communication station STA-0 starts transmitting the transmission signal in response to the start of the transmission of the beacon from the communication station STA-0 and the transmission is ended after a while. The transmission signal from the communication station STA-1 is similar and if the transmission information amount is ended in a time period shorter than the space of beacons, then it is expected that the transmission requests from the communication stations STA-0 and STA-1 will not collide with each other. FIG. 22 shows the case in which three communication stations exist within the beacon radio wave reaching range similarly. Here, we assume the case in which a new communication station STA-2 joins this beacon radio wave reaching range. The beacon transmission timing of the communication station STA-2 may be either 20 [msec] or 60 [msec] shown in the sheet of drawing. However, the communication station STA-2 scans the media state before it determines the beacon transmission timing. When traffics are packet transmission P0 that follows the beacon B0 and packet transmission P1 that follows the beacon B1 shown in FIG. 22, if the communication station STA-2 transmits a beacon B2 at a timing of 20 [msec], then collisions of the beacons will be decreased. From this standpoint, it becomes possible for the communication station STA-2 to determine the beacon transmission time in consideration of the occupied state of the media, that is, the traffic amount of each communication state. This is especially effective for the case in which transmission activity becomes different considerably depending upon the communication station. Band Reservation for Transmitting Stream Data: Further, let us consider the case in which a communication station which transmits stream data of wide band exists within the system. The communication station intends to continuously transmit a signal of a constant band without collision. In this case, the transmission station increases a beacon transmission frequency within the superframe period. An example of this case will be described with reference to FIG. 23. It is customary that the superframe period in the channel is defined by the beacon space. In this embodiment, the beacons following the second beacon in one superframe period is transmitted mainly in order to obtain transmission and reception intervals and hence they are different from the original beacons that are transmitted to configure the network from a nature standpoint. In this specification, the beacons following the second beacon in one superframe period are referred to as “auxiliary beacons”. On the other hand, a minimum beacon space Bmin is stipulated in order to prevent the band (superframe period) from being filled with beacons and there is an upper limit on the number of communication stations that can be accommodated within the superframer period (mentioned hereinbefore). For this reason, when a new communication station joins the network, the auxiliary beacon has to be released in order to accommodate this new communication station in the superframe period. While FIG. 23 shows the case in which the beacons B1 and B1′ are transmitted continuously, the present invention is not limited thereto. When the communication station transmits the beacon, the beacon is immediately followed by the TPP field and it becomes possible to acquire the media without access acquisition contention. A communication station which strongly requires the right of possessing the media can get much more transmission rights by increasing the frequency at which the beacon is transmitted. Also, the “auxiliary beacon” need not always describe thereon beacon information. In order to decrease the overhead in which the beacons are transmitted a plurality of times, a packet category called a “false beacon for accommodating traffic” may be defined in which a flag of a message indicating that attribute of a packet is a kind of a beacon may be raised and traffic may be transmitted as the contents. For example, in a certain system, when the capacity reaches substantially its limit and quality of services that the network is providing at present cannot be guaranteed if much more traffic is accommodated, each communication station transmits as much beacons as possible. Thus, even when a new communication station joins the network, the beacon transmission timing cannot be given to such new communication station and the accommodation of the new communication station into this area can be refused. Eample of Use of Quiet (Quiet) Packet: While each station transmits a beacon periodically, since the traffic packet is transmitted in accordance with the CSMA (or PSMA) procedure, an accident will be caused by the transmission of the traffic packet from other station in which the beacon cannot be received. FIG. 24 shows an example of this case. In FIG. 24, it is assumed that, when communication stations STA1, STA2, STA3, STA4 exist, the communication station STA2 transmits information to the communication station STA1, the communication station STA3 exists in the area in which the transmission signal from the communication station STA2 can be received, the communication station STA3 intends to receive the beacon transmitted from the communication station STA4 and that the communication station STA2 exists in the area in which it cannot receive the beacon from the communication station STA4. In this example, at a time T0, the communication station STA4 transmits the beacon and the communication station STA3 starts receiving this transmitted beacon. However, since the communication station STA2 cannot receive the signal from the communication station STA4, this communication station starts transmitting information to the communication station STA1 at a time T1 in accordance with the random backoff procedure. The transmitted signal from this communication station STA2 interferes with the communication station STA3 so that this communication station becomes unable to receive the beacon from the communication station STA4. A quiet (Quiet) packet is used in order to avoid this accident. The quiet packet is a packet which transmits a message “This station will receive information from other station and wishes other station not to transmit a signal” to the neighboring stations. As shown in FIG. 25, the quiet packet describes thereon “target station of which information will be received by quiet packet transmission station (target)” and “transmission prohibit time”. In the example of FIG. 24, the communication station STA3 transmits the quiet packet at the time T3 before a time T4 which is the next TBTT field of the communication station STA4. When the communication station STA2 which received the quiet packet recognizes that the local station is not the target station of the quiet packet, it stops transmitting information until the time instructed by the quiet packet. On the other hand, although the quiet packet reaches the communication station STA4, when the communication station STA4 recognizes that the local station is the target station of the quiet packet, it neglect the quiet packet and transmits the beacon at the time T4 that is the TBTT field as it is planned to do. Thus, the communication station STA3 becomes able to receive the beacon without being disturbed by the communication station STA2. Example of Operation of Media Scan Method (PSMA: Preamble Sense Multiple Access): This embodiment uses the CSMA procedure as the access method and hence the fundamental method is to transmit information after it has confirmed the communication state. However, in the specification of the physical layer of the baseband unit of the communication station, such a case is considered in which information such as a reception electric field intensity (RSSI) cannot be used as media occupied information. For example, this case may be a communication system such as an ultra-wide band communication for making communication by using a wide band ranging from 30 GHz to 10 GHz. In such case, the existence of the packet can be recognized only by receiving the preamble of the unique word added to the leading portion of the packet. That is, this media scan method is collision avoidance control based upon the detection of the preamble and the transmission station transmits information after it has confirmed that the media state is clear. This is defined as “PSMA”. For this reason, even when the transmission station which intends to transmit information after it has changed from the sleep mode transmits any information, it starts media reception processing before a time of a predetermined time (MDI: Maximum Data Interval: maximum data interval (that is, maximum packet length)). When the above communication station detects the preamble of the packet transmitted from other communication station during this time period, it refrains from transmitting information. Since the communication station performs access control by detecting the preamble, the preamble is constantly added to the PHY frame. FIG. 26 shows a PHY frame format stipulated by a PHY layer (physical layer). The preamble added to the beginning of the PHY frame is composed of the known unique word. The communication station which receives information and the communication station which transmits information can recognize by detecting the preamble that the media is occupied. This state will be described with reference to FIG. 27. FIG. 27 is a diagram used to explain the case in which the communication stations STA0 and STA1 transmit information. FIG. 27A shows a transmission sequence of the communication station STA1, and FIG. 27B shows a transmission sequence of the communication station STA0. Then, FIGS. 27C, 27D show the states of the transmission unit and the reception unit of the communication station STA0 (high level: active mode, low level: sleep mode). At a time T1, the communication station STA1 starts transmitting a packet. Since the communication station STA0 is in the sleep mode at that time point, it is unable to recognize that the communication station STA1 has transmitted the packet. Thereafter, let it be assumed that the high-order layer informs of the communication station that the communication station STA0 has information to be transmitted at the time T1 (Tx request). Although the random backoff procedure is started at this time point according to the conventional IEEE802.11 system wireless LAN, since the communication station starts receiving information from the time T1, it cannot receive the preamble of the unique word and hence it cannot recognize that the media is being used by the communication station STA1. Therefore, there is then a possibility that the transmission of information from the communication station STA0 will interfere with the packet of the communication station STA1. Accordingly, when the communication station STA0 is placed in the active mode at the time T1, from this time point, it confirms during the maximum data space MDI (Max. Uniqueword Interval) that the media is clear. A time T2 is a time point that passed from the time T1 by MDI. The communication station STA0 energizes the receiver from the time T1 to the time T2 and starts transmitting information only when it does not detect the unique word (preamble of FIG. 25) of the packet. Let it be assumed that the high-order layer reports information to the communication station (Tx request). Since the communication station STA0 is set to the sleep mode immediately before the time T4, the communication station starts confirming during the time period from the time T4 to the MDI that the media is clear. Then, since the packet is transmitted from the communication station STA1 at a time T5 this time, the communication station STA0 detects the unique word to recognize the existence of this packet. The communication station STA0 starts the random backoff procedure from a time T6 at which the transmission of this packet is ended. If the communication station does not detect the unique word until a time T7 at which the timer is de-energized, then it transmits the packet at the time T7. While the present invention has been described so far on the assumption that the MDI is equal to the maximum packet length, when the communication station intends to transmit a large amount of data that cannot be transmitted by one packet, data transfer over a long period of time may be allowed by acquiring the access right once as shown in FIG. 28. As shown in FIG. 28, within the range of the maximum data transmission length obtained when the access right is acquired once, the data packet containing the payload may be repeatedly transmitted, whereby a large amount of data may be transmitted. FIG. 29 shows a transmission sequence used to continuously transmit a large number of packets. FIG. 29 is a sequence diagram similar to FIG. 27, wherein FIG. 29A shows a transmission sequence of the communication station STA1, FIG. 29B shows a transmission sequence of the communication station STA0 and FIGS. 29C, 29D show the states of the transmission unit and the reception unit at the communication station STA0 (high level: active mode, low level: sleep mode). At a time T0, the communication station STA1 starts transmitting the packet. After that, let it be assumed that the high-order layer informs the communication station STA0 that the communication station STA0 has information to be transmitted (Tx request). Since the communication station STA0 is placed in the sleep mode immediately before the time T1, it start confirming that the media is clear during a time period from the time T1 to the MDI. Then, in order to detect the unique word (preamble) of the packet transmitted from the communication station STA1 at the time T2, the communication station recognizes the existence of the packet transmitted from the communication station STA1. The communication station STA0 starts the random backoff procedure from the time T3 at which the transmission of this packet is ended. If the communication station does not detect the unique word until the time T4 at which the timer is de-energized, then the communication station transmits the packet at the time T4. While the values of the time, the space and the transmission rate have been described as examples thereof, the present invention is not limited thereto, and it is needless to say that other values may be set to those values without departing from the gist of the present invention. Also, while the exclusive communication apparatus for performing transmission and reception shown in FIG. 2 is constructed as the communication station in the above-mentioned embodiment, the present invention is not limited thereto and a board or a card for performing communication processing corresponding to the transmission unit and the reception unit in this embodiment may be attached to a personal computer apparatus for performing various data processing, for example, and software executed by the side of the computer apparatus may be installed on the baseband unit for processing.

<SOH> BACKGROUND ART <EOH>As media access control for wireless LAN system, access control standardized by IEEE (The Institute of Electrical and Electronics Engineers) 802.11 systems have been widely known so far. International Standard ISO/IEC 8802-11: 1999(E) ANSI/IEEE Std 802.11, 1999 Edition, Part II: Wireless LAN Medium Access Control (MAC) and Physical Layer (PHY) specifications or the like has described the details of the IEEE802.11. Networking in the IEEE802.11 is based on a concept of a BSS (Basic Service Set). Two kinds of BSS are available, that is, BBS defined by the infrastructure mode in which a master control station such as an access point (Access Point: AP) exists and IBSS (Independent BSS) defined by the ad hoc mode composed of only a plurality of mobile terminals (Mobile Terminal: MT). Operations of the IEEE802.11 in the infrastructure mode will be described with reference to FIG. 30 . In the BSS in the infrastructure mode, an access point for performing coordination should be absolutely provided within a wireless communication system. In FIG. 30 , assuming that a communication station SAT 0 , for example, is a communication station SA which functions as an access point, then BSSes within a range of radio waves near the local station are collected to construct a cell in the so-called cellular system. Mobile stations (SAT 1 , SAT 2 ) existing neat the access point are accommodated into the access point and joined the network as a member of the BSS. The access point transmits a control signal called a beacon at a proper time space. A mobile terminal that can receive this beacon recognizes that the access points exists near it and establishes connection between it and the access point. The communication station SAT 0 , which is the access point, transmits a beacon (Beacon) at a predetermined period space as shown on the right-hand side of FIG. 30 . The next beacon transmission time is sent into the beacon by a parameter called a target beacon transmit time (TBTT: Target Beacon Transmit Time). When a time reaches the TBTT field, the access point activates a beacon transmission procedure. Also, since a neighboring mobile terminal receives a beacon and is able to recognize the next beacon transmission time by decoding the inside TBTT field, depending on the cases (mobile terminal need not receive information), the receiver may be de-energized until the next TBTT field or a plurality of future target beacon transmission times and the mobile terminal may be placed in the sleep mode. This specification principally considers the gist of the present invention in which the network is operated without application of a master control station such as the access point, and hence the infrastructure mode will not be described any more. Next, communication operations according to the IEEE802.11 in the ad hoc mode will be described with reference to FIGS. 31 and 32 . On the other hand, in the IBSS in the ad hoc mode, after each communication station (mobile terminal) has negotiated with a plurality of communication stations, each communication station defines the IBSS independently. When the IBSS is defined, the communication station group determines the TBTT at every constant interval after negotiations. When each communication station recognizes the TBTT with reference to a clock within the local station, if it recognizes that other communication station has not transmitted the beacon after a delay of a random time, then the communication station transmits the beacon. FIG. 31 shows an example of the case in which two communication stations SAT 1 , SAT 2 constitute the IBSS. Accordingly, in this case, any one of communication stations belonging to the IBSS is able to transmit the beacon at each arrival of the TBTT field. Also, it is frequently observed that the beacons will conflict with each other. Further, also in the IBSS, according to the necessity, each communication station is placed in the sleep mode in which a power switch of its transmission and reception unit is turned off. A signal transmission and reception procedure in this case will be described with reference to FIG. 32 . In the IEEE82.11, when the sleep mode is applied to the IBSS, a certain time period from the TBTT is defined as an ATIM (Announcement Traffic Indication Message) Window (hereinafter referred to as an. “ATIM window”). During the time period of the ATIM window, since all communication stations belonging to the IBSS are operating the reception units, even the communication station which is being operated in the sleep mode fundamentally is able to receive communication in this time period. When each communication station has its own information for other communication station, after a beacon has been transmitted in the time period of this ATIM window, the communication station lets the reception side know that the communication station has its own information for other communication station by transmitting the ATIM packet to other communication station. The communication station, which has received the ATIM packet, causes the reception unit to continue operating until the reception from the station that has transmitted the ATIM packet is ended. FIG. 32 shows the case in which three communication stations STA 1 , STA 2 , STA 3 exist within the IBSS, by way of example. As shown in FIG. 32 , at the time TBTT, the respective communication stations STA 1 , STA 2 , STA 3 operate back-off timers while monitoring the media state over a random time. The example of FIG. 32 shows the case in which the communication station STA 1 transmits the beacon after the timer of the communication station STA 1 has ended counting in the earliest stage. Since the communication station STA 1 transmits the beacon, other two communication stations STA 2 and STA 3 do not transmit the beacon. The example of FIG. 32 shows the case in which the communication station STA 1 holds information for the communication station STA 2 , the communication station STA 2 holding information for the communication station STA 3 . At that time, as shown in FIGS. 32B, 32C , after having transmitted/received the beacons, the communication stations STA 1 and STA 2 energize the back-off timers while monitoring the states of the media again over the random time, respectively. In the example of FIG. 32 , since the timer of the communication station STA 2 has ended counting earlier, first, the communication station STA 2 transmits the ATIM message to the communication station STA 3 . As shown in FIG. 32A , when receiving the ATIM message, the communication station STA 3 feeds the message of the reception back to the communication station STA 2 by transmitting an ACK (Acknowledge) packet which is an acknowledge packet to the above communication station. After the communication station STA 3 has finished transmitting the ACK packet, the communication station STA 1 further energizes the back-off timer while monitoring the respective states of the media over the random time. When the timer finishes counting after a time set by the timer has passed, the communication station STA 1 transmits the ATIM packet to the communication station STA 2 . The communication station STA 2 feeds the message of the reception back to the communication station STA 1 by returning the ACK packet to the above communication station. When the ATIM packet and the ACK packet are exchanged within the ATIM window, also during the following interval, the communication station STA 3 energizes the receiver to receive information from the communication station STA 2 , and the communication station STA 2 energizes the receiver to receive information from the communication station STA 1 . When the ATIM window is ended, the communication stations STA 1 and STA 2 which hold the transmission information energize the back-off timers while monitoring the respective states of the media over the random time. In the example of FIG. 32 , since the timer of the communication station STA 2 has finished counting first, the communication station STA 2 first transmits the information to the communication station STA 3 . After this transmission of the information was ended, the communication station STA 1 energizes the back-off timer while monitoring again the respective states of the media over the random time, and after the timer is ended, it transmits the packet to the communication station STA 2 . In the above-mentioned procedure, a communication station which has not received the ATIM packet within the ATIM window or which does not hold information de-energizes the transmitter and receiver until the next TBTT field and it becomes possible to decrease power consumption. Next, the access contention method of the IEEE802.11 system will be described with reference to FIG. 33 . In the above explanation, while we have described “communication station energizes the back-off timer while monitoring the states of the media over the random time”, let us make additional explanation to this case. In the IEEE802.11 system, four kinds of IFS are defined as packet spaces (IFS: Inter Frame Space) extending from the end of the immediately-preceding packet to the transmission of the next packet. Of the four kinds of the inter frame spaces, three inter frame spaces will be described. As shown in FIG. 33 , as the IFS, there are defined SIFS (Short IFS), PIFS (PCF IFS) and DIFS (DCF IFS) in the sequential order of short inter frame space. According to the IEEE802.11, a CSMA (Carrier Sense Multiple Access) is applied as the fundamental media access procedure. Accordingly, before the transmission unit transmits some information, the communication station energizes the backoff timer over the random time while monitoring the state of the media. If it is determined that the transmission signal does not exist during this time period, then the transmission unit is given a transmission right. When the communication station transmits the ordinary packet in accordance with the CSMA procedure (called a DCF: Distributed Coordination Function), after the transmission of some packet has been ended, the state of the media of only the DIFS is monitored. Unless the transmission signal exists during this time period, then the random backoff is made. Further, unless the transmission signal exists during this time period, the transmission unit is given a transmission right. On the other hand, when a packet such as ACK packet which has an exceptionally large emergency is transmitted, the transmission unit is allowed to transmit the packet after the SIFS packet space. Thus, it becomes possible to transmit the packet with the large emergency before the packet that is to be transmitted in accordance with the ordinary CSMA procedure. Different kinds of packet spaces IFS are defined for this reason. Packet transmission contention is prioritized depending upon whether the IFS is the SIFS or the PIFS or the DIFS. The purpose of using the PIFS will be described later on. Next, the RTS/CTS procedure in the IEEE802.11 will be described with reference to FIGS. 34 and 35 . In network under the ad hoc environment, it is generally known that a problem of a hidden terminal arises. As a methodology for solving the most part of this problem, there is known a CSMA/CA based upon the RTS/CTS procedure. The IEEE802.11 also uses this methodology. An example of operation in the RTS/CTS procedure will be described with reference to FIG. 34 . FIG. 34 shows an example of the case in which some information (DATA) is transmitted from a communication station STA 0 to a communication station STA 1 . Before transmitting actual information, the communication station STA 0 transmits an RTS (Request To Send) packet to the communication station STA 1 which is an information destination station in accordance with the CSMA procedure. When the communication station STA 1 received this packet, it transmits a CTS (Clear To Send) packet which feeds information indicative of the reception of the RTS packet back to the communication station STA 0 to the communication station. When the communication station STA 0 which is the transmission side receives the CTS packet without accident, the communication station regards that the media is clear and transmits an information (Data) packet immediately. After the communication station STA 1 receives this information packet without accident, it returns the ACK packet and the transmission of one packet is ended. Actions that will occur in this procedure will be described with reference to FIG. 35 . In FIG. 35 , it is assumed that a communication station STA 2 may transmit information to a communication station STA 3 . Having confirmed by the CSMA procedure that the media is clear during a predetermined period, the communication station STA 2 transmits the RTS packet to the communication station STA 3 . This packet is also received by the neighbor communication station STA 1 of the communication station STA 2 . Because the communication station STA 1 receives the RTS packet and becomes aware that the station STA 2 intends to transmit some information, it recognizes that the media is occupied by the station STA 2 until the transmission of such information is ended, and it also becomes aware of the fact that the media is occupied without monitoring the media during this time period. This work is called an NAV (Network Allocation Vector). The RTS packet and the CTS packet have durations of time in which the media is occupied in the transaction written thereon. Returning to the description, having received the RTS packet transmitted from the communication station STA 2 to the communication station STA 3 , the communication station STA 1 becomes aware of the fact that the media is placed in the occupied state during a time period designated by the RTS packet, and hence it refrains from transmitting information. On the other hand, the communication station STA 3 which received the RTS packet returns the CTS packet to the communication station to feed information indicative of the reception of the RTS packet back to the communication station STA 2 . This CTS packet is also received by a neighbor communication station STA 4 of the communication station STA 3 . The communication station STA 4 recognizes by decoding the content of the CTS packet that information is transmitted from the communication station STA 2 to the communication station STA 3 , and it becomes aware of the fact that the media will be occupied during a time period designated by the CTS packet. Hence, it refrains from transmitting information. When the above-described RTS packet and CTS packet are transmitted and received, the transmission is prohibited between “neighboring station of the communication station STA 2 which is the transmission station” which could receive the RTS packet and “neighboring station of the communication station STA 3 which is the reception station” which could receive the CTS packet, whereby information can be transmitted from the communication station STA 2 to the communication station STA 3 and the ACK packet can be returned without being disturbed by the sudden transmission from the neighboring station. Next, a band reserve means in the IEEE802.11 system will be described with reference to FIG. 36 . In the above-mentioned IEEE802.11 system access control, access contention based on the CSMA procedure is executed, and hence it is impossible to guarantee and maintain a constant band. In the IEEE802.11 system, a PCF (Point Coordination Function) exists as a mechanism for guaranteeing and maintaining the band. However, the basis of the PCF is polling and it does not operate in the ad hoc mode but it operates only in the infrastructure mode under control of the access point. Specifically, in order to execute the access control while the band is being guaranteed, a coordinator such as an access point is required and all controls are carried out by the access point. For reference, operations of the PCF will be described with reference to FIG. 36 . In FIG. 36 , it is assumed that the communication station STA 0 is the access point and that the communication stations STA 1 and STA 2 joined in the BSS managed by the access point STA 0 . Also, it is assumed that the communication station STA 1 transmits information while it guarantees the band. Having transmitted the beacon, for example, the communication station STA 0 performs polling to the communication station STA 1 at the SIFS space (CF-Poll in FIG. 36 ). The communication station STA 1 which received the CF-Poll is given a right to transmit data and is thereby allowed to transmit data at the SIFS space. As a result, the communication station STA 1 transmits the data after the SIFS space. When the communication station STA 0 returns the ACK packet for the transmitted data and one transaction is ended, the communication station STA 0 again performs polling to the communication station STA 1 . FIG. 36 shows also the case in which polling of this time is failed due to some reason, that is, the state in which the polling packet shown as the CF-Poll follows the SIFS space. Specifically, when the communication station STA 0 becomes aware that no information is transmitted from the communication station STA 1 after the SIFS space elapsed since it has performed polling, it regards that the polling is failed and performs polling again after the PIFS space. If this polling is successful, then data is transmitted from the communication station STA 1 and the ACK packet is returned. Even when the communication station STA 2 holds the transmitted packet during a series of this procedure, since the communication station STA 0 or STA 1 transmits information at the SIFS or PIFS space before the DIFS time space elapses, the right to transmit information is never moved to the communication station STA 2 and hence the communication station STA 1 to which the polling is performed is constantly given a priority. Official Gazette of Japanese laid-open patent application No. 8-98255 discloses an example of access control of such wireless communication. When access control of wireless communication is carried out without such master control station (access point), as compared with the case in which communication is carried out with the master control station, there were various restrictions. To be concrete, the following problems arise. Problem 1: Selection of Coordinator For example, as shown in FIG. 37 , let it be assumed that a network is configured by the above-mentioned IEEE802.11 system when communication stations 10 to 17 are located in the scattered state and communication ranges 10 a to 17 a in which the communication stations 10 to 17 can directly communicate with each other. In such case, if the network is configured in the infrastructure mode, then there arises a problem of how to select a communication station that should be operated as the access point (coordinator). In the IEEE802.11 system, a communication station accommodated within the BSS may communicate with only a communication station which belongs to the same BSS, and the access point is operated as a gateway to other BSS. In order to efficiently make networking on the whole of the system, there are various arguments such as to select which location of the communication station as the access point or how to configure again the network when the access point is de-energized. Although it is desirable that the network could be configured without the coordinator, the infrastructure mode of the IEEE802.11 system cannot meet with such requirements. Problem 2: Disagreement of Achievable Area In the ad hoc mode of the IEEE802.11 system, although the network can be configured without the coordinator, it is assumed that the IBSS is constructed by a plurality of communication stations located at the surrounding areas. For example, as shown in FIG. 37 , it is assumed that the communication stations 10 , 11 , 12 , 13 (STA 0 , STA 1 , STA 2 , STA 3 ) are accommodated within the same IBSS. Then, although the communication station 11 (STA 1 ) can communicate with the communication stations 10 , 12 , 13 (STA 0 , STA 2 , STA 3 ), the communication station 10 (STA 0 ) cannot directly communicate with the communication station 12 (STA 2 ). In such case, according to the beacon transmission procedure of the IEEE802.11 system, it is frequently observed that the communication station 10 (STA 0 ) and the communication station 12 (STA 2 ) transmit the beacons at the same time, and at that time, the communication station 11 (STA 1 ) becomes unable to receive a beacon, which causes a problem. Further, as shown in FIG. 37 , for example, let it be assumed that the communication stations 15 , 16 , 17 (STA 5 , STA 6 , STA 7 ) constitute an IBSS (IBSS-A) and that the communication stations 10 , 11 , 12 , 13 (STA 0 , STA 1 , STA 3 , STA 3 ) constitute an IBSS (IBSS-B). At that time, since the two IBSSes are operating completely independently, an interference problem does not arise between the two IBSSes. Here, let it be considered the case in which a new communication station 14 (STA 4 ) appears on the network. Then, the communication station 14 (STA 4 ) is able to receive both signals from the IBSS-A and the IBSS-B. When the two IBSSes are coupled together, although the communication station STA 4 can enter both of the IBSS-A and the IBSS-B, the IBSS-A is operated in accordance with the rule of the IBSS-A and the IBSS-B is operated in accordance with the rule of the IBSS-B. Then, there is a possibility that collision of the beacons and collision of the ATIM packets will occur, which also raises a problem. Problem 3: Method of Realizing Power Save Mode In the ad hoc mode, the power save mode can be realized by transmitting the ATIM packets with each other within the ATIM window according to the random access. When information to be transmitted is a small amount of information such as bits, an overhead required by the ATIM packets increases, and a methodology in which the ATIM packets are to be exchanged according to the random access is very inefficient. Problem 4: Band Reserve in Network Without Coordinator Also, according to the IEEE802.11 system, in the ad hoc mode, a mechanism for carrying out band reserve does not exist, and hence there is no method but to constantly follow the operation of the CSMA procedure. Problem 5: Incompleteness of RTS/CTS Procedure In the RTS/CTS procedure of the IEEE802.11 system, not only a communication station which received the CTS packet but also a communication station which received the RTS packet is prohibited from transmitting information. However, in the case shown in FIG. 35 , the station that is prohibited from transmitting information is only the communication station STA 4 and the communication station STA 1 does not affect “transmission of DATA from the communication station STA 2 to the communication station STA 3 ”. In the RTS/CTS procedure, to prohibit the communication station which received the RTS packet from transmitting information requires a large margin to the safety side and this is one of the factors which degrade a system throughput. Problem 6: Considerations on Separation of BBSES by TDMA In the scenario described in the above-mentioned Problem 2 (in FIG. 37 , the communication stations STA 5 , STA 6 , STA 7 constitute the IBSS (IBSS-A) and the communication stations STA 0 , STA 1 , STA 2 , STA 3 constitute the IBSS (IBSS-B)), as a method for solving the problem which arises when the communication station STA 4 appears to couple both of the IBSSes, there exists a method for separating the IBSS-A and the IBSS-B by a TDMA (Time Division Multiple Access: time division multiple access) system. An example of this case is shown in FIG. 38 . This is a method used in an ARIB STD-T70 (HiSWANa) system and the like. A time zone that is exclusively used for a sub-network is constructed in a frame of some BBS. However, according to this method, spatial recycling of resources is aborted and hence utilization ratio is decreased considerably, which also causes a problem. In view of the aforesaid aspects, it is an object of the present invention to provide excellent wireless communication system, wireless communication apparatus and wireless communication method and computer program in which the problems arising when a wireless system such as a wireless LAN is constructed as a decentralized distributed type network without control and controlled relationship such as a master station and slave stations can be solved. Other object of the present invention is to provide excellent wireless communication system, wireless communication apparatus and wireless communication method and computer program in which data can be transmitted while collisions are being avoided in a decentralized distributed type network. A further object of the present invention is to provide excellent wireless communication system, wireless communication apparatus and wireless communication method and computer program in which collisions of beacons can be suitably avoided among a plurality of communication stations in a network configured when communication stations transmit beacons with each other. Yet a further object of the present invention is to provide excellent wireless communication system, wireless communication apparatus and wireless communication method and computer program in which a decentralized distributed type wireless network can be suitably formed while collisions of beacons that communication stations transmitted with each other can be avoided.

<SOH> BRIEF DESCRIPTION OF DRAWINGS <EOH>FIG. 1 is an explanatory diagram showing an example in which communication apparatus are located according to an embodiment of the present invention; FIG. 2 is a block diagram showing an example of an arrangement of a communication apparatus according to an embodiment of the present invention; FIG. 3 is a timing chart showing an example of a wireless communication system according to an embodiment of the present invention; FIG. 4 is a timing chart showing an example of timing at which beacons are transmitted according to an embodiment of the present invention; FIG. 5 is an explanatory diagram showing part of beacon description information according to an embodiment of the present invention; FIG. 6 is an explanatory diagram showing an example of NOBI and NBAI processing procedures according to an embodiment of the present invention; FIG. 7 is an explanatory diagram showing an example of the manner in which a transmission prohibit interval is defined according to an embodiment of the present invention; FIG. 8 is an explanatory diagram showing a first example of a beacon collision scenario according to an embodiment of the present invention; FIG. 9 is an explanatory diagram showing a second example of a beacon collision scenario according to an embodiment of the present invention; FIG. 10 is an explanatory diagram showing a beacon transmission offset according to an embodiment of the present invention; FIG. 11 is an explanatory diagram showing part of beacon description information according to an embodiment of the present invention; FIG. 12 is a block diagram showing an example of an M-sequence generating circuit according to an embodiment of the present invention; FIG. 13 is a flowchart showing an example of timing control processing according to an embodiment of the present invention; FIG. 14 is an explanatory diagram showing an example of a manner of determining a packet space according to an embodiment of the present invention; FIG. 15 is an explanatory diagram showing an example of a transmission prioritized interval according to an embodiment of the present invention; FIG. 16 is an explanatory diagram showing the transmission prioritized interval and a conflict transmission interval according to an embodiment of the present invention; FIG. 17 is an explanatory diagram showing an example of a packet format according to an embodiment of the present invention; FIG. 18 is an explanatory diagram showing an example of a beacon signal format according to an embodiment of the present invention; FIG. 19 is a timing chart showing an example (example 1) of the communication state at a communication station according to an embodiment of the present invention; FIG. 20 is a timing chart showing an example (example 2) of the communication state at a communication station according to an embodiment of the present invention; FIG. 21 is an explanatory diagram showing an example of a manner of distributing a time-axis resource according to an embodiment of the present invention; FIG. 22 is an explanatory diagram showing an example of information which is used to determine beacon transmission timing according to an embodiment of the present invention; FIG. 23 is an explanatory diagram showing an example of band reserve processing according to an embodiment of the present invention; FIG. 24 is an explanatory diagram showing an example of the manner in which a quiet packet is used according to an embodiment of the present invention; FIG. 25 is an explanatory diagram showing an example of an arrangement of a quiet packet according to an embodiment of the present invention; FIG. 26 is an explanatory diagram showing an example of an arrangement of a PHY frame according to an embodiment of the present invention; FIG. 27 is an explanatory diagram showing an example (example 1) of media scan according to an embodiment of the present invention; FIG. 28 is an explanatory diagram showing an example of the manner in which data is transmitted a plurality of times according to an embodiment of the present invention; FIG. 29 is an explanatory diagram showing an example (example 2) of media scan according to an embodiment of the present invention; FIG. 30 is an explanatory diagram showing an example (infrastructure mode) of a conventional wireless communication system; FIG. 31 is an explanatory diagram showing an example (ad hoc mode) of a conventional wireless communication system; FIG. 32 is an explanatory diagram showing an example of a signal transmission procedure in the ad hoc mode according to the prior art; FIG. 33 is an explanatory diagram showing an example of a packet space in the conventional wireless communication system; FIG. 34 is an explanatory diagram showing an example of a CSMA/CA procedure in the conventional wireless communication system; FIG. 35 is an explanatory diagram showing an example of CSMA/CA operation in the conventional wireless communication system; FIG. 36 is an explanatory diagram showing an example of band reserve transmission in the conventional wireless communication system; FIG. 37 is an explanatory diagram showing an example of the communication state in the conventional wireless communication system; and FIG. 38 is an explanatory diagram showing an example of an arrangement of a sub-slot in the conventional wireless communication system. detailed-description description="Detailed Description" end="lead"?

20041118

20100831

20050331

95461.0

BRANDT, CHRISTOPHER M

WIRELESS COMMUNICATION SYSTEM, APPARATUS, METHOD AND COMPUTER PROGRAM PRODUCT INCLUDING TIMED BEACON TRANSMISSION CONTROL

UNDISCOUNTED

ACCEPTED

ACCEPTED

Switching circuit and a method of operation thereof

This invention relates to the operation of a switching circuit, such as a bridge circuit. The invention provides a method of generating pulsed first and second switching signals for switching first and second switches of a switching circuit further comprising an output and that receives a DC signal of voltage +Vs, wherein switching of the first and second switches produces voltage pulses of +Vs, OV and −Vs at the output; the method comprising the steps of: receiving a voltage demand signal; and generating the first and second switching signals according to a rule that the first switching signal shall have a single pulse of a first determined width and the second switching signal shall remain in one state, the combination of the first and second switching signals producing an average voltage at the output being substantially equal to the demanded voltage.

1. A method of generating pulsed first and second switching signals for switching first and second switches of a switching circuit further comprising an output and that receives a DC signal of voltage +VS, wherein switching between various combinations of on and off states of the first and second switches produces a voltage at the output with pulses at levels of +VS, 0V and −VS; the method comprising the steps of: (a) receiving a voltage demand signal indicative of a desired voltage to be supplied at the output in a period; and (b) generating the first and second switching signals according to a first rule that the first switching signal shall have a single pulse of a first determined width within the period and, subject to a second rule that the pulse width of the resulting voltage at the output must not fall below a minimum pulse width, that the second switching signal shall remain in one state throughout the period; the first determined width being such that the combination of the first and second switching signals when applied to the first and second switches respectively produce an average voltage at the output for the period being substantially equal to the desired voltage. 2. The method of claim 1 comprising the step of generating the first and second switching signals according to a rule that pulse widths below the minimum pulse width are avoided by departing from the rule that the second switching signal shall remain in one state throughout a period in favour of a rule that the second switching signal shall have a single pulse of a second determined width within the period to create a voltage pulse at the output of either +VS or −VS. 3. The method of claim 2 comprising the step of adding the second determined width to the first determined width such that the voltage pulse at the output of +VS or −VS resulting from the pulse in the second switching signal is balanced by an equal width of voltage pulse at the output of −VS or +VS respectively resulting from the increased first determined width of the first switching signal. 4. The method of claims 2 comprising the step of generating the first and second switching signals according to a rule that the leading and trailing edges of the first switching signal do not coincide with either the leading or trailing edge of the second switching signal. 5. The method of claim 1 comprising the step of generating the first and second switching signals according to a rule that any pulse should be positioned symmetrically about the centre of the period. 6. The method of claim 5 comprising the step of generating the first and second switching signals according to the rule that where pulses cannot be centred symmetrically, the longer and shorter sides of the asymmetric pulses are alternated between the leading edge side and the trailing edge side for successive asymmetric pulses. 7. The method of claim 1 further comprising the step of noise shaping the first and second switching signals. 8. A method of operating a switching circuit comprising a bridge circuit having an input that receives a DC signal of voltage +VS, an output and first and second arms having first and second switches respectively, the first and second arms being connected to opposed ends of the output, the method comprising the steps of: (a) generating pulsed first and second switching signals in accordance with any preceding claim; and (b) supplying the first and second switching signals to the first and second switches respectively thereby to cause the first and second switches to switch between on and off states, switching between various combinations of on and off states producing an electrical signal across the output with voltage pulses at levels of +VS, 0V and VS and with an average voltage for the period substantially equal to the desired voltage. 9. The method of claim 8, wherein either the first or second determined pulse width is generated with reference to a voltage signal indicative of the DC signal such that the determined pulse width compensates for fluctuations in the DC supply. 10. The method of claim 9, wherein the voltage signal is passed through a filter to obtain a predictive measure of fluctuations in the DC supply. 11. The method of claim 10, wherein the voltage signal is passed through a finite impulse response filter. 12. The method of claim 8, wherein either the first or second determined pulse width is generated to include additional width to compensate for a voltage drop across a diode and/or transistor in the bridge circuit. 13. The method of claim 12, wherein the additional width is calculated with reference to a current signal indicative of the current flowing through the output and a representative resistance of the diode or transistor. 14. The method of claim 8, wherein the width of a pulse of the first or second switching signals is generated to include additional width to compensate for a voltage offset caused by slow response times in the first or second switch. 15. The method of claim 1, wherein the first and second switches are transistors and the method comprises the step of switching the transistors between on and off states corresponding to substantially maximum and substantially minimum current flow respectively through the transistors. 16. The method of claim 1 comprising the step of receiving a current demand signal indicative of a desired current to be supplied to the output in a period and calculating the voltage demand signal indicative of a desired voltage to be supplied to the output that results in an electrical signal being supplied to the output during the period with a current substantially equal to the desired current. 17. The method of claim 16, wherein the step of calculating the voltage demand signal is performed with reference to a model of the load characteristic of a load connected to the output. 18. The method of claim 16 further comprising the step of generating the voltage demand signal with reference to a current signal indicative of the current flowing through the output. 19. A computer program comprising program code means for performing the method steps of claim 1 when the program is run on a computer and/or other processing means associated with the switching circuit. 20. A computer program product comprising program code means stored on a computer readable medium for performing the method steps of claim 1 when the program is run on a computer and/or other processing means associated with the switching circuit. 21. A switching circuit operable to receive a DC signal of voltage +VS and that comprises first and second switches, an output and processing means programmed to perform the method steps of claim 1. 22. A switching circuit according to claim 21, further comprising a noise shaper operable to noise shape the first and second switching signals. 23. A bridge circuit comprising an input operable to receive a DC signal of voltage +VS, an output and first and second arms having first and second switches respectively, the first and second arms being connected to opposed ends of the output and processing means programmed to perform the method steps of claim 8. 24. A bridge circuit according to claim 23, further comprising voltage signal sensor operable to produce a voltage signal and wherein the processing means is programmed to perform the method steps of claim 9. 25. A bridge circuit according to claim 24, further comprising a filter arranged to receive the voltage signal. 26. A bridge circuit according to claim 25, wherein the filter is a finite impulse response filter. 27. (canceled) 28. (canceled) 29. (canceled) 30. (canceled) 31. (canceled)

This invention relates to the operation of a switching circuit comprising first and second switches that are switched by pulsed first and second switching signals. The switching circuit may comprise a bridge circuit operated to produce a voltage across a load connected to an output of the bridge circuit in accordance with a required voltage. For example, a presently contemplated application of the present invention is in driving an electromagnet in response to a demanded force to be provided by the electromagnet that must be met to a very high tolerance. The force produced by the electromagnet can be controlled in response to either current demands or voltage demands, because control of either current or voltage affects the force produced by the electromagnet. In addition, the current controller can be operated in response to force demands, although this must be converted into a current or voltage demand. Even where the current controller is operated in voltage demand mode with demanded voltages being set across the electromagnet, this will of course influence the current flowing through the electromagnet and so the term ‘current controller’ is used to cover operation in response to voltage or current or field demands. Where the current controller is operated in response to voltage demands, high-frequency voltage pulses may be applied to the electromagnet because the large inductance associated with an electromagnet leads to a slow response time in the current so that it smoothly follows drifts in the average voltage applied across the electromagnet. A known switching circuit is shown in FIG. 1. As can be seen, the switching circuit comprises a half-bridge circuit with an electromagnet connected across its output. Control of the voltage across the electromagnet is achieved by switching a pair of transistors positioned on opposed arms of the bridge circuit (the other opposed arms containing diodes to complete the half-bridge circuit) to alter the polarity of the voltage across the electromagnet between +VS and −VS. A current or voltage demand for a period will be received periodically and switching signals generated to match this demand. The switching signals are supplied at the points marked A and B to control the transistors such that they are switched between maximum and minimum conducting states (their linear region is not used due to poor power efficiency). The diodes in the half-bridge circuit ensure that current flows in one direction only through the electromagnet, in this case from right to left in FIG. 1. The current controller is operated such that the transistors are switched concurrently: when both transistors are on (i.e. conducting), a voltage of +VS is applied across the electromagnet and when the transistors are off (i.e. non-conducting), a voltage of −VS is applied across the electromagnet. The duty cycles at +VS and −VS within each period determine the average current delivered to the electromagnet in that period, remembering that the inductance of the electromagnet ensures that the current smoothly follows the voltage rather than sharply jumping with each voltage pulse. Hence, by switching the transistors at appropriate times, the desired current can be delivered to the electromagnet. A reservoir capacitor is included to hold current drawn from the electromagnet that cannot be passed back to the DC supply. The pulsed voltage signal that produces these duty cycles is implemented using pulsed switching signals supplied to the transistors. The switching signals are modulated according to a pulse width modulation scheme according to an analogue-implemented scheme, such that the width of the pulses within a period are varied so that the pulse at +VS is varied relative to the remaining time at −VS to produce the desired current. Alternatively, a pulse density modulation scheme may be used, as is well known in the art. A problem with the above switching circuit is that its performance is limited by the distortion in the leading and trailing edges of the switching pulses provided to switch the transistors. This is particularly severe for short pulses where there is little time for the waveform to settle between the leading and trailing edges of the pulse. Furthermore, each switching event inevitably causes a power loss in the circuit. In the case of the above example where transistors are used in a half-bridge circuit, the power loss associated with switching the transistors dominates over all other power losses. Accordingly, the performance of the switching circuit is degraded in response to both of these problems. As will be appreciated, these problems are not limited to the switching circuit described above but are general across a broad spectrum of switching circuits employing slow or power-demanding switches. Moreover, these problems are often exacerbated by repeated switching. For example, pulse density modulation is a commonly used modulation scheme but is problematic in that the transistors must be switched on and off many times to achieve the required voltage using density modulation of fixed-width pulses. According to a first aspect, the invention resides in a method of generating pulsed first and second switching signals for switching first and second switches of a switching circuit further comprising an output and that receives a DC signal of voltage +VS, wherein switching between various combinations of on and off states of the first and second switches produces a voltage at the output with pulses at levels of +VS, 0V and −VS; the method comprising the steps of: (a) receiving a voltage demand signal indicative of a desired voltage to be supplied at the output in a period; and (b) generating the first and second switching signals according to a rule that the first switching signal shall have a single pulse of a first determined width within the period and the second switching signal shall remain in one state throughout the period, the first determined width being such that the combination of the first and second switching signals when applied to the first and second switches respectively produce an average voltage at the output for the period being substantially equal to the desired voltage. Using this method of leaving the second switching signal in one state throughout the period is advantageous because only one transistor is switched in a period rather than both. This is convenient in reducing power losses in the bridge circuit and in avoiding switching delays. Moreover, inaccuracies that are present upon switching in a pulsed scheme, e.g. ringing seen in the otherwise flat tops of the pulses and slow response times leading to sloping rather than vertical leading and trailing edges of the pulses, are alleviated. The above switching scheme will lead to a period having pulses of solely +VS or solely −VS relative to the 0V baseline. As will be appreciated, if a number of positive average voltages are required over consecutive periods, one switch can be left in one state throughout all these periods (the on state, the other switch being switched on and off to give voltages of +VS and 0V). Similarly, for negative voltages, one switch can be left in an off state and the other switch is switched between on and off states to give voltages of 0V and −VS. It is only where the average voltage crosses through zero that both first and second switches will need to be switched (with one switch needing to be switched at the very start of the next period). This leads to significant reductions in power losses in the bridge circuit. Using pulsed switching signals is advantageous as it allows an all-digital implementation and, moreover, it means that the voltage supplied to the output is also pulsed, although there will be pulses of +VS and −VS relative to the 0V baseline. Essentially, the method comprises the step of generating the first and second switching signals according to a pulse width modulation (PWM) scheme. Modulating the switching sequences to a PWM scheme means that the pulsed voltages supplied to the output are also modulated to a PWM scheme. This is because the voltage supplied to the output steps each time there is a pulse edge in either of the switching signals, hence the edge positions of the switching signals determine the edge positions of the voltage pulses supplied to the output. The switching signals may have a digital modulation (i.e. to two levels with high and low values corresponding to the switches being on/conducting or off/non-conducting), but the combination of on and off switch states results in the three levels (+VS, 0V and −VS) of the bipolar PWM voltages supplied to the output. The voltage supplied to the output depends on the states of the first and second switches as follows. When both switches are on, the output sees a voltage of +VS. When both switches are off, the output sees a voltage of −VS. Finally, when one switch is on and the other is off, irrespective of which way round, the output sees a voltage of 0V. As will be appreciated, using pulses at levels of +VS, 0V and −VS allows an average voltage within the range of +VS and −VS to be produced for that period. For example, if a voltage of 0.5VS is desired, then a voltage of +VS can be supplied to the output for half of the period and a voltage of 0V for the other half. Using bipolar switching, i.e. switching between three voltage levels +VS, 0V and −VS, gives advantages over using unipolar switching, i.e. switching between +VS and −VS only. For example, an additional one bit of resolution is acquired using bipolar switching for a given timing clock frequency as voltage drops of VS are possible rather than just the voltage drops of 2VS obtained with unipolar switching. Alternatively, the same resolution can be obtained using only half the timing clock frequency. Use of bipolar switching according to the above method introduces ‘cross-over distortion’. This occurs when a signal of average voltage close to 0V is required. In this case, the required widths of the voltage pulses supplied to the output and hence the pulses of the switching signals tend to zero. Producing very narrow pulses is very difficult due to the slow rise and fall times of the pulse edges and due to ringing. The rising edge followed by the ringing top whilst the voltage settles to its final value will be of a substantially fixed width and, similarly, the falling edge will also be of a substantially fixed width. In wider pulses, these effects are mitigated by the relatively long period at steady voltage. Conversely, where the pulse width is so narrow that there is no time to settle to a steady voltage, control of the average voltage seen by the output is severely limited. Hence, at low voltage demands where very narrow pulses are required, the level of distortion is greatly enhanced and this is known as ‘cross-over distortion’. Optionally, the method may comprise the step of generating the first and second switching signals according to a rule that the pulse width of the resulting voltage at the output must not fall below a minimum pulse width. Conveniently, this alleviates the enhanced distortion described above. By pulse widths, it should be remembered that these are the widths of the pulses at +VS and −VS relative to the 0V baseline. Conveniently, pulse widths below the minimum pulse width are avoided by departing from the rule that the second switching signal shall remain in one state throughout a period in favour of generating the first and second switching signals according to a rule that the second switching signal shall have a single pulse of a second determined width within the period to create a voltage pulse at the output of either +VS or −VS. Operating the primary rule that one switch remains in one state throughout a period and only the other is switched produces pulses of +VS and 0V or −VS and 0V only. The secondary rule of switching both first and second switches during a period, although not concurrently, is advantageous when small voltages are required because it generates voltages of +VS and −VS relative to a 0V baseline. In this way, a small average positive voltage or small average negative voltage can be generated from a combination of wider +VS and −VS pulses that, in turn, can be generated from wider pulses of the first and second switching signals. This increase in control of the average voltage supplied to the output outweighs the disadvantage of introducing further switching within each period. Optionally, the method may comprise the step of adding the second determined width to the first determined width such that the voltage pulse at the output of +VS or −VS resulting from the pulse in the second switching signal is balanced by an equal width of voltage pulse at the output of −VS or +VS respectively resulting from the increased first determined width of the first switching signal. Accordingly, there is no net increase or decrease in the average voltage supplied to the output during the period. Preferably, the method may comprise the step of generating the first and second switching signals according to a rule that the leading and trailing edges of the first switching signal do not coincide with either the leading or trailing edge of the second switching signal. Following this method, the first and second switches are not switched concurrently. Operating only one switch at a time is advantageous because the voltage drops that occur at the output may be halved at each switching event. This is particularly advantageous where the voltage drop of 2VS is large enough to cause insulation breakdown of any components of the bridge circuit or any connected load. Conversely, adopting bipolar switching allows the bridge circuit to be run from a higher voltage DC source without fear of insulation breakdown upon switching. Furthermore, the power of the unwanted components in the output waveform at harmonics of the pulse repetition frequency is reduced from a fixed high level to a lower level which drops as the signal drops. The method may comprise the step of generating the first and second switching signals according to a rule that any pulse should be positioned symmetrically about the centre of the period. This is so-called uniform PWM and leads to a voltage being supplied to the output that is also symmetric about the centre of the period. Other forms of PWM are possible, such as leading edge or trailing edge PWM. Preferably, the method may comprise the step of generating the first and second switching signals according to the rule that where pulses cannot be centred symmetrically, the longer and shorter sides of the asymmetric pulses are alternated between the leading edge side and the trailing edge side for successive asymmetric pulses. For example, where a period extends over an even number of timing clock cycles, a pulse occupying an odd number of clock cycles cannot be created symmetrically within the period: one clock cycle must be added either to the leading edge or to the trailing edge of the otherwise symmetric pulse. By performing the method herein defined, noise is suppressed that would otherwise result from always adding weight to the leading edge or always to the trailing edge. Optionally, the method may further comprise the step of noise shaping the first and second switching signals. Advantageously, this noise shaping may be second-order noise shaping, i.e. noise shaping that compensates for the quantisation error in the previous two periods. The invention also resides in a method of operating a switching circuit comprising a bridge circuit having an input that receives a DC signal of voltage +VS, an output and first and second arms having first and second switches respectively, the first and second arms being connected to opposed ends of the output, the method comprising the steps of: (a) generating pulsed first and second switching signals according to the first aspect of the invention; and (b) supplying the first and second switching signals to the first and second switches respectively thereby to cause the first and second switches to switch between on and off states, switching between various combinations of on and off states producing an electrical signal across the output with voltage pulses at levels of +VS, 0V and −VS and with an average voltage for the period substantially equal to the desired voltage. Optionally, either the first or second determined pulse width is generated with reference to a voltage signal indicative of the DC signal such that the determined pulse width compensates for fluctuations in the DC supply. Voltage fluctuations in the DC supply will manifest themselves as pulse amplitude modulation in the voltage supplied to the output and so the desired voltage will not be met by the average voltage supplied to the output over the period. By adding or subtracting width to/from the pulse or pulses of the first and/or second switching signal, the lost or gained amplitude can be compensated for by adjusting the width of the voltage pulse or pulses supplied to the output. Advantageously, the voltage signal is passed through a filter to obtain a predictive measure of fluctuations in the DC supply. This may alleviate problems in the finite response time in relaying the voltage signal and in generating the switching signals for the successive period. The voltage signal may be passed through a finite impulse response filter. The first or second determined pulse width may be generated to include additional width to compensate for a voltage drop across a diode and/or transistor in the bridge circuit. Conveniently, the additional width is calculated with reference to a current signal indicative of the current flowing through the output and a representative resistance of the diode or transistor. If these voltage drops are not compensated for, the voltage supplied to the output will be less than the desired voltage. Optionally, the width of a pulse of the first or second switching signals is generated to include additional width to compensate for a voltage offset caused by slow response times in the first or second switch. Slowness in the response of the switches will lead to sloping leading and trailing edges of the pulses seen in the voltage supplied to the output. If the slope is not equal, the average voltage supplied to the output over the period will not match the desired voltage. Preferably, the first and second switches are transistors and the method comprises the step of switching the transistors between on and off states corresponding to substantially maximum and substantially minimum current flow respectively through the transistors. The transistors may be MOSFET transistors, for example. Optionally, the method comprises the step of receiving a current demand signal indicative of a desired current to be supplied to the output in a period and calculating the voltage demand signal indicative of a desired voltage to be supplied to the output that results in an electrical signal being supplied to the output during the period with a current substantially equal to the desired current. In this way, the current controller may take a current demand and operate by calculating a corresponding voltage demand locally. Optionally, the step of calculating the voltage demand signal is performed with reference to a model of the load characteristic of a load connected to the output. For example, a look-up table may be constructed listing required voltages to generate the desired currents. Alternatively, a polynomial relationship or similar may be derived such that the required voltage can be calculated given a desired current. Preferably, the step of generating the voltage demand signal may be performed with reference to a current signal indicative of the current flowing through the output. In this way, adjustments may be made to compensate for any difference between the desired current and the actual current measured at the output. One way of achieving this is to calculate the difference between tube desired current and actual measured current and subtract this from the current demand signal prior to calculating the voltage demand. The invention also resides in a computer program comprising program code means for performing the method steps described herein above when the program is run on a computer and/or other processing means associated with the bridge circuit. Furthermore, the invention also resides in a computer program product comprising program code means stored on a computer readable medium for performing the method steps described herein above when the program is run on a computer and/or other processing means associated with the bridge circuit. From another aspect, the invention also resides in a switching circuit operable to receive a DC signal of voltage +VS and that comprises first and second switches, an output and processing means programmed to perform the method steps described herein above. Optionally, the switching circuit may further comprise a noise shaper operable to noise shape the first and second switching signals. The invention also resides in a bridge circuit comprising an input operable to receive a DC signal of voltage +VS, an output and first and second arms having first and second switches respectively, the first and second arms being connected to opposed ends of the output and processing means programmed to perform the method steps described herein above. The bridge circuit may optionally include any of a voltage signal sensor, a filter (including a finite impulse response filter), a diode and/or transistor or a current signal sensor. The invention will now be described, by way of example only, by reference to the accompanying drawings in which: FIG. 1 shows a half-bridge circuit 14; FIG. 2 is a schematic representation of a current controller according to a first embodiment of the present invention; FIG. 3a is a schematic representation of the switching signal generator 28 of FIG. 2; FIG. 3b is a schematic representation of the noise shaper 46 of FIG. 3a; FIG. 4 is a schematic representation of the voltage sensor system 34 of FIG. 2; FIGS. 5a-d shows, for a single period only, switching signals 24a, 24b for the transistors 20a, 20b as provided at points A and B of FIG. 1 for four different switching modes and the resultant voltage (labelled as Vmag for brevity) seen by the electromagnet 10; and FIG. 6 is a schematic representation of part of a second embodiment of a current controller that can be operated in either voltage demand or current demand mode. A current controller that may be operated in accordance with the method of the invention is illustrated in the schematic sketch of FIG. 2. As will be clear, the current controller supplies current to an electromagnet 10. The electromagnet 10 may, for example, be one of an array of such electromagnets used to levitate a raft supporting moving machinery that is subject to resonant vibrations thereby isolating the resonances from any surrounding structure. In this embodiment, the current controller supplies current to the electromagnet 10 in response to a voltage demand signal 12. The voltage demand signal 12 is generated in accordance with a desired force to be generated by the electromagnet 10. For example, the voltage demand signal 12 may be generated by a global controller (not shown) that gathers information about the vibrations of the raft supporting the moving machinery from a number of motion sensors over successive periods of time. The global controller may then determine the force that should be generated by each electromagnet 10 to reduce the resonances during each successive period. Once the force is determined, the global controller may calculate the required voltage to be applied to the electromagnet 10 for each successive period to realise the desired force and supply this to the current controller as the voltage demand signal 12. Alternatively, the global controller could supply a signal indicative of the desired force to the current controller, with the current controller calculating the corresponding voltage demand signal 12 locally. The current supplied to the electromagnet 10 is regulated by a switching circuit in the form of a half-bridge circuit 14 that corresponds to the one shown in FIG. 1. The half-bridge circuit 14 comprises a bridge whose opposed arms have a pair of diodes 16 and a pair of transistors 20a, 20b. The supply input to the half-bridge circuit 14 is supplied with a DC voltage of +VS, obtained as a filtered DC supply 22 as will be described in more detail later. The electromagnet 10 is connected across the output of the half-bridge circuit 14. Switching signals 24a, 24b are applied to the transistors 20a, 20b at points A, B respectively. The transistors may be of the MOSFET type, although other commonly available types are equally employable. The transistors 20a, 20b are run between on and off states, i.e. between states of minimum and maximum current flow, rather than using the linear region of their conductance where power losses are greater. The switching signals 24a, 24b control the transistors 20a, 20b respectively to operate the half-bridge circuit 14 in one of three modes. In the first mode, both transistors 20a, 20b are switched ‘on’, i.e. into a conducting state, so that the electromagnet 10 sees a voltage of +VS and current flows through the electromagnet 10 in a forward path from transistor 20a to transistor 20b, i.e. from right to left. In the second mode, one of the transistors 20a, 20b is switched ‘on’ and the other is switched ‘off’, i.e. into a non-conducting state. As will be readily apparent, in this mode the electromagnet 10 sees a voltage of 0V and current can only flow through one loop of the half-bridge circuit 14. When transistor 20a is switched on and transistor 20b is switched off, current flows in the upper loop of the half-bridge circuit 14 shown in FIG. 1. Conversely, when transistor 20b is switched on and transistor 20a is switched off, current flows through the lower loop of the half-bridge circuit 14 of FIG. 1. However, irrespective of which transistor 20a, 20b is on and which is off, current always flows through the electromagnet 10 from right to left: this current will drop in magnitude according to the resistive losses in the current path. Finally, in the third mode both transistors 20a, 20b are switched off. The reservoir capacitor 26 connected across the filtered DC supply 22 and the large inductance of the electromagnet 10 ensures current flows through the electromagnet 10 along a reverse path through both diodes 16. Accordingly, the electromagnet 10 sees a voltage of −VS and, again, current flows through the electromagnet 10 from right to left. This current flow will diminish in magnitude as the reservoir capacitor 26 discharges through resistive losses. It will be appreciated that the above arrangement leads to unidirectional current flow through the electromagnet 10. Furthermore, it will be evident that this current flow may be controlled by supplying suitable switching signals 24a, 24b to transistors 20a, 20b respectively thereby to set voltages of +VS, 0V or −VS across the electromagnet 10. The switching signals 24a, 24b for each successive period of time are generated by a switching signals generator system 28 operable in response to the voltage demand signal 12. The average current flowing through the electromagnet 10 during any one period may be varied by altering the duty cycles at each of the voltage levels +VS, 0V or −VS during the period. A maximum increase in current flow will correspond to a voltage of +VS being set throughout a period and a maximum decrease in current flow will correspond to a voltage of −VS being set throughout a period. In addition to generating the switching signals 24a, 24b in response to the voltage demand signal 12, the switching signals generator system 28 may also take account of two further signals when generating the appropriate switching signals 24a, 24b. These signals are a voltage sensor signal 30 and a current sensor signal 32. The voltage sensor signal 30 is a predictive measure of voltage fluctuations in the filtered DC supply 22 provided at the input of the half-bridge circuit 14. The voltage sensor signal 30 is generated by a voltage sensor system 34 that measures fluctuations in the voltage supplied by a DC supply 36 after it has passed through a filter 38 as will be described in more detail below. Turning now to the current sensor signal 32, this signal 32 is generated by a current sensor 40 that measures the current produced by the half-bridge circuit 14 that flows through the electromagnet 10 as will be described in more detail below. Essentially, the current sensor signal 32 is used by the switching signals generator system 28 to account for voltage drops in the transistors 20a, 20b and slow rise and fall times in the voltage pulses seen by the electromagnet 10 due to its capacitance. Although it is not essential for the switching signals generator system 28 to generate the switching signals 24a, 24b with regard to the voltage sensor signal 30 or the current sensor signal 32, far better noise control can be achieved if it is as will become evident below. The elements of the switching signals generator system 28 will now be described in more detail. As can be seen most clearly from FIG. 3a, the voltage demand signal 12, the voltage sensor signal 30 and the current sensor signal 32 are passed to a voltage pulse width generator 42. The voltage pulse width generator 42 calculates the required voltage pulse width 44 for the period to match the voltage demand signal 12 for that period, compensating for any predicted voltage fluctuations in the filtered DC supply 22 by reference to the voltage sensor signal 30 and for any voltage drops in the half-bridge circuit 14 by reference to the current sensor signal 32. For example, if the voltage demand signal 12 demands a voltage of ½VS for the period, the voltage pulse width generator 42 will generate a pulse of +VS to occupy half the period, the other half of the period being set to 0V. The calculated voltage pulse width 44 is then passed to a noise shaper 46 where quantisation noise in the signal is shaped such that noise is suppressed at the frequencies of interest at the expense of increased noise at higher frequencies. The noise shaper 46 is shown in more detail in FIG. 3b and will be discussed in greater detail below. After noise shaping, the resulting voltage pulse width 48 is then passed to a switching signals pulse width generator 50 that calculates the pulse widths for each of the switching signals 24a, 24b passed to the transistors 20a, 20b. These switching signal pulse widths 52 are set to correspond to the noise shaped voltage pulse width 48 passed on by the noise shaper 46. The switching signal pulse widths 52 are calculated with respect to the current sensor signal 32 (carried through from the voltage pulse width generator 42 and the noise shaper 46) to compensate for slow rise and fall times in the voltage across the electromagnet 10 following switching of the transistors 20a, 20b. In addition, the switching signal pulse widths 52 are combined to give the compensated voltage pulse width 53. Now that the switching signals' pulse widths 52 are known, they are passed on to a pulse width quantiser 54 to have the required width matched to the nearest available quantised level within the bit resolution of the quantising scheme. The quantised switching signals pulse widths 56 are used to calculate the corresponding quantised voltage pulse width 57, which will differ from the compensated voltage pulse width 53 within the limits of quantisation. The differences between the switching signals pulse widths 52 and the quantised switching signals pulse widths 56 and the compensated voltage pulse width 53 and the quantised voltage pulse width 57 are, of course, quantisation errors and they manifest themselves as quantisation noise. The quantised voltage pulse width 57 is sent back through a feedback loop 58 to the noise shaper 46 such that the quantisation noise is reduced. The quantised switching signals pulse widths 56 are then passed to a switching signals edge position generator 60 that calculates the appropriate edge positions for the switching signals 24a, 24b. The calculated switching signals edge positions 62 are then converted to the actual switching signals 24a, 24b by a switching signals generator 64 with reference to a precision timing clock 66 thereby ensuring accuracy and synchronisation. Finally, the switching signals 24a, 24b are passed to the transistors 20a, 20b respectively at points A and B of FIG. 1 respectively. Operation of the transistors 20a, 20b causes the voltage across the electromagnet 10 to vary between the values of +VS, 0V and −VS thereby forming quantised voltage pulses to match the quantised voltage pulse width 57. The noise shaper 46 of FIG. 3a is shown in more detail in FIG. 3b. As can be seen, the voltage pulse width 44 is passed to a junction 68 where the noise-shaped quantisation error 70 is subtracted. In actual fact, a second-order noise-shaping scheme is used where a weighted fraction of the noise-shaped quantisation error from the last-but-one period is combined with the noise-shaped quantisation error 70 from the previous period before being subtracted. This produces a noise-shaped voltage pulse width 48 that contains a compensation for the additional voltage added or missed due to the quantisation error of the previous periods. The noise-shaped voltage pulse width 48 is then used for generating the switching signals pulse widths 52 that are used in turn to generate the quantised switching signals pulse widths 56 from which the quantised voltage pulse width 57 is deduced as described above. The quantised voltage pulse width 57 is passed along the feedback loop 58 where it is subtracted from the compensated voltage pulse width 53 at the junction 72 to give the quantisation error 74. Following that, the quantisation error 74 is processed by a noise shaping filter 76 that uses second-order noise-shaping to suppress the quantisation noise across the frequency band of interest, as is well known in the art. Next, the processed quantisation error 78 produced by the noise shaping filter 76 is passed through a one period delay at 80 to ensure that the processed quantisation error is subtracted from the voltage pulse width 44 for the successive period. Hence, the negative feedback loop is completed. The voltage sensor system 34 will now be described in more detail with particular reference to FIG. 4. As mentioned above, the supply input to the half-bridge circuit 14 is supplied with a filtered DC supply 22. This is obtained from a DC supply 36 that is passed through a filter 38 to remove as much mains ripple as possible that may be present in the signal from the DC supply 36. In addition, there will be some intermodulation of the filtered DC supply 22 due to variations in the potential across the reservoir capacitor 26 in the half-bridge circuit 14 as it charges and discharges in response to variations in current flowing through the electromagnet 10. The intermodulation will manifest themselves as an amplitude modulation in the quantised voltage pulses seen by the electromagnet 10. Clearly, deviation from the desired +VS, 0V or −VS pulse levels will lead to the voltage demand signal 12 not being met and the current flowing through the magnet will drift from that necessary to create the intended magnetic fields (e.g. to isolate vibrations in the moving machinery). To compensate for unwanted fluctuations in the filtered DC supply 22, a predictive voltage sensor system 34 is used. Signal-processing delays mean that direct feedthrough of fluctuations in the filtered DC supply 22 would arrive at the switching signals generator 28 too late to provide effective compensation. Hence, a the feedforward predictive voltage sensor system 34 is used. A voltage sensor 82 measures the filtered DC supply 22 as shown in FIG. 4. The reciprocal of these measurements is calculated at 84 for use by a 7-tap finite impulse response (FIR) filter 86. These components are readily available as will be appreciated by those skilled in the art. The FIR filter 86 is used to predict the likely value of 1/VS across the next period and passes this value as the voltage sensor signal 30 to the switching signals generator 28 such that weight can be added or subtracted to the voltage pulse width 44 proportionate to an expected increase or decrease in voltage respectively. The quality of control of the electromagnet 10 is also affected by the finite and non-trivial time taken for the voltage seen by the electromagnet 10 to fall upon switching off of one of the transistors 20a, 20b (among other factors, as will be explained below). The linear decay of the voltage is caused because the voltage can only fall as fast as the current can discharge the capacitance inherent in the electromagnet 10. The current is measured by the current sensor 40, shown in FIG. 2, and the resulting current sensor signal 32 is passed to the switching signal generator 28 so that the switching signals pulse widths 52 can be calculated to compensate for the slow decay in voltage corresponding to the current measured in the previous period. Now that the components of the current controller have been described, there follows a presentation of the method of operation of the current controller with particular attention being paid to how the widths of the pulses in the voltage seen by the electromagnet 10 and the pulses in the switching signals 24a, 24b are determined. Each period begins with a voltage demand 12 being received by the switching signals generator 28 that, in turn, calculates the required switching signals 24a, 24b that will produce an average voltage across the electromagnet 10 for the period to match the voltage demand 12. The switching signals generator 28 then passes the switching signals 24a, 24b to the transistors 20a, 20b respectively, correctly synchronised to the period by reference to a precision timing clock 66. As can best be seen from FIG. 3a, the voltage demand 12 is received by the voltage pulse width generator 42. As mentioned above, the voltage pulse width 44 in seconds is generated assuming that a single pulse of either +VS or −VS relative to a baseline of 0V will be used. The voltage pulse width 44 is generated with regard to fluctuations in the filtered DC supply 22, according to a predictive measure of Vs for the period which is supplied as the voltage sensor signal 30 which can be written as (1/VS)est. Furthermore, account is also taken of the forward voltage drop of the diodes 16 (Vdiode) and the transistors 20a, 20b. If these effects were not accounted for, an output voltage offset and change in output voltage amplitude would be seen. The voltage drop across the transistors 20a, 20b is known to vary significantly over typical operating conditions. To estimate the size of the voltage drop, a value of the transistors' 20a, 20b drain-source resistance (RDS) is obtained from the corresponding device data sheet for a representative operating point. This resistance is used in conjunction with the current sensor signal 32 (which gives the current Imag flowing through the electromagnet 10) to estimate the forward voltage drop of the transistors 20a, 20b. The value of Vdiode is assumed to be constant across the operating conditions of the current controller and so is obtained by choosing a value representative of a typical operating point from the corresponding device data sheet. Finally, a small DC offset voltage correction (Voffset) is used for fine adjustment of the output voltage: this value is obtained by calibration. The demanded voltage 12 (Vdemand) is adjusted by the addition of the voltage drops in the diodes 16 and transistors 20a, 20b and the offset voltage correction, to compensate for those losses (use of positive and negative signs for the offset ensure correct compensation). The required voltage pulse width 44 (Wreq) can hence be calculated from: W req = ( V demand + V diode + I mag · R DS + V offset ) · ( 1 V S ) est · W full equation ⁢ ⁢ ( 1 ) where Wfull is the maximum pulse width in seconds. In this example, a pulse repetition frequency of 64 kHz was used and the frequency of the timing clock was 32.768 MHz giving a period width of 15.625 μs. Of course, other pulse repetition frequencies can be substituted depending on noise demands and expense or availability of components to cope with higher frequencies. It will be noted from equation (1) that the voltage pulse width 44 will carry a sign reflecting the polarity of the voltage demanded, i.e. it will be positive for voltage demands 12 in the range 0V to +VS and negative for voltage demands 12 in the range 0V to −VS. This sign is carried throughout the subsequent calculations. Furthermore, the voltage pulse width 44 is a measure of the time away from the 0V base line and hence is the width of the pulse at +VS and the pulse at −VS. Whilst equation (1) leads to a high level of accuracy, not all or any of the terms contained in the first set of brackets (other than Vdemand) need be included where a reduction in the performance of the electromagnet 10 can be tolerated. The voltage pulse width 44 is then passed to the noise shaper system 46 to produce a noise-shaped voltage pulse width 48 (Wsh). This is calculated with reference to the quantisation error in the width of the previous period's pulse (WQE-1) and also with reference to the quantisation error in the width of the last-but-one period's pulse (WQE-2) as mentioned above. The noise-shaped voltage pulse width 48 is given by: W sh = W req - 2 ⁢ ⁢ cos ⁡ ( 2 ⁢ π · f notch f PRF ) · W QE - 1 + W QE - 2 where fPRF is the pulse repetition frequency (64 kHz, as mentioned above) and where fnotch is the chosen frequency for the inevitable notch in the noise spectrum of the shaped noise. In the present embodiment, this was chosen to be 1 kHz. The noise-shaped voltage pulse width 48 is then passed to the switching signals pulse width generator 50 that generates the corresponding widths for the pulses in the switching signals 24a, 24b. However, there are four modes of switching the transistors 20a, 20b and the correct mode must be implemented. Accordingly, these four modes are now detailed with reference to FIGS. 5a-d. To summarise what has been discussed previously in this respect, the following voltages are seen by the electromagnet 10 when the transistors 20a, 20b are switched as follows: transistor states voltage both on +Vs one on, one off 0 V both off −Vs FIG. 5a shows the switching sequence where the voltage demand 12 is for a positive voltage, i.e. in the range of 0 to +VS. To avoid the power losses inherent in each switching operation of either transistor 20a, 20b, the default switching mode is a so-called ‘class B’ mode where only one transistor 20a is switched during a period whilst the other transistor 20b is left in its on state throughout the period. In this way, no power is lost in transistor 20b due to switching. In addition, in many types of application the voltage demand 12 is likely to remain positive or negative for many successive periods so that one transistor 20a, 20b can be left in a steady state over those periods thereby avoiding any power loss inherent in switching that transistor 20a, 20b. As can be seen, a single pulse in switching signal 24a is generated centrally within the period to provide a voltage across the electromagnet 10 with a single corresponding pulse of +VS (hatched in FIG. 5a) rising from a baseline of 0V to give the demanded positive voltage. FIG. 5b shows a second mode of operation corresponding to a voltage demand 12 for a negative voltage, i.e. in the range of 0 to −VS. Again, class B switching of the transistors 20a, 20b is used, this time with transistor 20a being left in an off state throughout the period and transistor 20b being switched with its switching signal 24b having a central pulse within the period. The resulting voltage seen by the electromagnet 10 has a pair of −VS pulses extending from the 0V baseline at the beginning and end of the period. Hence, the two pulses hatched in FIG. 5b combine to form the required negative voltage pulse. Therefore it is not the central pulse of switching signal 20b that gives the −VS pulse, but rather the peripheral regions. Accordingly, it is the full width of the period less the width of the central pulse in the switching signal 24b that corresponds to the width of the −Vs pulse in the voltage seen by the electromagnet 10. It will be appreciated that, as above, a transistor (20a in this case) can be left in a steady state where successive negative voltages are demanded. Strictly speaking, a further mode ought to be mentioned for the sake of completeness, namely that arising when a zero voltage is demanded. This can be implemented by leaving transistors 20a off and 20b on throughout the period. Whilst class B switching is preferred due to the reduction in power losses in having to switch both transistors 20a and 20b within a period, a conflicting demand arises where small positive or small negative voltages are demanded. In the case of a small positive voltage, this leads to a narrow pulse in the voltage seen by the electromagnet 10 such that the voltage must rapidly step up to +VS then down to 0V. In the case of a small negative voltage, the problem lies in the start and end of successive periods where the voltage must rapidly step down to −VS then up to 0V. Slow response of the transistors 20a, 20b and ringing adds distortion to the square edges of the pulses leading to a lack of voltage control. These effects become problematic for a characteristic small pulse width where the steady flat region between ringing waveforms is lost. This leads to a loss of linearity in the current controller. To overcome this problem, a threshold pulse width Wthresh is set and when a pulse width below this is required to meet a voltage demand 12, switching changes to so-called ‘class AB’ mode where both transistors 20a, 20b are switched in a period. FIG. 5c shows a case of class AB switching for a small positive voltage demand 12. If implemented using class B switching, a single pulse in the voltage seen by the electromagnet 10 would arise that is below the threshold width. To avoid this, the transistor 20a is switched to produce a central on pulse with the a width equal to the threshold width plus the demanded width and, rather than leaving the transistor 20b in its on state throughout the period, it is switched to produce a central on pulse occupying most of the period. The resulting potential seen by the electromagnet 10 starts and ends with small downwardly-extending pulses at −VS where both transistors 20a, 20b are off (indicated by the unbroken hatched areas) which steps to regions at 0V where transistor 20b is on and transistor 20a is off, these regions meeting at a central pulse at +VS where both transistors 20a, 20b are on (indicated by the broken hatched area). The widths of the hatched areas have been exaggerated for the sake of clarity and should not be used to gauge actual threshold widths. The average potential seen by the electromagnet 10 over the period corresponds to the broken hatched area less the unbroken hatched areas which clearly results in a net small positive voltage. In a similar vein, FIG. 5d shows the case of class AB switching in response to a small negative voltage demand 12 that, if class B switching were to be used, would result in a width of the −VS pulse between successive periods that is below the threshold width. To maintain the minimum −VS pulse width, transistor 20b is switched to have an on pulse extending centrally over most of the period. Transistor 20a, rather than being left in an off state as in class B switching, is switched to have a central on pulse. The resulting potential seen by the electromagnet 10 has a shape corresponding to that described above with reference to FIG. 5c, except that now the unbroken hatched areas corresponding to −VS combine to be larger than the broken hatched area corresponding to +VS, hence resulting in the electromagnet 10 seeing a small negative average potential. Accordingly, the type of switching mode is determined by testing the following conditions: Wsh≧0 condition (1) |Wsh|−Wcap≧Wthresh condition (2) where Wcap is a width adjustment calculated to compensate for capacitance in the electromagnet 10 (Cmag). This capacitance causes slow rise and fall times between the voltage levels seen by the electromagnet 10, as mentioned above, and so has the effect of artificially lengthening the pulses. Hence, control is lost. The width adjustment is calculated from: W cap = C mag 2 ⁢ MAX ⁢ { I mag , I min } where the largest of the current through the electromagnet 10 (Imag) or a minimum current value (Imin) is used. The minimum current value corresponds to a lower limit of current used in this calculation to avoid dividing by zero and other problems encountered where only small currents flow through the electromagnet 10. The type of switching appropriate for the outcome of testing conditions (1) and (2) is presented below: condition (1) condition (2) switching mode illustrated in yes yes +class B no yes −class B yes no +class AB no no −class AB The switching signal pulse widths 52 are then calculated for the appropriate switching modes as follows. In the equations below, WA and WB are the widths of the pulses of switching signals 24a and 24b respectively. WEA and WEB are the net effective errors in the actual width of the pulses generated in response to the switching signals 24a and 24b respectively (the values are determined through calibration). Wmin is a fixed offset to be added when in class AB mode. +class B WA=|Wsh|−Wcap−WEA WB=Wfull i.e. transistor 20a has a pulse of the noise shaped voltage pulse width 48 less compensation for capacitance and net effective errors, whilst transistor 20b remains on throughout the period. −class B WA=0 WB=Wfull−|Wsh|Wcap−WEB i.e. transistor 20a remains off throughout the period, whilst transistor 20b has a central pulse equal to the full period width less the noise shaped voltage pulse width 48 (remembering that the noise shaped voltage pulse width 48 reflects the voltage pulse width at −VS whereas we are now setting a width for a pulse in the switching signal generating the central region at 0V) and also less compensation for capacitance and net effective errors. +class AB WA=|Wsh|+(Wmin+Wcap)−Wcap−WEA WB=Wfull−(Wmin+Wcap)−Wcap−WEB i.e. transistor 20a has a pulse of the noise shaped voltage pulse width 48 plus the fixed offset to ensure the threshold width is exceeded less compensation for capacitance and net effective errors, whilst transistor 20b remains on throughout the period less the fixed offset to ensure no net gain in output voltage across the electromagnet 10 and less compensation for capacitance and net effective errors. −class AB WA=(Wmin+Wcap)−Wcap−WEA WB=Wfull−|Wsh|−(Wmin+Wcap)−Wcap−WEB i.e. similar to the case of −class B switching, but now transistor 20a contains a pulse with the fixed offset width less compensation for capacitance and net effective errors, whilst transistor 20b has a reduction in width in its central pulse corresponding to the fixed offset to ensure a minimum gap between voltage changes between periods. The switching signals pulse widths 52 have now been calculated, but these widths 52 are in seconds and can take any value in the range of 0 s to the full width of the period (the reciprocal of the pulse repetition frequency, i.e. 15.625 μs). However, as the final switching signals are pulse width modulated, the switching signals pulse widths 52 must be converted to cycle counts of the precision timing clock 66 such that they are quantised to match the number of available cycle counts in one period (it has been noted above that the combination of pulse repetition frequency and precision timing clock 66 frequency fclock gives 512 cycle counts per period). This function is performed by the switching signals pulse width quantiser 54. The switching signals pulse width quantiser 54 calculates the number of cycle counts (NA and NB for transistors 20a and 20b respectively) from the simple formulae below and passes these values on as the quantised switching signals pulse widths 56. NA=|round(fclock·WA)| NB=|round(fclock·WB)| NA and NB are also used to calculate the quantisation error 74 (WQE) according to the formula: W QE = ( N A f clock - W A ) + ( N B f clock - W B ) WQE is then used as WQE-1 and WQE-2 in following periods, as described above. With the quantised switching signals pulse widths 56 known in units of cycle counts of the precision timing clock 66, the switching signals edge position generator 60 generates the precise cycle counts where the edges of the pulses of the switching signals 24a, 24b will occur. The pulses are positioned using alternate-odd-asymmetry in order to minimise signal distortion. This distortion arises from where pulses of an odd number of cycle counts are needed. Such pulses cannot be positioned centrally within the period given the constraint that the edges must coincide with the start and end of cycle counts. If the pulses were always positioned to be half a cycle early or half a cycle late, distortion would result. This distortion is minimised by using alternate odd asymmetry, i.e. by alternating the offset between the leading and trailing edge halves of the period. Put into algorithms, the on edge position and off edge positions for transistor 20a are given by: if NA is even then: ONA = ½(Nfull − NA) else: ONA = ½(Nfull − NA + dA) and dA = −dA and: OFFA = ONA + NA where Nfull is the maximum number of cycle counts (512) and dA is initially set to +1 and its value is carried through from one period to the next. As will be appreciated, the edge positions for transistor 20b are determined in corresponding fashion (i.e. with the ‘A’ subscripts swapped for ‘B’ subscripts). With the edge positions of the pulses in the switching signals 24a, 24b known, these values are passed to the switching signals generator 64 as the switching signals edge positions 62. The switching signals generator 64 then synchronises the switching signals edge positions 62 to the cycle counts of the precision timing clock 66 to produce the actual switching signals 24a, 24b which are then passed to the transistors 20a, 20b respectively. Hence, the half-bridge circuit 14 is operated to produce an average voltage across the electromagnet 10 corresponding to the voltage demand 12. The person skilled in the art will appreciate that modifications can be made to the embodiments described hereinabove without departing from the scope of the invention. For example, the above embodiment describes a current controller that supplies current to the electromagnet 10 in response to a voltage demand signal 12 that may be generated in accordance with a desired force by a global controller. However, the current controller may operate in response to a current demand signal 88 rather than a voltage demand signal 12. This signal may be generated by the global controller in much the same way as described with respect to generation of the voltage demand signal 12 of the first embodiment. Such an arrangement is shown in FIG. 6: this Figure is equivalent to FIG. 2 but shows the additional elements required to operate in a current demand mode. Whilst all elements from FIG. 2 (and those shown in detail in FIGS. 3 and 4) would be included in the current controller, only those relevant to this discussion of the current demand mode are shown in FIG. 6 for the sake of clarity. As will be evident, the major change is the inclusion of a control loop indicated generally at 87. In one mode of operation, current demand signal 88 (labelled as 88a for the sake of clarity) is compared with the current sensor signal 32 at a comparator 90. The current sensor signal 32 is derived from the output of the current sensor 40 and provides a measure of the current passing through the electromagnet 10. Comparing the current sensor signal 32 with the current demand signal 88a provides an error signal 92 that represents deviation in current through the electromagnet 10 away from the demanded current. The error signal 92 is passed to a filter 94 that incorporates control loop gain, a control loop filter and a current-to-voltage transfer model to produce voltage demand signal 12a. The voltage demand signal 12a is passed to the switching signals generator system 28 via a three-way switch 96. Inaccuracies in the current-to-voltage transfer model are compensated by the control loop 87 using the current sensor 40. The performance of the current controller is dependent more on the noise performance and accuracy of the current sensor 40 than the accuracy of the current-to-voltage transfer model. If necessary, a combination of current sensors may be used, to give the best dynamic range for example. In an alternative mode of operation where the control loop 87 that compensates for drifts in electromagnet current (via current sensor signal 32) is not required, the current demand signal 88 can be passed directly at 88b to a voltage demand generator 100, as shown in FIG. 6. The voltage demand generator 100 generates the voltage demand signal 12b by using a filter containing a model of the electromagnet load characteristic so that the voltage demand generator 100 can predict the appropriate voltage demand necessary to produce the required current demand 88. The voltage demand signal 12b is passed to the switching signals generator system 28 via a three-way switch 96. Of course, the accuracy of the eventual current passed to the electromagnet 10 is heavily dependent upon the accuracy of the load model generating the voltage demand signal 12b. If desired, the current controller can be adapted to operate in either voltage demand or current demand mode. For example, the three-way switch 96 could be used to switch between the voltage demand input 12a provided by the filter 94 or the voltage demand input 12b provided by the voltage demand generator 100 or a direct voltage demand input 12c (i.e. a line carrying a voltage demand direct from a global controller or similar) to produce the voltage demand signal 12 passed to the switching signals generator system 28.

20040702

20080325

20050324

76625.0

KAPLAN, HAL IRA

SWITCHING CIRCUIT AND A METHOD OF OPERATION THEREOF

UNDISCOUNTED

ACCEPTED

ACCEPTED

Spiral wound membrane element and a process for preventing telescoping of the filter element

A process for ultrafiltration using a spiral wound membrane filter is disclosed where the pressure in the space between the filter element and the pressure vessel is higher than or equal to the pressure inside the filter element. Using these conditions the static force created by the pressure provides a high friction between different sheets in the spiral wound filter element, which efficient prevents unwinding or telescoping of the filter element. Using this configuration it is possible to perform the ultrafiltration using a higher differential pressure across the filter element than would otherwise have been possible which leads to a higher efficiency and a low energy consumption. Further an anti telescoping device (ATD) and a spiral wound filter element, which are particular suited for the disclosed process, are described.

1. Filter assembly for ultrafiltration comprising in a pressure vessel one or more filter elements with antitelescoping devices (ATD) located upstreams and downstreams for each filter element, wherein the filter elements comprises one or more membranes, each consisting of a central permeate spacer covered on both sides by separating membranes, connected at one edge with a permeate pipe and blocked at the three other edges, wound around a central permeate pipe with a concentrate spacer allowing fluid from the space between the wound filter element and the pressure vessel to flow into the wound filter element in a direction tangential to the cross-section of the filter element, so that the membranes and concentrate spacers are lying alternating in the wound element; and wherein the inlet to the space between the wound filter element and the pressure vessel is free and the outlet from said space is restricted so that no flow or only a limited flow is allowed from said space to the space after the respective wound filter element characterized in that, the wound filter elements are provided with means for securing that the pressure inside the retentate channels of the filter element is equal to or lower than the pressure in the space between the filter element and the pressure vessel at the same longitudinal position over the whole length of the element. 2. Filter assembly according to claim 1, wherein the ATD is formed having a ring abutting to the outlet side of the wound filter element preventing fluid flowing out from the filter element in a distance from the central permeate pipe higher than d, where d is a distance smaller than the radius of the spiral wound membrane element. 3. Filter assembly according to claim 1, wherein the means for securing that the pressure at the inlet of the filter element is equal to or lower that the pressure in the space between the filter element and the pressure vessel at the same longitudinal position is a flow restrictor placed at the inlet to the spiral wound filter element. 4. Filter assembly according to claim 3, wherein the flow restrictor is made in one piece with the ATD. 5. Filter assembly according claim 1, wherein the concentrate spacers are protruding from the separating membranes. 6. Process for ultrafiltration using a filter assembly according to claim 1, wherein a cross section at any position along the filter element the pressure in the space between the filter element and the pressure vessel is at least 0.01 bar higher than the pressure inside the filter element. 7. Process according to claim 6, wherein the pressure difference between the inlet and the outlet of a filter element is in the range of 0.5 to 5 bar/m. 8. Process according to claim 7, wherein the pressure difference between the inlet and the outlet of a filter element is in the range of 1-3 bar/m. 9. Process according to claim 6, wherein fluid to be filtered is an aqueous solution. 10. Process according to claim 10, wherein the fluid to be treated is milk, whey or a fermentation broth. 11. Anti telescoping device (ATD) for use in a filter assembly according to claim 1, comprising means for securing that fluid can not or only in a limited extend flow out of the space between the proximal filter element and the pressure vessel, means for securing a free flow of the concentrate into the space between the distal filter element and the pressure vessel, and means for restricting flow of concentrate to the inlet of the distal spiral wound filter element in order to secure that the pressure at the inlet of said distal filter element is lower that the pressure in the space between the filter element and the pressure vessel at a corresponding position.

The invention relates to an improved method for ultra filtration, an anti telescoping device (ATD) particular suited for use in said method and an ultra filter particular suited for use in said method. BACKGROUND FOR THE INVENTION The use of ultra filtration to concentrate a feed stream by passing smaller molecules through the filter, while retaining larger molecules are well known in the industry. Uses of ultrafilters are in particular widespread within the dairy industry and in the pharmaceutical industry. Another well-known use is known as reverse osmosis where essentially all molecules larger that water is retained and the permeate is pure water. Reverse osmosis is used e.g. for desalting seawater in order to produce sweet water for household use or irrigation. The basis for all these uses is membranes having suitable permeability properties for the intended use. As the throughput obviously is dependent on the surface area of the membrane it is desirable to use large areas of membrane. In order to avoid voluminous process equipment, such membranes are often arranged in a spiral wound configuration. Typical spiral wound filters consist of 1 to 6 spiral wound elements coupled in a serial flow mode and placed in a cylindrical pressure vessel. Typical spiral wound elements consist of one or more membranes of approximately 1×1 m, wound to a roll having a final diameter of 10-20 cm and a length of approximately 1 m. Between two membranes in the roll is placed a permeable porous medium for conduction of fluid, the concentrate spacer, to ensure that the concentrate can flow over the membrane in order to be distributed all over the surface and to continuously rinse the membrane from accumulating solids. It is known in the area to provide the filter elements with a hard impermeable shell outside the wound filter element in order to keep the element tightly wound. In this configuration flow in and out of the filter element will be through the ends in an axial direction. The flow inside the concentrate spacer may be in an axial or a non-axial direction, where the non-axial direction is in a spiralling tangential movement from the outside towards the centre of the wound spiralling element. It is known within the area that some designs of the concentrate spacer allow tangential spiralling movements whereas other designs do not. Each membrane is typically composed of a porous central conducting medium, the permeate spacer, connected to a central permeate pipe, and on each side of the permeate spacer a separating membrane is provided. The assembly is blocked at the three edges not connected to the permeate pipe e.g. by glue, in order to secure that only fluid penetrating the separating membranes can enter into the permeate spacer. Often a porous permeable tissue, the trim spacer, is wound around the spiral wound filtration element in order to minimize the space that inevitable occur between the spiral wound element and the pressure vessel. At each end of the filter elements and in the interspace between two elements when two or more spiral wound elements are present in a cylindrical vessel anti telescoping devices (ATD) are usually provided, which serve as separators between two elements and to reduce the tendency of the spiral wound elements to unwind by telescoping. A number of different designs of ATDs are known within the area. U.S. Pat. No. 4,296,951 discloses an spheroidal interconnector for filtration modules comprising an molded spheroidal body of elastomeric material having coaxial bores for receiving the respective ends of permeate tubes. These interconnectors are useful at various pressure ranges. U.S. Pat. No. 4,301,013 discloses a spiral membrane module with controlled by-pass seal, where a material is provided in the space between the exterior surface of the filtration module and the interior surface of the cylindrical vessel in order to prevent accumulation of any product in this compartment. U.S. Pat. No. 4,855,058 discloses a high recovery spiral wound membrane module comprising means for providing radial flow for the feed-concentrate mixture to an extend sufficient to achieve a conversation of 30% or greater while maintaining turbulent or chopped laminar flow. U.S. Pat. No. 6,224,767 disclose a fluid separation element assembly where the anti telescoping devises are detachable making them reusable when the membrane elements has reached the end of their efficient life and have to be replaced by new elements. In use the fluid to be concentrated is forced into the inlet of the pressure vessel and is pressed through the filter elements mainly in the axial direction, even though some filter elements also provide for some flow in the radial direction. However a part of the fluid will pass the filter element through the space between the filter element and the cylindrical vessel creating a by-pass flow. The person skilled in the art will appreciate that the pressure drop along the filter element is dependent on the flow resistance encountered at the route the liquid travels. Therefore the pressure profile in the space between the filter element and the vessel will be different from the pressure profile at a path inside the spiral wound filter element even though the starting and final pressures are identical, i.e. at some locations the pressure is identical, at some locations the pressure is higher in the space between the filter element and the vessel and at some locations it is lower. In the locations where the pressure is higher inside the filter element than in the space between the filter element and the vessel there is a tendency of the spiral wound element to unwind or to telescope with the result that channels are formed inside the filter element, which significantly reduces the efficiency of the filter element. In practice it is experienced that the tendency to unwinding or telescoping increases with higher pressure gradients and flow velocity of the liquid with the consequence that the unwinding or telescoping effect limits the pressure gradient that can be applied to a spiral wound element, and because the pressure difference is the driving force in the filtration operation the efficiency of said filter element is limited. It is desired to be able to operate spiral wound filter element at higher-pressure gradients in order to enhance the efficiency of the filter element. SHORT DESCRIPTION OF THE INVENTION The present inventors has realized that the filtration using a spiral wound ultra filter can be improved by a process for ultrafiltration using one or more spiral would membrane filter elements arranged in a cylindrical pressure vessel, where each filter sections comprises one or more membranes, each consisting of a central permeate spacer covered on both sides by the separating membrane, connected at one edge with a permeate pipe and blocked at the three other edges, wound around the central permeate pipe with a concentrate spacer so the membranes and the concentrate spacers are lying alternating in the wound element and allowing the fluid from the space between the filter element and the pressure vessel entering into the concentrate spacer in a tangential spiralling direction, where in a cross section at any location along the filter element the pressure in the space between the spiral wound membrane filter sections and the cylindrical pressure vessel is higher than or equal to the pressure in the concentrate spacers between two membranes. In ultrafiltration plants using spiral wound elements according to the prior art the space between the filter element and the pressure vessel will provide a smaller flow resistance than the concentrate spacers inside the wound filter element with the consequence that the linear velocity of the fluid in the space between the filter element and the pressure vessel is higher than inside the wound filter element. The physical laws for fluids as expressed by the Bernoulli equation, teaches that fluids travelling at a higher velocity will exert a smaller static pressure compared with fluids travelling at a lower velocity. Consequently the skilled person will appreciate that in such an ultrafiltration plant according to the prior art the pressure inside the wound filter element will at some positions be higher that the pressure in the space between the wound filter element and the pressure vessel. In the process according to the invention the pressure creates a force directed from the periphery of the pressure vessel to the centre of the vessel. This force increases the friction between adjacent sheets in the roll, which secures that the spiral wound elements is kept in place without any unwinding and telescoping even when higher pressure than usually is applied to such filter elements. This enables the filter elements to be operated at pressures significantly higher that the pressures used in the prior art, such as a difference of 2 bar of more between the entrance and the outlet of a filter element having a length of approximately 1 m. Such a high pressure difference provides for a higher efficiency of the filtration element, which again secures that a higher concentrating per area of separating membrane may be achieved using this process and. Further a lower energy consumption compared with processes according to the prior art may be achieved. Such advantageous pressure may be established by designing the filter in a way so that the passage between the spiral wound element and the pressure vessel is open for incoming fluid at the entrance of the filter element and blocked or restricted at the outlet of the filter element. In this way the pressure will be established according to the process of the invention. The beneficial pressure conditions according to the invention may be established by use of anti telescoping devices (ATD), comprising an element that when placed in the cylindrical pressure vessel secures that concentrate coming from the preceding filter element or the inlet can not pass the ATD or only pass the ATD in a limited extend at a distance from the central permeate pipe higher than d, where d is smaller that the diameter of the spiral wound membrane filter sections, and where the concentrate streaming out of the preceding filter element is able to flow freely into the space between the following filter element and the pressure vessel. In a preferred embodiment this ATD is provided with a flow restrictor that secures that the incoming fluid in the following filter element meets the end of the filter element at a lower pressure than said fluid meets the periphery of said filter element. In another preferred embodiment the filter element used in the process according to the invention is comprising one or more membranes, each consisting of a central permeate spacer covered on both sides by the separating membrane, connected at one edge with a permeate pipe and blocked at the three other edges, wound around the central permeate pipe with a concentrate spacer so that the membranes and the concentrate spacers are lying alternating in the wound element wherein the concentrate can enter into the concentrate spacer in a spiralling tangential direction from the space between the filter sections and the cylindrical pressure vessel. SHORT DESCRIPTION OF THE DRAWINGS FIG. 1. Schematic presentation of an ultra filter consisting of three spiral wound filter elements (1), a cylindrical pressure vessel (2), an inlet (4), an outlet for concentrate (5) and an outlet for permeate (7), an inlet ATD (9), two intermediate ATDs (8) and an outlet ATD (10). FIG. 2. is a diagram showing the pressure profile of a typical prior art ultra filter where Pi is the inlet pressure, Po is the outlet pressure, and X is the distance from the start of the spiral wound pressure element. FIG. 3. is a diagram showing the pressure profile in a spiral wound module according to the invention. FIG. 4. is a diagram showing the pressure profile in a spiral wound module having a flow restrictor inserted before the inlet end of the spiral wound element. FIG. 5. is a cross section of one embodiment of the ATD according to the invention, showing a cross section between the central permeate pipe (not shown) and the pressure vessel (2). A ring (12) seals off the flow in the outer part of the filter provided with a lip-seal (13) sealing off to the vessel and an opening (14) that allows the feed/concentrate to enter into the space between the following spiral wound element and the pressure vessel. FIG. 6. shows another embodiment of the ATD according to the invention further provided with a flow restrictor (15) and a ring (16) abutting to the outer part of the following filter element sealing off between the flow restrictor (15) and the opening (14). FIG. 7. is a schematic presentation of the pressure profile along a filter having three spiral wound filter elements separated by ATD's according to the invention provided with flow restrictors. FIG. 8. shows the flow of concentrate in the filter similar to the one described in FIG. 7. FIG. 9. shows a cross section of a spiral wound filter where (21) is the pressure vessel, (22) is the space between the filter and the pressure vessel, (23) is a permeable tissue surrounding the filter element, (24) is a concentrate spacer, (25) is a filter membrane, and the arrows (27-28) show the flow of liquid tangentially into the concentrate spacer (24) of the spiral wound element. FIG. 10, shows an embodiment of the ATD according to the invention where the compartment (30) receiving the outlet from the preceding spiral wound element is formed so the flow resistance is increasing with the distance from the centre of the element, and the compartment (31) from where the inlet to the following element is formed so the flow resistance is decreasing with the distance from the centre of the element. FIG. 11, shows a filtration unit comprising four spiral wound filtration elements separated by ATD according to another embodiment of the invention, with indications of the flow inside the unit. In this embodiment the permeate in the central permeate tube can not pass the ATD, but is withdrawn by permeate outlets (32) provided in every second ATD. By providing suitable counter pressure at the outlets it is possible to adjust the net driving pressure of each filtration element. FIG. 12, shows a schematic cross section of the filtration unit used in the examples. DETAILED DESCRIPTION OF THE INVENTION The present invention is related to ultra filtration where the ultrafilter is comprising one or more spiral wound elements contained in a cylindrical pressure vessel, where a incoming fluid comprising one or more dissolved compounds is concentrated with the simultaneously creation of a permeate comprising the low molecular components of the incoming fluid. Different terms may be used for such separations performed using such a spiral wound filter in a pressure vessel depending on the actual cut off value of the particular membrane in question such as ultra filtration, micro filtration and reverse osmosis. The person skilled in the art will appreciate that the present invention is not restricted to any particular of these terms or to membranes having cut-off values in a particular range, but the invention may be used with any of these separations, even though the description is mainly explained in relation to ultra filtration. Spiral wound elements as such are well known within the area. The invention may in principle be performed using any spiral wound filtration element having separating membranes and concentrate spacers wound around a central permeate pipe, which spiral wound elements allow tangential entry into the concentrate spacer from the space between the filter element and the pressure vessel. Membranes for use in spiral wound elements consist of a central sheet, the permeate spacer, receiving and transporting permeate to the central permeate pipe. On each side of the permeate spacer is attached a separating membrane, and this assembly is blocked at the edges e.g. by glue in order to secure that the only fluid entering into the permeate spacer is entering through the separating membranes and can only escape form the permeate spacer via the unblocked edge and is thereby led into the central permeate pipe. The separating membrane may be selected having a cut-off value that is suitable for the intended use. The cut-off value should in this description be understood in the usual way as the highest molecular weight that a compound able to penetrate the membrane may have. Spiral wound elements are made by winding the membranes attached to the central permeate pipe around said pipe. Between two membranes in the spiral wound elements are inserted a sheet, the concentrate spacer, for transport of the incoming fluid being increasingly more concentrated as the low molecular components pass through the membranes. The function of the permeate spacers and the concentrate spacers is to keep the spacing in where they are placed open for conduit of liquid at the intended pressure of operation. Spiral wound elements; membranes and spacers well known within the prior art may be used in performing the present invention. In order to distinguish different positions in an ultra filtration filter or at a spiral wound filter element the term “preceding” is to be understood as closer to the inlet, whereas the term “following” is to be understood as closer to the outlet for concentrate. During mounting of spiral wound elements in pressure vessels a space between the spiral wound element and the pressure vessel inevitable occur. In this description this space is also termed the slot. The filtration according to the invention is performed by securing that in a cross section of the pressure vessel at any position the pressure in the slot is higher than or equal to the pressure in a concentrate spacer inside the spiral wound element. This pressure distribution reduces the tendency of the spiral wound element to unwind or telescope during operation. Using this particular pressure distribution in the filter it is possible to operate spiral wound filter elements at a higher pressure difference across a filter element than would have been possible if the pressure distribution was different. By use of a higher pressure difference across the filter element the pressure across the membranes increases which leads to a higher throughput per square area of separating membrane present in the filter element. Obviously this is advantageous because the capacity of the filter is increased resulting in a decreased need for investments for equipment. Further the process may be performed having low energy consumption. In principle the maximal pressure difference between the inlet and the outlet of the ultra filter or the spiral wound filter elements may be determined by the compressibility of the wound membrane and spacers. The person skilled in the art will appreciate that the spacers used in a filter element in order to be sufficient porous may be compressed under a high mechanical burden. It is not desired to compress any components of the spiral wound filter because compression may create altered conducting properties. Therefore the pressure difference between the inlet and the outlet should be selected so no compression of the membranes and the spacers occur. In use the pressure difference between the inlet and the outlet of a filtration element is higher that approximately 1 bar per meter filtration element, preferably in the range of 1-5 bar/m, more preferred in the range of 1.5-3 bar/m and most preferred approximately 2 bar/m. The pressure in the slot is preferably at least 0.01 bar higher that the pressure inside the filtration element. A pressure in the slot higher than or equal to the pressure inside the module at a transverse cross-section may be provided by securing that the fluid can enter into the slot from the inlet side but not flow out of the slot in the outlet side of the filter element or only flow out of the slot at the outlet side of the filter element at a limited extend. In this way a higher pressure compared to the inner parts of the filtration element is created in the slot. The expression “in a limited extend” is intended to mean that a small flow out of the slot is allowed in an amount sufficient to prevent formation of dead pockets without flow of liquid anywhere in the filtration unit but sufficient low to secure that essentially all the fluid passes through the filter. The skilled person will appreciate that in sanitary systems e.g. for use in the food or pharmaceutical industry it is crucial that no dead pockets are present because such dead pockets may allow establishment micro organisms which obviously is unacceptable. Flow in a limited extend may be provided by arranging a flow resistance at the outlet of the slot such as a narrow passage for the fluid, e.g. holes in the sealing. The flow in a spiral wound filter element operated according to the invention is indicated in figure 8. Without wishing to be bound by the theory it is believed that the higher pressure in the slot than inside the spiral wound element creates a force on the membranes directed towards the centre of the element which force secures that the friction between different sheets in the spiral wound element is increased and consequently the tendency to lateral movements between sheets are reduced resulting in a reduced tendency to unwinding or telescoping. In FIG. 2 a diagram of the pressure in the slot and inside the element is shown for a filter element operated according to the prior art. As it appears from FIG. 2, the pressure in the slot is at several positions along the filter element higher than or equal to the pressure inside the module. Therefore a static outwards force is created which reduces the friction between different sheets of the element. Contrary in filter elements operated according to the invention, where the pressures are indicated in FIG. 3, the static force created by differences in pressure between different compartments is directed to the centre of the pressure vessel which will increase the friction between adjacent sheets in the spiral wound filter and will therefore prevent movement of one sheet in respect of the adjacent sheet and prevent unwinding of the element. In the end of the filter element proximal to the inlet there are essentially no pressure difference between the slot and the inside of the element is found, whereas the difference increases along the length of the element. In one embodiment a flow restrictor is placed in front of the spiral wound element in a way so that fluid can flow into the slot beside the flow restrictor. The flow restrictor serves to secure that the pressure in the proximal part of the filter element is below the pressure in the slot at the particular place. The properties of the flow restriction is selected so a sufficient pressure difference is created between the entrance of the filter element and the pressure in the slot in a position corresponding to the end of the filter element most proximal to the inlet. Preferably said difference is larger that 0.01 bar, more preferred in the range of 0.05 to 0.1 bar. The flow restrictor may be made of any material capable of restricting the flow to the proximal end of the filter element and sufficient strong to endure the pressure. It is within the skills of the person skilled in the art to determine which materials are suitable for such a flow restrictor. With use of a flow restrictor the pressure profile of a filter element will be as indicated in figure 4. At each end of the filter element and if more than one filter element is provided in a pressure vessel between two filter elements ATDs are placed. An ATD that is particular suited for use according to the present invention is an anti telescoping device (ATD) for separating two spiral wound membrane filter sections in an ultrafiltration unit according to the invention, comprising an element that when placed in the cylindrical pressure vessel secures that concentrate coming from the inlet or the preceding filter element can not or only in a limited extend pass the ATD at a distance from the central permeate pipe longer than d, where d is smaller that the diameter of the spiral wound membrane filter elements, whereas concentrate coming from the preceding filter element freely can flow into the slot between the following filter element and the pressure vessel. This design secures that the fluid can not or only in a limited extend flow from the slot between the preceding filter element into the interspace between two elements, and simultaneously can fluid flow from said interspace into the slot between the following filter element and the pressure vessel. Arranged in this way the ATD according to the invention secures the beneficial pressure distribution in the process according to the invention. The distance d is selected so that the ratio between d and the radius of the pressure vessel is in the range of 0.4 to 0.95, preferably in the range of 0.75 to 0.95, and most preferred in the range of 0.8 to 0.9. Passage of fluid in a limited extend may also be regarded as a controlled bypass of fluid. It may be beneficial to have a controlled bypass in order to secure that fluid is flowing in all parts of the filtration unit and that no “dead pockets” without movement of fluid can appear. This is in particular important in applications within the food or pharmaceutical industries where bacterial growth may establish in dead pockets and therefore must dead pockets be avoided in these applications of sanitary reasons. In one embodiment the ATD may be provided with means for sealing to the pressure vessel. Such means for sealing are well known within the area. Examples of such means for sealing can be selected from lip sealings and O-rings. In another preferred embodiment the ATD may be provided with flow resistance for the fluid flowing out of the preceding filter element, where the flow resistance is increasing with the distance from the centre of the filtration element. Similar the ATD may be designed so that resistance for the fluid flowing into the following filtration element is decreasing with the distance from the centre of the filter element. These varying flow resistances secure that the pressure inside the filtration element is increasing with the distance from the centre of the filter element. Varying flow resistance may be provided by designing the ATD in a way so that the compartment from which the fluid flows in (31) or out (30) is wedge shaped, where the highest flow resistance is at the point of the wedge. In a preferred embodiment the ATD is further provided with a ring abutting on the outer part of the following filter element so that the fluid is unable to enter into the outer concentrate spacers, but able to enter into the inner concentrate spacers and also able to unhindered to flow into the following slot. The ring abutting on the following filter element preferably has a dimension so it is able to block inflow into the filter element in a distance Dr from the outer surface of the filter where the ratio between Dr and the radius of the pressure vessel is in the range of 0.7 to 0.9. The ATD is further provided with structures to establish a sufficient face of contact with the preceding and following filter elements in order to be able to withstand the pressure applied without unacceptable deformation of the filter elements or the ATD. In this connection unacceptable deformation is to be understood as a deformation that significantly reduced the lifetime or efficiency of the filter elements. Suitable structures designed to provide said face of contact may be selected among radial ribs, rings, perforated plates etc, as it will be known within the area. In another preferred embodiment of the invention the ATD is designed in a way so that the permeate in the central permeate tube can not pass the ATD, but instead ATDs are provided with permeate outlets (32). In this way the central permeate is divided into segments each spanning from one ATD to another ATD and each segment provided with a separate outlet. By providing a suitable counter pressure at each permeate outlet it is possible to adjust the net driving pressure, i.e. the pressure difference between the inlet of said filtration element and the permeate outlet of said filtration element, across the separating membranes of each spiral wound filtration element. This is particular advantageous for filtration units containing several spiral wound filtration elements in order to secure that the net driving pressure is essentially identical across each spiral wound filtration element. Each ATD may be provided with one permeate outlet or every second ATD may be provided with two permeate outlets one at each side as indicated in FIG. 11. It is within the skills of the person skilled in the art to select suitable dimensions and materials for the ATD's. In one embodiment the ATD comprise a flow restrictor connected to the ATD in a way that secures that fluid entering the following filter element must pass this flow restrictor but fluid can freely flow into the slot between the following filter element and the pressure vessel without passing the flow restrictor. The flow restrictor secures that the pressure in the slot is higher than the pressure inside the filter elements at all positions along the filter element. In the present invention it is preferred that the filter elements are made in such a way that the concentrate can enter into the concentrate spacer in a spiralling tangential direction from the space between the filter sections and the cylindrical pressure vessel. This secures that the fluid in the slots is flowing into the filter elements as schematically shown in FIG. 9. Flow of liquid into the filter in a tangentially direction further introduces a circulating flow in the slots which again secures that no dead pockets without movement of fluid is present in the pressure vessel. Further the circulating flow secures that no deposits are formed in the slots, which is imperative for use in industries where a high hygienic standard is required. One preferred way to provide for the fluid being able to enter into the filter in a tangentially direction is to design the filter element so that the membranes are not protruding over the concentrate spacer. More preferred the concentrate spacer is protruding to the separating membranes (FIG. 9). Because the process according to the invention to a large extend eliminates the problem of telescoping the process may be performed under conditions mainly determined by the properties of the used membranes and the product to be processed in the ultra filter. However, it is preferred that the process is performed under a pressure difference in the range of 0.5-5 bar/m and a temperature of 1-100° C. The process according to the invention may in principle be used in any industry where ultrafiltrations are used in order to concentrate or fractionate aqueous solutions. In particular the process may be performed within the dairy industry, the pharmaceutical industry and the biotechnological industry. In one preferred embodiment the process according to the invention is used for concentration of a proteinaceous substance in an aqueous medium. A particular preferred aqueous medium is milk or whey. EXAMPLES An arrangement according to FIG. 12 was used for filtrations, where the dimensions and streams were as indicated in the table below. The terms in the table are as indicated in FIG. 12. ex 1 ex 2 ex 3 ex 4 r0 mm 14 14 14 14 r1 mm 18 18 18 18 r2 mm 55 45 35 26.5 r3 mm 75 75 77 79 R mm 80 80 80 80 r4 mm 100 85 82.5 81.5 g1 mm 16 19 13 7 g2 mm 12 11.5 6 2.4 h mm 3 5.5 3 1.2 r4-R mm 20 5 2.5 1.5 A(r1, r2) mm2 8485 5344 2830 1188 A(r2, g1) mm2 5529 5372 2859 1165 A(r3, g2) mm2 5655 5419 2903 1191 A(r3, h) mm2 1414 2592 1451 596 A(r4, R) mm2 10053 2513 1257 754 A(r3, r4) mm2 13744 5026 2756 1261 Qfeed m3/h 25 25 17 17 axial/radial 0.50 0.50 0.50 0.50 flow radial flow m3/h 12.5 12.5 8.5 8.5 Qr Axial flow m3/h 12.5 12.5 8.5 8.5 Qa v(r1, r2) m/s 0.82 1.30 1.67 3.97 v(r2, g1) m/s 1.26 1.29 1.65 4.05 v(r3, g2) m/s 1.23 1.28 1.63 3.96 v(r3, r4) m/s 0.51 1.38 1.71 3.75 v(r3, h) m/s 2.46 1.34 1.63 3.96 v(r4, R) m/s 0.96 1.34 1.85 3.10 In the table the expression A(r1,r2) is intended to mean the area between the r1 and r2. Similar the expression v(r1,r2) is intended to mean the velocity of the stream passing between r1 and r2. Other expressions are to be understood similarly. In all the tested examples the filtrations were performed well without any undesired unwinding or telescoping of the filter element.

<SOH> BACKGROUND FOR THE INVENTION <EOH>The use of ultra filtration to concentrate a feed stream by passing smaller molecules through the filter, while retaining larger molecules are well known in the industry. Uses of ultrafilters are in particular widespread within the dairy industry and in the pharmaceutical industry. Another well-known use is known as reverse osmosis where essentially all molecules larger that water is retained and the permeate is pure water. Reverse osmosis is used e.g. for desalting seawater in order to produce sweet water for household use or irrigation. The basis for all these uses is membranes having suitable permeability properties for the intended use. As the throughput obviously is dependent on the surface area of the membrane it is desirable to use large areas of membrane. In order to avoid voluminous process equipment, such membranes are often arranged in a spiral wound configuration. Typical spiral wound filters consist of 1 to 6 spiral wound elements coupled in a serial flow mode and placed in a cylindrical pressure vessel. Typical spiral wound elements consist of one or more membranes of approximately 1×1 m, wound to a roll having a final diameter of 10-20 cm and a length of approximately 1 m. Between two membranes in the roll is placed a permeable porous medium for conduction of fluid, the concentrate spacer, to ensure that the concentrate can flow over the membrane in order to be distributed all over the surface and to continuously rinse the membrane from accumulating solids. It is known in the area to provide the filter elements with a hard impermeable shell outside the wound filter element in order to keep the element tightly wound. In this configuration flow in and out of the filter element will be through the ends in an axial direction. The flow inside the concentrate spacer may be in an axial or a non-axial direction, where the non-axial direction is in a spiralling tangential movement from the outside towards the centre of the wound spiralling element. It is known within the area that some designs of the concentrate spacer allow tangential spiralling movements whereas other designs do not. Each membrane is typically composed of a porous central conducting medium, the permeate spacer, connected to a central permeate pipe, and on each side of the permeate spacer a separating membrane is provided. The assembly is blocked at the three edges not connected to the permeate pipe e.g. by glue, in order to secure that only fluid penetrating the separating membranes can enter into the permeate spacer. Often a porous permeable tissue, the trim spacer, is wound around the spiral wound filtration element in order to minimize the space that inevitable occur between the spiral wound element and the pressure vessel. At each end of the filter elements and in the interspace between two elements when two or more spiral wound elements are present in a cylindrical vessel anti telescoping devices (ATD) are usually provided, which serve as separators between two elements and to reduce the tendency of the spiral wound elements to unwind by telescoping. A number of different designs of ATDs are known within the area. U.S. Pat. No. 4,296,951 discloses an spheroidal interconnector for filtration modules comprising an molded spheroidal body of elastomeric material having coaxial bores for receiving the respective ends of permeate tubes. These interconnectors are useful at various pressure ranges. U.S. Pat. No. 4,301,013 discloses a spiral membrane module with controlled by-pass seal, where a material is provided in the space between the exterior surface of the filtration module and the interior surface of the cylindrical vessel in order to prevent accumulation of any product in this compartment. U.S. Pat. No. 4,855,058 discloses a high recovery spiral wound membrane module comprising means for providing radial flow for the feed-concentrate mixture to an extend sufficient to achieve a conversation of 30% or greater while maintaining turbulent or chopped laminar flow. U.S. Pat. No. 6,224,767 disclose a fluid separation element assembly where the anti telescoping devises are detachable making them reusable when the membrane elements has reached the end of their efficient life and have to be replaced by new elements. In use the fluid to be concentrated is forced into the inlet of the pressure vessel and is pressed through the filter elements mainly in the axial direction, even though some filter elements also provide for some flow in the radial direction. However a part of the fluid will pass the filter element through the space between the filter element and the cylindrical vessel creating a by-pass flow. The person skilled in the art will appreciate that the pressure drop along the filter element is dependent on the flow resistance encountered at the route the liquid travels. Therefore the pressure profile in the space between the filter element and the vessel will be different from the pressure profile at a path inside the spiral wound filter element even though the starting and final pressures are identical, i.e. at some locations the pressure is identical, at some locations the pressure is higher in the space between the filter element and the vessel and at some locations it is lower. In the locations where the pressure is higher inside the filter element than in the space between the filter element and the vessel there is a tendency of the spiral wound element to unwind or to telescope with the result that channels are formed inside the filter element, which significantly reduces the efficiency of the filter element. In practice it is experienced that the tendency to unwinding or telescoping increases with higher pressure gradients and flow velocity of the liquid with the consequence that the unwinding or telescoping effect limits the pressure gradient that can be applied to a spiral wound element, and because the pressure difference is the driving force in the filtration operation the efficiency of said filter element is limited. It is desired to be able to operate spiral wound filter element at higher-pressure gradients in order to enhance the efficiency of the filter element.

20041110

20080708

20050324

63230.0

KIM, SUN U

SPIRAL WOUND MEMBRANE ELEMENT AND A PROCESS FOR PREVENTING TELESCOPING OF THE FILTER ELEMENT

SMALL

ACCEPTED

ACCEPTED

Leaf stripper, more particularly designed for selective vine leaf stripping

The invention relates to a leaf stripper which is intended more specifically for stripping vine leaves. The inventive leaf stripper consists of a stripping head (1) which is equipped with a rotary drum comprising an open-work cylindrical side wall (3), means of rotating said drum, suction means (4) which can be used to generate a suction air stream that passes through the aforementioned open-work cylindrical side wall (3) of the drum, a means of channeling the air stream through a portion modifying the side wall and a cutting means (14) which is installed close to the side wall portion of the rotating suction drum and which is positioned parallel or essentially parallel to the axis of rotation (A-A) of the drum. The invention is characterized in that the open-work cylindrical wall (3) of the drum (2) is made from a flexible, deformable material which is permeable to the air stream.

1. Leaf stripping machine for selective leaf stripping of a vine, comprising: at least one leaf stripping head with a rotating drum comprised of a lateral cylindrical opened wall; means for driving the drum in rotation; an aspirating means creating an intake air flow going through the lateral cylindrical opened wall of the drum; a means to channel air flow through a varying portion of the lateral wall; and a cutting means installed near the portion of the lateral wall of the turning intake drum and oriented in parallel or approximately parallel to its axis of rotation, wherein the cylindrical opened walls of the drums is comprised of a flexible and deformable material that is permeable to the flow of air. 2. Leaf stripping machine according to claim 1, wherein the opened cylindrical wall of the drum is comprised of a metallic fabric comprised of meshes or interlaced metallic rings of the “coat of mail” type. 3. Leaf stripping machine according to claim 1, wherein tangential rotational speed of the drum is at least equal to speed of movement during work. 4. Leaf stripping machine according to claim 1, wherein the wall, being flexible and deformable drum is affixed to elements of the circular upper end and lower end and comprised of a deformable semi-rigid material. 5. Leaf stripping machine according to claim 4, wherein the drum is suspended with a rotating ability by an upper circular end element thereof. 6. Leaf stripping machine according to claim 1, further comprising means for tensioning the flexible wall in a vertical direction. 7. Leaf stripping machine according to claim 6, wherein the tension means are comprised of a spring acting by compression and arranged around the lower axle of rotation of the drum, this spring being set against the lower part of the drum. 8. Leaf stripping machine according to claim 1, wherein a supplementary means for pulling leaves arranged in parallel to an axle of the drum, and recessed from the cutting bar relative to the vegetation during work. 9. Leaf stripping machine according to claim 8, wherein the supplementary means for pulling leaves is comprised of a rotating feeder coupled to a rotating guide device. 10. Leaf stripping machine according to claim 8, wherein the supplementary means for pulling leaves is placed in contact with the lateral wall of the drum or very close to it. 11. Leaf stripping machine according to claim 9, wherein the rotating feeder comprises an axle along which flexible vertical blades are affixed. 12. Leaf stripping machine according to claim 9, wherein the rotating feeder is comprised of a brush. 13. Leaf stripping machine according to claim 9, wherein tangential speed of the rotating feeder is at least equal to the tangential speed of the drum. 14. Leaf stripping machine according to claim 1, further comprising a comb is arranged in parallel to and in front of the cutting bar, considering direction of movement during work. 15. Leaf stripping machine according to claim 1, further comprising a cutting assembly arranged behind a diametral plane of the rotating drum oriented perpendicularly to movement axis of the leaf stripping head during work. 16. Leaf stripping machine according to claim 1, wherein vertical portions that define the aspirating opening of the means for channeling the air flow running against the internal surface of the lateral wall of the drum and wherein said vertical portions are comprised of a flexible impermeable material. 17. Leaf stripping machine according to claim 16, wherein said means for channeling the flow of air is comprised of an impermeable cloth affixed over the rigid or semi-rigid frame. 18. Leaf stripping machine according to claim 1, wherein a vertical cutting bar has an orientation forming an angle on the order of ±45° and, preferably, an angle on the order of 20° with a radius of the rotating intake drum passing by the active edge of the cutting bar. 19. Leaf stripping machine according to claim 1, wherein means for driving the drum in rotation comprise a vertical roller motor arranged outside the drum and at least one vertical counter-contact roller placed inside the drum, the opened cylindrical wall of the drum being pinched between the roller motor and the counter-contact roller. 20. Leaf stripping machine according to claim 1, wherein means for driving the drum in rotation comprise a vertical roller motor arranged outside the drum and a pair of counter-contact roller having parallel axes placed inside the drum and mounted with an ability to pivot around a vertical axle in the manner of a bogie, the opened cylindrical wall of the drum located pinched between the roller motor and the pair of counter-contact roller. 21. Leaf stripping machine according to claim 19, further comprising a common motorization for driving in rotation of the rotating drums; activation of the cutting bar, and driving in rotation the feeder. 22. Leaf stripping machine according to claim 21, wherein said common motorization is comprised of a hydraulic motor that drives: an eccentric having a connecting rod coupled to an upper end of the blade of the cutting bar; a coupling shaft connecting the vertical shaft of the eccentric and the upper end of the axle of the feeder; and a vertical shaft for driving the roller motor arranged at a distance from the vertical coupling shaft and connected to the latter by a transmission. 23. Leaf stripping machine according to claim 19, wherein the counter-contact roller or the pair of counter-contact rollers is subjected to the action of elastic pushing mechanisms that keep permanently pressure against the internal surface of the lateral wall. 24. Leaf stripping machine according to claim 1, wherein the leaf stripping head is suspended on a carrier chassis constructed and equipped with means permitting separating it from or bringing it together with the movement axis; wherein a working position of the leaf stripping head relative to the axis is regulated by a servo system acting as a function of the deformations supported by the flexible lateral wall of the drum during work. 25. Leaf stripping machine according to claim 24, wherein the servo system comprises means for detection of deformations of the lateral wall of the drum, which are housed inside the drum. 26. Leaf stripping machine according to claim 25, wherein the detection means are comprised of at least one sensor housed inside the rotating drum, near the lateral flexible opened wall of the drum. 27. Leaf stripping machine according to claim 26, wherein said detection means are comprised of a plurality of sensors positioned inside the rotating drum in a vertical alignment, at a distance from each other. 28. Leaf stripping machine according to claim 26, wherein each sensor is comprised of a sensor using the Hall effect coupled to a sensor comprised of, a contact shaft, preferably in a curved shape, in contact with the flexible wall of the drum, said sensor supporting a magnet acting together with the sensor using the Hall effect mounted affixed, in order to detect and measure the deformations of the flexible wall. 29. Leaf stripping machine according to claim 22, wherein the servo system comprises an electric jack equipped with an electronic board for servo control using an algorithm determining successive deformations of the lateral wall of the leaf stripping drum as a function of analysis and treatment of signals by the sensors, the servo system acting on a deformable parallelogram on which the leaf stripping head is suspended in a manner so as to obtain the optimum position of the leaf stripping drum relative to the vegetation during work.

RELATED U.S. APPLICATIONS Not applicable. STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT Not applicable. REFERENCE TO MICROFICHE APPENDIX Not applicable. FIELD OF THE INVENTION The invention involves a leaf stripping machine specifically designed for selective leaf stripping of a vine. BACKGROUND OF THE INVENTION Leaf stripping is a technique that consists in eliminating a more or less sizeable quantity of leaves located in the fructiferous zone of plants. Done manually for a long time in some vineyards, this operation, which aims to improve the quality of the harvest and to make easier the manual work of thinning and picking, is experiencing a growing interest with the development of mechanical leaf stripping. The interests in leaf stripping are manifold: Promote the aeration of bunches of grapes in order to reduce rot; Promote thinning in order to improve the coloration (thicker grape skin); Thin out the vegetation layer in the fructiferous zone for better penetration and localization of treatments (botrytis; oidium; gray mold; grape worm; mildew) Improve the maturation of the grapes by a better exposure to the sun (grapes heavier, flavors more developed and a better sanitary state of the grape harvest); Promote access to the grapes in order to reduce the time of labor in manual operations such as thinning (−50%), manual harvesting (−30% to −40%); Reduce the foliage in order to limit the losses of juice due to the intake of leaves from the rest of the harvest when it is done mechanically; and Make drying easier in case of rain by a better exposure to the sun and a better aeration. Leaf stripping thus turns out to be an operation that is very much of interest and that corresponds well to the problem of optimization of tasks and the pursuit of quality of the harvest. Several machines and processes have been proposed to date and some of them are currently still being used to accomplish this work. According to a technique for leaf stripping developed by the applicant, in order to accomplish the task, a machine is used that consists of an open rotary drum, an intake mechanism that makes it possible to generate an intake flow of air that passes from the drum through the lateral cylindrical wall having lateral openings, a mechanism to direct the flow of air through a varying portion of the lateral wall, in a manner so as to catch and pin the leaves against the open lateral wall of the rotary drum, and a system for leaf stripping that makes it possible to pick off the leaves pinned against this wall. For example, in the document FR-2,417,932-A, a device for leaf stripping is described that uses an open rotary cylindrical cage to roll on the vegetation layer and inside of it, a hollow cylinder is housed affixed and equipped with an opening. An aspirator mounted above the inside hollow cylinder makes it possible to create, inside of the inside cylinder, a partial vacuum that has the effect of sucking in the leaves of the vegetation and pinning them against the open rotary cage facing the opening of the fixed cylinder. Contact rollers mounted on articulated supports are applied under pressure against the lateral surface of the cage and are driven in rotation by this surface. The leaves come to get caught between the turning open drum and the contact rollers, and are torn off of the branches under the force of traction resulting from the movement of the machine. A priori, the principle of parting of the foliage by means of an intake flow of a turbine through an open rotary drum that makes it possible to pull and pin the leaves on the lateral surface of the drum appears clever and economical. It does not appear, however, that the machine described in the document FR-2,417,932 was put on the market, and to the knowledge of the applicant, no stripping machine using this principle is being marketed today. The failure of this machine results certainly from the fact that the principle of separating the leaves using frictional contact rollers does not appear to be able to be applied concretely for several reasons. Following the description and the drawings of document FR-2,417,932, the articulated supports mounted on springs carrying the contact rollers are assigned to be arranged, during work, in the vegetation layer; this arrangement can not be applied due to the fact that these supports rub in the vegetation layer and hinder the aspiration of the leaves because they push back the vegetation; it is not possible to arrange the mechanical instruments in the vegetation layer beyond the wall of the rotary cage, since they would collide with and be torn off by various obstacles located in the axis of the vine row, such as stakes, guy wires, and above all, poles. Due to the fact that a relatively sizeable force is necessary in order to remove the leaves by tearing them off, it is hardly probable that the force generated by friction of the contact rollers on the drum will be sufficient, especially if the leaves or the vine shoots become positioned between the wall of the cage and the contact rollers. This device, as a result of its position relative to the vegetation layer, and as a result of its principle of separating the leaves by tearing them off, can only cause jamming of the system by accumulation of the plants and damage to the vine. According to the document FR-2,808,964 A, the applicant has proposed a leaf stripping machine more specifically designed for stripping the leaves of a vine, consisting of at least one leaf stripping head, consisting of an open rotary drum, an aspiration mechanism making it possible to create an intake air flow going through the lateral cylindrical opened wall of this drum, a mechanism to channel this air flow through a varying portion of the lateral wall, and a cutting mechanism installed near the portion of the lateral wall of the turning intake drum oriented in parallel or approximately parallel to its axis of rotation, the cutting mechanism is arranged behind a diametral plane of the rotating drum oriented perpendicularly to the direction of movement of the machine during work. This machine represents a first stage of progress to the extent that it makes it possible to perform leaf stripping with a quality comparable to a trimming of the vegetation layer, taking into account the fact that the leaves are cut and not torn, contrary to the solutions previously proposed which remove the leaves by tearing them off using blades or knives, or jamming contact rollers. After separating, the leaves remain pinned against the opened lateral wall of the turning drum and are driven outside the intake field by the rotation of this wall. When the portion of the lateral wall covered with cut leaves is isolated from the intake field by the channeling baffle of the intake flow, the leaves, no longer subjected to the attraction of the air flow, fall due to gravity. This result comprises another advantage, because it eliminates projections of torn leaves likely to cause risks of disease as a result of the particles and dust propelled by blast of the turbine onto the adjacent vine rows. However, it has been noted that the quantity of the leaves removed remained insufficient to obtain all of the sought-after results, the partial vacuum generated by the aspirator mechanism does not always exert a strong enough traction action to move the leaves that are only pinned against the turning drum, in the direction of the cutting mechanism. The document WO 01/87047 A describes an evolution of the leaf stripping machine shown in the document FR-2,808,964 A. According to this document, the leaf stripping head or each leaf stripping head of the leaf stripping machine consists of a tracked guide mechanism comprised of an endless opened belt wound, on the one hand, on the turning aspirating drum and, on the other hand, on a second drum arranged in front of the aspirating drum, the endless opened belt having, on the side of the leaf stripping machine assigned to face the vegetation layer, comprised of the vine row, during work, a trajectory or rectilinear portion, parallel to the path of movement of the leaf stripping machine, in a manner so as to have a planar support surface. The opened tracked mechanism created in this way has the function of ensuring a good guidance and stability of the leaf stripping head on the vegetation layer. It ensures a flexible support of the leaf stripping head on the vegetation layer, while avoiding crushing the vegetation layer as a result of its large contact surface. On the other hand, the cutting mechanism of the machine described in the document WO-01/87047 is comprised of a spiral cutting bar consisting of, on the one hand, a cutting screw comprised of a cylindrical rotary shaft equipped with a spiral threading having at least one sharp edge and, on the other hand, a bed knife comprised of a fixed cylindrical sleeve, open laterally, and inside of which the cutting screw is housed. It has been observed that the machine constructed in this way tears the leaves to pieces and tears off a non-negligible quantity of young vine shoots. In summary, though the two versions of the leaf stripping machines described, respectively, in the document FR-2,808,964 A, and in the document WO 01/87047 A have made it possible to simplify the technical nature of utilization of the equipment, while improving the quality of the leaf stripping machine, it has been noted: that the adjustment of the intensity of the leaf stripping is still difficult and depends on the dexterity of the driver of the machine; that the percentage of leaves cut to pieces or lacerated is not always negligible; and that the quantity of injuries inflicted on the grape bunches, especially when the leaf stripping is done late in the season, still remains an unresolved problem for the wine-growers. The invention notably has the objective of proposing solutions to the problems mentioned above. BRIEF SUMMARY OF THE INVENTION For this purpose, a leaf stripping machine of the type described in the document FR-2,808,964 A has been considered, consisting of a rotating drum that has an opened lateral cylindrical wall, mechanisms for driving this drum in rotation, an aspirating mechanism that makes it possible to generate an intake air flow through the opened lateral cylindrical wall of this drum, a mechanism to channel this air flow through a varying portion of the lateral wall, and a cutting mechanism installed near the portion of the lateral wall of the rotating intake drum and oriented parallel or approximately parallel to the axis of rotation of the drum, this cutting mechanism being arranged behind a diametral plane of the rotating drum oriented perpendicularly to the axis of movement of the leaf stripping head of the leaf stripping machine during work. According to a first characteristic arrangement of the invention, the opened lateral cylindrical wall of the drum is made of a flexible material, whereby this opened flexible and deformable wall is preferably and advantageously comprised of meshes or interlaced metallic rings of the “coat of mail” type. This flexible and deformable wall makes possible a better adaptation to the shape of the vegetation layer and to the obstacles present in it, avoids the crushing of the fruits and allows the installation, inside the drum, of sensor heads and/or stacked sensors that make it possible to measure the pressure exerted by the drum at different heights of the vegetation layer, in a manner so as to control the instruments ensuring the good positioning of the drum, relative to the vegetation layer. In this way, it is possible to regulate in a very precise manner the penetration of the drum into the vegetation and to ensure a continuous and perfect following of the vegetation layer. Due to the fineness of the meshes of the lateral wall of the drum, the suctioned air is filtered and no remnants are sent into the vine by the aspirator above the machine. According to another interesting characteristic arrangement of the invention, a supplementary mechanism for pulling the leaves is arranged parallel to the cutter bar and set back from it relative to the vegetation during work. In an advantageous way, this supplementary pulling mechanism can be comprised of a rotating “feeder” coupled to a rotational drive device. This supplementary pulling mechanism has the advantageous function of pulling in even more leaves and keeping them pinned against the lateral opened surface of the drum, so that they do not come out again. Using this device, the leaves pinned against the drum are pulled in the direction of rotation of the drum and during this movement, the petioles of the leaves are cut by the cutting bar. Thus, tearing or crumbling of the leaves is avoided and as a result, so is the possibility for the propagation of certain diseases (cryptogamic or others) due to the dispersion of the remnants of the tenderized leaves that have been torn to pieces. This clean cut of the leaves produces a leaf stripping of a quality comparable to that of manual leaf stripping. According to another important characteristic arrangement of the invention, the leaf stripping head or each leaf stripping head of the leaf stripping machine is suspended on a carrier chassis constructed and equipped with mechanisms making it possible to spread apart or bring together the leaf stripping head(s) of the movement axis of the leaf stripping machine, the working position of the leaf stripping head or of each of the leaf stripping heads relative to the axis being regulated by a system acting as a function of the deformations undergone by the flexible lateral wall of the drum and resulting from the support of it on the vegetation in the course of work. In this manner, an excellent monitoring of the profile of the vegetation layer is obtained, while modulating the force of contact of the drum on the vegetation layer, in order to not crush the grape bunches due to pressure that is too large. BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS The goals, characteristics and advantages above, and still others, are best brought out in the description that follows and the attached drawings in which: FIG. 1 is an elevation view of a first embodiment example of a leaf stripping machine according to the invention, shown hitched to the rear of a traditional farm tractor. FIG. 2 is a planar view of this leaf stripping machine consisting of two symmetrical leaf stripping heads, one of which is shown schematically, the leaf stripping machine being shown in the course of work on a vine row. FIG. 3 is an elevation view and facing view of one of the leaf stripping heads or modules of the leaf stripping machine shown without its carrier chassis. FIG. 4 is a planar view of FIG. 3. FIG. 5 is a front view of this leaf stripping head. FIG. 6 is a rear view of this leaf stripping head. FIG. 7 is a facing view of the leaf stripping machine consisting of two leaf stripping heads or modules arranged on both sides of a vine row, one of the modules being shown in an axial section. FIG. 8 is an axial section view of a leaf stripping drum. FIG. 9 is a section view along the line 9-9 of FIG. 8. FIG. 10 is a transverse section view of a leaf stripping module. FIG. 11A is a detail view, in a plane, showing the positioning of the entire section and the device for driving the drum in rotation. FIG. 11B is a detail view, in a plane, showing another embodiment mode of the device for driving the drum in rotation. FIG. 12 is a longitudinal section view of the mechanisms for motorization ensuring the driving of the rotating drum, the cutting bar, and the rotating feeder. FIG. 13 is a synoptic view of the servo-control of a leaf stripping module. FIG. 14 is a detailed planar view showing a sensor housed in the rotating drum in order to detect deformations of the flexible lateral wall of the drum when it is moved in rotation on the vegetation of the vine row. FIG. 15 is a detail vertical section view showing the deformation of the flexible wall of the rotating drum detected by the stacked sensors, during its passage over obstacles (here the grape bunches). FIG. 16 is a view having a schematic character and in a plane showing the cylindrical conformation of the lateral wall of the drum of the leaf stripping head when it rolls on the vegetation layer without encountering any obstacles. FIG. 17 is a view similar to FIG. 16 and showing the withdrawal of the lateral support surface of the rotating drum when it encounters an obstacle (grape bunches, for example). FIG. 18 is a sequential view showing the functioning of the servo system of the leaf stripping modules or heads. DETAILED DESCRIPTION OF THE INVENTION Reference is made to the drawings to describe an advantageous embodiment example, though in no way restrictive, of the leaf stripping machine according to the invention. Though reference is made, in the following portion of the present document, solely to the use of this leaf stripping machine in order to make a leaf stripping machine specifically for the vine, it is obvious that such a usage is not restrictive and that this machine can be used in order to perform leaf stripping of other plants cultivated in the form of aligned shrubs. This leaf stripping machine is of the type described in the document FR-2,808,964 A. It consists of at least one leaf stripping head or module 1 comprising a rotary aspirating drum 2 consisting of an opened cylindrical wall 3. In a preferred manner, the leaf stripping machine consists of two leaf stripping heads or modules 1 designed to be placed on both sides of the vegetation of the vine row, during work, in a manner so as to fit tightly around the fructiferous zones, all along its movement from one end of the row to the other. The opened drum has, for example, a height of between 400 mm and 800 mm, according to the leaf stripping models, and a diameter on the order of 450 mm. An aspirating turbine, for example, comprised of a helicoidal vacuum generator 4 activated by a hydraulic motor M1, is installed above the drum 2, in order to create a partial vacuum inside the drum, which generates an intake flow going through the opened lateral wall of the drum, causing the “gluing” of leaves of vegetation layer on the opened wall or grid of the drum. Inside the drum 2, affixed and housed near the opened lateral wall 3 of the drum, is a mechanism for channeling the flow of air, this mechanism being advantageously comprised of a baffle 5, having a shape that is determined in order to optimize the efficiency of the aspirating system. This baffle 5 comprises a lateral wall 5a and a base 5b by the intermediary of which it is rigidly connected to a lower horizontal element 6a of the frame 6 of the leaf stripping head, for example, by means of an axle 7 supporting the lower bearing 8 that ensures the rotational guidance of the drum 2. An opening 9 is arranged in the lateral wall 5a of the baffle. This opening extends, for example, over a height that is approximately equal to the height of the opened lateral wall 3 of the rotary drum and has a width on the order of 220 mm to 260 mm corresponding to an arc on the order of 70° to 80°. The major part of the area corresponding to the width of the opening 9 is arranged behind a diametral plane P-P of the opened rotary drum 2 perpendicular to the axis of movement X-X of the leaf stripping head 1 during work, as FIGS. 16 and 17 show. The opening 9 of the baffle 5 is arranged near the opened cylindrical wall 3 of the rotary drum 2, in a manner so that the baffle ensures, on the one hand, the waterproofedness over a large part of the circumference of the opened drum, and, on the other hand, it channels, inside the drum, the air sucked in by the opening 9. It is understood that the air sucked in by the turbine 4 is channeled in the form of an intake flow that goes through a varying portion of the rotating cylindrical wall, the positioning and dimensions of this portion of the opened wall corresponding approximately to those of the opening. The opening 9 and the portion of the opened wall passing by which is in front of it thus comprise an intake vent arranged in a zone of the drum designed to be in contact with the vegetation layer of the vine row. According to this principle of aspiration of the leaves by direct contact with the vegetation layer, it appears that the partial vacuum flow necessary in order to catch and pin the leaves against the opened cylindrical wall of the drum can be relatively weak relative to the leaf stripping machines of other types that stay relatively far from the vegetation layer, which requires a very sizeable partial vacuum, thus much power in order to suck in the leaves into the cutting section. The fixed baffle 5 has, laterally, an approximately cylindrical shape. In the principle of the rotary contact cage, the intensity of the leaf stripping is proportional to the partial vacuum generated by the intake. The volume of the leaves cut can thus be regulated as a function of the vacuum force of the fan. This regulation of the vacuum force can, for example, be done either by making the speed of rotation of the turbine vary, or by slowing down the air output of the turbine. The leaves are adhered by the vacuum on the cylindrical grid of the rotary drum. Under the combined effect of the pneumatic suction and the mechanical rotation of the drum, the leaves are pulled from the vegetation layer. The leaves, lighter than the grapes, also provide a larger surface for suction, in a manner such that a relatively weak partial vacuum, due to the density difference, is sufficient to “glue” the leaves against the opened lateral surface of the rotary drum, without necessarily attracting the grapes. A cutting mechanism is installed near the mouth of the suction 9 of the rotary drum, in parallel or approximately parallel to the axis of rotation A-A of it. The cutting mechanism can be advantageously comprised of an alternating cutting bar 14 consisting of a mobile blade 14a and a fixed bed knife 14b, or a linear movement cutting bar, or of any other device. The cutting bar 14 is oriented in a manner so as to form an angle of ±45° and, preferably, an angle on the order of 20° with a radius of the rotating intake drum 2 passing by the active edge of the cutting bar. It extends, preferably, over a height corresponding to the height of the opened lateral portion of the drum that has the vacuum flow passing through it. A rigid, horizontal shaft in the form of a ski 38 is fixed on the lower part of the structure of the leaf stripping head; this shaft extends in front of the lower end of the cutting bar 14, in order to protect it, for example in case of an encounter with a very twisted vine stock. According to a significant characteristic arrangement of the invention, the lateral wall 3 of the rotary drum 2 is comprised of a flexible material permeable to the air current. This flexible material permeable to the air current can be advantageously comprised of a metallic fabric formed from a multitude of meshes or interlaced metallic rings. A flexible metallic fabric of this type is generally designated by the name “coat of mail”. The small rings that comprise this metallic fabric have, for example, a diameter on the order of 4 mm and a thickness on the order of 5/10 mm. The upper and lower edges of this flexible opened lateral wall 3 are affixed to circular upper end elements 10 and circular lower end elements 11, respectively, these end elements being made in a semi-rigid deformable material such as, for example, rubber, polyurethane, or other semi-rigid plastic deformable material. The opened drum thus made is suspended, with a rotational capacity, by the intermediary of its upper end element 10 and contact rollers 12, on the case 13 enclosing the intake turbine 4. The upper element 10 of the drum 2 is, for example, united in rotation with a circular track 10a that moves over the contact rollers 12 on vertical axles mounted on the cylindrical wall of the case 13, and subjected to the action of elastic pressure mechanisms against the track. A spring 45 acting by compression and arranged around the vertical axis 7 is interposed between the bottom 5b of the baffle 5 and the lower guide bearing 8 of the drum 2, comprising an element of the base vertically mobile from it in order to extend the coat of mail 3 in the vertical direction. The parts 5c, 5d of the baffle that define the aspirating mouth of the turning drum 2, rub against the internal surface of the lateral wall 3 of the drum. For this purpose, at least the parts 5c, 5d of the baffle 5 are made of a flexible material. In an advantageous manner, the baffle 5 can be made of a flexible material, such as, for example, an impermeable cloth affixed to a rigid or semi-rigid frame. According to another characteristic arrangement of the invention, a supplementary mechanism for pulling leaves is arranged behind the cutting mechanism 14 taking into consideration the direction of movement of the leaf stripping machine, during work, or, more specifically, the reverse direction to the direction of rotation of the turning drum 2 of the leaf stripping head of the machine. In advantageous manner, this supplementary pulling mechanism can be comprised of a rotary feeder 16 tangent to the lateral wall 3 of the drum 2 and coupled to a rotational drive device, this rotary feeder being arranged in parallel to the cutting bar 14 and set back from it relative to the vegetation during work. This rotary feeder 16 consists, for example, of an axle 16a, along which vertical flexible blades 16b are affixed, oriented radially or at an incline from front to back considering the direction of rotation of the axle. It can also be comprised of a rotary brush. The rotary feeder 16 is arranged next to the cutting bar and it is located in contact with the flexible side wall 3 of the drum 2, or very close to it (the maximum spacing being on the order of 8 mm). The rotary feeder 16 and the aspirating drum 2 are driven in rotation in the opposite direction and “downstream”. The leaves pinned on the opened lateral wall of the rotating drum 2 under the action of the partial vacuum created by the turbine 4 are then found to be pinched between the wall and the feeder and pulled towards the rear of the drum. The pinching combines with the intake vacuum to keep the leaves pinned against the lateral wall of the drum, in order to improve the pulling of the leaves, which are detached when their petioles are cut by the cutting bar. According to an embodiment mode of the invention, a comb 15 can be arranged in parallel and in front of the cutting bar, considering the direction of the movement of the leaf stripping machine (arrow f1), or, more specifically, the direction opposite the direction of rotation (arrow f2) of the rotating drum, during work (FIG. 16). This comb 15 comprises a plurality of stacked horizontal teeth or barrettes, slightly spaced, the spacing between the teeth being, for example, on the order of 5 to 15 mm. Preferably, this comb 15 is replaceable and it is, for example, affixed in a manner so that it can be removed on the fixed bed knife 14b of the cutting bar. In this way, it is possible to rapidly mount a comb whose spaces between teeth are adapted to the condition of the vegetation, which can be very variable as a function of the time of the leaf stripping or the variety of the grape. The rotational driving of the drum 2 is done using a vertical roller motor 17 and a counter-contact roller having a vertical axle 18 or a pair of counter-contact rollers 18′ with the parallel vertical axles mounted with the ability to pivot around a vertical axle, in the manner of a bogie (FIG. 10). The roller motor 17 is arranged outside the drum 2 while the counter-contact roller 18 or the pair of the counter-contact rollers 18′ is placed inside the drum. The flexible opened lateral wall 3 of the drum is pinched between the roller motor 17 and the counter-contact roller 18, or the pair of counter-contact rollers 18′ in a manner so that starting the rotation of the roller motor has the effect of driving in rotation the drum 2 suspended by means of the contact rollers 12. The counter-contact roller 18 or the pair of counter-contact rollers 18′ is subjected to the action of elastic pushing mechanisms 37 which hold it permanently under pressure against the internal surface of the flexible lateral wall 3 of the drum which is thus found to be held constantly applied against the drive roller 17. A flexible vertical flap 39 affixed to a rigid vertical element 40 of the frame of the leaf stripping head can be arranged behind the pulling roller 16, in order to prevent the cut leaves or vine shoots from being able to be taken between the roller motor 17 and the lateral wall 3 of the drum 2. A common motorization makes possible: the driving in rotation of the rotating drum 2; the operation of the cutting bar 14; and the driving in rotation of the feeder 16. This common motorization consists of, for example, a hydraulic motor M2 whose output shaft 19 is coupled to the vertical shaft 20 of an eccentric 21 whose connecting rod 22 is coupled, by the intermediary of a ball joint 23 and a link 24 to the upper end of the blade 14a of the cutting bar 14. In this way, the starting of the rotation of the shaft 20 of the eccentric 21 ensures an alternating longitudinal movement of the blade 14a of the cutting bar. The lower end of the vertical shaft 20 of the eccentric is connected, for example, by the intermediary of a coupling shaft 25, to the upper end of the axle 16a of the rotary feeder 16. It is understood that starting the rotation of the shaft 20 of the eccentric 21 also ensures the rotation of the feeder 16 arranged in the axial extension of the shaft. The motorization consists of another vertical shaft 26 arranged at a distance from the vertical coupling shaft 25 and connected to this shaft by a transmission, comprised of, for example, a flexible strap wound around the wheels set on these shafts 25, 26, respectively. Preferably, this transmission comprises a belt 27 wound, on the one hand, on a pulley 28 set on the coupling shaft 25, and, on the other hand, on a pulley 29 set on the shaft 26 whose lower end is coupled to the upper end of the vertical axle 17a of the drive roller 17. The receiving pulley 29 has a diameter approximately equal to or slightly greater than that of the driving pulley 28, in a manner so that when the shaft 25 is set into rotation, the shaft 26 is driven in rotation at a speed approximately equal to or slightly slower than that of the shaft 25. In other words, the tangential speed of the rotating feeder 16 is at least equal to the tangential speed of the drum 2, or slightly greater than that of the drum. On the other hand, the rotational speed of the drum 2 is equal to or approximately equal to the speed of movement of the leaf stripping machine during work. If you consider that the drum(s) 2 of the leaf stripper roll(s) over the vegetation V, an immobile contact of the drum(s) relative to the vegetation results at a time T. Thus, there is no friction between the leaf stripper, the bunches of grapes and the lateral wall 3 of the drums. The motorization described above is housed in a case 30 affixed, laterally, to an upper element 6b of the framework of the leaf stripping head. The vertical shafts 20 and 26 are mounted so as to rotate in the bearings 31 and 32, respectively, installed in the case 30. According to another characteristic arrangement of the invention, the leaf stripping head comprises a servo system that enables, at its leaf stripping head 1 or at each of its leaf stripping heads or modules 1, to follow the profile of the vegetation layer while regulating the contact force of the drum(s) 2 on the vegetation layer, in order to not crush the grape bunches. In the case of a leaf stripper equipped with two symmetrical leaf stripping heads, each leaf stripping head is controlled independently of the other one. The servo control consists of at least one sensor 33 housed inside the rotating drum 2, near the flexible opened lateral wall 3 of the drum. In an advantageous manner, several stacked sensors are positioned inside the rotating drum 2, preferably at an equal distance from each other, the extreme sensors (upper and lower) of this vertical alignment being arranged at a distance from the upper and lower edges, respectively of the opened lateral wall 3. The sensors 33 can be advantageously comprised of sensors using the Hall effect installed affixed and coupled to the stacked sensors 42A, 42B, 42C,42D, . . . placed in contact with the flexible opened lateral wall 3 of the drum 2. Each sensor 42 is, for example, comprised of a contact shaft with a curved shape supporting a magnet that acts together with the Hall effect sensor 33 to which this sensor is connected, in a manner so that the movements of this sensor 42 are detected and measured by the sensor 33. As a result, the sensors 33 make it possible to detect and measure the deformations of the flexible lateral wall of the drum, resulting from the encounter of obstacles or an abnormal pressure of the leaf stripping drum on the vegetation. They make it possible to activate the electromechanical instruments or other instruments that control the positioning of the leaf stripping drum relative to the vegetation or vegetation layer V, and, as a result, to correct the position of the drum and ensure a continuous following of the vegetation layer. The flexibility of the lateral wall 3 makes it possible to press on each sensor 42A, 42B, 42C, 42D, . . . , over a distance on the order of 60 mm. The leaf stripping head or each leaf stripping head 1 of the leaf stripper is carried by a frame 36, making it possible to mount it behind (FIGS. 1 and 2) or in front of a farm tractor. It is suspended in a pendulum-like manner, for example, by means of an articulation by a horizontal axle 46, connecting a vertical element of its frame 6 to a vertical element of the frame 36 (FIG. 3). This carrier chassis 36 is (in a manner that is itself known from the prior art) constructed and equipped with mechanisms that make it possible: to move apart or move together the leaf stripping head or each leaf stripping head 1, relative to the movement axis Y-Y of the leaf stripper, the mechanisms advantageously comprising a deformable suspension parallelogram 36a made by an upper part of the chassis; and to regulate the position of the leaf stripping drum(s) 2 relative to the vertical; these movements being controlled by the servo system as a function of the information transmitted by the sensors 33. The servo system consists of another activator 41, for example, comprised of an electric jack provided with an electronic board 43 for management of the servo control using an algorithm that makes it possible to determine successive deformations of the flexible lateral wall of the drum as a function of the instructions sent by the sensors 33. A potentiometer 44 makes it possible to adjust this information in order to regulate the pressure of the leaf stripping module on the vegetation. The electronic board 43 sends the information to the activator 41 which acts on the deformable parallelogram 36a on which the leaf stripping head 1 is suspended, or each leaf stripping head (1), in a manner so as to obtain an optimum position of the leaf stripping drums 2 relative to the vegetation during work. A potentiometer 45 coupled to the main axis of the parallelogram limits the minimum and maximum distance of the jack. According to this servo system, an intermediate pushed-back position of the sensors is defined to correspond, for example, to a pushed-in position on the order of 20 mm and at this position, the leaf stripping head maintains a stable position; a more sizeable pushed-in position of the sensors drives a pulling back of the leaf stripping head, while the relaxation of pressure on the sensors drives the movement of the leaf stripping head and its application against the vegetation layer. The sequential representation of FIG. 18 shows this functioning. On the left of the drawing, the pressure of the vegetation against the lateral wall of the drum 2 of the leaf stripping head 1 is normal, the sensors are moderately pushed-in, the position of the leaf stripping head is stable. In the center of the drawing, the vegetation layer has a pro-eminent part, the pressure of the vegetation against the lateral wall of the drum is more sizeable, the sensors 42 are very pushed-in, and activate the sensors 33 that send the information to the electronic board 43, the leaf stripping head 1 moves back. On the right of the drawing, the vegetation is not in contact with the drum 2 of the leaf stripping head 1, the sensors are relaxed, the leaf stripping head comes to press against the vegetation. When there is a hole in the vegetation, the sensors 42 are totally decompressed and the leaf stripping head gets closer to the axis of the vine row. In an advantageous and known manner (WO-01/87047A), a cutting bar 34 or other cutting mechanism such as an alternating cutting bar can be arranged vertically in front of the rotary drum of the leaf stripping head or each leaf stripping head. This cutting bar 34 activated by a hydraulic motor M3 is carried by an element 35 of the leaf stripping machine chassis and is arranged at a sufficient distance from the leaf stripping drum 2, in a manner so that the cutting fragments do not disturb the work of the leaf stripper. When the leaf stripper comprises two leaf stripping heads, they are arranged on both sides of the vine row and can move in a manner to more or less fit tightly around the row and also to open and re-close at the input and output of the row, respectively. Leaf stripping is thus possible on the two sides of the row, or, alternatively, on one or the other sides. During leaf stripping on only one side, the drum that is located on the other side of the paling can continue to roll over the vegetation, which makes it possible for the paling to be held between two drums and to not be pushed from one side or the other. The absence of leaf stripping action on the side where this action is not desired is obtained by stopping the intake vacuum of the inactive leaf stripping head. The leaf stripper according to the invention can be easily installed on an inter-row tractor, or on a spanning tractor, or on a multi-function tool holder. It can also be self-propelled.

<SOH> BACKGROUND OF THE INVENTION <EOH>Leaf stripping is a technique that consists in eliminating a more or less sizeable quantity of leaves located in the fructiferous zone of plants. Done manually for a long time in some vineyards, this operation, which aims to improve the quality of the harvest and to make easier the manual work of thinning and picking, is experiencing a growing interest with the development of mechanical leaf stripping. The interests in leaf stripping are manifold: Promote the aeration of bunches of grapes in order to reduce rot; Promote thinning in order to improve the coloration (thicker grape skin); Thin out the vegetation layer in the fructiferous zone for better penetration and localization of treatments (botrytis; oidium; gray mold; grape worm; mildew) Improve the maturation of the grapes by a better exposure to the sun (grapes heavier, flavors more developed and a better sanitary state of the grape harvest); Promote access to the grapes in order to reduce the time of labor in manual operations such as thinning (−50%), manual harvesting (−30% to −40%); Reduce the foliage in order to limit the losses of juice due to the intake of leaves from the rest of the harvest when it is done mechanically; and Make drying easier in case of rain by a better exposure to the sun and a better aeration. Leaf stripping thus turns out to be an operation that is very much of interest and that corresponds well to the problem of optimization of tasks and the pursuit of quality of the harvest. Several machines and processes have been proposed to date and some of them are currently still being used to accomplish this work. According to a technique for leaf stripping developed by the applicant, in order to accomplish the task, a machine is used that consists of an open rotary drum, an intake mechanism that makes it possible to generate an intake flow of air that passes from the drum through the lateral cylindrical wall having lateral openings, a mechanism to direct the flow of air through a varying portion of the lateral wall, in a manner so as to catch and pin the leaves against the open lateral wall of the rotary drum, and a system for leaf stripping that makes it possible to pick off the leaves pinned against this wall. For example, in the document FR-2,417,932-A, a device for leaf stripping is described that uses an open rotary cylindrical cage to roll on the vegetation layer and inside of it, a hollow cylinder is housed affixed and equipped with an opening. An aspirator mounted above the inside hollow cylinder makes it possible to create, inside of the inside cylinder, a partial vacuum that has the effect of sucking in the leaves of the vegetation and pinning them against the open rotary cage facing the opening of the fixed cylinder. Contact rollers mounted on articulated supports are applied under pressure against the lateral surface of the cage and are driven in rotation by this surface. The leaves come to get caught between the turning open drum and the contact rollers, and are torn off of the branches under the force of traction resulting from the movement of the machine. A priori, the principle of parting of the foliage by means of an intake flow of a turbine through an open rotary drum that makes it possible to pull and pin the leaves on the lateral surface of the drum appears clever and economical. It does not appear, however, that the machine described in the document FR-2,417,932 was put on the market, and to the knowledge of the applicant, no stripping machine using this principle is being marketed today. The failure of this machine results certainly from the fact that the principle of separating the leaves using frictional contact rollers does not appear to be able to be applied concretely for several reasons. Following the description and the drawings of document FR-2,417,932, the articulated supports mounted on springs carrying the contact rollers are assigned to be arranged, during work, in the vegetation layer; this arrangement can not be applied due to the fact that these supports rub in the vegetation layer and hinder the aspiration of the leaves because they push back the vegetation; it is not possible to arrange the mechanical instruments in the vegetation layer beyond the wall of the rotary cage, since they would collide with and be torn off by various obstacles located in the axis of the vine row, such as stakes, guy wires, and above all, poles. Due to the fact that a relatively sizeable force is necessary in order to remove the leaves by tearing them off, it is hardly probable that the force generated by friction of the contact rollers on the drum will be sufficient, especially if the leaves or the vine shoots become positioned between the wall of the cage and the contact rollers. This device, as a result of its position relative to the vegetation layer, and as a result of its principle of separating the leaves by tearing them off, can only cause jamming of the system by accumulation of the plants and damage to the vine. According to the document FR-2,808,964 A, the applicant has proposed a leaf stripping machine more specifically designed for stripping the leaves of a vine, consisting of at least one leaf stripping head, consisting of an open rotary drum, an aspiration mechanism making it possible to create an intake air flow going through the lateral cylindrical opened wall of this drum, a mechanism to channel this air flow through a varying portion of the lateral wall, and a cutting mechanism installed near the portion of the lateral wall of the turning intake drum oriented in parallel or approximately parallel to its axis of rotation, the cutting mechanism is arranged behind a diametral plane of the rotating drum oriented perpendicularly to the direction of movement of the machine during work. This machine represents a first stage of progress to the extent that it makes it possible to perform leaf stripping with a quality comparable to a trimming of the vegetation layer, taking into account the fact that the leaves are cut and not torn, contrary to the solutions previously proposed which remove the leaves by tearing them off using blades or knives, or jamming contact rollers. After separating, the leaves remain pinned against the opened lateral wall of the turning drum and are driven outside the intake field by the rotation of this wall. When the portion of the lateral wall covered with cut leaves is isolated from the intake field by the channeling baffle of the intake flow, the leaves, no longer subjected to the attraction of the air flow, fall due to gravity. This result comprises another advantage, because it eliminates projections of torn leaves likely to cause risks of disease as a result of the particles and dust propelled by blast of the turbine onto the adjacent vine rows. However, it has been noted that the quantity of the leaves removed remained insufficient to obtain all of the sought-after results, the partial vacuum generated by the aspirator mechanism does not always exert a strong enough traction action to move the leaves that are only pinned against the turning drum, in the direction of the cutting mechanism. The document WO 01/87047 A describes an evolution of the leaf stripping machine shown in the document FR-2,808,964 A. According to this document, the leaf stripping head or each leaf stripping head of the leaf stripping machine consists of a tracked guide mechanism comprised of an endless opened belt wound, on the one hand, on the turning aspirating drum and, on the other hand, on a second drum arranged in front of the aspirating drum, the endless opened belt having, on the side of the leaf stripping machine assigned to face the vegetation layer, comprised of the vine row, during work, a trajectory or rectilinear portion, parallel to the path of movement of the leaf stripping machine, in a manner so as to have a planar support surface. The opened tracked mechanism created in this way has the function of ensuring a good guidance and stability of the leaf stripping head on the vegetation layer. It ensures a flexible support of the leaf stripping head on the vegetation layer, while avoiding crushing the vegetation layer as a result of its large contact surface. On the other hand, the cutting mechanism of the machine described in the document WO-01/87047 is comprised of a spiral cutting bar consisting of, on the one hand, a cutting screw comprised of a cylindrical rotary shaft equipped with a spiral threading having at least one sharp edge and, on the other hand, a bed knife comprised of a fixed cylindrical sleeve, open laterally, and inside of which the cutting screw is housed. It has been observed that the machine constructed in this way tears the leaves to pieces and tears off a non-negligible quantity of young vine shoots. In summary, though the two versions of the leaf stripping machines described, respectively, in the document FR-2,808,964 A, and in the document WO 01/87047 A have made it possible to simplify the technical nature of utilization of the equipment, while improving the quality of the leaf stripping machine, it has been noted: that the adjustment of the intensity of the leaf stripping is still difficult and depends on the dexterity of the driver of the machine; that the percentage of leaves cut to pieces or lacerated is not always negligible; and that the quantity of injuries inflicted on the grape bunches, especially when the leaf stripping is done late in the season, still remains an unresolved problem for the wine-growers. The invention notably has the objective of proposing solutions to the problems mentioned above.

<SOH> BRIEF SUMMARY OF THE INVENTION <EOH>For this purpose, a leaf stripping machine of the type described in the document FR-2,808,964 A has been considered, consisting of a rotating drum that has an opened lateral cylindrical wall, mechanisms for driving this drum in rotation, an aspirating mechanism that makes it possible to generate an intake air flow through the opened lateral cylindrical wall of this drum, a mechanism to channel this air flow through a varying portion of the lateral wall, and a cutting mechanism installed near the portion of the lateral wall of the rotating intake drum and oriented parallel or approximately parallel to the axis of rotation of the drum, this cutting mechanism being arranged behind a diametral plane of the rotating drum oriented perpendicularly to the axis of movement of the leaf stripping head of the leaf stripping machine during work. According to a first characteristic arrangement of the invention, the opened lateral cylindrical wall of the drum is made of a flexible material, whereby this opened flexible and deformable wall is preferably and advantageously comprised of meshes or interlaced metallic rings of the “coat of mail” type. This flexible and deformable wall makes possible a better adaptation to the shape of the vegetation layer and to the obstacles present in it, avoids the crushing of the fruits and allows the installation, inside the drum, of sensor heads and/or stacked sensors that make it possible to measure the pressure exerted by the drum at different heights of the vegetation layer, in a manner so as to control the instruments ensuring the good positioning of the drum, relative to the vegetation layer. In this way, it is possible to regulate in a very precise manner the penetration of the drum into the vegetation and to ensure a continuous and perfect following of the vegetation layer. Due to the fineness of the meshes of the lateral wall of the drum, the suctioned air is filtered and no remnants are sent into the vine by the aspirator above the machine. According to another interesting characteristic arrangement of the invention, a supplementary mechanism for pulling the leaves is arranged parallel to the cutter bar and set back from it relative to the vegetation during work. In an advantageous way, this supplementary pulling mechanism can be comprised of a rotating “feeder” coupled to a rotational drive device. This supplementary pulling mechanism has the advantageous function of pulling in even more leaves and keeping them pinned against the lateral opened surface of the drum, so that they do not come out again. Using this device, the leaves pinned against the drum are pulled in the direction of rotation of the drum and during this movement, the petioles of the leaves are cut by the cutting bar. Thus, tearing or crumbling of the leaves is avoided and as a result, so is the possibility for the propagation of certain diseases (cryptogamic or others) due to the dispersion of the remnants of the tenderized leaves that have been torn to pieces. This clean cut of the leaves produces a leaf stripping of a quality comparable to that of manual leaf stripping. According to another important characteristic arrangement of the invention, the leaf stripping head or each leaf stripping head of the leaf stripping machine is suspended on a carrier chassis constructed and equipped with mechanisms making it possible to spread apart or bring together the leaf stripping head(s) of the movement axis of the leaf stripping machine, the working position of the leaf stripping head or of each of the leaf stripping heads relative to the axis being regulated by a system acting as a function of the deformations undergone by the flexible lateral wall of the drum and resulting from the support of it on the vegetation in the course of work. In this manner, an excellent monitoring of the profile of the vegetation layer is obtained, while modulating the force of contact of the drum on the vegetation layer, in order to not crush the grape bunches due to pressure that is too large.

20040701

20060829

20050421

71430.0

FABIAN-KOVACS, ARPAD

LEAF STRIPPER, MORE PARTICULARLY DESIGNED FOR SELECTIVE VINE LEAF STRIPPING

SMALL

ACCEPTED

ACCEPTED

Oral insulin therapy

Pharmaceutical dosage forms for oral administration to a patient for the treatment of diabetes, comprising insulin and a delivery agent that facilitates insulin transport in a therapeutically effective amount to the bloodstream and that result in a lower incidence of vascular diseases associated with the repeated administration of insulin are disclosed. Also disclosed is a method of attenuating the undesirable incidence of diseases associated with chronic dosing of insulin is provided whereby the oral administration to a patient of insulin along with a suitable delivery agent that facilitates the absorption of insulin from the gastrointestinal tract of the patient in a therapeutically effective amount, for treatment of diabetes.

1-58. (canceled) 59. An oral dosage form comprising a dose of unmodified insulin that achieves a therapeutically effective reduction in blood glucose after oral administration to a human diabetic patient as compared to an untreated diabetic patient. 60. The oral dosage form of claim 59, wherein said dose of unmodified insulin achieves a comparable reduction in blood glucose concentration in human diabetic patients compared to a subcutaneous insulin injection in those patients, while providing a lower plasma concentration of insulin in the peripheral circulation under acute, sub-acute or chronic conditions as compared to the peripheral plasma insulin concentration obtained via the subcutaneous injection. 61. The oral dosage form of claim 60, wherein said lower plasma insulin concentration is at least about 20%. 62. The oral dosage form of claim 59, wherein said oral dosage form provides a ratio of portal vein to peripheral plasma insulin concentration from about 2.5:1 to about 6:1. 63. The oral dosage form of claim 59, wherein said dosage form is solid. 64. The oral dosage form of claim 59, wherein the oral dosage form provides a tmax for plasma insulin concentration at a time point from about 0.1 to about 1.5 hours after oral administration to said patients. 65. The oral dosage form of claim 64, wherein at least about 80% of the blood glucose concentration reduction caused by said dose of insulin occurs within about 2 hours after oral administration of said dosage form. 66. The oral dosage form of claim 59, wherein said dosage form upon pre-prandial oral administration to human diabetic patients causes the mean blood glucose concentration in said patients to be reduced for the first hour after oral administration relative to a mean baseline (fasted) blood glucose concentration in said patients. 67. The oral dosage form of claim 59, wherein said oral dosage form upon pre-prandial oral administration provides a mean blood glucose concentration which does not vary by more than about 40% for the first hour after oral administration, relative to a mean baseline (fasted) blood glucose concentration in said patients, where a meal is eaten by said patients within about one half hour of oral administration of said dosage form. 68. The oral dosage form of claim 59, which provides a mean blood glucose concentration which does not vary by more than about 30% for the first hour after oral administration. 69. The oral dosage form of claim 59, wherein said dose of insulin achieves a tmax for plasma insulin concentration at a time point from about 0.25 to about 1.5 hours after oral administration to a human diabetic patient, and upon preprandial administration to the patient provides effective control of blood glucose concentration in response to a meal as manifested by providing a blood glucose concentration which does not vary by more than about 40% for the first hour after oral administration from the baseline (fasted) blood glucose concentration in the patient, and provides a return to baseline plasma insulin levels in the patient no later than 4 hours after oral administration. 70. The oral dosage form of claim 69, wherein the insulin is a form of human regular insulin. 71. The oral dosage form of claim 69, wherein the oral dosage form is solid. 72. The oral dosage form of claim 59, wherein the oral dosage form is in the form of a tablet or capsule. 73. The oral dosage form of claim 59, wherein the dose of unmodified insulin contained in the dosage form is from about 50 Units to about 600 Units (from about 2 to about 23 mg). 74. The oral dosage form of claim 59, wherein the dose of unmodified insulin contained in the dosage form is from about 100 Units (3.8 mg) to about 400 Units (15.3 mg) insulin. 75. The oral dosage form of claim 59, wherein the dose of unmodified insulin is from about 150 Units (5.75 mg) to about 300 Units (11.5 mg). 76. The oral dosage form of claim 59, which provides a tmax for plasma insulin concentration at about 0.1 to about 1.5 hours after oral administration. 77. The oral dosage form of claim 59, which provides a tmax for plasma insulin concentration at about 0.25 to about 0.5 hours after oral administration. 78. The oral dosage form of claim 59, wherein the dosage form begins delivering insulin into the portal circulation to achieve peak levels within about 30 minutes or less. 79. The oral solid dosage form of claim 59, further comprising an effective amount of a delivery agent of the formula or a pharmaceutically acceptable salt thereof, wherein i. X is hydrogen or halogen; and ii. R is substituted or unsubstituted C1-C3 alkylene, substituted or unsubstituted C1-C3 alkenylene, substituted or unsubstituted C1-C3 alkyl (arylene), substituted or unsubstituted C1-C3 aryl (alkylene). 80. The oral solid dosage form of claim 79, wherein X is a halogen. 81. The oral solid dosage form pharmaceutical composition of claim 80, wherein said halogen is chlorine. 82. The oral solid dosage form of claim 79, wherein R is C3 alkylene. 83. The oral solid dosage form of claim 79, wherein said peak plasma delivery agent concentration occurs within two hours of oral administration. 84. The oral solid dosage form of claim 79, wherein said delivery agent is 4-[(4-chloro, 2-hydroxybenzoyl)amino]butanoic acid. 85. The oral solid dosage form of claim 79, which provides a peak plasma delivery agent concentration that is from about 1,000 to about 100,000 ng/ml within about 0.1 to about 1.5 hours after oral administration. 86. The oral solid dosage form of claim 79, which produces a maximal decrease in blood glucose in treated patients from about 0.1 to 1 hour post oral administration. 87. The oral solid dosage form of claim 79, which produces a maximal decrease in blood glucose in treated patients at about 40 minutes post oral administration. 88. The oral solid dosage form of claim 59, which produces a decreased blood glucose in fasted human patients by at least 10% within one hour post oral administration. 89. The oral dosage form of claim 59, further comprising an effective amount of a pharmaceutically acceptable delivery agent that facilitates absorption of said insulin from the gastrointestinal tract of human diabetic patients, and oral dosage form capable of being orally administered to a human diabetic patient to provide a therapeutic effect. 90. The oral dosage form of claim 89, wherein the effective amount of said delivery agent is from about 1 mg to about 800 mg. 91. The oral dosage form of claim 89, wherein the effective amount of said delivery agent is from about 100 mg to about 600 mg. 92. A method of treating impaired glucose tolerance, achieving glucose homeostasis, treating early-stage diabetes, or treating late-stage diabetes, comprising administering to a human patient an oral dosage form of unmodified insulin that achieves a therapeutically effective reduction in blood glucose after oral administration to a human diabetic patient. 93. The method of claim 92, wherein the oral dosage form is administered on a chronic basis. 94. The method of claim 92, wherein the unmodified insulin that achieves a comparable reduction in blood glucose concentration in human diabetic patients compared to a subcutaneous insulin injection in those patients, while providing a lower concentration of insulin in the peripheral blood circulation under acute, sub-acute or chronic conditions as compared to the peripheral plasma insulin concentration obtained via the subcutaneous injection. 95. The method of claim 92, wherein the unmodified insulin that achieves a therapeutically effective reduction in blood glucose after oral administration to a human diabetic patient and provides a ratio of portal vein to peripheral plasma insulin concentration from about 2.5:1 to about 6:1. 96. The method of claim 92, wherein the unmodified insulin that achieves a therapeutically effective reduction in blood glucose after oral administration to a human diabetic patient, wherein the dose of unmodified insulin is from about 100 Units (3.8 mg) to about 400 Units (15.3 mg) insulin. 97. The method of claim 92, wherein the unmodified insulin that achieves a therapeutically effective reduction in blood glucose after oral administration to a human diabetic patient and that provides a tmax for plasma insulin concentration at about 0.1 to about 1.5 hours after oral administration. 98. The method of claim 92, wherein the unmodified insulin that achieves a therapeutically effective reduction in blood glucose after oral administration to a human diabetic patient and that provides a tmax for plasma insulin concentration at about 0.25 to about 0.5 hours after oral administration. 99. The method of claim 92, wherein the unmodified insulin that achieves a therapeutically effective reduction in blood glucose after oral administration to a human diabetic patient, wherein the dosage form begins delivering insulin into the portal circulation (via absorption through the mucosa of the stomach) to achieve peak levels within about 30 minutes or less. 100. The method of claim 92, wherein said dosage form is solid. 101. The method of claim 100, wherein the solid dosage form is in the form of a tablet or capsule. 102. The method of claim 92, wherein said dosage form further comprises an effective amount of a delivery agent of the formula or a pharmaceutically acceptable salt thereof, wherein i. X is hydrogen or halogen; and ii. R is substituted or unsubstituted C1-C3 alkylene, substituted or unsubstituted C1-C3 alkenylene, substituted or unsubstituted C I—C3 alkyl (arylene), substituted or unsubstituted C1-C3 aryl (alkylene). 103. The oral solid dosage form of claim 102, wherein X is a halogen. 104. The method of claim 103, wherein said halogen is chlorine. 105. The method of claim 102, wherein R is C3 alkylene. 106. A method of providing a therapeutically effective orally administrable unit dose of unmodified insulin, comprising combining from about 2 to about 23 mg of unmodified insulin with from about 1 to about 800 mg of a pharmaceutically acceptable delivery agent that facilitates absorption of said insulin from the gastrointestinal tract of human diabetic patients, and orally administering said unit dose to a human diabetic patient to provide a therapeutic effect. 107. The method of claim 106, wherein said pharmaceutically acceptable delivery agent is from about 100 mg to about 600 mg 108. A method of treating a human diabetic patient, comprising orally administering an oral dosage form comprising an effective dose of insulin pre-prandially to a human diabetic patient, such that an insulin tmax at a time point from about 0.25 to about 1.5 hours after oral administration is attained and blood glucose concentration of the patient is effectively controlled in response to the meal as manifested by providing a blood glucose concentration which does not vary by more than about 40% for the first hour after oral administration from the baseline (fasted) blood glucose concentration in the patient, and which provides a return to baseline plasma insulin levels in the patient no later than 4 hours after oral administration. 109. The method of claim 108, wherein the insulin included in said oral dosage form is a human regular insulin. 110. A method of treating diabetics, comprising orally administering to diabetic patients on a chronic basis an oral insulin treatment comprising a dose of unmodified insulin together with a delivery agent that facilitates the absorption of the insulin from the gastrointestinal tract to provide a therapeutically effective reduction in blood glucose and a peak blood plasma insulin concentration that is reduced relative to the peak blood plasma insulin concentration of an equivalent therapeutically effective reduction in blood glucose concentration achieved by subcutaneous injection of insulin. 111. The method of claim 110, wherein the incidence of a disease state associated with chronic insulin administration is reduced as a result of said chronic administration. 112. The method of claim 110, wherein the method provides a reduced expression of genes associated with vascular disease as compared to the level of expression of genes associated with vascular disease resulting from an equivalent reduction in blood glucose concentration achieved in a population of patients via subcutaneous injection of insulin. 113. The method of claim 112, wherein the genes associated with vascular disease are selected from the group consisting of early response genes, genes associated with cytokines, genes associated with adhesion molecules, genes associated with lipid peroxidation, genes associated with thrombosis and combinations thereof. 114. The method of claim 113, wherein the early response genes are selected from the group consisting of c-myc, jun B, Egr-1, Ets-1 and combinations thereof. 115. The method of claim 110, wherein plasminogen activator inhibitor concentrations resulting from the method are lower as compared to the plasminogen activator inhibitor concentrations resulting from an equivalent therapeutically effective reduction in blood glucose concentration achieved by subcutaneous injection of insulin. 116. The method of claim 110, wherein pro-inflammatory cytokine concentrations resulting from the method are lower as compared to the pro-inflammatory cytokine concentrations resulting from an equivalent therapeutically effective reduction in blood glucose concentration achieved by subcutaneous injection of insulin. 117. The method of claim 110, wherein the delivery agent is a compound having the formula: or a pharmaceutically acceptable salt thereof, wherein i. X is a halogen or hydrogen; ii. R is substituted or unsubstituted C1-C12 alkylene, or a substituted or unsubstituted C1-C12 alkenylene. 118. The method of claim 117, wherein the delivery agent is 4-[(4-chloro, 2-hydroxybenzoyl)amino-butanoic acid or a derivative or analog thereof. 119. The method of claims 110, wherein the insulin is selected from the group consisting of recombinant human insulin, bovine insulin, porcine insulin and functional equivalents thereof. 120. A method of treating diabetes and reducing the incidence and or severity of hyperinsulinemia associated with chronic dosing of insulin, comprising orally administering on a chronic basis to a diabetic patient a dose of insulin and a delivery agent that facilitates the absorption of the dose of insulin from the gastrointestinal tract to provide therapeutically effective control and/or reduction in blood glucose concentrations, and a mean systemic plasma insulin concentration of the diabetic patient that is reduced relative to the mean systemic plasma insulin concentration provided by subcutaneous injection of insulin in an amount effective to achieve equivalent control and/or reduction in blood glucose concentration in a population of human diabetic patients. 121. A method of reducing the incidence and/or severity of one or more disease states associated with chronic administration of insulin, comprising treating diabetic patients via oral administration on a chronic basis with a therapeutically effective dose of a pharmaceutical composition which comprises insulin and a delivery agent that facilitates the absorption of insulin from the gastrointestinal tract, such that the pharmaceutical composition provides a therapeutically effective reduction in blood glucose and a peak serum insulin concentration of the diabetic patient that is reduced relative to the peak serum insulin concentration of an equivalent therapeutically effective reduction in blood glucose concentration achieved by subcutaneous injection of insulin. 122. The method of claim 121, wherein the disease state is cardiovascular disease, and wherein the method provides a reduced expression of genes associated with vascular disease as compared to the level of expression of genes associated with vascular disease resulting from an equivalent reduction in blood glucose concentration achieved in a population of patients via subcutaneous injection of insulin. 123. The method of claim 122, wherein the genes associated with vascular disease are selected from the group consisting of early response genes, genes associated with cytokines, genes associated with adhesion molecules, genes associated with lipid peroxidation, genes associated with thrombosis and combinations thereof. 124. The method of claim 123, wherein the early response genes are selected from the group consisting of c-myc, jun B, Egr-1, Ets-1 and combinations thereof. 125. The method of claim 121, wherein the disease state is selected from the group consisting of a neuropathy, a nephropathy, a retinopathy, an arteriopathy, atherosclerosis and combinations thereof. 126. The method of claim 121, wherein the disease state is selected from the group consisting of coronary artery disease, hypertensive cardiomyopathy and congestive heart failure. 127. The method of claim 110, wherein said disease state is vascular diseases. 128. A method of treating diabetes and reducing the incidence and or severity of hyperinsulinemia associated with chronic dosing of insulin, comprising orally administering on a chronic basis to a diabetic patient a dose of insulin and a delivery agent that facilitates the absorption of the dose of insulin from the gastrointestinal tract to provide a therapeutically effective reduction in blood glucose and a peak serum insulin concentration of the diabetic patient that is reduced relative to the peak serum insulin concentration of an equivalent therapeutically effective reduction in blood glucose concentration achieved by subcutaneous injection of insulin. 129. A method of reducing the exposure of the vasculature of diabetic patients to hyperinsulinemic conditions, comprising orally administering an oral insulin treatment comprising a dose of insulin together with a delivery agent which facilitates the absorption of said insulin from the gastrointestinal tract on a chronic basis to diabetic patients to reduce blood glucose levels in said diabetic patients by a desired amount, such that the concentration of insulin circulating in the blood of said diabetic patients as a result of insulin treatment is reduced relative to the peak serum insulin concentration of an equivalent therapeutically effective reduction in blood glucose concentration achieved by subcutaneous injection of insulin. 130. A method of attenuating processes resulting from the reaction to a mild injurious stimulus in multiple areas of the response to increases in mRNA during insulin treatment, comprising orally administering an oral insulin treatment comprising a dose of insulin together with a delivery agent which facilitates the absorption of said insulin from the gastrointestinal tract on a chronic basis to diabetic patients to reduce blood glucose levels in said diabetic patients by a desired amount, such that the concentration of insulin circulating in the blood of said diabetic patients as a result of insulin treatment is reduced relative to the peak serum insulin concentration of an equivalent therapeutically effective reduction in blood glucose concentration achieved by subcutaneous injection of insulin. 131. A method of treating diabetic patients, comprising orally administering an oral insulin treatment comprising a dose of insulin together with a delivery agent which facilitates the absorption of said insulin from the gastrointestinal tract on a chronic basis to diabetic patients to reduce blood glucose levels in said diabetic patients by a desired amount, such that the concentration of insulin circulating in the blood of said diabetic patients as a result of said oral insulin treatment is not substantially greater than normal physiological levels.

FIELD OF THE INVENTION This invention relates to the oral delivery of therapeutic proteins in a therapeutically effective amount to the bloodstream. This invention further relates to oral administration of proteins as active agents as part of a therapeutic regimen. This invention further relates to the oral administration of insulin in a therapeutically effective amount for the treatment of diabetes. This invention further relates to compositions of a delivery agent and insulin for oral administration that facilitates insulin transport in a therapeutically effective amount to the bloodstream for the treatment of diabetes. This invention further provides methods for the preparation of a composition comprising insulin for oral administration. The present invention further relates to methods for reducing adverse effects on the vascular system that are associated with insulin therapy. More specifically, the present invention relates to methods that reduce the incidence of diseases associated with systemic hyperinsulinemia. The present invention is also directed to oral pharmaceutical dosage forms that are administrable on a chronic basis to diabetics, in part to achieve such results. BACKGROUND OF THE INVENTION Proteins, carbohydrates and other biological molecules (“biological macromolecules”) are finding increasing use in many diverse areas of science and technology. For example, proteins are employed as active agents in the fields of pharmaceuticals, vaccines and veterinary products. Unfortunately, the use of biological macromolecules as active agents in pharmaceutical compositions is often severely limited by the presence of natural barriers of passage to the location where the active agent is required. Such barriers include the skin, lipid bi-layers, mucosal membranes, severe pH conditions and digestive enzymes. Oral delivery of active agents is a particularly desirable route of administration, because of safety and convenience considerations and because oral delivery replicates the physiologic mode of insulin delivery. In addition, oral delivery provides for more accurate dosing than multidose vials and can minimize or eliminate the discomfort that often attends repeated hypodermic injections. There are many obstacles to successful oral delivery of biological macromolecules. For example, biological macromolecules are large and are amphipathic in nature. More importantly, the active conformation of many biological macromolecules may be sensitive to a variety of environmental factors, such as temperature, oxidizing agents, pH, freezing, shaking and shear stress. In planning oral delivery systems comprising biological macromolecules as an active agent for drug development, these complex structural and stability factors must be considered. In addition, in general, for medical and therapeutic applications, where a biological macromolecule is being administered to a patient and is expected to perform its natural biological function, delivery vehicles must be able to release active molecules, at a rate that is consistent with the needs of the particular patient or the disease process. One specific biological macromolecule, the hormone insulin, contributes to the normal regulation of blood glucose levels through its release by the pancreas, more specifically by the B-cells of a major type of pancreatic tissue (the islets of Langerhans). Insulin secretion is a regulated process which, in normal subjects, provides stable concentrations of glucose in blood during both fasting and feeding. Diabetes is a disease state in which the pancreas does not release insulin at levels capable of controlling glucose levels. Diabetes is classified into two types. The first type is diabetes that is insulin dependent and usually appears in young people. The islet cells of the pancreas stop producing insulin mainly due to autoimmune destruction and the patient must inject himself with the missing hormone. These Type 1 diabetic patients are the minority of total diabetic patients (up to 10% of the entire diabetic population). The second type of diabetes (type 2) is non-insulin dependent diabetes, which is caused by a combination of insulin resistance and insufficient insulin secretion. This is the most common type of diabetes in the Western world. Close to 8% of the adult population of various countries around the world, including the United States, have Type 2 diabetes, and about 30% of these patients will need to use insulin at some point during their life span due to secondary pancreas exhaustion. Diabetes is the sixth leading cause of death in the United States and accounted for more than 193,000 deaths in 1997. However, this is an underestimate because diabetes contributes to substantially many deaths that are ultimately ascribed to other causes, such as cardiovascular disease. Complications resulting from diabetes are a major cause of morbidity in the population. For example, diabetic retinopathy is the leading cause of blindness in adults aged 20 through 74 years, and diabetic kidney disease accounts for 40% of all new cases of end-stage renal disease. Diabetes is the leading cause for amputation of limbs in the United States. Heart disease and strokes occur two to four times more frequently in adults with diabetes than in adult non-diabetics. Diabetes causes special problems during pregnancy, and the rate of congenital malformations can be five times higher in the children of women with diabetes. The main cause of mortality with Diabetes Mellitus is long term micro- and macro-vascular disease. Cardiovascular disease is responsible for up to 80% of the deaths of Type II diabetic patients. See, for example, Kirpichnikov et al., Trends Endocrinol Metab 12, 225-30 (2001); Garcia et al., Diabetes 23, 105-11 (1974); Haffner et al., N Engl J Med 339, 229-34 (1998); Sowers, Arch Intert Med 158, 617-21 (1998); Khaw, K. T. et al., Bmj 322, 15-8 (2001). Diabetics have a two- to four-fold increase in the risk of coronary artery disease, equal that of patients who have survived a stroke or myocardial infarction. See, for example, Haffner et al., N Engl J Med 339, 229-34 (1998); Sowers, Arch Intern Med 158, 617-21(1998). This increased risk of coronary artery disease combined with an increase in hypertensive cardiomyopathy manifests itself in an increase in the risk of congestive heart failure. Stratton et al., Bmj 321, 405-12 (2000); Shindler, D. M. et al., Am J Cardiol 77, 1017-20 (1996). These vascular complications lead to neuropathies, retinopathies and peripheral vascular disease. See Kirpichnikov et al., Trends Endocrinol Metab 12, 225-30 (2001). There is a need for diabetes treatments that will decrease the prevalence of such vascular disease in diabetes patients. The beneficial effects of tight glycemic control on the chronic complications of diabetes are widely accepted in clinical practice. However, only recently it has been firmly established that elevated blood glucose levels are a direct cause of long-term complications of diabetes. The Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS) both showed that control of blood glucose at levels as close to normal as possible prevents and retards development of diabetic retinopathy, nephropathy, neuropathy, and microvascular disease. Drug therapy of diabetes type II has consisted of oral antidiabetic agents and insulin if and when the oral agents fail. Insulin therapy in type I diabetes is essential and is intended to replace the absent endogenous insulin with an exogenous insulin supply. Because insulin is a protein drug (MW approx. 6000 Da) that is not absorbed in the gastrointestinal tract, it ordinarily C requires parenteral administration such as by subcutaneous injection. The problem of providing bioavailable unmodified human insulin, in a useful form, to the ever increasing population of diabetics has occupied physicians and scientists for almost 100 years. Many attempts have been made to solve some of the problems of stability and biological delivery of this small protein. Most diabetic patients self-administer insulin by daily subcutaneous injections. However, the limitations of multiple daily injections, such as inconvenience, poor patient acceptability, compliance and the difficulty of matching postprandial insulin availability to postprandial requirements, are some of the better known shortcomings of insulin therapy. Despite studies demonstrating the beneficial effects of tight glycemic control on chronic complications of diabetes, clinicians are not particularly keen on aggressive insulin therapy, particularly in the early stages of the disease, and this is widely accepted in clinical practice. The unmet challenge of achieving tight glycemic control is due, in part, to the shortcomings of the available subcutaneous route of insulin administration and the fear of hypoglycemia. In addition to the practical limitations of multiple daily injections discussed above, the shortcomings of the commonly available subcutaneous route of insulin administration have resulted in the generally inadequate glycemic control associated with many of the chronic complications associated with diabetes. Elevated systemic levels of insulin lead to increased glucose uptake, glycogen synthesis, glycolysis, fatty acid synthesis and triacylglycerol synthesis, leading to the expression of key genes that result in greater utilization of glucose. In the field of insulin delivery, where multiple repeated administrations are required on a daily basis throughout the patient's life, it would be desirable to create compositions of insulin that maintain protein tertiary structure so as not to alter physiological clinical activity and stability and do not require injections. It would also be desirable to provide compositions of insulin that could be orally administrable, e.g., absorbed from the gastrointestinal tract in adequate concentrations, such that insulin is bioavailable and bioactive after oral administration. Oral absorption allows delivery directly to the portal circulation. A method of providing insulin without the need for injections has been a goal in drug delivery. Insulin absorption in the gastrointestinal tract is prevented by its large size and enzymatic degradation. It would be desirable to create an oral pharmaceutical formulation of a drug such as insulin (which is not normally orally administrable due to, e.g., insufficient absorption from the gastrointestintal tract), which formulation would provide sufficient absorption and pharmacokinetic/pharmacodynamic properties to provide the desired therapeutic effect. Insulin exemplifies the problems confronted in the art in designing an effective oral drug delivery system for biological macromolecules. The medicinal properties of insulin can be readily altered using any number of techniques, but its physicochemical properties and susceptibility to enzymatic digestion have precluded the design of a commercially viable oral or alternate delivery system. Accordingly, there is a need for a method of administering insulin to patients in need of insulin wherein those patients are not subject to systemic hyperinsulinema, which by itself can increase the risk of vascular disease (that is normally associated with such chronic insulin treatments, as discussed above). In other words, it is desirable to provide compositions and methods for treating diabetes without the drawbacks of systemic hyperglycemia to decrease the incidence of vascular complications and other detrimental effects. SUMMARY OF THE INVENTION It is one object of the present invention to provide useful oral pharmaceutical formulations of drugs that are not considered orally administrable due, e.g., to insufficient absorption of the drugs from the gastrointestinal tract, which formulations are therapeutically effective. It is a further object of the present invention to provide useful pharmaceutical formulations of insulin for oral administration which are therapeutically effective. It is a further object of the present invention to provide delivery agents that may be orally administered together with a drug that is not considered orally administrable due to, e.g., insufficient absorption of the drug from the gastrointestinal tract, so that the drug is absorbed in adequate amounts from the gastrointestinal tract to provide the desired therapeutic effect, such as insulin. It is an object of the present invention to provide compositions comprising a delivery agent and insulin for oral administration. It is an object of the present invention to provide compositions of a delivery agent and insulin for oral administration that facilitates insulin transport in a therapeutically effective amount to the bloodstream for the treatment of diabetes, for the treatment of impaired glucose tolerance, for the purpose of achieving glucose homeostasis, for the treatment of early stage diabetes, for the treatment of late stage diabetes, and/or to serve as replacement for type I diabetic patients. It is an object of the present invention to provide methods for the preparation of a composition comprising insulin and delivery agent for oral administration, which result in an orally administrable unit dose that provides a desired therapeutic effect. It is an object of the present invention to provide a delivery agent(s) that can be utilized in an amount that facilitates the preparation of an oral unit dosage form of a drug that is not considered orally administrable by itself due to poor absorption, etc., and results in an orally administrable unit dose that provides a desired therapeutic effect. It is an object of the invention to reduce the risk of disease states associated with chronic systemic hyperinsulinemia of conventional insulin therapy. It is another object of the invention to provide a method for reducing the incidence in vascular diseases associated with chronic systemic hyperinsulinemia caused by parenteral insulin therapy in diabetics. It is another object of the invention to delay the time to onset of vascular diseases associated with chronic systemic hyperinsulinemia caused by parenteral insulin therapy in diabetics. It is another object of the invention to reduce the severity of vascular diseases associated with chronic systemic hyperinsulinemia caused by parenteral insulin therapy in diabetics. It is another object of the invention to reduce the exposure of the non-portal vasculature to hyperinsulinemic conditions. It is another object of the invention to attenuate the complex series of systemic processes resulting from the reaction to insulin treatment. It is a further object of the invention to provide a method and a pharmaceutical formulation which can reduce systemic blood insulin concentrations while providing therapeutically effective treatment of diabetes. It is a further object of the invention to provide a method and a pharmaceutical formulation which may help decrease the instances and severity of the vascular complications and resultant conditions (such as, e.g., retinopathy, neuropathy, nephropathy) associated with Diabetes Mellitus. It is a further object of the invention to lower the exposure of the systemic vasculature to insulin during insulin treatment. It is a further object of the invention to reduce the incidence and/or severity of macro- and micro-vascular complications associated with insulin therapy in diabetics, which leads to neuropathies, retinopathies, peripheral vascular disease, cardiac complications and cerebrovascular complications. In accordance with the above objects and others, the invention is directed in part to an oral solid dosage form comprising a dose of unmodified insulin that achieves a reduction in blood glucose concentration in human diabetic patients comparable to a subcutaneous insulin injection in those patients, while providing a lower (e.g., 20% or greater) totals dose of insulin in the peripheral blood circulation under acute, sub-acute and chronic conditions as compared to the peripheral blood insulin concentration obtained via the subcutaneous injection. The invention is also directed in part to an oral solid dosage form comprising a dose of unmodified insulin that achieves a therapeutically effective reduction in blood glucose after oral administration to a human diabetic patient, and which maintains a physiological (portal/peripheral) gradient, and in certain embodiments provides a ratio of portal vein insulin concentration to peripheral blood insulin concentration from about 2.5:1 to about 6:1, and preferably from about 4:1 to about 5:1. The invention is further directed in part to an oral dosage form comprising a dose of unmodified insulin that achieves a therapeutically effective reduction in blood glucose after oral administration to human diabetic patients, the oral solid dosage form providing an insulin tmax at a time point from about 0.25 to about 1.5 hours after oral administration to said patients, at least about 80% of the blood glucose concentration reduction caused by said dose of insulin occurring within about 2 hours after oral administration of said dosage form. The invention is further directed in part to an oral dosage form comprising a therapeutically effective amount of unmodified insulin, said dosage form upon pre-prandial oral administration to human diabetic patients causing the post prandial mean plasma glucose concentration in said patients to be reduced for the first hour after oral administration relative to a mean baseline (fasted) plasma glucose concentration (in the absence of sufficient insulin) in said patients. The invention is further directed in part to an oral dosage form comprising a therapeutically effective amount of unmodified insulin, said oral dosage form upon pre-prandial oral administration provides a mean plasma glucose concentration which does not vary by more than about 40% (and more preferably not more than 30%) for the first hour after oral administration, relative to a mean baseline (fasted) plasma glucose concentration in said patients, where a meal is eaten by said patients within about one half hour of oral administration of said dosage form. In preferred embodiments of the oral dosage forms of the invention described above, the oral dosage form is solid, and is preferably provided incorporated within a gelatin capsule or is contained in a tablet. In certain preferred embodiments, the dose of unmodified insulin contained in the dosage form is from about 50 Units to about 600 Units (from about 2 to about 23 mg), preferably from about 100 Units (3.8 mg) to about 450 Units (15.3 mg) insulin, and most preferably from about 150 Units (5.75 mg) to about 300 Units (11.5 mg), based on the accepted conversion of factor of 26.11 Units per mg. In certain preferred embodiments, the dosage forms of the invention provide a tram for insulin at about 0.1 to about 1.5 hours, and more preferably by about 0.25 to about 0.5 hours, after oral administration. In certain preferred embodiments, the tmax for insulin occurs at less than about 100 minutes after oral administration of the composition, preferably at less than about 45 minutes, more preferably at less than about 40 minutes, and still more preferably at about 22 minutes after oral administration of the composition. In certain preferred embodiments, the composition provides a tam for glucose reduction at about 0.25 to about 1.5 hours, more preferably by about 0.75 to about 1.0 hours, after oral administration. In certain preferred embodiments, the tmax for glucose reduction occurs preferably at less than about 120 minutes, more preferably at less than about 80 minutes, and most preferably at about 45 minutes, after oral administration of the composition. In certain preferred embodiments of the invention, the dosage forms begin delivering insulin into the portal circulation (via absorption through the mucosa of the stomach) to achieve peak levels within about 30 minutes or less. In certain embodiments of the dosage forms described above, in the absence of a delivery agent, the dose of unmodified insulin is not adequately absorbed from the gastrointestinal tract when administered orally to render a desired effect. In certain preferred embodiments, in the absence of a delivery agent, the dose of insulin is not sufficiently absorbed when orally administered to a human patient to provide a desirable therapeutic effect but said dose provides a desirable therapeutic effect when administered to said patient by another route of adminstration. The invention in such embodiments is further directed to an oral dosage form comprising a dose of unmodified insulin together with a pharmaceutically acceptable delivery agent in an amount effective to facilitate the absorption of said insulin, such that a therapeutically effective amount of said dose of insulin is absorbed from the gastrointestinal tract of human diabetic patients. In certain preferred embodiments, the pharmaceutical composition comprises from about 1 mg to about 800 mg of said delivery agent, preferably about 50 to about 600, more preferably from about 100 to about 400, most preferably about 200. In certain embodiments, the composition provides a peak plasma delivery agent concentration Cmax from about 1,000 and about 150,000 ng/ml, and a tmax at about 0.25 to about 1.5 hours, and more preferably by about 0.25 to about 0.75 hours, most preferably 0.5 hours, after oral administration. For purposes of the present invention, a preferred delivery agent is identified via chemical nomenclature as 4-[(4-chloro, 2-hydroxybenzoyl)amino]butanoic acid. In certain preferred embodiments, the delivery agent is a sodium salt, preferably monosodium salt. Alternatively, the same compound is identified by the alternative nomenclature monosodium N-(4-chlorosalicyloyl)-4-aminobutyrate, or by the short name “4-CNAB”. The invention is further directed in part to a method of treatment of diabetes in humans, comprising administering one or more unit doses of the dosage forms described above and in further sections of the present specification. The invention is further directed in part to a method of treatment of impaired glucose tolerance, achieving glucose homeostasis, early stage diabetes, and late stage diabetes in humans, comprising administering one or more unit doses of the dosage forms described above and in further sections of the present specification on a chronic basis. The invention is also related to a method of orally treating mammals with an active agent (i.e., insulin) that is not sufficiently absorbed when orally administered to provide a desirable therapeutic effect but that provides a desirable therapeutic effect when administered by another route of adminstration, comprising orally administering said active agent together with a delivery agent which facilitates the absorption of insulin from the gastrointestinal tract, having one or more of the further characteristics set forth above. The invention is further directed to a method of providing a therapeutically effective orally administrable unit dose of unmodified insulin, comprising combining from about 2 to about 23 mg of unmodified insulin with from about 100 to about 600 mg of a pharmaceutically acceptable delivery agent which facilitates absorption of said insulin from the gastrointestinal tract of human diabetic patients, and orally administering said unit dose to a human diabetic patient to provide a therapeutic effect. In preferred embodiments, the total weight of the unit dose is from about 102 mg to about 800 mg. The present invention is also directed in part to a method of treating human diabetic patients comprising orally administering to human diabetic patients on a chronic basis an oral insulin treatment comprising a dose of unmodified insulin together with a delivery agent that facilitates the absorption of the dose of insulin from the gastrointestinal tract to provide a therapeutically effective reduction in blood glucose and a blood plasma insulin concentration that is reduced relative to the systemic blood insulin concentration of an equivalent therapeutically effective reduction in blood glucose concentration achieved by subcutaneous injection of insulin. The invention is also directed to a method of reducing the incidence and/or severity of one or more disease states associated with chronic administration of insulin, comprising treating human diabetic patients via oral administration on a chronic basis with a therapeutically effective dose of a (preferably solid) pharmaceutical composition comprising a dose of unmodified insulin and a delivery agent that facilitates the absorption of said unmodified insulin from the gastrointestinal tract in an effective amount such that the pharmaceutical composition provides therapeutically effective control of mean blood glucose concentration and a mean systemic blood insulin concentration in diabetic patients that is reduced on a chronic basis relative to the mean systemic blood insulin concentration provided by chronic subcutaneous administration of insulin in an amount effective to achieve equivalent control of mean blood glucose concentration in a population of human diabetic patients. The invention is further directed to a method of treating diabetes and reducing the incidence of systemic hyperinsulinemia associated with chronic dosing of insulin, comprising orally administering on a chronic basis to a diabetic patient a dose of insulin and a delivery agent that facilitates the absorption of the dose of insulin from the gastrointestinal tract to provide a therapeutically effective reduction and/or control in blood glucose and a mean systemic blood insulin concentration of the diabetic patient that is reduced relative to the mean systemic blood insulin concentration provided by subcutaneous injection of insulin in an amount effective to achieve equivalent reduction and/or control in a population of human diabetic patients. The mean values of insulin concentration determination obtained in patients who have been administered subcutaneous insulin are well known to those skilled in the art. The following terms will be used throughout the application as defined below: Diabetic patient—refers to humans suffering from a form of diabetes. IGT—means impaired glucose tolerance. Diabetes—is deemed to encompass type I and type 2 diabetes, unless specifically specified otherwise. Biological macromolecule—biological polymers such as proteins and polypeptides. For the purposes of this application, biological macromolecules are also referred to as macromolecules. Delivery agent—refers to carrier compounds or carrier molecules that are useful in the oral delivery of therapeutic agents. “Delivery agent” may be used interchangeably with “carrier”. Therapeutically effective amount of insulin—an amount of insulin included in the oral dosage forms of the invention which are sufficient to achieve a clinically significant control of blood glucose concentrations in a human diabetic patient either in the fasting state or in the fed state effective, during the dosing interval. Effective amount of delivery agent—an amount of the delivery agent that promotes the absorption of a therapeutically effective amount of the drug from the gastrointestinal tract. Organic solvents—any solvent of non-aqueous origin, including liquid polymers and mixtures thereof. Organic solvents suitable for the present invention include: acetone, methyl alcohol, methyl isobutyl ketone, chloroform, 1-propanol, isopropanol, 2-propanol, acetonitrile, 1-butanol, 2-butanol, ethyl alcohol, cyclohexane, dioxane, ethyl acetate, dimethylformamide, dichloroethane, hexane, isooctane, methylene chloride, tert-butyl alchohol, toluene, carbon tetrachloride, or combinations thereof. Peptide—a polypeptide of small to intermediate molecular weight, usually 2 or more amino acid residues and frequently but not necessarily representing a fragment of a larger protein. Protein—a complex high polymer containing carbon, hydrogen, oxygen, nitrogen and usually sulfur and composed of chains of amino acids connected by peptide linkages. Proteins in this application refer to glycoproteins, antibodies, non-enzyme proteins, enzymes, hormones and peptides. The molecular weight range for proteins includes peptides of 1000 Daltons to glycoproteins of 600 to 1000 kiloDaltons. Reconstitution—dissolution of compositions or compositions in an appropriate buffer or pharmaceutical composition. Unit-Dose Forms—refers to physically discrete units suitable for human and animal subjects and packaged individually as is known in the art. It is contemplated for purposes of the present invention that dosage forms of the present invention comprising therapeutically effective amounts of insulin may include one or more unit doses (e.g., tablets, capsules) to achieve the therapeutic effect. Unmodified insulin—means insulin prepared in any pharmaceutically acceptable manner or from any pharmaceutically acceptable source which is not conjugated with an oligomer such as that described in U.S. Pat. No. 6,309,633 and/or which not has been subjected to amphiphilic modification such as that described in U.S. Pat. Nos. 5,359,030; 5,438,040; and/or 5,681,811. As used herein, the phrase “equivalent therapeutically effective reduction” means that a maximal reduction of blood glucose concentration achieved by a first method of insulin administration (e.g. via oral administration of insulin in a patient(s)) is not more 20%, and preferably not more than 10% and even more preferably not more than 5% different from a maximal reduction of blood glucose concentration after administration by a second method (e.g., subcutaneous injection) in the same patient(s) or a different patient requiring the same reduction in blood glucose level. The term “AUC” as used herein, means area under the plasma concentration-time curve, as calculated by the trapezoidal rule over the complete dosing interval, e.g., 24-hour interval. The term “Cmax” as it is used herein is the highest plasma concentration of the drug attained within the dosing interval. The term “tmax” as it is used herein is the time period which elapses after administration of the dosage form at which the plasma concentration of the drug attains the Cmax within the dosing interval. The term “multiple dose” means that the human patient has received at least two doses of the drug composition in accordance with the dosing interval for that composition. The term “single dose” means that the human patient has received a single dose of the drug composition and the drug plasma concentration has not achieved steady state. Unless specifically designated as “single dose” or at “steady-state” the pharmacokinetic parameters disclosed and claimed herein encompass both single dose and steady-state conditions. The term “mean”, when preceding a pharmacokinetic value (e.g., mean tmax) represents the arithmetic mean value of the pharmacokinetic value unless otherwise specified. The term “Bioavailability” as used herein means the degree or ratio (%) to which a drug or agent is absorbed or otherwise available to the treatment site in the body. This is calculated by the formula Rel . ⁢ Bioavailability ⁡ ( % ) = Dose ⁢ ⁢ ⁢ SC Dose ⁢ ⁢ Oral ⨯ AUC INS ⁢ Oral AUC INS ⁢ SC ⨯ 100 The term “Biopotency” as used herein means the degree or ratio (%) to which a drug or agent is effective to the treatment site in the body. This is calculated by the formula Rel . ⁢ Biopotency ⁡ ( % ) = Dose ⁢ ⁢ SC Dose ⁢ ⁢ Oral ⨯ AUC GIR ⁢ Oral AUC GIR ⁢ SC ⨯ 100 The term “Frel” as used herein means the relative bioavailability of insulin calculated by comparing dose corrected oral insulin AUC with the dose corrected SC insulin AUC. Kel is the terminal elimination rate constant calculated by linear regression of the terminal linear portion of the log concentration vs. time curve The term “AUC(0-x)” as used herein means the area under the plasma concentration-time curve using linear trapezoidal summation from time 0 to time×hours post-dose. The term “AUC(0-t)” as used herein means the area under the plasma concentration-time curve using linear trapezoidal summation from time zero to time t post-dose, where t is the time of the last measurable concentration (Ct). The term “AUC(0-inf)” as used herein means the area under the plasma concentration-time curve from time 0 to infinity, AUC(0-inf)=AUC(0-t)+Ct/Kel. The term “AUC% Extrap” as used herein means the percentage of the total AUC(0-inf) obtained by extrapolation. The term “AUEC(0-x)” as used herein means the area under the effect-time curve calculated using the linear trapezoidal summation from time 0 to the concentration at time×hours post-dose. The term “AUEC(0-t)” as used herein means the area under the effect-time curve calculated using the linear trapezoidal summation from time 0 to the concentration at time t hours post-dose, where t is the time of the last measurable effect (E). The term “AURC(0-x)” as used herein means the area under the response-time curve calculated using the linear trapezoidal summation from time zero to the concentration at time×(Baseline Subtracted AUEC). The term “AURC(0-t)” as used herein means the area under the response-time curve calculated using the linear trapezoidal summation from time zero to the concentration at time t (Baseline Subtracted AUEC), where t is the time of the last measurable response (R). The term “Cb” as used herein means the maximum observed plasma insulin concentration prior to intervention for hypoglycemia. The term “CL/F” as used herein means the apparent total body clearance calculated as Dose/AUC(0-inf). The term “Eb” as used herein means the maximum observed effect (baseline subtracted) prior to intervention for hypoglycemia. The term “Emax” as used herein means the maximum observed effect (baseline subtracted). The term “MRT” as used herein means the mean residence time calculated as the ratio of the Area Under the first moment of the plasma concentration-time curve (AUMC) and the area under the plasma concentration-time curve, (AUMC)/AUC(0-inf). The term “Rmax” as used herein means the maximum observed response (total response), i.e., minimum glucose concentration. The term “Rb” as used herein means the maximum observed response (total response) prior to hypoglycemic intervention. The term “tb” as used herein means the time to reach insulin/glucose plasma concentration prior to hypoglycemic intervention. The term “tc” as used herein means the time to reach glucose concentration change from baseline prior to hypoglycemic intervention. The term “tRmax” as used herein means the time to reach maximum response. The term “tEmax” as used herein means time of the maximum effect (obtained without interpolation). The term “t1/2” as used herein means the terminal half-life calculated as ln(2)/Kel. The term “Vd/F” as used herein means the apparent volume of distribution calculated as (CL/F)/Kel. As used herein and in the appended claims, the singular forms “a,” “an,” and “the,” include plural referents unless the context clearly indicates otherwise. Thus, for example, reference to “a molecule” includes one or more of such molecules, “a reagent” includes one or more of such different reagents, reference to “an antibody” includes one or more of such different antibodies, and reference to “the method” includes reference to equivalent steps and methods known to those of ordinary skill in the art that could be modified or substituted for the methods described herein. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention belongs. Although any methods, compositions, reagents, cells, similar or equivalent to those described herein can be used in the practice or testing of the invention, the preferred methods and materials are described herein. All publications mentioned herein are incorporated herein, including all figures, graphs, equations, illustrations, and drawings, to describe and disclose specific information for which the reference was cited in connection with. The publications discussed above are provided solely for their disclosure before the filing date of the present application. Nothing herein is to be construed as an admission that the invention is not entitled to antedate such disclosure by virtue of prior invention. Throughout this description, the preferred embodiment and examples shown should be considered as exemplars, rather than as limitations on the present invention. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 shows mean (+SD) plasma concentration/time profiles of 4-CNAB following the administration of 4-CNAB alone to healthy male volunteers. FIG. 2 shows mean (+SD) plasma concentration/time profiles of 4-CNAB following the administration of insulin/4-CNAB capsules to healthy male volunteers. FIGS. 3A, 3B and 3C show mean (+SD) plasma insulin concentration/time profiles following the administration of 150 Units/200 mg (Insulin/4-CNAB), 100 Units/600 mg, 10 Units SC insulin and oral placebo treatment in non-hypoglycemic subjects. FIGS. 4A and 4B show mean (+SD) plasma insulin concentration/time profiles following the administration of 100 Units/300 mg (Insulin/4-CNAB), 100 Units/450 mg, 150 Units/100 mg, 150 Units USP oral insulin and oral placebo treatment in non-hypoglycemic subjects. FIG. 5 shows C-peptide concentration versus time after oral dosing of 4-CNAB alone, Placebo and 150 U human insulin alone. FIG. 6 shows mean (+SD) plasma C-peptide concentration/time profiles following the administration of 150 Units/200 mg (Insulin/4-CNAB), 100 Units/600 mg, 10 Units SC insulin and oral placebo treatment in non-hypoglycemic subjects. FIG. 7 shows the % decrease in C-peptide versus time after administering insulin subcutaneously and orally in the presence of 4-CNAB. FIG. 8 shows mean (+SD) plasma C-peptide concentration/time profiles following the administration of 100 Units/300 mg (Insulin/4-CNAB), 100 Units/450 mg, 150 Units/100 mg, 150 Units USP Insulin and oral placebo treatment profiles in non-hypoglycemic subjects. FIGS. 9A and 9B show the mean (+SD) glucose concentration/time profiles following the administration of 150 Units/200 mg (Insulin/4-CNAB), 100 Units/600 mg, 10 Units SC insulin and oral placebo treatment in non-hypoglycemic subjects. FIGS. 10A and 10B show Fe Mean (+SD) glucose concentration/time profiles following the administration of 100 Units/300 mg (Insulin/4-CNAB), 100 Units/450 mg, 150 Units/100 mg, 150 Units USP oral insulin and oral placebo treatment in non-hypoglycemic subjects. FIGS. 11A, 11B and 11C show mean (+SD) glucose concentration percent change from baseline/time profiles following the administration of 150 Units/200 mg (insulin/4-CNAB), 100 Units/600 mg, 10 Units SC insulin and oral placebo treatment in non-hypoglycemic subjects. FIG. 12 shows mean (+SD) glucose concentration percent change from baseline/time profiles following the administration of 100 Units/300 mg (Insulin/4-CNAB), 100 Units/450 mg, 150 Units/100 mg, 150 Units USP oral insulin and oral placebo treatment in non-hypoglycemic subjects. FIG. 13 shows time plots for mean plasma insulin concentrations (baseline corrected) for treatments using 300 U oral insulin/400 mg 4-CNAB, 150 U oral insulin/200 mg 4-CNAB and 15 SC insulin. FIG. 14 shows C-peptide measurements for insulin delivered orally and subcutaneously. FIG. 15 shows time plots for glucose infusion rates for insulin delivered orally and subcutaneously. FIG. 16 shows a plot of the arithmetic means of postprandial blood glucose excursions for all subjects. FIG. 17 shows a plot of 4-CNAB plasma concentrations (ng/mL) vs. time (arithmetic means). FIG. 18 shows a plot of insulin plasma concentrations (pmol/l) vs. time (arithmetic means). FIG. 19 shows a plot of C-peptide plasma concentrations (nmol/l) vs. time (arithmetic means). FIG. 20 shows mean concentration/time profiles of 4-CNAB plasma concentration after a single oral dose of 4-CNAB/insulin for three treatment groups (fasting, breakfast 30 or 20 minutes post-dose). FIG. 21 shows mean concentration/time profiles of plasma glucose concentration after a single oral dose of 4-CNAB/insulin for three treatment groups (fasting, breakfast 30 or 20 minutes post-dose). FIG. 22 shows plasma glucose versus time for patients given one capsule containing a mixture of insulin in a stepwise fashion (3 patients received 200 U insulin, 5 patients received 300 U insulin and 4 patients received 400 U insulin) and a fixed dose of 300 mg 4-CNAB. FIG. 23 shows plasma glucose versus time for patients administered a capsule contained 300 U or 400 U insulin and 300 mg of 4-CNAB. FIG. 24 shows a comparison of blood glucose levels over a time period 180 minutes following single administration of insulin orally and subcutaneously (mean±SE). FIG. 25 shows the serum insulin levels over a time period of 180 minutes following single administration orally and subcutaneously (mean±SE). FIG. 26 shows Glucokinase and G6 Pase mRNA expression compared to sham dosing. FIG. 27 shows Fru-1, 6-P and 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase mRNA expression compared to sham dosing. FIG. 28 shows PEPCK mRNA expression compared to sham dosing. FIG. 29 shows Glycogen synthase mRNA expression compared to sham dosing. FIGS. 30A and 30B show early response gene mRNA expression compared to sham dosing. FIG. 31 shows insulin-like Growth Factor Binding Protein mRNA expression compared to sham dosing. FIG. 32 shows Intracellular Adhesion Molecule—1 mRNA expression compared to sham dosing. FIGS. 33A and 33B shows Cytokine mRNA expression compared to sham dosing. FIG. 34 shows Lipid Peroxidation enzyme mRNA expression compared to sham dosing. FIG. 35 shows Plasminogen Activator Inhibitors mRNA expression compared to sham dosing. FIG. 36 shows NPY, TGF-beta, ICAM-1 and 12-LO mRNA expression compared to sham dosing. FIG. 37 shows THY-1, VEGF-B and Integrin aE2 mRNA expression compared to sham dosing. FIG. 38 shows a comparison of blood glucose levels over a time period 180 minutes following single administration of insulin orally and subcutaneously (mean±SE) in a Streptozotocin diabetic model. FIG. 39 shows the serum insulin levels over a time period of 180 minutes following single administration orally and subcutaneously (mean±SE) in a Streptozotocin diabetic model. DETAILED DESCRIPTION Hyperinsulinemia (elevated blood concentrations of insulin) is caused by the administration of insulin in a location (and manner) which is not consistent with the normal physiological route of delivery. In normal healthy humans, insulin is released from the pancreas into the portal vein, which transfers the insulin to the liver. The liver utilizes a large portion of the insulin which it receives from the portal circulation. Glucose is the principal stimulus to insulin secretion in humans. Glucose enters the β cell by facilitated transport, and is then phosphorylated by glucokinase. Expression of glucokinase is primarily limited to cells and tissues involved in the regulation of glucose metabolism, such as the liver and the pancreatic β cells. The capacity of sugars to undergo phosphorylation and subsequent glycolysis correlates closely with their ability to stimulate insulin release. Insulin circulates in blood as the free monomer, and its volume distribution approximates the volume of extracellular fluid. Under fasting conditions, the concentration of insulin in portal blood is, e.g., about 2-4 ng/ml, whereas the systemic (peripheral) concentration of insulin is, e.g., about 0.5 ng/ml, in normal healthy humans, translating into, e.g., a 5:1 ratio. Insulin is administered parenterally, usually by subcutaneous injection. In human diabetics who receive insulin via subcutaneous injection, the ratio is changed to about 0.75:1. Thus, in such diabetic patients, the liver does not receive the necessary concentrations of insulin to adequately control blood glucose. It has been an unmet goal in the art to imitate normal insulin levels in the portal and systemic circulation via oral administration of insulin. By virtue of the present invention, the ratio of portal (unmodified) insulin concentration to systemic (unmodified) insulin concentration approaches in human diabetic patients approaches that which is obtained in normal healthy humans. The chronic administration of oral dosage forms of the present invention result in a higher portal insulin concentration and lower systemic insulin concentration over time than that obtained with an equi-effective dose of insulin administered subcutaneously (i.e., which provide similar control of blood glucose levels). By virtue of the present invention, lower levels of hyperinsulinemia are obtained, e.g., systemic insulin concentrations are at least about 20% lower when compared to a comparably effective subcutaneous dose of insulin. Transient peaks in insulin levels which may occur by virtue of the oral administration of insulin in accordance with the present invention is not believed to be associated with vascular diseases. Typically, insulin is not absorbed to any extent through the gastrointestinal tract, presumably due to its size and potential for enzymatic degradation. The present invention provides pharmaceutical compositions that are useful as delivery agents in the oral delivery of an active agent that is not generally considered by those skilled in the art to be administrable via the oral route, such as insulin. Such compositions serve to make insulin bioavailable and absorbable through the gastrointestinal mucosa when orally administered. In normal, healthy human subjects, insulin secretion is a tightly regulated process which provides stable blood concentrations of glucose regardless of whether or not the subject has ingested a meal (i.e., fasting and fed states). Insulin is secreted by the beta cells of the islets of Langerhans of the pancreas and has three basic effects: enhanced rate of glucose metabolism; decreased blood glucose concentration; and increased glycogen stores in the tissues. Diabetes mellitus results from a dual defect of insulin resistance and “burn out” of the beta cells of the pancreas. Insulin facilitates (and increases the rate of) glucose transport through the membranes of many cells of the body, particularly skeletal muscle and adipose tissue. In very basic terms, the liver plays a key role in the metabolism of glucose as follows: in the presence of excess insulin, excess glucose, or both, the liver takes up large quantities of glucose from the blood; and in the absence of insulin or when the blood glucose concentration falls very low, the liver gives glucose back to the blood. Thus, the liver acts as a key blood glucose buffer mechanism by keeping blood glucose concentrations from rising too high or from falling too low. When evoked by the presence of glucose (e.g., after a solid meal is ingested), insulin secretion is biphasic: the first phase reaches a peak after 1 to 2 minutes and is short-lived, whereas a second phase of secretion has a delayed onset but a longer duration. Thus, secretion of insulin rises rapidly in normal human subjects as the concentration of blood glucose rises above base levels (e.g., 100 mg/100 ml of blood) and the turn-off of insulin secretion is also rapid, occurring within minutes after reduction in blood glucose concentrations back to the fasting level. The exact mechanism by which insulin release is stimulated by increased glucose levels is not fully understood, but the entry of glucose into the beta cells of the pancreas and its metabolism is required. Insulin treatment of diabetics is typically accomplished in such a manner so as to administer enough insulin so that the patient will have normal carbohydrate metabolism. For example, the diabetic patient may administer a single dose of one of the long-acting insulins each day subcutaneously, with an action lasting about 24 hours. Additional quantities of regular insulin, with a duration of action of, e.g., 5-6 hours, may be subcutaneously administered at those times of the day when the patient's blood glucose level tends to rise too high, such as at meal times. The oral insulin formulations of the present invention provide an advantageous result over the subcutaneously administered insulin which is currently the state of the art, beyond the benefit of ease of administration, pain-free administration, and the potential for improved patient compliance. By administration of the oral insulin formulations of the present invention, the blood levels of insulin which occur upon the first (initial) phase of insulin secretion by the pancreas can be simulated. The first phase of insulin secretion, while of short duration, has an important role in priming the liver to the metabolic events ahead (meal). Because subcutaneously administered insulin does not undergo portal circulation, this result is not possible with subcutaneously administered insulin. Thus, in certain preferred embodiments of the present invention, the oral insulin formulations of the invention may be administered to a patient at meal time, and preferably slightly before (e.g., about 0.5 hours before) ingestion of a solid meal, such that the peak insulin levels are attained at the time of the meal. As a further advantage in certain preferred embodiments, the administration of a relatively short-acting insulin (e.g., such as the insulin used to prepare the capsules administered in the clinical studies reported in the appended Examples (human regular insulin (Humulino® R from Eli Lilly and Company)) will further result in blood insulin levels returning to baseline levels within about 4 hours (and preferably within about 3 hours or less) after oral administration of the oral insulin formulations of the present invention. By virtue, e.g., of the lowered C-peptide levels obtained via treatment of human diabetic patients with the oral insulin formulations of the invention, the oral formulations and methods of the invention may be considered to be beta cell-sparing. The present invention provides a method of administering insulin and pharmaceutical compositions useful for administering insulin such that the insulin is bioavailable and absorbable from the gastrointestinal tract and such that the incidence of vascular diseases normally associated with chronic dosing of insulin is attenuated. The delivery agents of the invention enable insulin to be orally absorbable through the mucosa of the stomach. Following oral administration of the pharmaceutical compositions of the present invention, the delivery agent passes though the mucosal barriers of the gastrointestinal tract and is absorbed into the blood stream where it can be detected in the plasma of subjects. The level of delivery agent in the bloodstream as measured in the plasma is dose-dependent. The delivery agent facilitates the absorption of insulin administered therewith (either in the same dosage form, or simultaneously therewith), or sequentially (in either order, as long as both the delivery agent and insulin are administered within a time period which provides both in the same location, e.g., the stomach, at the same time). As disclosed below, oral administration of insulin, in particular using the delivery agents disclosed herein, effectively reduces the incidence of vascular and other disease states that are associated with traditional dosing of insulin, i.e., subcutaneously. The preferred pharmaceutical compositions of the invention comprise a combination of insulin and a delivery agent in a suitable pharmaceutical carrier or excipient as understood by practitioners in the art. The means of delivery of the pharmaceutical composition can be, for example, a capsule, compressed tablet, pill, solution, freeze-dried, powder ready for reconstitution or suspension suitable for administration to the subject. The pharmaceutical compositions and method of the present invention provide a number of advantages in addition to convenience, acceptance and patient compliance. Insulin absorbed in the gastrointestinal tract mimics the physiology of insulin secreted by the pancreas because both are released into the portal vein and carried directly to the liver. Absorption into the portal circulation maintains a peripheral-portal insulin gradient that regulates insulin secretion. The present invention comprises pharmaceutical compositions and method for oral insulin delivery that enable achieving low blood glucose without having high levels of systemic insulin. Preferably, the pharmaceutical composition includes insulin as the active agent. As used herein, “insulin” refers to insulin from a variety of sources. Naturally occurring insulin and structurally similar bioactive equivalents (insulin analogues including short acting and analogues with protracted action) can be used. Insulin useful in the invention can be isolated from different species of mammal. For example, animal insulin preparations extracted from bovine or porcine pancreas can be used. Insulin analogues, derivatives and bioequivalents thereof can also be used with the invention. In addition to insulin isolated from natural sources, the present invention can use insulin chemically synthesizing using protein chemistry techniques such as peptide synthesis. Analogues of insulin are also suitable for the present invention. The insulin used in the present invention may be obtained by isolating it from natural sources or by chemically synthesizing it using peptide synthesis, or by using the techniques of molecular biology to produce recombinant insulin in bacteria or eucaryotic cells. Analogs of insulin are also provided by the present invention. Insulin from other species of mammal may also be used in the present invention. The physical form of insulin may include crystalline and/or amorphous solid forms. In addition, dissolved insulin may be used. Other suitable forms of insulin, including, but not limited to, synthetic forms of insulin, are described in U.S. Pat. Nos. 4,421,685, 5,474,978, and 5,534,488, the disclosure of each of which is hereby incorporated by reference in its entirety. The most preferred insulin useful in the pharmaceutical compositions and methods of the present invention is human recombinant insulin. Human recombinant insulin can be prepared using genetic engineering techniques that are well known in the art. Recombinant insulin can be produced in bacteria or eucaryotic cells. Functional equivalents of human recombinant insulin are also useful in the invention. Recombinant human insulin can be obtained from a variety of commercial sources. For example, insulin (Zinc, human recombinant) can be purchased from Calbiochem (San Diego, Calif.). Alternatively, human recombinant Zinc-Insulin Crystals: Proinsulin Derived (Recombinant DNA Origin) USP Quality can be obtained from Eli Lilly and Company (Indianapolis, Ind.). All such forms of insulin, including insulin analogues (including but not limited to Insulin Lispro, Insulin Aspart, Insulin Glargine, Insulin Detemir) are deemed for the purposes of this specification and the appended claims are considered to be encompassed by the term “insulin.” The present invention provides compositions of recombinant human zinc insulin and a delivery agent as a drug for oral administration of insulin in humans. In yet further embodiments of the invention, the active agent is not insulin but instead is an active agent of a biological nature suitable for use in the present invention including, but not limited to, proteins; polypeptides; peptides; hormones; polysaccharides, and particularly mixtures of muco-polysaccharides; carbohydrates; lipids; other organic compounds; and particularly compounds which by themselves do not pass (or which pass as only a fraction of the administered dose) through the gastrointestinal mucosa and/or are susceptible to chemical cleavage by acids and enzymes in the gastrointestinal tract; or any combination thereof. Further examples of active agents of a biological nature include, but are not limited to, the following, including synthetic, natural or recombinant sources thereof: growth hormones, including human growth hormones (hGH), recombinant human growth hormones (rhGH), bovine growth hormones, and porcine growth hormones; growth hormone-releasing hormones; interferons, including a, D and y; interleukin-1; interleukin-2; insulin, including porcine, bovine, human, and human recombinant, optionally having counter ions including sodium, zinc, calcium and ammonium; insulin-like growth factor, including IGF-1; heparin, including unfractionated heparin, heparinoids, dermatans, chondroitins, low molecular weight heparin, very low molecular weight heparin and ultra low molecular weight heparin; calcitonin, including salmon, eel, porcine and human; erythropoietin; atrial naturetic factor, antigens; monoclonal antibodies; somatostatin; protease inhibitors; adrenocorticotropin, gonadotropin releasing hormone; oxytocin; leutinizing-hormone-releasing-hormone; follicle stimulating hormone; glucocerebrosidase; thrombopoietin; filgrastim; prostaglandins; cyclosporin; vasopressin; cromolyn sodium (sodium or disodium chromoglycate); vancomycin; desferrioxamine (DFO); parathyroid hormone (PTH), including its fragments; antimicrobials, including anti-fungal agents; vitamins; analogs, fragments, mimetics or polyethylene glycol (PEG)-modified derivatives of these compounds; or any combination thereof. In one embodiment of this invention, the protein active agents have a molecular weight of less than or equal to 10,000 Daltons. In another embodiment of this invention, protein active agents have a molecular weight of about 6,000 Daltons. In another embodiment of this invention, protein active agents have a molecular weight of greater than or equal to 10,000 Daltons. According to an alternate embodiment of the present invention, protein active agents have a molecular weight that is greater than or equal to 20,000 Daltons. In a further embodiment, protein active agents have a molecular weight that is greater than or equal to 30,000 Daltons. According to an alternate embodiment, protein active agents have a molecular weight that is greater than or equal to 40,000 Daltons. According to another alternate embodiment, protein active agents have a molecular weight that is greater than or equal to 50,000 Daltons. Insulin entry into the bloodstream produces a decrease in plasma glucose levels. Therefore, oral absorption of insulin may be verified by observing the effect on a subject's blood sugar following oral administration of the composition. In a preferred embodiment of the invention, the oral dosage forms of the invention facilitate the oral delivery of insulin, and after insulin is absorbed into the bloodstream, the composition produces a maximal decrease in blood glucose in treated patients from about 20 to about 60 minutes after oral administration. In another embodiment of the present invention, the pharmaceutical composition produces a maximal decrease in blood glucose in treated patients from about 30 to about 50 minutes post oral administration. More particularly, the pharmaceutical composition produces a maximal decrease in blood glucose in treated patients at about 40 minutes after oral administration. The magnitude of the decrease in blood glucose produced by insulin absorbed into the bloodstream following entry into the gastrointestinal tract varies with the dose of insulin. In certain embodiments of the invention, human diabetic patients show a maximal decrease in blood glucose by at least 10% within one hour post oral administration. In another embodiment, human diabetic patients show a maximal decrease in blood glucose by at least 20% within one hour post oral administration, alternatively, at least 30% within one hour post oral administration. Normal levels of blood glucose vary somewhat throughout the day and in relation to the time since the last meal. One goal of the present invention is to provide oral compositions of insulin that facilitate achieving close to normal levels of blood glucose throughout the 24-hour daily cycle. In a preferred embodiment of the invention, wherein the pharmaceutical composition includes insulin or an insulin analog as the active agent and a delivery agent in an amount effective to achieve a fasting blood glucose concentration from about 90 to about 110 mg/dl. In another preferred embodiment of the invention, wherein the pharmaceutical composition includes insulin or an insulin analog as the active agent and a delivery agent in an amount effective to achieve a fasting blood glucose concentration from about 95 to about 105 mg/dl, more preferably, the subject manifests fasting blood glucose concentrations at about 100 mg/dl. In the time after a meal is consumed, blood glucose concentration rises in response to digestion and absorption into the bloodstream of carbohydrates derived from the food eaten. The present invention provides oral compositions of insulin that prevent or control very high levels of blood glucose from being reached and/or sustained. More particularly, the present invention provides compositions which facilitate achieving normal levels of blood glucose after a meal has been consumed, i.e., post-prandial. In a preferred embodiment of the invention, the pharmaceutical composition includes insulin as the active agent and a delivery agent in an amount effective to achieve a post-prandial blood glucose concentration from about 130 to about 170 mg/dl. In another preferred embodiment of the invention, the pharmaceutical composition includes insulin or an insulin analog as the active agent and a delivery agent in an amount effective to achieve a post-prandial blood glucose concentration from about 140 to about 160 mg/dl, more preferably, the subject manifests fasting blood glucose concentrations at less than about 160 mg/dl. The present invention provides pharmaceutical compositions for oral administration which includes insulin or an insulin analog as the active agent and a delivery agent in an amount effective to achieve pre-prandial (before a meal is consumed) blood glucose concentration from about 95 to about 125 mg/dl. In a preferred embodiment, the present invention provides pharmaceutical compositions for oral administration which includes insulin or an insulin analog as the active agent and a delivery agent in an amount effective to achieve pre-prandial blood glucose concentration from about 100 to about 120 mg/dl. The present invention provides pharmaceutical compositions for oral administration which include insulin as the active agent and a delivery agent in an amount effective to achieve blood glucose concentrations within the normal range during the evening period from about 70 to about 120 mg/dl. In a preferred embodiment, the present invention provides pharmaceutical compositions for oral administration which include insulin or an insulin analog as the active agent and a delivery agent in an amount effective to achieve blood glucose concentrations at 3 AM from about 80 to about 120 mg/dl. In certain preferred embodiments, the methods and pharmaceutical compositions provide the pharmacokinetic parameters set forth in U.S. Provisional Applications Nos. 60/346,746 and 60/347,312, the disclosure of each of which is incorporated herein by reference. The amount of delivery agent necessary to adequately deliver insulin into the blood stream of a subject needing the therapeutic effect of insulin can vary depending on one or more of the following; chemical structure of the particular delivery agent; the nature and extent of interaction of insulin and the delivery agent; the nature of the unit dose, i.e., solid, liquid, tablet, capsule, suspension; the concentration of delivery agent in the GI tract, the feeding state of the subject, the diet of the subject, the heath of the subject and the ratio of delivery agent to insulin. In preferred embodiments, the oral dosage forms of the present invention comprise a mixture of insulin and a delivery agent, e.g., monosodium N-(4-chlorosalicyloyl)-4-aminobutyrate (4-CNAB), a novel compound discovered by Emisphere Technologies, Inc., or separately containing insulin and the delivery agent. In further embodiments of the present invention, the oral dosage forms described herein are orally administered as described herein in combination with an additional therapy to treat diabetes, impaired glucose tolerance, or to achieve glucose homeostasis, said additional therapy comprising, for example, an additional drug such as sulfonylurea, a biguanide, an alpha-glucosidase, insulin delivered via a different pathway (e.g., parenteral insulin), and/or an insulin sensitizer. In further embodiments of the invention, the oral dosage forms described herein reduce the likelihood of hypoglycemic events, mainly because of two reasons: (a) one cannot hyperinsulinize the liver, because even under hyperinsulinemia the liver uptake of glucose will be unchanged. Unlike the peripheral tissue, the liver will only cease producing endogenous insulin and not sequester additional glucose; and (b) the short peak of insulin (e.g., as shown in the appended examples) shows that even if insulin were to reach high peripheral levels, the peak drops precipitously. The effect of absorption of insulin is manifested in human patients treated with the pharmaceutical compositions of the present invention by observing reductions in C-peptide concentration following oral treatment. For example, in one embodiment of the invention, the pharmaceutical composition comprises insulin as the active agent and the compound 4-CNAB as a delivery agent to facilitate the oral delivery of insulin, and, after insulin is absorbed into the bloodstream, the composition produces a maximal decrease in C-peptide concentration in treated patients from about 80 and about 120 minutes post oral administration. More particularly, the composition produces a decrease in C-peptide concentration post administration, e.g., a maximal decrease in C-peptide concentration in treated patients from about 90 and about 110 minutes post oral administration. Absorption of insulin can be detected in subjects treated with the pharmaceutical compositions of the present invention by monitoring the plasma levels of insulin after treatment. The time it takes for an active agent to reach a peak in the bloodstream (tmax) may depend on many factors such as the following: the nature of the unit dose, i.e., solid, liquid, tablet, capsule, suspension; the concentration of active agent and delivery agent in the GI tract; the feeding state of the subject; the diet of the subject; the health of the subject and the ratio of active agent to the delivery agent. In a preferred embodiment of the invention, wherein the pharmaceutical composition includes the compound 4-CNAB as the delivery agent and insulin as the active agent, the composition provides a peak plasma insulin concentration from about 0.1 to about 1 hour after oral administration. In another embodiment, the composition provides a peak plasma insulin concentration from about 0.2 to about 0.6 hours after oral administration. In a preferred embodiment, the composition provides a peak plasma insulin concentration from about 0.3 to about 0.4 hours after oral administration. In another embodiment, the composition provides a peak plasma insulin concentration within about 1 hour after oral administration. In certain preferred embodiments of the invention, the pharmaceutical composition comprises insulin as the active agent and the compound 4-CNAB as a delivery agent to facilitate the oral delivery of insulin, and after insulin is absorbed into the bloodstream, the plasma insulin levels in treated patients peak at about 20 minutes post oral administration with a second peak at about 105 minutes. In preferred embodiments, the compositions of the present invention include an active agent (e.g., insulin) and a delivery agent that serves to render the active agent orally absorbable through the mucosa of the stomach. Accordingly, the present invention solves the problem of oral absorption of macromolecules by providing delivery agents that facilitate transport of such biomolecules through the gastrointestinal system and into the bloodstream where the active agent can perform its necessary biological role. As a result of the present invention, effective oral drug delivery methods are provided to increase the oral bioavailability and absorption of drugs that are currently administered parenterally. In other preferred embodiments, the delivery agents used in the invention have the following structure: wherein X is one or more of hydrogen, halogen, hydroxyl or C1-C3 alkoxy, and R is substituted or unsubstituted C1-C3 alkylene, substituted or unsubstituted C1-C3 alkenylene. In certain preferred embodiments, the delivery agents of the invention preferably have the following structure: wherein X is halogen, and R is substituted or unsubstituted C1-C3 alkylene, substituted or unsubstituted C1-C3 alkenylene. In a preferred embodiment of the present invention, the pharmaceutical composition includes a delivery agent wherein X is chlorine and R is C3 alkylene. In another preferred embodiment of the present invention, the pharmaceutical composition includes the compound 4-[(4-chloro, 2-hydroxybenzoyl)amino]butanoic acid as a delivery agent for the oral delivery of insulin, preferably the monosodium salt thereof. The delivery agents may be in the form of the carboxylic acid or salts thereof. Suitable salts include, but are not limited to, organic and inorganic salts, for example alkali-metal salts, such as sodium, potassium and lithium; alkaline-earth metal salts, such as magnesium, calcium or barium; ammonium salts; basic amino acids, such as lysine or arginine; and organic amines, such as dimethylamine or pyridine. Preferably, the salts are sodium salts. The salts may be mono- or multi-valent salts, such as monosodium salts and di-sodium salts. The salts may also be solvates, including ethanol solvates, and hydrates. Other suitable delivery agents that can be used in the present invention include those delivery agents described U.S. Pat. Nos. 5,650,386, 5,773,647, 5,776,888, 5,804,688, 5,866,536, 5,876,710, 5,879,681, 5,939,381, 5,955,503, 5,965,121, 5,989,539, 5,990,166, 6,001,347, 6,051,561, 6,060,513, 6,090,958, 6,100,298, 5,766,633, 5,643,957, 5,863,944, 6,071,510 and 6,358,504, the disclosure of each of which is incorporated herein by reference. Additional suitable delivery agents are also described in International Publications Nos. WO 01/34114, WO 01/21073, WO 01/41985, WO 01/32130, WO 01/32596, WO 01/44199, WO 01/51454, WO 01/25704, WO 01/25679, WO 00/50386, WO 02/02509, WO 00/47188, WO 00/07979, WO 00/06534, WO 98/25589, WO 02/19969, WO 00/59863, WO 95/28838, WO 02/20466 and WO 02/19969, and International Patent Applications Nos. PCT/US02/06610 and PCT/US02/06295, the disclosure of each of which is incorporated herein by reference. Salts of the delivery agent compounds of the present invention may be prepared by methods known in the art. For example, sodium salts may be prepared by dissolving the delivery agent compound in ethanol and adding aqueous sodium hydroxide. The compounds described herein may be derived from amino acids and can be readily prepared from amino acids by methods known by those with skill in the art based upon the present disclosure and the methods described in International Publications Nos. WO 96/30036, WO 97/36480, WO 98/34632 and WO 00/07979, and in U.S. Pat. Nos. 5,643,957 and 5,650,386, the disclosure of each of which is incorporated herein by reference. For example, the compounds may be prepared by reacting the single amino acid with the appropriate acylating or amine-modifying agent, which reacts with a free amino moiety present in the amino acid to form amides. Protecting groups may be used to avoid unwanted side reactions as would be known to those skilled in the art. The delivery agents may also be prepared by the methods of International Patent Application No. PCT/US01/21073, the disclosure of which is incorporated herein by reference. The delivery agents may also be prepared by alkylation of the appropriate salicylamide according to the methods of International Publication No. WO 00/46182, the disclosure of which is incorporated herein by reference. The salicylamide may be prepared from salicylic acid via the ester by reaction with sulfuric acid and ammonia. In addition, poly amino acids and peptides comprising one or more of these compounds may be used. An amino acid is any carboxylic acid having at least one free amine group and includes naturally occurring and synthetic amino acids. Poly amino acids are either peptides (which are two or more amino acids joined by a peptide bond) or are two or more amino acids linked by a bond formed by other groups which can be linked by, e.g., an ester or an anhydride linkage. Peptides can vary in length from dipeptides with two amino acids to polypeptides with several hundred amino acids. The delivery agent compound may be purified by recrystallization or by fractionation on one or more solid chromatographic supports, alone or linked in tandem. Suitable recrystallization solvent systems include, but are not limited to, ethanol, water, heptane, ethyl acetate, acetonitrile, methanol and tetrahydrofuran and mixtures thereof. Fractionation may be performed on a suitable chromatographic support such as alumina, using methanol/n-propanol mixtures as the mobile phase; reverse phase chromatography using trifluoroacetic acid/acetonitrile mixtures as the mobile phase; and ion exchange chromatography using water or an appropriate buffer as the mobile phase. When anion exchange chromatography is performed, preferably a 0-500 mM sodium chloride gradient is employed. Following oral administration of the pharmaceutical compositions of the present invention, the delivery agent passes though the mucosal barriers of the GI tract and is absorbed into the blood stream where it can be detected in the plasma of subjects. The level of delivery agent in the bloodstream as measured in the plasma is dose-dependent. The delivery agent facilitates the absorption of the drug (active agent) administered therewith (either in the same dosage form, or simultaneously therewith), or sequentially (in either order, as long as both the delivery agent and the drug are administered within a time period which provides both in the same location, e.g., the stomach, at the same time). In certain preferred embodiments of the invention, a peak plasma concentration (Cmax) of the delivery agent achieved after oral administration is preferably from about 10 to about 250,000 ng/ml, after oral administration, preferably from about 100 to about 125,000, and preferably the peak plasma concentration of the delivery agent is from about 1,000 to about 50,000 ng/ml, after oral administration. More preferably, the peak plasma concentration of the delivery agents of the present invention is from about 5,000 to about 15,000 ng/ml, after oral administration. The time it takes for the delivery agent to reach a peak in the bloodstream (tmax) may depend on many factors such as the following: the nature of the unit dose, i.e., solid, liquid, tablet, capsule, suspension; the concentration of delivery agent in the GI tract; the feeding state of the subject; the diet of the subject; the health of the subject and the ratio of delivery agent to the active agent. The delivery agents of the present invention are rapidly absorbed from the gastrointestinal tract when orally administered in an immediate release dosage form, and preferably provide a peak plasma concentration within about 0.1 to about 8 hours after oral administration, and preferably at about 0.1 to about 3 hours after oral administration. In preferred embodiments, the tmax of the delivery agent occurs at about 0.3 to about 1.5 hours after oral administration. In certain embodiments, the delivery agent achieves a tmax within about 2 hours after oral administration, and most preferably, within about 1 hour after oral administration. The amount of delivery agent necessary to adequately deliver an active agent into the blood stream of a subject needing the therapeutic effect of that active agent may vary depending on one or more of the following; the chemical nature of the active agent; the chemical structure of the particular delivery agent; the nature and extent of interaction from about the active agent and delivery agent; the nature of the unit dose, i.e., solid, liquid, tablet, capsule, suspension; the concentration of delivery agent in the GI tract; the feeding state of the subject; the diet of the subject; the health of the subject and the ratio of delivery agent to the active agent. In a certain preferred embodiment of the invention, the amount of the delivery agent preferred for the pharmaceutical composition is from about 1 mg to about 2,000 mg delivery agent, more preferably from about 1 mg to about 800 mg of said delivery agent, more preferably from about 50 mg to about 700 mg of said delivery agent, even more preferably from about 70 mg to about 700 mg of said delivery agent, still more preferably from about 100 to about 600 mg. Preferably, the delivery agent is 4-CNAB. Since the amount of delivery agent required to deliver a particular active agent is variable and the amount of active agent required to produce a desired therapeutic effect is also a variable, the ratio of active agent to delivery agent may vary for different active agent/delivery agent combinations. In certain preferred embodiments of the invention where the oral pharmaceutical composition includes insulin as the active agent and the delivery agent is the compound 4-CNAB, the amount of the delivery agent included in the pharmaceutical composition may be from about 100 mg to about 600 mg of said delivery agent. In certain preferred embodiments of the invention, the pharmaceutical composition includes insulin as the active agent and the delivery agent is the monosodium salt of 4-CNAB, the ratio of insulin [Units] to delivery agent [mg] ranges from 10:1 [Units/mg] to 1:10 [Units/mg], preferably, the ratio of insulin [Units] to delivery agent [mg] ranges from 5:1 [Units/mg] to 0.5:1 [Units/mg]. Preferred insulin doses in a single administration are about 5 to about 1000 insulin units USP, preferably from about 50 to about 400, more preferably from about 150 to about 400, and still more preferably from about 150 to about 300 units. The optimum ratio of insulin to delivery agent can vary depending on the delivery agent. Optimizing the ratio of insulin to delivery agent is within the knowledge of one skilled in the art. In a preferred embodiment of the invention, wherein the pharmaceutical composition includes the compound 4-CNAB as the delivery agent and insulin as the active agent, the composition provides a peak plasma delivery agent concentration within about 0.1 to about 3 hours after oral administration. In certain preferred embodiments where the pharmaceutical composition includes the compound 4-CNAB as the delivery agent and insulin as the active agent, the peak plasma concentration of delivery agent attained is from about 8,000 to about 37,000 ng/ml. The mechanism by which 4-CNAB facilitates the gastrointestinal absorption of insulin has not yet been fully elucidated. The current working hypothesis is that 4-CNAB interacts with insulin non-covalently, creating more favorable physicochemical properties for absorption. This working hypothesis is provided for explanation purposes only and is not intended to limit the present invention or the appended claims in any way. A preferred embodiment of the invention provides methods for reducing the incidence of vascular disease associated with chronic dosing of insulin. The methods in a preferred embodiment comprise treating human diabetic patients on a chronic basis with an oral and a delivery agent or pharmaceutically acceptable salt thereof that facilitates the absorption of insulin from the gastrointestinal tract (i.e., bioavailable). The delivery agent may be used directly by mixing one or more such agents with the active agent (e.g., unmodified insulin) prior to administration. The delivery agent and active agent may be mixed in dry powder form or wet granulated together. To this mixture, other pharmaceutically acceptable excipients may be added. The mixture may be then tableted or placed into gelatin capsules containing a unit dose of the active agent and the delivery agent. Alternatively, the delivery agent/active agent mixture may be prepared as an oral solution or suspension. The delivery agent and active agent do not need to be mixed together prior to administration, such that, in certain embodiments, the unit dose of active agent (with or without other pharmaceutically acceptable excipients) is orally administered without the delivery agents of this invention, and the delivery agent is separately orally administered (with or without other pharmaceutically acceptable excipients) before, after, or simultaneously with the active agent. In certain preferred embodiments, the oral dosage forms of the present invention are solid. The unmodified insulin in dry powder form is stable, and in certain preferred embodiments is simply mixed in a desirable ratio with the delivery agent. The dry powder mixture may then be filled into gelatin capsules, with or without optional pharmaceutical excipients. Alternatively, the unmodified insulin in dry powder form may be mixed with the delivery agent together with optional pharmaceutical excipients, and the mixture may be tableted in accordance with standard tableting procedures known to those having ordinary skill in the art. The present invention also provides methods for treating human diabetic patients with active agents that are not inherently bioavailable, such as for example treating diabetics with insulin. More particularly, the present invention provides method of treating humans with an oral dosage form of a pharmaceutical composition, wherein the pharmaceutical composition includes the following: first, an active agent or a pharmaceutically acceptable salt thereof, which is not orally bioavailable when dissolved or suspended in aqueous solution, wherein the active agent provide a therapeutic effect when administered to a subject by another means (e.g., via subcutaneous injection); and, second, an effective amount of a delivery agent or a pharmaceutically acceptable salt thereof, which renders the active agent orally absorbed (e.g., bioavailable). In certain embodiments, the method comprises the following steps: first, contacting the active agent (e.g., insulin) with said delivery agent, and thereafter orally administering the pharmaceutical composition. Alternatively, the method comprises administering the insulin and the delivery agent in such a manner that the insulin and delivery agent contact each other in-vivo (e.g., in the stomach), such that the delivery agent is available to facilitate absorption of the insulin through the stomach mucosa. The dosage forms of the present invention may be produced by first dissolving the active agent and delivery agents into one solution or separate solutions. The solvent will preferably be an aqueous solution, but organic solvents or aqueous organic solvent mixtures may be used when necessary to solubilize the delivery agent. If two solutions are used, the proportions of each necessary to provide the correct amount of either active agent or delivery agent are combined and the resulting solution may be dried, by lyophilization or equivalent means. In one embodiment of the invention, the oral dosage form may be dried and rehydrated prior to oral administration. The administration mixtures may be prepared, e.g., by mixing an aqueous solution of the delivery agent with an aqueous solution of the active ingredient, such as insulin, just prior to administration. Alternatively, the delivery agent and the biologically or chemically active ingredient can be admixed during the manufacturing process. The solutions may optionally contain additives such as phosphate buffer salts, citric acid, acetic acid, gelatin, and gum acacia. Stabilizing additives may be incorporated into the delivery agent solution. With some drugs, the presence of such additives promotes the stability and dispersibility of the agent in solution. The stabilizing additives may be employed at a concentration ranging from about 0.1 and 5% (W/V), preferably about 0.5% (W/V). Suitable, but non-limiting, examples of stabilizing additives include gum acacia, gelatin, methyl cellulose, polyethylene glycol, carboxylic acids and salts thereof, and polylysine. The preferred stabilizing additives are gum acacia, gelatin and methyl cellulose. The amount of active agent, e.g., insulin, is an amount effective to accomplish the purpose of the particular active agent. The amount in the composition is a therapeutically effective dose, i.e., a pharmacologically or biologically effective amount. However, the amount can be less than a pharmacologically or biologically effective amount when the composition is used in a dosage unit form, such as a capsule, a tablet or a liquid, because the dosage unit form may contain a multiplicity of delivery agent/biologically or chemically active agent compositions or may contain a divided pharmacologically or biologically effective amount. The total effective amounts can then be administered in cumulative units containing, in total, pharmacologically or biologically or chemically active amounts of biologically or pharmacologically active agent. The total amount of active agent, and particularly insulin, to be used can be determined by those skilled in the art. However, it has surprisingly been found that with some biologically or chemically active agents, the use of the presently disclosed delivery agents provides extremely efficient delivery. The amount of delivery agent in the present composition is a delivery effective amount and can be determined for any particular delivery agent/active agent combination by methods known to those skilled in the art. The oral dosage forms of the present invention, containing a mixture of the active agent, e.g., insulin and the delivery agent, e.g., 4-CNAB or separately containing the active agent and the delivery agent, may include additional materials known to those skilled in the art as pharmaceutical excipients. Any excipient or ingredient, including pharmaceutical ingredients or excipients. Such pharmaceutical excipients include, for example, the following: Acidifying agents (acetic acid, glacial acetic acid, citric acid, fumaric acid, hydrochloric acid, diluted hydrochloric acid, malic acid, nitric acid, phosphoric acid, diluted phosphoric acid, sulfuric acid, tartaric acid); Aerosol propellants (butane, dichlorodifluoro-methane, dichlorotetrafluoroethane, isobutane, propane, trichloromonofluoromethane); Air displacements (carbon dioxide, nitrogen); Alcohol denaturants (denatonium benzoate, methyl isobutyl ketone, sucrose octacetate); Alkalizing agents (strong ammonia solution, ammonium carbonate, diethanolamine, diisopropanolamine, potassium hydroxide, sodium bicarbonate, sodium borate, sodium carbonate, sodium hydroxide, trolamine); Anticaking agents (see glidant); Antifoaming agents (dimethicone, simethicone); Antimicrobial preservatives (benzalkonium chloride, benzalkonium chloride solution, benzelthonium chloride, benzoic acid, benzyl alcohol, butylparaben, cetylpyridinium chloride, chlorobutanol, chlorocresol, cresol, dehydroacetic acid, ethylparaben, methylparaben, methylparaben sodium, phenol, phenylethyl alcohol, phenylmercuric acetate, phenylmercuric nitrate, potassium benzoate, potassium sorbate, propylparaben, propylparaben sodium, sodium benzoate, sodium dehydroacetate, sodium propionate, sorbic acid, thimerosal, thymol); Antioxidants (ascorbic acid, acorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, hypophosphorous acid, monothioglycerol, propyl gallate, sodium formaldehyde sulfoxylate, sodium metabisulfite, sodium thiosulfate, sulfur dioxide, tocopherol, tocopherols excipient); Buffering agents (acetic acid, ammonium carbonate, ammonium phosphate, boric acid, citric acid, lactic acid, phosphoric acid, potassium citrate, potassium metaphosphate, potassium phosphate monobasic, sodium acetate, sodium citrate, sodium lactate solution, dibasic sodium phosphate, monobasic sodium phosphate); Capsule lubricants (see tablet and capsule lubricant); Chelating agents (edetate disodium, ethylenediaminetetraacetic acid and salts, edetic acid); Coating agents (sodium carboxymethyl-cellulose, cellulose acetate, cellulose acetate phthalate, ethylcellulose, gelatin, pharmaceutical glaze, hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose phthalate, methacrylic acid copolymer, methylcellulose, polyethylene glycol, polyvinyl acetate phthalate, shellac, sucrose, titanium dioxide, carnauba wax, microcystalline wax, zein); Colorants (caramel, red, yellow, black or blends, ferric oxide); Complexing agents (ethylenediaminetetraacetic acid and salts (EDTA), edetic acid, gentisic acid ethanolmaide, oxyquinoline sulfate); Desiccants (calcium chloride, calcium sulfate, silicon dioxide); Emulsifying and/or solubilizing agents (acacia, cholesterol, diethanolamine (adjunct), glyceryl monostearate, lanolin alcohols, lecithin, mono- and di-glycerides, monoethanolamine (adjunct), oleic acid (adjunct), oleyl alcohol (stabilizer), poloxamer, polyoxyethylene 50 stearate, polyoxyl 35 caster oil, polyoxyl 40 hydrogenated castor oil, polyoxyl 10 oleyl ether, polyoxyl 20 cetostearyl ether, polyoxyl 40 stearate, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, propylene glycol diacetate, propylene glycol monostearate, sodium lauryl sulfate, sodium stearate, sorbitan monolaurate, soritan monooleate, sorbitan monopalmitate, sorbitan monostearate, stearic acid, trolamine, emulsifying wax); Filtering aids (powdered cellulose, purified siliceous earth); Flavors and perfumes (anethole, benzaldehyde, ethyl vanillin, menthol, methyl salicylate, monosodium glutamate, orange flower oil, peppermint, peppermint oil, peppermint spirit, rose oil, stronger rose water, thymol, tolu balsam tincture, vanilla, vanilla tincture, vanillin); Glidants and/or anticaking agents (calcium silicate, magnesium silicate, colloidal silicon dioxide, talc); Humectants (glycerin, hexylene glycol, propylene glycol, sorbitol); Plasticizers (castor oil, diacetylated monoglycerides, diethyl phthalate, glycerin, mono- and di-acetylated monoglycerides, polyethylene glycol, propylene glycol, triacetin, triethyl citrate); Polymers (e.g., cellulose acetate, alkyl celloloses, hydroxyalkylcelloloses, acrylic polymers and copolymers); Solvents (acetone, alcohol, diluted alcohol, amylene hydrate, benzyl benzoate, butyl alcohol, carbon tetrachloride, chloroform, corn oil, cottonseed oil, ethyl acetate, glycerin, hexylene glycol, isopropyl alcohol, methyl alcohol, methylene chloride, methyl isobutyl ketone, mineral oil, peanut oil, polyethylene glycol, propylene carbonate, propylene glycol, sesame oil, water for injection, sterile water for injection, sterile water for irrigation, purified water); Sorbents (powdered cellulose, charcoal, purified siliceous earth); Carbon dioxide sorbents (barium hydroxide lime, soda lime); Stiffening agents (hydrogenated castor oil, cetostearyl alcohol, cetyl alcohol, cetyl esters wax, hard fat, paraffin, polyethylene excipient, stearyl alcohol, emulsifying wax, white wax, yellow wax); Suspending and/or viscosity-increasing agents (acacia, agar, alginic acid, aluminum monostearate, bentonite, purified bentonite, magma bentonite, carbomer 934p, carboxymethylcellulose calcium, carboxymethylcellulose sodium, carboxymethycellulose sodium 12, carrageenan, microcrystalline and carboxymethylcellulose sodium cellulose, dextrin, gelatin, guar gum, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, magnesium aluminum silicate, methylcellulose, pectin, polyethylene oxide, polyvinyl alcohol, povidone, propylene glycol alginate, silicon dioxide, colloidal silicon dioxide, sodium alginate, tragacanth, xanthan gum); Sweetening agents (aspartame, dextrates, dextrose, excipient dextrose, fructose, mannitol, saccharin, calcium saccharin, sodium saccharin, sorbitol, solution sorbitol, sucrose, compressible sugar, confectioner's sugar, syrup); Tablet binders (acacia, alginic acid, sodium carboxymethylcellulose, microcrystalline cellulose, dextrin, ethylcellulose, gelatin, liquid glucose, guar gum, hydroxypropyl methylcellulose, methycellulose, polyethylene oxide, povidone, pregelatinized starch, syrup); Tablet and/or capsule diluents (calcium carbonate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulfate, microcrystalline cellulose, powdered cellulose, dextrates, dextrin, dextrose excipient, fructose, kaolin, lactose, mannitol, sorbitol, starch, pregelatinized starch, sucrose, compressible sugar, confectioner's sugar); Table disintegrants (alginic acid, microcrystalline cellulose, croscarmellose sodium, corspovidone, polacrilin potassium, sodium starch glycolate, starch, pregelatinized starch); Tablet and/or capsule lubricants (calcium stearate, glyceryl behenate, magnesium stearate, light mineral oil, polyethylene glycol, sodium stearyl fumarate, stearic acid, purified stearic acid, talc, hydrogenated vegetable oil, zinc stearate); Tonicity agent (dextrose, glycerin, mannitol, potassium chloride, sodium chloride); Vehicle: flavored and/or sweetened (aromatic elixir, compound benzaldehyde elixir, iso-alcoholic elixir, peppermint water, sorbitol solution, syrup, tolu balsam syrup); Vehicle: oleaginous (almond oil, corn oil, cottonseed oil, ethyl oleate, isopropyl myristate, isopropyl palmitate, mineral oil, light mineral oil, myristyl alcohol, octyldodecanol, olive oil, peanut oil, persic oil, seame oil, soybean oil, squalane); Vehicle: solid carrier (sugar spheres); Vehicle: sterile (bacteriostatic water for injection, bacteriostatic sodium chloride injection); Viscosity-increasing (see suspending agent); Water repelling agent (cyclomethicone, dimethicone, simethicone); and Wetting and/or solubilizing agent (benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, docusate sodium, nonoxynol 9, nonoxynol 10, octoxynol 9, poloxamer, polyoxyl 35 castor oil, polyoxyl 40, hydrogenated castor oil, polyoxyl 50 stearate, polyoxyl 10 oleyl ether, polyoxyl 20, cetostearyl ether, polyoxyl 40 stearate, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, sodium lauryl sulfate, sorbitan monolaureate, sorbitan monooleate, sorbitan monopalmitate, sorbitan monostearate, tyloxapol). This list is not meant to be exclusive, but instead merely representative of the classes of excipients and the particular excipients which may be used in oral dosage forms of the present invention. In the case of insulin, oral delivery may have advantages beyond convenience, acceptance and compliance issues. Insulin absorbed in the gastrointestinal tract mimics the physiology of insulin secreted by the pancreas because both are released into the portal vein and carried directly to the liver. Absorption into the portal circulation maintains a peripheral-portal insulin gradient that regulates insulin secretion. In its first passage through the liver, roughly 60% of the insulin is retained and metabolized, thereby reducing the incidence of peripheral hyperinsulinemia, a factor in diabetes related systemic complications. A feared and not uncommon complication of insulin treatment and other oral antidiabetic agents is hypoglycemia. The present invention relates in part to a method of treating human diabetics via the chronic oral administration of insulin together with a drug delivery agent that enhances the absorption of insulin (e.g., from the duodenum) such that a therapeutically effective control and/or reduction in blood glucose is achieved while effecting a reduction in the systemic blood insulin concentration (serum insulin level) on a chronic basis required to achieve the reduction in blood glucose concentration, e.g., relative to the serum insulin level required to achieve therapeutic efficacy via subcutaneous injection of insulin. Whereas traditional subcutaneous insulin dosing shifts the point of entry of insulin into the circulation from the natural site (the portal vein) to the systemic circulation, the oral dosing method of the present invention shifts the site of insulin entry back to the portal vein. The effect of this route of dosing is two fold. First, by targeting the liver directly, a greater control of glucose may be achieved. Various studies have shown that intraportal delivery of insulin can yield a comparable control of glucose at infusion rates lower than those required by peripheral administration. (Stevenson, R. W. et al., Insulin infusion into the portal and peripheral circulations of unanaesthetized dogs, Clin Endocrinol (Oxf) 8, 335-47 (1978); Stevenson, R. W. at al., Effect of intraportal and peripheral insulin on glucose turnover and recycling in diabetic dogs, Am J Physiol 244, E190-5 (1983); Shishko, P. I. et al., I. U. Comparison of peripheral and portal (via the umbilical vein) routes of insulin infusion in IDDM patients, Diabetes 41, 1042-9 (1992). Because the insulin will undergo first-pass metabolism prior to entering the systemic circulation, a lower serum concentration is achieved. This may, in turn, alleviate any detrimental effects of insulin on non-target tissues. In normal healthy humans, the physiologic ratio of blood insulin concentration in the portal vein as compared to systemic (peripheral) blood insulin concentration is greater than about 2:1. In contrast, administration of insulin to human diabetic patients has been found to shift this ratio of portal vein insulin blood concentration to systemic insulin blood concentration to about 0.75:1. By virtue of the present invention, the ratio of concentration of unmodified insulin in the portal circulation to systemic circulation approaches the normal physiological ratio, e.g., from about 2:1 to about 6:1. One aspect of the physiological response to the presence of insulin is the stimulation of glucose transport into muscle and adipose tissue. It has been reported that hyperglycemia (elevated blood glucose levels) and/or hyperinsulinemia is a cause of vascular diseases associated with diabetes. Impairment to the vascular system is believed to be the reason behind conditions such as microvascular complications or diseases (retinopathy (lesions in the small blood vessels and capillaries supplying the retina of the eye); neuropathy (impairment of the function of the autonomic nerves, leading to abnormalities in the function of the gastrointestinal tract and bladder, and also loss of feeling in lower extremities); nephropathy (lesions in the small blood vessels and capillaries supplying the kidney, which may lead to kidney disease)); or macrovascular complications or diseases (e.g., cardiovascular disease; etc.). The present invention provides a method of attenuating and/or reducing the incidence of diseases associated with exposure to systemic hyperinsulinemia by the oral administration to a patient a dosage form in accordance with the invention comprising unmodified insulin, preferably along with a suitable drug delivery agent that facilitates the absorption of insulin from the gastrointestinal tract of the patient in a therapeutically effective amount, for treatment of diabetes. Both the methods and pharmaceutical compositions useful for oral administration of insulin are within the scope of the invention. The methods and oral compositions of the invention can attenuate and/or reduce the incidence of cardiovascular disease associated with chronic dosing of insulin. It is believed that orally administering insulin with the compositions of the invention will decrease the complications associated with vascular disease by lowering the systemic vasculature's exposure to insulin that is greater than normal physiological levels. With a first passage through the liver, roughly 50% of the insulin is retained and metabolized, thereby reducing the incidence of peripheral hyperinsulinemia. In certain embodiments, the invention provides a method of treating diabetics comprising orally administering to diabetic patients on a chronic basis an oral insulin treatment comprising a dose of insulin together with a delivery agent which facilitates the absorption of the dose of insulin from the gastrointestinal tract to provide a therapeutically effective reduction in blood glucose and a peak serum insulin concentration that is reduced relative to the peak serum insulin concentration of an equivalent therapeutically effective reduction in blood glucose concentration achieved by subcutaneous injection of insulin. In certain embodiments, this method can result in the reduction of the incidence of a disease state associated with chronic insulin administration, which disease states include, for example, cardiovascular diseases. Cardiovascular diseases include, for example, congestive heart failure or coronary artery disease, neuropathy, nephropathy, retinopathy, arteriopathy, atherosclerosis, hypertensive cardiomyopathy and combinations thereof. In some embodiments, the invention provides a method of reducing the incidence and/or severity of one or more disease states associated with chronic administration of insulin comprising treating diabetic patients via oral administration on a chronic basis of a therapeutically effective dose of a pharmaceutical composition which comprises insulin and a delivery agent that facilitates the absorption of insulin from the gastrointestinal tract, such that the pharmaceutical composition provides a therapeutically effective reduction in blood glucose and a peak serum insulin concentration of the diabetic patient that is reduced relative to the peak serum insulin concentration of an equivalent therapeutically effective reduction in blood glucose concentration achieved by subcutaneous injection of insulin. Disease states associated with chronic administration of insulin for which the incidence and/or severity can be reduced by the method described herein include, for example, cardiovascular diseases, such as congestive heart failure or coronary artery disease. Other disease states include, for example, neuropathy, nephropathy, retinopathy, arteriopathy, atherosclerosis, hypertensive cardiomyopathy and combinations thereof. In some embodiments, the method of reducing the incidence and/or severity of one or more disease states associated with chronic administration of insulin can provide for a reduced expression of genes associated with vascular disease as compared to the level of expression of genes associated with vascular disease resulting from an equivalent reduction in blood glucose concentration achieved in a population of patients via subcutaneous injection of insulin. The genes associated with vascular disease can include, for example, early response genes, genes associated with cytokines, genes associated with adhesion molecules, genes associated with lipid peroxidation, genes associated with thrombosis and combinations thereof. Early response genes can include, for example, c-myc, jun B, Egr-1, Ets-1 and combinations thereof. The methods provided herein relating to oral administration of insulin and oral administration of insulin on a chronic basis, in some embodiments, provide for obtaining plasminogen activator inhibitor concentrations that are lower as compared to the plasminogen activator inhibitor concentrations resulting from an equivalent therapeutically effective reduction in blood glucose concentration achieved by subcutaneous injection of insulin. These methods also can provide for obtaining pro-inflammatory cytokine concentrations that are lower than pro-inflammatory cytokine concentrations resulting from an equivalent therapeutically effective reduction in blood glucose concentration achieved by subcutaneous injection of insulin. In some embodiments, the invention provides a method of treating diabetes and reducing the incidence and or severity of hyperinsulinemia associated with chronic dosing of insulin, comprising orally administering on a chronic basis to a diabetic patient a dose of insulin and a delivery agent that facilitates the absorption of the dose of insulin from the gastrointestinal tract to provide a therapeutically effective reduction in blood glucose and a peak serum insulin concentration of the diabetic patient that is reduced relative to the peak serum insulin concentration of an equivalent therapeutically effective reduction in blood glucose concentration achieved by subcutaneous injection of insulin. In some embodiments, the invention provides a method of screening a drug for vascular injury associated with route of administering the drug, comprising administering a drug to a first test animal parenterally, administering the drug to a second test animal orally, and comparing the expression of early response genes selected from the group consisting of c-myc, c-fos, Jun B, Erg-1 and combinations thereof for the first and second test animal, wherein an increase in the expression of one or more early response genes is indicative of vascular injury. In some embodiments, the step of measuring the change in expression is done using gene chip analysis and can comprise measuring the changes in mRNA expression. In some embodiments, the invention provides a method of reducing the incidence of and/or the severity of disease states or of vascular diseases associated with chronic insulin administration to diabetics, comprising orally administering an oral insulin treatment comprising a dose of insulin together with a delivery agent that facilitates the absorption of said insulin from the gastrointestinal tract on a chronic basis to diabetic patients to reduce blood glucose levels in said diabetic patients by a desired amount, such that the concentration of insulin circulating in the blood of said diabetic patients as a result of insulin treatment is reduced relative to the peak serum insulin concentration of an equivalent therapeutically effective reduction in blood glucose concentration achieved by subcutaneous injection of insulin. In some embodiments, the invention provides a method for reducing the incidence of, the severity of, or the incidence and severity of vascular diseases associated with chronic insulin therapy in diabetics, comprising orally administering an oral insulin treatment comprising a dose of insulin together with a delivery agent that facilitates the absorption of said insulin from the gastrointestinal tract on a chronic basis to diabetic patients to reduce blood glucose levels in said diabetic patients by a desired amount, such that the concentration of insulin circulating in the blood of said diabetic patients as a result of insulin treatment is reduced relative to the peak serum insulin concentration of an equivalent therapeutically effective reduction in blood glucose concentration achieved by subcutaneous injection of insulin. In some embodiments, the invention provides a method of attenuating processes resulting from the reaction to a mild injurious stimulus in multiple areas of the response to increases in mRNA during insulin treatment, comprising orally administering an oral insulin treatment comprising a dose of insulin together with a delivery agent that facilitates the absorption of said insulin from the gastrointestinal tract on a chronic basis to diabetic patients to reduce blood glucose levels in said diabetic patients by a desired amount, such that the concentration of insulin circulating in the blood of said diabetic patients as a result of insulin treatment is reduced relative to the peak serum insulin concentration of an equivalent therapeutically effective reduction in blood glucose concentration achieved by subcutaneous injection of insulin. In some embodiments, the invention provides a method of treating diabetic patients, comprising orally administering an oral insulin treatment comprising a dose of insulin together with a delivery agent that facilitates the absorption of said insulin from the gastrointestinal tract on a chronic basis to diabetic patients to reduce blood glucose levels in said diabetic patients by a desired amount, such that the concentration of insulin circulating in the blood of said diabetic patients as a result of said oral insulin treatment is not substantially greater than normal physiological levels. DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS In order that this invention may be better understood, the following examples are set forth. These examples are for the purpose of illustration only and are not to be construed as limiting the scope of the invention in any manner. EXAMPLE 1 Plasma Delivery Agent Design and Efficiency Delivery agents 1-3 were investigated for their ability to penetrate the GI mucosa. The plasma concentration of each delivery agent was measured in human subjects after oral administration of delivery agent loaded capsules as a measure of each delivery agent's penetration efficiency. See Tables 1 and 2. TABLE 1 Structures of Delivery Agents 1-3 Delivery Agent 1 (SNAC) Delivery Agent 2 (SNAD) Delivery Agent 3 (4-CNAB) TABLE 2 Delivery Agent Plasma Concentrations in Humans Variables Delivery Agent AUC Delivery Agent X n Dose (Mg) (ng · hr/ml) 1 (SNAC) H 7 750 3499 2 (SNAD) H 9 750 2037 3 (4-CNAB) Cl 3 800 47478 Blood sampling for plasma delivery agent concentration determination (2 mL in sodium heparin tube) were drawn 15 minutes before dosing, and at 5, 10, 15, 30, and 45 minutes and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose (14 samples per treatment) for delivery agent measurements in all treatment groups. Two 18-gauge IV lines were situated prior to dosing; one for blood sampling, and the other for potential infusion of 20% glucose for subjects in groups 2 and 3. The subjects in group 1 only had one cannula inserted. The blood samples were centrifuged at 3000 rpm for a period of fifteen minutes at a temperature from about 2° C. to 8° C., within one hour of sample collection. Using a plastic pipette and without disturbing the red cell layer, the plasma from the collection tube was pipetted in duplicate for each analysis, blood glucose, Human Insulin, C-peptide, delivery agent into pre-labeled polypropylene tubes. The samples were stored at −70° C. until analysis. The indicated doses were ingested by healthy human volunteers and the plasma concentrations of the delivery agents were monitored over time and the area under the curve (AUC) calculated. Surprisingly, as provided in Table 2, oral administration of 800 mg delivery agent number 3 with X as chlorine and n equal to 3 alkyl produced an approximately 13.5 fold greater penetration of the GI mucosa in humans than did oral administration of 750 mg of delivery agent 1 having n equal 7 alkyl. Similarly, oral administration of 800 mg of delivery agent number 3 produced more than a 23 fold greater penetration of the GI mucosa in humans than did oral administration of 750 mg of delivery agent 2 having n equal to 9 alkyl. Similar results were obtained when delivery agents 1-3 were administered orally to monkeys and the plasma concentrations of the delivery agents monitored over time and the AUC calculated. As provided in Table 3, oral administration of 300 mg of delivery agent number 3 with X as chlorine and n equal to 3 alkyl produced a more than 11 fold greater penetration of the GI mucosa in monkeys than did oral administration of 300 mg of delivery agent 1 having n equal to 7 alkyl. See Table 3. Further, 300 mg of delivery agent 3 displayed a more than 6 fold greater penetration of the GI mucosa in monkeys than did oral administration of 300 mg of delivery agent 2 having n equal to 9 alkyl. See Table 3. TABLE 3 Delivery Agent Plasma Concentrations in Monkeys Delivery Agent AUC Delivery Agent X n Dose (Mg) (ng · hr/ml) 1 (SNAC) H 7 300 45 2 (SNAD) H 9 300 82 3 (4-CNAB) Cl 3 300 499 EXAMPLE 2 Comparison of the Delivery Efficiency of Delivery Agents 1-3 Next, delivery agents 1-3 were compared for the ability to efficiently transport an active agent across the GI mucosa in a biologically active form by determining the relationship between delivery agent dose, dose of active agent and the glucose response. See Table 4. The effective dose of delivery agent necessary to deliver a therapeutic dose of active agent and produce a therapeutic effect was measured. See Table 4. For delivery agent 3, the active agent was insulin, and the therapeutic effect was determined by the ability of the delivery agent/insulin combination to lower serum glucose by at least 10% within one hour post administration. For delivery agents 1 and 2, the active agent was heparin, and the therapeutic effect was determined by [Emisphere: please fill in] TABLE 4 Effective Clinical Dose of Delivery Agent in Humans Delivery Agent Delivery Agent X N Dose (Mg) 1 (SNAC) H 7 2400 2 (SNAD) H 9 1500 3 (4-CNAB) Cl 3 200 Again, as shown in Table 4, delivery agent 3 with X as chlorine and n equal to 3 alkyl was approximately 12 fold more efficient in facilitating insulin transit across the GI mucosa in a biologically active form than was delivery agent 1 having n equal to 7 alkyl. Similarly, delivery agent no. 3 was 7.5 fold more efficient in facilitating transport of insulin across the GI mucosa in a biologically active form than was delivery agent 2 having n equal to 9 alkyl. See Table 4. Most importantly, only delivery agent 3 is efficient enough at facilitating transport of biologically active insulin to allow packaging of a therapeutically effective dose of insulin plus delivery agent into a single capsule. EXAMPLE 3 Preparation of the Delivery Agent 4-CNAB The compound corresponding to the following structure may be prepared as described below: 4-Chlorosalicylic acid (10.0 g, 0.0579 mol) was added to a one-neck 250 ml round-bottomed flask containing about 50 ml methylene chloride. Stirring was begun and continued for the remainder of the reaction. The coupling agent 1,1-carbonyldiimidazole (9.39 g, 0.0579 mol) was added as a solid in portions to the flask. The reaction was stirred at room temperature for approximately 20 minutes after all of the coupling agent had been added and then ethyl-4-aminobutyrate hydrochloride (9.7 g, 0.0579 mol) was added to the flask with stirring. Next, triethylamine (10.49 ml, 0.0752 mol) was added dropwise from an addition funnel. The addition funnel was rinsed with methylene chloride. The reaction was allowed to stir at room temperature overnight. The reaction was poured into a separatory funnel and washed with 2N HCl and an emulsion formed. The emulsion was left standing for two days and was then filtered through celite in a fritted glass funnel. The filtrate was put back in a separatory funnel to separate the layers. The organic layer was dried over sodium sulfate, which was then filtered off and the filtrate concentrated by rotary evaporation. The resulting solid material was hydrolyzed with 2N NaOH, stored overnight under refrigeration, and then hydrolyzing resumed. The solution was acidified with 2N HCl and the solids that formed were isolated, dried under vacuum, and recrystallized twice using methanol/water. Solids precipitated out overnight and were isolated and dried. The solids were dissolved in 2N NaOH and the pH of the sample was brought to pH 5 with 2N HCl. The solids were collected and HPLC revealed a single peak. These solids were then recrystallized in methanol/water, isolated, and then dried under vacuum, yielding 4.96 g (33.0%) of 4-(4 chloro-2-hydroxybenzoyl)aminobutyric acid, (C11H12CINO4; Molecular weight 257.67). A melting point of 131-133° C. was determined. Combustion analysis revealed the following content: % C: 51.27 (calc.), 51.27 (found); % H, 4.69 (calc.), 4.55 (found); % N, 5.44 (calc.), 5.30 (found). Proton H NMR Analysis revealed: (d6-DMSO): d 13.0, s, 1H(COOH); d 12.1, s, 1H(OH); d 8.9, t, 1H (NH); d 7.86, d, 1H(H ortho to amide); d 6.98, d, 1H(H ortho to phenol OH); d 6.96, d, 1H, (H meta to amide); d 3.33, m, 2H(CH2 adjacent to NH); d 2.28, t, 2H(CH2 adjacent to COOH); d 1.80, m, 2H (aliphatic CH2 beta to NH and CH2 beta to COOH). 4-CNAB Preparation for Human Studies 4-CNAB for the human dosings (Monosodium N-(4-chlorosalicyloyl)-4-amino-butyrate) was made under good manufacturing practices (GMP) conditions by Regis Technologies, Inc. (Morton Grove, Ill.) according to the methods of International Publication No. WO 00/46182 except that the starting material 4-chlorosalicylic acid (purchased from Ihara Chemical Industry Co. Inc, Ltd., Tokyo, Japan and Aapin Chemicals Ltd., Oxfordshire, UK) was used and converted to the amide via a methyl ester using 0.14 equivalents sulfuric acid in methanol and then about 4 equivalents ammonia in methanol. The alkylating agent used was ethyl-4-bromobutyrate. The monosodium salt of 4-CNAB was made according to the following method on a 40 kilogram scale. 4-CNAB free acid (500 g, 1.94 mol, FW=257.67) was charged to a 22 L five neck round bottom flask. The flask was equipped with an overhead stirrer, a thermocouple temperature read out, a reflux condenser and a heating mantle, and was placed under nitrogen. Reagent grade acetone (13 L) was added to the reactor and the mixture was agitated. The 4-CNAB/acetone mixture was heated to 50° C. to dissolve any solids. A hazy brown solution was achieved. The 50° C. solution was pumped through a warm pressure filter (dressed with Whatman #1 filter paper, ˜5 microns, 18.5 sq. in. area) into a clean 22 L reactor to remove sodium chloride and other insolubles. The pressure dropped across the filter to about 20 psig at the end of filtration. The reactor containing the clear yellow filtrate was agitated and heated. At 50° C. the reactor was removed from heat. The clear filtrate was charged with 50% sodium hydroxide solution (155 g, 1.94 mol) as rapidly as possible, while maintaining a vigorous agitation. (An overcharge will result in the undesirable formation insoluble disodium salts. A slight undercharge is preferable because the free acid is removed during the final filtration step.) The reaction mixture exothermed to approximately 52° C. Precipitates formed and the product gelled before becoming clear again. After the base addition was completed and the temperature leveled, the solution became cloudy and increased in viscosity. The reaction was refluxed for 2 hours at 60° C., while agitating vigorously. The reaction mixture continued to thicken, forming solid chunks. The slurry became light pink and foamed. The reactor contents were cooled to ambient temperature over 3 to 4 hours. The ambient temperature was held for 30 minutes. The precipitated solids were isolated on a filter funnel. The isolated product was not washed. The resulting 4-CNAB monosodium salt was dried in vacuo at 40 to 50° C. for 16 to 24 hours to give 490 grams (1.75 mol, 90% yield, FW=279.65). The insulin for the subcutaneous injection was HUMULIN® R injection insulin from Eli Lilly and Company (Indianapolis, Ind.). All capsules containing 200 mg 4-CNAB and 150 insulin units USP were prepared as follows. First, the total amount of delivery agent material necessary for filling the delivery agent alone capsules and the delivery agent plus insulin composition capsules was prepared by weighing 3160 g of 4-CNAB. The 3160 g 4-CNAB was then milled in a Quadro comil, model 197S mill with screen number 2A 050 G 037 19 136 (1270 micron). Next, 1029 g of the milled 4-CNAB was passed through a #35 mesh screen. Then, the pass through screened material was transferred into a 4 quart shell and blended using for example, a V blender, at 25 rpm for 10.2 minutes. The resultant blended material was used to fill capsules. In this case, a Fast Cap Capsule Filler was used with a size 3 Fast Cap Encapsulation tray. The empty capsules weighed approximately 48 mg each and were filled with an average fill weight of 205.6 mg of 4-CNAB alone. Thus, the dose of the delivery agent alone capsules was 205.6 mg. The insulin compositions were prepared by first dispensing 31.8 g of recombinant human zinc crystalline insulin (Potency 26.18 Units per mg) proinsulin derived (recombinant DNA origin) USP quality) from Eli Lilly and Company (Indianapolis, Ind.) into an appropriately sized plastic bag. Next, sequential 30 g additions of the milled and screened 4-CNAB were added to the bag until approximately 510 g had been added. The bag was thoroughly mixed after each 30 g addition of 4-CNAB by shaking and inversion. In order to add and mix the next 532.5 g of 4-CNAB, the 541.8 g mixture of insulin and 4-CNAB was transferred to a V blender and mixed again at 25 rpm for 10.2 minutes. Next, the remaining 4-CNAB was added to the blender and the entire mixture was mixed in the blender at 25 rpm for 10.2 minutes. Finally, the resulting composition was dispensed as described above into empty capsules. The final capsules contained an average of 5.7 mg insulin (equivalent to 150 units insulin) and 200.5 mg of 4-CNAB or a ratio of 1:57.3, insulin: 4-CNAB. Multiple samples of the final blend were ran on HPLC to verify uniformity and were found to be uniform. EXAMPLE 4 Previous Non-clinical Studies with 4-CNAB and Insulin/4-CNAB The present invention comprising compositions of insulin and the delivery agent 4-CNAB was evaluated for safety and toxicity in a nonclinical program that included pharmacological screening, pharmacokinetic profiling, and toxicity assessments in rats and monkeys. In general, animal physiological responses to 4-CNAB alone and to Insulin/4-CNAB were comparable. Pharmacokinetic studies in mice, rats and monkeys have shown that 4-CNAB is absorbed rapidly following oral administration, and subsequently cleared from the body. 4-CNAB did not demonstrate potential activity in any of the primary molecular targets evaluated in receptor binding screening assays. Four genotoxicity studies have been conducted with 4-CNAB, with no positive findings. Based on 14-day oral repeated dose toxicity studies, the NOAEL (No-Adverse Effect Level) was estimated to be 500 mg/kg in Sprague-Dawley rats, and 400 mg/kg in rhesus monkeys. In toxicology studies, 4-CNAB doses from 400 mg to 2000 mg were evaluated. Following 14-day oral repeated dose toxicity studies in rats and monkeys, the estimated No Adverse Effect Level (NOAEL) for 4-CNAB was 500 mg/kg in Sprague-Dawley rats and 400 mg/kg in rhesus monkeys; therefore, the monkey appeared to be the most sensitive species. The highest proposed dose of 2000 mg 4-CNAB in man (<30 mg/kg) is 12-16 fold lower than the NOAEL in monkeys (i.e., NOAEL=400 mg/kg 4-CNAB alone and in combination with 15 U/kg insulin). The absolute bioavailability of insulin in monkeys was about 1% or less. In the toxicology studies, there were no findings in rats attributed to insulin at an oral dose level of 15 U/kg in combination with 4-CNAB doses as high as 2000 mg/kg. In monkeys, an insulin dose of 15 U/kg was associated with a single hypoglycemic episode in combination with a 4-CNAB dose of 1200 mg/kg in one monkey; there were no effects at 15 U/kg insulin in combination with lower doses. Non-clinical studies in rats and monkeys demonstrated that, over the range tested, insulin absorption increases with increasing doses of 4-CNAB. Similarly, for a fixed oral dose of 4-CNAB, insulin absorption increases with increasing doses of insulin. Oral insulin absorption was evaluated in rats at varying doses of both insulin and 4-CNAB. Significant increases in serum insulin concentrations were observed following the administration of insulin at doses of 4.55, 6.5, 9.75, and 13 Units/kg in the presence of a fixed 4-CNAB dose (200 mg/kg). The mean peak serum insulin levels were 31, 44, 85, and 132 μU/mL respectively. Insulin absorption was dose dependent and increased as the dose of insulin increased. Oral administration of aqueous solutions of insulin alone (13 Units/kg) or 4-CNAB alone (200 mg/kg) did not result in any significant increases in serum insulin levels. Significant increases in serum insulin concentrations were also observed following the administration of 4-CNAB at doses of 50, 100, 200, and 300 mg/kg in the presence of a fixed insulin dose (13 Units/kg). The mean peak serum insulin levels were 9, 39, 103, and 157 μU/mL, respectively. Insulin absorption was dose dependent and increased as the dose of 4-CNAB increased. Based on the above nonclinical information, the starting insulin dose of 150 insulin Units USP (which is about 7-fold lower than the 15 U/kg no effect dose in monkey) was selected. EXAMPLE 5 A single center, double-blind, randomized placebo-controlled study undertaken in healthy human subjects in order to assess the safety and tolerability of escalating single oral doses of 4-CNAB capsules and insulin/4-CNAB capsules. A subcutaneous (SC) insulin treatment group was added to allow comparison of the combined treatment against an existing standard treatment, and an oral insulin alone treatment group was also included to further evaluate the effect of 4-CNAB on oral insulin absorption. One objective of this study was to evaluate the safety and tolerability of single oral doses of 4-CNAB and of Insulin/4-CNAB capsules in healthy subjects. Other objectives of this study were to assess the PK of 4-CNAB when given alone and when given as part of the Insulin/4-CNAB combination, to assess the PK of insulin and the effect of increasing proportions of 4-CNAB on insulin PK and to assess the effects on blood glucose following single oral doses of 4-CNAB alone or Insulin/4-CNAB. The study allowed the investigation of the effect of 4-CNAB on oral insulin PK and PD to be studied across a range of doses and to be compared with SC and oral insulin alone treatments. Control treatments of 10 Units SC insulin, 150 USP Units oral insulin alone, oral placebo and SC placebo allowed the tolerability, PK and effects of 4-CNAB and Insulin/4-CNAB to be evaluated effectively. Simultaneous measurement of C-peptide protein allowed the correction for endogenous insulin. Food given at 6 h post-dose also allowed its effect on insulin and glucose to be observed. Parallel groups were used due to the number of treatments administered and also reduced the length of the study. The double-blind nature of subject and physician ensured minimal bias. Male subjects aged between 18 and 50 years were recruited and were chosen to be representative of the general healthy population, which was deemed suitable for such a study. Selection criteria (inclusion and exclusion) were chosen to ensure that the subjects were healthy and therefore at minimal risk from the study procedures and to side effects of Insulin/4-CNAB. The subjects were in good health as determined based on medical history, physical examination and clinical laboratory studies at screening. The subjects were within the permissible deviations (+/−15%) of ideal weight according to the 1983 tables of desirable weights issued by the adjusted Metropolitan Life Insurance Co. All laboratory values (hematology, serum chemistries, and urinalysis) obtained during screening were generally within normal ranges. The laboratory tests were conducted in a fasted state and glucose measured. However, for clinical laboratory values outside of the normal range, the laboratory test was repeated once. The subjects had 12-lead ECG recorded within 14 days prior to the study start, and results indicated a normal recording or a non-clinically significant abnormality. Within each treatment period in each group, eight subjects were planned to receive active treatment and two subjects to receive placebo. In Group 1, there were four escalating single doses of 4-CNAB (400, 800, 1400 and 2000 mg) and each subject received either all four of these escalating doses or three escalating single doses and one dose of placebo. In Group 2 there were three treatments (10 Units of SC insulin and 2 escalating oral doses of Insulin/4-CNAB; 150 Units/200 mg, 100 Units/600 mg) and each subject received either all three of these treatments or two of these treatments and one placebo treatment. In Group 3 there were three escalating oral doses of Insulin/4-CNAB (100 Units/300 mg, 100 Units/450 mg and 150 Units/100 mg) and one SC dose of 150 Units of insulin. Each subject received either all four of these treatments or three of these treatments and one placebo treatment. For all groups, there was a washout period of at least 72 hours between treatment periods. Twenty-nine volunteers, divided among three groups (9 in group 1, and 10 in each of groups 2 and 3), participated in this study. Randomization was stratified such that any individual subject received placebo only on a single occasion or not at all. Two subjects in each group received placebo. Group 1 received four escalating oral doses of 4-CNAB capsules or placebo (see Table 5), with each subject receiving four active treatments or three active treatments and one placebo treatment. For each treatment, seven subjects received active treatment and two received placebo, according to the pre-prepared randomization code. TABLE 5 Group 1 - 4-CNAB alone (4 escalating doses) Group 1: 4-CNAB only # of Subjects & # of Subjects on Treatment: 4-CNAB Dose placebo # of Capsules Treatment 1 7 subjects 400 mg 2 2 Treatment 2 7 subjects 800 mg 2 4 Treatment 3 7 subjects 1400 mg 2 7 Treatment 4 7 subjects 2000 mg 2 10 Group 2 received three escalating oral doses of Insulin/4-CNAB capsules or placebo (see Table 6), with each subject receiving three active treatments or two active treatments and one placebo treatment. For each treatment, eight subjects received active treatment and two received placebo, according to the pre-prepared randomization code. TABLE 6 Group 2 - Insulin/4-CNAB (2 escalating doses) and SC insulin alone (1 dose) Group 2 # of Subjects & # of Insulin/4-CNAB Insulin/4-CNAB Dose Subjects # of Treatment (Unit Insulin/mg 4-CNAB) on placebo Capsules Treatment 1 8 subjects 10 IU insulin 2 0 subcutaneous/0 mg 4-CNAB Treatment 2 8 subjects 150/200 2 1 Treatment 3 8 subjects 100/600 2 4 Group 3 received three oral doses of Insulin/4-CNAB capsules or placebo and one oral dose of Insulin capsule alone or placebo (see Table 7), with each subject receiving four active treatments or three active treatments and one placebo treatment. For each treatment, eight subjects received active treatment and two received placebo, according to the pre-prepared randomization code. TABLE 7 Group 3 - Insulin/4-CNAB (3 escalating doses) and Insulin alone (1 dose) # of Subjects & Group 3 Insulin/4-CNAB Dose # of Insulin/4-CNAB (Unit Insulin/mg 4- Subjects on # of Treatment: CNAB) placebo Capsules Treatment 1 8 subjects 100/300 2 2 Treatment 2 8 subjects 100/450 2 3 Treatment 3 8 subjects 150/100 2 1 Treatment 4 8 subjects 150/0 2 1 The 4-CNAB alone and Insulin/4-CNAB capsules were prepared by AAIPharma Inc., Wilmington N.C. The 4-CNAB used for the capsules was manufactured under cGMP compliance. The Insulin used to prepare the capsules was Zinc-Insulin Crystals Human: Proinsulin Derived (Recombinant DNA Origin) USP Quality obtained from Eli Lilly and Company (Indianapolis, Ind.). Insulin used for the SC dosing was provided by Medeval Ltd. This insulin was zinc-insulin crystals human: proinsulin derived (recombinant DNA origin) equivalent to Humulin R (trade name Humulin S injection 100 Units/mL). Placebo capsules consisted of Size 3 hard gelatin capsules filled with 200 mg of Methocel E15 Premium LV. Each capsule was stored frozen at or below minus 10° C., was brought to room temperature (between 15 and 30° C.) before opening, and was not left at room temperature for more than 4 hours Capsules were administered with 240 mL water. For all groups, there was a washout period of at least 72 hours between treatment periods. After each dosing, safety data (i.e., vital signs, blood glucose, and available 4-CNAB plasma concentrations) were collected and evaluated before proceeding to the next dose level. On day one of each study treatment period, study medication (capsules or SC dose) were administered at approximately 8:00 AM following an 8-hour minimum overnight fast. The capsules were administered with 240 mL of water with subjects in an upright position. The total administration time did not exceed 2.5 minutes. The SC dose of insulin solution or placebo (saline) was injected in the abdominal wall as a single bolus administration. Each treatment period lasted between 12 and 24 hours. The appearance of the prepared active and placebo study treatments was identical, and, therefore, maintenance of blinding from treatment appearance was not an issue in this study. Administration of the medication was supervised, and, therefore, non-compliance was not an issue in this study. Subjects fasted overnight for a minimum of 8 hours prior to morning dosing until 6 hours after dosing, after which each subject ate a full meal, including at least two slices of bread. Subjects were provided with standard high carbohydrate meals and snacks. Water was allowed ad libitum, except for 1 hour prior through to 1 hour after administration of each treatment (apart from that required for dosing). Subjects were asked to refrain from xanthine or xanthine related agents, grapefruit containing products, Seville oranges and marmalade during the 24 hours prior to dosing and throughout the study periods. No concomitant medication, apart from acetominophen (paracetamol), was allowed during the study, and no alcohol was allowed for 24 hours prior to admission and while resident in the clinical unit. Non-smokers or smokers who smoked up to five cigarettes a day were recruited. Smoking was not allowed while resident in the Clinical Unit Subjects were asked to avoid strenuous physical activity and contact sports from 48 hours prior to Day-1 until the end of the residential period. Dose escalation within each group continued until two subjects per treatment exhibited a blood glucose level of less than 54 mg/dl (3.0 mmol/L). Once this dose had been identified, there was an adaptable approach to exploring changing the ratios of insulin and 4-CNAB. The chosen insulin dose was no higher than the insulin dose that caused the blood glucose level of 54 mg/dL (3.0 mmol/L), and the dose of 4-CNAB was not higher than that already given. Safety assessments included physical examinations, medical history, vital signs, 12-lead electrocardiogram (ECG) monitoring, laboratory evaluations and checking for adverse events. Activity parameters included blood glucose, insulin, C-peptide, and 4-CNAB plasma concentration measurements. For insulin/4-CNAB treatment Groups 2 and 3, subjects' blood samples (1 drop per sample) were drawn at 15 minutes before dosing, and at 5, 10, 15, 20, 25, 30, 35, 40, and 50 minutes and at 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose (21 samples per treatment for Insulin/4-CNAB dosing groups) for plasma glucose, insulin and C-peptide measurements. For the 4-CNAB alone treatment Group 1, blood samples were collected before dosing (−15 minutes), and at 30 minutes and at 2 hr post-dose for blood glucose measurements. For the insulin alone control group (minimum 3 subjects), blood samples (3 mL in sodium heparin tube) were drawn at 15 minutes before dosing, and at 10, 20, 30, 40, 50 minutes and 1, 1.25, 2, 2.5, 3 and 6 hr post-dose (12 samples per treatment). The blood samples for glucose were assayed in real time using a Glucometer®. These measurements were used for detection of onset of hypoglycemia, so rescue action could be taken where necessary. Plasma glucose, insulin and C-peptide measurements were done according to standard procedures. Two 18-gauge IV lines were situated prior to dosing; one for blood sampling, and the other for potential infusion of 20% glucose for subjects in Groups 2 and 3, if required for the treatment of hypoglycemia. The subjects in Group 1 only had one cannula inserted. Blood samples for plasma glucose, insulin and C-peptide analyses were stored between 2° C. and 8° C. immediate after sampling and prior to centrifugation. Blood samples for were centrifuged at 3000 rpm for a period of 15 minutes at a temperature between 2° C. and 8° C. within one hour of sample collection. Using a plastic pipette and without disturbing the red cell layer, the plasma from the collection tube was pipetted into pre-labelled polypropylene tubes and stored at −70° C. Total blood volume (including study screening and safety assessment) collected from each subject for the entire study did not exceed 625 mL for subjects in Group 3, and 487 mL for subjects in Group 2, and 380 mL for subjects in Group 1. The concentration of 4-CNAB in plasma was determined using a combination of liquid chromatography and Mass spectrometry assay known as LC-MS/MS. The method involves protein precipitation followed by separation on liquid chromatography using a Hypersil BDS column and a mobile phase consisting of methanol and acetate buffer. The eluting peaks were quantified by MS/MS. The equipment used for the determination of 4-CNAB in plasma comprises of an Agilent 1100 modular HPLC system with a Micromass Quattro Micro MS/MS detector. HPLC and AR grade chemicals and reagents were used throughout the study. Pharmacokinetic and Pharmacodynamic Assessments Plasma glucose was measured based on a timed-endpoint method using a BECKMAN Synchron CX system that mixes exact proportions of reagents that catalyse the phosphorylation of glucose. The Synchron CX measures changes in the absorbance spectrum at 340 nm at a fixed time interval. The change in absorbance is directly proportional to the concentration of glucose in the sample. Plasma C-peptide was measured using a DELFIA C-peptide kit, based on a solid phase, two-site fluoroimmunometric assay, which used the direct sandwich technique in which two monoclonal antibodies are directed against antigenic determinants on the C-peptide molecule. Reagent dissociates europium ions from the labeled antibody, which form fluorescent chelates with the reagent. The fluorescence is directly proportional to the concentration of C-peptide in the sample. On the basis of plasma concentrations of 4-CNAB and insulin, PK analysis was performed using non-compartmental PK methods as implemented in WinNonlin™ Professional version 3.2. The profiles for insulin and C-peptide corrected insulin were evaluated up to 6 hours as food was given 6 hours following insulin treatment. The following parameters were derived for 4-CNAB: Cmax, tmax, AUC(0-1), AUC(0-inf), AUC% Etrap, Kel, t1/2, CL/F, Vd/F, MRT(0-t), MRT(0-inf) and and Frel. The following parameters were derived for insulin and C-peptide corrected insulin: Cmax, tmax, AUC(0-2), AUC(0-6), AUC(0-t) and concentrations (Cb) and corresponding time (tb) immediately prior to intervention for hypoglycemia. On the basis of plasma concentrations of glucose, PD analysis was performed using WinNonlin™ Professional version 3.2. The profiles for glucose, glucose change from baseline and glucose percentage change from baseline were evaluated up to 6 hours as food was given 6 hours following insulin treatment. The following PD parameters were computed for plasma glucose concentration: AURC(0-2), AURC(0-t) (total response), Rmax (minimum value), tRmax and concentrations (Rb) and corresponding time (tb) immediately prior to intervention for hypoglycemia. The following PD parameters were computed for plasma glucose concentration change from baseline: AUEC(0-2), AUEC(0-t) (baseline subtracted), Emax (baseline subtracted), tEmax (obtained without interpolation), percent change from baseline and concentrations (Ec) and corresponding time (tc) immediately prior to intervention for hypoglycemia. The above parameters were to be summarized using descriptive statistics (mean, standard deviation (SD), coefficient of variation (CV %), standard error of the mean (SE), minimum (Min), median, maximum (Max), and sample size (N) by treatment group. Individual data was reported by dose, by subject. For the PK analysis of insulin, analysis was conducted for both measured insulin and C-peptide corrected insulin concentrations. This was done using concentrations of the precursor C-peptide and the following equation: Corrected Insulin Concentration=Insulin Concentration−(Baseline Ratio×C-peptide) where Baseline ⁢ ⁢ ⁢ Ratio = Insulin ⁢ ⁢ Concentration C - peptide ⁢ ⁢ Concentration at each time point Similarly, in order to take into account baseline levels of glucose, PD analysis was conducted based on the percent change (decrease or increase) in glucose concentration from the baseline, where baseline was taken as the pre-dose concentration levels, rather than absolute values only. The glucose concentration percent change from baseline values were also calculated, and profiles were tabulated and plotted. Thus, Glucose ⁢ % ⁢ ⁢ Change ⁢ ⁢ from ⁢ ⁢ ⁢ Baseline = ( Glucose ⁢ ⁢ Conc . - Baseline ⁢ ⁢ Glucose ⁢ ⁢ Conc . Baseline ⁢ ⁢ Glucose ⁢ ⁢ Conc . ) ⨯ 100 where Glucose Change from Baseline=(Glucose Conc.−Baseline Glucose Conc.). The additional parameters AUC(0-2) for insulin and C-peptide corrected insulin and AURC(0-2) and AUEC(0-2) for glucose and glucose change from baseline, respectively, were calculated because the maximum change in insulin and glucose appeared to occur during the first 2 hours following dosing. For insulin no extrapolation was possible for the vast majority of subjects therefore elimination half-life rate constant Kel and hence AUC(0-inf) could not be calculated. Since food was given at 6 hours following dosing, AUC, AURC and AUEC were calculated up to 6 hours for insulin and glucose respectively which gave a more accurate measure of the effect of Insulin/4-CNAB on insulin and glucose concentrations. For glucose change from baseline, Emax was taken as the maximum reduction up to 6 hours post-dose. The plasma concentration-time profiles for 4-CNAB were evaluated in those subjects who received 4-CNAB or Insulin/4-CNAB treatments. Insulin, C-peptide and glucose concentration-time profiles following administration of all treatments were evaluated for the 20 subjects in Groups 2 and 3. Pharmacokinetic (“PK”) parameters for 4-CNAB, insulin and C-peptide corrected insulin, and pharmacodynamic (“PD”) parameters for glucose concentration change from baseline, respectively were calculated for subjects whether they required hypoglycemic rescue or not. Concentrations from subjects who required food/drink due to hypoglycemia were excluded from descriptive statistics. PK and PD parameters were summarized separately for these subjects, except following SC insulin where descriptive statistics were provided for all eight subjects who required intervention with food/drink due to hypoglycemia. A number of subjects experienced hypoglycemia during treatments and were given food (chocolate, fruit or orange juice) in order to raise blood glucose levels. These subjects were excluded from the concentration-time summary statistics and the summary PK and PD parameters were presented separately from subjects who did not require hypoglycemic rescue. For those subjects who experienced hypoglycemia, additional parameters of Cb and tb values for insulin, Rb and tb values for glucose and Ec and tc values for glucose change from baseline were recorded that reflected the concentration and time immediately prior to hypoglycemic rescue. 4-CNAB Pharmacokinetics Individual plasma-concentrations of 4-CNAB following all treatments were tabulated. Mean (+SD) plasma concentration/time profiles of 4-CNAB following the administration of 4-CNAB alone or insulin/4-CNAB capsules to healthy male volunteers are shown in FIGS. 1 (Group 1) and 2 (Groups 2 and 3). The mean 4-CNAB concentration-time profiles following escalating oral doses of 4-CNAB alone (FIG. 1) showed rapid absorption with peak concentrations achieved at median times of approximately 0.62 h. After reaching the maximum concentration, 4-CNAB concentrations rapidly declined in a biphasic manner. The maximum concentrations Cmax and exposure (i.e. AUCs) clearly increased with increasing dose. When the combination capsules of Insulin/4-CNAB were administered (FIGS. 2A and 2B), 4-CNAB maximum levels were reached at approximately the same time as with 4-CNAB treatments alone and 4-CNAB peak concentrations clearly increased with increasing amounts of 4-CNAB in combination with insulin. The combined treatment of 100 Units Insulin/600 mg 4-CNAB which contained the highest dose of 4-CNAB, resulted in the highest mean peak concentration while the lowest mean peak concentration was observed following the administration of lowest dose of 150 Units Insulin/100 mg 4-CNAB. Mean values±SD, and ranges in parenthesis for tmax, for each treatment for 4-CNAB in plasma following 4-CNAB alone and Insulin/4-CNAB treatments are given below together with descriptive statistics. Pharmacokinetic parameters of 4-CNAB following oral administration of capsules of 4-CNAB alone are summarized in Table 8 below for (Group 1), and mean (+SD) plasma concentration/time profiles are shown in FIG. 1. TABLE 8 PK Parameters of 4-CNAB alone (Group 1) 4-CNAB Dose Parameter 400 mg 800 mg 1400 mg 2000 mg Cmax (ng/mL) 22315 ± 11456 38011 ± 15804 103321 ± 14590 135199 ± 86565 tmax (h) 0.50 (0.50-0.50) 0.50 (0.50-0.75) 0.75 (0.50-0.77) 0.75 (0.50-1.50) AUC(0-t) (ng · h/mL) 22232 ± 6760 44343 ± 14478c 143620 ± 33809 204136 ± 102850 AUC(0-inf) 26708 ± 12209 49409 ± 15057b 153815 ± 38110 192013 ± 37147a (ng · h/mL) Kel (l/h) 0.11 ± 0.78 0.12 ± 0.04b 0.18 ± 0.14 0.06 ± 0.03a t1/2 (h) 12.0 ± 13.4 5.90 ± 1.55b 6.3 ± 4.1 15.3 ± 6.9a Cl/F (mL/min) 294 ± 122 290 ± 88b 160 ± 38 178 ± 32a Vd/F (L) 220 ± 130 156 ± 82b 81 ± 50 245 ± 131a MRT(0-t) (h) 1.60 ± 0.23 1.75 ± 0.22c 1.60 ± 0.20 1.73 ± 0.31 MRT(0-inf) (h) 7.30 ± 11.55 2.60 ± 0.53b 3.06 ± 1.71 7.45 ± 2.36a Values are given as Mean ± standard deviation (except tmax, where median (range) is given) as N = 7 except: a= 3, b= 4 and c= 5 The Pharmacokinetic parameters of 4-CNAB following the administration of 4-CNAB in combination with insulin (Groups 2 and 3) are summarized in Table 9 below, and mean (+SD) plasma concentration/time profiles for Groups 2 and 3 are shown in FIG. 2. TABLE 9 PK Parameters of 4-CNAB with Insulin (Groups 2 and 3) Insulin (Units)/4-CNAB(mg) Parameter 100/300 100/450 100/600 150/100 150/200 Cmax (ng/mL) 8904 ± 6353 23183 ± 7933 35790 ± 12291 6195 ± 3605 10143 ± 5094 tmax (h) 0.50 0.50 0.50 0.50 0.50 (0.27-0.75) (0.27-4.00) (0.25-0.77) (0.25-1.00) (0.25-0.55) AUC(0-t) 8745 ± 5517 25988 ± 4408 36636 ± 5764 4675 ± 1076 10018 ± 1894 (ng · h/MI) AUC(0-inf) 9238 ± 5938 26831 ± 4564 37571 ± 5432 4918 ± 1100 10281 ± 2078 (ng · h/mL) Kel (l/h) 0.19 ± 0.12 0.1852 ± 0.06 0.19 ± 0.06 0.22 ± 0.14 0.25 ± 0.09 t1/2 (h) 5.3 ± 3.3 4.1 ± 1.2 4.1 ± 1.2 4.8 ± 3.4 3.2 ± 1.4 Cl/F (mL/min) 834 ± 527 287 ± 49 271 ± 38 352 ± 68 338 ± 75 Vz/F (L) 324 ± 239 101 ± 35 96 ± 35 148 ± 102 89 ± 35 MRT(0-f) (h) 1.51 ± 0.16 1.79 ± 0.50 1.45 ± 0.17 1.42 ± 0.56 1.59 ± 0.23 MRT(0-inf) (h) 2.43 ± 0.82 2.30 ± 0.46 1.90 ± 0.58 2.39 ± 1.39 1.97 ± 0.39 Values are given as Mean ± standard deviation (except tmax, where median (range) is given). Mean is of eight subjects. As can be seen from the mean concentration-time profiles in FIG. 1 and the resulting values of Cmax and AUC(0-inf) following 4-CNAB alone doses, levels (Cmax) of 4-CNAB and exposure (AUCs) generally increased with 4-CNAB doses, as both Cmax and AUC values increased in a dose-dependent manner for the 400 mg and 800 mg doses. In the 4-CNAB alone treatment groups, the Cmax ranged between 22315±11456 ng/mL and 135199±86565 for doses of 400 mg and 2000 mg, respectively. The time of maximum 4-CNAB concentration was consistent across all doses with median values ranging between 0.50-0.75 hours. Mean elimination half-life values for 4-CNAB were variable and ranged between 5.90 and 15.3 hours due to the variability in the terminal elimination phase and difficulty in estimating the elimination rate constants. However, the MRT values were more consistent and ranged from 1.4 to 1.8 hours. The mean 4-CNAB concentration-time profiles of FIG. 2 and parameters Cmax and AUC shown in Table 9 above for 4-CNAB following 100 Units Insulin/4-CNAB and 150 Units Insulin/4-CNAB combinations indicate increasing 4-CNAB absorption with increasing 4-CNAB dose. Generally, 4-CNAB absorption increased with increasing dose of 4-CNAB with the exception of the 100 Units Insulin/300 mg 4-CNAB treatment. In the Insulin/4-CNAB combination group, the highest values for Cmax occurred following 100 Units Insulin/600 mg 4-CNAB (35790±12291 ng/mL) and the lowest following 150 Units Insulin/100 mg 4-CNAB (6195±3605 ng/mL). Mean values of elimination half-life for 4-CNAB were less variable for the combination capsules and ranged between 3.2 hours and 5.3 hours between the dose group. Table 10 shows a summary of Groups 1, 2 and 3 (average of all subjects in treatment groups), showing Cmax, tmax and area under the curve (AUC) of the delivery agent 4-CNAB, based upon unaudited data. TABLE 10 4-CNAB Cmax and tmax Group/Treatment 4-CNAB Dose Cmax [ng/mL] tmax [hr](range) AUC 1/1 400 22,314.6 ± 11,455.7 0.5 (0.5) 22,373.3 1/2 800 32,693.2 ± 16,719.5 0.5 (0.5-0.75) 42,716.6 1/3 1400 97,544.6 ± 15,381.2 0.5 (0.5-0.75) 144,017.1 1/4 2000 121,937.6 ± 63,321.7 0.75 (0.5-1.5) 212,919.3 2/1 None NA NA NA 2/2 200 9,163.3 ± 2,980.5 0.5 (0.25-0.5) 10,005.2 2/3 600 33,184.6 ± 13,303.8 0.5 (0.25-0.75) 36,659.9 3/1 300 8,656.9 ± 6,617.9 0.5 (0.25-0.75) 8,738.8 3/2 450 20,101.7 ± 9,344.9 0.5 (0.25-4.0) 25,948.0 3/3 100 5,168.4 ± 4,332.9 0.25 (0.25-1.0) 4,708.6 3/4 None NA NA NA Insulin Pharmacokinetics Individual plasma-concentrations of insulin following all treatments were tabulated. Mean (+SD) plasma insulin concentration/time profiles for non-hypoglycemic subjects following the administration of treatments are shown in FIGS. 3A-C and 4A-B. FIGS. 3A, 3B and 3C show mean (+SD) plasma insulin concentration/time profile following the administration of 150 Units/200 mg (Insulin/4-CNAB) (n=5), 100 Units/600 mg (n=7), 10 Units SC insulin (n=8) and oral placebo (n=10) treatment in non-hypoglycemic subjects (Group 2) (FIG. 3C shows this profile using unaudited data). FIGS. 4A and 4B show Mean (+SD) plasma insulin concentration/time profiles following the administration of 100 Units/300 mg (Insulin/4-CNAB) (n=7), 100 Units/450 mg (n=7), 150 Units/100 mg (n=8), 150 Units USP oral insulin (n=8) and oral placebo (n=10) treatment in non-hypoglycemic subjects (Group 3). Mean insulin concentrations in non-hypoglycemic subjects reached peak levels between 0.4 and 0.6 hours following dosing before declining steeply to return to baseline levels after approximately 1 h. Increases in insulin absorption and exposure were observed with increasing doses (when changing from the 150 Units Insulin/100 mg 4-CNAB treatment to the 150 Units Insulin/200 mg 4-CNAB treatment) as expected. Based on Cmax and AUC values it was clear that the combined Insulin/4-CNAB treatments enabled insulin absorption significantly compared to 150 Units oral insulin alone and oral placebo. There was no insulin absorption when 150 Units insulin was dosed alone. Following 10 Units SC insulin, the mean profile for insulin concentrations was erratic, with two peak concentrations of approximately 300 pmol/L occurring at around 2 and 4 hours post-dose. Mean values±SD of insulin PK parameters for all subjects, non-hypoglycemic subjects and hypoglycemic subjects for each treatment are given in the Tables 11 and 12 below. TABLE 11 PK Parameters of insulin following dosing of subjects in Group 2 Insulin (Units)/4-CNAB (mg) Parameter 150/200 100/600 10 Units SC Oral Placeboc All Subjects N 8 8 8 11 Cmaxa (pmol/L) 226.9 ± 174.8 159.3 ± 125.6 374.8 ± 141.7 90.7 ± 91.3 tmaxa (h) 0.42 (0.17-1.75) 0.33 (0.25-1.50) 1.88 (1.58-4.00) 0.50 (0.00-6.00) AUC(0-2) (pmol · h/L) 180.68 ± 173.6 106.9 ± 101.6 414.3 ± 181.5 66.0 ± 22.5 AUC(0-6) (pmol · h/L) 366.8 ± 367.1 212.4 ± 187.0 1228.5 ± 378.1 222.9 ± 127.4 Non-hypoglycemic N 5 7 — 10 Subjects Cmaxa (pmol/L) 114.6 ± 75.7 120.1 ± 64.2 NA 77.0 ± 83.5 tmaxa (h) 0.33 (0.17-0.45) 0.33 (0.25-0.42) NA 0.50 (0.00-6.00) AUC(0-2) (pmol · h/L) 57.2 ± 16.5 72.5 ± 30.5 NA 66.4 ± 23.6 AUC(0-6) (pmol · h/L) 103.3 ± 30.9 149.7 ± 63.5 NA 202.9 ± 114.7 Hypoglycemic N 3 1 8 1 Subjects Cmaxa (pmol/L) 414.0 ± 106.7 NA 374.8 ± 141.7 NA tmaxa (h) 0.58 (0.42-1.75) NA 1.88 (1.58-4.00) NA AUC(0-2) (pmol · h/L) 386.6 ± 56.6 NA 414.3 ± 181.5 NA AUC(0-6) (pmol · h/L) 805.8 ± 84.6 NA 1228.5 ± 378.1 NA Cb (pmol/L) 62.0 ± 25.5 NA 168.3 ± 77.5 NA tb (h) 1.00 (0.62-1.00) NA 1.00 (0.75-1.25) NA In Table 11: values are given as Mean ± SD (except tmax, where median (range) is given). aMaximum concentration and corresponding time insulin concentration up to 6 hr. bInsulin concentration and corresponding time immediately prior to recovery from hypoglycemia. cOral placebo values combined for Groups 2 and 3. NA = not applicable; either 2 subjects or less. TABLE 12 PK Parameters of insulin following dosing of subjects in Group 3 Insulin (Units)/4-CNAB (mg) 150 Oral Insulin Units Oral Parameter 100/300 100/450 150/100 Alone Placebob All Subjects N 8 8 8 8 11 Cmaxa 91.0 ± 63.4 152.5 ± 123.5 95.6 ± 43.1 38.4 ± 12.8 90.7 ± 91.3 (pmol/L) tmaxa (h) 0.29 0.38 0.25 0.43 0.50 (0.08-1.53) (0.25-3.02) (0.18-0.28) (0.17-3.00) (0.00-6.00) AUC(0-2) 80.5 ± 55.6 108.5 ± 91.9 69.1 ± 20.5 51.8 ± 15.5 66.0 ± 22.5 (pmol · h/L) AUC(0-6) 182.0 ± 73.3 279.2 ± 309.0 163.8 ± 56.9 135.2 ± 47.1 222.9 ± 127.4 (pmol · h/L) Non- N 7 7 8 8 10 Hypoglycemic Cmaxa 69.7 ± 21.4 112.4 ± 53.1 95.6 ± 43.1 38.4 ± 12.8 77.0 ± 83.5 Subjects (pmol/L) tmaxa (h) 0.25 0.33 0.25 0.43 0.50 (0.08-0.42) (0.25-0.42) (0.18-0.28) (0.17-3.00) (0.00-6.00) AUC(0-2) 61.3 ± 12.6 78.3 ± 36.2 69.1 ± 20.5 51.8 ± 15.5 66.4 ± 23.6 (pmol · h/L) AUC(0-6) 167.3 ± 62.3 173.4 ± 83.1 163.8 ± 56.9 135.2 ± 47.1c 202.9 ± 114.7 (pmol · h/L) In Table 12: values are given as Mean ± SD (except tmax, where median (range) is given). aMaximum concentration and corresponding time insulin concentration up to 6 hr. bOral placebo values combined for Groups 2 and 3. cValue corresponds to AUC(0-t) for 6 h sampling schedule. NA = not applicable; either two subjects or less. Mean Cmax insulin values in non-hypoglycemic subjects following 100 Units Insulin/300 mg 4-CNAB, 100 Units Insulin/450 mg 4-CNAB and 100 Units Insulin/600 mg 4-CNAB were 69.9±21.4 pmol/L, 112.4±53.1 pmol/L and 120.1±64.2 pmol/L, respectively. The times of peak insulin concentrations ranged between approximately 0.1 and 0.4 h for all Insulin/4-CNAB combined treatments. The insulin concentration was lowest following 150 USP Units oral insulin alone indicating no absorption of insulin when oral administration of insulin alone was administered. Mean Cmax insulin values for all subjects (non-hypoglycemic and hypoglycemic subjects) were highly variable. Following 100 Units Insulin/300 mg 4-CNAB, 100 Units Insulin/450 mg 4-CNAB and 100 Units Insulin/600 mg 4-CNAB, mean Cmax values were 91.0±63.4 pmol/L, 152.5±123.5 pmol/L, and 159.3±125.6 pmol/L, respectively. The median times of peak insulin concentrations ranged between approximately 0.25 and 0.4 h for all Insulin/4-CNAB combined treatments. Individual C-peptide plasma concentrations following treatments were calculated. Pharmacokinetic parameters of C-peptide corrected insulin following dosing of subjects in Group 2 are summarized below in Table 13. TABLE 13 PK Parameters of C-peptide corrected insulin (Group 2) Insulin (Units)/4-CNAB (mg) Parameter 150/200 100/600 10 Units SC Oral Placeboc All Subjects N 8 8 8 11 Cmaxa (pmol/L) 186.9 ± 137.2 118.7 ± 87.7 304.5 ± 130.9 56.3 ± 90.4 tmaxa (h) 0.42 0.33 1.88 0.30 (0.17-1.75) (0.33-1.50) (1.50-4.00) (0.00-6.00) AUC(0-2) (pmol · h/L) 116.1 ± 126.5 50.0 ± 60.15 355.2 ± 170.2 7.4 ± 25.0 AUC(0-6) (pmol · h/L) 146.9 ± 193.0 47.4 ± 75.3 942.8 ± 333.0 53.5 ± 132.5 Non- N 5 7 — 10 hypoglycemic Cmaxa (pmol/L) 97.5 ± 75.8 95.0 ± 61.0 NA 46.3 ± 88.7 Subjects tmaxa (h) 0.33 0.33 NA 0.30 (0.17-0.45) (0.25-0.42) (0.00-6.00) AUC(0-2) (pmol · h/L) 25.9 ± 20.0 29.4 ± 15.5 NA 5.44 ± 25.4 AUC(0-6) (pmol · h/L) 11.1 ± 39.2 21.8 ± 22.1 NA 37.1 ± 127.3 Hypoglycemic N 3 1 8 1 Subjects Cmaxa (pmol/L) 335.8 ± 34.16 NA 304.5 ± 130.9 NA tmaxa (h) 0.58 NA 1.88 NA (0.42-1.75) (1.50-4.00) AUC(0-2) (pmol · h/L) 266.5 ± 31.0 NA 355.2 ± 170.2 NA AUC(0-6) (pmol · h/L) 373.4 ± 65.2 NA 942.8 ± 333.0 NA Cb (pmol/L) 44.2 ± 31.25 NA 159.5 ± 75.6 NA tb (h) 1.00 NA 1.00 NA (0.62-1.00) (0.75-1.25) NA In Table 13, values are given as Mean ± SD (except tmax, where median (range) is given) and aMaximum concentration and corresponding time C-peptide corrected insulin concentration up to 6 hr. bC-peptide corrected Insulin concentration and corresponding time immediately prior to recovery from hypoglycemia. cOral placebo values combined for Groups 2 and 3. NA-not applicable; either 2 subjects or less. Pharmacokinetic parameters of C-peptide corrected insulin following dosing of subjects in Group 3 are summarized below in Table 14: TABLE 14 PK Parameters of C-peptide corrected insulin (Group 3) Insulin (Units)/4-CNAB (mg) 150 Oral Insulin Parameter 100/300 100/450 150/100 Units Alone Oral Placebob All Subjects N 8 8 8 7 11 Cmaxa 63.8 ± 61.1 109.4 ± 83.2 66.6 ± 41.7 16.0 ± 7.5 56.3 ± 90.4 (pmol/L) tmaxa (h) 0.42 0.38 0.25 2.00 0.30 (0.17-1.53) (0.25-3.02) (0.18-6.02) (0.17-2.50) (0.00-6.00) AUC(0-2) 32.9 ± 57.4 47.7 ± 64.8 15.2 ± 16.2 10.8 ± 16.6 7.4 ± 25.0 (pmol · h/L) AUC(0-6) 49.7 ± 92.2 81.5 ± 185.6 10.9 ± 35.2 21.5 ± 42.0 53.5 ± 132.5 (pmol · h/L) Non- N 7 7 8 7 10 Hypoglycemic Cmaxa 45.1 ± 33.5 84.1 ± 46.1 66.6 ± 41.7 16.0 ± 7.5 46.3 ± 88.7 Subjects (pmol/L) tmaxa (h) 0.42 0.33 0.25 2.00 0.30 (0.17-0.50) (0.25-0.50) (0.18-6.02) (0.17-2.50) (0.00-6.00) AUC(0-2) 15.4 ± 31.4 25.7 ± 19.8 15.2 ± 16.2 10.8 ± 16.6 5.44 ± 25.4 (pmol · h/L) AUC(0-6) 37.4 ± 92.2 16.8 ± 33.0 10.9 ± 35.2 21.5 ± 42.0 37.1 ± 127.3 (pmol · h/L) In Table 14, values are given as Mean ± SD (except tmax, where median (range) is given) and: aMaximum concentration and corresponding time insulin concentration up to 6 hours. bOral placebo values combined for Groups 2 and 3. FIG. 5 shows the mean (+SD) plasma C-peptide concentration/time profile after oral dosing of 4-CNAB alone, Placebo and 150 U human insulin alone (Group 1). FIG. 6 shows the mean (+SD) plasma C-peptide concentration/time profiles following the administration of 150 Units/200 mg (Insulin/4-CNAB), 100 Units/600 mg, 10 Units SC insulin and oral placebo treatment in non-hypoglycemic subjects (Group 2), except for SC insulin where mean profile is for hypoglycemic subjects. FIG. 8 shows the mean (+SD) plasma C-peptide concentration/time profiles following the administration of 100 Units/300 mg (Insulin/4-CNAB), 100 Units/450 mg, 150 Units/100 mg, 150 Units USP Insulin and oral placebo treatment profiles in non-hypoglycemic subjects (Group 3). FIG. 7 shows mean (+SD) C-peptide concentration percent change from baseline/time profiles for subjects Group 2 following the administration of treatments. Mean Cmax values of C-peptide corrected insulin for all subjects achieved following 150 Units/200 mg and 100 Units/600 mg treatments were 186.9±137.2 pmol/L and 118.7±87.7 pmol/L, respectively. For non-hypoglycemic subjects, following treatments containing 100 Units/300 mg, 100 Units/450 mg and 100/600 mg, there appeared to be a dose-dependent relationship in terms of C-peptide corrected insulin exposure based on Cmax and AUC0-2 values with increasing doses of 4-CNAB. An increase in insulin exposure was also observed when changing from the 150 Units Insulin/100 mg 4-CNAB treatment to the 150 Units Insulin/200 mg 4-CNAB treatment. Mean C-peptide concentrations declined almost immediately following dosing of the combined Insulin/4-CNAB treatments achieving the greatest decline between 0.5 and 1.0 hours. Concentrations then appeared to return to baseline levels after approximately 2 hours following dosing. Following oral placebo and 150 Units oral insulin alone there was little change in C-peptide concentrations from baseline. The mean profile following 10 Units SC insulin is for subjects who experienced hypoglycemia (8 out of 8 subjects) and were given food/drink in order to increase their blood glucose levels. C-peptide is a byproduct of endogenous insulin excretion. After giving oral insulin, the oral insulin suppresses the production of endogenous insulin, and it leads to decline of c-peptide production. The decrease of the C-peptide levels after oral administration of insulin/4-CNAB, and litter change of C-peptide levels after insulin alone or placebo dosing, clearly demonstrated effective absorption of human insulin in this study. Following administration of 10 Units of SC insulin, all eight subjects required hypoglycemic recovery with food/drink and hence it was impossible to calculate relative bioavailability and potency for the combined oral Insulin/4-CNAB treatments. Typically, the median times of peak concentrations were around 0.3-0.4 h for all treatments except for 150 USP oral insulin alone and for SC insulin, which had median tmax times of approximately 2.00 hours. From these data, it was clear that little of the 150 USP oral insulin was absorbed. The lack of insulin absorbed following 150 USP oral insulin alone compared to the Insulin/4-CNAB treatments indicates the effectiveness of the oral delivery agent 4-CNAB on oral absorption of human insulin. For the Insulin/4-CNAB combined treatments containing 100 Units insulin, there appeared to be a dose-dependent relationship in terms of C-peptide corrected insulin absorption and exposure based on Cmax and AUC(0-2) values with increasing doses of 4-CNAB. Increases in insulin absorption and exposure were also observed for the 150 Units insulin doses (when changing from the 150 Units Insulin/100 mg 4-CNAB treatment to the 150 Units Insulin/200 mg 4-CNAB treatment) as expected. Based on Cmax and AUC values, it was clear that the combined Insulin/4-CNAB treatments enabled significant insulin absorption as compared to 150 Units oral insulin alone and oral placebo. Based upon the above data, the following pharmacokinetic conclusions can be drawn: The exposure to 4-CNAB increased with increasing doses of 4-CNAB alone. The exposure to 4-CNAB appeared to increase with increasing doses of 4-CNAB in the combined Insulin/4-CNAB treatments with the exception of 100 Units Insulin/300 mg 4-CNAB treatment. The exposure to C-peptide corrected insulin increased with increasing proportions of 4-CNAB as part of the treatment. There was no absorption of insulin following oral administration of 150 Units oral insulin alone. Oral absorption of insulin was greatest following administration of the combined treatments containing 150 Units Insulin/200 mg 4-CNAB and 100 Units Insulin/600 mg 4-CNAB. Pharmacodynamic Results FIGS. 9A and 9B show the mean (+SD) glucose concentration/time profiles following the administration of 150 Units/200 mg (Insulin/4-CNAB) (n=5), 100 Units/600 mg (n=7), 10 Units SC insulin (n=8) and oral placebo (n=10) treatment in non-hypoglycemic subjects (Group 2). FIGS. 10A and 10B show the mean (+SD) glucose concentration/time profiles following the administration of 100 Units/300 mg (Insulin/4-CNAB) (n=7), 100 Units/450 mg (n=7), 150 Units/100 mg (n=8), 150 Units USP oral insulin (n=8) and oral placebo (n=10) treatment in non-hypoglyceric subjects (Group 3). Mean glucose concentrations began to decline after approximately 0.2 hours following dosing of the combined Insulin/4-CNAB treatments, Rmax of the combined Insulin/4-CNAB treatments was observed to be between 0.5 and 1.0 hours following dosing. Concentrations then appeared to return to baseline levels after approximately 2 hours following dosing. Following oral placebo and 150 Units oral insulin alone there was only a slight change in glucose concentrations indicating little absorption of insulin. The mean profile following 10 SC Units of insulin is for subjects who experienced hypoglycemia (8 out of 8 subjects) and were given food/drink in order to increase their blood glucose levels. Individual PD parameters of glucose following all treatments for hypoglycemic and non-hypoglycemic subjects were listed together with descriptive statistics. Individual plasma glucose concentration changes from baseline were tabulated, and individual glucose concentration changes from baseline/time profiles were prepared. Mean values±SD of glucose PD parameters for all subjects, non-hypoglycemic subjects and hypoglycemic subjects for each treatment are given in Tables 15 and 16 below and profiles are shown in FIGS. 9A-B and 10A-B. TABLE 15 PD Parameters of plasma glucose (Group 2) Insulin (Units)/4-CNAB (mg) Parameter 150/200 100/600 10 Units SC Oral Placeboc All Subjects N 8 8 8 11 Rmaxa (mmol/L) 3.95 ± 0.80 4.65 ± 0.30 3.31 ± 0.42 5.03 ± 0.23 tRmaxa (h) 0.63 0.58 1.00 6.0 (0.58-3.00) (0.50-6.00) (0.67-3.00) (0.33-6.00) AURC(0-2) (mmol · h/L) 11.2 ± 1.8 10.85 ± 0.68 10.40 ± 1.36 11.10 ± 0.72 AURC(0-6) (mmol · h/L) 33.3 ± 2.6 31.88 ± 1.23 32.02 ± 4.66 32.55 ± 2.41 Non- N 5 7 None 10 hypoglycemic Rmaxa (mmol/L) 4.40 ± 0.45 4.66 ± 0.32 NA 5.02 ± 0.24 Subjects tRmaxa (h) 0.58 0.58 NA 6.0 (0.58-3.00) (0.50-6.00) (0.33-6.00) AURC(0-2) (mmol · h/L) 10.42 ± 2.19 10.66 ± 0.43 NA 10.95 ± 0.55 AURC(0-6) (mmol · h/L) 31.60 ± 0.87 31.78 ± 1.28 NA 31.94 ± 1.40 Hypoglycemic N 3 1 8 1 Subjects Rmaxa (mmol/L) 3.20 ± 0.69 NA 3.31 ± 0.42 NA tRmaxa (h) 1.00 NA 1.00 NA (0.58-1.00) (0.67-3.00) AURC(0-2) (mmol · h/L) 12.47 ± 2.81 NA 10.40 ± 1.36 NA AURC(0-6) (mmol · h/L) 36.03 ± 1.88 NA 32.02 ± 4.66 NA Rb (mmol/L) 3.23 ± 0.75 NA 3.45 ± 0.41 NA tb (h) 1.00 NA 1.00 NA (0.62-1.00) (0.75-1.25) In Table 15, values are given as Mean ± SD (except tmax, where median (range) is given) and aMinimum concentration and corresponding time in blood glucose concentration up to 6 hr post-dose. bGlucose concentration and corresponding time immediately prior to recovery from hypoglycemia. cOral placebo values combined for Groups 2 and 3. NA—not applicable; either 2 subjects or less. TABLE 16 PD Parameters of plasma glucose (Group 3) Insulin (Units)/4-CNAB (mg) 150 Oral Insulin Parameter 100/300 100/450 150/100 Units Alone Oral Placebob All Subjects N 8 8 8 8 11 Rmaxa 4.93 ± 0.55 4.58 ± 0.49 5.01 ± 0.20 5.08 ± 0.20 5.03 ± 0.23 (mmol/L) tRmaxa (h) 0.63 0.67 0.71 6.00 6.0 (0.08-6.00) (0.50-6.00) (0.50-6.00) (0.62-6.00) (0.33-6.00) AURC(0-2) 11.10 ± 0.66 10.77 ± 0.81 11.02 ± 0.47 11.06 ± 0.69 11.10 ± 0.72 (mmol · h/L) AURC(0-6) 32.6 ± 1.75 32.34 ± 2.90 32.39 ± 0.92 32.15 ± 1.41 32.55 ± 2.41 (mmol · h/L) Non-Hypoglycemic N 7 7 8 8 10 Subjects Rmaxa 5.07 ± 0.39 4.71 ± 0.32 5.01 ± 0.20 5.08 ± 0.20 5.02 ± 0.24 (mmol/L) tRmaxa (h) 0.67 0.67 0.71 6.00 6.0 (0.08-6.00) (0.50-6.00) (0.50-6.00) (0.62-6.00) (0.33-6.00) AURC(0-2) 11.19 ± 0.69 10.57 ± 0.64 11.02 ± 0.47 11.06 ± 0.69 10.95 ± 0.55 (mmol · h/L) AURC(0-6) 32.91 ± 1.50 31.47 ± 1.61 32.39 ± 0.92 32.15 ± 1.41c 31.94 ± 1.40 (mmol · h/L) In Table 16, values are given as Mean ± SD (except tmax, where median (range) is given) and aMinimum concentration and corresponding time in plasma insulin concentration up to 6 hr post-dose. bOral placebo values combined for Groups 2 and 3. cValue corresponds to AURC(0-t) for 6 h sampling schedule. Following the combined Insulin/4-CNAB treatments, plasma glucose concentrations declined rapidly until approximately 0.75 h, then gradually increased to return to baseline levels after about 2.00 hour post-dose. From the profiles above, the maximum glucose concentration change from baseline for the Insulin/4-CNAB combination occurred following 150 Units Insulin/200 mg 4-CNAB. The treatment that had the next greatest effect on glucose appeared to be the 100 Units/600 mg 4-CNAB treatment. These findings correlated well with the peak concentrations of C-peptide corrected insulin levels achieved following these two treatments (See Table 12). Subjects who received 10 Units of SC insulin experienced the greatest decline in glucose concentrations, which hence lead to hypoglycemic response and recovery, by intervention with food/drink intake. Individual PD parameters for glucose percent changes from baseline following all treatments for hypoglycemic and non-hypoglycemic subjects were tabulated and individual glucose concentration percent changes from baseline-time profiles were created, together with descriptive statistics. Mean values±SD of glucose change from baseline PK parameters for all subjects, non-hypoglycemic subjects and hypoglycemic subjects for treatment Groups 2 and 3 are given in the Tables 17 and 18 below. Mean (+SD) glucose concentration percent change from baseline/time profiles for non-hypoglycemic subjects following the administration of treatments are shown in FIGS. 11A-11C (Group 2) (FIG. 11C shows this profile using unaudited data) and FIG. 12 (Group 3), except for SC insulin where mean profile is for hypoglycemic subjects. In addition, the mean maximum percentage change from baseline up to 6 hours post-dose is also given in these tables below. TABLE 17 PD Parameters for Change in plasma glucose from baseline (Group 2) Insulin (Units)/4-CNAB (mg) Parameter 150/200 100/600 10 Units SC Oral Placeboc All Subjects N 8 8 8 11 Emaxa (mmol/L) −1.65 ± 1.08 −0.88 ± 0.48 −2.28 ± 0.40 −0.54 ± 0.21 % Changeb −28.64 ± 17.80 −15.92 ± 7.30 −39.82 ± 8.26 −8.05 ± 6.23 tEmaxa (h) 0.68 0.58 1.00 6.00 (0.58-3.00) (0.50-0.83) (0.75-3.00) (0.33-6.00) AUEC(0-2) (mmol · h/L) −0.01 ± 1.59 −0.25 ± 0.86 −0.71 ± 1.32 0.05 ± 0.52 AUEC(0-6) (mmol · h/L) −0.35 ± 1.72 −2.11 ± 5.24 −1.40 ± 4.41 −0.65 ± 2.07 Non- N 5 7 — 10 hypoglycemic Emaxa (mmol/L) −1.02 ± 0.70 −0.89 ± 0.51 NA −0.54 ± 0.22 Subjects % Changeb −18.34 ± 11.85 −16.08 ± 7.87 NA −9.49 ± 3.67 tEmaxa (h) 0.67 0.58 NA 6.00 (0.58-3.00) (0.50-0.83) (0.33-6.00) AUEC(0-2) (mmol · h/L) −0.42 ± 0.63 −0.49 ± 0.59 NA −0.09 ± 0.27 AUEC(0-6) (mmol · h/L) −0.94 ± 1.37 −1.66 ± 1.74 NA −1.22 ± 0.93 Hypoglycemic N 3 1 8 — Subjects Emaxa (mmol/L) −2.70 ± 0.66 NA −2.28 ± 0.40 NA % Changeb −45.80 ± 11.02 NA −39.82 ± 8.26 NA tEmaxa (h) 1.00 NA 1.00 NA (0.62-1.00) (0.75-3.00) AUEC(0-2) (mmol · h/L) −2.70 ± 0.66 NA NA NA AUEC(0-6) (mmol · h/L) 1.00 NA 1.00 NA (0.62-1.00) (0.75-1.25) Ec (mmol/L) 0.67 ± 2.64 NA −0.71 ± 1.32 NA tc (h) 0.63 ± 2.06 NA −1.40 ± 4.41 NA In Table 17, values are given as Mean ± SD (except tmax, where median (range) is given) and: aMaximum change from baseline and corresponding time up to 6 h = (Glucose Concentration − Baseline Concentration). bMaximum % change from baseline up to 6 h = (Glucose Concentration − Baseline Concentration/Baseline Concentration*100). cGlucose concentration change from baseline and corresponding time immediately prior to recovery from hypoglycemia. dOral placebo values combined for Groups 2 and 3. NA—not applicable; either 2 subjects or less. TABLE 18 PD Parameters for Change in glucose concentration baseline (Group 3) Insulin (Units)/4-CNAB (mg) 150 Oral Insulin Oral Parameter 100/300 100/450 150/100 Units Alone Placebob All Subjects N 8 8 8 7 11 Emaxa −0.75 ± 0.50 −0.94 ± 0.46 −0.66 ± 0.21 −0.79 ± 0.43 −0.54 ± 0.21 (mmol/L) % Changeb −14.19 ± 9.98 −16.98 ± 8.28 −11.62 ± 3.28 −12.41 ± 6.48 −8.05 ± 6.23 tEmaxa (h) 0.69 0.67 3.42 6.00 6.00 (0.08-6.02) (0.50-6.00) (0.50-6.02) (0.67-6.00) (0.33-6.00) AUEC(0-2) −0.26 ± 0.41 −0.26 ± 0.63 −0.29 ± 0.34 −0.63 ± 0.77 0.05 ± 0.52 (mmol · h/L) AUEC(0-6) −1.50 ± 1.41 −0.73 ± 2.67 −1.59 ± 1.16 −3.01 ± 2.44d −0.65 ± 2.07 (mmol · h/L) Non- N 7 7 8 7 10 Hypoglycemic Emaxa −0.26 ± 0.96 −0.80 ± 0.27 −0.66 ± 0.21 −0.79 ± 0.43 −0.54 ± 0.22 Subjects (mmol/L) % Changeb −12.64 ± 9.70 −14.47 ± 4.60 −11.62 ± 3.28 −12.41 ± 6.48 −9.49 ± 3.67 tEmaxa (h) 4.00 0.67 3.42 6.00 6.00 (0.10-6.00) (0.50-6.00) (0.50-6.02) (0.67-6.00) (0.33-6.00) AUEC(0-2) −0.31 ± 0.41 −0.46 ± 0.32 −0.29 ± 0.34 −0.63 ± 0.77 −0.09 ± 0.27 (mmol · h/L) AUEC(0-6) −1.54 ± 1.51 −1.61 ± 0.98 −1.59 ± 1.16 −3.01 ± 2.44d −1.22 ± 0.93 (mmol · h/L) In Table 18: aMaximum change from baseline and corresponding time up to 6 h = (Glucose Concentration − Baseline Concentration). bMaximum % change from baseline up to 6 h = (Glucose Concentration − Baseline Concentration/Baseline Conc). cOral placebo values combined for Groups 2 and 3. dValue corresponds to AUEC(0-t) for 6 h sampling schedule. Table 19 below shows a comparison of the effects of the insulin and 4-CNAB combinations in Groups 2 and 3, based upon unaudited data. TABLE 19 Comparison of Effects of Oral Insulin (Groups 2 and 3) Basal Insulin Insulin % Max % Max Insulin Carrier # of Insulin tmax Cmax Glucose C-peptide (Units) (Mg) Subjects (uU/ml) (Min) (uU/ml) Reduction Reduction 10 (SC) 0 8 4.3 ± 2.5 105 54.5 ± 25.6 32.3 ± 9.6 54.3 ± 9.8 150 (PO) 200 8 4.1 ± 1.9 25 26.6 ± 18.2 23.7 ± 13.2 37.5 ± 16.9 100 (PO) 600 8 4.4 ± 2.3 20 18.1 ± 11.3 14.6 ± 7.5 33.1 ± 13.0 100 (PO) 300 8 3.8 ± 3.4 25 9.5 ± 6.3 8.8 ± 10.2 21.7 ± 16.2 100 (PO) 450 8 5.1 ± 2.2 20 19.1 ± 9.0 14.5 ± 8.0 32.6 ± 12.7 150 (PO) 100 8 4.8 ± 1.8 15 14.5 ± 7.7 8.8 ± 5.1 17.9 ± 13.1 The greatest change from baseline of glucose based on Emax was produced by the 150 Units/200 mg followed by the 100 Units/600 mg and 100 Units/450 mg treatments giving values of −1.0±0.7 mmol/L, −0.9±0.5 mmol/L and −0.8±0.3 mmol/L, respectively in non-hypoglycemic subjects. The effect of insulin on maximum glucose change from baseline appeared to increase with increasing doses of 4-CNAB and plasma concentrations of C-peptide corrected insulin, ranging between −0.3±1.0 mmol/L and −0.9±0.5 mmol/L for 100 Units Insulin/300 mg 4-CNAB and 100 Units Insulin/600 mg 4-CNAB treatments, respectively. In general, there was a good correlation between increasing Insulin/4-CNAB doses and C-peptide corrected plasma insulin concentrations and maximum plasma glucose percent reduction from baseline. The greatest percent reduction in plasma glucose concentration was achieved after oral dosing of the 150 Units/200 mg treatment followed by the 100 Units/450 mg and 100 Units/600 mg treatments giving maximum percent reduction values of −28.64±17.80%, −16.98±8.28% and −15.92±7.30%, respectively. For these treatments, similar AUEC(0-2) values were observed, all approximately −0.4 mmol.h/L as well as similar tEmax median times of approximately 0.6 h. Maximum % reduction in glucose concentrations from baseline increased with increasing doses of 4-CNAB, with values ranging between −12.6 and −16.1% for the 100 Units Insulin/300 mg 4-CNAB and 100 Units Insulin/600 mg 4-CNAB treatments, respectively. A similar good correlation was observed between maximum glucose percent change (reduction from baseline) and Insulin/4-CNAB doses and C-peptide corrected insulin concentrations. The greatest percent change (decline) in glucose levels was produced in subjects receiving 10 Units SC insulin (−39.82±8.26%), (Emax: −2.28±0.5 mmol/L) which led to the need for hypoglycemic recovery, and in subjects receiving oral dose of 150 Units/200 mg (−28.64±17.80 Based upon the above data, the following pharmacodynamic conclusions can be drawn: The effect of insulin on the mean maximum glucose concentration change from baseline (Emax) appeared to increase with increasing doses of 4-CNAB as part of the combined treatments. In general an increasing effect on glucose concentration change from baseline and glucose concentration percent change from baseline were observed with increasing Insulin/4-CNAB doses and C-peptide corrected insulin concentrations. Based on the mean maximum glucose concentration change from baseline (Emax), 100 Units Insulin/600 mg 4-CNAB and 150 Units Insulin/200 mg 4-CNAB appeared to elicit a greater PD response compared to oral placebo and 150 Units oral insulin alone, indicating the effectiveness of the deliver agent in delivering insulin. The effect of any of the oral Insulin/4-CNAB combinations in lowering glucose levels was less than that observed for SC insulin. Discussion and Overall Conclusions There were no deaths or serious adverse effects in this study. All subjects passed screening and completed the study, and none withdrew from the study for study drug related reasons. There were no clinically significant abnormal results as assessed by vital signs, ECG, clinical laboratory parameters (except blood glucose) and physical examination. There were 42 adverse effects (AEs) following treatments that were thought to be related to study drug. Oral administration of 4-CNAB alone was well tolerated. The safety profiles following 4-CNAB alone were very good with very few AEs. Most treatment-related AEs were reported following 150 Units Insulin/200 mg 4-CNAB (n=7) and after 100 Units Insulin/450 mg 4-CNAB (n=6) in addition to sixteen events following 10 Units SC insulin. Forty-one of the total treatment related 42 AEs were classified as mild in severity. The most common treatment-emergent AEs reported during the study were hypoglycemia (26), headache (12) and dizziness (5). During the 26 episodes of hypoglycemia, subjects required rescue treatment on twenty occasions, i.e., food/drink in order to raise their blood glucose, on twenty occasions. Of these, twelve were following 10 Units SC insulin and there were following 150 Units Insulin/200 mg 4-CNAB. The exposure to 4-CNAB appeared to increase with increasing doses of 4-CNAB when given alone. Oral administration of 4-CNAB alone had no significant effect on plasma glucose levels in human subjects. C-peptide corrected plasma insulin increased with increasing doses of 4-CNAB, demonstrating effective oral delivery and absorption of human insulin. Mean 4-CNAB peak plasma concentrations and AUC appeared to increase with increasing doses of 4-CNAB either when given alone or as part of the Insulin/4-CNAB treatments, with the exception of the 100 Units Insulin/300 mg 4-CNAB treatment. The median time of maximum 4-CNAB concentration was similar (around 0.6 hours) for 4-CNAB alone and when given as the combined Insulin/4-CNAB treatment. The half-life of 4-CNAB was highly variable when given alone but more consistent with a half-life value of around 4 hours when given with insulin. The variability in the half-life was due to the variable in the terminal elimnation phase and difficulty in estimating the elimination rate constants. However, the MRT values were more consistent and ranged from 1.4 to 1.8 hours for all treatments The oral absorption and exposure of insulin based on Cmax and AUC(0-2) increased with increasing doses of 4-CNAB, indicating effective absorption of insulin with increasing levels of 4-CNAB. The absorption and exposure to insulin following Insulin/4-CNAB treatments was clearly greater than when given 150 USP oral insulin alone. Based on the mean maximum percent plasma glucose reduction, the treatments 100 Units Insulin/600 mg 4-CNAB and 150 Units Insulin/200 mg 4-CNAB appeared to elicit a greater PD response compared to oral placebo or 150 Units oral insulin alone, indicating the effectiveness of the delivery agent in delivering insulin and producing a subsequent effect. Mean C-peptide corrected insulin Cmax ranged between 45.1±33.5 pmol/L, 95.0±61.0 pmol/L, and 97.5±75.8 pmol/L for doses of 100 Units Insulin/300 mg 4-CNAB, 100 Units Insulin/600 mg 4-CNAB, and 150 Units Insulin/200 mg 4-CNAB respectively. Unfortunately, because all eight subjects required rescue with food after 10 Units SC insulin due to hypoglycemia, it was difficult to obtain an accurate measure of insulin relative bioavailability of the Insulin/4-CNAB treatments compared to SC dosing. Increases in mean Emax and AUEC(0-2) were seen with increasing levels of 4-CNAB as part of Insulin/4-CNAB treatments and with increasing plasma concentrations of C-peptide corrected insulin.Mean maximum glucose % reduction from baseline ranged between −12.64±9.7% and −14.47±4.6% for the 100 Units Insulin/300 mg 4-CNAB and 100 Units Insulin/600 mg 4-CNAB treatments, respectively. The values for AUEC(O-2) ranged between −0.31±0.41 mmol.h/L and −0.49±0.59 for the 100 Units Insulin/300 mg 4-CNAB and 100 Units Insulin/600 mg 4-CNAB treatments, respectively. Thus, the effect of insulin on the mean maximum plasma glucose concentration change from baseline (Emax) increased with increasing doses of 4-CNAB and was significantly greater than oral insulin alone and placebo for all combined treatments indicating the effectiveness of the delivery agent in delivering insulin. In general, an increasing effect of oral insulin on plasma glucose concentration change from baseline and percent change from baseline was observed with increasing Insulin/4-CNAB doses. EXAMPLE 6 Comparison of Pharmacodynamic and Pharmacokinetic Properties of Oral Insulin vs. Subcutaneous (Sc) Regular Insulin in Type 2 Diabetic Patients A single-center, open-label, randomized, active controlled, 3-period crossover study was conducted in ten patients with type 2 diabetes in order to compare the pharmacodynamic (PD) and pharmacokinetic (PK) characteristics of an oral insulin formulation with SC regular insulin using the glucose clamp technique and in order to get a first impression about the metabolic effect of oral insulin in the main target population. The glucose clamp technique was applied to compare the time-action profiles of the orally applied insulin in comparison to SC regular insulin. This method utilizes negative feedback from frequent blood glucose sample values to adjust a glucose infusion to maintain a defined and constant blood glucose level. The glucose infusion rate therefore becomes a measure of the pharmacodynamic effect of any insulin administered. A primary objective of this study was to compare the PK and PD effect of two doses of an oral insulin capsule formulation (300 U Insulin/400 mg 4-CNAB in 2 capsules, and 150 U Insulin/200 mg 4-CNAB in one capsule) with that of 15 U SC injected regular insulin. Relative bioavailability and biopotency of the two oral formulations vs. SC injection was determined, inter-subject variability was investigated for selected PD and PK parameters. Male subjects between 35 and 70 years old, inclusive, with type 2 diabetes mellitus as defined by the American Diabetes Association (1998 Diabetes care, 21: S5-S19) for more than one year were chosen. Subjects included in the study had BMI<36 kg/m2, had stable glycemic control (HbA1C<11%), were off all oral hypoglycemic agents 24 hours prior to each study dosing day and off any investigational drug for at least four (4) weeks prior to Visit 1, refrained from strenuous physical activity beginning 72 hours prior to admission and through the duration of the study, and were confined to the clinical research unit as required by the protocol. Subjects maintained a constant body weight (+/−2 kg). At Visit 1, the subjects arrived at the clinic in a fasted state (no caloric intake for at least 12 hours). The subjects' height, weight, body mass index (BMI), vital signs and medical history were recorded, and a physical examination was done. An electrocardiogram (ECG) was performed for all subjects as well as local screening laboratory tests. The oral treatment provided was Insulin/4-CNAB (Monosodium N-(4-chlorosalicyloyl)-4-aminobutyrate (4-CNAB). The insulin used to prepare the capsules was Zinc-Insulin Crystals Human: Proinsulin Derived (Recombinant DNA Origin) USP Quality obtained from Eli Lilly and Company (Indianapolis, Ind.). Each Insulin/4-CNAB capsule contained 150 Insulin Units USP and 200 mg 4-CNAB, and was prepared by AAI Pharma, Inc., Wilmington, N.C. Two tablets were given to those who received the 300 U oral Insulin/400 mg 4-CNAB treatments. Insulin/4-CNAB capsules were provided in HDPE bottles, each of which contained 40 capsules and a polyester coil. Each bottle had a heat-induction seal and a child-resistant cap, and were stored frozen at or less than minus 10° C. On the day of dosing, the appropriate number of capsules was removed from the freezer and brought to room temperature (between 15 and 30° C.) for about one hour. Capsules were used within four hours of dispensing, and unopened bottles were not left at room temperature for more than four hours. The SC injection was U-100 human regular insulin (Humulin® R from Eli Lilly and Company), at a dose of 15 U, supplied in 1.5-mL cartridges-100 units/mL, provided by Profil. The Insulin was stored in the refrigerator within a temperature range of 5-8° C. At Visit 2, each subject was randomized to one of the two possible treatment sequences. Each subject received one of the two treatments during a glucose clamp procedure: an oral treatment (treatment A) of 300 U oral Insulin/400 mg 4-CNAB (in 2 capsules) or one SC treatment (treatment B) of 15 U regular SC insulin. At Visit 3, the subjects received the alternative treatment A or B, i.e., the one they did not receive in Visit 2, in conjunction with a glucose clamp procedure according to their randomization sequence. Only subjects having received both treatments by the end of Visit 3 were regarded as completers. A final examination (Visit 4) was performed after Visit 3, preferably immediately after the glucose clamp procedures were completed, but no longer than 14 days after Visit 3. All the subjects were invited to attend a third treatment day (Visit 5), on which they received another oral treatment (treatment C) of a single dose of 150 U of the oral Insulin/200 mg 4-CNAB (one capsule). Eight of ten patients received the treatment C. A “second” final medical examination (Visit 6) was performed after Visit 5, preferably immediately after the glucose clamp procedures were completed, but no longer than 14 days after Visit 5. The assignment of the treatments within each sequence is described in Table 21 below: TABLE 21 Treatment Treatment Period Sequence 1 (Visit 2) 2 (Visit 3) 3 (Visit 5) 1 A B C (optional) 2 B A C (optional) The SC insulin dose of 15 U was selected to fall within a range typical for type 2 diabetic patients. The oral dose of 150 U insulin (combined with 200 mg 4-CNAB) estimated to be equivalent to the SC dose was a 10-fold scale-up compared with the SC dose, based on previous investigational studies. The oral dose of 300 U insulin (combined with 400 mg 4-CNAB) was a 20-fold scale-up compared with the SC dose. Since the three treatments were single dose administrations, a cross-over design was the most appropriate in order to keep patient numbers low and to reduce data variability. SC injection of 15 U regular insulin is a common standard treatment and was therefore used as control. Two oral insulin doses were chosen to demonstrate a dose dependency of PK and PD parameters and to investigate whether or not the suppressive effect on hepatic glucose production could be seen also at the reduced oral dose of 150 U. All treatment periods started in the morning after an overnight fast of at least 12 hours. Dosing was performed following a period of 6 hrs of stabilization of the blood glucose by means of the glucose clamp. The subjects received the oral insulin capsules with 200 mL of water in an upright position. For s.c. insulin administration, a 29 gauge needle was inserted perpendicularly into a raised skinfold in the left lower quadrant of the abdominal wall, approximately 10 cm from the umbilicus. For oral insulin administration, the capsules were administered with 200 mL of water to the patients in an upright position. The total administration time did not exceed 2.5 minutes. Subjects remained upright for four hours after taking the study drug. During each study visit, stabilized individual blood glucose concentrations were maintained after drug administration using a glucose clamp procedure. The glucose clamp technique [DeFronzo, et al. 1979, Glucose Clamp Technique: A Method of Quantifying Insulin Secretion and Resistance, Am. J. Physiol. 237: E214-E223.] was use to compare the time-action profiles of the orally-applied insulin to s.c. insulin. This method utilizes negative feedback from frequent blood glucose sample values to adjust a glucose infusion to maintain euglycemia. The glucose infusion rate becomes a measure of the pharmacodynamic effect of any insulin administered. The patients' fasting blood glucose concentration at Visit 2 (measured before the baseline insulin infusion was established) was the target level for the glucose clamp experiments. At the following clamps, the fasting blood glucose concentrations were not allowed to differ more than 4 mmol/L (72 mg/dL) from this individualized clamp level, otherwise the visits were postponed for at least 24 hrs. In each treatment arm, all patients received the same SC or oral insulin dose. The patients' fasting blood glucose concentration, measured before the baseline insulin infusion was established, was the target level for the glucose clamp experiments. During the consecutive glucose clamp experiments, the fasting blood glucose concentration was not allowed to differ more than 4 mmol/L (72 mg/dL) from this individualized clamp level, otherwise the visits were postponed for at least 24 hrs. The clamp level was adjusted by a variable intravenous (IV) insulin infusion and glucose infusion rate during a 6 hour baseline period before dosing. During the last 2 hours before administration of the study medication, the insulin infusion was set to a rate of 0.2 mU/kg/min, which rate was not changed until the end of the experiment. At t=0 minutes, exogenous insulin was administered by oral administration or by SC injection. The PD response elicited by the study medication was registered for another 6 hours. No food intake was allowed during this period, but water could be consumed as desired. During each study period, blood samples were collected for the determination of plasma insulin concentrations, plasma C-peptide and plasma glucose concentration. Sampling occurred from 6 hrs before dosing and continued for 6 hrs after the dose was administered. Blood samples were collected via a venous cannula. Blood samples were collected relative to the administration of the study drug (1) prior to study of drug administration at −1 and −0.5 hrs, (2) immediately after study drug administration (time 0), and (3) post administration of the study drug at 10, 20, 30, 40, 50 min, and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 5, and 6 hrs The glucose clamp procedure was performed using a Biostator (glucose controlled insulin infusion system—GCIIS, Life Science Instruments, Elkhart, Ind., USA). A 17-gauge PTFE catheter was inserted into an antecubital vein for blood sampling and kept patent with 0.15 mol/L saline. A dorsal hand vein or lateral wrist vein of the same arm was cannulated in retrograde fashion for insertion of an 18-gauge PTFE double lumen catheter connected to the glucose sensor of the Biostator. The catheterized hand was placed in a hot box and warmed to an air temperature of 55° C. On the contralateral arm, a third vein was cannulated with an 18-gauge PTFE catheter to infuse a glucose solution (20% in water). Into the same vein, an insulin solution (regular human insulin in 0.15 mol/L saline diluted with 2 mL of the patient's blood per 100 mL) was continuously infused by means of a syringe pump (Perfusor Secura FT, Braun, Melsungen, Germany). Blood samples were collected from each patient during each treatment period for determination of plasma insulin concentrations, plasma C-peptide, and plasma glucose. Glucose infusion rates and blood glucose measurements were measured continuously during the glucose clamp procedure. All treatments were identical in their sample collection and monitoring periods for all visits. After a 6 hours pre-dose baseline period for stabilization of blood glucose concentrations at the desired clamp level, the clamp procedure after study drug administration lasted 6 hours. The blood samples were centrifuged at 3000 rpm for a period of fifteen minutes at a temperature between 2° C.-8° C., within one hour of sample collection. Using a plastic pipette and without disturbing the red cell layer, the plasma from the collection tube was pipetted in pre-labeled polypropylene tubes for each analysis of plasma insulin, C-peptide, and plasma glucose (approximately 0.3-0.5 μl each). The samples were stored at −20° C. until analysis. Safety was monitored by vital sign measurements and documentation of adverse events (AE) during all visits throughout the study. No food intake was permitted until the clamp procedure was completed but the patients were allowed to drink water ad libitum. After the last blood sample had been obtained, subjects were provided with a meal. During the study, insulin therapy and the chronic use of all agents that, in the evaluation of the investigator might have interfered with the interpretation of trial results or were known to cause clinically relevant interference with insulin action, glucose utilization or recovery from hypoglycemia, were prohibited. Intake of all oral hypoglycemic agents was stopped 24 hours prior to each study dosing day and was not resumed until the end of the clamp procedures. Blood glucose concentration and GIR determinations were made continuously from −6 hrs prior to administration of the study drug up to 6 hrs post-administration of the study drug by the Biostator. These data were recorded at 1-minute intervals throughout the treatment period. Safety assessments included AEs, laboratory data, vital signs, physical examinations and ECGs. Safety data and pharmacokinetic/pharmacodynamic data were analyzed for all subjects. Pharmacokinetic/pharmacodynamic data were also analyzed for the subset of 8 patients who received the third study treatment. Pharmacokinetic and pharmacodynamic data were statistically analyzed for subjects that received at least the first two treatments (visit 1 to 4) and for subjects who completed all three treatment visits (visit 1 to 6). The primary PD endpoint of the study was the area under the glucose infusion rate curve (AUCGIR) in the first hr after drug administration (AUCGIR 0-1h). The secondary endpoints for pharmacodynamic assessment were the following parameters: Maximum glucose infusion rate (GIRmax), time to GIRmax (tGIRmax), area under the glucose infusion rate curve in defined time-intervals (AUCGIR 0-2h, AUCGIP 0-3h, AUCGIR 0-4h, AUCGIR0-5h, AUCGIR 0-6h), time to early and late half-maximum glucose infusion rate (early and late TGIR 50%), and maximum reduction of C-peptide concentrations. The secondary endpoints for pharmacokinetic assessment were the following parameters: Maximum plasma insulin concentrations (CINSmax), time to CINSmax (tINSmax), area under the insulin concentration curves in defined time-intervals (AUCINS 0-1h, AUCINS 0-2h, AUCINS 0-3h AUCINS 0-4h, AUCINS 0-5h AUCINS 0-6h). Inter-subject variability was investigated for selected PD and PK parameters. Plasma concentrations of insulin, as shown in Table 23 below, were determined by a good laboratory practice (GLP) validated microparticle enzyme immunoassay (MEIA). TABLE 22 Summary of Plasma Insulin Concentrations (pmol/L) 300 U 150 U 15 U SC oral oral Time Point N Mean SD N Mean SD N Mean SD Time 0 10 4.6 7.3 10 9.2 9.9 8 0.3 0.9 10 minutes 10 5.7 10.8 10 50.3 62.4 8 59.6 44.7 20 minutes 10 13.7 18.3 10 429.6 474.6 8 188.3 162.6 30 minutes 10 41.2 32.5 10 409.5 268.1 8 192.5 250.6 40 minutes 10 94.9 63.1 10 366.2 258.2 8 114.3 158.9 50 minutes 10 109.4 75.6 10 214.2 185.8 8 79.8 121.7 60 minutes 10 116.4 63.2 10 122.1 108.2 8 50.2 69.5 75 minutes 10 137.4 86.5 10 48.2 37.3 8 30.3 38.6 90 minutes 10 116.5 50.9 10 20.6 28.2 8 19.5 25.9 105 minutes 10 132.2 72.4 10 7.5 12.9 8 11.5 14.9 120 minutes 10 119.1 70.2 10 19.1 22.1 8 17.1 15.7 150 minutes 10 129.8 51.1 10 10.0 14.1 8 8.3 11.6 180 minutes 10 149.6 61.3 10 9.1 13.6 8 17.0 23.4 210 minutes 10 146.8 71.8 10 4.9 7.0 8 17.7 24.9 240 minutes 10 138.2 64.6 10 5.1 5.9 8 22.0 31.1 300 minutes 10 129.8 42.5 10 8.1 17.2 8 12.0 15.4 360 minutes 10 87.7 56.7 10 2.4 4.5 8 14.2 16.4 In Table 22, baseline corrected values were used, i.e., pre-dose baseline values were subtracted, and in case of a negative result, the value was set to zero. FIG. 13 shows time plots for mean plasma insulin concentrations (baseline corrected) for treatments using 300 U oral insulin/400 mg 4-CNAB, 150 U oral insulin/200 mg 4-CNAB and 15 SC insulin. Table 23 below shows a Summary of C-Peptide Levels (nmol/L): TABLE 23 Summary of C-Peptide Levels 15 U SC 300 U oral 150 U oral Time Point N Mean SD N Mean SD N Mean SD −60 minutes 10 1.02 0.42 10 0.95 0.37 8 0.86 0.33 −30 minutes 10 1.05 0.40 10 0.98 0.36 8 0.86 0.30 Time 0 10 1.04 0.39 10 0.99 0.30 8 0.95 0.35 10 minutes 10 1.05 0.42 10 1.00 0.31 8 1.00 0.38 20 minutes 10 1.07 0.47 10 1.01 0.34 8 1.02 0.37 30 minutes 10 1.09 0.46 10 1.02 0.38 8 1.01 0.34 40 minutes 10 1.11 0.47 10 1.02 0.36 8 0.97 0.28 50 minutes 10 1.05 0.43 10 1.01 0.36 8 0.99 0.36 60 minutes 10 1.04 0.39 10 0.97 0.35 8 1.00 0.36 75 minutes 10 1.07 0.45 10 1.00 0.41 8 0.99 0.34 90 minutes 10 1.03 0.44 10 1.04 0.38 8 0.92 0.30 105 minutes 10 1.01 0.43 10 1.06 0.36 8 0.94 0.33 120 minutes 10 0.99 0.45 10 1.04 0.36 8 0.95 0.36 150 minutes 10 1.01 0.50 10 1.04 0.34 8 1.01 0.38 180 minutes 10 0.99 0.44 10 1.07 0.38 8 1.08 0.46 210 minutes 10 0.97 0.40 10 1.04 0.40 8 1.03 0.38 240 minutes 10 0.94 0.31 10 1.11 0.45 8 1.00 0.37 300 minutes 10 0.96 0.36 10 1.07 0.44 8 0.99 0.43 360 minutes 10 0.92 0.34 10 1.07 0.39 8 0.97 0.42 FIG. 14 shows a plot of C-peptide [mnol/l] vs. time for 15 IU s.c., 300 IU oral and 150 IU oral. As shown in FIG. 14, C-peptide measurements showed no significant changes during the treatment periods. The parameters assessed in this study were standard measurements appropriate for comparing the PK and PD properties of insulin absorption after oral administration and SC injection. The use of a glucose clamp with a Biostator minimized the likelihood of the onset of symptomatic hypoglycemia. Calculations based upon the plasma insulin concentrations or glucose infusion rates from the glucose clamp procedure reflect standard PK or PD calculations commonly used for the glucose clamp technique. The primary PD endpoint of the study was the area under the glucose infusion rate curve (AUCGIR) in the first hr after drug administration (AUCGIR 0-1h) PK and PD data were statistically analyzed for subjects that received at least the first 2 treatments (Visit 1 to 4) and for subjects who completed all three treatment visits (Visit 1 to 6). PD parameters used for analysis were the maximum glucose infusion rate after application of the study drugs (GIRmax), the time to maximum glucose infusion rate (tGIRmax), time to half-maximum GIR values before GIRmax (early tGIR 50%), time to half-maximum GIR values after GIRmax (late tGIR 50%), and the area under the glucose infusion rate versus time curves from 0 to 60, 120, 180, 240, 300, and 360 min after dosing, and from 180 to 360 min post dose (AUCGIR 0-1h, AUCGIR 0-2h, AUCGIR 0-3h AUCGIR 0-4h, AUCGIR 0-5h, AUCGIR 0-6h, AUCGIR 3-6h, respectively). In addition, plasma concentrations of C-peptide and plasma glucose concentrations were used for PD analysis. GIRmax, tGIRmax and early and late tGIR 50% were calculated by fitting a polynomial function (6th order) to each individual's GIR profile after subtraction of the mean baseline GIR. Areas under the curve (AUCs) were calculated from the raw data using the trapezoidal rule. PK parameters were calculated using non-compartmental methods. PK parameters determined included the maximum plasma insulin concentration (CINSmax), time to maximum insulin concentration (tINSmax), and the area under the plasma insulin concentration versus time curves from 0 to 1, 2, 3, 4, 5 and 6 hrs after application of the study drugs (AUCINS 0-1h, AUCINS 0-2h, AUCINS 0-3h, AUCINS 0-4h, AUCINS 0-5h and AUCINS 0-6h, respectively). The calculation of AUCs from time of dosing until return to baseline concentration (AUCINS 0-t′) was omitted as in some patients insulin concentrations did not return to baseline measurement within 360 min post dosing. The PK and PD data obtained were used for comparative analysis of the treatments with 15 U SC insulin and 300 U oral insulin. All tests were performed against a 2-sided alternative hypothesis, with a significance level of 5% (α=0.05). The tests were declared statistically significant if the calculated p-value was <0.05. In view of the small sample size and some outliers, a first analysis was done using non-parametric tests only (signed Wilcoxon rank tests and Kruskal-Wallis tests). However, the Kolmogorov-Smirnov test indicated normal distribution for all PK and PD parameters. Therefore, parametric tests paired t-tests and ANOVAs) were performed in addition. Although there were no substantial differences between the results of the non-parametric and the parametric tests, it was decided that the non-parametric results were used for the presentation of the data. Safety data included AEs, laboratory data, vital signs, physical examinations, and ECGs. Vital signs (systolic and diastolic blood pressure, respiration rate, heart rate, and body temperature) for each treatment group were summarized at baseline (defined as the −30 min time point) and at the end of each study day. Ten patients with type 2 diabetes were planned (5 patients assigned to each of 2 sequences) with complete data for analysis. One patient dropped out prior to any treatment and was replaced as per protocol. Therefore, the number of enrolled patients was eleven. Ten patients completed the study with the originally planned two treatments. Eight of these ten patients accepted the offer to attend an additional oral treatment of 150 U Insulin/200 mg 4-CNAB due to protocol amendment, and this additional treatment was not performed in random order. PK/PD data were also analyzed for the subset of eight patients who received the second oral study treatment Analysis of Pharmacokinetics and Pharmacodynamics PK and PD data were analyzed for the 10 patients who received the study treatments A and B (oral 300 U Insulin/400 mg 4-CNAB, SC 15 U regular insulin) and had evaluable data. PK and PD data were also analyzed for the amended group of 8 patients who received the second oral study treatment (treatment C: oral 150 U Insulin/200 mg 4-CNAB). All included patients with treatment received at least 2 treatments (one oral and one SC treatment) as planned in the protocol. The following Table 24 summarizes the pharmacokinetic and pharmacodynamic parameters calculated for the different treatments. TABLE 24 Comparisons of the PK and PD Parameters Mean ± SD Oral 300 U Insulin/ Oral 150 U Insulin/ SC 15 U 400 mg 4-CNAB 200 mg 4-CNAB Regular Insulin Parameter (n = 10) (n = 8) (n = 10) Insulin AUC0-1h (μU × mL−1 × min) 2559.25 ± 1831.45 1099.58 ± 1221.15 542.31 ± 296.26 AUC0-2h (μU × mL−1 × min) 2926.58 ± 2104.23 1337.14 ± 1407.11 1801.97 ± 789.43 AUC0-3h (μU × mL−1 × min) 3046.75 ± 2169.16 1463.59 ± 1443.01 3122.81 ± 1242.82 AUC0-4h (μU × mL−1 × min) 3106.67 ± 2212.98 1649.43 ± 1541.90 4576.31 ± 1817.96 AUC0-5h (μU × mL−1 × min) 3172.83 ± 2262.81 1819.01 ± 1593.02 5916.31 ± 2208.85 AUC0-6h (μU × mL−1 × min) 3225.33 ± 2319.66 1949.64 ± 1623.949 7003.81 ± 2440.251 Cmax (μU/mL) 93.44 ± 71.18 37.90 ± 39.23 32.7 ± 10.59 tmax (min) 27.00 ± 9.49 22.50 ± 7.0 160.5 ± 82.78 Glucose Infusion Rate AUC0-1h (mg/kg) 172.63 ± 85.54 58.08 ± 39.99 27.38 ± 32.22 AUC0-2h (mg/kg) 297.11 ± 142.73 102.62 ± 88.94 136.54 ± 106.54 AUC0-3h (mg/kg) 321.19 ± 146.29 116.96 ± 78.26 271.43 ± 191.04 AUC0-4h (mg/kg) 343.31 ± 140.47 142.00 ± 85.76 421.33 ± 264.76 AUC0-5h (mg/kg) 364.40 ± 135.36 160.28 ± 99.64 548.83 ± 342.71 AUC0-6h (mg/kg) 374.10 ± 134.70 190.77 ± 133.38 650.70 ± 380.16 GIRmax (mg/kg/min) 4.35 ± 2.23 2.12 ± 0.89 3.57 ± 1.79 tGIRmax (min) 39.80 ± 16.00 131.63 ± 146.04 255.30 ± 108.15 Early t50% (min) 13.40 ± 6.48 103.50 ± 140.90 150.40 ± 87.44 Late t50% (min) 114.70 ± 78.74 NA NA The pharmacokinetic and pharmacodynamic parameters discussed here are the averages and standard deviations of the individual values. The oral dose of 300 U Insulin/400 mg 4-CNAB showed a faster and higher rise in plasma insulin concentrations indicating a faster onset of action than the SC treatment (AUCINS 0-1h oral 300 U vs. SC 15 U: 2559±1831 vs. 542±296 μU×mL−1×min, p<0.01; CINS max oral 300 U vs. SC 15 U: 93:71 vs. 33±11 μU/mL, p<0.01; tINSmax oral 300 U vs. SC 15 U: 27±9 vs. 161±83 min, p<0.01). Accordingly, this trend is mirrored in the pharmacodynamic (GIR) results, as expected, with a significantly faster onset of the PD effect after the oral treatment compared to the SC treatment (AUCGIR 0-1h oral 300 U vs. SC 15 U: 173±86 vs. 27±32 mg/kg, p<0.01; tGIRmax oral 300 U vs. SC 15 U: 40±16 vs. 255±108 min, p<0.01; early t50% oral 300 U vs. SC 15 U: 13±6 vs. 150±87 min, p<0.01). The maximum glucose infusion rates, shown in FIG. 15, showed no statistically significant difference, although the initial level of glucose infused was higher from oral insulin than from SC insulin. Relative bioavailability (based on PK results) and biopotency (based on PD results) of the two oral insulin doses in comparison to the SC administration were calculated as defined hereinabove. Relative bio-availability of oral insulin is listed in the Table 25. Respective values for bio-potency for oral insulin are listed in Table 26. TABLE 25 Summary of Relative Bioavailability of Insulin Time interval n Mean SD SEM Max Min Median Bioavailability (%): 300 U oral vs. 15 U SC 0-60 10 43.7 60.5 19.1 198.2 7.2 18.3 0-120 10 13.0 20.1 6.4 69.1 2.9 7.0 0-180 10 7.8 12.7 4.0 43.5 1.8 3.9 0-240 10 4.9 7.3 2.3 25.4 1.3 2.6 0-300 10 3.4 4.1 1.3 14.6 1.0 2.1 0-360 10 2.7 3.0 1.0 11.0 0.8 1.8 180-360 10 0.3 0.3 0.1 1.1 0.0 0.1 Bioavailability (%): 150 U oral vs. 15 U SC 0-60 8 21.4 19.8 7.0 53.3 0.4 14.7 0-120 8 8.4 6.8 2.4 16.8 0.1 7.8 0-180 8 5.4 4.3 1.5 10.3 0.1 5.7 0-240 8 4.0 3.1 1.1 7.6 0.0 4.6 0-300 8 3.4 2.7 0.9 6.8 0.0 3.8 0-360 8 3.1 2.4 0.9 6.2 0.0 3.4 180-360 8 1.5 1.6 0.6 3.7 0.0 1.0 TABLE 26 Summary of Relative Biopotency of Oral Insulin Time interval n mean SD SEM Max Min Median Biopotency (%): 300 U oral vs. 15 U SC 0-60 7 54.90 91.93 34.74 261.44 5.54 19.90 0-120 9 11.70 9.21 3.07 32.76 3.65 8.12 0-180 9 5.76 3.41 1.14 13.56 2.03 4.85 0-240 10 21.14 54.94 17.37 177.45 2.19 3.56 0-300 10 47.53 140.38 44.39 447.03 1.56 3.12 0-360 10 31.01 89.44 28.28 285.54 1.10 2.69 Biopotency (%): 150 U oral vs. 15 U SC 0-60 5 110.86 193.40 86.49 455.95 11.74 23.52 0-120 7 12.86 13.59 5.14 40.76 3.23 6.94 0-180 7 6.66 6.17 2.33 19.53 1.58 6.28 0-240 8 4.03 3.56 1.26 10.67 0.00 2.86 0-300 8 3.55 3.22 1.14 9.74 0.00 2.52 0-360 8 3.15 2.77 0.98 7.93 0.00 2.40 Table 27 shows a comparison of the relative bioavailability and biopotency for oral insulin. TABLE 27 Comparisons of Relative Bioavailability and Biopotency (Mean ± SD) Oral 300 U Insulin/400 mg 4-CNAB Oral 150 U Insulin/200 mg 4-CNAB TIME (n = 10) (n = 8) INTERVAL Bioavailability (%) Biopotency (%) Bioavailability (%) Biopotency (%) 0-1 hr 43.7 ± 60.5 54.9 ± 91.9 (n = 7) 21.4 ± 19.8 110.9 ± 193.4 (n = 5) 0-2 hrs 13.0 ± 20.1 11.7 ± 9.2 (n = 9) 8.4 ± 6.8 12.9 ± 13.6 (n = 7) 0-3 hrs 7.8 ± 12.7 5.8 ± 3.4 (n = 9) 5.4 ± 4.3 6.7 ± 6.2 (n = 7) 0-4 hrs 4.9 ± 7.3 21.1 ± 54.9 4.0 ± 3.1 4.0 ± 3.6 0-5 hrs 3.4 ± 4.1 47.5 ± 140.4 3.4 ± 2.7 3.5 ± 3.2 0-6 hrs 2.7 ± 3.0 31.0 ± 89.4 3.1 ± 2.4 3.2 ± 2.8 Relative biopotency (based on PD results) of 300 U oral Insulin/400 mg 4-CNAB was as high as 54.9±91.9% in the first hr after application, and 31.0±89.4% over 6 hrs. Respective values for bioavailability (based on PK results) were 43.7±60.5%, and 2.7±3.0%. The unexpected increase in mean relative biopotency for the time intervals 0-4, 0-5 and 0-6 hrs accounts for Patient 101 whose values were calculated only for these three time periods and which were up to 100-fold higher than those found for the other patients (177.45%, 447.03%, and 285.54%, respectively). The oral dose of 150 U Insulin/200 mg 4-CNAB also showed a faster rise in plasma insulin concentrations compared to the SC treatment (AUCINS 0-1h oral 150 U vs. SC 15 U: 1100±1221 vs. 542±296 μU×mL−1×min; tINSmax oral 300U vs. SC 15U: 23±7 vs. 161±83 min), whereas the observed maximum plasma concentrations were similar for both treatments (CINSmax oral 150 U vs. SC 15 U: 38±39 vs. 33±11 μU/mL). Accordingly, GIR results for the oral 150 U insulin dose showed a faster onset of the PD effect (AUCGIR 0-1h oral 150 U vs. SC 15 U: 58±40 vs. 27±32 mg/kg; tGIRmax oral 150 U vs. SC 15 U: 132±146 vs. 255±108 min; early t50% oral 150 U vs. SC 15 U: 104±141 vs. 150±87 min). The maximum glucose infusion rate was lower after the oral than after the SC treatment (GIRmax.oral 150 U vs. SC 15 U: 2.1±0.9 vs. 3.6±1.8 mg/kg/min). These findings indicate that suppression of hepatic glucose production can be achieved also by the lower dose of 150 U oral insulin. Relative biopotency of 150 U oral Insulin/200 mg 4-CNAB was 110.9±193.4% in the first hour after application, and 3.2±2.8% over 6 hours. Respective values for bioavailability were 21.4±19.8%, and 3.1±2.4%. The abnormal high mean relative biopotency of 110.9% in the first hour results from an extremely high value of 455.95% found for Patient 102 and the fact that values of only 5 patients were available. Because of the mentioned distortion of the biopotency means, the medians are considered to be a more suitable representation of the data. Comparison of the PK and PD data of the two oral insulin doses suggests a nearly linear dose relationship of the PK parameters AUCINS and CINS max. The PD response, as represented by AUCGIR and GIRmax, also increases with dose but in a less clear fashion. Pharmacokinetic/Pharmacodynamic Conclusions This first glucose clamp study demonstrated that orally applied insulin exhibits a pronounced metabolic effect. In view of the presented PD and PK properties, and the advantages of an oral administration (high portal insulin concentrations, convenience of administration), Insulin/4-CNAB seems to be a very attractive candidate for pre-prandial (before meal) insulin therapy in type 1 and type 2 diabetic patients. All treatments evaluated during the study were safe and well tolerated. No adverse events were observed following oral administration of Insulin/4-CNAB capsules or subcutaneous injection of regular insulin. EXAMPLE 7 Comparison between Oral Insulin and s.c. Short Acting Postprandial Blood Glucose Excursions A randomized, 3-period crossover, double-blind, double-dummy study was conducted in order to compare the effect (i.e., the postprandial pharmacokinetic and pharmacodynamic profiles) of an oral insulin formulation with that of s.c. administered short acting insulin on postprandial blood glucose excursions in Type 2 Diabetic subjects without any antidiabetic medication. A primary objective of this study was to compare the effect of an oral insulin formulation (300 U insulin combined with 400 mg 4-CNAB in 2 capsules, each capsule containing 150 U insulin/200 mg 4-CNAB) with that of 12 U subcutaneous (s.c.) injected short acting insulin [Humalog® injection 100 U/ml from Eli Lilly and Company] on postprandial blood glucose excursions. The postprandial blood glucose excursions were assessed after a standardized breakfast intake. Fifteen male subjects between 35 and 70 years old, inclusive, with type 2 diabetes mellitus as defined by the American Diabetes Association (1998 Diabetes care, 21: S5-S19) for more than one year were chosen. Subjects included in the study had BMI<36 kg/m21, had stable glycemic control (HbA1C<11%), were off all oral hypoglycemic agents 24 hours prior to each study dosing day and off any investigational drug for at least four (4) weeks prior to Visit 1, refrained from strenuous physical activity beginning 72 hrs prior to admission and through the duration of the study, and were confined to the clinical research unit as required by the protocol. Subjects maintained a constant body weight (+/−2 kg). All patients received the same oral and SC injection treatments in a randomized sequence. At visit 1, each patient was randomized to one of six possible treatment sequences (see Table 28). On four separate occasions, patients received one of the four possible treatments prior to a standardized breakfast: 300 U oral Insulin/400 mg 4-CNAB (2 capsules, each capsule containing 150 U Insulin/200 mg 4-CNAB), 150 U oral Insulin/200 mg 4-CNAB (one capsule), 12 U SC short-acting insulin (Humalog®), and no supplemental insulin (placebo). During the first three treatment periods, 300 U oral, 12 U SC and placebo insulin were administered in random order and under blinded conditions (double-dummy technique). During the fourth treatment period, the patients received 150 U oral insulin in an open fashion. The overall study design is illustrated in Table 28 below. TABLE 28 Overall Study Design Randomization Visit 1 Visit 2 Visit 3 Visit 4 Visit 5 Visit 6 Visit 7 Visit 8*) Screening Session 1 Session 2 Session 3 Final Screening Session 4 Final Visit Visit*) 300 U oral insulin or 12 U SC or 150 U placebo oral *)For all patients, Visits 7 and 8 were combined (i.e., final examination was performed at Visit 7, immediately after finishing experimental procedures). The SC insulin dose of 12 U was selected to fall within a range typical for type 2 diabetic patients. The oral dose of 300 U insulin (in combination with 400 mg 4-CNBA) had been shown to be effective in Example 5 above. The oral dose of 150 U insulin (in combination with 200 mg 4-CNBA) was chosen to investigate whether or not an effect on hepatic glucose production could be achieved also by a lower insulin dose. The time point of study drug administration (SC injection: 15 minutes prior to meal intake; oral administration: 30 minutes prior to meal intake) was selected in order to match the PK and PD properties of the administered insulin formulations with the postprandial rise of blood glucose. The wash-out period between the first three treatment sessions was 1-20 days. The duration of each session was approximately 8-9 hours, and all experiments were performed after an overnight fast of approx. 12 hours. At Visit 1 (screening visit), the patients came to the clinical research unit in a fasted state (i.e., not having had any caloric intake for at least 12 hours). The patients' physical statistics, medical history and social habits recorded, and a physical examination performed. Not more than 14 days later, at Visit 2, each patient was randomized to one of six treatment sequences shown in Table 40 below and received either one of the two active treatments (300 U oral Insulin/400 mg 4-CNAB or 12 U short-acting SC insulin) or no supplemental insulin (placebo). Thirty minutes after oral and fifteen minutes after SC drug administration, the patients ate a standardized breakfast, and postprandial blood glucose concentrations were monitored for six hours. Serial blood samples were also collected in regular intervals for measurement of plasma insulin, 4-CNAB, and C-peptide concentrations. The study patients were released from the institute at the end of the treatment session. At Visits 3 and 4, the study patients returned to the clinical unit to receive the alternative treatments in conjunction with the test meal according to their treatment sequence. All experimental procedures and measurements were identical with those of the preceding treatment days. A final examination (Visit 5) was performed after Visit 4, preferably immediately after the experimental procedures were completed, but no longer than fourteen days after Visit 4. The patients were invited to attend a fourth treatment session (Visit 7) with a single oral administration of 150 U Insulin/200 mg 4-CNAB thirty minutes prior to a test meal. All experimental procedures and measurements were the same as on the preceding treatment days. Patients attended a screening (Visit 6), no more than twenty days prior to the additional session, as well as a final examination (Visit 8), preferably immediately after the experimental procedures of Visit 7 were completed, but no longer than fourteen days thereafter. Visits 7 and 8 were generally combined (i.e., for all patients final examination was performed at Visit 7, immediately after completion of experimental procedures). The patients were randomly assigned to one of the following treatment sequences: TABLE 29 Treatments Administered Treatment Treatment Period Sequence 1 (Visit 2) 2 (Visit 3) 3 (Visit 4) 4 (Visit 7) 1 300 U Oral 12 U SC Placebo 150 U Oral 2 300 U Oral Placebo 12 U SC 150 U Oral 3 12 U SC 300 U Oral Placebo 150 U Oral 4 12 U SC Placebo 300 U Oral 150 U Oral 5 Placebo 12 U SC 300 U Oral 150 U Oral 6 Placebo 300 U Oral 12 U SC 150 U Oral According to the double-dummy technique, each patient received on the first three treatment sessions (Visits 2-4), in addition to his scheduled treatment administration (oral or SC), the alternative administration (SC or oral) as placebo preparation. On sessions without supplemental insulin, both treatments (oral and SC) were placebo preparations. On the last treatment session (Visit 7), all patients received in an open fashion one oral dose of 150 U Insulin/200 mg 4-CNAB. Based on the six sequences shown above, the following treatments were administered during the study: Sequence 1: Visit 2: Two insulin capsules 30 minutes, one SC placebo injection 15 minutes before meal. Visit 3: Two placebo capsules 30 minutes, one SC insulin injection 15 minutes before meal Visit 4: Two placebo capsules 30 minutes, one SC placebo injection 15 minutes before meal Visit 7: One insulin capsule 30 minutes before meal Sequence 2: Visit 2: Two insulin capsules 30 minutes, one SC placebo injection 15 minutes before meal. Visit 3: Two placebo capsules 30 minutes, one SC placebo injection 15 minutes before meal Visit 4: Two placebo capsules 30 minutes, one SC insulin injection 15 minutes before meal Visit 7: One insulin capsule 30 minutes before meal Sequence 3: Visit 2: Two placebo capsules 30 minutes, one SC insulin injection 15 minutes before meal. Visit 3: Two insulin capsules 30 minutes, one SC insulin injection 15 minutes before meal Visit 4: Two placebo capsules 30 minutes, one SC placebo injection 15 minutes before meal Visit 7: One insulin capsule 30 minutes before meal Sequence 4: Visit 2: Two placebo capsules 30 minutes, one SC insulin injection 15 minutes before meal. Visit 3: Two placebo capsules 30 minutes, one SC placebo injection 15 minutes before meal Visit 4: Two insulin capsules 30 minutes, one SC placebo injection 15 minutes before meal Visit 7: One insulin capsule 30 minutes before meal Sequence 5: Visit 2: Two placebo capsules 30 minutes, one SC placebo injection 15 minutes before meal. Visit 3: Two placebo capsules 30 minutes, one SC insulin injection 15 minutes before meal Visit 4: Two insulin capsules 30 minutes, one SC placebo injection 15 minutes before meal Visit 7: One insulin capsule 30 minutes before meal Sequence 6: Visit 2: Two placebo capsules 30 minutes, one SC placebo injection 15 minutes before meal. Visit 3: Two insulin capsules 30 minutes, one SC placebo injection 15 minutes before meal Visit 4: Two placebo capsules 30 minutes, one SC insulin injection 15 minutes before meal Visit 7: One insulin capsule 30 minutes before meal The 4-CNAB used for the capsules was manufactured under GMP compliance. The Insulin used to prepare the capsules was Zinc-Insulin Crystals Human: Proinsulin Derived (Recombinant DNA Origin) USP Quality obtained from Eli Lilly and Company (Indianapolis, Ind.). The Insulin/4-CNAB capsules contained 150 Insulin Units USP and 200 mg 4-CNAB. The insulin/4-CNAB capsules were prepared by AAI Pharma Inc., Wilmington N.C. Insulin/4-CNAB capsules were provided in HDPE bottles, each of which contained 40 capsules and a polyester coil. Each bottle had a heat-induction seal and a child-resistant cap, and were stored frozen at or less than minus 10° C. On the day of dosing, the appropriate number of capsules was removed from the freezer and brought to room temperature (between 15 and 30° C.) for about one hour. Capsules were used within four hours of dispensing, and unopened bottles were not left at room temperature for more than four hours. The subjects ingested the meal fifteen minutes after drug administration. Blood glucose concentrations were monitored for six hours after glucose ingestion, and serial blood samples were collected in regular intervals for measurement of insulin concentration, 4-CNAB concentration, C-peptide, and blood glucose, providing information for pharmacokinetic and pharmacodynamic determinations. Blood glucose concentrations were determined immediately after sample collection and documented. All experiments were identical in their sample collections and monitoring period for all visits. The experimental procedure after the meal intake lasted for six hours (+1 hour baseline period for stabilization of blood glucose concentrations at the desired preprandial blood glucose level). During each treatment session, blood samples were collected for determination of plasma concentrations of 4-CNAB, insulin and C-peptide, and for blood glucose concentration. Sampling started 1 hour before intake of the test meal and continued until 6 hours thereafter. Blood samples were drawn via a venous cannula and collected related to the start of the test meal at time point 0. The timing of scheduled samples could be adjusted according to clinical needs or needs for pharmacokinetic data. The duration of each session was approximately 8-9 hours. All experiments were performed after an overnight fast of approximately 12 hours. The studies started in the morning. A 17-gauge PTFE catheter was inserted into an arm vein for blood sampling for measurement of blood glucose, and for plasma insulin, 4-CNAB and C-peptide concentrations. The line was kept patent with 0.15-mol/L (0.9%) sterile saline. At time-point-15, exogenous insulin was administered by oral insulin administration or by subcutaneous injection at two of the three experimental days. At time point 0, subjects ingested a standardized breakfast at every study day (visits 2-4 and 7). The oral treatments (Insulin/4-CNAB capsules and placebo capsules) were administered 30 minutes, and the injections (short-acting insulin and placebo solution) 15 minutes, before start of meal intake. The pharmacodynamic response elicited was studied by measurements of blood glucose concentrations in 5 minute intervals for another six hours, and no food intake was allowed during this period, although water was consumed as desired. Blood samples for blood glucose determination (0.25 mL per sample) were taken at −1 min (baseline), 5 minutes after start of meal intake and thereafter in 5 minute intervals until 120 minutes, 10 minute intervals until 240 minutes, and 15 minute intervals until 360 minutes after start of meal intake (45 samples per session). Blood glucose concentrations were measured immediately after sample collection using an automated GOD method (Super GL Ambulance Glucose Analyzer, Ruhrtal Labortechnik, Delecke-Möhnesee, Germany). Blood samples for determination of 4-CNAB plasma concentrations (2 mL in sodium heparin tube) were drawn 10, 20, 30, 40, 60, 90, 120, 240 and 360 minutes after start of meal intake (9 samples per session). Blood samples for determination of insulin and C-peptide plasma concentrations (5 mL in sodium heparin tube) were drawn at −60 and −30 minutes, at time 0 (start of meal intake), and after 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150, 180, 210, 240, 300, and 360 minutes (19 samples per session). Plasma concentrations of insulin were determined by a GLP-validated microparticle enzyme immunoassay (MEIA). In case of a hypoglycemia (defined as blood glucose concentrations below 60 mg/dl), a blood glucose concentration of 60 mg/dl was maintained by means of a variable-rate intravenous infusion of 20% glucose. The glucose infusion rate was adopted, if necessary, in relation to the blood glucose concentrations measured to maintain this blood glucose level. In case of blood glucose values exceeding 350 mg/dl for more than 60 minutes, the experiments were aborted and the subject was treated with additional s.c. insulin to normalize his blood glucose concentrations. Blood samples for the determination of plasma insulin concentrations, 4-CNAB and C-peptide were collected at defined intervals, as discussed above. Plasma samples were stored at approximately −20° C. (4-CNAB at −70° C.) until determination by immunoassay is performed. After the end of the sampling period, the study subjects were released from the clinic. Inter-subject variability for selected pharmacodynamic and pharmacokinetic parameters was assessed. Incidence of postprandial hypoglycemia was assessed for each subject and across the study population. Blood glucose excursions (i.e., differences between pre-prandial and postprandial blood glucose concentrations) registered after the ingestion of the meal were used to evaluate pharmacodynamic parameters of the two insulin administration routes and compared with the same data obtained for the study day without any supplemental insulin. From these measurements, the area under the glucose infusion rate versus time curve from 0-6 hours (and other time intervals), the maximal blood glucose excursion (Cmax) and time to the maximal blood glucose excursion (tmax) were analyzed. For pharmacodynamic assessment, the following parameters were calculated: Maximal blood glucose excursion (BGmax), time to BGmax (tBGmax) Area under the blood glucose excursion curve in defined time-intervals (AUCBG 0-1h, AUCBG 0-2h, AUCBG 0-3h, AUCBG 0-4h, AUCBG 0-6h), maximal absolute blood glucose concentrations (BGabsmax), time to BGabsmax (tBGabsmax). For pharmacokinetic assessment the following parameters were calculated: Maximal plasma insulin concentrations (INSmax), time to INSmax (tINSmax), Area under the glucose infusion rates in defined time-intervals (AUCIns 0-1h, AUCIns 0-2h, AUCIns 0-3h, AUCIns 0-4h, AUCIns 0-6h) and maximum reduction of C-peptide concentrations Plasma insulin concentrations were subjected to appropriate pharmacokinetic analyses. Parameters determined include Cmax, tmax, and the area under the plasma concentration versus time curve from the time of dosing until a return to the baseline measurement (AUC0-t′), where t′ is the time that the level of plasma insulin concentration returns to the baseline. In addition, other pharmacokinetic parameters, such as t1/2, elimination rate constant (λz) and partial AUC values, were calculated, if considered appropriate, for each individual subject enrolled within the study. Pharmacodynamics As measurement of a pharmacodynamic effect of oral Insulin/4-CNAB capsules, the blood glucose excursions measured over 6 hours were considered, and the area under the blood glucose excursion vs. time curve in the first two hours after start of meal intake (AUC0-2h) was defined as primary pharmacodynamic endpoint. Based upon individual blood glucose excursion data, the mean time profiles with standard deviation) of the blood glucose excursions per treatment were plotted. FIG. 16 shows a plot of the arithmetic means of postprandial blood glucose excursions (mg/dL) vs. time for all subjects. As indicated in FIG. 16, mean blood glucose excursions of the different treatments reach their maxima between 1 and 2 hours after start of meal intake and then return towards baseline. The time to maximal glucose excursion (median) was 1.3 hours for SC 12 U short-acting insulin, 1.7 hours for placebo, 1.8 hours for oral 150 U Insulin/200 mg 4-CNAB, and 2.2 hours for oral 300 U Insulin/400 mg 4-CNAB. The lowest overall excursions were achieved with the 12 U SC short-acting insulin injection. Compared to both oral insulin treatments and placebo, blood glucose excursions after SC injection are markedly lower during the period from 45 to 360 minutes and, after crossing the baseline at about 180 minutes, values become increasingly negative until 360 minutes after meal intake. After oral 300 U Insulin/400 mg 4-CNAB, a sharp decline from baseline can be seen until −20.8 mg/dL at 15 minutes, followed by a return to baseline at 30 minutes. Thus, during approximately the first hour, the dose of 300 U oral Insulin/400 mg 4-CNAB led to lower excursions even when compared to injection. Thereafter, rise and subsequent decline of the curve follows the pattern seen for oral 150 U Insulin/200 mg 4-CNAB dosage and no treatment (placebo). No differences could be seen between 150 U oral Insulin/200 mg 4-CNAB and no treatment (placebo). Based on the profiles, the parameters, AUC0-1h, AUC0-2h, AUC0-3h, AUC0-4h, AUC0-6h and Cmax were calculated, as presented in Table 30 below. TABLE 30 Treatment Oral Oral 150 U 300 U SC 12 U Insulin/ Insulin/ Short- 200 mg 400 mg acting 4-CNAB 4-CNAB insulin Placebo Parameter Mean STD Mean STD Mean STD Mean STD AUC0-1h (h * mg/dL) 24.5 15.2 6.9 15.0 13.1 8.5 25.3 9.1 AUC0-2h (h * mg/dL) 94.3 46.3 69.8 38.0 44.9 32.8 97.8 28.5 AUC0-3h (h * mg/dL) 154.1 74.1 138.2 60.4 61.4 57.5 160.2 54.0 AUC0-4h (h * mg/dL) 200.1 105.9 195.2 81.4 50.0 83.6 202.1 84.9 AUC0-6h (h * mg/dL) 233.9 164.3 250.8 140.6 −21.1 119.4 214.2 143.7 Cmax (mg/dL) 90.5 38.1 85.8 28.3 50.7 25.8 88.3 27.7 This data indicates that AUC0-1h is lowest following the 300 U oral Insulin/400 mg 4-CNAB dosage. Up to 2 hours and 3 hours, the AUCs are still smaller than the AUCs of 150 U oral Insulin/200 mg 4-CNAB and no treatment (placebo), but larger than the AUCs of 12 U SC short-acting insulin. However, for 4 hours and 6 hours, no difference can be seen between the oral applications and no treatment. For 150 U oral Insulin/200 mg 4-CNAB, all AUCs are more or less equal to those obtained under no treatment. Mean maximum blood glucose excursions (Cmax) after both oral insulin administrations and after no treatment are similar and clearly higher than Cmax after the SC injection. The test results can be summarized as follows: When Cmax and AUCs for 3 hours and more are considered, no statistically significant differences of the oral treatments compared to no treatment (placebo) could be established. On the other hand, both oral treatments differ significantly from SC insulin injection, with oral treatments leading to higher mean values. With regard to the primary endpoint AUC0-2h, a single oral dose of 300 U Insulin/400 mg 4-CNAB, administered 30 minutes prior to a standardized test meal, caused a statistically significant reduction of postprandial blood glucose excursions in comparison to no treatment (placebo). However, the effect was significantly lower than after SC injection of 12 U short-acting insulin. The effect of 150 U oral Insulin/200 mg 4-CNAB was not significantly different from no treatment (placebo). Pharmacokinetics From the blood samples taken, the individual plasma concentrations of 4-CNAB, insulin and C-peptide were also determined, and summary concentration vs. time profiles were plotted. FIG. 17 shows profiles of 4-CNAB plasma concentrations (ng/mL) vs. time (arithmetic means). As seen in FIG. 17, plasma 4-CNAB concentrations show a rapid decline within the first two hours after start of meal intake. After 2 hours, concentrations are less than 10% of the levels seen after 10 minutes. The results indicate that markedly higher concentrations might have been be reached in the time between intake of the Insulin/4-CNAB capsules and the first measurement 10 minutes after start of meal intake. Concentrations after intake of 400 mg 4-CNAB are approximately twice as high as after intake of 200 mg. FIG. 18 shows profiles of insulin plasma concentrations (pmol/l) vs. time (arithmetic means). As shown in FIG. 18, highest mean insulin plasma concentrations are reached after the 150 U oral dose, followed by 300 U oral, placebo, and 12 U SC injection. The curve of oral 300 U Insulin/400 mg 4-CNAB shows two maxima, the first at 0 min and the second at 120 min. The peak at 0 min is due to one particular patient who contributed with a value of 1803 pmol/L the most to this marked shift of mean insulin concentration. Almost all patients showed a more or less marked isolated increase of insulin concentrations at time 0 but not to such an extent as that patient. In addition, the rise of insulin concentrations under placebo is explained by the patients' endogenous insulin production, induced by the meal intake. FIG. 19 shows profiles of C-peptide plasma concentrations (nmol/l) vs. time (arithmetic means). Mean plasma concentrations of C-peptide, the indicator of endogenous insulin production, increased after all treatments. Decreasing, or more or less constant C-peptide concentrations, were seen only in a few patients and only after SC injection of short-acting insulin. This may reflect the fact that in most of the patients the ability to produce endogenous insulin was still maintained. As expected, the 150 U oral insulin dose and placebo show the most marked increase, whereas the increases after the 300 U oral dose and the 12 U SC injection are clearly lower. Based on the insulin concentration vs. time profiles, the parameters Cmax, tmax and AUC from time 0 to the time when the baseline insulin level was reached again (AUC0-t*) were calculated, as presented in Table 31 below. TABLE 31 AUC0-t* Cmax tmax (h * pmol/L) (pmol/L) (h) Treatment Mean STD Mean STD Median MIN MAX 0ral 150 U Insulin/200 mg 1469.42 684.92 461.50 219.29 2.00 0.50 3.00 4-CNAB 0ral 300 U Insulin/400 mg 923.06 354.59 418.53 382.46 1.50 0.00 3.50 4-CNAB SC 12 U Short- 791.52 417.95 315.83 155.09 1.38 0.50 3.50 acting insulin Placebo 1093.47 466.46 388.53 185.82 2.00 0.50 3.50 t* denotes time when baseline insulin level is reached again, or last data point (360 min) This data indicates that mean insulin plasma concentration vs. time profiles showed the highest AUC after 150 U oral insulin, followed by placebo, 300 U oral insulin, and 12 U SC injection. Highest mean Cmax was reached after 150 U oral insulin, followed by 300 U oral insulin, placebo, and 12 U SC injection. The median time until Cmax (tmax) was longest for 150 U oral insulin and placebo, followed by 300 U oral insulin and 12 U SC injection. Conclusions The primary objective of this study was to compare the effect of orally administered 300 U Insulin/400 mg 4-CNAB with that of 12 U subcutaneously injected short-acting insulin (Humalog®) on postprandial blood glucose excursions after a standardized breakfast. With respect to AUC0-2h as main parameter for pharmacodynamic evaluation, the highest effect on blood glucose excursions was found for 12 U SC short-acting insulin, followed by oral 300 U Insulin/400 mg 4-CNAB, oral 150 U Insulin/200 mg 4-CNAB and placebo, and the effects of the two latter appeared more or less equal. However, these results were not consistent for all calculated AUCs. During the first hour, 300 U oral insulin were superior to 12 U SC, and this order changed when the AUCs for more than 2 hours were compared: both oral treatments were no longer significantly different from no treatment (placebo), but the 12 U SC injection showed still a significant difference and clearly smaller AUCs. After the 300 U oral insulin dose, mean blood glucose excursions turned (until −20.8 mg/dL at 15 minutes after start of meal intake) and returned to baseline at 30 minutes. This transient decline could be seen in most of the patients, but only in one particular with a baseline blood glucose below 80 mg/dL did it lead to a hypoglycemic episode. These findings may indicate a rapid onset of action of orally administered 300 U Insulin/400 mg 4-CNAB prior to considerable absorption of carbohydrates from the test meal. Therefore, a time span of 30 minutes between dose administration and start of meal intake might be too long. Mean fasting blood glucose values at baseline (−1 minute) which served as reference for the calculation of excursions, were 124.38 mg/dL (99.10-172.00) for oral 150 U Insulin/200 mg 4-CNAB, 120.26 mg/dL (72.20-175.00) for oral 300 U Insulin/400 mg 4-CNAB, 143.11 mg/dL (104.00-190.00) for 12 U SC short-acting insulin, and 137.32 mg/dL (93.10-183.00) for placebo. With regard to these baseline values, the four treatments were split into two groups: the two oral treatments with values around 120 mg/dL, and the SC injection together with placebo showing values around 140 mg/dL. This finding may be explained by early action of the oral insulin formulations in the time between dose administration and start of meal intake, which is not covered by the profiles. However, the described non-homogeneity is not considered to impair the quality of the results. The concentration vs. time profiles for 4-CNAB display only the elimination of the substance from plasma. The absorption phase and the maximum concentrations are missed. In the time between −30 and +10 minutes, a rapid rise followed by a rapid decline can be assumed, and the achieved maximum concentrations should be markedly higher than the values seen at 10 minutes after start of meal intake. Therefore, further investigations of 4-CNAB pharmacokinetics should include an appropriate number of samples from the first hour following dose administration. The insulin profiles showed the highest AUC after 150 U oral insulin, followed by placebo, 300 U oral insulin, and 12 U SC short-acting insulin. The marked increase of mean plasma insulin concentrations after placebo indicates that the patients' ability of endogenous insulin production, induced by meal intake, was still maintained. Also the high AUC for 150 U oral insulin probably reflects mainly endogenous insulin production, and also the curves of the other treatments may account for a certain amount of endogenous insulin. The C-peptide plasma concentration profiles confirm this view and also indicate the release of considerable amounts of endogenous insulin. The levels were highest after 150 U oral insulin, followed by placebo, 300 U oral insulin, and 12 U SC short-acting insulin. As expected, the 150 U oral dose and placebo led to the most marked increase, whereas the increase after the 300 U oral dose and the 12 U SC injection was clearly lower, and these findings correlate with the blood glucose lowering effect seen for the different treatments: the lower the effect of the external insulin dose, the higher were the amounts of C-peptide as indicator of endogenous insulin production. The insulin concentration vs. time profiles seen for both oral doses in this study are considerable different from those obtained in Example 6, where mean insulin concentrations were back to baseline after approximately two hours and where maximum concentrations occurred after about half an hour. These differences might be due to the influence of the meal, stimulating endogenous insulin release and also possibly interfering with the resorption of the oral insulin preparations. In Example 6, patients were fasting during the entire experiment, and endogenous insulin production was suppressed by a constant low-dose insulin infusion. Therefore, the concentration vs. time curves of Example 6 represent more the pure pharmacokinetics of the administered exogenous insulin, whereas in the present study the effects of exogenous and endogenous insulin are overlapping. No adverse events were reported in this study. There were no treatment related findings of clinical laboratory safety parameters, vital signs, ECG or physical examination. The five hypoglycemic episodes that occurred in four patients remained symptomless due to immediate intervention with intravenous glucose infusion. Only one of the episodes was due to oral 300 U Insulin/400 mg 4-CNAB, and the majority (⅘) occurred after 12 U SC short-acting insulin injection. Accordingly, all study treatments were well tolerated. Overall, the study results suggest (based on the primary endpoint AUC0-2h) that orally administered 300 U Insulin/400 mg 4-CNAB are effective in lowering the postprandial rise of blood glucose in type 2 diabetic patients. However, the effect is smaller than after injection of 12 U SC short-acting insulin, which is significantly superior to both oral administrations. The oral dose of 150 U Insulin/200 mg 4-CNAB is similar effective as no treatment (placebo). At both doses, orally administered Insulin/4-CNAB seems to be well tolerated. EXAMPLE 8 A single-center, open label, randomized, single dose, 3-way cross-over study was conducted in type 1 diabetes mellitus patients to investigate the effect of food on the absorption and pharmacokinetics of insulin after a single dose of oral 4-CNAB/insulin, and to determine the effect of food on the pharmacodynamics of glucose and C-peptide after a single oral dose of 4-CNAB/insulin. For the diabetic volunteers, male or postmenopausal female subjects between 18 and 65 years old, inclusive, each with type 1 diabetes mellitus as defined by the American Diabetes Association (1998 Diabetes care, 21: S5-S19) were studied. Subjects had a body mass index of between 18 and 30 kg/m2 and had glycemic control HgA1c at screening <10%. Patients also had negative test for antibodies against insulin at screening, fasting blood glucose at screening <12.0 mmol/l, and fasting C-peptide at screening <0.2 nmol/ml. For the healthy control volunteers, male subjects between 18 and 65 years old, inclusive, for more than one year were chosen. Subjects included in the study had between 18 and 30 kg/m2. For diabetic patients, the study consisted of an eligibility screening period, three study periods and a follow-up exam at the conclusion of the last period. The three study periods included the following: administration of single doses of 4-CNAB/insulin followed by fasting (treatment A), followed by an ADA breakfast 20 minutes after dosing (treatment B), and followed by an ADA breakfast 20 minutes after dosing (treatment C). The study was conducted using an open label, randomized, crossover design with an interval of at least 7 days between treatments. The patients fasted overnight. The type 1 diabetics were randomized to treatment A or treatment 3 in periods 1 and 2. In period 3, all diabetics received treatment C. A total of eight type 1 diabetic patients were enrolled. As a control group, two healthy volunteers were enrolled. For healthy control subjects, the study consisted of an eligibility screening period, one study period and a follow-up exam at the conclusion of the period. The healthy control subjects were not receiving any medication but served as a control for the effect of breakfast on insulin production. Blood sampling and safety assessments followed the same schedule as for the diabetics. The healthy control subjects received the standard ADA breakfast at the same time as the type 1 diabetics in one study period (treatment D). A typical standard ADA breakfast comprises approximately 30% fat, 50% carbohydrates and 20% protein. Such a breakfast could include, for example, three slices of whole wheat bread, 15 g of low-fast margarine, 15 g of low-caloric jelly, 20 g of 30% fat cheese, 15 g of meat (ham, etc.), 200 ml of 2% fat milk, and coffee tea or water (no sugar). The study design is presented in Tables 32 and 33 below TABLE 32 Study design for Type I diabetics End of week Treatment third −3 to −1 A Treatment B Treatment C period Eligibility 4-CNAB/ 4-CNAB/insulin 4-CNAB/insulin follow-up screening insulin ADA breakfast ADA breakfast fasting 30 min after 20 min dosing after dosing TABLE 33 Study Design for Healthy volunteers week −3 to −1 Treatment D End of period Eligibility screening no dosing follow-up ADA breakfast This study tested the effect of a standard ADA breakfast administered 30 or 20 minutes after dosing on the absorption and pharmacokinetics of 4-CNAB/insulin administered as oral capsules. A control group of healthy subjects received a standard ADA breakfast in one period to measure the amount of insulin produced for this breakfast in healthy control subjects. The type I diabetic patientss were taken off their regular long-acting insulin 24 hrs prior to dosing and their glucose levels were controlled prior to dosing by overnight insulin infusion. The following treatments were administered to the type 1 diabetics according to the randomization schedule (see below) a) 400 mg 4-CNAB/300 IU insulin followed by fasting; b) 400 mg 4-CNAB/300 IU insulin followed by an ADA breakfast 30 minutes after dosing; c) 400 mg 4-CNAB/300 IU insulin followed by an ADA breakfast 20 minutes after dosing. Prior to dosing, the patients fasted overnight. The patients received an insulin infusion overnight. The study drug was administered 30 minutes after infusion was stopped (dosing at approximately 9:00 am). In one period, the oral dose was followed by fasting until 3 hours after dosing. In the two other periods, the oral dose is followed by intake of a standard ADA-breakfast 30 or 20 minutes after dosing. On day one of each study period, study medication was administered to subjects. Only an ADA breakfast was administered to the healthy volunteers. The type I diabetics stopped their regular long acting insulin 24 hrs prior to dosing but were allowed to use their immediate acting insulin up to their entry into the clinic around 3:00 p.m. on day 1. They received 4-6 units (depending on their weight) of regular insulin subcutaneously (s.c.) at approximately 5:30 p.m. on day 1 and a standard dinner thirty minutes after the administration of s.c. insulin. Between 8:30 and 9:00 p.m., the diabetics received a snack. At approximately 9:00 p.m. on day −1, an i.v. infusion of insulin was started at the infusion rate indicated in Table 36. The composition of the insulin infusion and the infusion rate were dependent on the patient's weight and blood glucose concentration, as described in Tables 34 and 35. TABLE 34 Composition of insulin infusate Insulin (U/L) Patient weight (kg) 80 60-65 88 65-70 96 70-75 104 75-80 112 80-85 124 85-90 140 90-95 180 >95 TABLE 35 Infusion algorithm Plasma glucose conc. Infusion rate [mmol/liter (mg/dL)] (ml/h) <5.5 (<99)a 0 5.5-6.6 (100-119) 5 6.7-7.7 (120-139) 10 7.8-8.8 (140-159) 15 8.9-9.9 (160-179) 20 10-13.3 (180-239) 40 >13.3 (>240) 60 The infusion rate was adjusted, if necessary, based on the results of blood glucose measurements done every 60 minutes. A blood sample (one drop) for assessment of real-time blood glucose using a Glucocard® was taken from an indwelling cannula, and the blood glucose concentration was adjusted to remain between 6 and 8 mmol/l. The insulin infusion was stopped 30 minutes before drug administration at approximately 9:00 a.m. on day 1. At times when no insulin was needed, only normal saline was administered. The 4-CNAB (Sodium N-[4-(4-chloro-2-hydroxybenzoyl)amino]butyrate) was manufactured by Emisphere Technologies, Inc. of Tarrytown, N.Y. in 400 mg strength oral capsules. Glucose stablization prior to dosing was done with Actrapid, manufactured by Novo Nordisk and having an active compound of insulin, at 100 U/ml strength, via i.v. infusion. The insulin for subcutaneous injection was also Actrapid, at 100 U/ml strength. The type I diabetics stopped their regular long acting insulin 24 hrs prior to dosing but were allowed to use their immediate acting insulin up to their entry into the clinic around 3:00 p.m. on day-1. They received 4-6 units of regular insulin s.c. at approximately 5:30 p.m. on day-1 and received a standard dinner thirty minutes after the administration of s.c. insulin. Between 8:30 and 9:00 p.m., the diabetics received a snack and were then were fasted until the next morning. At approximately 9:00 p.m., an i.v. infusion of insulin was started. The insulin infusion was stopped 30 minutes before drug administration at approximately 9:00 a.m. on day 1. On day 1 of each study period, study medication was administered to subjects in the upright position and was swallowed (not chewed) with 200 mL of water (subjects did not lie down for three hours after dosing). Depending on the treatment given, the patients received a standard ADA breakfast 30 or 20 minutes after dosing or they continued fasting. After the 3 hour blood sample was drawn, patients were allowed to resume their normal pattern of meals and resume using their regular long or immediate acting insulin. Water was allowed ad libitum during the study, except for 1 hour prior to and up to 1 hour after drug administration in each treatment. The healthy control subjects did not receive any medication but received a standard ADA breakfast at the same time as the diabetics (approximately 9:30 a.m. on day 1) after an overnight fast. The controls resumed normal meals after the 3-hour blood sample was taken. Study participants did not take any prescription or non prescription medication (with the exception of paracetamol, (acetaminophen) and topical medication) for 14 days prior to entrance into the clinical research facility and for the duration of the study period. The exception to this rule follows: type 1 diabetics continued their insulin therapy and fixed comedication which was used unaltered during the last 6 months. Methylxanthine-containing beverages or food (coffee, tea, coke, chocolate), grapefruit juice, and alcohol were not allowed from 48 hours (2 days) prior to entrance into the clinical research center and during the study. During each period of the study a series of blood samples were taken for 4-CNAB and insulin pharmacokinetic analyses. The term pre-dose refers to the time that the group of diabetics receives 4-CNAB/insulin. The healthy control subjects do not receive medication. Blood samples for pharmacokinetic analysis of 4-CNAB and insulin were drawn 30, 15 and 5 minutes prior to and at 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150, 180, 210, and 240 minutes after 4-CNAB/insulin administration (17 samples per subject per period). Blood samples for plasma glucose were drawn 30, 15 and 5 minutes prior to and at 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150, 180, 210, and 240 minutes after administration (17 samples per subject per period). Blood samples for C-peptide were drawn 30 and 5 minutes prior to and 30, 60, 90, 120, 180 and 240 minutes after administration (8 samples per subject per period). For healthy control subjects, a blood sample (one drop) was analyzed for real-time at pre-dose of 4-CNAB/insulin to the diabetic patients, 30, 60, 90, 120, 150, 180 and 240 min after each drug administration on day 1 (8 samples per subject per period). Blood samples for pharmacokinetic analysis of 4-CNAB and insulin were drawn 30, 15 and 5 min prior to and at 10, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 210, and 240 min after drug administration (16 samples per subject per period). Blood samples for plasma glucose were drawn at 30, 15 and 5 min prior to and at 10, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 210, and 240 min after drug administration (16 samples per subject per period). Blood samples for C-peptide were drawn at 30 and 5 min prior to and at 30, 60, 90, 120, 180 and 240 min after drug administration (8 samples per subject per period). The blood samples (6 mL each) were taken via an indwelling Venflon® catheter or by direct venipuncture into sodium heparin-containing tubes. The blood samples were centrifuged at 1500×g for fifteen minutes at a temperature between 2° C. and 8° C., within one hour of sample collection. The total volume of about 450 mL (type 1 diabetics) or about 180 mL (healthy control subjects) blood was taken during the study. Diabetic patients received 4-6 units (depending on their weight) of regular insulin subcutaneously (s.c.) at approximately 5:30 p.m. on day 1. Insulin infusion started at 9:00 p.m. on day 1, and the pump stopped 30 min before dosing of 4-CNAB/insulin on day 1 at approximately 9:00 a.m. A blood sample (one drop) was analyzed for real-time glucose every 60 minutes during the time of insulin infusion and at pre-dose, 30, 60, 90, 120, 150, 180 and 240 minutes after each drug administration on day 1 (8 samples per subject per period). The blood samples were taken from the indwelling canula (with obturator), one drop per assessment, and were analyzed for glucose in real time using a Glucocard®. The pharmacokinetic parameters determined or calculated from the plasma concentration time data for 4-CNAB and insulin were Cmax, tmax, Kel, t1/2, AUClast (area under the plasma concentration-time curve up to time t, where t is the last time point with concentrations above the lower limit of quantitation (linear trapezoidal rule)), AUC(0-inf), AUClast+Clast/kel, and % AUCextrap (percentage of estimated part for the calculation of AUC(0-inf):(AUC(0-inf)−AUClast)/AUC(0-inf))*100%)). The following pharmacodynamic parameters were computed from the plasma concentration-time data of glucose and C-peptide (both original and baseline subtracted data) using non-compartmental analysis: Emax, temax, and AUEClast (area under the effect-time curve calculated using linear trapezoidal summation from time zero to time t, where t is the time of the last measurable effect (E). Pharmacokinetic/Pharmacodynamic Evaluation In this section, the effect of food on the absorption and pharmacokinetics of 4-CNAB and insulin and on the pharmacodynamics of glucose and C-peptide after a single oral dose of 4-CNAB/insulin is presented. FIG. 20 shows mean profiles of 4-CNAB plasma concentration data for all three treatment groups. As shown in FIG. 20, the concentration-time profiles for the three treatment groups (fasting, breakfast 30 or 20 minutes post-dose) were almost identical. Individual data under fasting conditions for six out of eight subjects showed a clear 4-CNAB peak around 30 minutes post-dose, while for two subjects (Subjects 106 and 108) the 4-CNAB concentrations did not show a clear peak but a prolonged elevation. When having a breakfast 30 minutes post-dose, seven out of eight subjects showed a clear peak around 30 minutes post-dose, while one subject (Subject 104) showed a flattened peak. When having a breakfast 20 minutes post-dose, all eight subjects showed a clear 4-CNAB peak between 20 and 40 minutes post-dose. In general plasma 4-CNAB was rapidly absorbed and concentration-time profiles were not affected by breakfast at 20 or 30 minutes post-dose. For insulin, no mean profiles were presented because of the high variability between and within the subjects. With regard to the individual profiles, a slight decrease in insulin concentrations was observed pre-dose, and this was the result of the overnight insulin infusion that was stopped at 30 minutes prior to dosing of study medication. Under fasting conditions, peak insulin concentrations ranged from 245 to 4450 pmol/L. When subjects had a breakfast 30 minutes post-dose, the peak insulin concentrations ranged from 87 to 2486 pmol/L. When subjects had a breakfast 20 minutes post-dose, the peak insulin concentrations ranged from 84 to 1260 pmol/L. Healthy subjects showed peak insulin concentrations of 254 and 662 pmol/L following breakfast. The majority of insulin peaks, whether high or low, appeared around 20 minutes post-dose. However, in four cases a double insulin peak was observed. In one other case, one late insulin peak was observed, and the late appearing insulin peaks did not correlate with a decrease in glucose. In general, the insulin peak was accompanied by a slight decrease or stabilization of glucose. However, the height in insulin concentrations reached did not correlate with the extent of glucose lowering. Each subject showed remarkable intra-individual variation in insulin concentration. The healthy subjects showed a mild (peak insulin: 254 mmol/L for one subject) to moderate (peak insulin 662 mmol/L for one subject) increase of plasma insulin concentrations from around 1 hour after breakfast until 2 hours after breakfast or until 3 hours after breakfast. Due to the considerable variation in insulin plasma concentrations between and within subjects, no effect of food intake on insulin plasma concentration-time profiles could be concluded. FIG. 21 shows mean concentration-time profiles of plasma glucose. In reference to FIG. 21, the majority of patients showed a slight increase of glucose concentration pre-dose, which might be related to the overnight insulin infusion which was stopped 30 minutes prior to dosing of study medication. Under fasting conditions, plasma glucose concentrations showed a slight increase from around 60 minutes post-dose onwards. When patients had a breakfast 20 or 30 minutes post-dose, plasma glucose concentrations increased faster and reached higher values. Under fasting conditions, a very slight dip in glucose between 10 to 60 minutes was observed. When patients had a breakfast 30 minutes post-dose, the dip was slightly more pronounced. When patients had a breakfast 20 minutes post-dose, no clear dip in glucose was observed. The healthy subjects showed a mild increase in glucose between 1 and 2 hours after breakfast. With regard to C-peptide, for the majority of the samples, the plasma C-peptide concentrations were below the LOQ. Therefore, no descriptive statistics or profiles are shown. For 4-CNAB pharmacokinetic parameters were calculated as planned. In addition, for three parameters (Cmax, tmax and AUC) partial values were calculated for the periods 0-20 minutes post-dose, 0-30 minutes post-dose and 0-3 h post-dose. For Insulin, only Cmax, tmax and AUC values for the periods 0-20 minutes post-dose, 0-30 minutes post-dose and 0-3 h post-dose were calculated. No pharmacodynamic parameters for glucose and C-peptide were calculated. Summary statistics for the PK parameters of 4-CNAB are presented in Table 36 and PK parameters derived for 4-CNAB from the periods 0-20 minutes post-dose, 0-30 minutes post-dose and 0-3 hrs post-dose are presented in Table 37. TABLE 36 Summary statistics of plasma 4-CNAB pharmacokinetic parameters Cmax tmax* AUC0-inf t1/2 (ng/mL) (h) (ng · h/mL) (h) Fasting 21750 0.42 (0.33-0.67) 20713 (±7161) 0.86 (±0.69) (±7506) Breakfast 24016 0.50 (0.33-0.67) 18404 (±3956) 0.70 (±0.11) 30 min (±6700) post-dose Breakfast 24957 0.42 (0.33-0.67) 17983 (±4628) 0.65 (±0.08) 20 min (±8047) post-dose *Median (min-max) Under fasting conditions, average Cmax values were lower compared to fed conditions, while AUC0-inf values showed the opposite. However, the standard deviation for both Cmax, AUC0-inf and t1/2 was high. For all treatments, the maximum concentration was reached shortly after dosing, 25 to 30 minutes post-dose. The average half life was slightly shorter under fed conditions compared to the fasting condition. TABLE 36 Summary statistics of plasma 4-CNAB pharmacokinetic parameters Cmax tmax AUC (ng/mL) (h) (ng · h/L) 0-20 minutes Fasting 20670 (±7503) 0.33 (±0) 2898 (±1476) Breakfast 30 18809 (±4453) 0.33 (±0) 2275 (±669) min post-dose Breakfast 20 20642 (±9237) 0.33 (±0) 2800 (±1312) min post-dose 0-30 minutes Fasting 21533 (±7918) 0.39 (±0.09) 6295 (±2657) Breakfast 30 23973 (±6794) 0.48 (±0.06) 5958 (±1515) min post-dose Breakfast 20 24554 (±8130) 0.42 (±0.09) 6367 (±2300) min post-dose 0-3 hours Fasting 21750 (±7506) 0.44 (±0.13) 18318 (±3355) Breakfast 30 24016 (±6700) 0.50 (±0.09) 17073 (±3581) min post-dose Breakfast 20 24957 (±8047) 0.46 (±0.15) 16490 (±4547) min post-dose For the 0-20 minutes period, no differences in Cmax, tmax and AUC between the different treatment groups were theoretically to be expected. For Cmax, indeed no clear differences were observed, but for AUC the mean value was lower for the group who received breakfast 30 minutes post-dose compared to the other two treatment groups. If food intake affected the pharmacokinetics of 4-CNAB, it was expected that for the 0-30 minutes period, a difference in Cmax, tmax and AUC was observed between the group who received breakfast 20 minutes post-dose and the other two treatment groups. However, this was not observed. For all three treatment groups, Cmax was reached almost within 30 minutes post-dose; mean Cmax (0-30 minutes) values were only slightly lower compared to the Cmax (0-3 hrs). For insulin, summary statistics for the PK parameters derived from insulin for the periods 0-20 min, 0-30 minutes and 0-3 h post-dose are presented in Table 37. TABLE 37 Summary statistics of plasma insulin pharmacokinetic parameters Cmax tmax AUC (pmol/L) (h) (pmol · h/L) 0-20 minutes A Fasting 1040 (±1549) 0.29 (±0.07) 220 (±325) B Breakfast 30 min 751 (±835) 0.33 (±0) 133 (±138) post-dose C Breakfast 20 min 418 (±439) 0.31 (±0.06) 80 (±75) post-dose 0-30 minutes A Fasting 1176 (±1527) 0.31 (±0.11) 284 (±353) B Breakfast 30 min 751 (±835) 0.33 (±0) 227 (±249) post-dose C Breakfast 20 min 430 (±430) 0.33 (±0.09) 127 (±120) post-dose 0-3 hours A Fasting 1332 (±1436) 0.51 (±0.40) 472 (±377) B Breakfast 30 min 871 (±808) 0.39 (±0.18) 386 (±429) post-dose C Breakfast 20 min 430 (±430) 0.33 (±0.09) 177 (±120) post-dose For the 0-20 minutes period, no differences in Cmax, tmax and AUC between the different treatment groups were theoretically to be expected. However, clear differences were observed for mean Cmax and AUC, although considerable variation was reported. Cmax and AUC values were considerable lower under fed conditions compared to fasting conditions. If food intake affected the pharmacokinetics of insulin it was expected that for the 0-30 minutes period, a difference in Cmax, tmax and AUC was observed between the group who received breakfast 20 minutes post-dose and the other two treatment groups. However, this was not observed; the group who had breakfast 30 minutes post-dose showed also a clear difference when compared to fasting, which was not expected. It appears that there is considerable within subject variation in the absorption of insulin. On basis of the current results, it appears that there is no effect of breakfast on insulin absorption when given at 30 or 20 minutes post-dose. However, in some subjects in fasting condition or having had breakfast 30 minutes post-dose, a late insulin peak was seen whereas this is never seen in subjects having breakfast 20 minutes post-dose. Therefore, an effect of food intake 20 minutes post-dose cannot be excluded. Conclusions Absorption of 4-CNAB was rapid, and food intake at 30 and 20 minutes after dosing showed no effect on the pharmacokinetics of 4-CNAB. For all three treatment groups, 4-CNAB-profiles showed a high degree of similarity. In addition, no clear differences between treatment for pharmacokinetic parameters Cmax, tmax and AUC derived from 4-CNAB were observed. It could be concluded that food had no effect on 4-CNAB whether breakfast was eaten 20 or 30 minutes post-dose. Absorption of insulin showed high variety between and within subjects (between treatments), due to which no firm conclusion about the influence of food intake 30 or 20 minutes following dosing could be made. No correlation between 4-CNAB and insulin was observed. This might be related to the time when and the location where insulin is released from its carrier 4-CNAB. Unfortunately, very limited information on this process is available. From the present results it could not be concluded that food affected the pharmacokinetic parameters obtained from plasma insulin concentration data. Food intake caused an increase in plasma glucose concentrations but did not affect the effect of 4-CNAB/insulin on glucose in Type I diabetic patients. In diabetic patients, plasma glucose concentration data showed a steeper increase after breakfast compared to fasting conditions, which was expected. In general, the insulin peak was accompanied by a slight decrease or stabilization of glucose. However, the height in insulin concentrations reached did not correlate with the extent of glucose lowering. Plasma C-peptide concentrations were too low to perform any statistical analysis. It is not expected that 4-CNAB/insulin will change these minimal levels. No effect of food intake on C-peptide could be concluded in Type I diabetic patients. The number of AEs was highest when breakfast was taken 30 minutes after dosing of 4-CNAB/insulin. The majority of AEs was hyperglycemia, which might be expected in Type I diabetic patients. No hypoglycemia was observed, while this was expected. Probably the 4-CNAB/insulin dose was too low, although, high insulin peaks were observed. With regard to vital signs, ECG and clinical chemistry there were no clinical significant observations. Glucose measurements using Glucocard® showed high glucose concentrations, especially following breakfast. Patients received concomitant medication to treat these hyperglycaemic events. A single oral dose of 400 mg 4-CNAB/300 IU insulin in combination with food or under fasting conditions was safe and well tolerated. EXAMPLE 9 An open-label, single-dose, crossover study was conducted in order to compare the safety, pharmacokinetics, and pharmacodynamics of orally administered 4-CNAB/Insulin in fasting type 2 diabetic patients serving as their own controls, and to compare blood glucose, insulin and C-peptide levels following a standard meal in type 2 patients given their regular medication, with that of blood glucose, insulin and C-peptide levels following a standard meal with 4-CNAB/Insulin. Twenty-four (24) volunteers, between 46 and 70 years old, each with type 2 diabetes mellitus were studied. Patients had a body mass index of between 21 and 35 and had stable glycemic control (HgA1c ranged from 5.9 to 11.6%). Fifteen patients were on antidiabetic medication (either Metformin or Acarbose), and 9 patients controlled their diabetes by diet alone. All participants who were on medication did not take their antidiabetic drug 24 hours prior to study The diabetic volunteers were divided into two groups—in one group, twelve patients were studied in a fasting state, and in a second group, twelve patients were studied before and during standard meal. Every patient served as his own control and was tested without getting the insulin/4-CNAB mixture. With respect to Group 1, following a minimum of 8 hour overnight fast, subjects were given one capsule containing a mixture of insulin in a stepwise fashion (3 patients received 200U insulin, 5 patients received 300U insulin and 4 patients received 400U insulin) and a fixed dose of 300 mg 4-CNAB as a delivery agent. In the control session, a placebo was administered to these same patients. See FIG. 22 for a plot of plasma glucose vs. time for Group 1 subjects. With respect to Group 2, subjects had a standard meal (350 kcal) after a minimum of 8 hour overnight fast. Twenty minutes prior to the ingestion of food, the patients were administered a capsule contained 300U or 400U insulin (six patients received 300U insulin and six patients received 400U of insulin) and 300 mg of 4-CNAB. In the control session, these same patients took their own regular medication, either 850 mg Metformin or 100 mg Acarbose. Subjects who control their diabetes on diet alone had their meal (47 g of carbohydrates (54%) and 350 kcal total calories) without any drug. See FIG. 23 for a plot of plasma glucose vs. time for Group 2 subjects. Due to the fact that blood glucose level was not reduced by 30% (in average of the first three fasting subjects), the dose was increased to 300U insulin. Then, since the blood glucose level was not reduced by 30% with 300U insulin (in average of the 3 subjects), in both groups (fasting and standard meal), the dose of insulin was increased to 400U insulin. The delivery agent 4-CNAB was supplied by Emisphere Technologies Inc., of Tarrytown, N.Y., and was stored at room temperature desiccated until use. Recombinant Human Zinc Insulin was shipped directly by Eli Lilly and Company, and was stored at −20 C. Standard capsules were made of gelatin, size 0° C. A catheter was inserted into the antecubital arm vein of each patient. Blood was withdrawn at baseline twice, 5 to 10 minutes apart, and at timed intervals after the administration of the capsule. In group 1, the fasting group, blood was withdrawn during the first hour every 5 minutes and thereafter every 10-20 minutes. In group 2, the standard meal group, blood was withdrawn during the first two hours every 10 minutes and thereafter every 20 minutes. In both groups, blood samples were withdrawn until blood glucose reached basal levels. All plasma samples were analyzed for glucose, insulin, C-peptide and the delivery agent 4-CNAB. Blood glucose levels were measured in real time using two Elite Glucometers (Bayer corporation, Elkhart, Indianapolis, Ind., USA). At the end of the trial, plasma glucose concentrations were measured, using an Enzymatic UV test of Roche Diagnostics (Roche Diagnostics Indianapolis, Ind., USA). Plasma insulin and C-peptide were determined using radio-immunoassay kits produced by Linco Research, Inc., St. Charles, Mo., USA. Results and Conclusions While the results were highly variable, there was a clear trend indicating in most subjects the absorption of insulin and its biological effect causing either hypoglycemia or a suppressed elevation of blood glucose, following meals. In the meal session, when the effect of the insulin administered was compared to the effect of the anti-diabetic drug given, there was only a small difference in the blood glucose values, demonstrating the fact that oral insulin was biologically effective even during meals. As in previous examples provided herein employing non-diabetic volunteers, the rise in insulin levels appeared 10-30 minutes after the capsule was swallowed and preceded the drop in blood glucose levels (when there was a drop.) The C-peptide levels were measured in order to evaluate the extent of enteral absorption of insulin. The absorption of insulin caused a drop in the C-peptide levels, particularly in the standard meal group, indicating a decrease in endogenous insulin secretion due to the absorption of the insulin and the resulting hypoglycemia. Fasting diabetic type 2 volunteers given increasing dose of insulin (200U to 400U insulin) orally with 300 mg delivery agent 4-CNAB demonstrated a decrease in glucose levels and a moderate increase in insulin levels. In the standard meal group, the insulin capsule caused higher insulin levels and a decrease in C-peptide level. In most cases, following the ingestion of the capsule, there was a decrease in plasma glucose levels, and the nadir appeared after 10-30 minutes in the fast group. In patients with the standard meal who received their regular antidiabetic agent, the 4-CNAB/Insulin capsule “covered” their meal no less than, and sometimes even better than, the Metformin or the Acarbose. In most of the patients in the standard meal group, the C-peptide levels were suppressed, pointing to the fact that the secretion of endogenous hormone was partially abolished. Plasma insulin levels were elevated in most of the subjects in the fasting group. These levels were not always followed by a reduction in the glucose levels. No adverse events were detected during the trial or a few weeks later, except for one subject who complained of mild headaches five minutes after ingestion of the capsule, probably not associated with the trial mixture. It is concluded that this oral insulin preparation is safe and efficient. There is, however, a need for further improvement in absorption of the biologically active insulin. ADDITIONAL EXAMPLES In order that the method of reducing the incidence and/or severity of one or more disease states associated with chronic administration of insulin may be better understood, the following examples are set forth. These examples are for the purpose of illustration only and are not to be construed as limiting the scope of the invention in any manner. The delivery agent 4-CNAB was prepared by Emisphere Technologies, Tarrytown, N.Y. Insulin (Zinc, Human Recombinant) was purchased from Calbiochem (San Diego, Calif.). The Insulin potency was approximately 26 USP units/mg. Insulin was stored as a lyophilized solid at −20° C. In solution, it was stored as frozen aliquots (15 mg/mL) that were subjected to only one freeze-thaw cycle. An aqueous insulin stock solution was prepared (at pH 7.5) with a final insulin concentration of approximately 15 mg/mL. Delivery agents were dissolved in water with subsequent additions of sodium hydroxide or hydrochloric acid to both dissolve the delivery agent and to titrate the dosing solution to pH 7.5-8.5. The required amount of insulin was added to the delivery agent solution before dosing. Insulin levels in the rats were assayed using the Insulin ELISA Test Kit [DSL, Webster, Tex. Cat. #DSL-10-1600]. The assay covered the range 3.125 to 250 mU/mL. Blood glucose levels in the rats were measured using a glucometer, One-Touch Basic Blood Glucose Monitoring System, manufactured by Lifescan Inc. (Milpitas, Calif.). Animal Model A total of 60 male Sprague-Dawley rats were fasted for 24 hours and then anesthetized with Thorazine (1.5 mg/kg, im) and Ketamine (44 mg/kg, im). They were then divided into the following 5 treatment groups: 1. H2O (p.o. 1 mL/kg) 2. Carrier (p.o., 1 mL/kg; 200 mg/kg) 3. Insulin (p.o., 1 ml/kg; 0.5 mg/kg) 4. Insulin and Carrier (p.o., 1 ml/kg; 0.5 mg/kg Insulin and 200 mg/kg 1182) 5. Insulin (s.c., 0.05 mg/kg) There were twelve animals per group, with three being sacrificed at 30, 60, 120 and 180 minutes. For serum insulin and blood glucose monitoring, 0.4 mL of blood was drawn from the tail artery. Following euthanasia, an aorta sample was removed and snap-frozen in liquid nitrogen. All animal studies where conducted in accordance with the IACUC approved protocols. Animals received streptozotocin (65 mg/kg, iv) after acclimation to the facility. Blood glucose was measured at 24, 48, and 72 hours after injection. Those animals with blood glucose greater than 150 mg/dl were fasted 12 hours and received treatment as described. Hybridization Sample Preparation Total RNA was prepared from the frozen tissue sample following the protocol for use of Trizol Reagent (Invitrogen, Inc., Carlsbad, Calif.). The samples were then further cleaned up by use of the Qiagen Midi Kit (Valencia, Calif.). Quality of each RNA sample was assessed using agarose gel electrophoresis and UV absorbance at 260 and 280. Acceptable RNA samples were pooled in equal quantities on a mass basis. This pooled sample was used to prepare cDNA following the protocol provided by Affymetrix. This sample was then used as template in an ii: vitro transcription labeling and amplification reaction using the Enzo BioArray High Yield RNA Transcript Labeling Kit (Affymetrix Inc., Santa Clara, Calif.). 15 μg of labeled transcript was then fragmented and used to prepare a hybridization solution as described in the Affymetrix GeneChip Protocol, Affymetrix, Inc., 2000. GeneChip Analysis The samples were hybridized to a Test Array and 5′ to 3′ ratios, detection limit, and image quality were assessed to ensure the quality of the labeled sample. Acceptable samples were then hybridized to an Affymetrix Rat U34A array. Washing and staining of these arrays was performed using the standard Affymetrix protocols. Array quality was assessed in the same manner as the Test array. Acceptable samples were analyzed both in the expression patterns seen across the group as well as pair wise in the following manner: 1. Group 2 vs. Group 1 2. Group 3 vs. Group 1 3. Group 4 vs. Group 1 4. Group 5 vs. Group 1 5. Group 4 vs. Group 5 6. Group 4 vs. Group 2 EXAMPLE 12 Fold change were determined by the Affymetrix Microarray Suite Software package and values below 2 fold were considered insignificant. This software package analysis compares the individual members of each probe set to determine a Difference Call. In this report all calculated fold changes are used in the figures, however in the results and discussion only those fold changes that received an Increasing or Decreasing call by the Affymetrix software were used to draw conclusions. These data are included in Table 38 below. TABLE 38 Fold Change Data From Genechip Analysis of Oral and SC Dosing of Insulin Subcutaneously Direct P.O. to S.C. Orally Dosed Dosed Comparison Time (minutes) 60 120 180 60 120 180 30 60 120 180 12-LO 2.7 −3.4 −2.1 5.8 4.3 −6.4 −1.6 −2.2 −14.3 3 6-Phosphofructo-2- 1.2 3.3 1.8 1.2 3.2 1.4 −1.3 −1 −1.1 1.3 kinase/fructose-2,6- bisphosphatase a-actin −1.2 1.6 3.8 −1.2 1.6 3.8 1.1 −1.1 1.1 2 c-myc −2.4 −1.6 1.9 1 −1 3.8 −1.1 −2.6 −1.6 1.1 desmin −15.7 −2.8 8.4 −15.7 −2.8 8.4 −1.4 −28.2 6.6 −3 Egr-1 −2.1 1.1 5.6 2.3 1.6 6.9 1.6 −4.7 −1.4 −1.2 Fru-1,6-P −1.7 −1.4 −3.3 −2.2 1 −2.9 −1.3 −1.8 −1.4 −2.2 G6Pase −25.1 −12.2 2.8 1.2 −8.1 17.1 7.1 −35 −6.8 −8.7 Glycogen −14.2 −4.1 1.6 4.6 −33.4 1.8 −1.4 −57.6 10.5 −1.1 Phosphorylase Glycogen synthase −1.1 9.4 −1.4 −2.3 5.3 −1.2 −2.3 2.2 1.8 −1.2 gp130 3.7 1.3 1.7 3.3 1.8 1.3 1.4 1.2 −1.6 1.4 GSK3 beta −2.5 −1.4 1.5 −4.2 −1 1.4 1.8 1.9 −1.4 1.2 Hexokinase II 1.1 9.8 2.2 −1.6 5.3 1.6 2.8 2.1 2 1.2 HO-1 −4.9 −1.5 2.5 −1.6 5.8 1.8 1.8 −3.3 −6 1.4 ICAM-1 −2.5 −1.1 1.6 −1.9 1.8 2.9 1.9 −1.3 −1.9 −1.8 IGFBP-1 3 −39.2 −2 2.4 −3.1 −1.6 −1.1 1.4 −6.3 −1.2 IGFBP-2 −1.1 −15.8 1.5 −1.3 −6.9 1.1 1.7 1.2 −2.3 1.4 IGFBP-3 −2.5 1.4 2 −1.4 1.6 1.1 −1.2 −1.6 −1.1 1.8 IL-6 −1.7 1.9 −1.7 −2 3.8 1.4 −1.4 1.8 −1.6 −2.4 Jun B −6.1 −6.6 −2.6 −1.3 1.3 1.9 1.3 −3.3 −4 −6.5 PAI-1 −2.6 1.5 −1 1.1 2.6 1.8 −1.1 −2.8 −1.7 −1.6 PAI-2 4.8 2.1 −2 2.3 2.1 −1.4 2.6 2.3 1.3 −1.4 PEPCK −1.6 2.1 −1.4 −1.4 2.1 −1.8 2.8 −1.1 −1 1.3 SM22 1.1 1.1 2.1 1.1 1.1 2.1 −1.5 1.1 1 1.2 vimentin −1.6 3.1 1.3 −1.5 2.8 −1 −1.1 −1 1.1 1.3 The numbers in bold in Table 38 indicate values that the Affymetrix Microarray Suite software gave an Increasing or Decreasing call. EXAMPLE 13 Pharmacokinetics and Pharmacodynamics FIG. 24 shows a graph of blood glucose (mg/mL) over time following a single administration with subcutaneous and oral delivery. This figure shows that the administration of insulin orally, using 4-CNAB as a carrier, yielded approximately 95% of the glucose depression seen with the traditional subcutaneous dosing. However, as shown in FIG. 25, which shows the serum insulin (mU/mL) over time using the administrations of FIG. 24, the serum insulin C required to achieve this depression however, in the orally administered animals was approximately 30% of those receiving subcutaneous injections. The tmax was also about 15 minutes later for the subcutaneous sample. The depression in blood glucose was likely eliminated by the continued administration of anesthesia in order to continue blood sampling. EXAMPLE 14 Glucose Regulation Glycolysis/Gluconeogenesis occurs through three main cycles that can be driven in both a glycolytic and gluconeogenic direction. From a glycolytic standpoint, the first cycle is the Glu/Glu-6-Pase Cycle, which converts glucose to Glc-6-P. This is followed by the Fru-6-P/Fru-1, 6-P2 Cycle, and the Pyruvate/PEPCK Cycle. Glu/Glu-6-Pase Cycle In muscle tissue, glucose is converted to Glc-6-P by hexokinase. See Granner et al., J Biol Chem 265, 10173-6 (1990). In the studies, both subcutaneous and orally administered insulin yielded elevations in the mRNA levels of the enzyme Hexokinase II. FIG. 26 shows Glucokinase and G6 Pase mRNA expression compared to sham dosing. As shown in FIG. 26, despite the lower serum insulin levels, the orally dosed animals showed a 2-fold higher level of hexokinase 11 at 120 minutes. Direct comparison of the arrays from the orally dosed and subcutaneously dosed animals indicates a 2.8-fold higher mRNA level at 30 minutes. Fru-6-P/Fru-1, 6-P2 Cycle The bi-functional enzyme 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase serves as a switch between gluconeogenesis and glycolysis. Insulin administration has been shown to drive increases in this enzyme. Granner et al., J Biol Chem 265, 10173-6. (1990); Lemaigre et al.,. Biochem J 303, 1-14. (1994); Denton. et al., Adv Enzyme Regul 36, 183-98 (1996). FIG. 20 shows Fru-1, 6-P and 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase mRNA expression compared to sham dosing. In our studies and as shown in FIG. 27, this enzyme showed a nearly identical pattern of expression between the two routes of administration with no significant differences in gene expression being observed. The enzyme Fructose 1,6-bisphosphatase catalyzes the conversion of Fru-1, 6-P2 to Fru-6-P, the gluconeogenesis side of this cycle. This mRNA is induced by diabetes and starvation and reduced by insulin administration. As shown in FIG. 27 and similar to 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase, the pattern of expression for this enzyme is nearly identical in both sets of test animals. Pyruvate/PEP Cycle Phosphoenolpyruvate carboxykinase (PEPCK) is a key enzyme in the gluconeogenesis pathway converting oxaloacetate to phosphoenolpyruvate. It is known to be down regulated by insulin. See, for example, Granner et al., J Biol. Chem. 265, 10173-6. (1990); Lemaigre et al. Biochem J303, 1-14. (1994); Denton, R. M. et al., Adv Enzyme Regul 36, 183-98 (1996); Gabbay et al., J Biol Chem 271, 1890-7 (1996). FIG. 21 shows PEPCK mRNA expression compared to sham dosing. As shown in FIG. 28, little difference is seen in the expression levels of this mRNA. Glycogen Synthesis Insulin is also known to increase the rate of glucose conversion to glycogen. This is performed by linking glucose-1-P molecules into a branched chain. This chain then serves as a store of glucose to be utilized in hypoglycemic states. Glycogen Synthase enzyme is responsible for extending the chain of glucose molecules. Administration of insulin is known to up-regulate this enzyme. Vestergaard et al., Dan Med Bull 46, 13-34 (1999). FIG. 29 shows glycogen synthase mRNA expression compared to sham dosing. As shown in FIG. 29, oral dosing and subcutaneous dosing produced nearly identical patterns of expression in the levels of this enzyme, with oral dosing yielding nearly twice the increase in mRNA at 120 minutes. The enzyme Glycogen Synthase Kinase 3 is involved in the inhibition of glycogen synthesis through the phosphorylation of glycogen synthase. As shown in FIG. 29, the expression pattern of this enzyme in the two dosing samples was very similar, exhibiting an initial decrease that returns to sham levels at 120 and 180 minutes. Subcutaneous dosing achieved a slightly stronger down regulation at 60 minutes; however, this difference was not seen in the direct comparison between the two GeneChips. The enzyme Glycogen Phosphorylase is responsible for the breakdown of the glycogen chain. Insulin is known to normalize phosphorylase levels in diabetic animals. In our studies, as shown in FIG. 29, a dramatic difference in the levels of this enzyme was observed. The oral dosing achieved an immediate decrease in mRNA levels that slowly increased to sham levels at 180 minutes. The subcutaneous dosing yielded an early up regulation that was reversed dramatically at 120 minutes and returned to near sham levels at 180 minutes. The differences seen between the oral and subcutaneous dosings were observed in comparison to sham as well as to each other. EXAMPLE 15 Vascular Response to Injury Vascular diseases are commonly described as a response to injury. The vessel is exposed to a stimulus (injury) that leads to a progression of responses designed to repair damage to the vessel wall. This injury may be in several forms, including oxidative stress, mechanical stress, viral infection and changes in shear stress. Though the injury itself is variable, the response to injury has many common aspects. Early response genes are up regulated leading to the transcription of genes for cellular migration and proliferation as well as the recruitment of inflammatory cells to the site of injury. As the response continues, enzymes that lead to matrix remodeling will be expressed. The result is generally the thickening of the arterial wall through smooth muscle proliferation and atherosclerotic plaque formation. The clinical result is the arteriopathies associated with diabetes. In this application, a method for examining the mRNA levels of genes associated with various forms of vascular injury is described. Vascular diseases are a complex set of processes that involve numerous changes in mRNA levels. While the mRNA markers of vascular injury presented here were seen in this specific study, several others are likely to exist. These include early response genes (i.e. c-myb and c-fos), cytokines (i.e. interleukins, and chemokines), growth factors and their receptors (i.e. fibroblast growth factor, vascular endothelial growth factor, and transforming growth factor beta), adhesion molecules (i.e. selecting, and integrins), extracellular matrix proteins (i.e. collagen and actin), matrix metalloproteinases and their inhibitors, cell cycle proteins (i.e. cyclins and cyclin dependent kinases), and protein kinases (i.e. mitogen activated protein kinases, and protein kinase C), some of which are presented here. This list continues to grow as vascular disease becomes better understood, and which markers are in a particular sample may vary. Early Response Genes One of the initial markers of arterial injury is the expression of transcription factors in control of the subsequent expression of proteins responsible for potentiating the vascular response to injury. These early response genes include c-myc, c-fos, jun, and Egr-1. FIGS. 30A and 30B show early response gene mRNA expression compared to sham dosing. In our studies, and as shown in FIGS. 30A and 30B, a differential expression in the levels of Egr-1, c-myc, Jun B and Ets-1 was observed. Egr-1 is associated with several elements of the vascular response to injury. Its expression is very low in uninjured vessels but increases with mechanical or oxidative injury. Egr-1 has been demonstrated to drive increases in mRNA levels of cytokines, adhesion molecules, growth factors and members of the coagulation cascade. In our study and as shown in FIGS. 30A and 30B, Egr-1 is immediately up regulated by subcutaneous insulin administration to a level 4.7-fold higher than with oral. Oral administration does not induce an early increase in Egr-1 mRNA levels. Instead, levels are maintained at near sham levels until at 180 minutes when they are elevated to slightly below that of the subcutaneously animals. Balloon injury to rat aortae leads to a rapid increase in mRNA for Jun B. Jun and Fos bind to form the heterodimeric transcription factor AP-1. This factor leads to the expression of adhesion molecules, cytokines, and other factors involved in the response to injury. As shown in FIGS. 30A and 30B, Jun B expression remained near sham levels at all time points; however, direct comparison between arrays indicates significantly higher levels in the subcutaneously dosed samples at 120 and 180 minutes. Though both levels are near control at 120 and 180 minutes, a comparison between the two arrays shows a significant decrease in expression in the orally dosed sample. The switch in the cell cycle state from the dormant Go to the proliferative GI is accompanied by increased levels of c-myc. Vascular damage induces expression of c-myc, and inhibition of c-myc through antisense oligonucleotides prevents intimal hyperplasia following balloon injury in the rat and porcine. It is therefore a critical marker of vascular injury. As shown in FIGS. 30A and 30B, subcutaneous dosing and not oral dosing lead to a significant increase in the mRNA levels of c-myc at 180 minutes. The orally dosed samples remained at near sham levels; however no significant difference between the two dosing routes was seen when compared directly. Ets-1 mRNA levels for subcutaneous and oral dosing are shown in FIG. 30A. EXAMPLE 16 Insulin-Like Growth Factor Family Insulin-like growth factor (IGF) I and II are a single chain polypeptides sharing homology with proinsulin. They play an important role in systemic glucose metabolism but have also been shown to effect cell cycle progression, mitogenesis, cell migration and apoptosis. Much of IGF's function is regulated by IGF-binding proteins (IGFBPs). In general, IGFBPs bind to IGF, preventing its binding to the IGF receptor. IGFBP-3 is the most prevalent in this respect, binding >90% of the IGF in adult serum. Though their primary function is the regulation of IGF, IGFBPs have been shown to have a biological effect at sites of vascular injury. IGFBP-1 stimulates the migration of vascular smooth muscle cells (VSMC) independent of IGF-1. IGFBP-1 to −5 have been shown to be expressed in restenotic tissue suggesting a role in the arterial response to vascular injury. FIG. 31 shows IGFBP mRNA expression compared to sham dosing. As shown in FIG. 31, no significant difference in the expression of IGF-1, IGF-2 or the IGF receptor was seen between the two dosing routes. However, there were drastic differences seen with the IGFBPs. IGFBP-1 was reduced 39-fold as opposed to 3-fold, and IGFBP-2 was reduced 15-fold compared to 6-fold at two hours compared to the sham dosing. In both cases the IGFBP expression is decreased, opposite to the effect seen in vascular injury. The mechanism driving this change may be beyond that of a direct effect of insulin on the VSMC's. Nonetheless, it is clear that the level of IGFBP-1 and -2 expression is higher in the subcutaneously dosed animals and this correlates with an increased response to injury. Little change was observed in IGFBP-3. EXAMPLE 17 Adhesion Molecules One of the initial steps in arteriopathies is the adhesion of inflammatory cells to the vessel wall. This is mediated by adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1), the selectins and the integrins. Changes in the levels of mRNA for these genes were examined, and FIG. 32 shows intercellular adhesion molecule-1 mRNA expression compared to sham dosing. As shown in FIG. 32, no significant effect was seen in either dosing group except in the case of ICAM-1. ICAM-1 was increased at 180 minutes in the subcutaneously dosed animals. Increased expression of ICAM-1 is seen in several different forms of vascular injury, and is associated with the recruitment of inflammatory cells to the site of injury. This difference is seen both in the comparison to sham and in the direct comparison of the arrays from the two dosing groups. EXAMPLE 18 Cytokines Sites of vascular injury communicate their inflamed state via the expression of pro-inflammatory cytokines that through both autocrine and paracrine effects regulate the expression of growth factors, cytokines, adhesion factors, and matrix metalloproteinases. Of these one found commonly at sites of vascular disease is interleukin-6 (IL-6). VSMCs are not initially susceptible to IL-6 stimulation as they do not express either the IL-6 receptor or glycoprotein 130 (gp130), both of which allow IL-6 signaling. VSMCs are the first cells in which gp130 has been shown to be up regulated. FIGS. 33A and 33B show cytokine mRNA expression compared to sham dosing. In our studies and as shown in FIGS. 33A and 33B, gp130 was seen to be equally increased in both subcutaneously and orally dosed animals. However, a significant increase in IL-6 mRNA was seen only in the subcutaneously dosed group, as shown in FIGS. 33A and 33 This is a critical difference as it shows the aorta of the both groups getting “primed” for a response to injury, but only the subcutaneous dosing actually drives significant production of the expected signal. Cytokine data are represented graphically also for the cytokines Eotaxin, MCP-1, IL-12 and EL-13 in FIG. 33 EXAMPLE 19 Lipid Peroxidation Several proteins associated with the metabolism of lipids and the oxidation of LDL have been implicated in the progression of atherosclerosis. It has been suggested that the oxidation of LDL produces agents that recruit monocytes, promote their adhesion to the endothelium, and inhibit macrophages from migrating. These steps lead to the formation of foam cells and the fatty streak found in atherosclerotic lesions. 12-lipoxygenase (12-LO) has been demonstrated to drive atherosclerotic lesion formation, and it has also been documented to be significantly up regulated in the vascular response to injury. It therefore is of critical importance in this setting. FIG. 34 shows lipid peroxidation mRNA expression compared with sham dosing. As shown in FIG. 34, at 60 minutes, there is a 5.8-fold increase in the subcutaneously dosed samples as compared to a 2.7-fold in the orally dosed. In the orally dosed samples, this up-regulation is reversed at 120 and 180 minutes with 3.4- and 2.1-fold reductions in mRNA levels compared to sham. In the subcutaneously dosed animals, the mRNA levels remain high until 180 minutes, at which time a 6.4-fold decrease is observed. It is important to note that the values at 120 minutes represent greater than 14-fold higher levels of this mRNA in the subcutaneously dosed samples. Heme Oxygenase-1 (HO-1) is induced by mildly oxidized LDL. It serves a protective antioxidant function through elimination of heme and the further antioxidant capabilities of its reaction products. As shown in FIG. 24, the mRNA levels of this gene are seen to be 6-fold higher in the subcutaneously dosed animals when compared to the orally dosed animals at 60 minutes. Though the function of this enzyme is protective, its up regulation represents a response to injury and may well be in response to the increased levels of 12-LO or its stimulation of LDL oxidation. EXAMPLE 20 Thrombosis Fibrin deposition within the arterial wall is believed to play a major role in atherosclerosis. Through their fibrinolytic activity, the plasminogen activators block this from occurring. These protective actions are blocked by the plasminogen activator inhibitors (PAI-1 and -2). FIG. 35 shows plasminogen activator inhibitors mRNA expression compared to sham dosing. In our study, as shown in FIG. 35, PAI-1 levels were elevated in the subcutaneous samples only. A 2.6-fold increase over sham and a 2.8-fold increase over oral were seen at 120 minutes. A 2.6-fold decrease in these levels was seen in the oral samples at 60 minutes, which returned to sham levels at 120 and 180 minutes. PAI-2 expression was similar in both sets of dosing. At 60 minutes, the orally dosed samples exhibited a significantly greater (4.8-fold) level of PAI-2. This elevation is not present at 120 and 180 minutes. There was no significant difference between the two dosing routes for this RNA. EXAMPLE 21 Additional markers are illustrated in FIG. 36, which compares the effects of subcutaneous delivery of insulin and oral delivery of insulin on the mRNA expression of NPY, TGF-beta, ICAM-1 and 12-LO. EXAMPLE 22 Comparison of mRNA expression between subcutaneous delivery of insulin and oral delivery of insulin are shown for the markers THY-1, VEGF-B and Integrin aE2 in FIG. 37. For the oral delivery data, the effects on mRNA expression of two different dosages are shown. EXAMPLE 23 Pharmacokinetics and Pharmacodynamics in a Streptozotocin Diabetic Model FIG. 38 shows a graph of blood glucose (mg/mL) over time following a single administration with subcutaneous and oral delivery for a streptozotocin diabetic model. Two different oral dosages of insulin are demonstrated. FIG. 39 shows the serum insulin levels (mU/mL) over time using the administrations of FIG. 38. Controls for Gene Chip Studies As control groups, the carrier and insulin were orally administered separately. The results of these GeneChips were analyzed to identify any possible activities of the individual components of the composition. The carrier alone samples generated no consistent and significant changes in mRNA levels in the aorta. The same is true for the insulin alone samples. Discussion The examples discussed above demonstrate the ability of an oral composition of insulin to alleviate the undesirable effects on the vasculature of the traditional subcutaneous dosing at the level of messenger RNA regulation, and document changes in glucose metabolism caused by altering the dosing route. The pharmacodynamic data demonstrates the ability of the orally dosed composition to achieve a glucose depression similar to that of the traditional dosing method. Though the pharmacodynamic data is similar, the pharmacokinetic data shows a greatly lower serum insulin level in the orally dosed composition compared with that of the traditional dosing method. The difference in serum insulin level must be a result of direct administration of the insulin to the liver. The liver reacts to the bolus of insulin in two ways. First, it accelerates glycolysis, glycogen synthesis and other mechanisms associated with hyperinsulinemia. Second, first-pass metabolism decreases the level of insulin reaching the systemic circulation. The result is a rapid decrease in blood glucose and a decrease in the level of insulin to which the systemic circulation is exposed. In achieving a similar glucose control as subcutaneous dosing while lowering the exposure of the peripheral circulation to insulin, the undesirable effects of insulin on non-target tissues can be prevented. Although not considered a major site of glucose metabolism, VSMCs do possess glucose regulatory capacity and therefore yield insight into differences in the peripheral response to changing the dosing route. What is surprising is that despite drastically lower levels of circulating insulin, little difference in the mRNA levels of key enzymes involved in glucose regulation is observed. In fact, the levels seen for hexokinase II and glycogen synthase suggest a stronger response to the oral composition. We conclude that natural regulation of glucose involves the liver controlling peripheral glucose metabolism and utilization through a messenger other than insulin. The fact that higher circulating levels of insulin can compensate for the loss of this natural process may simply be due to the fact that the two proteins bind the same or similar receptors. The IGF system is a prime candidate for such secondary signaling and is known to exhibit glucose regulatory activity. IGFBP-1 and -2 were down regulated in both sets of data. This is contrary to published data on vascular injury and may not be associated with a vascular injury response so much as playing a role in glucose control. The data previously reported on the liver's response to changes in dosing route of insulin does not demonstrate a differential response in either the IGF's or their binding proteins. This does not rule out this pathway, as no data is available on the proteases responsible for degradation of the IGFBP's. It is quite possible that the liver responds to elevated insulin levels by releasing IGFBP proteases that then degrade IGFBP's freeing IGF to drive a reduction in glucose. Further study is required to determine if this is the case, but the liver and aorta gene array data supports this hypothesis. If correct, this hypothesis supports the use of an oral composition of insulin simply based on its ability to mimic the natural glucose control pathway. There are numerous disease states related to diabetes, including associated neuropathies, nephropathies and retinopathies. These may be due, at least in part, to the degradation of the microvasculature after chronic dosing of insulin. Because orally administered insulin can achieve a greater glucose depression with a lower systemic level of insulin, a lower incidence of diabetes related disorders results. Using gene micro-arrays, we were able to monitor numerous areas of the vascular response to injury in animals receiving our oral composition and the traditional subcutaneous insulin. The first step is to assess any effects from administration of the carrier alone. It is believed that, upon entering the systemic circulation, the carrier and insulin no longer interact due to the dilution effect. An exhaustive analysis of the array data from animals receiving the carrier without insulin was performed including adding a second three-hour experiment to try to further identify any response. The analysis yielded no mRNA's whose levels appear to be affected by administration of the carrier. To clarify, any response seen in the carrier alone samples was also seen in the animals receiving insulin orally without carrier suggesting that the effect was due to an experimental parameter not accounted for in the sham dosing. This study is not designed to identify specific genes regulated by the carrier, as such a study would require multiple animals at each time point. Nonetheless, this data supports the view that the carrier has a minimal effect on the vasculature. The vascular response to injury is a complex set of processes that occur over an extended period of time. Some of these, such as atherosclerotic plaque formation, occur over years or even decades, while the more rapid examples, such as Restenosis, occur on the order of months. Thus, the time scale for studying vascular damage in animal models is on the order of days or weeks and not hours. In this study, we aimed to identify any signs of vascular injury induced by a single dose of insulin and to document any effect changing the route of administration had on these markers. While this may have been a rather optimistic approach, since the type of injury is mild and the time course very short compared to standard models of vascular injury, the results quite remarkably demonstrate qualitatively that oral dosing of insulin beyond simply mimicking the natural route of entry, also attenuates the injury to the vasculature. It was determined that subcutaneous insulin dosing lead to higher levels of three key early response genes, while a significant increase in only one of these genes was seen with oral dosing. Likewise, elevated levels of IL-6 and ICAM-1 were seen only in the subcutaneously dosed animals. These genes represent the early signs of the cell proliferation as well as the start of an inflammatory response, and their expression can trigger a cascade of events leading to deterioration of the vessel wall. Subcutaneous dosing also generated higher levels of 12-lipoxygenase, PAI-1, PAI-2 and heme oxygenase-1. This second set of genes can be responsible for creating further injury to the vasculature in the form of thrombus and oxidized LDL. Repeated expression of these genes could lead to atherosclerosis and thrombosis. It was found that oral dosing of insulin prevented elevations in all of these genes, except an elevation of PAI-2 that was not significantly different from that seen with subcutaneous dosing. Together, this data suggest the clear advantage of oral dosing of insulin over subcutaneous dosing of insulin of lessened incidence of vascular diseases. The data from the subcutaneously dosed animals presents a picture of a healthy aorta at the earliest stages of an extended vascular response to injury. The data from the orally dosed animals clearly indicates a dramatic attenuation of this response. By administering insulin orally, elevations in the levels of genes associated with cellular proliferation and migration, inflammatory cell recruitment, and atherosclerotic plaque formation were almost entirely avoided. It is remarkable that this difference is so clear even following only a single administration of insulin. It was initially believed that multiple dosings would be required before a clear difference in aorta mRNA levels was achieved. In light of this data, it is easy to see how chronic subcutaneous dosing can lead to the increased incidence of vascular diseases and their associated clinical complications. Ongoing studies are currently being conducted which support the increased incidence of vascular disease in chronic subcutaneous dosing. Furthermore, the data suggests that the peripheral glucose metabolism may be similar despite a decrease in circulating insulin levels. Our results show that returning insulin delivery to its natural site of entry into the circulation and consequently lowering the peripheral insulin levels can achieve a lower incidence of the diseases associated with diabetes. While we have described a number of embodiments of this invention, various modifications of the invention in addition to those shown and described herein will become apparent to those skilled in the art from the foregoing description. Such modifications are intended to fall within the scope of the appended claims. In the preceding specification, the invention has been described with reference to specific exemplary embodiments and examples thereof. It will, however, be evident that various modifications and changes may be made thereto without departing from the broader spirit and scope of the invention as set forth in the claims that follow. The specification and drawings are accordingly to be regarded in an illustrative manner rather than a restrictive sense. While we have hereinbefore described a number of embodiments of this invention, it is apparent that our basic constructions can be altered to provide other embodiments which utilize the processes and compositions of this invention. Therefore, it will be appreciated that the scope of this invention is to be defined by the claims appended hereto rather than by the specific embodiments which have been presented hereinbefore by way of example.

<SOH> BACKGROUND OF THE INVENTION <EOH>Proteins, carbohydrates and other biological molecules (“biological macromolecules”) are finding increasing use in many diverse areas of science and technology. For example, proteins are employed as active agents in the fields of pharmaceuticals, vaccines and veterinary products. Unfortunately, the use of biological macromolecules as active agents in pharmaceutical compositions is often severely limited by the presence of natural barriers of passage to the location where the active agent is required. Such barriers include the skin, lipid bi-layers, mucosal membranes, severe pH conditions and digestive enzymes. Oral delivery of active agents is a particularly desirable route of administration, because of safety and convenience considerations and because oral delivery replicates the physiologic mode of insulin delivery. In addition, oral delivery provides for more accurate dosing than multidose vials and can minimize or eliminate the discomfort that often attends repeated hypodermic injections. There are many obstacles to successful oral delivery of biological macromolecules. For example, biological macromolecules are large and are amphipathic in nature. More importantly, the active conformation of many biological macromolecules may be sensitive to a variety of environmental factors, such as temperature, oxidizing agents, pH, freezing, shaking and shear stress. In planning oral delivery systems comprising biological macromolecules as an active agent for drug development, these complex structural and stability factors must be considered. In addition, in general, for medical and therapeutic applications, where a biological macromolecule is being administered to a patient and is expected to perform its natural biological function, delivery vehicles must be able to release active molecules, at a rate that is consistent with the needs of the particular patient or the disease process. One specific biological macromolecule, the hormone insulin, contributes to the normal regulation of blood glucose levels through its release by the pancreas, more specifically by the B-cells of a major type of pancreatic tissue (the islets of Langerhans). Insulin secretion is a regulated process which, in normal subjects, provides stable concentrations of glucose in blood during both fasting and feeding. Diabetes is a disease state in which the pancreas does not release insulin at levels capable of controlling glucose levels. Diabetes is classified into two types. The first type is diabetes that is insulin dependent and usually appears in young people. The islet cells of the pancreas stop producing insulin mainly due to autoimmune destruction and the patient must inject himself with the missing hormone. These Type 1 diabetic patients are the minority of total diabetic patients (up to 10% of the entire diabetic population). The second type of diabetes (type 2) is non-insulin dependent diabetes, which is caused by a combination of insulin resistance and insufficient insulin secretion. This is the most common type of diabetes in the Western world. Close to 8% of the adult population of various countries around the world, including the United States, have Type 2 diabetes, and about 30% of these patients will need to use insulin at some point during their life span due to secondary pancreas exhaustion. Diabetes is the sixth leading cause of death in the United States and accounted for more than 193,000 deaths in 1997. However, this is an underestimate because diabetes contributes to substantially many deaths that are ultimately ascribed to other causes, such as cardiovascular disease. Complications resulting from diabetes are a major cause of morbidity in the population. For example, diabetic retinopathy is the leading cause of blindness in adults aged 20 through 74 years, and diabetic kidney disease accounts for 40% of all new cases of end-stage renal disease. Diabetes is the leading cause for amputation of limbs in the United States. Heart disease and strokes occur two to four times more frequently in adults with diabetes than in adult non-diabetics. Diabetes causes special problems during pregnancy, and the rate of congenital malformations can be five times higher in the children of women with diabetes. The main cause of mortality with Diabetes Mellitus is long term micro- and macro-vascular disease. Cardiovascular disease is responsible for up to 80% of the deaths of Type II diabetic patients. See, for example, Kirpichnikov et al., Trends Endocrinol Metab 12, 225-30 (2001); Garcia et al., Diabetes 23, 105-11 (1974); Haffner et al., N Engl J Med 339, 229-34 (1998); Sowers, Arch Intert Med 158, 617-21 (1998); Khaw, K. T. et al., Bmj 322, 15-8 (2001). Diabetics have a two- to four-fold increase in the risk of coronary artery disease, equal that of patients who have survived a stroke or myocardial infarction. See, for example, Haffner et al., N Engl J Med 339, 229-34 (1998); Sowers, Arch Intern Med 158, 617-21(1998). This increased risk of coronary artery disease combined with an increase in hypertensive cardiomyopathy manifests itself in an increase in the risk of congestive heart failure. Stratton et al., Bmj 321, 405-12 (2000); Shindler, D. M. et al., Am J Cardiol 77, 1017-20 (1996). These vascular complications lead to neuropathies, retinopathies and peripheral vascular disease. See Kirpichnikov et al., Trends Endocrinol Metab 12, 225-30 (2001). There is a need for diabetes treatments that will decrease the prevalence of such vascular disease in diabetes patients. The beneficial effects of tight glycemic control on the chronic complications of diabetes are widely accepted in clinical practice. However, only recently it has been firmly established that elevated blood glucose levels are a direct cause of long-term complications of diabetes. The Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS) both showed that control of blood glucose at levels as close to normal as possible prevents and retards development of diabetic retinopathy, nephropathy, neuropathy, and microvascular disease. Drug therapy of diabetes type II has consisted of oral antidiabetic agents and insulin if and when the oral agents fail. Insulin therapy in type I diabetes is essential and is intended to replace the absent endogenous insulin with an exogenous insulin supply. Because insulin is a protein drug (MW approx. 6000 Da) that is not absorbed in the gastrointestinal tract, it ordinarily C requires parenteral administration such as by subcutaneous injection. The problem of providing bioavailable unmodified human insulin, in a useful form, to the ever increasing population of diabetics has occupied physicians and scientists for almost 100 years. Many attempts have been made to solve some of the problems of stability and biological delivery of this small protein. Most diabetic patients self-administer insulin by daily subcutaneous injections. However, the limitations of multiple daily injections, such as inconvenience, poor patient acceptability, compliance and the difficulty of matching postprandial insulin availability to postprandial requirements, are some of the better known shortcomings of insulin therapy. Despite studies demonstrating the beneficial effects of tight glycemic control on chronic complications of diabetes, clinicians are not particularly keen on aggressive insulin therapy, particularly in the early stages of the disease, and this is widely accepted in clinical practice. The unmet challenge of achieving tight glycemic control is due, in part, to the shortcomings of the available subcutaneous route of insulin administration and the fear of hypoglycemia. In addition to the practical limitations of multiple daily injections discussed above, the shortcomings of the commonly available subcutaneous route of insulin administration have resulted in the generally inadequate glycemic control associated with many of the chronic complications associated with diabetes. Elevated systemic levels of insulin lead to increased glucose uptake, glycogen synthesis, glycolysis, fatty acid synthesis and triacylglycerol synthesis, leading to the expression of key genes that result in greater utilization of glucose. In the field of insulin delivery, where multiple repeated administrations are required on a daily basis throughout the patient's life, it would be desirable to create compositions of insulin that maintain protein tertiary structure so as not to alter physiological clinical activity and stability and do not require injections. It would also be desirable to provide compositions of insulin that could be orally administrable, e.g., absorbed from the gastrointestinal tract in adequate concentrations, such that insulin is bioavailable and bioactive after oral administration. Oral absorption allows delivery directly to the portal circulation. A method of providing insulin without the need for injections has been a goal in drug delivery. Insulin absorption in the gastrointestinal tract is prevented by its large size and enzymatic degradation. It would be desirable to create an oral pharmaceutical formulation of a drug such as insulin (which is not normally orally administrable due to, e.g., insufficient absorption from the gastrointestintal tract), which formulation would provide sufficient absorption and pharmacokinetic/pharmacodynamic properties to provide the desired therapeutic effect. Insulin exemplifies the problems confronted in the art in designing an effective oral drug delivery system for biological macromolecules. The medicinal properties of insulin can be readily altered using any number of techniques, but its physicochemical properties and susceptibility to enzymatic digestion have precluded the design of a commercially viable oral or alternate delivery system. Accordingly, there is a need for a method of administering insulin to patients in need of insulin wherein those patients are not subject to systemic hyperinsulinema, which by itself can increase the risk of vascular disease (that is normally associated with such chronic insulin treatments, as discussed above). In other words, it is desirable to provide compositions and methods for treating diabetes without the drawbacks of systemic hyperglycemia to decrease the incidence of vascular complications and other detrimental effects.

<SOH> SUMMARY OF THE INVENTION <EOH>It is one object of the present invention to provide useful oral pharmaceutical formulations of drugs that are not considered orally administrable due, e.g., to insufficient absorption of the drugs from the gastrointestinal tract, which formulations are therapeutically effective. It is a further object of the present invention to provide useful pharmaceutical formulations of insulin for oral administration which are therapeutically effective. It is a further object of the present invention to provide delivery agents that may be orally administered together with a drug that is not considered orally administrable due to, e.g., insufficient absorption of the drug from the gastrointestinal tract, so that the drug is absorbed in adequate amounts from the gastrointestinal tract to provide the desired therapeutic effect, such as insulin. It is an object of the present invention to provide compositions comprising a delivery agent and insulin for oral administration. It is an object of the present invention to provide compositions of a delivery agent and insulin for oral administration that facilitates insulin transport in a therapeutically effective amount to the bloodstream for the treatment of diabetes, for the treatment of impaired glucose tolerance, for the purpose of achieving glucose homeostasis, for the treatment of early stage diabetes, for the treatment of late stage diabetes, and/or to serve as replacement for type I diabetic patients. It is an object of the present invention to provide methods for the preparation of a composition comprising insulin and delivery agent for oral administration, which result in an orally administrable unit dose that provides a desired therapeutic effect. It is an object of the present invention to provide a delivery agent(s) that can be utilized in an amount that facilitates the preparation of an oral unit dosage form of a drug that is not considered orally administrable by itself due to poor absorption, etc., and results in an orally administrable unit dose that provides a desired therapeutic effect. It is an object of the invention to reduce the risk of disease states associated with chronic systemic hyperinsulinemia of conventional insulin therapy. It is another object of the invention to provide a method for reducing the incidence in vascular diseases associated with chronic systemic hyperinsulinemia caused by parenteral insulin therapy in diabetics. It is another object of the invention to delay the time to onset of vascular diseases associated with chronic systemic hyperinsulinemia caused by parenteral insulin therapy in diabetics. It is another object of the invention to reduce the severity of vascular diseases associated with chronic systemic hyperinsulinemia caused by parenteral insulin therapy in diabetics. It is another object of the invention to reduce the exposure of the non-portal vasculature to hyperinsulinemic conditions. It is another object of the invention to attenuate the complex series of systemic processes resulting from the reaction to insulin treatment. It is a further object of the invention to provide a method and a pharmaceutical formulation which can reduce systemic blood insulin concentrations while providing therapeutically effective treatment of diabetes. It is a further object of the invention to provide a method and a pharmaceutical formulation which may help decrease the instances and severity of the vascular complications and resultant conditions (such as, e.g., retinopathy, neuropathy, nephropathy) associated with Diabetes Mellitus. It is a further object of the invention to lower the exposure of the systemic vasculature to insulin during insulin treatment. It is a further object of the invention to reduce the incidence and/or severity of macro- and micro-vascular complications associated with insulin therapy in diabetics, which leads to neuropathies, retinopathies, peripheral vascular disease, cardiac complications and cerebrovascular complications. In accordance with the above objects and others, the invention is directed in part to an oral solid dosage form comprising a dose of unmodified insulin that achieves a reduction in blood glucose concentration in human diabetic patients comparable to a subcutaneous insulin injection in those patients, while providing a lower (e.g., 20% or greater) totals dose of insulin in the peripheral blood circulation under acute, sub-acute and chronic conditions as compared to the peripheral blood insulin concentration obtained via the subcutaneous injection. The invention is also directed in part to an oral solid dosage form comprising a dose of unmodified insulin that achieves a therapeutically effective reduction in blood glucose after oral administration to a human diabetic patient, and which maintains a physiological (portal/peripheral) gradient, and in certain embodiments provides a ratio of portal vein insulin concentration to peripheral blood insulin concentration from about 2.5:1 to about 6:1, and preferably from about 4:1 to about 5:1. The invention is further directed in part to an oral dosage form comprising a dose of unmodified insulin that achieves a therapeutically effective reduction in blood glucose after oral administration to human diabetic patients, the oral solid dosage form providing an insulin t max at a time point from about 0.25 to about 1.5 hours after oral administration to said patients, at least about 80% of the blood glucose concentration reduction caused by said dose of insulin occurring within about 2 hours after oral administration of said dosage form. The invention is further directed in part to an oral dosage form comprising a therapeutically effective amount of unmodified insulin, said dosage form upon pre-prandial oral administration to human diabetic patients causing the post prandial mean plasma glucose concentration in said patients to be reduced for the first hour after oral administration relative to a mean baseline (fasted) plasma glucose concentration (in the absence of sufficient insulin) in said patients. The invention is further directed in part to an oral dosage form comprising a therapeutically effective amount of unmodified insulin, said oral dosage form upon pre-prandial oral administration provides a mean plasma glucose concentration which does not vary by more than about 40% (and more preferably not more than 30%) for the first hour after oral administration, relative to a mean baseline (fasted) plasma glucose concentration in said patients, where a meal is eaten by said patients within about one half hour of oral administration of said dosage form. In preferred embodiments of the oral dosage forms of the invention described above, the oral dosage form is solid, and is preferably provided incorporated within a gelatin capsule or is contained in a tablet. In certain preferred embodiments, the dose of unmodified insulin contained in the dosage form is from about 50 Units to about 600 Units (from about 2 to about 23 mg), preferably from about 100 Units (3.8 mg) to about 450 Units (15.3 mg) insulin, and most preferably from about 150 Units (5.75 mg) to about 300 Units (11.5 mg), based on the accepted conversion of factor of 26.11 Units per mg. In certain preferred embodiments, the dosage forms of the invention provide a tram for insulin at about 0.1 to about 1.5 hours, and more preferably by about 0.25 to about 0.5 hours, after oral administration. In certain preferred embodiments, the t max for insulin occurs at less than about 100 minutes after oral administration of the composition, preferably at less than about 45 minutes, more preferably at less than about 40 minutes, and still more preferably at about 22 minutes after oral administration of the composition. In certain preferred embodiments, the composition provides a tam for glucose reduction at about 0.25 to about 1.5 hours, more preferably by about 0.75 to about 1.0 hours, after oral administration. In certain preferred embodiments, the t max for glucose reduction occurs preferably at less than about 120 minutes, more preferably at less than about 80 minutes, and most preferably at about 45 minutes, after oral administration of the composition. In certain preferred embodiments of the invention, the dosage forms begin delivering insulin into the portal circulation (via absorption through the mucosa of the stomach) to achieve peak levels within about 30 minutes or less. In certain embodiments of the dosage forms described above, in the absence of a delivery agent, the dose of unmodified insulin is not adequately absorbed from the gastrointestinal tract when administered orally to render a desired effect. In certain preferred embodiments, in the absence of a delivery agent, the dose of insulin is not sufficiently absorbed when orally administered to a human patient to provide a desirable therapeutic effect but said dose provides a desirable therapeutic effect when administered to said patient by another route of adminstration. The invention in such embodiments is further directed to an oral dosage form comprising a dose of unmodified insulin together with a pharmaceutically acceptable delivery agent in an amount effective to facilitate the absorption of said insulin, such that a therapeutically effective amount of said dose of insulin is absorbed from the gastrointestinal tract of human diabetic patients. In certain preferred embodiments, the pharmaceutical composition comprises from about 1 mg to about 800 mg of said delivery agent, preferably about 50 to about 600, more preferably from about 100 to about 400, most preferably about 200. In certain embodiments, the composition provides a peak plasma delivery agent concentration C max from about 1,000 and about 150,000 ng/ml, and a t max at about 0.25 to about 1.5 hours, and more preferably by about 0.25 to about 0.75 hours, most preferably 0.5 hours, after oral administration. For purposes of the present invention, a preferred delivery agent is identified via chemical nomenclature as 4-[(4-chloro, 2-hydroxybenzoyl)amino]butanoic acid. In certain preferred embodiments, the delivery agent is a sodium salt, preferably monosodium salt. Alternatively, the same compound is identified by the alternative nomenclature monosodium N-(4-chlorosalicyloyl)-4-aminobutyrate, or by the short name “4-CNAB”. The invention is further directed in part to a method of treatment of diabetes in humans, comprising administering one or more unit doses of the dosage forms described above and in further sections of the present specification. The invention is further directed in part to a method of treatment of impaired glucose tolerance, achieving glucose homeostasis, early stage diabetes, and late stage diabetes in humans, comprising administering one or more unit doses of the dosage forms described above and in further sections of the present specification on a chronic basis. The invention is also related to a method of orally treating mammals with an active agent (i.e., insulin) that is not sufficiently absorbed when orally administered to provide a desirable therapeutic effect but that provides a desirable therapeutic effect when administered by another route of adminstration, comprising orally administering said active agent together with a delivery agent which facilitates the absorption of insulin from the gastrointestinal tract, having one or more of the further characteristics set forth above. The invention is further directed to a method of providing a therapeutically effective orally administrable unit dose of unmodified insulin, comprising combining from about 2 to about 23 mg of unmodified insulin with from about 100 to about 600 mg of a pharmaceutically acceptable delivery agent which facilitates absorption of said insulin from the gastrointestinal tract of human diabetic patients, and orally administering said unit dose to a human diabetic patient to provide a therapeutic effect. In preferred embodiments, the total weight of the unit dose is from about 102 mg to about 800 mg. The present invention is also directed in part to a method of treating human diabetic patients comprising orally administering to human diabetic patients on a chronic basis an oral insulin treatment comprising a dose of unmodified insulin together with a delivery agent that facilitates the absorption of the dose of insulin from the gastrointestinal tract to provide a therapeutically effective reduction in blood glucose and a blood plasma insulin concentration that is reduced relative to the systemic blood insulin concentration of an equivalent therapeutically effective reduction in blood glucose concentration achieved by subcutaneous injection of insulin. The invention is also directed to a method of reducing the incidence and/or severity of one or more disease states associated with chronic administration of insulin, comprising treating human diabetic patients via oral administration on a chronic basis with a therapeutically effective dose of a (preferably solid) pharmaceutical composition comprising a dose of unmodified insulin and a delivery agent that facilitates the absorption of said unmodified insulin from the gastrointestinal tract in an effective amount such that the pharmaceutical composition provides therapeutically effective control of mean blood glucose concentration and a mean systemic blood insulin concentration in diabetic patients that is reduced on a chronic basis relative to the mean systemic blood insulin concentration provided by chronic subcutaneous administration of insulin in an amount effective to achieve equivalent control of mean blood glucose concentration in a population of human diabetic patients. The invention is further directed to a method of treating diabetes and reducing the incidence of systemic hyperinsulinemia associated with chronic dosing of insulin, comprising orally administering on a chronic basis to a diabetic patient a dose of insulin and a delivery agent that facilitates the absorption of the dose of insulin from the gastrointestinal tract to provide a therapeutically effective reduction and/or control in blood glucose and a mean systemic blood insulin concentration of the diabetic patient that is reduced relative to the mean systemic blood insulin concentration provided by subcutaneous injection of insulin in an amount effective to achieve equivalent reduction and/or control in a population of human diabetic patients. The mean values of insulin concentration determination obtained in patients who have been administered subcutaneous insulin are well known to those skilled in the art. The following terms will be used throughout the application as defined below: Diabetic patient—refers to humans suffering from a form of diabetes. IGT—means impaired glucose tolerance. Diabetes—is deemed to encompass type I and type 2 diabetes, unless specifically specified otherwise. Biological macromolecule—biological polymers such as proteins and polypeptides. For the purposes of this application, biological macromolecules are also referred to as macromolecules. Delivery agent—refers to carrier compounds or carrier molecules that are useful in the oral delivery of therapeutic agents. “Delivery agent” may be used interchangeably with “carrier”. Therapeutically effective amount of insulin—an amount of insulin included in the oral dosage forms of the invention which are sufficient to achieve a clinically significant control of blood glucose concentrations in a human diabetic patient either in the fasting state or in the fed state effective, during the dosing interval. Effective amount of delivery agent—an amount of the delivery agent that promotes the absorption of a therapeutically effective amount of the drug from the gastrointestinal tract. Organic solvents—any solvent of non-aqueous origin, including liquid polymers and mixtures thereof. Organic solvents suitable for the present invention include: acetone, methyl alcohol, methyl isobutyl ketone, chloroform, 1-propanol, isopropanol, 2-propanol, acetonitrile, 1-butanol, 2-butanol, ethyl alcohol, cyclohexane, dioxane, ethyl acetate, dimethylformamide, dichloroethane, hexane, isooctane, methylene chloride, tert-butyl alchohol, toluene, carbon tetrachloride, or combinations thereof. Peptide—a polypeptide of small to intermediate molecular weight, usually 2 or more amino acid residues and frequently but not necessarily representing a fragment of a larger protein. Protein—a complex high polymer containing carbon, hydrogen, oxygen, nitrogen and usually sulfur and composed of chains of amino acids connected by peptide linkages. Proteins in this application refer to glycoproteins, antibodies, non-enzyme proteins, enzymes, hormones and peptides. The molecular weight range for proteins includes peptides of 1000 Daltons to glycoproteins of 600 to 1000 kiloDaltons. Reconstitution—dissolution of compositions or compositions in an appropriate buffer or pharmaceutical composition. Unit-Dose Forms—refers to physically discrete units suitable for human and animal subjects and packaged individually as is known in the art. It is contemplated for purposes of the present invention that dosage forms of the present invention comprising therapeutically effective amounts of insulin may include one or more unit doses (e.g., tablets, capsules) to achieve the therapeutic effect. Unmodified insulin—means insulin prepared in any pharmaceutically acceptable manner or from any pharmaceutically acceptable source which is not conjugated with an oligomer such as that described in U.S. Pat. No. 6,309,633 and/or which not has been subjected to amphiphilic modification such as that described in U.S. Pat. Nos. 5,359,030; 5,438,040; and/or 5,681,811. As used herein, the phrase “equivalent therapeutically effective reduction” means that a maximal reduction of blood glucose concentration achieved by a first method of insulin administration (e.g. via oral administration of insulin in a patient(s)) is not more 20%, and preferably not more than 10% and even more preferably not more than 5% different from a maximal reduction of blood glucose concentration after administration by a second method (e.g., subcutaneous injection) in the same patient(s) or a different patient requiring the same reduction in blood glucose level. The term “AUC” as used herein, means area under the plasma concentration-time curve, as calculated by the trapezoidal rule over the complete dosing interval, e.g., 24-hour interval. The term “C max ” as it is used herein is the highest plasma concentration of the drug attained within the dosing interval. The term “t max ” as it is used herein is the time period which elapses after administration of the dosage form at which the plasma concentration of the drug attains the C max within the dosing interval. The term “multiple dose” means that the human patient has received at least two doses of the drug composition in accordance with the dosing interval for that composition. The term “single dose” means that the human patient has received a single dose of the drug composition and the drug plasma concentration has not achieved steady state. Unless specifically designated as “single dose” or at “steady-state” the pharmacokinetic parameters disclosed and claimed herein encompass both single dose and steady-state conditions. The term “mean”, when preceding a pharmacokinetic value (e.g., mean t max ) represents the arithmetic mean value of the pharmacokinetic value unless otherwise specified. The term “Bioavailability” as used herein means the degree or ratio (%) to which a drug or agent is absorbed or otherwise available to the treatment site in the body. This is calculated by the formula Rel . ⁢ Bioavailability ⁡ ( % ) = Dose ⁢ ⁢ ⁢ SC Dose ⁢ ⁢ Oral ⨯ AUC INS ⁢ Oral AUC INS ⁢ SC ⨯ 100 The term “Biopotency” as used herein means the degree or ratio (%) to which a drug or agent is effective to the treatment site in the body. This is calculated by the formula Rel . ⁢ Biopotency ⁡ ( % ) = Dose ⁢ ⁢ SC Dose ⁢ ⁢ Oral ⨯ AUC GIR ⁢ Oral AUC GIR ⁢ SC ⨯ 100 The term “F rel ” as used herein means the relative bioavailability of insulin calculated by comparing dose corrected oral insulin AUC with the dose corrected SC insulin AUC. K el is the terminal elimination rate constant calculated by linear regression of the terminal linear portion of the log concentration vs. time curve The term “AUC (0-x) ” as used herein means the area under the plasma concentration-time curve using linear trapezoidal summation from time 0 to time×hours post-dose. The term “AUC (0-t) ” as used herein means the area under the plasma concentration-time curve using linear trapezoidal summation from time zero to time t post-dose, where t is the time of the last measurable concentration (C t ). The term “AUC (0-inf) ” as used herein means the area under the plasma concentration-time curve from time 0 to infinity, AUC (0-inf) =AUC (0-t) +Ct/K el . The term “AUC % Extrap ” as used herein means the percentage of the total AUC (0-inf) obtained by extrapolation. The term “AUEC (0-x) ” as used herein means the area under the effect-time curve calculated using the linear trapezoidal summation from time 0 to the concentration at time×hours post-dose. The term “AUEC (0-t) ” as used herein means the area under the effect-time curve calculated using the linear trapezoidal summation from time 0 to the concentration at time t hours post-dose, where t is the time of the last measurable effect (E). The term “AURC (0-x) ” as used herein means the area under the response-time curve calculated using the linear trapezoidal summation from time zero to the concentration at time×(Baseline Subtracted AUEC). The term “AURC (0-t) ” as used herein means the area under the response-time curve calculated using the linear trapezoidal summation from time zero to the concentration at time t (Baseline Subtracted AUEC), where t is the time of the last measurable response (R). The term “C b ” as used herein means the maximum observed plasma insulin concentration prior to intervention for hypoglycemia. The term “CL/F” as used herein means the apparent total body clearance calculated as Dose/AUC (0-inf) . The term “E b ” as used herein means the maximum observed effect (baseline subtracted) prior to intervention for hypoglycemia. The term “E max ” as used herein means the maximum observed effect (baseline subtracted). The term “MRT” as used herein means the mean residence time calculated as the ratio of the Area Under the first moment of the plasma concentration-time curve (AUMC) and the area under the plasma concentration-time curve, (AUMC)/AUC (0-inf) . The term “R max ” as used herein means the maximum observed response (total response), i.e., minimum glucose concentration. The term “R b ” as used herein means the maximum observed response (total response) prior to hypoglycemic intervention. The term “t b ” as used herein means the time to reach insulin/glucose plasma concentration prior to hypoglycemic intervention. The term “t c ” as used herein means the time to reach glucose concentration change from baseline prior to hypoglycemic intervention. The term “t Rmax ” as used herein means the time to reach maximum response. The term “t Emax ” as used herein means time of the maximum effect (obtained without interpolation). The term “t 1/2 ” as used herein means the terminal half-life calculated as ln(2)/K el . The term “V d /F” as used herein means the apparent volume of distribution calculated as (CL/F)/K el . As used herein and in the appended claims, the singular forms “a,” “an,” and “the,” include plural referents unless the context clearly indicates otherwise. Thus, for example, reference to “a molecule” includes one or more of such molecules, “a reagent” includes one or more of such different reagents, reference to “an antibody” includes one or more of such different antibodies, and reference to “the method” includes reference to equivalent steps and methods known to those of ordinary skill in the art that could be modified or substituted for the methods described herein. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention belongs. Although any methods, compositions, reagents, cells, similar or equivalent to those described herein can be used in the practice or testing of the invention, the preferred methods and materials are described herein. All publications mentioned herein are incorporated herein, including all figures, graphs, equations, illustrations, and drawings, to describe and disclose specific information for which the reference was cited in connection with. The publications discussed above are provided solely for their disclosure before the filing date of the present application. Nothing herein is to be construed as an admission that the invention is not entitled to antedate such disclosure by virtue of prior invention. Throughout this description, the preferred embodiment and examples shown should be considered as exemplars, rather than as limitations on the present invention.

20050314

20080930

20061019

67193.0

A61K3828

BRADLEY, CHRISTINA

ORAL INSULIN THERAPY

SMALL

ACCEPTED

A61K

ACCEPTED

Communication system and method for data web session transfer

A method of operating a communications system such that connections supporting a communications session being run on a first terminal (1) may be diverted to a second terminal (2) such that the session may be coninued on the second terminal comprises the steps of creating a user profile on a server device (3), the user profile identifying a plurality of terminals (1,2), generating from the user profile a set of parameters defining a virtual terminal (12, 22), storing, as parameters of the virtual terminal, details of a current communications session (11) made using a first terminal, on instruction from one of the user terminals (1, 2), diverting the routing of a communications connection supporting the session from the first terminal (1) to a second terminal (2), and and transferring the details of the current session (11) to the second terminal for use in continuing the session. This process allows a user to continue a session on a second terminal if it becomes more convenient to do so, rather than having to start a new session and potentially losing any information obtained whilst using the first terminal.

1. A communications system arranged such that connections to a first terminal supporting a communications session on the first terminal may be diverted during the course of the session such that the session may be continued on a second terminal, the communications system comprising: a server device for processing calls, means for creating a user profile on the server device, the user profile identifying a plurality of terminals, means for generating from the user profile a set of parameters defining a virtual terminal a store for parameters of the virtual terminal, said parameters being details of a current communications session made using a first terminal, means for diverting, on instructions from a user device, the routing of a communications connection supporting the session from the first terminal to a second terminal, means for transferring the details of the current session to the second terminal for use in continuing the session. 2. Apparatus according to claim 1, comprising means for storing information relating to each of the plurality of terminals, and means for adapting the details of the current communications session in accordance with the terminal to which the session is to be diverted on receipt of a diversion instruction. 3. Apparatus according to claim 2, comprising means for translation of a session into a data handling protocol suitable for the terminal. 4. A method of operating a communications system such that a connection to a first terminal supporting a communications session on the first terminal may be diverted during the course of the session such that the session may be continued on a second terminal, the method comprising the steps of creating a user profile on a server device, the user profile identifying a plurality of terminals, generating from the user profile a set of parameters defining a virtual terminal, storing, as parameters of the virtual terminal, details of a current communications session made using a first terminal, on instruction from the user, diverting the routing of a communications connection supporting the session from the first terminal to a second terminal, and transferring the details of the current session to the second terminal for use in continuing the session. 5. A method according to claim 4, comprising the further steps of storing information relating to each of the plurality of terminals, and on receipt of a diversion instruction adapting the details of the current communications session in accordance with the terminal to which the session is to be diverted. 6. A method according to claim 5, wherein the session is translated into a data handling protocol suitable for the terminal. 7. A method according to claim 4, wherein the diversion of routing is initiated by an instruction transmitted from the second terminal to the server device. 8. A method according to claim 7, wherein the diversion of routing is initiated by an instruction transmitted from the first terminal to the second terminal, causing the second terminal to transmit an instruction to the server device.

Users often have a number of different communications devices for use in different contexts. For example the user may need have a requirement for mobility, so that he can access communications facilities from a number of different locations or whilst on the move. He may also, from time to time, need the ability to view a large screen or to generate “hard copy” output, requiring a printing capability. However, mobile devices have of necessity to be small, so large screens and printers are not normally associated with such devices. For this reason, a user may have a mobile device and a “desktop” device, the former having a smaller capability set than the latter. These devices function independently, which means the user has to define preferences and profiles for each device. It would be very convenient to unify a user's range of communication devices so they all share common preferences and act as a single “virtual” terminal in which the devices are differentiated by certain attributes such as mobility and output capabilities (screen size, availability of print facilities etc). Using this unified approach would allow the user to set profiles on this virtual terminal (by inputting an instruction using one of its constituent devices), to arrange that all devices are notified of these changes. This would allow a user to start an operation such as a computing session on one device and continue it on another. For example, a user at home may have spent several hours searching web pages related to a particular topic and may then require access to these from work. As another example, a user surfing an internet site using a personal computer may wish to continue surfing whilst travelling. One device-unifying system is a product called “Hipbone”. This is discussed, for example, in “E-Business Essentials” by Cade Metz, PC Magazine Jun. 21, 2000: “People Who Need People” by Jim Sterne in Inc magazine—Sep. 15, 2000 “Many Happy Returnees”, by J Blackwood, Computer Shopper Aug. 8, 2001 “Digital Devices: Navigating the Web with friends” in Interactive Week, Feb. 4, 2000 A similar system known as E-CoBrowse is described by Chong and Sakauchi at page 803-808 of the “Proceedings of the IASTED International Conference”—Las Vegas USA, November 2000. Hipbone and E-Co-Browse are multi-party collaboration tools that enable individuals to co-browse the same web page and also send annotations and chat (to support their collaboration). They work purely at the URL level, whereby user's browsers are synchronised to request the same URL. They provide an Internet co-navigation service, which allows sales staff to ‘connect browsers’ with their customers and jointly view online product demonstrations, fill out complex web forms, and work through online transactions together. Among its key features are “True Shared Browsing”, which allows customer service and sales representatives (“agents”) to co-browse with customers and navigate the web together, and synchronises the agent's and customer's activities. Using this, real-time Interaction is achievable, all participants being allowed to direct the browser with the results echoed to each participant's browser. Hipbone's software supports functions such as authentication using “cookies” and order transaction processing. Using the shared browser allows form filling to be echoed to all participants. Forms can therefore be filled in using assistance from the serving participant (sales representative). Hipbone's high level architecture is based on a proxy mechanism. Basically, every web response is held on the central application server accessed by the shared browsers. However, there is no network based representation of the web session state (history, bookmarks, cookies, etc) and a user would not be able to switch from using one device to using another unless the second device had already been connected to the session from the outset. Systems such as the “Netscape” flexible roaming access function provide data synchronisation so that a user can copy data between two devices—for example a laptop computer and a desktop computer—when they are connected to each other. In this way, if a user has modified a state using one of the devices whilst either or both devices are ‘offline’, that state can be updated on the other device once the offline devices are re-connected. International Patent Specification WO00/70838 (Patil) describes a system that maintains a network-based record of the user's preferences and session information, allowing the user to access his personal information (eg. previous web pages, bookmarks, etc) from different devices. However, if the user, having begun work on one device, desires to contimue on another device, he would have to store the results of the web session he was using, log-off one device and then go to the other device, relog in, and then select the stored details of the previous web session that he wishes to use. None of these systems allow a user to continue an individual communications session on a different terminal to that on which the session was started. According to the present invention, there is provided a communications system arranged such that connections to a first terminal supporting a communications session on the first terminal may be diverted during the course of the session such that the session may be continued on a second terminal, the communications system comprising: a server device for processing calls, means for creating a user profile on the server device, the user profile identifying a plurality of terminals, means for generating from the user profile a set of parameters defining a virtual terminal a store for parameters of the virtual terminal, said parameters being details of a current communications session made using a first terminal, means for diverting, on instructions from a user device, the routing of a communications connection supporting the session from the first terminal to a second terminal, means for transferring the details of the current session to the second terminal for use in continuing the session. According to a second aspect, the invention comprises method of operating a communications system such that a connection to a first terminal supporting a communications session on the first terminal may be diverted during the course of the session such that the session may be continued on a second terminal, the method comprising the steps of creating a user profile on a server device, the user profile identifying a plurality of terminals, generating from the user profile a set of parameters defining a virtual terminal, storing, as parameters of the virtual terminal, details of a current communications session made using a first terminal, on instruction from the user, diverting the routing of a communications connection supporting the session from the first terminal to a second terminal, and transferring the details of the current session to the second terminal for use in contiuing the session. The invention gives the user the ability to instantaneously transfer a current data session to a range of various devices (e.g. PC to PC, PC to WAP Phone, WAP phone to PDA, etc). Any data session information may be transferred between terminals to create a session's state, for example bookmark history, browsing history, or form elements. Multiple sessions can be run, which can all be submitted to the destination device. In contrast with the prior art systems discussed above, in the present invention the session is transmitted to the destination device and run on that device. The session that has been transmitted from the source device is closed. The system can handle transfers requiring authorisation and those which are unrestricted. This means that sessions will be accessible from a range of different devices such as personal digital assistants, mobile phones, IP phones, Personal computers and many other types of devices. The present invention's architecture will also allow different web based transfer applications to be present. For example, email applications based on session transfer may be incorporated with relative ease. An embodiment of the invention will now be described, with reference to the Figures, in which FIG. 1 is a schematic representation of the various components making up the system, with an indicaion of the information flows which take place when the system is in operation FIG. 2 is a schematic representation of the information transfers used in generating a session FIG. 3 is a schematic representation of the use of the system to access data using terminals having different capabilities FIG. 4 is a schematic representation of the information transfers used in transferring a session from one terminal to another FIG. 5 is a schematic representation of the use of the system to transfer data generated as html forms As can be seen from FIG. 1, from a high level perspective, the following components are provided. Browser applications 11, 21 running on respective terminals 1, 2 are capable of providing HTML (hypertext markup language) browsing capabilities and display any incoming active sessions. They can also each run a terminal application 12, 22. This application manages web data sessions, which may be present on a user's device 1, 2. It also processes any incoming sessions. Session information, holding such information such as the session's web page and form parameter values etc, can be stored by the terminals and transferred between them. The central server 3 is used for holding the session information, and also provides other data which can be used by the terminals. In particular, it holds a user profile, which holds any ‘User Specific’ attributes such as sessions, bookmarks etc. These include permanent attributes, attributes changeable on a specific command from the user, or attributes generated automatically, tracking the operation of the individual terminals. The basic steps involved within the process will now be described, with reference to FIG. 1. A more detailed dwscription of the process will follow with reference to FIGS. 2, 3, 4 and 5 A user logs into the system by using an interface to the server 3 appropriate to the terminal 1 that he is using. For example he may use a WAP interface for telephones, or HTML for devices capable of supporting that protocol, such as PCs and PDAs (Personal computers and personal digital assistants). A user profile is created on the main server 3. Once the user profile has been created, the user is invited to set any relevant preferences, which are then loaded onto the terminal. The user can then run the web browser 11. Note that the terminal 1 will also allow other applications to be executed such as Email clients. Once the web browser 11 has been launched, the user can select a “Session Tracking” option. From this point onwards, the operation of the browser 11 is tracked by the terminal application 12. The server 3 therefore stores the user's web history and browsed web pages within a session object. When the user wants to ‘transfer’ a session, the destination device 2 has to be selected via the web browser 11, for example by clicking on a transfer button on the browser screen (step 503), to transfer the session. This causes a transfer request 505 to be sent to the destination device's terminal application 22. Having received an incoming request, the destination terminal application 22 requests the relevant session from the server 3 (step 508). The specified session is then transferred and displayed in the destination device's web browser 12 (step 512) The invention gives the user the ability to instantaneously transfer a web session to a range of various devices (E.g. PC to PC, PC to WAP Phone etc) Two sequence diagrams are shown as FIGS. 2 and 4, which illustrate how sessions are created and transferred. Note that FIG. 4 applies to devices that can poll their input/output ports. Mobile devices and PDAs that do not have polling features will request the sessions directly through a Web interface from the server 3. As shown in FIG. 2, a user who has logged into the system using a terminal application 12 running on a terminal 1, is first presented with the terminal screen (step 401), which allows a web browser to be opened, as will be discussed (steps 407, 408). Also at logon, a session panel 31 is loaded on the server 3 (step 402) and a device list retrieval process 34 is initiated (step 403). The session panel 31 is a process which records the details of the session that is running, to allow those details to be transferred to another device when required. The device list retrieval process 34 retrieves a list of devices available to the user to which the session may be transferred, or which may require updating of functions such as voice mail activation. The list is stored in a user profile 33 and retrieved by the central server 3 (step 405) in response to a request 404 from the device list function 34. The device list may be amended by the processor 34 during the session (step 406), for example by changing settings of forwarding instructions. The terminal screen presented to the user (step 402) includes an option to allow access to a web browser. Selecting this (step 407) opens the web browser 11 (step 408). The terminal can then retrieve attributes stored from previous sessions from the central server 3 (step 409). Thus the user logs into the server using a special application and then selects to open a web browser. In an alternative arrangment a standard web browser could itself have a facility to select the session-tracking feature which would then enable the server based session logging and transfer to take place when the user loads his standard browser. Some form of authentication (ie. username) would probably still be required, but the aim is to make this much easier to use and also allow users to use their standard web browser rather than a special one, which avoids the need for the user having to install a special tracking application on each device. Mobile devices and PDAs accessing the server will require the content to be revised for their display capabilities. Thus, a PC accessing the server 3 (step 409, see FIG. 2) can use standard html language and protocols. As shown in FIG. 3, a WAP—enabled telephone 4 accessing the server 3 (step 419) requires the session language to be converted by the server from html (as used in the PCs 1,2 and the server 3) into a language usable by the terminal 4 to which the session is to be transferred. The server 3, holding the user profile which includes the characteristics and capabilities of each terminal, performs the necessary conversion when it receives a request to transfer a session to such a terminal. Similarly, a PDA can use html, but with some limitations generally as a result of its small screen size and the relatively small bandwidth available for communication out the full data. If a request to transfer to a PDA 5 is received (step 429), the data server adapts the session accordingly by removing such functions. The session run on the data server 3 (“virtual terminal”) is tracked in html, so that if transfer to a html-compatible terminal is required, the full capability can be made available. If the user has “Session Tracking” enabled, all browsed web pages are cached on the main server 3. The user sends a request to register a session (step 410) from the terminal application 12 to the central server 3. A session identity is then generated by the server 3 and stored (step 411) in the user profile 33 and transmitted to the user terminal 12 (step 412). This session is then added to the session panel 31 running on the server 3 (step 413). As will now be discussed with reference to FIG. 4, other terminals can then retrieve these sessions. For example, the user could be browsing a search engine, and want to transfer the web session to another device, for example a mobile phone. As another example, the user may wish to move visual output from a mobile device with small display to a fixed device with a larger screen. In order to do this, the user may accesses the session by making a request to the main server. Having requested the session from the main server, the current session can be retrieved. The form is already filled with the correct search parameters. Once the session has been transferred to the other device, the user can continue to surf the web site. In FIG. 4 it is assumed that the transfer is initiated from the device 1 initially running the session, but there may be situations, for example when the first device 1 has been disabled, when a transfer may be initiated from the device 2 to which the session is to be transferred. The transfer process starts when the user accesses the device list 34 from a first terminal 1 and selects a second terminal 2 to which he wishes to transfer (step 501). He then generates an instruction (502) for the browser 11 to initiate the transfer. The browser in turn instructs the terminal application 12 (step 503) to construct the transfer instruction (step 504) which is then transmitted to the corresponding terminal application 22 in the second terminal 2 (step 505). From this point the terminal 2 and central server 3 co-operate in a number of steps (509-513) similar to those performed in setting up a session initailly (409-413, FIG. 2) More specifically, the browser 21 in the destination terminal 2 retrieves the user attributes from the central server (step 509) and sends a request to register a session (step 510) from the terminal application 22 to the central server 3. The session identity previously stored (step 411) in the user profile 33 is retrieved (step 511) and transmitted to the user terminal 12 (step 512). This session is then added to a session panel 32 associated with the destination terminal 2 and running on the server 3 (step 513). The destination terminal 21 next transmits an acknowledgment that the transfer has been successful back to the originating terminal (step 514) which updates its own copy of the session panel 31 running on the server 3 (step 515). As shown in FIG. 5, one useful feature of the invention is the ability to 30 transfer html forms and their respective values, that is to say not only the blank form stored on a website, but the values inserted in that form during a session. In order to transfer the form, the destination browser 21 first checks to see whether ‘Session Tracking’ has been activated. If so, when the transfer (step 512) takes place, the relevant data is extracted, and transmitted to the Server 3 (step 503-509). The form can then be rebuilt by the server 3 in its current state (step 510,511), and downloaded to the destination terminal 2 (step 512). Note that if the source and destination terminals 1, 2 are of different types the layout and other features of the form may differ. The system only requires that both versions have corresponding fields for data entry, and that the server 3 can transfer entries from a given field in one version to the corresponding field in the other.

20040707

20081028

20050210

94555.0

HUQ, FARZANA B

COMMUNICATION SYSTEM AND METHOD FOR DATA WEB SESSION TRANSFER

UNDISCOUNTED

ACCEPTED

ACCEPTED

Method and plant for biological treatment of aqueous effluents for purification thereof

The invention relates to a method for the biological treatment of effluents contaminated with impurities of urban or industrial origin, characterised in employing a single aeration tank (1) with a high mass charge in which the raw effluent or mechanically pre-treated effluent is mixed without previous decantation with a free microbial culture of the activated sludge type, growing in a lightly aerated medium, of the order of 0.1 to 0.2 kg O2/kg BOD5 removed, the organic charge applied having a value equal to or greater than at least 2 kg COD/kgSM/day, preferably equal to or greater than 4 kg COD/kgSM/day, the hydraulic residence time for the raw effluent in the single aeration tank being between 30 and 90 minutes, preferably between 40 and 60 minutes.

1. A method for the biological treatment of effluents contaminated with impurities of municipal or industrial origin, characterized in that it employs a single aeration tank (1) with high mass loading in which the raw or mechanically pretreated effluent is mixed, without prior settling, with a free microbial culture of the activated sludge type, growing in a lightly aerated medium, of the order of 0.1 to 0.2 Kg O2/kg BOD5 removed, the applied organic loading being equal to or greater than at least 2 Kg COD/kg SM/day, preferably equal to or greater than 4 Kg COD/Kg SM/day, the hydraulic residence time of the raw effluent in the single aeration tank being between 30 and 90 minutes, and preferably between 40 and 60 minutes, and in that, in said single aeration tank (1) a portion of the dissolved carbon pollution and nearly the entire colloidal and particulate fraction of the effluent are biosorbed by the activated sludge floc. 2. The method as claimed in claim 1, characterized in that the value of said mass loading is above 1.5 kg BOD5/Kg SM/day, with a solid matter concentration between 0.5 and 2.5 gSM/1, giving rise to applied volumetric loadings above 3 kg BOD5/m3/day. 3. The method as claimed in claim 1, characterized in that it is controlled at the anaerobiosis limit, by regulating the dissolved oxygen content to values between 0.1 and 1 g/l. 4. The method as claimed in claim 1, characterized in that the very high loading sludge has a suspended matter concentration of the order of 0.5 to 2.5 g/l, and preferably between 0.6 and 1.5 g/l. 5. The method as claimed in claim 1, characterized in that a regulation system is provided, by adjustment of the recirculation rate of the mixed liquor in the single aeration tank, this regulation being carried out so as to maintain the solid matter (suspended matter+biomass) within a preset range, preferably between about 1.0 and 1.5 g/l, and it is carried out by the continuous measurement of the turbidity of the activated sludge or of the mixed liquor, this measurement being combined with a slaving of the recirculation or extraction rate of said mixed liquor. 6. The method as claimed in claim 1, characterized in that it comprises a regulation of the air input in the single tank (1), in order to maintain a low dissolved oxygen setpoint, of the order of 0.1 to 1 mg/l. 7. An installation for putting into practice the method as claimed in claim 1, characterized in that it comprises: a free culture reactor (1) in which the free culture grows in an aerated medium, in which a portion of the dissolved carbon pollution and nearly the entire colloidal and particulate fraction of the effluent are biosorbed by the activated sludge floc, said reactor, which constitutes said single aeration tank, comprising continuous or intermittent air input means (2), the mixing energy being supplied mechanically in this case, means (3) for continuous measurement of the turbidity of the activated sludge or of the mixed liquor and means for measuring the dissolved oxygen concentration, of which the data are processed by a servo system for slaving, on the one hand, the mixed liquor recirculation or extraction rate to maintain a constant solid matter content in said reactor and, on the other hand, the air input to maintain a low residual dissolved oxygen content in said reactor, an intermediate clarifier (4) which separates the sludge from the depolluted effluent, and a sludge recirculation circuit (5) from the intermediate clarifier to the free culture reactor, the recirculation (or extraction) rate being slaved to the turbidity measurement in the reactor. 8. The installation as claimed in claim 7, characterized in that the reactor 1 operating with very high loading activated sludge takes the form of an integral mixing aeration tank. 9. The installation as claimed in claim 7, characterized in that the sensor (3) is positioned directly in the biological reactor (1). 10. The installation as claimed in claim 7, characterized in that the sensor (3) is positioned at the outlet of said reactor, on the water line supplying the associated clarifier (4).

The present invention relates to the biological treatment of aqueous effluents, such as, in particular, domestic wastewater and industrial wastewater, for the purpose of their purification. More particularly, the invention relates to an improved method and device for the biological treatment of such effluents, employing free cultures of microorganisms according to the activated sludge technique in order to remove the carbon pollution present in the effluents to be treated. Among the known purification processes that use free cultures of microorganisms, those using so-called “low loading” activated sludges have come into increasingly frequent use. These methods of the “extensive” type have the feature of working with low applied mass and volumetric loadings, with high hydraulic residence times and a medium settling sludge, which leads to the construction of rather large structures, in terms of aeration tanks as well as clarification systems. Moreover, the devices that put these conventional purification methods into practice generally require a chain of specialized units which carry out in succession the screening, sediment removal, degreasing and primary settling of the effluent to be treated, these units being positioned upstream of the step of actual biological treatment with activated sludge. This explains why the installations of the prior art are costly, in terms of their construction as well as their operation and maintenance. To alleviate these drawbacks, the present invention provides a method for the biological treatment of effluents contaminated with impurities of municipal or industrial origin, characterized in that it employs a single aeration tank with high mass loading in which the raw or mechanically pretreated effluent is mixed, without prior settling, with a free microbial culture of the activated sludge type, growing in a lightly aerated medium, of the order of 0.1 to 0.2 kg O2/kg BOD5 removed, the applied organic loading being equal to or greater than at least 2 Kg COD/Kg SM/day, preferably equal to or greater than 4 Kg COD/Kg SM/day, the hydraulic residence time of the raw effluent in the single aeration tank being between 30 and 90 minutes, and preferably between 40 and 60 minutes. This explains why the overall system, which, in an installation of the prior art, consists of the primary settler and the aeration tank, is replaced, according to the invention, by a single aeration tank with a high mass loading. It is known that the mass loading is defined by the ratio of the daily pollution flow expressed in COD or in BOD5 to the quantity of dry matter present in the aeration tank. For the putting into practice of the method of the invention, the value of this mass loading must be above 1.5 Kg COD/Kg SM/day, and with a solid matter concentration between 0.5 and 2.5 g SM/l, which gives rise to applied volumetric loadings above 3 kg BOD5/m3/day. Thanks to these features according to the invention, the volume of the single aeration tank is reduced to the minimum by a factor of 10, in comparison with the activated sludge treatment tank of the conventional installations with prolonged aeration and low applied loading. The method of the invention as described above is based on biosorption: in a very high loading aeration tank, portion of the dissolved carbon pollution, and nearly the entire colloidal and particulate fraction, are biosorbed by the activated sludge floc. In effect, the fact that, according to the invention, the purifying action is based primarily on biosorption mechanisms and not on oxidation or fermentation biological mechanisms, and that the method serves to avoid a primary settling and the use of sediment removal and degreasing, serves to maintain a high content of colloidal and particulate matter in the effluent to be treated, these compounds promoting the biosorption. Biosorption can be described as a physicochemical mechanism in which the removal of the pollution corresponds to a rapid transfer of matter from the liquid phase to the floc, by adsorption, absorption and trapping. Three mechanisms immediately occur when the effluent enters into contact with the sludge (see Eikelboom-1982 in Bulking of Activated Sludge: Preventive and Remedial Methods, Ellis Horward Publ., Chichester, 90-105“Biosorption and prevention of bulking sludge by mean of a high floc loading”) and are superimposed in the overall mechanism called “biosorption”, that is: 1-the retention of the colloidal products by physicochemical adsorption on the floc (“surface fixation”), which leads to a bulking thereof; 2-the retention of the suspended matter by imbrication in the biological floc; 3-the extra- and intracellular absorption of the soluble organic matter by the microorganisms. At the very short hydraulic residence times imposed by the present invention (30 to 90 minutes), the microbial population does not have sufficient time to hydrolyze and to metabolize the adsorbed pollution. By contrast, absorption reflects the bacterial behavior and its capacity to accumulate nutrient reserves: intracellular “storage” for subsequent oxidation can correspond to 50% of the mass of the microorganism (see Ekama G. A. et al., 1979, journal WPCF, 51, 3, 534-556 “Dynamic behavior of the activated sludge process”). In the method according to the present invention, this absorption is only made possible if the bacteria are maintained in a situation of “stress”, which implies a minimal input of oxidation energy. In consequence, according to one feature of the method of the invention, the method is controlled at the anaerobiosis limit, by regulating the dissolved oxygen content at values between 0.1 and 1 g/l. This explains why the method according to the invention as described above is based on the trapping of the pollution by the “Activated Sludge” adsorbent and without biological degradation by oxidation or fermentation, the activated sludge used changing continuously at high applied mass loading, while maintaining a low aeration to guarantee the mixing energy for the system and sufficient energy for the biosorption. The high applied loading levels promote the adsorption and absorption mechanisms, while keeping the biomass in a state of maintenance with a virtually zero growth rate. These conditions, which are characteristic of the method of the invention, confer outstanding properties on the very high loading sludge, and particularly the following: the settlable pollution preserved in the absence of primary pretreatment serves to ballast the floc formed and thereby to achieve excellent clarification; the sludge index is remarkable with values in the range of 40 ml/g, values which are not obtained in the high loading method, according to the prior art, in which the aeration tank is preceded by a primary settler; the very good quality of the very high loading sludge, which has a suspended matter concentration of the order of 0.5 to 2.5 g/l, preferably between 0.6 and 1.5 g/l (these values can be compared with the values of 3 to 4 g/l which are recommended in the prior art, particularly in FR-A-2 594 113) serves to apply high upward velocities (>2 m/h) in the clarifier which is associated with the single aeration tank, as described below; aeration is a parameter that influences the performance of any biological system; paradoxically, according to the method of the invention, for a very high loading sludge, the oxygen demand is maintained limiting in order to guarantee a good biosorption, at the cost of a lower purification efficiency on the easily assimilable organic matter; this limitation of the oxidation metabolism is even more easily obtained if the hydraulic residence time is kept at a low value. The advantage of a system with a high or very high applied loading, according to the present invention, over the low loading systems, is considerable. Such so-called “intensive” systems allow the design of much more compact structures with the same volume of incoming pollution to be treated, in terms of the aeration tank as well as the clarification system, the sludges having excellent settling properties. The biosorption mechanism taking place in the method of the present invention is characterized by higher reaction kinetics (factor of 2 to 3) than the biological reactions observed in conventional activated sludges, and with a low air input (0.1 to 0.2 Kg O2/kg BOD5 removed compared with 0.6 Kg O2/kg BOD5 removed respectively). As to the reaction times, the orders of magnitude are as follows: 15 minutes for biosorption according to the method of the invention; about 30 to 45 minutes for metabolization according to conventional methods. The method according to the present invention is clearly distinguished from the prior art of the so-called very high loading methods, by specific conditions of use of the free culture, allowing for continuous growth in a lightly aerated medium and at high applied mass loading, to promote the mechanisms of biosorption and BOD storage. Thus, the very high loading activated sludge method developed by Professor Boehnke (see Boehnke B. et al., 1997, Water Environment & Technology, 23-27 “AB Process removes organics and nutrients” and Boehnke B. et al., 1998, Water Engineering & Management, 31-34 “Cost-effective reduction of high-strength wastewater by adsorption-based activated sludge technology”) does not refer to biosorption mechanisms, but to a microbiological selection pressure, leading to a specificity by adaptation of the biocenosis, reflected by the appearance of a bacterial population specific to the Very High Loading methods, in other words, metabolically more active methods. In this prior art, no reference is made to biosorption as an essential purifying mechanism, this mechanism only being used as a buffer during loading surges. Furthermore, the purification efficiencies are low (in the neighborhood of 50% for BOD5), whereas the method of the present invention serves to obtain average reductions in the range of 75% for BOD5 and 80% for SM. In terms of intensive methods, the prior art does not enable a person skilled in the art to control the implementation and the running of an activated sludge method, like the high loading or very high loading method, covered by the invention. In fact, it is well known to a person skilled in the art that these systems are very sensitive to loading surges, hydraulic or biological overloads, resulting in a rapid degradation of the efficiency and of the quality required of the treated water (in terms of carbon pollution and suspended matter). Thus, conventionally, during rainfall events, in which a degradation is observed in the composition of the water to be treated, these intensive methods prove to be inappropriate with a risk of leaching, potentially very rapid, of the solid matter present in the reactor, making the treatment of the effluent to the requisite quality impossible, the restoration of a normal situation occurring after up to more than 48 hours. The method covered by the invention, like any so-called intensive biological system, demonstrates very high responsiveness to the variations in the parameters of the untreated water. Considering the high ratio of pollution to the biomass present and consequently the low biomass concentration (1 to 2 g/l of SM), a wide variation in the properties of the untreated water very quickly upsets the equilibrium of the system. Unlike the prolonged aeration activated sludge method, that is, a so-called extensive system, the very high loading method only has a low buffer capacity. A significant decrease in the effluent concentrations immediately causes leaching of the biomass present in the system. Similarly, a significant increase in the untreated water pollutant loading contents rapidly causes an increase in the suspended matter concentration in the single aeration tank, and a possible overloading of the clarifier associated with it, as shown below. In order to make the method of the present invention more flexible, enabling it to withstand variations in volumetric or mass loading, a regulation system is provided, by adjustment of recirculation rate of the mixed liquor in the single aeration tank, this regulation being carried out so as to maintain the solid matter (suspended matter+biomass) within a preset range, preferably between about 1.0 and 1.5 g/l, and it is carried out by the continuous measurement of the turbidity of the activated sludge or of the mixed liquor, this measurement being combined with a slaving of the recirculation or extraction rate of said mixed liquor. According to the invention, a regulation of the air input in the single tank can also be provided, in order to maintain a low dissolved oxygen setpoint, for example between 0.1 and 1 mg/l. In fact, the excess dissolved oxygen can be used to oxidize the very easily assimilable organic matter, which must be avoided in the case of the process according to the invention, in which an attempt is made to promote the biosorption mechanism. Another subject of the invention is an installation for putting into practice the method described above. This installation is characterized in that it comprises: a free culture reactor in which the free culture grows in an aerated medium, this reactor, which constitutes said single aeration tank, comprising continuous or intermittent air input means with associated mixing, means for continuous measurement of the turbidity of the activated sludge or of the mixed liquor and means for measuring the dissolved oxygen concentration, of which the data are processed by a servo system for slaving, on the one hand, the mixed liquor recirculation or extraction rate to maintain a constant solid matter content in said reactor and, on the other hand, the air input to maintain a low residual dissolved oxygen content in said reactor, an intermediate clarifier which separates the 20, sludge from the depolluted effluent, and a sludge recirculation circuit from the intermediate clarifier to the free culture reactor, the recirculation (or extraction) rate being slaved to the turbidity measurement in the reactor. Other features and advantages of the present invention will appear from the description provided below, with reference to the drawings appended hereto, which illustrate a nonlimiting embodiment. In the drawings: FIG. 1 shows an installation according to the present invention and, FIG. 2 is a curve showing the variation in the biosorption constant as a function of the applied loading in an embodiment of the method of the invention. Reference to FIG. 1 shows that, in this embodiment, the device according to the invention comprises a reactor, or single aeration tank, with activated sludge under high loading, designated by the reference numeral 1, this reactor comprising continuous or intermittent air input means 2, the mixing energy being supplied mechanically, with a system for slaving to the dissolved oxygen content, and a turbidity measurement probe 3. In this embodiment, an intermediate settler 4 is associated with the reactor 1 in order to separate the sludge from the depolluted effluent. The installation further comprises a sludge recirculation circuit 5 from the intermediate settler 4 to the free culture reactor 1, the sludge recirculation rate (or sludge extraction rate from the intermediate settler 4) being slaved to the turbidity measurement supplied by the probe 3. Together with this basic equipment of the device according to the invention, various means of a known type can be provided, serving to supplement the effluent treatment. Thus, the device can comprise a second stage 6 which can be: a biomass nitrification reactor attached to a fixed or mobile support (depending on the suspended matter release limitations), receiving the intermediate effluent from the settler-clarifier 4; a biomass denitrification reactor attached to a fixed or mobile support (depending on the suspended matter release limitations), receiving the intermediate effluent from the nitrification reactor. The assimilable carbon necessary can be supplied externally (in the form of methanol for example), or from anaerobic digestion of the sludge extracted from the reactor, said sludge being highly fermentable; an anaerobic digestion reactor or any other sludge hydrolysis system for liquefying the fermentable fraction of this sludge and supplying the easily assimilable carbon necessary for the denitrification process or for a methanation process; the remaining sludge made inert after hydrolysis being separated by any suitable method such as centrifugation, microfiltration; a methanation reactor for producing biogas and thereby supplying a portion of the energy necessary for the operation of the method. Preferably, the reactor 1 operating with very high loading activated sludges takes the form of an aeration tank, known, in terms of chemical engineering, by the name of “integral mixing bioreactor” which achieves effective mixing with low energy consumption; since the properties of the water are the same at all points of the tank, the biosorption mechanism is promoted. This type of tank has the drawback of being sensitive to the variations in flow rate and properties of the liquid to be treated, factors which are very frequently observed in the field of wastewater treatment. Since, according to the invention, the oxygen content is slaved, said sensitivity to the flow rate and pollution flow will have no repercussions on the treatment of the effluent. As mentioned above, in order to enable the reactor 1 to withstand variations in volumetric or mass loading, the invention provides a control system, by adjustment of the recirculation rate of the mixed liquor (circuit 5), to maintain the solid matter (SM+biomass) within the preset range, preferably in the neighborhood of 1.0-1.5 g/l, as specified above. For this purpose, the turbidity is continuously measured, using the probe turbidimeter 3, or any other suitable sensor known to a person skilled in the art, for example: particle counter, spectrophotometer, etc., this measurement being combined with a device for slaving the recirculation or extraction rate of the mixed liquor. With the help of correlations taken from correction charts, this measurement serves to roughly characterize the content of suspended solid matter in the medium, thereby describing the operating conditions of the installation. The practical advantage of using this parameter for regulating activated sludge purification methods has already been emphasized. Thus, FR-A-2 784 093 describes a method of automated recirculation management developed in order to control the sludge residence time in secondary clarification in the activated sludge methods, and this method uses a signal representing the sludge concentration obtained using a sensor positioned in the recirculation line. Moreover, FR-A-2 795 713 uses the turbidity measurement to characterize the pollutant load present in the untreated water, this measurement being associated with the colloidal and particulate pollution. In the present invention, the signal obtained must represent the solid matter concentration, the biosorption mechanism not occurring exclusively with the microorganisms but also with the suspended matter present in the sludge. In these conditions, in the device according to the invention, the sensor such as 3 must be positioned either directly in the biological reactor 1 as shown in FIG. 1, or at the outlet of said reactor, on the water line supplying the associated clarifier 4. The sensor is positioned according to the rules of the art known to a person skilled in the art, in accordance with the type of sensor chosen. The regulation put into practice according to the invention can consist in defining four suspended matter SM concentration intervals, in the single aeration tank 1. Each interval corresponds to an adapted operation, either of the mixed liquor recirculation pump from the clarifier 4 to the aeration tank 1, or of the sludge extraction pump. Monitoring the suspended matter SM concentration from the slaving of the extraction flow rate serves to obtain a total flow rate that varies only slightly (wastewater+recirculation) through the system. Thanks to this regulation, it is possible to reduce the variations in suspended matter concentration, in normal periods, and then to return rapidly to normal operation in case of disturbances due, for example, to loading surges, rainfall events etc. Preferably, the setpoints defined are as follows: target concentration 1.5 g/l, concentration deviation ±0.3 g/l, floor concentration 1 g/l. During a rainfall event, the dilution of the pollutants present in the untreated water causes a drop in the applied solid matter in the reactor 1. This variation immediately causes an increase in the recirculation rate or a decrease in the extraction rate, to avoid any risk of leaching (removal of solid matter present in the reactor). During daily peaks, the pollutant concentrations increase, as well as the applied loadings; this variation immediately causes a reduction of the recirculation rate or an increase of the extraction rate, to avoid a saturation of the clarifier, which would result in sludge losses in the treated water. The table below shows the implementation of this regulation. According to another feature of the present invention, a regulation of the air input is also provided in order to maintain a low dissolved oxygen setpoint. This regulation, based on the generation of two different air flow setpoints depending on the dissolved oxygen concentration in the aeration tank 1, and of which the implementation is well known to a person skilled in the art, will serve to constantly maintain a residual dissolved oxygen content of between 0.1 and 1 mg/l. The regulation can also be obtained by stopping the aeration and supplying the mixing energy by mechanical means. Thus, according to the invention, two distinct parameters are slaved: the recirculation or extraction rate of the mixed liquor to maintain a constant solid matter content in the biological reactor 1, and the control of the air input means 2 to maintain a low residual dissolved oxygen content in the biological reactor. As it may be understood, the combination of a very high loading activated sludge method with an optimized control system, based on the slaving of the mixed liquor recirculation or extraction means and the air input means, serves not only to obtain a high level of treatment of the carbon pollution in a compact reactor associated with an equally compact clarifier, but above all, to control the method and its performance over time, even during hydraulic overload periods. The example of implementation given in the table below shows the leaching resistance, in an installation according to the invention operating under high loading, without slaving on the one hand, and with slaving on the other, and FIG. 2 shows the variation curve of the biosorption constant Ao as a function of the applied mass loading Cma, expressed as total COD. An examination of this curve shows that the higher the applied loading, the higher the biosorption constant. Examples of VHL (very high loading): leaching resistance Without SM CMa CODt SM slaving (g/l) Kg CODt/Kg SM/day efficiency (%) efficiency (%) Day 1 1.5 13.6 64 71 Day 2 LEACHING Day 3 0.4 17.3 45 51 Day 4 1.0 22.8 44 50 Day 5 1.4 14.7 58 65 With SM CMa CODt SM slaving (g/l) Kg CODt/Kg SM/day efficiency (%) efficiency (%) Day 1 2.0 10.8 64 73 Day 2 1.8 Day 3 1.7 9.8 62 68 Day 4 1.9 10.7 61 67 Day 5 2.0 9.7 58 75

20050125

20071002

20060629

69012.0

C02F312

PRINCE JR, FREDDIE GARY

METHOD AND PLANT FOR BIOLOGICAL TREATMENT OF AQUEOUS EFFLUENTS FOR PURIFICATION THEREOF

UNDISCOUNTED

ACCEPTED

C02F

ACCEPTED

Device for opening and closing the hood of a folding-top convertible motor vehicle

A device comprising, additionally to the main jack, a balancing jack designed to facilitate manual opening of the hood from the in a forward movement for storing luggage in the trunk, and manual closure of hood in the opposite direction. The balancing jack has its base linked to the main jack and the free end of its piston rod fixed in articulation to the hood. It is designed so as not to obstruct the operation of the main jack for automatically opening or closing the hood. The device further comprises means for actuating the balancing jack to enable the hood to be manually opened or closed.

1-9. (cancelled) 10. A device for opening and closing a hood of a trunk provided on a folding-top convertible vehicle comprising a bodywork, a foldable roof, the trunk, and said hood thereof, the trunk having a bottom, the device including: controlling means for controlling a first opening of the hood in a forward direction to store luggage in the trunk and a second opening of said hood in an opposite backward direction to pass and store a folded roof in the trunk, a main jack operated for controlling said first and second openings, said main jack having a base which is articulated on a part of the bodywork adjacent to the bottom of the trunk, and a rod having an end fixed to said hood, a balancing jack adapted to facilitate a manually-operated opening of the hood in the forward direction and a manually-operated closing of the hood in the opposite backward direction, the balancing jack having a base connected to the main jack and a rod having an end articulated on the hood, the balancing jack being arranged to prevent interference with operation of the main jack for automatically opening and closing the hood, balancing jack inactivation means for making the balancing jack inactive so as to authorize automatic opening or closing of the hood, and balancing jack activation means for making the balancing jack active so as to authorize manual opening or closing of the hood. 11. The device of claim 10, further comprising an intermediate member having a substantially S shape, a lower end fixed in an articulated manner to the base of the balancing jack, and a top end articulated on said end of the rod of the main jack. 12. The device of claim 11, further comprising locking means for detachably fixing the top end of the intermediate member to the hood, and displacing means for displacing said locking means so that the top end of the intermediate member is released from the hood. 13. The device of claim 12, wherein: the hood is provided with a hook pivotally installed on the hood, the top end of the intermediate member is provided with a latch, and the hook is adapted to engage said latch to fix the top end of the intermediate member to the hood. 14. The device of claim 13, wherein the hook has a part which is shaped so that it can be pushed by the latch when the hood is being closed, and the hook is adapted to engage the latch when said hood is closed. 15. The device of claim 14, wherein the hook is arranged so as to pivot about a first pin with respect to the hood, and the latch comprises a second pin parallel to the first pin, and a spring being arranged to permanently urge the hook in the closing direction of the hook. 16. The device of claim 13, wherein the hood comprises pivoting means for pivoting the hook in order to release said hook from a position engaged with the latch. 17. The device of claim 13, wherein the hood comprises a cable having a first end fixed to the hook and a second end fixed to a control element supported by the hood, for pivoting the hook in order to engage said hook with said latch or to release said hook from said engagement. 18. The device of claim 10, wherein the hood has a front edge and a back edge which are both connected to the bodywork of the vehicle by means of respective front locks and back locks, each having the function of locking and articulating the hood such that said hood is adapted to be opened in either the backward direction or the forward direction. 19. A folding-top convertible vehicle, comprising a folding-top, a trunk, a trunk hood, a bodywork, and a device for opening and closing said trunk hood, the device including: controlling means for controlling a first opening of the hood in a forward direction to store luggage in the trunk and a second opening of said hood in an opposite backward direction to pass and store a folded roof in the trunk, a main jack operated for controlling said first and second openings, said main jack having a base which is articulated on a part of the bodywork adjacent to a bottom of the trunk, and a rod having an end fixed to said hood, a balancing jack adapted to facilitate a manually-operated opening of the hood in the forward direction and a manually-operated closing of the hood in the opposite backward direction, the balancing jack having a base connected to the main jack and a rod having an end articulated on the hood, the balancing jack being arranged to prevent interference with operation of the main jack for automatically opening and closing the hood, balancing jack inactivation means for making the balancing jack inactive so as to authorize automatic opening or closing of the hood, and balancing jack activation means for making the balancing jack active so as to authorize manual opening or closing of the hood. 20. The vehicle of claim 19, further comprising an intermediate member having a substantially S shape, a lower end fixed in an articulated manner to the base of the balancing jack, and a top end articulated on said end of the rod of the main jack. 21. The vehicle of claim 20, further comprising locking means for detachably fixing the top end of the intermediate member to the hood, and displacing means for displacing said locking means so that the top end of the intermediate member is released from the hood. 22. The vehicle of claim 21, wherein: the hood is provided with a hook pivotally installed on the hood, the top end of the intermediate member is provided with a latch, and the hook engages said latch to fix the top end of the intermediate member to the hood. 23. The vehicle of claim 22, wherein the hook has a part which is shaped so that it can be pushed by the latch when the hood is closing, and the hook is adapted to automatically engage the latch when the hood is closing. 24. The vehicle of claim 23, wherein the hook is arranged so as to pivot about a first pin with respect to the hood, and the latch comprises a second pin parallel to the first pin, and a spring being arranged to permanently urge the hook in the closing direction of the hook. 25. The vehicle of claim 22, wherein the hood comprises pivoting means for pivoting the hook in order to release said hook from a position engaged with the latch. 26. The vehicle of claim 22, wherein the hood comprises a cable having a first end fixed to the hook and a second end fixed to a control element supported by the hood, pivoting the hook in order to engage said hook with said latch or to be released from said engagement. 27. The vehicle of claim 19, wherein the hood has a front edge and a back edge which are both connected to the bodywork of the vehicle by means of respective front locks and back locks, each having the function of locking and articulating the hood such that said hood is adapted to be opened in either the backward direction or the forward direction.

BACKGROUND OF THE INVENTION This invention relates to a device for opening and closing the hood of a folding-top convertible motor vehicle. For example, French patent application FR-A-2 777241 in the name of the applicant describes a device of the above-mentioned type that includes means for controlling opening of the hood in the forward direction to store luggage in the trunk and opening of the said hood in the backward direction to pass and store the folded roof in the trunk. This opening is controlled by at least one main jack, the base of which is installed in an articulated manner on a part of the bodywork adjacent to the bottom of the trunk, and the free end of the rod of which is fixed to the said hood. However, it happens that some users of such a device would like to be able to open and close the hood of the trunk of their vehicle manually, for example so that they can control such an operation without needing to enter inside the said vehicle. SUMMARY OF THE INVENTION The purpose of this invention is to overcome the disadvantages of known devices and to propose a device of the above-mentioned type for manually opening and closing the hood of the trunk of a convertible vehicle. According to this invention, the device of the above-mentioned type is characterised in that it also comprises for each main jack a balancing jack adapted to facilitate manual opening of the hood in the forward direction for the storage of luggage in the trunk, and manual closing of the said trunk in the opposite direction, this balancing jack having its base connected to the main jack and the free end of its rod fixed in an articulated manner to the hood and being arranged so that it does not hinder operation of the main jack for automatically opening and closing of the hood, the device also including means for making the balancing jack inactive so as to authorise automatic opening or closing of the hood, and means for making the balancing jack active so as to authorise manual opening or closing of the hood. The device thus enables the two operating modes (automatic and manual), of the hood opening and closing operations. According to one advantageous embodiment of the invention, the device comprises an intermediate device substantially in the shape of an S of which the lower end is fixed in an articulated manner to the base of the balancing jack and of which the top end is fixed in an articulated manner to the free end of the rod of the main jack. According to one preferred embodiment of the invention, the device also comprises locking means for detachably fixing the top end of the intermediate device to the hood, and means for displacing the said locking means to release the top end of the intermediate device from the hood. Thus, when the top end of the intermediate device is fixed to the hood, the main jack can automatically open and close the hood. On the other hand, when the top end of the intermediate device is separated from the hood, the hood can be opened or closed manually with the assistance of the balancing jack. Other special features and advantages of this invention will become clear from the following description given below. BRIEF DESCRIPTION OF THE DRAWINGS Among the appended drawings given as non-limitative examples only: FIG. 1 is a diagrammatic longitudinal sectional view of a vehicle illustrating a device according to the prior art; FIG. 2 is a view similar to FIG. 1 illustrating an embodiment of the device according to the invention, the hood being in its closed position; FIG. 3 is a view similar to FIG. 2, the hood being in its backward open position; FIG. 4 is a view similar to FIG. 2, the hood being in its forward open position; FIG. 5 is an enlarged diagrammatic view of a detail of FIG. 2. DETAILED DESCRIPTION OF PREFERRED EMBODIMENT(S) In the embodiment shown in FIG. 1, the hood 1 of the trunk 2 of a folding-top convertible vehicle (not shown) can be opened in the forward direction along the direction of arrow 3, towards the position marked la, to store luggage in the trunk and more generally for access to the trunk from the back of the vehicle. The hood 1 may also be opened in the backward direction along the direction of arrow 4 towards the position marked 1b, to pass and store the folded roof in the trunk 2. Opening of the hood 1 is controlled by at least one main jack 5, the base 6 of which is installed in an articulated manner on a part 7 of the bodywork 8 adjacent to the bottom 9 of the trunk 2. In general, a main jack 5 is installed on each side of the trunk 2 along a corresponding lateral wall in the trunk 2. The free end 10 of the rod 11 of the jack 5 is fixed to the hood 1. The front edge 12 and the back edge 13 of the hood 1 are connected to the bodywork 8 of the vehicle by means of corresponding front locks 14 and back locks 15, each having the function of locking and articulating the hood 1 such that the said hood 1 can open in either the backward direction (arrow 4) or the forward direction (arrow 3). In the detailed description of an embodiment of the device according to this invention, the same reference numbers are used for elements of the invention that are identical to elements mentioned above in the device according to the prior art. According to this invention, the device 20 also comprises, for each main jack 5, a balancing jack 21 adapted to facilitate manual opening of the hood 1 in the forward direction, in the direction of arrow 3, to store luggage in the trunk 2 and manual closing of the said hood 1 in the reverse direction. The balancing jack 21 is any known type of balancing jack that is independent and does not require any connection to any energy source whatsoever. The balancing jack 21 has its base 22 connected to the main jack 5, and the free end 23 of its rod 24 fixed to the hood 1 in an articulated manner. The balancing jack 21 is arranged so that it does not hinder the operation of the main jack 5 for automatic opening or closing of the hood 1. The device 20 also comprises means 25 for making the balancing jack 21 inactive so as to authorise automatic opening or closing of the hood 1, and means for making the balancing jack 21 active so as to authorise manual opening or closing of the hood 1. As shown in FIGS. 2 to 4, the device 21 comprises an intermediate device 26 approximately in the form of an S, of which the lower end 27 is fixed in an articulated manner to the base 22 of the balancing jack 21 and of which the top end 28 is fixed in an articulated manner to the free end 10 of the rod 11 of the main jack 5. In the embodiment shown, the intermediate device 26 comprises a main body 29 extending approximately parallel to the main jack 5 and the balancing jack 21 when the hood 1 is in its closed position shown in FIG. 2. The lower end 27 of the device 26 is composed of a transverse prolongation of the body 29 extending under the balancing jack 21. The top end 28 of the intermediate device 26 consists of a transverse prolongation of the body 29 extending above the main jack 5. The device 20 comprises locking means 30 for detachably fixing the top end 28 of the intermediate device 26 to the hood 1, and means for displacing the said locking means 30 so as to release the top end 28 of the intermediate device 26 from the hood 1. In the example in FIG. 5, the hood 1 is provided with a hook 31 pivotally installed on the hood 1. The top end 28 of the intermediate device 26 is provided with a latch 32, the hook 31 being adapted to engage the latch 32 to fix the top end 28 of the intermediate device 26 to the hood 1. In this example, the bottom part 33 of the hook 31 is shaped so that it can be pushed by the latch 32 when the hood 1 closes, as shown diagrammatically by arrow 34, and the hook 31 is adapted to automatically engage the latch 32 when the hood 1 is closed. In this example, the hook 31 is arranged so as to be able to pivot about a first pin 35 with respect to the hood 1, and the latch 32 is a second pin 32 approximately parallel to the first pin 35. A spring 37 is arranged to permanently urge the hook 31 in the closing direction of the hook 31, this direction being shown diagrammatically by arrow 38. In this case the spring 37 is a tension spring fixed at a first end 39 to a plate 40 fixed to the hood 1 and at its other end 41 to the hook 31. The hood 1 also comprises means 42 for pivoting the hook 31 in order to release it from its position engaged with the latch 32 shown in FIG. 5. In this case, the hood 1 comprises a cable 43, one end 44 of which is fixed to the hook 31 and the other end 45 of which is fixed to a control element, shown diagrammatically in 46, supported by the hood 1, which for example may be a push-button or a lever of any known type supported on the hood 1 and which may also control a lock of any type whatsoever, shown diagrammatically in 16. In the example in FIG. 5, the first pivot pin 35 of the hook 31 is supported by plate 40, and the end 44 of the cable 43 is located on the hook 31 opposite the end 41 of the spring 37 with respect to the pin 35. The plate 40 also supports a stop 47, and the hook 31 is held in permanent contact with this stop by the tension applied by the spring 37. In this example, tension applied to the cable 43 in the direction of the arrow 48 towards the right in the figure, makes the hook 31 to pivot in the direction of the arrow 49 in the clockwise direction in the figure, to release the hook 31 from its position engaged with the latch 32. This operation eliminates all connections between the plate 40 and firstly the hood 1, and secondly the top end 28 of the intermediate device 26. Under these conditions, with the main jack 5 not being activated, an upward force in the direction of the arrow 3 applied to the back edge 13 of the hood 1 makes it possible to open the hood 1 as far as its open position la to provide access to the trunk 2, the balancing jack 21, facilitating this opening manoeuvre and holding the hood 1 in its open position. On the other hand, pushing downwards on the back edge 13 of the hood 1 makes the hood 1 to pivot in the direction of arrow 4 as far as its closed position in FIG. 2 with the assistance of the balancing jack 21. In these two manoeuvres, the user can thus proceed in the same way as for a trunk hood with manual opening or closing, with the same habits and the same care and caution reflexes. At the end of the closing operation, the bottom part 33 of the hook 31 comes into contact with the latch 32 and is shaped so as to make the hook 31 to pivot in the direction of the arrow 49 against the action of the spring 37 until the tip 50 of the hook 31 can pass under the latch 32. This final operation puts the cable 43 and the control element 46 back into the position that each occupies when the hook 31 is in its position engaged with the latch 32 to fix the top end 28 of the intermediate device 26 to the hood 1. Thus, when the hook 31 is engaged with the latch 32, as shown diagrammatically in FIG. 5, the balancing jack 21 is locked in its retracted position and the jack 5 can control automatic opening and closing of the hood 1 in either direction (arrow 4 in FIG. 3). On the contrary, when the hook 31 is pivoted by pulling the cable 43 so as to move said hook away from its position engaged with the latch 32, the balancing jack 21 is released while the main jack 5 is inactive, and it is possible to open the hood manually in the forward direction to access the trunk 2 or to close the trunk manually, the trunk opening and closing operations being facilitated by the balancing jack 21. Obviously, this invention is not limited to the embodiments that have just been described, and many changes and modifications could be made to them without going outside the scope of the invention. For example, it would thus be possible to replace the mechanical locking means 30 described above by equivalent hydraulic or electrical means fulfilling the same function to obtain the same result. Conventional guide and/or support means could also be provided between the intermediate device 26 and firstly the first main jack 5, and secondly the balancing jack 21.

<SOH> BACKGROUND OF THE INVENTION <EOH>This invention relates to a device for opening and closing the hood of a folding-top convertible motor vehicle. For example, French patent application FR-A-2 777241 in the name of the applicant describes a device of the above-mentioned type that includes means for controlling opening of the hood in the forward direction to store luggage in the trunk and opening of the said hood in the backward direction to pass and store the folded roof in the trunk. This opening is controlled by at least one main jack, the base of which is installed in an articulated manner on a part of the bodywork adjacent to the bottom of the trunk, and the free end of the rod of which is fixed to the said hood. However, it happens that some users of such a device would like to be able to open and close the hood of the trunk of their vehicle manually, for example so that they can control such an operation without needing to enter inside the said vehicle.

<SOH> SUMMARY OF THE INVENTION <EOH>The purpose of this invention is to overcome the disadvantages of known devices and to propose a device of the above-mentioned type for manually opening and closing the hood of the trunk of a convertible vehicle. According to this invention, the device of the above-mentioned type is characterised in that it also comprises for each main jack a balancing jack adapted to facilitate manual opening of the hood in the forward direction for the storage of luggage in the trunk, and manual closing of the said trunk in the opposite direction, this balancing jack having its base connected to the main jack and the free end of its rod fixed in an articulated manner to the hood and being arranged so that it does not hinder operation of the main jack for automatically opening and closing of the hood, the device also including means for making the balancing jack inactive so as to authorise automatic opening or closing of the hood, and means for making the balancing jack active so as to authorise manual opening or closing of the hood. The device thus enables the two operating modes (automatic and manual), of the hood opening and closing operations. According to one advantageous embodiment of the invention, the device comprises an intermediate device substantially in the shape of an S of which the lower end is fixed in an articulated manner to the base of the balancing jack and of which the top end is fixed in an articulated manner to the free end of the rod of the main jack. According to one preferred embodiment of the invention, the device also comprises locking means for detachably fixing the top end of the intermediate device to the hood, and means for displacing the said locking means to release the top end of the intermediate device from the hood. Thus, when the top end of the intermediate device is fixed to the hood, the main jack can automatically open and close the hood. On the other hand, when the top end of the intermediate device is separated from the hood, the hood can be opened or closed manually with the assistance of the balancing jack. Other special features and advantages of this invention will become clear from the following description given below.

20041026

20060228

20050303

81016.0

MORROW, JASON S

DEVICE FOR OPENING AND CLOSING THE HOOD OF A FOLDING-TOP CONVERTIBLE MOTOR VEHICLE

UNDISCOUNTED

ACCEPTED

ACCEPTED

Method and system for sending a message through a secure connection

The method and system enable secure forwarding of a message from a first computer to a second computer via an intermediate computer in a telecommunication network. A message is formed in the first computer or in a computer that is served by the first computer, and in the latter case, sending the message to the first computer. In the first computer, a secure message is then formed by giving the message a unique identity and a destination address. The message is sent from the first computer to the intermediate computer after which the destination address and the unique identity are used to find an address to the second computer. The current destination address is substituted with the found address to the second computer, and the unique identity is substituted with another unique identity. Then the message is forwarded to the second computer.

1. A method for secure forwarding of a message from a first computer to a second computer via an intermediate computer in a telecommunication network, comprising: a) forming a message in the first computer or in a computer that is served by the first computer, and in the latter case sending the message to the first computer, b) in the first computer, forming a secure message by giving the message a unique identity and a destination address, c) sending the secure message from the first computer to the intermediate computer, d) using said destination address and the unique identity to find an address to the second computer, e) substituting the current destination address with the found address to the second computer, f) substituting the unique identity with another unique identity, and g) forwarding the secure message with substituted current destination address and substituted unique identity to the second computer. 2. The method of claim 1 wherein the method further comprises forming the secure message in step b) by using an IPSec connection between the first computer and the second computer. 3. The method of claim 1 wherein the method further comprises performing a secure forwarding of the message by making use of or TLS protocols. 4. The method of claim 2 wherein the method further comprises manually performing a preceding distribution of keys to components for forming the IPSec connection. 5. The method of claim 2 wherein the method further comprises performing a preceding distribution of keys for forming the IPSec connection by an automated key exchange protocol. 6. The method of claim 5 wherein the method further comprises performing the automated key exchange protocol used for the preceding distribution of keys, for forming the IP Sec connection by means of a modified IKE key exchange protocol between the first computer and the intermediate computer and by means of a standard IKE key exchange protocol between the intermediate computer and the second computer. 7. The method of claim 2 wherein the method further comprises sending the message that is sent from the first computer in step c) as a packet that contains message data, an inner IP header containing the actual sender and receiver addresses, an outlet IP header containing the addresses of the first computer and the intermediate computer, the unique identity. 8. The method of claim 1 wherein the method further comprises the IPSec connection being one or more security associations (SA) and the unique identity being one or more SPI values. 9. The method of claim 1 wherein the method further comprises performing the matching in step d) by using a translation table stored at the intermediate computer. 10. The method of claim 1 wherein the method further comprises changing both the address and the SPI-value by the intermediate computer in steps e) and f). 11. The method of claim 1 wherein the method further comprises the first computer being a mobile terminal so that the mobility is enabled by modifying the translation table at the intermediate computer. 12. The method of claim 11 wherein the method further comprises performing the modification of the translation tables by sending a request for registration of the new address from the first computer to the intermediate computer. 13. The method of claim 12 wherein the method further comprises sending a reply to the request for registration from the intermediate computer to the first computer. 14. The method of claim 12 wherein the method further comprises authenticating or encrypting by IPSec the request for registration and/or reply. 15. The method of claim 4 wherein the method further comprises establishing the key distribution for the secure connections by establishing an IKE protocol translation table, and using the translation table to modify IP addresses and cookie values of IKE packets in the intermediate computer. 16. The method of claim 15 wherein the method further comprises establishing the key exchange distribution by generating an initiator cookie and sending a zero responder cookie to the second computer, generating a responder cookie in the second computer, establishing a mapping between IP addresses and IKE cookie values in the intermediate computer, and using the translation table to modify IKE packets in flight by modifying the external IP addresses and possibly IKE cookies of the IKE packets. 17. The method of claim 15 wherein the method further comprises modifying the modified IKE protocol between the first computer and the intermediate computer by transmitting the IKE keys from the first computer to the intermediate computer in order to decrypt and modify IKE packets. 18. The method of claim 15 wherein the method further comprises carrying out in the modified IKE protocol between the first computer and the intermediate computer the modification of the IKE packets by the first computer with the intermediate computer requesting such modifications. 19. The method of claim 17 wherein the method further comprises defining the address so that the first computer is identified for the second computer by the intermediate computer by means of an IP address taken from a pool of user IP addresses when forming the translation table. 20. The method of claim 1 wherein the method further comprises sending the secure message is by using an IPSec transport mode. 21. The method of claim 1 wherein the method further comprises sending the secure message by using an IPSec tunnel mode. 22. A telecommunication network for secure forwarding of messages, comprising: at least a first computer, a second computer and an intermediate computer, the first and the second computers having means for performing an IPSec processing, and the intermediate computer having translation tables to perform IPSec and IKE translation. 23. The telecommunication network of claim 22 wherein the translation table for IPSec translation had IP addresses of the intermediate computer to be matched with IP addresses of the second computer. 24. The telecommunication network of claim 22 wherein the translation tables for IKE translation consists of two partitions, one for the communication between the first computer and the intermediate computer and another for the communication between the intermediate computer and the second computer. 25. The telecommunication network of claim 24 wherein both partitions of the mapping table for, IKE translation contains translation fields for a source IP address, a destination IP address, initiator and responder cookies between respective computers. 26. The telecommunication network of claim 22 wherein there is another translation table for IKE translation containing fields for matching a given user to a given second computer.

TECHNICAL FIELD The method and system of the invention are intended to secure connections in telecommunication networks. Especially, it is meant for wireless Internet Service Provider (ISP) connections. TECHNICAL BACKGROUND An internetwork is a collection of individual networks connected with intermediate networking devices that function as a single large network. Different networks can be interconnected by routers and other networking devices to create an internetwork. A local area network (LAN) is a data network that covers a relatively small geographic area. It typically connects workstations, personal computers, printers and other devices. A wide area network (WAN) is a data communication network that covers a relatively broad geographic area. Wide area networks (WANS) interconnect LANs across normal telephone lines and, for instance, optical networks; thereby interconnecting geographically disposed users. There is a need to protect data and resources from disclosure, to guarantee the authenticity of data, and to protect systems from network based attacks. More in detail, there is a need for confidentiality (protecting the contents of data from being read) integrity (protecting the data from being modified, which is a property that is independent of confidentiality), authentication (obtaining assurance about she actual sender of data), replay protection (guaranteeing that data is fresh, and not a copy of previously sent data), identity protection (keeping the identities of parties exchanging data secret from outsiders), high availability, i.e. denial-of-service protection (ensuring that the system functions even when under attack) and access control. IPSec is a technology providing most of these, but not all of them. (In particulars identity protection is not completely handled by IPSec, and neither is denial-of-service protection.) The IP security protocols (IPSec) provides the capability to secure communications between arbitrary hosts, e.g. across a LAN, across private and public wide area networks (WANs) and across the internet IPSec can be used in different ways, such as for building secure virtual private networks, to gain a secure access to a company network, or to secure communication with other organisations, ensuring authentication and confidentiality and providing a key exchange mechanism. IPSec ensures confidentiality integrity, authentication, replay protection, limited traffic flow confidentiality, limited identity protection, and access control based on authenticated identities. Even if some applications already have built in security protocols, the use of IPSec further enhances the security. IPSec can encrypt and/or authenticate traffic at IP level. Traffic going in to a WAN is typically compressed and encrypted and traffic coming from a WAN is decrypted and decompressed. IPSec is defined by certain documents, which contain rules for the IPSec architecture. The documents that define IPSec, are, for the time being, the Request For Comments (RFC) series of the Internet Engineering Task Force (IETF), in particular, RFCs 2401-2412. Two protocols are used to provide security at the IP layer; an authentication protocol designated by the header of the protocol, Authentication Header (AH), and a combined encryption/authentication protocol designated by the format of the packet for that protocol, Encapsulating Security Payload (ESP) AH and ESP are however similar protocols, both operating by adding a protocol header. Both AH and ESP are vehicles for access control based on the distribution of cryptographic keys and the management of traffic flows related to these security protocols. Security association (SA) is a key concept in the authentication and the confidentiality mechanisms for IP. A security association is a one-way relationship between a sender and a receiver that offers security services to the traffic carried on it if a secure two-way relationship is needed, then two security associations are required. If ESP and AH are combined, or if ESP and/or AH are applied more than once, the term SA bundle is used, meaning that two or more SAs are used. Thus, SA bundle refers to one or more SAs applied in sequence, e.g. by first performing an ESP protection, and then an AH protection. The SA bundle is the combination of all SAs used to secure a packet. The term IPsec connection is used in what follows in place of an IPSec bundle of one or more security associations, or a pair of IPSec bundles—one bundle for each direction—of one or more security associations. This term thus covers both unidirectional and bi-directional traffic protection. There is no implication of symmetry of the directions, i.e., the algorithms and IPSec transforms used for each direction may be different. A security association is uniquely identified by three parameters. The first one, the Security Parameters Index (SPI), is a bit string assigned to this SA The SPI is carried in AH and ESP headers to enable the receiving system to select the SA under which a received packet will be processed. IP destination address is the second parameter, which is the address of the destination end point of the SA, which may be an end user system or a network system such as a firewall or a router. The third parameter, the security protocol identifier indicates whether the association is an AH or ESP security association. In each IPSec implementation, there is a nominal security association data base (SADB) that defines the parameters associated with each SA. A security association is normally defined by the following parameters. The Sequence Number Counter is a 32-bit value used to generate the sequence number field in AH or ESP headers. The Sequence Counter Overflow is a flag indicating whether overflow of the sequence number counter should generate an auditable event and prevent further transmission of packets on this SA. An Anti-Replay Window is used to determine whether an inbound AH or ESP packet is a replay. AH information involves information about the authentication algorithm, keys and related parameters being used with AH. ESP information involves information of encryption and authentication algorithms, keys, initialisation vectors, and related parameters being used with IPSec. AH information consists of the authentication algorithm, keys and related parameters being used with AH. ESP information consists of encryption and authentication algorithms, keys, cryptographic initialisation vectors and related parameters being used with ESP. The sixth parameter, Lifetime of this Security Association, is a time-interval and/or byte-count after which this SA must be replaced with a new SA (and new SPI) or terminated plus an indication of which of these actions should occur. IPSec Protocol Mode is either tunnel or transport mode. Maximum Transfer Unit (MTU), an optional feature, defines the maximum size of a packet that can be transmitted without fragmentation. Optionally an MTU discovery protocol may be used to determine the actual MTU for a given route, however, such a protocol is optional. Both AH and ESP support two modes used, transport and tunnel mode. Transport mode provides protection primarily for upper layer protocols and extends to the payload of an IP packet Typically, transport mode is used for end-to-end communication between two hosts. Transport mode may be used in conjunction with a tunnelling protocol, other than IPSec tunnelling, to provide a tunnelling capability. Tunnel mode provides protection to the entire IP packet and is usually used for sending messages through more than two components, although tunnel mode may also be used for end-to-end communication between two hosts. Tunnel mode is often used when one or both ends of a SA is a security gateway, such as a firewall or a router that implements IPSec. With tunnel mode, a number of hosts on networks behind firewalls may engage in secure communications without implementing IPSec. The unprotected packets generated by such hosts are tunnelled through external networks by tunnel mode SAs set up by the IPSec software in the firewall or secure router at boundary of the local network. To achieve this, after the AH or ESP fields are added to the IP packet, the entire packet plus security fields are treated as the payload of a new outer IP packet with a new outer IP header. The entire original, or inner, packet travels through a tunnel from one point of an IP network to another: no routers along the way are able to examine the inner IP packet. Because the original packet is encapsulated, the new larger packet may have totally different source and destination addresses, adding to the security. In other words, the first step in protecting the packet using tunnel mode is to add a new IP header to the packet; thus the “IP|payload” packet becomes “IP|IP|payload”. The next step is to secure the packet using ESP and/or AH. In case of ESP, the resulting packet is “IP|ESP|IP|payload”. The whole inner packet is covered by the ESP and/or AH protection. AH also protects parts of the outer header, in addition to the whole inner packet. The IPSec tunnel mode operates e.g. in such a way that if a host on a network generates an IP packet with a destination address of another host on another network, the packet is routed from the originating host to a security gateway (SGW), firewall or other secure router at the boundary of the first network. The SGW or the like filters all outgoing packets to determine the need for IPSec processing. If this packet from the first host to another host requires IPSec, the firewall performs IPSec processing and encapsulates the packet in an outer IP header. The source IP address of this outer IP header is this firewall and the destination address may be a firewall that forms the boundary to the other local network. This packet is now routed to the other host's firewall with intermediate routers examining only the outer IP header At the other host firewall, the outer IP header is stripped off and the inner packet is delivered to the other host. ESP in tunnel mode encrypts and optionally authenticates the entire inner IP packet, including the inner IP header AH in tunnel mode authenticates the entire inner IP packet, including the inner IP header, and selected portions of the outer IP header. The key management portion of IPSec involves the determination and distribution of secret keys. The default automated key management protocol for IPSec is referred to as ISAKMP/Oakley and consists of the Oakley key determination protocol and Internet Security Association and Key Management Protocol (ISAKMP). Internet key exchange (IKE) is a newer name for the ISAKMP/Oakley protocol. IKE is based on the Diffie-Hellman algorithm and supports RSA signature authentication among other modes. IKE is an extensible protocol, and allows future and vendor-specific features to be added without compromising functionality. IPSec has been designed to provide confidentiality, integrity, and replay protection for IP packets. However, IPSec is intended to work with static network topology, where hosts are fixed to certain subnetworks. For instance, when an IPSec tunnel has been formed by using Internet Key Exchange (IKE) protocol, the tunnel endpoints are fixed and remain constant. If IPSec is used with a mobile host, the IKE key exchange will have to be redone from every new visited network. This is problematic, because IKE key exchanges involve computationally expensive Diffie-Hellman key exchange algorithm calculations and possibly RSA calculations. Furthermore, the key exchange requires at least three round trips (six messages) if using the IKE aggressive mode followed by IKE quick mode, and nine messages if using IKE main mode followed by IKE quick mode. This may be a big problem in high latency networks, such as General Packet Radio Service (GPRS) regardless of the computational expenses. In this text, the term mobility and mobile terminal does not only mean physical mobility, instead the term mobility is in the first hand meant moving from one network to another, which can be performed by a physically fixed terminal as well. The problem with standard IPSec is thus that it has been designed for static connections. For instance, the end points of an IPSec tunnel mode SA are fixed. There is also no method for changing any of the parameters of an SA, other than by establishing a new SA that replaces the previous one. However, establishing SAs is costly in terms of both computation time and network latency. An example of a specific scenario where these problems occur is described next in order to illustrate the problem. In the scenario, there is a standard IPSec security gateway, which is used by a mobile terminal e.g. for remote access. The mobile terminal is mobile in the sense that it changes its network point of attachment frequently. A mobile terminal can in this text thus be physically fixed or mobile. Because it may be connected to networks administered by third parties, it may also have a point of attachment that uses private addresses—i.e., the network is behind a router that performs network address translation (NAT). In addition, the networks used by the mobile terminal for access may be wireless, and may have poor quality of service in terms of throughput and e.g. packet drop rate. Standard IPSec does not work well in the scenario. Since IPSec connections are bound to fixed addresses, the mobile terminal must establish a new IPSec connection from each point of attachment. If an automated key exchange protocol, such as IKE, is used, setting up a new IPsec connection is costly in terms of computation and network latency, and may require a manual authentication phase (for instance, a one-time password). If IPSec connections are set up manually, there is considerable manual work involved in configuring the IPSec connection parameters. Standard IPSec does e.g. not work through NAT devices at the moment. A standard IPSec NAT traversal protocol is currently being specified, but the security gateway in the scenario might not support an IPSec protocol extended in this way. Furthermore, the current IPSec NAT traversal protocols are not well suited to mobility. There are no provisions for improving quality of service over wireless links in the standard IPSec protocol. If the access network suffers from high packet drop rates, the applications running in the mobile host and a host that the mobile terminal is communicating with will suffer from packet drops. A known method of solving some of these problems is based on having an intermediate host between the mobile terminal and the IPSec security gateway. The intermediate host might be a Mobile IP home agent, that provides mobility for the connection between the mobile terminal and the home agent, while the connection from the mobile node to the security gateway is an ordinary IPSec connection. In this case, packets sent by an application in the mobile client are first processed by IPSec, and then by Mobile IP. In the general case, this implies both Mobile IP and IPSec header fields for packets exchanged by the mobile terminal and the home agent. The Mobile IP headers are removed by the home agent prior to delivering packets to the security gateway, and added when delivering packets to the mobile terminal. Because of the use of two tunnelling protocols (Mobile IP and IPSec tunnelling), the solution is referred to as “double tunnelling” in this document. The above method solves the mobility problem, at the cost of adding extra headers to packets. This may have a significant impact on networks that have low throughput such as the General Packet Radio System (GPRS). Another known method is again to use an intermediate host between the mobile client and the IPSec security gateway. The intermediate host has an IPSec implementation that may support NAT traversal, and possibly some proprietary extensions for improving quality of service of the access network, for instance. The mobile host would now establish an IPSec connection between itself and the intermediate host, and would also establish an IPSec connection between itself and the IPSec security gateway. This solution is similar to the first known method, except that two IPSec tunnels are used. It solves a different set of problems—for instance, NAT traversal—but also adds packet size overhead because of double IPsec tunnelling. A third known method is to use a similar intermediate host as in the second known method, but establish an IPSec connection between the mobile terminal and the intermediate host, and another, separate IPSec connection between the intermediate host and the security gateway. The IPSec connection between the mobile terminal and the intermediate host may support NAT traversal, for instance, while the second IPSec connection does not need to. When packets are sent by an application in the mobile terminal, the packets are IPSec-processed using the IPSec connection shared by the mobile terminal and the intermediate host. Upon receiving these packets, the intermediate host undoes the IPSec-processing. For instance, if the packet was encrypted, the intermediate host decrypts the packet. The original packet would now be revealed in plaintext to the intermediate host. After this, the intermediate host IPSec-processes the packet using the IPSec connection shared by the intermediate host and the security gateway, and forwards the packet to the security gateway. This solution allows the use of an IPSec implementation that support NAT traversal, and possibly a number of other (possibly vendor specific) improvements, addressing problems such as the access network quality of service variations. Regardless of these added features, the IPSec security gateway remains unaware of the improvements, and is not required to implement any of the protocols involved in improving service. However, the solution has a major drawback: the IPsec packets are decrypted in the intermediate host, and thus possibly sensitive data is unprotected in the intermediate host. Consider a business scenario where a single intermediate host provides improved service to a number of separate customer networks, each having its own standard IPSec security gateway. Having decrypted packets of various customer networks in plaintext form in the intermediate host is clearly a major security problem. To summarise, the known solutions either employ extra tunnelling, causing extra packet size overhead, or use separate tunnels, causing potential security problems in the intermediate host(s) that terminate such tunnels. THE OBJECT OF THE INVENTION The object of the invention is to develop a method for forwarding secure messages between two computers, especially, via an intermediate computer by avoiding the above mentioned disadvantages. Especially, the object of the invention is to forward secure messages in a way that enables changes to be made in the secure connection SUMMARY OF THE INVENTION The method and system of the invention enable secure forwarding of a message from a first computer to a second computer via an intermediate computer in a telecommunication network. It is mainly characterized in that a message is formed in the first computer or in a computer that is served by the first computer, and in the latter case, sending the message to the first computer. In the first computer, a secure message is then formed by giving the message a unique identity and a destination address. The message is sent from the first computer to the intermediate computer, whereafter said destination address and the unique identity are used to find an address to the second computer. The current destination address is substituted with the,found address to the second computer, and the unique identity is substituted with another unique identity. Then the message is forwarded to the second computer. The advantageous embodiments have the characteristics of the subclaims, Preferably, the first computer processes the formed message using a security protocol and encapsulates the message at least in an outer IP header. The outer IP header source address is the current address of the first computer, while the destination address is that of the intermediate computer. The message is then sent to the intermediate computer, which matches the outer IP header address fields together with a unique identifier used by the security protocol, and performs a translation of the outer addresses and the unique identity used by the security protocol. The translated packet is then sent to the second computer, which processes it using the standard security protocol in question. In the method of the invention, there is no extra encapsulation overhead as in the prior art methods. Also, the intermediate computer does not need to undo the security processing, e.g. decryption, and thus does not compromise security as in the prior art methods. Corresponding steps are performed when the messages are sent in the reverse direction, i.e. from the second computer to the first computer. Preferably, the secure message is formed by making use of the IPSec protocols, whereby the secure message is formed by using an IPsec connection between the first computer and the intermediate computer. The message sent from the first computer contains message data, an inner IP header containing actual sender and receiver addresses, an outer IP header containing the addresses of the first computer and the intermediate computer, a unique identity, and other security parameters. The unique identity is one or more SPI values and the other security parameters contain e.g. the IPsec sequence number(s). The number of SPI values depends on the SA bundle size (e.g. ESP+AH bundle would have two SPI values). In the following, when an SA is referred to, the same applies to an SA bundle. The other related security parameters, containing e.g. the algorithm to be used, a traffic description, and the lifetime of the SA, are not sent on the wire. Only SPI and sequence number are sent for each IPsec processed header (one SPI and one sequence number if e.g. ESP only is used; two SPIs and two sequence numbers if e.g. ESP+AH is used, etc.). Thus, the unsecured data packet message is formed by the sending computer, which may or may not be the first computer. The IP header of this packet has IP source and destination address fields (among other things). The packet is encapsulated e.g. wrapped inside a tunnel, and the resulting packet is secured. The secured packet has a new outer IP header, which contains another set of IP source and destination addresses (in the outer header—the inner header is untouched), i.e. there are two outer addresses (source and destination) and two inner addresses. The processed packet has a unique identity, the IPsec SPI value(s). An essential idea of the invention is to use the standard protocol (IPSec) between the intermediate computer and the second computer and an “enhanced IPSec protocol” between the first computer and the intermediate computer. IPsec-protected packets are translated by the intermediate computer, without undoing the IPsec processing. This avoids both the overhead of double tunneling and the security problem involved in using separate tunnels. The translation is performed e.g. by means of a translation table stored at the intermediate computer. The outer IP header address fields and/or the SPI-values are changed by the intermediate computer so that the message can be forwarded to the second computer. By modifying the translation table and parameters associated to a given translation table entry, the properties of the connection between the first and the intermediate computers can be changed without establishing a new IPsec connection, or involving the second computer in any way. One example of a change in the SA between the first computer and the intermediate computer is the change of addresses for enabling mobility. This can be accomplished in the invention simply by modifying the translation table entry address fields. Signaling messages may be used to request such a change. Such signalling messages may be authenticated and/or encrypted, or sent in plaintext. One method of doing authentication and/or encryption is to use an IPsec connection between the first computer and the intermediate computer. The second computer is unaware of this IPsec connection, and does not need to participate in the signalling protocol in any way. Several other methods of signalling exist, for instance, the IKE key exchange protocol maybe extended to carry such signalling messages. In the signalling, e.g. a registration request is sent from the first computer to the intermediate computer which causes the intermediate computer to modify the addresses in the mapping table and thus, the intermediate computer can identify the mobile next time a message is sent. Preferably, as a result of a registration request, a reply registration is sent from the intermediate computer back to the first computer. Other examples of possible modifications to the SA—or in general, the packet processing behaviour—between the first computer and the intermediate computer are the following. One example is the first computer and the intermediate computer perform some sort of retransmission protocol that ensures that the IPSec protected packets are not dropped in the route between the first and the intermediate computer. This may have useful applications when the first computer is connected using a network access method that has a high packet drop rate—for instance, GPRS. Such a protocol can be easily based on e.g. IPsec sequence number field and the replay protection window, which provide a way to detect that packet(s) have been lost. When a receiving host detects missing packets, it can send a request message for those particular packets. The request can of course be piggy-backed on an existing data packet that is being sent to the other host. Another method of doing the retransmissions may be based on using an extra protocol inside which the IPSec packets are wrapped for transmission between the first and intermediate computer. In any case, the second computer remains unaware of such a retransmission protocol. Another example is performing a Network Address Translation (NAT) traversal encapsulation between the first and the intermediate computer. This method could be based on e.g. using UDP encapsulation for transmission of packets between the first and the intermediate computer. The second computer remains unaware about this processing and does not even need to support NAT traversal at all. This is beneficial because there are several existing IPSec products that have no support for NAT traversal. The system of the invention is a telecommunication network for secure forwarding of messages and comprises at least a first computer, a second computer and an intermediate computer. It is characterized in that the first and the second computers have means to perform IPSec processing, and the intermediate computer have means to perform IPSec translation and possibly key exchange protocol, such as IKE, translation, preferably by means of mapping tables. The intermediate computer may perform IPSec processing related to other features, such as mobility signalling described above or other enhancements. The IPSec translation method is independent of the key exchange translation method. Also manual keying can be used instead of automatic keying. If automatic keying is used, any key exchange protocol can be modified for that purpose; however, the idea is to keep the second computer unaware of the interplay of the first and the intermediate computer. An automatic key exchange protocol may be used in the invention in several ways. The essential idea is that the second computer sees a standard key exchange protocol run, while the first and the intermediate computer perform a modified key exchange. The modified key exchange protocol used between the first and the intermediate computer ensures that the IPsec translation table and other parameters required by the invention are set up as a side-effect of the key exchange protocol. One such modified protocol is presented in the application for the IKE key exchange protocol. Each translation table consists of entries that are divided into two partitions. The first partition contains information fields related to the connection between the first computer and the intermediate computer, while the second partition contains information fields related to the connection between the intermediate computer and the second computer. The translation occurs by identifying the translation table entry by comparing against one partition, and mapping into the other. For traffic that is flowing from the first computer towards the second computer, through the intermediate computer, the entry is found by comparing the received packet against entries in the first partition, and then translating said fields using information found in the second partition of the same entry. For traffic flowing in the opposite direction, the second partition is used for finding the proper translation table entry, and the first partition for translating the packet fields. The IPSec translation table partitions consist of the following information: the IP local address and the IP remote address (tunnel endpoint addresses) and SPIs for sending and receiving data. As mentioned, a translation table entry consists of two such partitions, one for communication between first computer and the intermediate computer, and another for communication between the intermediate computer and the second computer. The invention described solves the above problems of prior art. The solution is based on giving the first computer, e.g. if it is mobile, an appearance of a standard computer for the second computer. Thus, the second computer will believe it is talking to a standard IPSec host, while the intermediate computer and the second computer will work together using a modified protocol, for instance a slightly modified IPSec and IKE that helps to accomplish this goal. There are, however, several other control protocols that could conceivably be used between the first and the intermediate computer. In the following, the invention is described more in detail by using figures by means of some embodiment examples to carry out the invention. The invention is not restricted to the details of the figures and accompanying text, or any existing protocols, such as the currently standardised IPSec or IKE. Especially, the invention can be concerned with other kinds of telecommunication networks wherein the method of the invention can be applied than that of the figures. FIGURES FIG. 1 illustrates an example of a telecommunication network of the invention. FIG. 2 describes generally an example of the method of the invention. FIG. 3 illustrates an example of an IPSec translation table used by the intermediate computer to change the outer IP address and SPI value. FIG. 4 describes a detailed example of how the SA is formed in the invention. FIG. 5 illustrates an example of translation tables for the modified key exchange of the invention. FIG. 6 shows a mapping table for identification values of the user Security Gateway (SGW) addresses. DETAILED DESCRIPTION OF THE INVENTION An example of a telecommunication network of the invention is illustrated in FIG. 1, comprising a first computer, here a client computer 1 served by an intermediate computer, here as a server 2, and a host computer 4, that is served by the second computer, here a security gateway (SGW) 3. The security gateway supports the standard IPSec protocol and optionally the IKE key exchange protocol. The client computer and the server computer support a modified IPSec and IKE protocol. The invention is not restricted to the topology of FIG. 1. In other embodiments, the first computer may e.g. be a router; or there might e.g. not be a host behind the second computer (in which case the first and the second computer are talking to each other directly), etc. The IPSec translations taking place in the scenario of FIGS. 1, 2, and 3 are discussed first. The IPSec connections (such as SAs) in the scenario may be established manually, or using some key exchange protocol, such as the Internet Key Exchange (IKE). To illustrate how a key exchange protocol would be used in the scenario of FIG. 1, a modified IKE protocol based on IKE translation is also presented later. In the invention, an IPSec connection is shared by the first computer and the second computer, while the intermediate computer holds information required to perform address and IPSec SPI translations for the packets. These translations accomplish the effect of “double tunnelling” (described in the technical background section), but with the method of the invention the confidentiality of the packets is not compromised, while simultaneously having no extra overhead when compared to standard IPSec. The intermediate computer does not know the cryptographic keys used to encrypt and/or authenticate the packets, and can thus not reveal their contents. The advantage of the invention is that the logical IPSec connection shared by the first and the second computer can be enhanced by the first and the intermediate computer without involvement of the second computer. In particular the so-called “ingress filtering” performed by some routers does not pose any problems when translations of addresses are used. In the example presented, each host also manages its own IPSec SPI space independently. In the example of FIG. 1, an IPSec connection is formed between the client computer 1 (the first computer) and the security gateway 3 (the second computer). To create an IPSec tunnel, a SA (or usually a SA bundle) is formed between the respective computers with a preceding key exchange. The key exchange between the first and the second computer can take place manually or it can be performed with an automatic key exchange protocol such as the IKE protocol. For performing said key exchange, a standard IKE protocol is used between the server 2 and the security gateway 3, and a modified IKE protocol is used between the client computer 1 and the server 2. An example of a modified IKE protocol that can be used in the invention is described in connection with FIG. 4. Messages to be sent to the host terminal 4 from the client computer 1 are first sent to the server 2, wherein an IPSec translation and an IKE translation takes place. After that the message can be sent to the security gateway 3, which sends the message further in plain text to the host terminal 4. The method of the invention, wherein messages in packet form are sent by routing to the end destination, is generally described in connection with FIG. 2. It is assumed in the following description that the IPSec connection between the first and second computer already is formed. The IPSec connection can be set up manually or automatically by e.g. an IKE exchange protocol which is described later. FIG. 2 illustrates the sequence of events that take place when the first computer, corresponding to the mobile terminal in FIG. 1, sends a packet to a destination host, labelled X in the figure, and when the host X sends a packet to the mobile terminal. IP packets consist of different parts, such as a data payload and protocol headers. The protocol headers in turn consist of fields. In step 1 of FIG. 2, the first computer, e.g. a mobile terminal, forms an IP packet that is to be sent to host X. Typically, this packet is created by an application running on the mobile terminal. The IP packet source address is the address of the mobile terminal, while the destination address is host X. The packet is processed using an IPSec tunnel mode SA, which encapsulates the IP packet securely. The example assumes that IPSec encryption and/or authentication of ESP type is used for processing the-packet, although the invention is not limited to the use of only ESP; instead, an arbitrary IPsec connection may be used. In said processing, a new IP header is constructed for the packet, with so-called outer IP addresses. The outer source address of the packet can be the same as the inner IP address—i.e., the address of the mobile terminal—but can be different, if the mobile terminal is visiting a network. The outer source address corresponds to the care of address obtained by the mobile terminal from the visited network, in this case. The outer destination address is the address of the intermediate computer. In addition to the new IP header, an ESP header is added, when using IPSec ESP mode. The SPI field of the ESP header added by the IPSec processing are set to the SPI value that the intermediate computer uses for receiving packets from the mobile terminal. In general, there may be more than one SPI field in a packet. The processing of packets in the intermediate computer is based on a translation table i.e. an IPSec translation table shown in FIG. 3. The table has been divided into two partitions. The left one, identified by the prefix “c-”, refers to the network connection between the first computer (host 1 in FIG. 1) and the intermediate computer (host 2 in FIG. 1). The right one, identified by the prefix “s-”, refers to the network connection between the intermediate computer and the second computer (computer 3 in FIG. 1). The postfix number (“−1”, “−2”, or “−3”) identifies the host in question. Thus, the address fields (“addr”) refer to outer addresses of a packet, while the SPI fields (“SPI”) refer to the receiver of packets, which packets were sent with this SPI. Thus, “c-SPI-2” is the SPI value used by host 2 (the intermediate computer) when receiving packets from host 1 (the first computer), and the SPI-value “c-SPI-1” is the SPI-value with which the first computer receives messages and the SPI-value with which the intermediate computer sends messages to the first computer and so on. In terms of FIG. 3, the outer source address would be “c-addr-1” (195.1.2.3), the outer destination address “c-addr-2” (212.90.65.1), while the SPI field would be “c-SPI-2” (0×12341234). The notation 0×NNNNNNNN indicates a 32-bit unsigned integer value, encoded using a hexadecimal notation (base 16). The inner source address is processed by IPSec in the first computer, and would typically be encrypted. In this example, the inner source address would be the static address of the mobile terminal, e.g. 10.0.0.1. When the intermediate computer receives the packet sent in step 1 described above, it performs an address and SPI translation, ensuring that the security gateway (host 3 of FIG. 1) can accept the packet. Most of the packet is secured using IPSec, and since the intermediate computer does not have the cryptographic keys to undo the IPSec processing done by the mobile terminal, it cannot decrypt any encrypted portions of the packet but is able to use the outer IP addresses and the incoming SPI value to determine how to modify the outer address and the SPI to suite the second computer, which is the next destination. SPI is now changed to 0×56785678 in the intermediate computer and the address is changed to the address of the second computer. This is done by means of the IPSec translation table of FIG. 3. The first row of FIG. 3 is a row that the intermediate computer has found that matches the packet in the example, and thus the intermediate computer chooses it for translation. The new outer source address s-addr-2 (212.90.65.1) is substituted for the outer source address c-addr-1 (195.1.2.3), and the new outer destination address s-addr-3 (103.6.5.4) is substituted for the outer destination address c-addr-2 (212.90.65.1). The new SPI value, s-SPI-3 (0×56785678), is substituted for the SPI value c-SPI-2 (0×12341234). If more than one SPI values are used, all the SPI values are substituted similarly. In the example, s-addr-2 and c-addr-2 happen to be the same on both partitions of the table. This is not necessarily so but the intermediate computer might use another address for sending. In step 2 of FIG. 2, the translated packet is sent further to the second computer. The inner IP packet has not been modified after that the first computer sent the packet. The second computer processes the packet using standard IPSec algorithms. The security gateway (the second computer) can e.g. decipher and/or check the authenticity of the packet, then remove the IPSec tunnelling, and forward the original packet towards the destination host, X. Thus, the entire original packet was unaffected by the translation as the IP header, and thus the address fields, was covered by IPSec. After uncovering the original packet from the IPsec tunnel, the second computer makes a routing decision based on the IP header of the original packet. In the example, the IP destination address is X (host X in FIG. 2), and thus the second computer delivers the packet either directly to X, or to the next hop router. In step 3 of FIG. 2, the packet is sent from the second computer (corresponding to SGW in FIG. 1) to host X, having now only the original source IP address 10.0.0.1 and the original destination IP address X in the IP header. Thus, in step 3, host X receives the packet sent by the second computer. Usually, an application process running on host X would generate some return traffic. This would cause an IP packet to be generated and sent to the second computer. If a packet is sent back from host X to the first computer (corresponding to the client computer in FIG. 1), steps analogous to steps 1-3 are performed. The packet is thus first sent to the second computer, with the source IP address being X and the destination IP address being 10.0.0.1, in step 4. The generated packet is then received by the second computer. The IPSec policy of the second computer requires that the packet be IPSec-processed using a tunnel mode IPSec SA. This processing is similar to the one in steps 1 and 2. A new, outer IP header is added to the packet in the second computer, after which the resulting packet is secured using the IPSec SA. The outer IP source address is set to s-addr-3 (103.6.5.4) while the outer IP destination address is set to s-addr-2 (212.90.65.1). The SPI field is set to s-SPI-2 (0×c1230012). In step 5, the resulting packet is sent to the address indicated by the new outer IP destination address, s-addr-2, the intermediate computer. The intermediate computer receives the packet and performs a similar address and SPI translation. The inner addresses are still the same, and are not modified by the intermediate computer. Since the packet intended to be sent to the first computer, the new, translated outer destination IP address indicate the address of the first computer. The resulting packet is sent to the first computer in step 6. As a result of step 6, the packet is received by the first computer. The IPSec processing is undone, i.e. decryption and/or authentication is performed, and the original packet is uncovered from the IPSec tunnel. The original packet is then delivered to the application running on the first computer. In case the first computer acts as a router, the packet may be delivered to a host in a subnet for which the first computer acts as a router. The first computer may be a mobile terminal, the outer address of which changes from time to time. The translation table is then modified using some form of signalling messages, as described in the summary section. Upon receiving a request for modifying a translation, the intermediate computer updates the related translation table entry to match the new information supplied by the first computer. The operation of the protocol then proceeds as discussed above. The above discussion is a limited example for illustration purposes. In other embodiments e.g. more than one SA for the connection—for instance, ESP followed by AH, can be used. This introduces two SPI values that must be translated. More than two is also, of course, possible. Furthermore, the example was considered for IPsec ESP only. The changes required for an embodiment in which AH (or ESP+AH) is used, are discussed next. Changes for Using AH: If the Authentication Header (AH) IPSec security transform is to be used, there are more considerations than in the previous example. In particular, modifications of the packet fields—even the outer IP header—are detected if AH is used. Thus, the following nominal processing is required by the first computer. The second computer performs standard IPSec processing also in this case. In step 1, when sending a packet, the first computer must perform IPsec processing using the SPI values and addresses used in the connection between the intermediate computer and the second computer. For instance, the SPI value would be s-SPI-3, the outer source address s-addr-2, and the outer destination address s-addr-3. The AH integrity check value (ICV) must be computed using these values. ICV is a value, which authenticates most of the fields of the packet. In practice, all fields that are never modified by routers are authenticated. After computing the AH integrity check value, the outer addresses and the SPI value are replaced with the values used between the first computer and the intermediate computer: c-addr-1 for the outer source address, c-addr-2 for the outer destination address, and c-SPI-2 for the SPI. In step 2, the intermediate computer performs the address and SPI translations as in the example with ESP described above. The resulting packet is identical to the one used by the first computer for the AH integrity check value calculation, except possibly for fields not covered by AH (such as the Time-To-Live field, the header checksum, etc). Thus, the AH integrity check value is now correct. In step 3, the second computer performs standard IPSec processing of AH. The packet, which now is uncovered from the tunnel is sent to the host X. As in the previous example, an application in host X usually generates a return packet that is to be sent to the first computer. This packet is sent to the second computer in step 4. Upon receiving the packet, the processing of the second computer are the same as in the example with ESP. The second computer computes an AH integrity check value of the tunneled packet it is sending to the mobile terminal. The integrity check value is computed against the outer source address of s-addr-3, outer destination address of s-addr-2, and the SPI value of s-SPI-2. In step 5, when the intermediate computer receives the packet, it performs ordinary translation of the packet. The new outer source address is c-addr-2, the outer destination address is c-addr-1, and the SPI value is c-SPI-1. At this point the AH integrity check value is incorrect, which was caused by the translations. When the mobile terminal receives the packet, it performs a translation of the current outer addresses and the SPI field for the original ones used by the second computer: s-addr-3 for the outer source address, s-addr-2 for the outer destination address, and s-SPI-2 for the SPI value. This reproduces the packet originally sent by the second computer, except possibly for fields not covered by AH. This operation restores the AH integrity check value to its original, correct value. The AH integrity check is then performed against these fields. Key Exchange Considerations The above example discussed the “steady state” IPSec translations performed by the intermediate computer. The IPSec SAs and the IPSec translation table entries may be set up manually, or using some automated protocol, such as the Internet Key Exchange (IKE) protocol. Because the security gateway (the second computer) is a standard IPSec host, it implements some standard key exchange protocol, such as IKE. The first computer and the intermediate computer may use some modified version of IKE, or any other suitable automatic key exchange protocol. The key exchange must appear as a standard key exchange according to the key exchange protocol supported by the security gateway (the second computer), such as IKE. Also, the overall key exchange performed by the first, intermediate, and second computer must establish not only cryptographic keys, but also the IPSec translation table entries. The overall key exchange protocol should not reveal the IPSec cryptographic keys to the intermediate computer to avoid even the potential for security problems. In the following, an example of a modified IKE protocol is presented to outline the functionality of such a protocol in the context of the invention. The protocol provides the functionality described above. In particular, the intermediate computer has no knowledge of the IPSec cryptographic keys established. The protocol is presented on a general level to simplify the presentation. The automatic IKE protocol is used prior to other protocols to provide strongly authenticated cryptographic session keys for the IPSec protocols ESP and AH. IKE performs the following functions: (1) security policy negotiation (what algorithms shall be used, lifetimes etc.), (2) a Diffie-Hellman key exchange, and (3) strong user/host authentication (usually using either RSA-based signatures or pre-shared authentication keys). IKE is divided into two phases: phase 1 and phase 2. Phase 1 negotiates and establishes cryptographic keys for internal use of the IKE protocol itself, and also performs the strong user or host authentication. Phase 2 negotiates and establishes cryptographic keys for IPSec. If IPSec tunnel mode is used, phase 2 also negotiates the kind of traffic that may be sent using the tunnel (so-called traffic selectors). The IKE framework supports several “sub-protocols” for phase 1 and phase 2. The required ones are “main mode” for phase 1, and “quick mode” for phase 2. These are used as illustrations, but the invention is not limited to these sub-protocols of IKE. For the security gateway (second computer), the IKE session seems to be coming from the address s-addr-2 in FIG. 3. Since there may be any number of mobile terminals served by the intermediate computer, the intermediate computer should either (1) manage a pool of addresses to be used for the s-addr-2 translation table address, thus providing each user with a separate “surrogate address”, or (2) use the same address (or a limited set of addresses), and ensure that the mobile terminals are identified using some other means than their IP address (IKE provides for such identification types, so this is not a problem). The modified IKE protocol specified is analogous to the IPSec translation table approach. However, instead of SPIs, the so-called IKE cookies are used as translation indices instead. IKE cookies are essentially IKE session identifiers, and are thus analogous to the IPSec SPI values, which is another form of a session or context identifier. There are two cookies: the initiator cookie, chosen by the host that initiates the IKE session, and the responder cookie, chosen by the host that responds to a session initiation. The essential features of the protocol are (1) that it appears to be an entirely ordinary IKE key exchange for the security gateway, (2) that the IPsec translation table entry is formed by the intermediate computer during the execution of the protocol, (3) that the first computer obtains all the necessary information for its packet processing, and (4) that the intermediate computer does not obtain the IPsec cryptographic session keys. The overall steps of the protocol are: 1. The first computer initiates the key exchange protocol by sending a message to the intermediate computer. This message is essentially the IKE main mode initiation message, with some modifications required for this application. 2. The intermediate computer determines which security gateway (second computer) to forward this IKE session to, and also establishes a preliminary IKE translation table entry based on the information available from the message. 3. The security gateway (the second computer) replies to the IKE main mode initiation message. 4. The intermediate computer completes the IKE mapping based on the reply message. 5. The modified IKE protocol run continues through IKE main mode (the phase 1 exchange), which is followed by quick mode (the phase 2 exchange). Extensions of standard IKE messages are used between the first computer and the intermediate computer to accomplish the extra goals required by this modified IKE protocol. In FIG. 4, the IKE session is described message by message. The following text indicates the contents of each message, and how they are processed by the various hosts. There are six main mode messages in the protocol, named mm1, mm2, . . . , mm6, and three quick mode messages, named qm1, qm2, and qm3. FIG. 5 illustrates the IKE translation table entry related to the modified IKE key exchange being performed. The bolded entries in each step are added or changed in that step as a result of the processing described in the text. The IKE translation table partition for the connection between the first computer and the intermediate computer is as follows (the field name in FIG. 5 is given in parentheses): Local and remote IP address (c-addr-1, c-addr-2) Initiator and responder cookie (c-icky, c-rcky) IKE identification of the first computer (c-userid, e.g. [email protected]) The IKE translation table partition for the connection between the intermediate computer and the second computer is as follows (the field name in FIG. 5 is given in parentheses): Local and remote IP address (s-addr-2, s-addr-3) Initiator cookie and responder cookie (s-icky, s-rcky) In addition to these entries, other data may be kept by the intermediate computer and/or the first computer. The key exchange is initiated by generating an initiator cookie and sending a zero responder cookie to the second computer. A responder cookie is generated in the second computer and a mapping between IP addresses and IKE cookie values in the intermediate computer is established. A translation table to modify IKE packets in flight by modifying the external IP addresses and possibly IKE cookies of the IKE packets is used. Either the modified IKE protocol between the first computer and the intermediate computer is modified such that the IKE keys are transmitted from the first computer to the intermediate computer for decryption and modification of IKE packets or, alternatively, the modified IKE protocol between the first computer and the intermediate computer is modified such that the IKE keys are not transmitted from the first computer to the intermediate computer for decryption and modification of IKE packets, and the modification of IKE packets is done by the first computer with the intermediate computer requesting such modifications. The latter alternative is discussed in the example that follows, since it is more secure than the first alternative. Extra information, such as user information and SPI change requests, to be sent between the first and the intermediate computer, is sent by appending the extra information to the standard IKE messages. The IKE standard has message encoding rules that indicate a definite length, thus the added extra information can be separated from the IKE message itself. The extra information fields are preferably encrypted and authenticated, for instance by using a secret shared by the first computer and the intermediate computer. The details of this process are not relevant to the invention. The extra information slot in each IKE message is called the message “tail” in the following. IKE messages consists of an IKE header, which includes the cookie fields and message ID field, and of a list of payloads. A payload has a type, and associated information. FIG. 4 considers an example of the routing of packets according to the invention considering IPSec security association set-up for distribution of keys. As in the foregoing FIG. 2, the session begins with sending a packet from the client (first computer) to the server (intermediate computer). The key exchange is initiated by the first computer. Thus, in step 1 of FIG. 4, the first computer constructs mm1. The IP header of the message contains the following values: IP source address: 195.1.2.3 (c-addr-1) IP destination address: 212.90.65.1 (c-addr-2) The IKE header contains the following values (step 1 in Figure X): Initiator cookie: CKY1 (c-icky) Responder cookie: 0 (c-rcky) Message ID: 0 The message contains the following payloads: A Security Association (SA) payload, which contains the IKE phase 1 security policy offers from the first computer. The message may contain additional payloads, such as Vendor Identification (VID) payloads, certificate requests/responses, etc. A VID payload can be used to indicate that the first computer supports the protocol described here. The message tail contains the following information: User identification type and value—the c-userid field. These are used by the intermediate computer to choose a security gateway to forward this session to. The identification type may be any of the IKE types, but additional types can be defined. An alternative to this field is to directly indicate the security gateway for forwarding. There are other alternatives as well, but these are not essential to the invention. In step 2, the mm1 is received by the intermediate computer. The intermediate computer examines the message, and forms the preliminary IKE translation table entry. FIG. 5, step 1 illustrates the contents of this preliminary entry. The c-userid field is sent in the mm1 tail. The intermediate computer then determines which security gateway to forward this IKE session to. The determination may be based on any available information, static configuration, load balancing, or availability requirements. The presented, simple method is to use the identification information in the mm1 tail to look up the first matching identification type and value from a table. An example of such a table is presented in FIG. 6. The identification mapping table of FIG. 6, is one method for choosing a security gateway that matches the incoming mobile terminal. The identification table would in this example be an ordered list of identification type/value entries, that match to a given security gateway address. When the incoming mobile terminal identification matches the identification in the table, the corresponding security gateway is used. For instance, [email protected] would match the first row of the table, i.e., the security gateway 123.1.2.3, while [email protected] matches the second row, i.e., the security gateway 103.6.5.4. The identification types include any identification types defined for the IKE protocol, and may contain other types as well, such as employee numbers, etc. Other methods of determining the security gateway to be used may be employed. One such method is for the mobile terminal to directly indicate a given security gateway to be used. The mobile terminal may also indicate a group of security gateways, one of which is used. The exact details are not relevant to the invention. In addition to determining the security gateway address, the intermediate computer determines which address its for communication between itself and the second computer. The same address as is used for the communication between the first and the intermediate computer may be used, but a new address may also be used. The address can be determined using a table similar to the one in FIG. 6, or the table of FIG. 6 may be extended to include this address. The intermediate computer then generates its own initiator cookie. This is done to keep the two session identifier spaces entirely separate, although the same initiator cookie may be passed as is. After these determinations, the preliminary translation table entry is modified. FIG. 5, step 2 illustrates the contents of the entry at this point. The original IP header fields are modified as follows (step 2 in FIG. 4): IP source address: 212.90.65.1 (s-addr-2) IP destination address: 103.6.5.4 (s-addr-3) The IKE header is modified as follows: Initiator cookie: CKY2 (s-icky) Responder cookie: 0 (s-rcky) Message ID: 0 The message tail is removed. The VID payload that identifies support for this modified protocol is also removed. The mm1 is then forwarded to the second computer. In step 3, the second computer responds with mm2. The IP header of the message contains the following values (step 3 in FIG. 4): IP source address: 103.6.5.4 (s-addr-3) IP destination address: 212.90.65.1 (s-addr-2) The IKE header contains the following values: Initiator cookie: CKY2 (s-icky) Responder cookie: CKY3 (s-rcky) Message ID: 0 The message contains the following payloads: Security Association (SA) payload. This is a reply to the offer by the first computer, and indicates which security configuration is acceptable for the second computer (this scenario assumes success, so the case of an error reply is not considered). Possibly optional IKE payloads, such as VID payloads, certificate requests/replies, etc. There is no message tail. In step 4, the mm2 is received by the intermediate computer. The intermediate computer updates its IKE translation table based on the received message. Step 3 in FIG. 5 illustrates the contents of the translation table entry at this point. The intermediate computer generates its own responder cookie, CKY4, and updates the translation table yet again. Step 4 in FIG. 5 illustrates the entry at this point. After this step, the translation table entry is complete, and the address and cookie translations are performed as in steps 1-4 for the following messages. The translated message contains the following IP header fields (FIG. 4, step 4) IP source address: 212.90.65.1 (c-addr-2) IP destination address: 195.1.2.3 (c-addr-1) The translated IKE header contains the following fields: Initiator cookie: CKY1 (c-icky) Responder cookie: CKY4 (c-rcky) The message contains the following payloads: The SA payload sent by the second computer. Any optional payloads sent by the second computer. A VID payload may be added to indicate support of this modified protocol to the first computer. A message tail is added, and contains the following information: Address and/or identification information of the chosen security gateway (the second computer). This information can be used by the client to choose proper authentication information, such as RSA keys. The message is then forwarded to the first computer. In step 5, the first computer constructs mm3. The message contains the following payloads: A Key Exchange (KE) payload, that contains Diffie-Hellman key exchange data of the first computer. A Nonce (NONCE) payload, that contains a random number chosen by the first computer. Possibly optional IKE payloads. The message is sent to the intermediate computer. In step 6, the mm3 is forwarded to the second computer. The contents of the message are not changed, only the IP header addresses and the IKE cookies, in the manner described in steps 1-4. In step 7, the second computer receives mm3 and responds with mm4. The message contains the following payloads: A Key Exchange (KE) payload, that contains Diffie-Hellman key exchange data of the second computer. A Nonce (NONCE) payload, that contains a random number chosen by the second computer. Possibly optional IKE payloads. In step 8, the mm4 is forwarded to the first computer. In step 9, the first computer constructs mm5, which is the first encrypted message in the session. All subsequent messages are encrypted using the IKE session keys established from the previous Diffie-Hellman key exchange (the messages mm3 and mm4) by means of hash operations, as described in the IKE specification. Note that the intermediate computer does not possess these keys, and can thus not examine the contents of any subsequent IKE messages. In fact, the intermediate computer has no advantage compared to a hostile attacker if it attempts to decipher the IKE traffic. Instead, the intermediate computer indirectly modifies some fields in the IKE messages by sending a modification request in the IKE message tail to the first computer, which does the requested modifications before IKE encryption processing. The message contains the following payloads: An Identification (ID) payload, that identifies the first computer to the second computer. This identification may be the same as the identification sent in the mm1 tail, but may differ from that. These two identifications serve different purposes: the mm1 tail identification (c-userid) is used to select a security gateway for IKE session forwarding (the second computer), while the ID payload in this message is used by the second computer for IKE authentication purposes, for instance, to select proper RSA authentication keys. A Signature (SIG) or Hash (HASH) payload, that serves as an authenticator. A signature payload is used if RSA- or DSS-based authentication is used, while a hash payload is used for pre-shared key authentication. There are other authentication methods in IKE, and IKE can also be extended with new authentication methods. These are not essential to the invention, and the following text assumes RSA authentication (i.e., use of the signature payload). Possibly optional IKE payloads. The message tail contains the-following information: The SPI value that the first computer wants to use for receiving IPsec-protected messages from the intermediate computer, i.e., the c-SPI-1 value of the IPsec translation table in FIG. 3. More than one SPI value could be transmitted here, but for simplicity, the following discussion assumes that only a single SPI is necessary (i.e. only one SA is applied for IPsec traffic processing). Extending the scheme to multiple SPIs is straightforward. In step 10, the mm5 is forwarded to the second computer. The intermediate computer removes the message tail, and performs the IKE translation discussed previously, and then forwards the message to the second computer. In step 11, the second computer receives the mm5 message, and authenticates the user (or the host, depending on what identification type is used). Assuming that the authentication succeeds, the second computer proceeds to authenticate itself to the first computer. The mm6 message contains the following payloads: An Identification (ID) payload, that identifies the second computer to the first computer. A Signature (SIG) payload (here RSA authentication is assumed). Possibly optional IKE payloads. In step 12, the mm6 is received by the intermediate computer. The intermediate computer does not change the message itself, but adds a tail with the following information: The SPI value that the intermediate computer wants the first computer to offer to the second computer in the qm1 message. Since the intermediate computer cannot access the contents of the IKE messages, this modification request is made using the message tail (see the discussion of step 9). The SPI value sent matches the s-SPI-2 field of the IPsec translation table of FIG. 3. The SPI value that the intermediate computer wants the first computer to use for messages sent to itself. This matches the c-SPI-2 field of the IPsec translation table of FIG. 3. The resulting message is forwarded to the first computer. In step 13, the first computer constructs qm1, which contains the following IKE payloads: A Hash (HASH) payload, that serves as an authenticator of the message. A Security Association (SA) payload, which contains the IKE phase 2 security policy offers from the first computer, i.e., the IPsec security policy offers. The SA payload contains the SPI value assigned to the first computer in the mm6 message, i.e., s-SPI-2 in FIG. 3. Optionally, a Key Exchange (KE) payload, if a new Diffie-Hellman key exchange is to be performed in phase 2 (this depends on the contents of the SA payload). A Nonce (NONCE) payload, which contains a random value chosen by the first computer. Optionally, two Identification (ID) payloads that indicate the IPsec traffic selectors that the first computer proposes for an IPsec tunnel mode SA. If IPsec transport mode is used, these are not necessary, but they may still be used. They may also be omitted if IPsec tunnel mode is used. The IKE header is the same as previously, except that the Message ID field now contains a non-zero 32-bit value, that serves as a phase 2 session identifier. This identifier remains constant for the entire quick mode exchange. The message is sent to the intermediate computer. In step 14, the intermediate computer forwards the qm1 message to the second computer. In step 15, the second computer inspects the security policy offers and other information contained in the qm1 message, and determines which security policy offer matches its own security policy (the case when no security policies match results in an error notification message). The second computer responds with qm2 message, that contains the following payloads: A Hash (HASH) payload, that serves as an authenticator of the message. A Security Association (SA) payload, which indicates the security policy offer chosen by the second computer. The message also contains the SPI value that the second computer wants to use when receiving IPsec-protected messages. The SPI value matches s-SPI-3 of the IPsec translation table in FIG. 3. Optionally, a Key Exchange (KE) payload, if a new Diffie-Hellman key exchange is to be performed in phase 2. A Nonce (NONCE) payload, which contains a random value chosen by the second computer. If Identification (ID) payloads were sent by the first computer, the second computer also sends Identification payloads. In step 16, the intermediate computer forwards the qm2 message to the first computer. In step 17, the first computer constructs qm3 message, which contains the following payloads: A Hash (HASH) payload, that serves as an authenticator of the message. The following information is sent in the message tail: The SPI value sent by the second computer in the qm2 message. This is sent here, because the intermediate computer cannot decrypt the qm2 message and look up the SPI from there. The SPI value matches s-SPI-3 of the IPsec translation table in FIG. 3. In step 18, the intermediate computer receives the qm3 and reads the s-SPI-3 value from the message tail. All the information required to construct the IPsec translation table entry is now gathered, and the entry can be added to the translation table. In particular, the information fields are as follows: c-addr-1: same as c-addr-1 of the IKE session (195.1.2.3). c-addr-2: same as c-addr-2 of the IKE session (212.90.65.1). c-SPI-1: received in the mm5 message tail from the first computer. c-SPI-2: chosen by the intermediate computer, sent to the first computer in the mm6 message tail. s-addr-2: same as s-addr-2 of the IKE session (212.90.65.1 in this example, may be different than c-addr-2). s-addr-3: same as s-addr-3 of the IKE session (103.6.5.4). s-SPI-2: chosen by the intermediate computer, sent to the first computer in mm6 message tail. s-SPI-3: sent by the second computer in qm2 to the first computer, which sends it to the intermediate computer in qm3 message tail. The intermediate computer forwards the qm3 message to the second computer, which completes the IKE key exchange, and the IPsec translation table set up. The IPsec cryptographic keys established using the modified IKE key exchange presented above are either derived from the Diffie-Hellman key exchange performed in IKE main mode, or from the (optional) Diffie-Hellman key exchange performed in quick mode. In both cases, the intermediate computer has no access to the shared secret established using the Diffie-Hellman algorithm. In fact, the intermediate computer has no advantage when compared to a random, hostile attacker. The above presentation was simplified and exemplified to increase clarity of the presentation. There are several issues not discussed, but these issues are not essential to the invention. Some of these issues are the following: The phase 1 used main mode. Any other IKE phase 1 exchange can be used; this changes the details of the protocol but not the essential ideas. There are other approaches than the one presented here. One approach is for the first computer to reveal the IKE keys to the intermediate computer, so that the second computer is able to modify the required fields of the message (namely, SPI values). The discussion assumes that the first computer initiates the IKE exchange. The opposite direction is possible, too, but requires more considerations. The commit bit feature of IKE is not used. Adding that is simple. Security gateway selection is based on a table lookup indexed by an identification type/value pair sent by the first computer. Other mechanisms are easy to implement. The discussion assumes a successful IKE key exchange. Error cases are easy to handle. Phase 1 policy lookup (when processing mm1 and mm2 messages) is not based on the identity of the IKE counterpart. This is not a major issue, since the phase 1 security policy can be independent of the counterpart without limiting usability. Phase 1 is a pre-requisite for executing the protocol in the example. This can be easily changed by moving some of the “tail” items to phase 2. The protocol establishes a pair of SAs, one for each direction, and manages the SPI value modifications of these SAs. It is easy to extend this to cover SA bundles with more than one SA, i.e., SAs applied in sequence (ESP followed by AH, for instance). This requires more than one SPI for each direction, but is easy to add to the protocol described. The invention is not concerned with the details of the key exchange protocol. The presented outline for one such protocol is given as an example, several other alternatives exist. The invention is also not concerned with the IKE key exchange protocol: other key exchange protocols exist, and similar ideas can be applied in using them in the content of the invention.

<SOH> TECHNICAL BACKGROUND <EOH>An internetwork is a collection of individual networks connected with intermediate networking devices that function as a single large network. Different networks can be interconnected by routers and other networking devices to create an internetwork. A local area network (LAN) is a data network that covers a relatively small geographic area. It typically connects workstations, personal computers, printers and other devices. A wide area network (WAN) is a data communication network that covers a relatively broad geographic area. Wide area networks (WANS) interconnect LANs across normal telephone lines and, for instance, optical networks; thereby interconnecting geographically disposed users. There is a need to protect data and resources from disclosure, to guarantee the authenticity of data, and to protect systems from network based attacks. More in detail, there is a need for confidentiality (protecting the contents of data from being read) integrity (protecting the data from being modified, which is a property that is independent of confidentiality), authentication (obtaining assurance about she actual sender of data), replay protection (guaranteeing that data is fresh, and not a copy of previously sent data), identity protection (keeping the identities of parties exchanging data secret from outsiders), high availability, i.e. denial-of-service protection (ensuring that the system functions even when under attack) and access control. IPSec is a technology providing most of these, but not all of them. (In particulars identity protection is not completely handled by IPSec, and neither is denial-of-service protection.) The IP security protocols (IPSec) provides the capability to secure communications between arbitrary hosts, e.g. across a LAN, across private and public wide area networks (WANs) and across the internet IPSec can be used in different ways, such as for building secure virtual private networks, to gain a secure access to a company network, or to secure communication with other organisations, ensuring authentication and confidentiality and providing a key exchange mechanism. IPSec ensures confidentiality integrity, authentication, replay protection, limited traffic flow confidentiality, limited identity protection, and access control based on authenticated identities. Even if some applications already have built in security protocols, the use of IPSec further enhances the security. IPSec can encrypt and/or authenticate traffic at IP level. Traffic going in to a WAN is typically compressed and encrypted and traffic coming from a WAN is decrypted and decompressed. IPSec is defined by certain documents, which contain rules for the IPSec architecture. The documents that define IPSec, are, for the time being, the Request For Comments (RFC) series of the Internet Engineering Task Force (IETF), in particular, RFCs 2401-2412. Two protocols are used to provide security at the IP layer; an authentication protocol designated by the header of the protocol, Authentication Header (AH), and a combined encryption/authentication protocol designated by the format of the packet for that protocol, Encapsulating Security Payload (ESP) AH and ESP are however similar protocols, both operating by adding a protocol header. Both AH and ESP are vehicles for access control based on the distribution of cryptographic keys and the management of traffic flows related to these security protocols. Security association (SA) is a key concept in the authentication and the confidentiality mechanisms for IP. A security association is a one-way relationship between a sender and a receiver that offers security services to the traffic carried on it if a secure two-way relationship is needed, then two security associations are required. If ESP and AH are combined, or if ESP and/or AH are applied more than once, the term SA bundle is used, meaning that two or more SAs are used. Thus, SA bundle refers to one or more SAs applied in sequence, e.g. by first performing an ESP protection, and then an AH protection. The SA bundle is the combination of all SAs used to secure a packet. The term IPsec connection is used in what follows in place of an IPSec bundle of one or more security associations, or a pair of IPSec bundles—one bundle for each direction—of one or more security associations. This term thus covers both unidirectional and bi-directional traffic protection. There is no implication of symmetry of the directions, i.e., the algorithms and IPSec transforms used for each direction may be different. A security association is uniquely identified by three parameters. The first one, the Security Parameters Index (SPI), is a bit string assigned to this SA The SPI is carried in AH and ESP headers to enable the receiving system to select the SA under which a received packet will be processed. IP destination address is the second parameter, which is the address of the destination end point of the SA, which may be an end user system or a network system such as a firewall or a router. The third parameter, the security protocol identifier indicates whether the association is an AH or ESP security association. In each IPSec implementation, there is a nominal security association data base (SADB) that defines the parameters associated with each SA. A security association is normally defined by the following parameters. The Sequence Number Counter is a 32-bit value used to generate the sequence number field in AH or ESP headers. The Sequence Counter Overflow is a flag indicating whether overflow of the sequence number counter should generate an auditable event and prevent further transmission of packets on this SA. An Anti-Replay Window is used to determine whether an inbound AH or ESP packet is a replay. AH information involves information about the authentication algorithm, keys and related parameters being used with AH. ESP information involves information of encryption and authentication algorithms, keys, initialisation vectors, and related parameters being used with IPSec. AH information consists of the authentication algorithm, keys and related parameters being used with AH. ESP information consists of encryption and authentication algorithms, keys, cryptographic initialisation vectors and related parameters being used with ESP. The sixth parameter, Lifetime of this Security Association, is a time-interval and/or byte-count after which this SA must be replaced with a new SA (and new SPI) or terminated plus an indication of which of these actions should occur. IPSec Protocol Mode is either tunnel or transport mode. Maximum Transfer Unit (MTU), an optional feature, defines the maximum size of a packet that can be transmitted without fragmentation. Optionally an MTU discovery protocol may be used to determine the actual MTU for a given route, however, such a protocol is optional. Both AH and ESP support two modes used, transport and tunnel mode. Transport mode provides protection primarily for upper layer protocols and extends to the payload of an IP packet Typically, transport mode is used for end-to-end communication between two hosts. Transport mode may be used in conjunction with a tunnelling protocol, other than IPSec tunnelling, to provide a tunnelling capability. Tunnel mode provides protection to the entire IP packet and is usually used for sending messages through more than two components, although tunnel mode may also be used for end-to-end communication between two hosts. Tunnel mode is often used when one or both ends of a SA is a security gateway, such as a firewall or a router that implements IPSec. With tunnel mode, a number of hosts on networks behind firewalls may engage in secure communications without implementing IPSec. The unprotected packets generated by such hosts are tunnelled through external networks by tunnel mode SAs set up by the IPSec software in the firewall or secure router at boundary of the local network. To achieve this, after the AH or ESP fields are added to the IP packet, the entire packet plus security fields are treated as the payload of a new outer IP packet with a new outer IP header. The entire original, or inner, packet travels through a tunnel from one point of an IP network to another: no routers along the way are able to examine the inner IP packet. Because the original packet is encapsulated, the new larger packet may have totally different source and destination addresses, adding to the security. In other words, the first step in protecting the packet using tunnel mode is to add a new IP header to the packet; thus the “IP|payload” packet becomes “IP|IP|payload”. The next step is to secure the packet using ESP and/or AH. In case of ESP, the resulting packet is “IP|ESP|IP|payload”. The whole inner packet is covered by the ESP and/or AH protection. AH also protects parts of the outer header, in addition to the whole inner packet. The IPSec tunnel mode operates e.g. in such a way that if a host on a network generates an IP packet with a destination address of another host on another network, the packet is routed from the originating host to a security gateway (SGW), firewall or other secure router at the boundary of the first network. The SGW or the like filters all outgoing packets to determine the need for IPSec processing. If this packet from the first host to another host requires IPSec, the firewall performs IPSec processing and encapsulates the packet in an outer IP header. The source IP address of this outer IP header is this firewall and the destination address may be a firewall that forms the boundary to the other local network. This packet is now routed to the other host's firewall with intermediate routers examining only the outer IP header At the other host firewall, the outer IP header is stripped off and the inner packet is delivered to the other host. ESP in tunnel mode encrypts and optionally authenticates the entire inner IP packet, including the inner IP header AH in tunnel mode authenticates the entire inner IP packet, including the inner IP header, and selected portions of the outer IP header. The key management portion of IPSec involves the determination and distribution of secret keys. The default automated key management protocol for IPSec is referred to as ISAKMP/Oakley and consists of the Oakley key determination protocol and Internet Security Association and Key Management Protocol (ISAKMP). Internet key exchange (IKE) is a newer name for the ISAKMP/Oakley protocol. IKE is based on the Diffie-Hellman algorithm and supports RSA signature authentication among other modes. IKE is an extensible protocol, and allows future and vendor-specific features to be added without compromising functionality. IPSec has been designed to provide confidentiality, integrity, and replay protection for IP packets. However, IPSec is intended to work with static network topology, where hosts are fixed to certain subnetworks. For instance, when an IPSec tunnel has been formed by using Internet Key Exchange (IKE) protocol, the tunnel endpoints are fixed and remain constant. If IPSec is used with a mobile host, the IKE key exchange will have to be redone from every new visited network. This is problematic, because IKE key exchanges involve computationally expensive Diffie-Hellman key exchange algorithm calculations and possibly RSA calculations. Furthermore, the key exchange requires at least three round trips (six messages) if using the IKE aggressive mode followed by IKE quick mode, and nine messages if using IKE main mode followed by IKE quick mode. This may be a big problem in high latency networks, such as General Packet Radio Service (GPRS) regardless of the computational expenses. In this text, the term mobility and mobile terminal does not only mean physical mobility, instead the term mobility is in the first hand meant moving from one network to another, which can be performed by a physically fixed terminal as well. The problem with standard IPSec is thus that it has been designed for static connections. For instance, the end points of an IPSec tunnel mode SA are fixed. There is also no method for changing any of the parameters of an SA, other than by establishing a new SA that replaces the previous one. However, establishing SAs is costly in terms of both computation time and network latency. An example of a specific scenario where these problems occur is described next in order to illustrate the problem. In the scenario, there is a standard IPSec security gateway, which is used by a mobile terminal e.g. for remote access. The mobile terminal is mobile in the sense that it changes its network point of attachment frequently. A mobile terminal can in this text thus be physically fixed or mobile. Because it may be connected to networks administered by third parties, it may also have a point of attachment that uses private addresses—i.e., the network is behind a router that performs network address translation (NAT). In addition, the networks used by the mobile terminal for access may be wireless, and may have poor quality of service in terms of throughput and e.g. packet drop rate. Standard IPSec does not work well in the scenario. Since IPSec connections are bound to fixed addresses, the mobile terminal must establish a new IPSec connection from each point of attachment. If an automated key exchange protocol, such as IKE, is used, setting up a new IPsec connection is costly in terms of computation and network latency, and may require a manual authentication phase (for instance, a one-time password). If IPSec connections are set up manually, there is considerable manual work involved in configuring the IPSec connection parameters. Standard IPSec does e.g. not work through NAT devices at the moment. A standard IPSec NAT traversal protocol is currently being specified, but the security gateway in the scenario might not support an IPSec protocol extended in this way. Furthermore, the current IPSec NAT traversal protocols are not well suited to mobility. There are no provisions for improving quality of service over wireless links in the standard IPSec protocol. If the access network suffers from high packet drop rates, the applications running in the mobile host and a host that the mobile terminal is communicating with will suffer from packet drops. A known method of solving some of these problems is based on having an intermediate host between the mobile terminal and the IPSec security gateway. The intermediate host might be a Mobile IP home agent, that provides mobility for the connection between the mobile terminal and the home agent, while the connection from the mobile node to the security gateway is an ordinary IPSec connection. In this case, packets sent by an application in the mobile client are first processed by IPSec, and then by Mobile IP. In the general case, this implies both Mobile IP and IPSec header fields for packets exchanged by the mobile terminal and the home agent. The Mobile IP headers are removed by the home agent prior to delivering packets to the security gateway, and added when delivering packets to the mobile terminal. Because of the use of two tunnelling protocols (Mobile IP and IPSec tunnelling), the solution is referred to as “double tunnelling” in this document. The above method solves the mobility problem, at the cost of adding extra headers to packets. This may have a significant impact on networks that have low throughput such as the General Packet Radio System (GPRS). Another known method is again to use an intermediate host between the mobile client and the IPSec security gateway. The intermediate host has an IPSec implementation that may support NAT traversal, and possibly some proprietary extensions for improving quality of service of the access network, for instance. The mobile host would now establish an IPSec connection between itself and the intermediate host, and would also establish an IPSec connection between itself and the IPSec security gateway. This solution is similar to the first known method, except that two IPSec tunnels are used. It solves a different set of problems—for instance, NAT traversal—but also adds packet size overhead because of double IPsec tunnelling. A third known method is to use a similar intermediate host as in the second known method, but establish an IPSec connection between the mobile terminal and the intermediate host, and another, separate IPSec connection between the intermediate host and the security gateway. The IPSec connection between the mobile terminal and the intermediate host may support NAT traversal, for instance, while the second IPSec connection does not need to. When packets are sent by an application in the mobile terminal, the packets are IPSec-processed using the IPSec connection shared by the mobile terminal and the intermediate host. Upon receiving these packets, the intermediate host undoes the IPSec-processing. For instance, if the packet was encrypted, the intermediate host decrypts the packet. The original packet would now be revealed in plaintext to the intermediate host. After this, the intermediate host IPSec-processes the packet using the IPSec connection shared by the intermediate host and the security gateway, and forwards the packet to the security gateway. This solution allows the use of an IPSec implementation that support NAT traversal, and possibly a number of other (possibly vendor specific) improvements, addressing problems such as the access network quality of service variations. Regardless of these added features, the IPSec security gateway remains unaware of the improvements, and is not required to implement any of the protocols involved in improving service. However, the solution has a major drawback: the IPsec packets are decrypted in the intermediate host, and thus possibly sensitive data is unprotected in the intermediate host. Consider a business scenario where a single intermediate host provides improved service to a number of separate customer networks, each having its own standard IPSec security gateway. Having decrypted packets of various customer networks in plaintext form in the intermediate host is clearly a major security problem. To summarise, the known solutions either employ extra tunnelling, causing extra packet size overhead, or use separate tunnels, causing potential security problems in the intermediate host(s) that terminate such tunnels.

<SOH> SUMMARY OF THE INVENTION <EOH>The method and system of the invention enable secure forwarding of a message from a first computer to a second computer via an intermediate computer in a telecommunication network. It is mainly characterized in that a message is formed in the first computer or in a computer that is served by the first computer, and in the latter case, sending the message to the first computer. In the first computer, a secure message is then formed by giving the message a unique identity and a destination address. The message is sent from the first computer to the intermediate computer, whereafter said destination address and the unique identity are used to find an address to the second computer. The current destination address is substituted with the,found address to the second computer, and the unique identity is substituted with another unique identity. Then the message is forwarded to the second computer. The advantageous embodiments have the characteristics of the subclaims, Preferably, the first computer processes the formed message using a security protocol and encapsulates the message at least in an outer IP header. The outer IP header source address is the current address of the first computer, while the destination address is that of the intermediate computer. The message is then sent to the intermediate computer, which matches the outer IP header address fields together with a unique identifier used by the security protocol, and performs a translation of the outer addresses and the unique identity used by the security protocol. The translated packet is then sent to the second computer, which processes it using the standard security protocol in question. In the method of the invention, there is no extra encapsulation overhead as in the prior art methods. Also, the intermediate computer does not need to undo the security processing, e.g. decryption, and thus does not compromise security as in the prior art methods. Corresponding steps are performed when the messages are sent in the reverse direction, i.e. from the second computer to the first computer. Preferably, the secure message is formed by making use of the IPSec protocols, whereby the secure message is formed by using an IPsec connection between the first computer and the intermediate computer. The message sent from the first computer contains message data, an inner IP header containing actual sender and receiver addresses, an outer IP header containing the addresses of the first computer and the intermediate computer, a unique identity, and other security parameters. The unique identity is one or more SPI values and the other security parameters contain e.g. the IPsec sequence number(s). The number of SPI values depends on the SA bundle size (e.g. ESP+AH bundle would have two SPI values). In the following, when an SA is referred to, the same applies to an SA bundle. The other related security parameters, containing e.g. the algorithm to be used, a traffic description, and the lifetime of the SA, are not sent on the wire. Only SPI and sequence number are sent for each IPsec processed header (one SPI and one sequence number if e.g. ESP only is used; two SPIs and two sequence numbers if e.g. ESP+AH is used, etc.). Thus, the unsecured data packet message is formed by the sending computer, which may or may not be the first computer. The IP header of this packet has IP source and destination address fields (among other things). The packet is encapsulated e.g. wrapped inside a tunnel, and the resulting packet is secured. The secured packet has a new outer IP header, which contains another set of IP source and destination addresses (in the outer header—the inner header is untouched), i.e. there are two outer addresses (source and destination) and two inner addresses. The processed packet has a unique identity, the IPsec SPI value(s). An essential idea of the invention is to use the standard protocol (IPSec) between the intermediate computer and the second computer and an “enhanced IPSec protocol” between the first computer and the intermediate computer. IPsec-protected packets are translated by the intermediate computer, without undoing the IPsec processing. This avoids both the overhead of double tunneling and the security problem involved in using separate tunnels. The translation is performed e.g. by means of a translation table stored at the intermediate computer. The outer IP header address fields and/or the SPI-values are changed by the intermediate computer so that the message can be forwarded to the second computer. By modifying the translation table and parameters associated to a given translation table entry, the properties of the connection between the first and the intermediate computers can be changed without establishing a new IPsec connection, or involving the second computer in any way. One example of a change in the SA between the first computer and the intermediate computer is the change of addresses for enabling mobility. This can be accomplished in the invention simply by modifying the translation table entry address fields. Signaling messages may be used to request such a change. Such signalling messages may be authenticated and/or encrypted, or sent in plaintext. One method of doing authentication and/or encryption is to use an IPsec connection between the first computer and the intermediate computer. The second computer is unaware of this IPsec connection, and does not need to participate in the signalling protocol in any way. Several other methods of signalling exist, for instance, the IKE key exchange protocol maybe extended to carry such signalling messages. In the signalling, e.g. a registration request is sent from the first computer to the intermediate computer which causes the intermediate computer to modify the addresses in the mapping table and thus, the intermediate computer can identify the mobile next time a message is sent. Preferably, as a result of a registration request, a reply registration is sent from the intermediate computer back to the first computer. Other examples of possible modifications to the SA—or in general, the packet processing behaviour—between the first computer and the intermediate computer are the following. One example is the first computer and the intermediate computer perform some sort of retransmission protocol that ensures that the IPSec protected packets are not dropped in the route between the first and the intermediate computer. This may have useful applications when the first computer is connected using a network access method that has a high packet drop rate—for instance, GPRS. Such a protocol can be easily based on e.g. IPsec sequence number field and the replay protection window, which provide a way to detect that packet(s) have been lost. When a receiving host detects missing packets, it can send a request message for those particular packets. The request can of course be piggy-backed on an existing data packet that is being sent to the other host. Another method of doing the retransmissions may be based on using an extra protocol inside which the IPSec packets are wrapped for transmission between the first and intermediate computer. In any case, the second computer remains unaware of such a retransmission protocol. Another example is performing a Network Address Translation (NAT) traversal encapsulation between the first and the intermediate computer. This method could be based on e.g. using UDP encapsulation for transmission of packets between the first and the intermediate computer. The second computer remains unaware about this processing and does not even need to support NAT traversal at all. This is beneficial because there are several existing IPSec products that have no support for NAT traversal. The system of the invention is a telecommunication network for secure forwarding of messages and comprises at least a first computer, a second computer and an intermediate computer. It is characterized in that the first and the second computers have means to perform IPSec processing, and the intermediate computer have means to perform IPSec translation and possibly key exchange protocol, such as IKE, translation, preferably by means of mapping tables. The intermediate computer may perform IPSec processing related to other features, such as mobility signalling described above or other enhancements. The IPSec translation method is independent of the key exchange translation method. Also manual keying can be used instead of automatic keying. If automatic keying is used, any key exchange protocol can be modified for that purpose; however, the idea is to keep the second computer unaware of the interplay of the first and the intermediate computer. An automatic key exchange protocol may be used in the invention in several ways. The essential idea is that the second computer sees a standard key exchange protocol run, while the first and the intermediate computer perform a modified key exchange. The modified key exchange protocol used between the first and the intermediate computer ensures that the IPsec translation table and other parameters required by the invention are set up as a side-effect of the key exchange protocol. One such modified protocol is presented in the application for the IKE key exchange protocol. Each translation table consists of entries that are divided into two partitions. The first partition contains information fields related to the connection between the first computer and the intermediate computer, while the second partition contains information fields related to the connection between the intermediate computer and the second computer. The translation occurs by identifying the translation table entry by comparing against one partition, and mapping into the other. For traffic that is flowing from the first computer towards the second computer, through the intermediate computer, the entry is found by comparing the received packet against entries in the first partition, and then translating said fields using information found in the second partition of the same entry. For traffic flowing in the opposite direction, the second partition is used for finding the proper translation table entry, and the first partition for translating the packet fields. The IPSec translation table partitions consist of the following information: the IP local address and the IP remote address (tunnel endpoint addresses) and SPIs for sending and receiving data. As mentioned, a translation table entry consists of two such partitions, one for communication between first computer and the intermediate computer, and another for communication between the intermediate computer and the second computer. The invention described solves the above problems of prior art. The solution is based on giving the first computer, e.g. if it is mobile, an appearance of a standard computer for the second computer. Thus, the second computer will believe it is talking to a standard IPSec host, while the intermediate computer and the second computer will work together using a modified protocol, for instance a slightly modified IPSec and IKE that helps to accomplish this goal. There are, however, several other control protocols that could conceivably be used between the first and the intermediate computer. In the following, the invention is described more in detail by using figures by means of some embodiment examples to carry out the invention. The invention is not restricted to the details of the figures and accompanying text, or any existing protocols, such as the currently standardised IPSec or IKE. Especially, the invention can be concerned with other kinds of telecommunication networks wherein the method of the invention can be applied than that of the figures.

20051019

20130101

20060803

59971.0

G06F15167

TOWFIGHI, AFSHAWN M

METHOD AND SYSTEM FOR SENDING A MESSAGE THROUGH A SECURE CONNECTION

UNDISCOUNTED

ACCEPTED

G06F

ACCEPTED

Method for controlling the hybrid drive of a vehicle

A method for controlling a hybrid drive of a vehicle is described, the hybrid drive including as propulsion motors an internal combustion engine and at least one electric motor/generator, and the output shafts of the propulsion motors being operatively linkable to a power train of the vehicle. The propulsion motors and an electrically activatable braking system of the vehicle are activated in a coordinated manner as a function of a negative torque request, taking this negative torque request into account.

1-10. (canceled) 11. A method for controlling a hybrid drive of a vehicle, the hybrid drive including as propulsion motors an internal combustion engine and at least one electric motor/generator, and output shafts of the propulsion motors being operatively linkable to a power train of the vehicle, the method comprising: activating the propulsion motors and an electrically activatable braking system of the vehicle in a coordinated manner, as a function of a negative torque demand, and taking the negative torque demand into account. 12. The method as recited in claim 11, further comprising: specifying a setpoint wheel braking torque for the braking system taking an operating state of the hybrid drive into account. 13. The method as recited in claim 11, wherein to specify the setpoint wheel braking torque, an instantaneous transmission output torque is gated with a request signal of a brake pedal. 14. The method as recited in claim 11, wherein a request signal delivered by a brake pedal is interpreted within a range that is defined by operation-related state data of the braking system and instantaneous torque or power potentials of the hybrid drive. 15. The method as recited in claim 11, wherein operating data of the internal combustion engine and of the electric motor/generator are taken into account for torque and power potentials of the hybrid drive. 16. The method as recited in claim 11, wherein an operating state of an on-board electrical system is taken into account for a torque and power potential of the electric motor/generator. 17. The method as recited in claim 16, wherein at least one of a battery state of charge, and a battery voltage is taken into account. 18. The method as recited in claim 11, wherein possible operating modes of the hybrid drive are taken into account for torque and power potentials. 19. The method as recited in claim 11, wherein a selected gear of the transmission is taken into account for torque and power potentials. 20. The method as recited in claim 11, wherein a shifting state of clutches of the hybrid drive is taken into account for torque and power potentials.

FIELD OF THE INVENTION The present invention relates to a method for controlling a hybrid drive of a vehicle, the hybrid drive including as propulsion motors an internal combustion engine and at least one electric motor/generator, and the output shafts of the propulsion motors being operatively linkable to a power train of the vehicle. BACKGROUND INFORMATION Hybrid drives for vehicles are conventional. In the hybrid drives addressed here, an internal combustion engine is combined with at least one electric motor/generator, so that a plurality of drive sources for the vehicle are available. According to requirements specified by a vehicle driver, the drive sources may optionally feed their driving torque into a power train of the vehicle. This results, in a conventional manner in various drive configuration possibilities, depending on concrete driving situations, which are used in particular to improve driver comfort and to reduce energy use, as well as to reduce pollutant emission. In hybrid drives for vehicles, serial arrangements, parallel arrangements and mixed arrangements of an internal combustion engine and electric motor/generators are conventional. Depending on the arrangement, the electric motor/generators may be connected to the power train of the engine directly or indirectly. For the operative linkage of the internal combustion engine and/or the electric motor/generators it is conventional to arrange them so that they are operatively linkable with each other using gearing, for example planetary gears and the like, and clutches. Optimum implementation of a driver's request for propulsion power from the hybrid drive requires coordinated activation of the propulsion motors of the hybrid drive, which is accomplished, as is conventional, by a device known as a control unit. The propulsion motors may be activated on the basis of a setpoint operating state of the hybrid drive to be determined by the control unit. The objective in determining this setpoint operating state is in particular low fuel consumption, dynamic drivability of the vehicle and low pollutant emission. Furthermore, it is generally conventional to equip vehicles with an electronically activatable braking system, for example an electrohydraulic or electromechanical brake. SUMMARY An example embodiment of a method according to the present invention may offer the advantage that by linking the activation of the hybrid drive of a vehicle with the activation of a braking system of the vehicle, optimum utilization of the available power of the vehicle is possible. Because, as a result of a request for negative torque, a coordinated activation of the propulsion machine and of a braking system of the vehicle occurs, which takes this request for negative torque into account, it becomes particularly advantageously possible for braking energy to be recovered taking into account boundary conditions of optimum power consumption, optimum comfort, and optimum safety. In particular, it is possible to lower fuel consumption of the internal combustion engine through recovery of braking energy by feeding it back into the on-board electrical system. The fed-back energy may be stored in particular in a high-performance battery—which is used to supply power to at least one electric motor/generator—and is available to be fed into the on-board electrical system if needed. BRIEF DESCRIPTION OF THE DRAWINGS The present invention is explained in greater detail below using an exemplary embodiment on the basis of the figures. FIG. 1 shows a block diagram of an example method according to the present invention. FIG. 2 shows a schematic view of the drive and braking system of a vehicle. FIG. 3 shows torque characteristic curves of a hybrid drive. DETAILED DESCRIPTION OF EXAMPLE EMBODIMENTS FIG. 1 shows a block diagram of a section of a control unit for activating a hybrid drive of a vehicle. Hybrid drive 100 includes an internal combustion engine 10 and at least one electric motor/generator 12. These operate through a transmission 14 on a power train of the vehicle. The engine control unit includes a device known as a coordinator 16 of longitudinal motions, i.e., in or opposite to an imaginary direction of travel of the vehicle. These longitudinal motions of the vehicle are triggered by a request of a vehicle driver, for example through an accelerator pedal 18 and a brake pedal 20. In addition, a request may be placed on the longitudinal motion of the vehicle by an automatic cruise control system 22. Accelerator pedal 18 and/or brake pedal 20 and/or automatic cruise control system 22 may request an acceleration or deceleration of the vehicle in the longitudinal direction, which is implemented by hybrid drive 100 or a brake device 24 of the vehicle. For coordinated activation of hybrid drive 100, i.e., of the individual components of hybrid drive 100, a device known as a coordinator 26 is provided. Drive coordinator 26 communicates with longitudinal motion coordinator 16 through a vehicle coordinator 28. The vehicle also includes an on-board electrical system 30 to supply electric motor/generator 12 and other electrical components of the vehicle. From accelerator pedal 18, coordinator 16 receives a signal 32, which requests a setpoint power at the output of transmission 14. From brake pedal 20, coordinator 16 receives a signal 34, which requests a setpoint torque at the wheels of the vehicle. The magnitude of signal 34 relates to the sum of the braking torques at the four wheels of the vehicle, and is thus proportional to a desired braking force that acts on the vehicle in the longitudinal direction. From automatic cruise control system 22, coordinator 16 receives a signal 36 that requests a longitudinal acceleration of the vehicle. Coordinator 16 evaluates and processes signals 32, 34 and 36, and provides a signal 38 corresponding to the setpoint braking torque that is requested from braking system 24. In addition, a signal 40 is provided by coordinator 16, which corresponds to a setpoint drive power at the output of transmission 14 and is requested by coordinator 26 for hybrid drive 100. Signal 40 is forwarded via coordinator 28 to coordinator 26. Corresponding to signal 40, coordinator 26 is responsible for determining the setpoint operating state of hybrid drive 100 and the resulting activation of propulsion motors 10 and 12. Propulsion motors 10 and 12 are activated in such a way that the setpoint drive power corresponding to signal 40 is implemented at the output of transmission 14. To this end, coordinator 26 gives internal combustion engine 10 a signal 42 which corresponds to a setpoint output torque of internal combustion engine 10. In addition, coordinator 26 gives a signal 44 to electric motors/generators 12 or, if there are a plurality of electric motors/generators 12, to electric motors/generators 12, which corresponds in each case to the setpoint output torques of electric motors/generators 12. At the same time, transmission 14 receives a signal 46 which corresponds to a setpoint gear or a setpoint transmission ratio of transmission 14. Internal combustion engine 10 supplies a signal 48 to coordinator 26, which corresponds to the instantaneous engine output torque of internal combustion engine 10. The electric motors/generators deliver instantaneous torque 50. In addition, transmission 14 supplies a signal 52 to coordinator 26 which corresponds to the instantaneous operating state of transmission 14. From signals 48, 50 and 52, coordinator 26 determines the instantaneous transmission output torque and makes it available to coordinator 28 as signal 54. The latter forwards signal 54 to the coordinator for longitudinal motion of the vehicle. From braking system 24, coordinator 16 receives a signal 56 that corresponds to the instantaneous wheel braking torque. Coordinator 26 receives from internal combustion engine 10 an additional available signal 58, which contains additional operating data about internal combustion engine 10. Internal combustion engine 10 has a maximum and a minimum engine output torque. These torques are variable via the engine speed according to a full load characteristic curve or a drag torque curve, and are a function of additional operating parameters such as engine temperature and the atmospheric air pressure. Furthermore, coordinator 26 receives a signal 60 from electric motor/generator 12. Each electric motor/generator 12 also has a maximum and a minimum output torque, which depends on the rotational speed. The maximum and minimum torques are in addition functions of the temperature of electric motor/generator 12 and of an indirect AC converter (FIG. 2). The potential torques also depend on the state of on-board electrical system 30, in particular a battery charge state and a battery voltage. On-board electrical system 30 transmits its instantaneous potential to electric motor/generator 12 as signal 62, SO that this data is also merged into signal 60. From the data from signals 58 and 60, coordinator 26 determines the torque potential or power potential of hybrid drive 100 at the output of transmission 14. A resulting signal 64 is communicated by coordinator 26 to coordinator 28. In this process, the physical correlations resulting from the constructional arrangement of combustion internal combustion engine 10, electric motor/generators 12 and transmission 14 in particular are also taken into account. Signal 64 also depends on possible operating modes of hybrid drive 100. Examples of possible operating modes are pure internal combustion engine mode, pure electrical mode and hybrid electrical-internal combustion engine mode. For each of these operating modes, a torque or power potential at the output of transmission 14 is determined and is reported to coordinator 28. Signal 64 also depends on the gear selected, i.e., the transmission ratio and on the shifting state of one or more clutches. In addition to the data about the gear currently selected, coordinator 26 also communicates to coordinator 28 the data signals for other possible gears. Coordinator 28 provides the torque and power potentials of hybrid drive 100 to coordinator 16 as signal 66. In so doing, coordinator 28 takes possible operating modes into account and communicates only the potentials of permitted operating modes. From braking system 24, coordinator 16 also receives a signal 68 which contains operation-dependent status data about braking system 24. This data may be for example an instantaneous braking force, a braking force gradient, or the like. On the basis of signals 66 and 68, coordinator 16 supplies a signal 70 to accelerator pedal 18 that specifies the range within which an interpretation of accelerator pedal 18 is possible. In addition, a signal 72 which defines the range within which an interpretation of brake pedal 20 is supposed to take place is fed to brake pedal 70. Furthermore, coordinator 16 gates signal 34 from brake pedal 20 with signal 54, which corresponds to the instantaneous transmission output torque of hybrid drive 100, and from that determines signal 38 as the specification for the setpoint wheel braking torque of braking system 24. Thus, the setpoint wheel braking torque (signal 38) is specified taking into account signal 62 supplied by on-board electrical system 30 and the supplied potential data. The latter is gated, via coordinator 26, with the data supplied by internal combustion engine 10, electric motor/generator 12 and transmission 14, so that by conveying the corresponding signals to coordinator 16 it is possible to achieve coordinated activation of hybrid drive 100, i.e., of internal combustion engine 10, electric motor/generator 12 and transmission 14, as well as of braking system 24, so that when braking system 24 is activated or when internal combustion engine 10 is in deceleration mode, optimum recovery of braking energy through deliberate generator operation of electric motor/generator 12 is possible. Through coordinated activation of propulsion motors 10 and 12 and of braking system 24, depending on the demands of brake pedal 20 (signal 34), the negative torque demand (deceleration wish) for the vehicle is optimally met. This largely prevents unnecessary losses. FIG. 2 shows in a block diagram the implementation of the control of a hybrid drive explained on the basis of FIG. 1. Parts equivalent to those in FIG. 1 are given the same reference symbols and are not explained again. Hybrid drive 100 includes internal combustion internal combustion engine 10, electric motor/generator 12 and transmission 14. A crankshaft 74 of internal combustion engine 10 is operatively linkable to electric motor/generator 12 through a first clutch 76. An output shaft 78 of electric motor/generator 12 is operatively linkable to an input shaft 82 of transmission 14 through a second clutch 80. An output shaft 84 of transmission 14 is operatively linked to drive shafts 86, which drive wheels 88, here indicated schematically. Brake devices 90 indicated here may act on wheels 88. Accelerator pedal 18, brake pedal 20 and automatic cruise control system 22 are connected to a control unit 92, which includes coordinators 16, 26 and 28 illustrated in FIG. 1. Internal combustion engine 10 is activatable through a controller 94. Electric motor/generator 12 is activatable via an indirect AC converter 96, while transmission 14 and clutches 76 and 80 are activatable via a clutch controller 96. Brake devices 90 are activatable by braking system 24. Control unit 92 is connected to controllers 94, 96, 98 in braking system 24 through a bus system (such as CAN) 102. The exchange of the data streams illustrated in FIG. 1 among the individual components for coordinated activation of internal combustion engine 10, electric motor/generator 12, transmission 14, and braking system 24 takes place via this bus 102. The representation in FIG. 2 makes it clear that the present invention may be easily integrated into existing vehicle structures. FIG. 3 illustrates via characteristic curves the profile of torque M as a function of a vehicle velocity V. At the same time the range of negative torques, converted to a braking force on the wheel, is shown. The family of curves is based on the assumption of the parallel hybrid drive 100 shown schematically in FIG. 2, having a 5-speed automatic transmission 14, and an electric motor/generator 12, which is positioned between a flywheel of combustion internal combustion engine 10 and transmission input shaft 82 through use of two automatically operable clutches 76 and 80. FIG. 3 shows for each of the gears, which are designated with 1., 2., 3., 4. and 5., the maximum drag torque of internal combustion engine 10 as characteristic curves 104, and the maximum drag torque of electric motor/generator 12, which corresponds to its minimum torque, as characteristic curve 106. In the pure internal combustion engine mode of hybrid drive 100, the potential is given by the profile of the drag torque of combustion internal combustion engine 10, while in the pure electric mode of hybrid drive 100 the potential is given by the profile of the minimal torque of electric motor/generator 12. In hybrid mode, these two torque characteristics—in reference to the particular gear—may be superimposed, so that the sum of the two curves results as the maximum potential.

<SOH> BACKGROUND INFORMATION <EOH>Hybrid drives for vehicles are conventional. In the hybrid drives addressed here, an internal combustion engine is combined with at least one electric motor/generator, so that a plurality of drive sources for the vehicle are available. According to requirements specified by a vehicle driver, the drive sources may optionally feed their driving torque into a power train of the vehicle. This results, in a conventional manner in various drive configuration possibilities, depending on concrete driving situations, which are used in particular to improve driver comfort and to reduce energy use, as well as to reduce pollutant emission. In hybrid drives for vehicles, serial arrangements, parallel arrangements and mixed arrangements of an internal combustion engine and electric motor/generators are conventional. Depending on the arrangement, the electric motor/generators may be connected to the power train of the engine directly or indirectly. For the operative linkage of the internal combustion engine and/or the electric motor/generators it is conventional to arrange them so that they are operatively linkable with each other using gearing, for example planetary gears and the like, and clutches. Optimum implementation of a driver's request for propulsion power from the hybrid drive requires coordinated activation of the propulsion motors of the hybrid drive, which is accomplished, as is conventional, by a device known as a control unit. The propulsion motors may be activated on the basis of a setpoint operating state of the hybrid drive to be determined by the control unit. The objective in determining this setpoint operating state is in particular low fuel consumption, dynamic drivability of the vehicle and low pollutant emission. Furthermore, it is generally conventional to equip vehicles with an electronically activatable braking system, for example an electrohydraulic or electromechanical brake.

<SOH> SUMMARY <EOH>An example embodiment of a method according to the present invention may offer the advantage that by linking the activation of the hybrid drive of a vehicle with the activation of a braking system of the vehicle, optimum utilization of the available power of the vehicle is possible. Because, as a result of a request for negative torque, a coordinated activation of the propulsion machine and of a braking system of the vehicle occurs, which takes this request for negative torque into account, it becomes particularly advantageously possible for braking energy to be recovered taking into account boundary conditions of optimum power consumption, optimum comfort, and optimum safety. In particular, it is possible to lower fuel consumption of the internal combustion engine through recovery of braking energy by feeding it back into the on-board electrical system. The fed-back energy may be stored in particular in a high-performance battery—which is used to supply power to at least one electric motor/generator—and is available to be fed into the on-board electrical system if needed.

20050125

20080520

20050616

77657.0

YOUNG, EDWIN

METHOD FOR CONTROLLING A HYBRID DRIVE OF A VEHICLE

UNDISCOUNTED

ACCEPTED

ACCEPTED

Swing and slide door

A door (6), for example in a vehicle, is mounted at one edge (8) for acurate movement about the axis of a shaft (16), and at the other edge (10) for displacement substantially in the plane of the door opening along rails (26, 28). Thus, on opening, the edge (8) swings outwards from the door opening before moving longitudinally away from the door opening, with the edge (10) being guided along the rails (26 and 28).

1-20. (canceled) 21. A door mounted on a structure for displacement between an open position and a closed position with respect to a door aperture in the structure, the door being connected to the structure by first guide means, which constrains a leading edge of the door, with respect to movement towards the open position, to execute an arcuate movement about an axis which is fixed to the structure, and by second guide means, which constrains a trailing edge of the door to execute a linear movement substantially parallel to the plane of the door aperture. 22. A door as claimed in claim 21, in which the first guide means comprises a door control lever which is mounted at one end for pivoting movement about an axis fixed to the structure, and is connected at the other end for pivotable movement relative to the door. 23. A door as claimed in claim 21, in which the axis of arcuate movement extends upwardly. 24. A door as claimed in claim 22, in which drive means is provided for pivoting the door control lever relative to the structure. 25. A door as claimed in claim 24, in which the drive means acts on a drive element which is rigidly connected to the door control lever. 26. A door as claimed in claim 22, in which the door control lever is one of two door control levers which are rigidly mounted on a common shaft which is rotatable about the axis. 27. A door as claimed in claim 26, in which the door control levers are connected to the door at the same perpendicular distance as each other from the axis. 28. A door as claimed in claim 21, in which the second guide means comprises a guide element mounted adjacent the trailing edge of the door, the guide element engaging a guide track which is fixed to the structure. 29. A door as claimed in claim 28, in which the guide track extends parallel to the door opening. 30. A door as claimed in claim 28, in which the guide track lies generally in a plane which is perpendicular to the axis of arcuate movement. 31. A door as claimed in claim 28, in which the guide track is one of two parallel, or almost parallel, guide tracks which are spaced apart in the direction of the axis of arcuate movement. 32. A door as claimed in claim 31, in which the guide tracks lie in or close to a common plane which is inclined to the axis of arcuate movement. 33. A door as claimed in claim 21, in which the door is curved about a generally horizontal axis. 34. A door as claimed in claim 21, in which the structure is a vehicle body having inner and outer skins. 35. A door as claimed in claim 34, in which the axis of arcuate movement extends between the skins. 36. A door as claimed in claim 34, in which the first guide means comprises a door control lever which is mounted at one end for pivoting movement about an axis fixed to the structure, and is connected at the other end for pivotable movement relative to the door; and a drive means is provided for pivoting the door control lever relative to the structure, wherein said drive means is disposed between the skins. 37. A door as claimed in claim 36, in which the door control lever projects through the outer skin of the vehicle body when the door is in the open position. 38. A door as claimed in claim 28, in which said structure is a vehicle body having inner and outer skins; and the guide track is disposed in a channel formed in the outer skin. 39. A door as claimed in claim 21, in which said structure is a vehicle body having inner and outer skins; and the guide track is disposed below a floor panel which is secured to the vehicle structure. 40. A vehicle having a door in accordance with claim 21.

This invention relates to a door, and is particularly, although not exclusively, concerned with a door for a vehicle. Sliding doors for vehicles are well known, in particular for providing passenger access to road and rail passenger vehicles. On opening, such doors move linearly into cavities in the vehicle structure on one or both sides of the door aperture. There are also so-called swing plug doors which are mounted on a swinging mechanism which enables them to swing outwardly and to the side of the door aperture. Some swing plug doors also have a sliding mechanism to enable the door to slide over the outside of the vehicle structure Doors which slide into cavities in the vehicle structure require a substantial amount of space to the side of the door aperture to accommodate the door. Such doors can therefore be used in railway vehicles, but they are inappropriate for shorter vehicles which do not have space for the cavities. Swing plug doors do not require the vehicle structure to extend significantly beyond the door aperture unless they also incorporate a sliding mechanism for increasing the lateral displacement of the door after it has moved outwardly of the door aperture. However, swing plug doors employ a lever arrangement to support the door and control its movement, and this mechanism often encroaches substantially into the interior of the vehicle when the door is closed. Such systems are consequently also inappropriate for use in small vehicles. According to the present invention there is provided a door mounted on a structure for displacement between an open position and a closed position with respect to a door aperture in the structure, the door being connected to the structure by first guide means, which constrains a leading edge of the door, with respect to movement towards the open position, to execute an arcuate movement about an axis which is fixed with respect to the structure, and by second guide means, which constrains a trailing edge of the door to execute a linear movement substantially parallel to the plane of the door aperture. In this specification reference to “leading” and “trailing” edges of the door refer to movement of the door during opening. The first guide means may comprise a door control lever which is pivotable at one end about an axis which is fixed with respect to the structure and which is pivotably connected at the other end to the door adjacent the leading edge. The axis about which the lever pivots may be substantially upright. Drive means may be provided for moving the door between the open and closed positions. The drive means may be mounted so as to rotate the door control lever, for example by acting on a drive element such as a lever or gear wheel which projects from the axis and is rigidly connected to the door control lever. In order to enhance the stability of the door, two door control levers may be provided. They may be fixed rigidly to a common shaft which defines the axis about which the door control levers move. The door control levers may have the same length as each other between the common shaft and the pivotal connection with the door. The second guide means may comprise a guide element which, is mounted adjacent the trailing edge of the door and which is slidable along a guide track, for example in the form of a rail, which is fixed to the structure. The guide track may lie in a plane which is perpendicular to the axis of the arcuate movement controlled by the first guide means. Thus, if that axis is generally upright, the guide track will extend generally horizontally, and parallel to the plane of the door opening. The second guide means may comprise two of the guide tracks, for example disposed adjacent the top and bottom of the door. The guide tracks may lie in a common plane which is inclined to the axis of arcuate movement. The door may be curved, or otherwise shaped, so that different portions of the door lie in different planes. For example, the upper portion of the door may be displaced inwardly (with respect to the structure) relatively to the lower part of the door. For example, the door, in its upper region, may be curved about a generally horizontal axis. With such a configuration, the door may flex under the action of the first and second guide means as the door moves between the open and closed positions. In a preferred embodiment, the structure is a vehicle body, the door being provided to provide passenger axis to the interior of the vehicle. The vehicle body may have inner and outer skins, in which case the axis of the arcuate movement may extend between the skins and, where drive means is provided, this may also be provided between the skins. If the door is controlled by means of one or more door control levers, then at least one of these levers may extend through an opening in the outer skin in the open position of the door. Similarly, where the first guide comprises upper and lower guide tracks, the upper guide track may be disposed in a channel in the outer skin. The lower guide track may be disposed below a floor of the vehicle. For a better understanding of the present invention, and to show how it may be carried into effect, reference will now be made, by way of example, to the accompanying drawings, in which: FIG. 1 shows a vehicle with doors in a closed position; FIG. 2 shows the vehicle with the doors in the open position; FIG. 3 shows the connections of the door to the mounting structure; FIG. 4 is a sectional view at an upper region of the door; FIG. 5 is a fragmentary view corresponding to FIG. 4; FIG. 6 is a sectional view of a lower region of the door; and FIG. 7 is a fragmentary view corresponding to FIG. 6. The vehicle shown in FIGS. 1 and 2 is intended for use in urban transport systems. In such a system, a fleet of the vehicles would be available to passengers. The vehicles would be driverless, and would circulate on dedicated trackways provided with appropriate guidance means. The vehicle comprises a main vehicle structure 2 having a door aperture 4 (preferably one on each side of the vehicle). Each aperture 4 is closed by a pair of doors 6 which can open, as shown in FIG. 2, to provide access to the interior of the vehicle. As shown in FIG. 2, when in the open position, the leading edge 8 of each door (with respect to the direction of movement of the door towards the open position) is displaced outwardly of the door aperture 4 whereas the trailing edge 10 remains substantially in the plane of the door aperture 4. The doors 6 are thus able to open without a significant outward swinging movement. Such swinging movements are undesirable in automatically operated doors, since they could bring the doors into contact with waiting passengers or objects at the side of the vehicle. Also, the oblique positions of the doors when open provides a funnelling effect to direct passengers into the vehicle. As shown in FIG. 3, the door 6 is supported by first guide means 12 at its leading edge 8, and by second guide means 14 at its trailing edge 10. The first guide means 12 comprises an upright shaft 16 which is supported at top and bottom by bearings (not shown) which are fixed with respect to the vehicle structure 2. Two door control levers 18 and 20 are secured rigidly to the shaft 16 adjacent its top and bottom ends. The two door control levers 18 and 20 extend parallel to each other and are of substantially the same length as each other. Each lever 18, 20 is connected to the door 6 at a position close to the leading edge 8 by means of self-aligning bearings 22. A drive element in the form of a lever 24 is rigidly secured to the shaft 16 at its lower end. At its end away from the shaft 16, the drive lever 24 is connected to a motor. The second guide means 14 comprises guide tracks in the form of rails 26 and 28 which are fixed to the vehicle structure 2 towards the top and bottom respectively of the door aperture 4. Sliders 30 and 32 respectively are mounted on the door 6 adjacent its trailing edge 10, and close to its top and bottom edges. The rails 26, 28 extend parallel to, or almost parallel to, the longitudinal axis of the vehicle and lie in, or close to, the plane of the door opening. The rails 26, 28 are thus parallel to, or almost parallel to, each other, and lie in or close to a common plane which is inclined to the axis of the shaft 16. This is because the door 6 is curved, particularly at its upper end, so that the vertical planes containing the rails 26 and 28 are spaced apart from each other, with the plane containing the rail 26 being displaced in the inboard direction of the vehicle. It should be noted that the top rail 26 may be slightly curved in order to permit the required movement of the door, and so the expression “almost parallel to” in this context embraces the possibility that deviation from a truly parallel configuration results from such curvature. The closed and open positions of the door 6 are represented respectively by the solid outline 6 and the dashed outline 6′. As the shaft 16 is rotated by the action of the motor on the drive lever 24, the door control levers 18 and 20 swing outwardly to move the leading edge 8 of the door through an arcuate path which takes it out of the plane of the door aperture 4 and longitudinally away from the door aperture. The trailing edge of the door 10, however, does not move out of the plane of the door opening 4, since it is guided by the rails 26. Because the rail 26 is situated nearer to the central plane of the vehicle than the rail 28, the rails 26 and 28 do not lie in a plane parallel to the axis of the shaft 16. Consequently, the door 6 will flex as it moves between the open and closed positions. It is consequently necessary for the door to be constructed with sufficient flexibility to allow this flexing to occur without excessive stress on the components. If such flexing is undesirable in any particular application, control of the trailing edge 10 of the door 6 can be achieved with only a single rail 26 or 28 and slider 30 or 32. FIGS. 4 and 5 show in more detail the configuration at the upper end of the trailing edge 10 of the door 6. The vehicle structure 2 comprises an outer skin 34 comprising a roof panel. At the edge of the roof panel 34 bordering the door opening 4, the roof panel 34 is extended to form a channel 36 which terminates at a seal 38. The door 6 comprises a door frame 40 to which a glass layer 42 is bonded to provide a window. A slide mount 44 is fixed to the door frame 40 by screws 46. The slide mount 44 comprises a spigot 48 on which the slider 30 is pivotably mounted by means of bushes 50. The slider 30 is retained on the spigot 48 by means of a circlip 52. A further bush 54 is retained within the slider 30 for engagement with the rail 26. FIGS. 6 and 7 show in greater detail the structure of the rail 28 and the slider 32 towards the lower end of the trailing edge 10 of the door 6. As shown in FIGS. 6 and 7, the vehicle structure comprises a frame 56 to which a protective beam 58 is fixed. A floor panel 60 is supported by the frame 56. A slider mounting 62 having a spigot 64 is secured to the door 6 by screws 66. The slider 32 is mounted on the spigot 64 by means of bushings 68. A bush 70 is accommodated in the slider 32 to engage the rail 28. The rails 26 and 28 are secured to the vehicle structure by means which are not shown in the drawings. It will be appreciated from FIGS. 4 to 7 that the rails 26 and 28 and the associated sliders 30 and 32 operate outside the passenger compartment of the vehicle. The channel 36 shields the upper rail 36 and slider 30 from contact by passengers in the vehicle, while the floor board 60 and the protective beam 58 similarly shields the lower rail 28 and the lower slider 32. As can be appreciated from FIG. 4, the vehicle structure comprises an outer skin 34. Although not shown, there is also an inner skin which is situated within the outer skin and defines the passenger enclosure. The shaft 16 is disposed between the inner and outer skins, as is the drive lever 24 and the motor connected to it. An opening, for example in the form of a slot, is provided in the outer skin 34 along which each door control lever 18, 20 moves as the door opens. The mechanism associated with the shaft 16 is thus shielded from the passenger compartment.

20041222

20080429

20050602

81016.0

MORROW, JASON S

SWING AND SLIDE DOOR

UNDISCOUNTED

ACCEPTED

ACCEPTED

Novel proteins and dnas thereof

A novel sodium-dependent bile acid transporter protein, an Na+/H+ exchange transporter protein, a P-type ATPase protein and a vanilloid receptor protein, and polynucleotides encoding these proteins are useful in screening preventives/remedies for hyperlipemia, arteriosclerosis, genital diseases or digestive diseases; respiratory diseases, renal diseases or digestive diseases; pancreatic diseases, central nerve diseases, digestive diseases or respiratory diseases; inflammatory diseases, rheumatoid diseases or diabetic neurosis; etc.

1. A protein comprising the same or substantially the same amino acid sequence as an amino acid sequence represented by SEQ ID NO: 1, SEQ ID NO: 14 or SEQ ID NO: 104, or a salt thereof. 2. A protein consisting of an amino acid sequence represented by SEQ ID NO: 1 or SEQ ID NO: 14, or a salt thereof. 3. A protein consisting of an amino acid sequence represented by SEQ ID NO: 104, or a salt thereof. 4. A partial peptide of the protein according to claim 1, or a salt thereof. 5. A polynucleotide comprising a polynucleotide encoding the protein according to claim 1 or the partial peptide thereof. 6. The polynucleotide according to claim 5, which is DNA. 7. A DNA consisting of a base sequence represented by SEQ ID NO: 2, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 14, SEQ ID NO: 105 or SEQ ID NO: 112. 8. A recombinant vector comprising the polynucleotide according to claim 5. 9. A transformant transformed with the recombinant vector according to claim 8. 10. A method of manufacturing a protein having an amino acid sequence represented by SEQ ID NO: 1, SEQ ID NO: 14 or SEQ ID NO: 104 or its salt or the partial peptide or its salt thereof, which comprises culturing the transformant according to claim 9, forming and accumulating said protein or the partial peptide thereof, and recovering it. 11. A pharmaceutical composition comprising the protein according to claim 1 or the partial peptide thereof, and a pharmaceutically acceptable carrier, excipient or diluent. 12. A pharmaceutical composition comprising the polynucleotide according to claim 5 and a pharmaceutically acceptable carrier, excipient or diluent. 13. An antibody to the protein according to claim 1, the partial peptide thereof, or a salt of the protein or partial peptide. 14. A pharmaceutical composition comprising the antibody according to claim 13 and a pharmaceutically acceptable carrier, excipient or diluent. 15. A diagnostic agent comprising the antibody according to claim 13. 16. A polynucleotide comprising a base sequence complementary or substantially complementary to the base sequence of the polynucleotide according to claim 5 or a part of the base sequence. 17. A pharmaceutical composition comprising the polynucleotide according to claim 16 and a pharmaceutically acceptable carrier, excipient or diluent. 18. A method of screening a compound or its salt that promotes or inhibits the activity of the protein or its salt according to claim 1 or the partial peptide or its salt thereof, which comprises using the protein or its salt according to claim 1 or the partial peptide or its salt thereof in a screening assay. 19. The screening method according to claim 18, wherein the activity of the protein or its salt according to claim 1 or the partial peptide or its salt thereof is the substrate transport activity of the protein. 20. A kit for screening a compound or its salt that promotes or inhibits the activity of the protein or its salt according to claim 1 or the partial peptide or its salt thereof, which comprises the protein or its salt according to claim 1 or the partial peptide or its salt thereof. 21. (canceled) 22. (canceled) 23. A method of screening a compound or its salt that promotes or inhibits the expression of a gene for the protein according to claim 1, which comprises using a polynucleotide encoding for said protein or partial peptide thereof in a screening assay. 24. A kit for screening a compound or its salt that promotes or inhibits the expression of a gene for the protein according to claim 1, which comprises a polynucleotide encoding for said protein, or partial peptide thereof. 25. (canceled) 26. (canceled) 27. A method for making a pharmacutical composition for treating or preventing hyperlipemia, arteriosclerosis, genital diseases or digestive diseases, said method comprising combining a therapeutic amount of at least one component selected from the group consisting of: i) a protein according to claim 1 or the partial peptide; ii) a polynucleotide encoding for the protein or partial peptide of claim 1; iii) an antibody to the protein according to claim 1, the partial peptide thereof; and iv) a polynucleotide comprising a base sequence complementary or substantially complementary to the base sequence of the polynucleotide encoding for the protein of claim 1, or the partial peptide thereof; and a pharmaceutically acceptable carrier, excipient or diluent. 28. A method for treating or preventing hyperlipemia, arteriosclerosis, genital diseases or digestive diseases, which comprises administering an effective amount of at least one therapeutic selected from the group consisting of: a protein according to claim 1 or the partial peptide; a polynucleotide encoding for the protein or partial peptide of claim 1; an antibody to the protein according to claim 1, the partial peptide thereof; and a polynucleotide comprising a base sequence complementary or substantially complementary to the base sequence of the polynucleotide encoding for the protein of claim 1, or the partial peptide thereof; to a mammal in need thereof. 29.-115. (canceled)

TECHNICAL FIELD The present invention provides a novel sodium-dependent bile acid transporter protein, an Na+/H+ exchange transporter protein, a P-type ATPase protein, a vanilloid receptor protein, polynucleotides encoding these proteins, antisense polynucleotides to the polynucleotides, antibodies to these proteins, compounds that promote or inhibit the activities of the proteins, a method of screening compounds that promote or inhibit the activities of the proteins, compounds obtained by the screening method, and the like. BACKGROUND ART Bile acid is synthesized in the liver and secreted into a small intestine, and plays an important role in promoting absorption of lipids, lipid-soluble vitamins and cholesterols in the small intestine. Bile acid is re-absorbed efficiently through the small intestine (ileum), returned via a portal vein to the liver and excreted again into bile (enterohepatic circulation). The cholesterol pool size in the body is subject to feedback regulation not only by cholesterol in a meal but also by bile acid in enterohepatic circulation, and thus hypercholesterolemia therapy is conducted by suppression of re-absorption of bile acid into intestines by using a bile acid adsorbent (anion exchange resin). The sodium-dependent bile acid transporter is considered to contribute to transport of bile acid. In humans, two isoforms of sodium-dependent bile acid transporter have been identified, and NTCP (Na+/taurocholate cotransporting polypeptide) is expressed mainly in the liver (J. Clin. Invest., 93, 1326-1331, 1994), while ISBT (ileal sodium/bile salt cotransporter) is expressed mainly in the ileum/kidney (J. Biol. Chem., 270, 27228-27234, 1995). With respect to ISBT, direct relationship between a gene mutation accompanied by amino acid substitution and insufficient absorption of bile acid is suggested (J. Clin. Invest., 99, 1880-1887, 1997). A Na+/H+ exchange transporter (NHE) is a typical cation antiporter, which couples in animal cells with Na+ inflow to discharge H+. NHE is divided into 2 major regions, that is, an amino terminal (N) region containing about 500 amino acids comprising a 10- to 13-times transmembrane region and a carboxyl terminal (C) region comprising about 300 amino acids, and its whole structure is common among isoforms. It is known that the former is an ion transport region comprising an amyloride-binding site, and the latter functions as an activity regulatory region. As isoforms of NHE in humans, 6 kinds of isoforms i.e. NHE1 to NHE3 and NHE5 to NHE7 are reported. NHE1 is distributed broadly in tissues, and involved in regulation of intracellular pH and cell volume. The activity of NHE1 is promoted by a growth factor or simulation with high osmotic pressure, resulting in an increase in intracellular pH. NHE3 is expressed in the kidney and small intestine, and plays an important role in absorption of Na+. It is thus known that the respective isoforms are different in their expression distribution, regulatory mechanism, and the effect of inhibitor. NHE1 is considered as one factor increasing intracellular Na+ levels after ischemia and participating in causing myocardial difficulties. It is also reported that the activity of NHE1 in patients with hypertension is significantly higher than in healthy persons. In mice spontaneously developing epilepsy, it is confirmed that the disease is caused by a mutation in NHE (Cell, 91, 139-148, 1997). P-type ATPase is a membrane enzyme participating in transport of various substrates by utilizing energy upon hydrolysis of ATP. The P-type ATPase is divided into 3 classes, depending on its substrate. Type-1 utilizes heavy metals such as Cu2+ ion and Cd2+ ion as the substrate, possesses an N-terminal characteristic structure involved in binding to heavy metals, and has an 8-times transmembrane structure. Wilson's disease is a disease accompanying an abnormality in Cu2+-ATPase participating in excretion of copper in the liver. Type-2 utilizes alkali metals (K+ ion, Na+ ion), alkaline earth metals (Ca2+ ion) or proton (H+) as the substrate. In particular, H+, K+-ATPase (proton pump) in stomach acid-secreting cells is a target of chemicals such as proton pump inhibitors (omeplazole, lansoprazole etc.) that are therapeutic products for stomach ulcer/duodenum ulcer/reflux esophagitis. Further, Na+, K+-ATPase (sodium pump) is a target of chemicals such as cardiac glycosides used for cardiac diseases, and its activity is inhibited by ouabain. Type-3 is the latest determined type, and utilizes aminophospholipids as the substrate. It is also called aminophospholipid translocase (flippase), and reversely transfer phospholipids selectively from outer to inner layers by using energy generated upon hydrolysis of ATP. It is estimated that uneven distribution of lipids on the biomembrane is thereby maintained. No significant difference in structure is recognized between type-2 and type-3, both of which have a 10-times transmembrane structure (Biochemistry, 34, 15607-15613, 1995; Science, 272, 1495-1497, 1996). Up to now, 17 isoforms of P-type ATPase of type-3 have been identified in mammals. Among them, FIC1 is expressed in tissues such as the pancreas, small intestine, liver etc., and the relationship between an alteration in its gene and hereditary cholestasis is reported (Nature Genet., 18, 219-224, 1998). The P-type ATPase of type 3 is considered to play an important role in transport of aminophospholipids and in uneven distribution of lipids on the biomembrane, but the detailed functions and structure of each isoform and the relationship thereof with the disease are not so revealed. As a pain receptor, a vanilloid receptor subtype 1 (VR1) is a non-selective cation channel with high Ca2+ permeability having outward rectification. It is known that VR1 has a 6-times transmembrane region, possesses an H5 region regarded as forming a pore between fifth and sixth transmembrane sites, and has 3 ankyrin repeat domains at the N-terminal thereof. In addition to VR1 (Biochemical and Biophysical Research Communications, 281, 1183, 2001), VRL (vanilloid receptor-like protein) 1 and VRL2 in humans have been cloned up to now, and have about 40% homology with VR1 respectively (Physiol Genomics 4, 165-174, 2001). Capsaicin has a vanillyl group and is thus called vanilloid, and is an extraneous ligand of vanilloid receptor. No intrinsic ligand has been revealed. Single electric current measurement revealed that VR1 is activated electrophysiologically directly by capsaicin. Further, VR1 is a receptor of multi-stimuli, which is activated not only by chemical stimulation with capsaicin or the like but also by heat stimulation regarded pain stimulation (at a temperature of higher than 43° C. that is a threshold temperature at which pain is induced in humans) and acid stimulation (tissues are acidified in inflammations and ischemia). VR1 is activated by stimuli (for example capsaicin, heat, proton) causing pain in the living body, and in a morbid state, these stimuli are considered to occur not singly but simultaneously. Receptiveness of every pain in the living body is not elucidated by only VR1, and the presence of other homologues and cofactors is also estimated. In the previously reported VR family, there are various expression sites and stimulation receptivity, and these are considered to function depending on one another, to transmit pain stimulation. The sodium-dependent bile acid transporter is considered to play an important role in transport of bile acid in the liver and small intestine, but its detailed mechanism and the relationship thereof with the disease are not so revealed. Full elucidation of the substrate specificity of the sodium-dependent bile acid transporter and its role in bile acid metabolism leads to development of therapeutic products for diseases associated with bile acid metabolism. As described above, NHE is involved in many morbid states, and elucidation of the mechanism of activation and regulation of each isoform of NHE leads to development of therapeutic products. Elucidation of detailed functions of P-type ATPase of type 3 leads to development of therapeutic products for diseases such as metabolic diseases, central nerve diseases, genital diseases and cancers associated with P-type ATPase of type 3. The above-mentioned capsaicin is used as an analgesic for relieving pains in diabetic neurosis and articular rheumatism, and thus elucidation of the structure, function and mutual relationship of VR family is considered to lead to development of therapeutic products for pains as a whole. DISCLOSURE OF INVENTION The present inventors made extensive study for solving the problem described above, and as a result they found a novel sodium-dependent bile acid transporter protein. The inventors found that the protein has 44% homology at the amino acid level with human ISBT, and its substrate is estrone sulfate and dehydroepiandrosterone sulfate, and as a result of further examination, they completed the present invention. The present inventors made extensive study for solving the problem described above, and as a result they found a novel Na+/H+ exchange transporter protein. The amino acid residues at the N-terminal side of the protein consisting of 707 residues were identical with those of the amino acid sequence of TRICH-21 described in WO 02/04520. For inhibiting the protein, it is anticipated that for example, cation (Na+, K+)/H+ exchange transport is inhibited, or transcription of the protein is inhibited to reduce the expression level. For activating the protein, it is anticipated that for example, cation (Na+, K+)/H+ exchange transport is promoted, a promoter for the protein is activated, or its mRNA is stabilized to promote the expression level. As a result of further examination on the basis of these findings, the present inventors arrived at the present invention. The present inventors made extensive study for solving the problem described above, and as a result they found a novel P-type ATPase. This protein has 67% homology at the amino acid level with P-type ATPase of type 3 i.e. P-type ATPase 8A1 (ATP8A1) (Biochem. Biophys. Res. Commun., 257, 333-339, 1999) and 95% homology with mouse P-type ATPase 8A2 (ATP8A2) (Physiol. Genomics (Online), 1, 139-150, 1999), and can function as P-type ATPase of type 3. For inhibiting the protein, it is anticipated that for example, transport of aminophospholipids is inhibited, or transcription of the protein is inhibited to reduce the expression level. For activating the protein, it is anticipated that for example, transport of aminophospholipids is promoted, a promoter for the protein is activated, or its mRNA is stabilized to promote the expression level. As a result of further examination on the basis of these findings, the present inventors arrived at the present invention. The present inventors made extensive study for solving the problem described above, and as a result they found a novel vanilloid receptor. This protein has 43% homology at the amino acid level with human vanilloid receptor subtype 1 and can function as a vanilloid receptor. For inhibiting the protein, it is anticipated that for example, cation permeation is inhibited, or transcription of the protein is inhibited to reduce the expression level. For activating the protein, it is anticipated that for example, cation permeation is promoted, a promoter for the protein is activated, or its mRNA is stabilized to promote the expression level. As a result of further examination on the basis of these findings, the present inventors arrived at the present invention. That is, the present invention provides: (1) A protein comprising the same or substantially the same amino acid sequence as an amino acid sequence represented by SEQ ID NO: 1, SEQ ID NO: 14 or SEQ ID NO: 104, or a salt thereof. (2) A protein consisting of an amino acid sequence represented by SEQ ID NO: 1 or SEQ ID NO: 14, or a salt thereof. (3) A protein consisting of an amino acid sequence represented by SEQ ID NO: 104, or a salt thereof. (4) A partial peptide of the protein according to the above-mentioned (1), or a salt thereof. (5) A polynucleotide comprising a polynucleotide encoding the protein according to the above-mentioned (1) or the partial peptide according to the above-mentioned (4). (6) The polynucleotide according to the above-mentioned (5), which is DNA. (7) A DNA consisting of a base sequence represented by SEQ ID NO: 2, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 14, SEQ ID NO: 105 or SEQ ID NO: 112. (8) A recombinant vector comprising the polynucleotide according to the above-mentioned (5). (9) A transformant transformed with the recombinant vector according to the above-mentioned (8). (10) A method of manufacturing the protein or its salt according to the above-mentioned (1) or the partial peptide or its salt according to the above-mentioned (4), which comprises culturing the transformant according to the above-mentioned (9), forming and accumulating the protein according to the above-mentioned (1) or the partial peptide according to the above-mentioned (4), and recovering it. (11) A medicine comprising the protein according to the above-mentioned (1) or the partial peptide according to the above-mentioned (4). (12) A medicine comprising the polynucleotide according to the above-mentioned (5). (13) An antibody to the protein according to the above-mentioned (1), the partial peptide according to the above-mentioned (4), or a salt of the protein or partial peptide. (14) A medicine comprising the antibody according to the above-mentioned (13). (15) A diagnostic agent comprising the antibody according to the above-mentioned (13). (16) A polynucleotide comprising a base sequence complementary or substantially complementary to the base sequence of the polynucleotide according to the above-mentioned (5) or a part of the base sequence. (17) A medicine comprising the polynucleotide according to the above-mentioned (16). (18) A method of screening a compound or its salt that promotes or inhibits the activity of the protein or its salt according to the above-mentioned (1) or the partial peptide or its salt according to the above-mentioned (4), which comprises using the protein or its salt according to the above-mentioned (1) or the partial peptide or its salt according to the above-mentioned (4). (19) The screening method according to the above-mentioned (18), wherein the activity of the protein or its salt according to the above-mentioned (1) or the partial peptide or its salt according to the above-mentioned (4) is the substrate transport activity of the protein. (19a) The screening method according to the above-mentioned (19), wherein the substrate is a steroid hormone or a metabolite thereof or bile acid. (19b) The screening method according to the above-mentioned (19a), wherein the substrate is a steroid hormone or a metabolite thereof. (19c) The screening method according to the above-mentioned (19b), wherein the steroid hormone or a metabolite thereof is estrogen, progestogen, androgen, mineral corticoid or glucocorticoid or a sulfate conjugate or glucuronide conjugate thereof. (19d) The screening method according to the above-mentioned (19b), wherein the steroid hormone or a metabolite is estrogen, androgen or a sulfate conjugate. (19e) The screening method according to the above-mentioned (19a), wherein the substrate is estrogen, dehydroepiandrosterone or a sulfate conjugate thereof. (20) A kit for screening a compound or its salt that promotes or inhibits the activity of the protein or its salt according to the above-mentioned (1) or the partial peptide or its salt according to the above-mentioned (4), which comprises the protein or its salt according to the above-mentioned (1) or the partial peptide or its salt according to the above-mentioned (4). (21) A compound or its salt that promotes or inhibits the activity of the protein or its salt according to the above-mentioned (1) or the partial peptide or its salt according to the above-mentioned (4), which is obtained by using the screening method according to the above-mentioned (18) or the screening kit according to the above-mentioned (19). (22) A medicine comprising the compound or its salt according to the above-mentioned (21). (23) A method of screening a compound or its salt that promotes or inhibits the expression of a gene for the protein according to the above-mentioned (1), which comprises using the polynucleotide according to the above-mentioned (5). (24) A kit for screening a compound or its salt that promotes or inhibits the expression of a gene for the protein according to the above-mentioned (1), which comprises the polynucleotide according to the above-mentioned (5). (25) A compound or its salt that promotes or inhibits the expression of a gene for the protein according to the above-mentioned (1), which is obtained by the screening method according to the above-mentioned (23) or the screening kit according to the above-mentioned (24). (26) A medicine comprising the compound or its salt according to the above-mentioned (25). (27) The medicine according to the above-mentioned (11), (12), (14), (17), (22) or (26), which is a prophylactic/therapeutic agent for hyperlipemia, arteriosclerosis, genital diseases or digestive diseases. (28) A prophylactic/therapeutic method for hyperlipemia, arteriosclerosis, genital diseases or digestive diseases, which comprises administering an effective amount of the compound or its salt according to the above-mentioned (21) or (25) into a mammal. (29) Use of the compound or its salt according to the above-mentioned (21) or (25) in producing a prophylactic/therapeutic agent for hyperlipemia, arteriosclerosis, genital diseases or digestive diseases. (30) A protein or its salt comprising an amino acid sequence identical or substantially identical with an amino acid sequence represented by SEQ ID NO: 18. (31) A protein consisting of an amino acid sequence represented by SEQ ID NO: 18, or a salt thereof. (32) A partial peptide of the protein according to the above-mentioned (30), or a salt thereof. (33) A polynucleotide comprising a polynucleotide encoding the protein according to the above-mentioned (30) or the partial peptide according to the above-mentioned (32). (34) The polynucleotide according to the above-mentioned (33), which is DNA. (35) A DNA consisting of a base sequence represented by SEQ ID NO: 19 or SEQ ID NO: 41. (36) A recombinant vector comprising the polynucleotide according to the above-mentioned (33). (37) A transformant transformed with the recombinant vector according to the above-mentioned (36). (38) A method of manufacturing the protein or its salt according to the above-mentioned (30) or the partial peptide or its salt according to the above-mentioned (32), which comprises culturing the transformant according to the above-mentioned (37), forming and accumulating the protein according to the above-mentioned (30) or the partial peptide according to the above-mentioned (32), and recovering it. (39) A medicine comprising the protein according to the above-mentioned (30) or the partial peptide according to the above-mentioned (32). (40) A medicine comprising the polynucleotide according to the above-mentioned (33). (41) An antibody to the protein according to the above-mentioned (30), the partial peptide according to the above-mentioned (32), or a salt of the protein or partial peptide. (42) A medicine comprising the antibody according to the above-mentioned (41). (43) A diagnostic agent comprising the antibody according to the above-mentioned (41). (44) A polynucleotide comprising a base sequence complementary or substantially complementary to the base sequence of the polynucleotide according to the above-mentioned (33) or a part of the base sequence. (45) A medicine comprising the polynucleotide according to the above-mentioned (44). (46) A method of screening a compound or its salt that promotes or inhibits the activity of the protein or its salt according to the above-mentioned (30) or the partial peptide or its salt according to the above-mentioned (32), which comprises using the protein or its salt according to the above-mentioned (30) or the partial peptide or its salt according to the above-mentioned (32). (47) A kit for screening a compound or its salt that promotes or inhibits the activity of the protein or its salt according to the above-mentioned (30) or the partial peptide or its salt according to the above-mentioned (32), which comprises the protein or its salt according to the above-mentioned (30) or the partial peptide or its salt according to the above-mentioned (32). (48) A compound or its salt that promotes or inhibits the activity of the protein or its salt according to the above-mentioned (30) or the partial peptide or its salt according to the above-mentioned (32), which is obtained by using the screening method according to the above-mentioned (46) or the screening kit according to the above-mentioned (47). (49) A medicine comprising the compound or its salt according to the above-mentioned (48). (50) A method of screening a compound or its salt that promotes or inhibits the expression of a gene for the protein according to the above-mentioned (30), which comprises using the polynucleotide according to the above-mentioned (33). (51) A kit for screening a compound or its salt that promotes or inhibits the expression of a gene for the protein according to the above-mentioned (30), which comprises the polynucleotide according to the above-mentioned (33). (52) A compound or its salt that promotes or inhibits the expression of a gene for the protein according to the above-mentioned (30), which is obtained by the screening method according to the above-mentioned (50) or the screening kit according to the above-mentioned (51). (53) A medicine comprising the compound or its salt according to the above-mentioned (52). (54) The medicine according to the above-mentioned (39), (40), (42), (45), (49) or (53), which is a prophylactic/therapeutic agent for respiratory diseases, renal diseases or digestive diseases. (55) A prophylactic/therapeutic method for respiratory diseases, renal diseases or digestive diseases, which comprises administering an effective amount of the compound or its salt according to the above-mentioned (48) or (52) into a mammal. (56) Use of the compound or its salt according to the above-mentioned (48) or (52) in producing a prophylactic/therapeutic agent for respiratory diseases, renal diseases or digestive diseases. (57) A protein comprising an amino acid sequence identical or substantially identical with an amino acid sequence represented by SEQ ID NO: 42, or its salt. (58) A protein consisting of an amino acid sequence represented by SEQ ID NO: 42, or a salt thereof. (59) A partial peptide of the protein according to the above-mentioned (57), or a salt thereof. (60) A polynucleotide comprising a polynucleotide encoding the protein according to the above-mentioned (57) or the partial peptide according to the above-mentioned (59). (61) The polynucleotide according to the above-mentioned (60), which is DNA. (62) A DNA consisting of a base sequence represented by SEQ ID NO: 43, SEQ ID NO: 60, SEQ ID NO: 61 or SEQ ID NO: 62. (63) A recombinant vector comprising the polynucleotide according to the above-mentioned (60). (64) A transformant transformed with the recombinant vector according to the above-mentioned (63). (65) A method of manufacturing the protein or its salt according to the above-mentioned (57) or the partial peptide or its salt according to the above-mentioned (59), which comprises culturing the transformant according to the above-mentioned (64), forming and accumulating the protein according to the above-mentioned (57) or the partial peptide according to the above-mentioned (59), and recovering it. (66) A medicine comprising the protein according to the above-mentioned (57) or the partial peptide according to the above-mentioned (59). (67) A medicine comprising the polynucleotide according to the above-mentioned (60). (68) An antibody to the protein according to the above-mentioned (57), the partial peptide according to the above-mentioned (59), or a salt of the protein or partial peptide. (69) A medicine comprising the antibody according to the above-mentioned (68). (70) A diagnostic agent comprising the antibody according to the above-mentioned (68). (71) A polynucleotide comprising a base sequence complementary or substantially complementary to the base sequence of the polynucleotide according to the above-mentioned (60) or a part of the base sequence. (72) A medicine comprising the polynucleotide according to the above-mentioned (71). (73) A method of screening a compound or its salt that promotes or inhibits the activity of the protein or its salt according to the above-mentioned (57) or the partial peptide or its salt according to the above-mentioned (59), which comprises using the protein or its salt according to the above-mentioned (57) or the partial peptide or its salt according to the above-mentioned (59). (74) A kit for screening a compound or its salt that promotes or inhibits the activity of the protein or its salt according to the above-mentioned (57) or the partial peptide or its salt according to the above-mentioned (59), which comprises the protein or its salt according to the above-mentioned (57) or the partial peptide or its salt according to the above-mentioned (59). (75) A compound or its salt that promotes or inhibits the activity of the protein or its salt according to the above-mentioned (57) or the partial peptide or its salt according to the above-mentioned (59), which is obtained by using the screening method according to the above-mentioned (73) or the screening kit according to the above-mentioned (74). (76) A medicine comprising the compound or its salt according to the above-mentioned (75). (77) A method of screening a compound or its salt that promotes or inhibits the expression of a gene for the protein according to the above-mentioned (57), which comprises using the polynucleotide according to the above-mentioned (60). (78) A kit for screening a compound or its salt that promotes or inhibits the expression of a gene for the protein according to the above-mentioned (57), which comprises the polynucleotide according to the above-mentioned (60). (79) A compound or its salt that promotes or inhibits the expression of a gene for the protein according to the above-mentioned (57), which is obtained by the screening method according to the above-mentioned (77) or the screening kit according to the above-mentioned (78). (80) A medicine comprising the compound or its salt according to the above-mentioned (79). (81) The medicine according to the above-mentioned (66), (67), (69), (72), (76) or (80), which is a prophylactic/therapeutic agent for pancreatic diseases, central nerve diseases, digestive diseases or respiratory diseases. (82) A prophylactic/therapeutic method for pancreatic diseases, central nerve diseases, digestive diseases or respiratory diseases, which comprises administering an effective amount of the compound or its salt according to the above-mentioned (75) or (79) into a mammal. (83) Use of the compound or its salt according to the above-mentioned (75) or (79) in producing a prophylactic/therapeutic agent for pancreatic diseases, central nerve diseases, digestive diseases or respiratory diseases. (84) A protein or its salt comprising an amino acid sequence identical or substantially identical with an amino acid sequence represented by SEQ ID NO: 66. (85) A protein consisting of an amino acid sequence represented by SEQ ID NO: 66, or a salt thereof. (86) A partial peptide of the protein according to the above-mentioned (84), or a salt thereof. (87) A polynucleotide comprising a polynucleotide encoding the protein according to the above-mentioned (84) or the partial peptide according to the above-mentioned (86). (88) The polynucleotide according to the above-mentioned (87), which is DNA. (89) A DNA consisting of a base sequence represented by SEQ ID NO: 67 or SEQ ID NO: 103. (90) A recombinant vector comprising the polynucleotide according to the above-mentioned (86). (91) A transformant transformed with the recombinant vector according to the above-mentioned (90). (92) A method of manufacturing the protein or its salt according to the above-mentioned (84) or the partial peptide or its salt according to the above-mentioned (86), which comprises culturing the transformant according to the above-mentioned (91), forming and accumulating the protein according to the above-mentioned (84) or the partial peptide according to the above-mentioned (86), and recovering it. (93) A medicine comprising the protein according to the above-mentioned (84) or the partial peptide according to the above-mentioned (86). (94) A medicine comprising the polynucleotide according to the above-mentioned (87). (95) An antibody to the protein according to the above-mentioned (84), the partial peptide according to the above-mentioned (86), or a salt of the protein or partial peptide. (96) A medicine comprising the antibody according to the above-mentioned (95). (97) A diagnostic agent comprising the antibody according to the above-mentioned (95). (98) A polynucleotide comprising a base sequence complementary or substantially complementary to the base sequence of the polynucleotide according to the above-mentioned (87) or a part of the base sequence. (99) A medicine comprising the polynucleotide according to the above-mentioned (98). (100) A method of screening a compound or its salt that promotes or inhibits the activity of the protein or its salt according to the above-mentioned (84) or the partial peptide or its salt according to the above-mentioned (86), which comprises using the protein or its salt according to the above-mentioned (84) or the partial peptide or its salt according to the above-mentioned (86). (101) A kit for screening a compound or its salt that promotes or inhibits the activity of the protein or its salt according to the above-mentioned (84) or the partial peptide or its salt according to the above-mentioned (86), which comprises the protein or its salt according to the above-mentioned (84) or the partial peptide or its salt according to the above-mentioned (86). (102) A compound or its salt that promotes or inhibits the activity of the protein or its salt according to the above-mentioned (84) or the partial peptide or its salt according to the above-mentioned (86), which is obtained by using the screening method according to the above-mentioned (100) or the screening kit according to the above-mentioned (101). (103) A medicine comprising the compound or its salt according to the above-mentioned (102). (104) A method of screening a compound or its salt that promotes or inhibits the expression of a gene for the protein according to the above-mentioned (84), which comprises using the polynucleotide according to the above-mentioned (87). (105) A kit for screening a compound or its salt that promotes or inhibits the expression of a gene for the protein according to the above-mentioned (84), which comprises the polynucleotide according to the above-mentioned (87). (106) A compound or its salt that promotes or inhibits the expression of a gene for the protein according to the above-mentioned (84), which is obtained by the screening method according to the above-mentioned (104) or the screening kit according to the above-mentioned (105). (107) A medicine comprising the compound or its salt according to the above-mentioned (106). (108) A method of determining a ligand to the protein or its salt according to the above-mentioned (84) or the partial peptide or its salt according to the above-mentioned (86), which comprises using the protein or its salt. (109) A method of screening a compound or its salt that alters the binding property between a ligand and the protein or its salt according to the above-mentioned (84) or the partial peptide or its salt according to the above-mentioned (86), which comprises using the protein, the partial peptide or its salt. (110) A kit for screening a compound or its salt that alters the binding property between a ligand and the protein or its salt according to the above-mentioned (84) or the partial peptide or its salt according to the above-mentioned (86), which comprises the protein, the partial peptide or its salt. (111) A compound or its salt that alters the binding property between a ligand and the protein or its salt according to the above-mentioned (84) or the partial peptide or its salt according to the above-mentioned (86), which is obtained by the screening method according to the above-mentioned (109) or the screening kit according to the above-mentioned (110). (112) A medicine comprising the compound or its salt according to the above-mentioned (111). (113) A medicine according to the above-mentioned (93), the above-mentioned (94), the above-mentioned (96), the above-mentioned (99), the above-mentioned (103), the above-mentioned (107) or the above-mentioned (112), which is a prophylactic/therapeutic agent for inflammatory diseases, rheumatoid diseases or diabetic neurosis. (114) A prophylactic/therapeutic method for inflammatory diseases, rheumatoid diseases or diabetic neurosis, which comprises administering an effective amount of the compound or its salt according to the above-mentioned (102), (106) or (111) into a mammal. (115) Use of the compound or its salt according to the above-mentioned (102), (106) or (111) in producing a prophylactic/therapeutic agent for inflammatory diseases, rheumatoid diseases or diabetic neurosis. BRIEF DESCRIPTION OF DRAWINGS FIG. 1 shows comparison in amino acid sequence between human TCH230 and ileum sodium-dependent bile acid transporter (ISBT). In FIG. 1, TCH230 shows an amino acid sequence of human TCH230; ISBT shows an amino acid sequence of ileum sodium-dependent bile acid transporter (ISBT); * shows the position of amino acid substitution (Ile->Val) derived from single nucleotide polymorphisms (SNPs). The symbol represented by opened square shows coincident amino acids between human TCH230 and ISBT. FIG. 2 shows the expression level of human TCH230 gene product in each tissue. The expression level is represented in terms of copy number per μl of cDNA solution. FIG. 3 shows the expression level of human TCH230 gene product in each tissue. The expression level is represented in terms of copy number per μl of cDNA solution. FIG. 4 shows the expression level of human TCH230 gene product in each tissue. The expression level is represented in terms of copy number per μl of cDNA solution. FIG. 5 shows the expression level of human TCH230 gene product in each tissue. The expression level is represented in terms of copy number per μl of cDNA solution. FIG. 6 shows comparisons in amino acid sequence among human TCH234, rat NHE4 and human NHE2. In FIG. 6, TCH23 shows an amino acid sequence of human TCH234; rat NHE4 shows an amino acid sequence of rat NHE4; human NHE2 shows an amino acid sequence of human NHE2; the symbol “A” shows an amyloid-binding site; and TM1 to TM13 show a transmembrane region respectively. The symbol represented by opened square shows coincident amino acids with those in human TCH234. FIG. 7 shows the expression level of human TCH234 gene product in each tissue. The expression level is represented in terms of copy number per μl of cDNA solution. FIG. 8 shows comparisons in amino acid sequence among human TCH212, ATP8A1 and mATP8A2. In FIG. 8, TCH212 shows an amino acid sequence of human TCH212; ATP8A1 shows an amino acid sequence of P-type ATPase 8A1; and mATP8A2 shows an amino acid sequence of mouse P-type ATPase 8A2. The symbol represented by opened square shows amino acids coincident with those in human TCH212. TM1 to 10 show a transmembrane region, respectively (continued to FIG. 9). FIG. 9 shows comparisons in amino acid sequence among human TCH212, ATP8A1 and mATP8A2. In FIG. 9, TCH212 shows an amino acid sequence of human TCH212; ATP8A1 shows an amino acid sequence of P-type ATPase 8A1; and mATP8A2 shows an amino acid sequence of mouse P-type ATPase 8A2. The symbol represented by opened square shows coincident amino acids with those in human TCH212. TM1 to 10 show a transmembrane region, respectively (continued from FIG. 8 to FIG. 10). FIG. 10 shows comparison in amino acid sequence among human TCH212, ATP8A1 and mATP8A2. In FIG. 10, TCH212 shows an amino acid sequence of human TCH212; ATP8A1 shows an amino acid sequence of P-type ATPase 8A1; and mATP8A2 shows an amino acid sequence of mouse P-type ATPase 8A2. The symbol represented by opened square shows coincident amino acids with those in human TCH212. TM1 to 10 show a transmembrane region, respectively (continued from FIG. 9). FIG. 11 shows the expression level of human TCH212 gene product in each tissue. The expression level is represented in terms of copy number per μl of cDNA solution. FIG. 12 shows the expression level of human TCH212 gene product in each tissue. The expression level is represented in terms of copy number per μl of cDNA solution. FIG. 13 shows comparison in amino acid sequence between human TCH200 and human VR1. In FIG. 13, TCH200 shows an amino acid sequence of human TCH200; and hVR1 shows an amino acid sequence of humanVR1. TM1 to 6 show a transmembrane region, respectively. A1 to 3h show Ankyrin repeat sequence. The symbol represented by opened square shows coincident amino acids between two sequences. FIG. 14 shows the expression level of human TCH200 gene product in each tissue. The expression level is represented in terms of copy number per μl of cDNA solution. FIG. 15 shows comparison in amino acid sequence between mouse TCH230 (SEQ ID NO: 112) and human TCH230 (SEQ ID NO: 1). In FIG. 15, hTCH230 shows an amino acid sequence of human TCH230; and mTCH230 shows an amino acid sequence of mouse TCH230. The symbol represented by opened square shows coincident amino acids between two sequences. FIG. 16 shows the expression level of mouse TCH230 gene product in each tissue cDNA. The expression level is represented in terms of copy number per μl of cDNA solution. FIG. 17 shows the expression level of mouse TCH230 gene product in each tissue. The expression level is represented as (copy number of mouse TCH230 per μl of cDNA solution/copy number of rodent GAPDH by equivalent amount of tissue cDNA). FIG. 18 shows the expression level of rat TCH230 gene product in each tissue. The expression level is represented as (copy number of rat TCH230 per μl of cDNA solution/copy number of rodent GAPDH by equivalent amount of tissue cDNA). FIG. 19 shows the result of measurement of incorporation of [6,7-3H(N)]-estrone sulfate into human TCH230-expressing CHO cell strain. The amount of the incorporated compound was expressed as count (cpm) upon incorporation of [6,7-3H(N)]-estrone sulfate for 1 hour. The amount was expressed as the average of the counts in 3 independent wells and standard deviation. In FIG. 19, the cell having vector pcDNA3.1(+) introduced into it is represented as Mock, and human TCH230-expressing CHO cell is expressed as TCH230, and the cells incorporating [6,7-3H(N)]-estrone sulfate with NaCl buffer are represented as Mock/NaCl and TCH230/NaCl respectively, and the cells incorporating [6,7-3H(N)]-estrone sulfate with NMDG buffer are expressed as Mock/NMDG and TCH230/NMDG respectively. FIG. 20 shows the result of measurement of incorporation of [1,2,6,7-3H(N)]-DHEA-S into human TCH230-expressing CHO cell strain. The amount of the incorporated compound was represented as count (cpm) upon incorporation of [1,2,6,7-3H(N)]-DHEA-S for 1 hour. The amount was represented as the average of the counts in 3 independent wells and standard deviation. In FIG. 20, the cell having vector pcDNA3.1(+) introduced into it is represented as Mock, and human TCH230-expressing CHO cell is represented as TCH230, and the cells incorporating [1,2,6,7-3H(N)]-DHEA-S with NaCl buffer are represented as Mock/NaCl and TCH230/NaCl respectively, and the cells incorporating [1,2,6,7-3H(N)]-DHEA-S with NMDG buffer are represented as Mock/NMDG and TCH230/NMDG respectively. FIG. 21 shows the expression level of mouse TCH234 gene product in each tissue. The expression level is represented as (copy number of mouse TCH234 per μl of cDNA solution/copy number of rodent GAPDH by equivalent amount of tissue cDNA). FIG. 22 shows the expression level of rat TCH234 gene product in each tissue. In the figure, the expression level shown on the ordinate is represented as ((copy number of rat TCH234 per μl of cDNA solution)/(copy number of rodent GAPDH by equivalent amount of tissue cDNA)×100,000)). FIG. 23 shows the amount of human TCH234 gene product expressed in each kind of tissue. In the figure, the expression level shown on the ordinate is represented as ((copy number of TCH234 per μl of cDNA solution)/(copy number of GAPDH by equivalent amount of tissue cDNA)×100,000)). FIG. 24 shows the expression level of mouse TCH212 gene product in each tissue. The expression level is represented as (copy number of mouse TCH212 per μl of cDNA solution)/(copy number of rodent GAPDH by equivalent amount of tissue cDNA). FIG. 25 shows the expression level of rat TCH212 gene product in each tissue. The expression level is represented as (copy number of rat TCH212 per μl of cDNA solution)/(copy number of rodent GAPDH by equivalent amount of tissue cDNA). FIG. 26 shows the expression level of mouse TCH200 gene product in each tissue. The expression level is represented as ((copy number of mouse TCH200 per μl of cDNA solution)/(copy number of rodent GAPDH by equivalent amount of tissue cDNA)×100,000)). FIG. 27 shows the expression level of human TCH230 gene product in normal cells. The expression level is represented as (relative expression amount×10,000). FIG. 28 shows the expression level of human TCH234 gene product in normal cells. The expression level is represented as (relative expression amount×10,000). FIG. 29 shows the expression level of human TCH200 gene product in normal cells. The expression level is represented as (relative expression amount×10,000). FIG. 30 shows the expression level of mouse TCH234 gene product in COPD model mouse lung. The expression level is represented as (relative expression amount×100,000,000). The result shows the average and standard error in each group. FIG. 31 shows the expression level of mouse TCH212 gene product in COPD model mouse lung. The expression level is represented as (relative expression amount×100,000,000). The result shows the average and standard error in each group. FIG. 32 shows the expression level of mouse TCH230 gene product in the large intestine of colitis model mouse. The expression level is represented as (relative expression amount×10,000,000). The result shows the average of duplicate measurements by independent TaqMan PCR. FIG. 33 shows the expression level of human TCH212 gene product in each tissue. The expression level is represented as copy number per μl of cDNA solution. BEST MODE FOR CARRYING OUT THE INVENTION A protein comprising the same or substantially the same amino acid sequence as an amino acid sequence represented by SEQ ID NO: 1, 14, 104, 18, 42 or 66 (hereinafter, sometimes referred as to the protein of the present invention) may be any protein derived from any cells (e.g., liver cells, splenocytes, nerve cells, glial cells, β cells of pancreas, bone marrow cells, mesangial cells, Langerhans' cells, epidermic cells, epithelial cells, goblet cells, endothelial cells, smooth muscular cells, fibroblasts, fibrocytes, myocytes, fat cells, immune cells (e.g., macrophage, T cells, B cells, natural killer cells, mast cells, neutrophil, basophil, eosinophil, monocyte), megakaryocyte, synovial cells, chondrocytes, bone cells, osteoblasts, osteoclasts, mammary gland cells, hepatocytes or interstitial cells, the corresponding precursor cells, stem cells, cancer cells, etc.), or any tissues where such cells are present, e.g., brain or any region of the brain (e.g., olfactory bulb, amygdaloid nucleus, basal ganglia, hippocampus, thalamus, hypothalamus, cerebral cortex, medulla oblongata and cerebellum), spinal cord, hypophysis, stomach, pancreas, kidney, liver, gonad, thyroid, gall-bladder, bone marrow, adrenal gland, skin, muscle, lung, gastrointestinal tract (e.g., large intestine and small intestine), blood vessel, heart, thymus, spleen, submandibular gland, peripheral blood, prostate, testis, ovary, placenta, uterus, bone, joint, skeletal muscle, etc. from human and non-human mammals (e.g., guinea pigs, rats, mice, chickens, rabbits, swine, sheep, bovine, monkeys, etc.), or the protein may also be a synthetic protein. Substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1 includes an amino acid sequence having at least about 50% homology, preferably at least about 70% homology, more preferably at least about 80% homology, still more preferably at least about 90% homology, further more preferably at least about 95% homology to the amino acid sequence represented by SEQ ID NO: 1. Preferable examples of the protein comprising substantially the same amino acid sequence as that represented by SEQ ID NO: 1 include a protein comprising substantially the same amino acid sequence as that represented by SEQ ID NO: 1 and having an activity substantially equivalent to that of a protein having the amino acid sequence represented by SEQ ID NO: 1, etc. Substantially the same amino acid sequence as that represented by SEQ ID NO: 14 includes an amino acid sequence having at least about 50% homology, preferably at least about 70% homology, more preferably at least about 80% homology, still more preferably at least about 90% homology, further more preferably at least about 95% homology to the amino acid sequence represented by SEQ ID NO: 14. Preferable examples of the protein comprising substantially the same amino acid sequence as that represented by SEQ ID NO: 14 include a protein comprising substantially the same amino acid sequence as that represented by SEQ ID NO: 14 and having an activity substantially equivalent to a protein having the amino acid sequence represented by SEQ ID NO: 14, etc. Substantially the same amino acid sequence as that represented by SEQ ID NO: 104 includes an amino acid sequence having at least about 75% homology, preferably at least about 80% homology, more preferably at least about 90% homology, still more preferably at least about 95% homology to the amino acid sequence represented by SEQ ID NO: 104. Preferable examples of he protein comprising substantially the same amino acid sequence as that represented by SEQ ID NO: 104 include a protein comprising substantially the same amino acid sequence as that represented by SEQ ID NO: 104 and having an activity substantially equivalent to that of a protein having the amino acid sequence represented by SEQ ID NO: 104, etc. The substantially equivalent activity includes, for example, substrate transport. The substrate includes, for example, steroid hormone, bile acid etc. The steroid hormone includes, for example, estrogen, progestogen, androgen, mineral corticoid, glucocorticoid, steroid chemicals or metabolites thereof (e.g., sulfate conjugates, glucuronide conjugates etc.) etc. The estrogen includes, for example, estrone, estradiol, estriol, estetrol etc. The progestogen includes, for example, progesterone, pregnanediol etc. The androgen includes, for example, dehydroepiandrosterone, testosterone, androstanedione, 5α-dihydrotestosterone, androsterone etc. The mineral corticoid includes, for example, aldosterone etc. The glucocorticoid includes, for example, cortisol, cortisone, corticosterone, dehydrocorticosterone etc. The steroid chemicals include, for example, dexamethasone, betamethasone, prednisolone, triamcinolone, fluorocortisone, clomiphene, tamoxifen, danazol etc. The bile acid includes, for example, taurocholic acid, glicocholic acid, cholic acid, lithocholic acid, deoxycholic acid, taurodeoxycholic acid, tauroursodeoxycholic acid, chenodeoxycholic acid, glicochenodeoxycholic acid, glicodeoxycholic acid etc. The terms “substantially equivalent” mean that the activity is inherently (e.g. physiologically or pharmacologically) equivalent. Therefore, although it is preferred that the above-mentioned substrate transport be equivalent (e.g., about 0.01- to 100-fold, preferably about 0.1- to 10-fold, more preferably about 0.5- to 2-fold), quantitative factors such as a level of the activity, a molecular weight of the protein, etc. may differ. The activities such as substrate transport or the like can be determined according to a publicly known method, for example, by a method described in Am. J. Physiol., 274, G157-169, 1998, or its modified method. Substantially the same amino acid sequence as that represented by SEQ ID NO: 18 includes an amino acid sequence having at least about 90% homology, preferably at least about 95% homology, more preferably at least about 97% homology, much more preferably at least about 99% homology to the amino acid sequence represented by SEQ ID NO: 18. Preferable examples of the protein comprising substantially the same amino acid sequence as that represented by SEQ ID NO: 18 include a protein comprising substantially the same amino acid sequence as that represented by SEQ ID NO: 18 and having an activity substantially equivalent to a protein having the amino acid sequence represented by SEQ ID NO: 18, etc. The substantially equivalent activity includes, for example, a cation (preferably monovalent cation such as Na+, K+, etc.)/H+ exchange transport activity. The terms “substantially equivalent” mean that the activity is inherently (e.g. physiologically or pharmacologically) equivalent. Therefore, although it is preferred that the cation (preferably monovalent cation such as Na+, K+, etc.)/H+ exchange transport activity be equivalent (e.g., about 0.01- to 100-fold, preferably about 0.1- to 10-fold, more preferably about 0.5- to 2-fold), quantitative factors such as a level of the activity, a molecular weight of the protein, etc. may differ. The activities such as the cation (preferably monovalent cation such as Na+, K+, etc.)/H+ exchange transport activity or the like can be determined according to a publicly known method, for example, by a method described in J. Biol. Chem., 274, 3978-3987, 1998, or its modified method. Substantially the same amino acid sequence as that represented by SEQ ID NO: 42 includes an amino acid sequence having at least about 96% homology, preferably at least about 97% homology, more preferably at least about 98% homology, much more preferably at least about 99% homology to the amino acid sequence represented by SEQ ID NO: 42. Preferable examples of the protein comprising substantially the same amino acid sequence as that represented by SEQ ID NO: 42 include a protein comprising substantially the same amino acid sequence as that represented by SEQ ID NO: 42 and having an activity substantially equivalent to that of a protein having the amino acid sequence represented by SEQ ID NO: 42, etc. The substantially equivalent activity includes, for example, transport of aminophospholipid. The terms “substantially equivalent” mean that the activity is inherently (e.g. physiologically or pharmacologically) equivalent. Therefore, although it is preferred that the transport of aminophospholipid be equivalent (e.g., about 0.01- to 100-fold, preferably about 0.1- to 10-fold, more preferably about 0.5- to 2-fold), quantitative factors such as a level of the activity, a molecular weight of the protein, etc. may differ. The activities such as the transport of aminophospholipid or the like can be determined according to a publicly known method, for example, by a method described in J. Biol. Chem., 275, 23378-23386, 1998, or its modified method. Substantially the same amino acid sequence as that represented by SEQ ID NO: 66 includes an amino acid sequence having at least about 45% homology, preferably at least about 50% homology, more preferably at least about 70% homology, still more preferably at least about 80% homology, further more preferably at least about 90% homology, further still more preferably at least about 95% homology to the amino acid sequence represented by SEQ ID NO: 66. Preferable examples of the protein comprising substantially the same amino acid sequence as that represented by SEQ ID NO: 66 include a protein comprising substantially the same amino acid sequence as that represented by SEQ ID NO: 66 and having an activity substantially equivalent to that of a protein having the amino acid sequence represented by SEQ ID NO: 66, etc. The substantially equivalent activity includes, for example, a cation (e.g., Ca+2 etc.) channel activity. The terms “substantially equivalent” mean that the activity is inherently (e.g. physiologically or pharmacologically) equivalent. Therefore, although it is preferred that the cation channel activity be equivalent (e.g., about 0.01- to 100-fold, preferably about 0.1- to 10-fold, more preferably about 0.5- to 2-fold), quantitative factors such as a level of the activity, a molecular weight of the protein, etc. may differ. The activities such as the cation channel activity or the like can be determined according to a publicly known method, for example, by a method described in Nature, 389, 816, 1997, or its modified method. The protein of the present invention includes, for example, (1) (i) amino acid sequences represented by SEQ ID NO: 1, SEQ ID NO: 14 or SEQ ID NO: 104, wherein at least 1 or 2 amino acids (for example approximately 1 to 200 amino acids, preferably approximately 1 to 150 amino acids, more preferably approximately 1 to 100 amino acids, still more preferably approximately 1 to 50 amino acids, further more preferably approximately 1 to 30 amino acids, further still more preferably approximately 1 to 10, and most preferably several (1 to 5) amino acids) are deleted, (ii) amino acid sequences represented by SEQ ID NO: 1, SEQ ID NO: 14 or SEQ ID NO: 104, to which at least 1 or 2 amino acids (for example approximately 1 to 200 amino acids, preferably approximately 1 to 150 amino acids, more preferably approximately 1 to 100 amino acids, still more preferably approximately 1 to 50 amino acids, further more preferably approximately 1 to 30 amino acids, further still more preferably approximately 1 to 10, and most preferably several (1 to 5) amino acids) are added, (iii) amino acid sequences represented by SEQ ID NO: 1, SEQ ID NO: 14 or SEQ ID NO: 104, into which at least 1 or 2 amino acids (for example approximately 1 to 200 amino acids, preferably approximately 1 to 150 amino acids, more preferably approximately 1 to 100 amino acids, still more preferably approximately 1 to 50 amino acids, further more preferably approximately 1 to 30 amino acids, further still more preferably approximately 1 to 10, and most preferably several (1 to 5) amino acids) are inserted, (iv) amino acid sequences represented by SEQ ID NO: 1, SEQ ID NO: 14 or SEQ ID NO: 104, wherein at least 1 or 2 amino acids (for example approximately 1 to 200 amino acids, preferably approximately 1 to 150 amino acids, more preferably approximately 1 to 100 amino acids, still more preferably approximately 1 to 50 amino acids, further more preferably approximately 1 to 30 amino acids, further still more preferably approximately 1 to 10, and most preferably several (1 to 5) amino acids) are substituted by other amino acids or (v) muteins comprising a combination of the amino acid sequences described in the above, (2) (i) an amino acid sequence represented by SEQ ID NO: 18, from which at least 1 or 2 amino acids (for example approximately 1 to 90 amino acids, preferably approximately 1 to 50 amino acids, more preferably approximately 1 to 30 amino acids, still more preferably approximately 1 to 10 amino acids, further more preferably several (1 to 5) amino acids) are deleted, (ii) an amino acid sequence represented by SEQ ID NO: 18, to which at least 1 or 2 amino acids (for example approximately 1 to 200 amino acids, preferably approximately 1 to 150 amino acids, more preferably approximately 1 to 100 amino acids, still more preferably approximately 1 to 50 amino acids, further more preferably approximately 1 to 30 amino acids, further still more preferably 1 to 10 amino acids and most preferably several (1 to 5) amino acids) are added, (iii) an amino acid sequence represented by SEQ ID NO: 18, into which at least 1 or 2 amino acids (for example approximately 1 to 200 amino acids, preferably approximately 1 to 150 amino acids, more preferably approximately 1 to 100 amino acids, still more preferably approximately 1 to 50 amino acids, further more preferably approximately 1 to 30 amino acids, further still more preferably 1 to 10 amino acids and most preferably several (1 to 5) amino acids) are inserted, (iv) an amino acid sequence represented by SEQ ID NO: 18, wherein at least 1 or 2 amino acids (for example approximately 1 to 200 amino acids, preferably approximately 1 to 150 amino acids, more preferably approximately 1 to 100 amino acids, still more preferably approximately 1 to 50 amino acids, further more preferably approximately 1 to 30 amino acids, further still more preferably 1 to 10 amino acids and most preferably several (1 to 5) amino acids) are substituted by other amino acids or (v) muteins comprising a combination of the amino acid sequences described in the above, (3) (i) an amino acid sequence represented by SEQ ID NO: 42, from which at least 1 or 2 amino acids (for example approximately 1 to 50 amino acids, preferably approximately 1 to 30 amino acids, more preferably approximately 1 to 10 amino acids, and most preferably several (1 to 5) amino acids) are deleted, (ii) an amino acid sequence represented by SEQ ID NO: 42, to which at least 1 or 2 amino acids (for example approximately 1 to 200 amino acids, preferably approximately 1 to 150 amino acids, more preferably approximately 1 to 100 amino acids, still more preferably approximately 1 to 50 amino acids, further more preferably approximately 1 to 30 amino acids, further still more preferably 1 to 10 amino acids and most preferably several (1 to 5) amino acids) are added, (iii) an amino acid sequence represented by SEQ ID NO: 42, into which at least 1 or 2 amino acids (for example approximately 1 to 200 amino acids, preferably approximately 1 to 150 amino acids, more preferably approximately 1 to 100 amino acids, still more preferably approximately 1 to 50 amino acids, further more preferably approximately 1 to 30 amino acids, further still more preferably 1 to 10 amino acids and most preferably several (1 to 5) amino acids) are inserted, (iv) an amino acid sequence represented by SEQ ID NO: 42, wherein at least 1 or 2 amino acids (for example approximately 1 to 200 amino acids, preferably approximately 1 to 150 amino acids, more preferably approximately 1 to 100 amino acids, still more preferably approximately 1 to 50 amino acids, further more preferably approximately 1 to 30 amino acids, further still more preferably 1 to 10 amino acids and most preferably several (1 to 5) amino acids) are substituted by other amino acids or (v) muteins comprising a combination of the amino acid sequences described in the above, and (4) (i) an amino acid sequence represented by SEQ ID NO: 66, from which at least 1 or 2 amino acids (for example approximately 1 to 200 amino acids, preferably approximately 1 to 150 amino acids, more preferably approximately 1 to 100 amino acids, still more preferably approximately 1 to 50 amino acids, further more preferably approximately 1 to 30 amino acids, further still more preferably 1 to 10 amino acids and most preferably several (1 to 5) amino acids) are deleted, (ii) an amino acid sequence represented by SEQ ID NO: 66, to which at least 1 or 2 amino acids (for example approximately 1 to 200 amino acids, preferably approximately 1 to 150 amino acids, more preferably approximately 1 to 100 amino acids, still more preferably approximately 1 to 50 amino acids, further more preferably approximately 1 to 30 amino acids, further still more preferably 1 to 10 amino acids and most preferably several (1 to 5) amino acids) are added, (iii) an amino acid sequence represented by SEQ ID NO: 66, into which at least 1 or 2 amino acids (for example approximately 1 to 200 amino acids, preferably approximately 1 to 150 amino acids, more preferably approximately 1 to 100 amino acids, still more preferably approximately 1 to 50 amino acids, further more preferably approximately 1 to 30 amino acids, further still more preferably 1 to 10 amino acids and most preferably several (1 to 5) amino acids) are inserted, (iv) an amino acid sequence represented by SEQ ID NO: 66, wherein at least 1 or 2 amino acids (for example approximately 1 to 200 amino acids, preferably approximately 1 to 150 amino acids, more preferably approximately 1 to 100 amino acids, still more preferably approximately 1 to 50 amino acids, further more preferably approximately 1 to 30 amino acids, further still more preferably 1 to 10 amino acids and most preferably several (1 to 5) amino acids) are substituted by other amino acids or (v) muteins comprising a combination of the amino acid sequences described in the above. When the amino acid sequence has undergone insertion, deletion or substitution as described above, the position of the insertion, deletion or substitution is not particularly limited. The proteins in the present specification are represented in accordance with the conventional way of describing peptides, that is, the N-terminus (amino terminus) at the left hand and the C-terminus (carboxyl terminus) at the right hand. In the proteins of the present invention including the protein comprising the amino acid sequence represented by SEQ ID NO: 1, the C-terminus is usually in the form of a carboxyl group (—COOH) or a carboxylate (—COO−) but may be in the form of an amide (—CONH2) or an ester (—COOR). Examples of the ester group shown by R include a C1-6 alkyl group such as methyl, ethyl, n-propyl, isopropyl, n-butyl, etc.; a C3-8 cycloalkyl group such as cyclopentyl, cyclohexyl, etc.; a C6-12 aryl group such as phenyl, α-naphthyl, etc.; a C7-14 aralkyl group such as a phenyl-C1-2-alkyl group, e.g., benzyl, phenethyl, etc., or an α-naphthyl-C1-2-alkyl group such as α-naphthylmethyl, etc.; and a pivaloyloxymethyl group or the like. Where the protein of the present invention has a carboxyl group (or a carboxylate) at a position other than the C-terminus, it may be amidated or esterified and such an amide or ester is also included within the protein of the present invention. As the ester group herein, the same esters as those described with respect to the above C-terminal are used. Furthermore, examples of the protein of the present invention include variants of the above proteins, wherein the N-terminal amino group residue (e.g. methionine residue) of the protein supra is protected with a protecting group (for example, a C1-6 acyl group such as a C1-6 alkanoyl group, e.g., formyl group, acetyl group, etc.); those wherein the N-terminal region is cleaved in vivo and the glutamyl group thus formed is pyroglutaminated; those wherein a substituent (e.g., —OH, —SH, amino group, imidazole group, indole group, guanidino group, etc.) on the side chain of an amino acid in the molecule is protected with a suitable protecting group (e.g., a C1-6 acyl group such as a C2-6 alkanoyl group, e.g., formyl group, acetyl group, etc.), or conjugated proteins such as glycoproteins having sugar chains bound thereto. Specific examples of the protein of the present invention include proteins comprising amino acid sequences represented by SEQ ID NO: 1, SEQ ID NO: 14, SEQ ID NO: 104, SEQ ID NO: 18, SEQ ID NO: 42 or SEQ ID NO: 66. Partial peptides of the protein of the present invention may be any peptides insofar as they are partial peptides of the protein of the present invention and preferably have properties identical with those of the protein of the present invention. For example, peptides having at least 5, preferably at least 10, more preferably at least 20, still more preferably at least 50, further more preferably at least 70, further still more preferably at least 100 and most preferably at least 200 amino acids in the amino acid sequence which constitutes the protein of the present invention are used. The partial peptide of the present invention may contain an amino acid sequence, wherein at least 1 or 2 amino acids (for example approximately 1 to 20 amino acids, preferably approximately 1 to 10 amino acids, more preferably several (1 to 5) amino acids) are deleted, to which at least 1 or 2 amino acids (for example approximately 1 to 20 amino acids, preferably approximately 1 to 10 amino acids, more preferably several (1 to 5) amino acids) are added, into which at least 1 or 2 amino acids (for example approximately 1 to 20 amino acids, preferably approximately 1 to 10 amino acids, more preferably approximately several (1 to 5) amino acids) are inserted, or in which at least 1 or 2 amino acids (for example approximately 1 to 20 amino acids, preferably approximately 1 to 10 amino acids, more preferably approximately several (1 to 5) amino acids) are substituted by other amino acids. The partial peptide of the present invention includes, for example, a peptide having an amino acid sequence in e.g. positions 1 to 28, 99 to 129, 180 to 193 or 246 to 286 in the amino acid sequence represented by SEQ ID NO: 1 or SEQ ID NO: 14, a peptide having an amino acid sequence in e.g. positions 40 to 60 or 330 to 350 in the amino acid sequence represented by SEQ ID NO: 18, a peptide having an amino acid sequence in e.g. positions 301 to 322, 941 to 952 or 1012 to 1028 in the amino acid sequence represented by SEQ ID NO: 42, a peptide having an amino acid sequence in e.g. positions 460 to 485 or 610 to 630 in the amino acid sequence represented by SEQ ID NO: 66, and a peptide having an amino acid sequence in e.g. positions 1 to 28, 99 to 129, 180 to 193 or 245 to 285 in the amino acid sequence represented by SEQ ID NO: 104. In the partial peptide of the present invention, the C-terminus is usually in the form of a carboxyl group (—COOH) or a carboxylate (—COO−) but may be in the form of an amide (—CONH2) or an ester (—COOR) as described above with respect to the protein of the present invention. Like the protein of the present invention, the partial peptide of the present invention includes those having a carboxyl group (or a carboxylate) at a position other than the C-terminus, those wherein an amino group of the N-terminal amino acid residue (e.g., methionine residue) is protected with a protecting group, those wherein the N-terminal region is cleaved in vivo and a glutamine reissue thus formed is pyroglutaminated, those wherein a substituent on the side chain of an amino acid in the molecule is protected with a suitable protecting group, or conjugated proteins such as glycoproteins having sugar chains bound thereto. The partial peptide of the present invention can also be used as an antigen for preparing an antibody. For the purpose of preparing the antibody of the present invention, mention can be made of, for example, a peptide having an amino acid sequence in e.g. positions 1 to 28, 99 to 129, 180 to 193 or 246 to 286 in the amino acid sequence represented by SEQ ID NO: 1 or SEQ ID NO: 14, a peptide having an amino acid sequence in e.g. positions 40 to 60 or 330 to 350 in the amino acid sequence represented by SEQ ID NO: 18, a peptide having an amino acid sequence in e.g. positions 301 to 322, 941 to 952 or 1012 to 1028 in the amino acid sequence represented by SEQ ID NO: 42, a peptide having an amino acid sequence in e.g. positions 460 to 485 or 610 to 630 in the amino acid sequence represented by SEQ ID NO: 66, and a peptide having an amino acid sequence in e.g. positions 1 to 28, 99 to 129, 180 to 193 or 245 to 285 in the amino acid sequence represented by SEQ ID NO: 104. As salts of the protein or partial peptide of the present invention, use is made of salts with physiologically acceptable acids (e.g., inorganic acids or organic acids) or bases (e.g., alkali metal salts), preferably physiologically acceptable acid addition salts. Examples of such salts are salts with inorganic acids (e.g., hydrochloric acid, phosphoric acid, hydrobromic acid, sulfuric acid), salts with organic acids (e.g., acetic acid, formic acid, propionic acid, fumaric acid, maleic acid, succinic acid, tartaric acid, citric acid, malic acid, oxalic acid, benzoic acid, methanesulfonic acid, benzenesulfonic acid) and the like. The protein or partial peptide of the present invention or salts thereof may be manufactured from the human and other warm-blooded animal cells or tissues described above by a publicly known protein purification method, or by culturing a transformant that comprises the DNA encoding the protein of the present invention. Furthermore, the protein or partial peptide or salts thereof may also be manufactured by the peptide synthesis method, which will be described below. Where the protein or its salts are manufactured from human and other mammalian tissues or cells, human or other mammalian tissues or cells are homogenized, then extracted with an acid or the like, and the extract is isolated and purified by a combination of chromatography techniques such as reverse phase chromatography, ion exchange chromatography, and the like. To synthesize the protein of the present invention, its partial peptide, or salts or amides thereof according to the present invention, commercially available resins that are used for protein synthesis may be used. Examples of such resins include chloromethyl resin, hydroxymethyl resin, benzhydrylamine resin, aminomethyl resin, 4-benzyloxybenzyl alcohol resin, 4-methylbenzhydrylamine resin, PAM resin, 4-hydroxymethylmethylphenyl acetamidomethyl resin, polyacrylamide resin, 4-(2′,4′-dimethoxyphenylhydroxymethyl)phenoxy resin, 4-(2′,4′-dimethoxyphenyl-Fmoc-aminoethyl)phenoxy resin, etc. Using these resins, amino acids in which α-amino groups and functional groups on the side chains are appropriately protected are condensed on the resin in the order of the sequence of the objective protein according to various condensation methods publicly known in the art. At the end of the reaction, the protein is excised from the resin and at the same time, the protecting groups are removed. Then, intramolecular disulfide bond-forming reaction is performed in a highly diluted solution to obtain the objective protein or the partial petide, or amides thereof. For condensation of the protected amino acids described above, a variety of activation reagents for protein synthesis may be used, and carbodiimides are particularly preferable. Examples of such carbodiimides include DCC, N,N′-diisopropylcarbodiimide, N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide, etc. For activation by these reagents, the protected amino acids in combination with a racemization inhibitor (e.g., HOBt, HOOBt) are added directly to the resin, or the protected amino acids are previously activated in the form of symmetric acid anhydrides, HOBt esters or HOOBt esters, followed by adding the thus activated protected amino acids to the resin. Solvents suitable for use to activate the protected amino acids or condense with the resin may be appropriately chosen from solvents known to be usable for protein condensation reactions. Examples of such solvents are acid amides such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, etc.; halogenated hydrocarbons such as methylene chloride, chloroform, etc.; alcohols such as trifluoroethanol, etc.; sulfoxides such as dimethylsulfoxide, etc.; ethers such as pyridine, dioxane, tetrahydrofuran, etc.; nitriles such as acetonitrile, propionitrile, etc.; esters such as methyl acetate, ethyl acetate, etc.; and appropriate mixtures of these solvents. The reaction temperature is appropriately chosen from the range known to be applicable to protein binding reactions and is usually selected in the range of approximately −20° C. to 50° C. The activated amino acid derivatives are used generally in an excess of 1.5 to 4 times. The condensation is examined by a test using the ninhydrin reaction; when the condensation is insufficient, the condensation can be completed by repeating the condensation reaction without removal of the protecting groups. When the condensation is yet insufficient even after repeating the reaction, unreacted amino acids are acetylated with acetic anhydride or acetylimidazole to cancel any possible adverse effect on the subsequent reaction. Examples of the protecting groups used to protect the amino groups of the starting materials include Z, Boc, t-pentyloxycarbonyl, isobornyloxycarbonyl, 4-methoxybenzyloxycarbonyl, Cl-Z, Br-Z, adamantyloxycarbonyl, trifluoroacetyl, phthaloyl, formyl, 2-nitrophenylsulphenyl, diphenylphosphinothioyl, Fmoc, etc. A carboxyl group can be protected by, e.g., alkyl esterification (in the form of linear, branched or cyclic alkyl esters of the alkyl moiety such as methyl, ethyl, propyl, butyl, t-butyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 2-adamantyl, etc.), aralkyl esterification (e.g., esterification in the form of benzyl ester, 4-nitrobenzyl ester, 4-methoxybenzyl ester, 4-chlorobenzyl ester, benzhydryl ester, etc.), phenacyl esterification, benzyloxycarbonyl hydrazidation, t-butoxycarbonyl hydrazidation, trityl hydrazidation, or the like. The hydroxyl group of serine can be protected through, for example, its esterification or etherification. Examples of groups appropriately used for the esterification include a lower (C1-6) alkanoyl group, such as acetyl group, an aroyl group such as benzoyl group, and a group derived from carbonic acid such as benzyloxycarbonyl group, ethoxycarbonyl group, etc. Examples of a group appropriately used for the etherification include benzyl group, tetrahydropyranyl group, t-butyl group, etc. Examples of groups for protecting the phenolic hydroxyl group of tyrosine include Bzl, Cl2-Bzl, 2-nitrobenzyl, Br-Z, t-butyl, etc. Examples of groups used to protect the imidazole moiety of histidine include Tos, 4-methoxy-2,3,6-trimethylbenzenesulfonyl, DNP, benzyloxymethyl, Bum, Boc, Trt, Fmoc, etc. Examples of the activated carboxyl groups in the starting materials include the corresponding acid anhydrides, azides, activated esters (esters with alcohols (e.g., pentachlorophenol, 2,4,5-trichlorophenol, 2,4-dinitrophenol, cyanomethyl alcohol, p-nitrophenol, HONB, N-hydroxysuccimide, N-hydroxyphthalimide, HOBt)). As the activated amino acids in which the amino groups are activated in the starting material, the corresponding phosphoric amides are employed. To eliminate (split off) the protecting groups, there are used catalytic reduction under hydrogen gas flow in the presence of a catalyst such as Pd-black or Pd-carbon; an acid treatment with anhydrous hydrogen fluoride, methanesulfonic acid, trifluoromethane-sulfonic acid or trifluoroacetic acid, or a mixture solution of these acids; a treatment with a base such as diisopropylethylamine, triethylamine, piperidine or piperazine; and reduction with sodium in liquid ammonia. The elimination of the protecting group by the acid treatment described above is carried out generally at a temperature of approximately −20° C. to 40° C. In the acid treatment, it is efficient to add a cation scavenger such as anisole, phenol, thioanisole, m-cresol, p-cresol, dimethylsulfide, 1,4-butanedithiol or 1,2-ethanedithiol, which is activated by ligand. Furthermore, 2,4-dinitrophenyl group known as the protecting group for the imidazole of histidine is removed by a treatment with thiophenol. Formyl group used as the protecting group of the indole of tryptophan is eliminated by the aforesaid acid treatment in the presence of 1,2-ethanedithiol or 1,4-butanedithiol, as well as by a treatment with an alkali such as a dilute sodium hydroxide solution and dilute ammonia. Protection of functional groups that should not be involved in the reaction of the starting materials, protecting groups, elimination of the protecting groups and activation of functional groups involved in the reaction may be appropriately selected from publicly known groups and publicly known means. In another method for obtaining the amides of the protein or partial peptide, for example, the α-carboxyl group of the carboxy terminal amino acid is first protected by amidation, and the peptide (protein) chain is then extended from the amino group side to a desired length. Thereafter, a protein or partial peptide in which only the protecting group of the N-terminal α-amino group in the peptide chain has been eliminated from the protein and a protein or partial peptide in which only the protecting group of the C-terminal carboxyl group has been eliminated are prepared. The two proteins or peptides are condensed in a mixture of the solvents described above. The details of the condensation reaction are the same as described above. After the protected protein or peptide obtained by the condensation is purified, all the protecting groups are eliminated by the method described above to give the desired crude protein or peptide. This crude protein or peptide is purified by various known purification means. Lyophilization of the major fraction gives the amide of the desired protein or peptide. To prepare the esterified protein or peptide, for example, the α-carboxyl group of the carboxy terminal amino acid is condensed with a desired alcohol to prepare the amino acid ester, which is followed by procedure similar to the preparation of the amidated protein or peptide above to give the ester form of the desired protein or peptide. The partial peptide of the present invention or its salts can be manufactured by publicly known methods for peptide synthesis, or by cleaving the protein of the present invention with an appropriate peptidase. For the methods for peptide synthesis, for example, either solid phase synthesis or liquid phase synthesis may be used. That is, the partial peptide or amino acids that can construct the partial peptide of the present invention are condensed with the remaining part. Where the product contains protecting groups, these protecting groups are removed to give the desired peptide. Publicly known methods for condensation and elimination of the protecting groups are described in (a) to (e) below. (a) M. Bodanszky & M. A. Ondetti: Peptide Synthesis, Interscience Publishers, New York (1966) (b) Schroeder & Luebke: The Peptide, Academic Press, New York (1965) (c) Nobuo Izumiya, et al.: Peptide Gosei-no-Kiso to Jikken (Basics and experiments of peptide synthesis), published by Maruzen Co. (1975) (d) Haruaki Yajima & Shunpei Sakakibara: Seikagaku Jikken Koza (Biochemical Experiment) 1, Tanpakushitsu no Kagaku (Chemistry of Proteins) IV, 205 (1977) (e) Haruaki Yajima, ed.: Zoku Iyakuhin no Kaihatsu (A sequel to Development of Pharmaceuticals), Vol. 14, Peptide Synthesis, published by Hirokawa Shoten After completion of the reaction, the product may be purified and isolated by a combination of conventional purification methods such as solvent extraction, distillation, column chromatography, liquid chromatography and recrystallization to give the partial peptide of the present invention. When the partial peptide obtained by the above methods is in a free form, the peptide can be converted into an appropriate salt form by a publicly known method; when the partial peptide is obtained in a salt form, it can be converted into a free form by a publicly known method. The polynucleotide encoding the protein of the present invention may be any polynucleotide so long as it comprises the base sequence encoding the protein of the present invention described above. The polynucleotide is preferably DNA. The DNA may also be any of genomic DNA, genomic cDNA library, cDNA derived from the cells or tissues described above, cDNA library derived from the cells or tissues described above, and synthetic DNA. The vector to be used for the library may be any of bacteriophage, plasmid, cosmid, phagemid and the like. In addition, the DNA can be amplified by reverse transcriptase polymerase chain reaction (hereinafter abbreviated as RT-PCR) with total RNA or mRNA fraction prepared from the above-described cells or tissues. The DNA encoding the protein of the present invention may be for example (1) DNA comprising the base sequence represented by SEQ ID NO: 2 or SEQ ID NO: 11, or DNA hybridizing under high stringent conditions with the base sequence represented by SEQ ID NO: 2 or SEQ ID NO: 11 and encoding a protein having properties substantially equivalent to those of a protein comprising the amino acid sequence represented by SEQ ID NO: 1, (2) DNA comprising the base sequence represented by SEQ ID NO: 13 or SEQ ID NO: 12, or DNA hybridizing under high stringent conditions with the base sequence represented by SEQ ID NO: 13 or SEQ ID NO: 12 and encoding a protein having properties substantially equivalent to those of a protein comprising the amino acid sequence represented by SEQ ID NO: 14, (3) DNA comprising the base sequence represented by SEQ ID NO: 105 or SEQ ID NO: 112, or DNA hybridizing under high stringent conditions with the base sequence represented by SEQ ID NO: 105 or SEQ ID NO: 112 and encoding a protein having properties substantially equivalent to those of a protein comprising the amino acid sequence represented by SEQ ID NO: 104, (4) DNA comprising the base sequence represented by SEQ ID NO: 19 or SEQ ID NO: 41, or DNA hybridizing under high stringent conditions with the base sequence represented by SEQ ID NO: 19 or SEQ ID NO: 41 and encoding a protein having properties substantially equivalent to those of a protein comprising the amino acid sequence represented by SEQ ID NO: 18, (5) DNA comprising the base sequence represented by SEQ ID NO: 43, SEQ ID NO: 60, SEQ ID NO: 61 or SEQ ID NO: 62, or DNA hybridizing under high stringent conditions with the base sequence represented by SEQ ID NO: 43, SEQ ID NO: 60, SEQ ID NO: 61 or SEQ ID NO: 62 and encoding a protein having properties substantially equivalent to those of a protein comprising the amino acid sequence represented by SEQ ID NO: 42, or (6) DNA comprising the base sequence represented by SEQ ID NO: 67 or SEQ ID NO: 103, or DNA hybridizing under high stringent conditions with the base sequence represented by SEQ ID NO: 67 or SEQ ID NO: 103 and encoding a protein having properties substantially equivalent to those of a protein comprising the amino acid sequence represented by SEQ ID NO: 66. As the DNA hybridizing under high stringent conditions with the base sequence represented by SEQ ID NO: 2 or SEQ ID NO: 11, there may be employed e.g. DNA comprising a base sequence having at least about 50% homology, preferably at least about 60% homology, more preferably at least about 70% homology, still more preferably at least about 80% homology, further more preferably at least about 90% homology to the base sequence represented by SEQ ID NO: 2 or SEQ ID NO: 11. As the DNA hybridizing under high stringent conditions with the base sequence represented by SEQ ID NO: 13 or SEQ ID NO: 12, there may be employed e.g. DNA comprising a base sequence having at least about 50% homology, preferably at least about 60% homology, more preferably at least about 70% homology, still more preferably at least about 80% homology, further more preferably at least about 90% homology to the base sequence represented by SEQ ID NO: 13 or SEQ ID NO: 12. As the DNA hybridizing under high stringent conditions with the base sequence represented by SEQ ID NO: 105 or SEQ ID NO: 112, there may be employed e.g. DNA comprising a base sequence having at least about 75% homology, preferably at least about 80% homology, more preferably at least about 90% homology, still more preferably at least about 95% homology to the base sequence represented by SEQ ID NO: 105 or SEQ ID NO: 112. As the DNA hybridizing under high stringent conditions with the base sequence represented by SEQ ID NO: 19 or SEQ ID NO: 41, there may be employed e.g. DNA comprising a base sequence having at least about 90% homology, preferably at least about 95% homology, more preferably at least about 97% homology, still more preferably at least about 99% homology to the base sequence represented by SEQ ID NO: 19 or SEQ ID NO: 41. As the DNA hybridizing under high stringent conditions with the base sequence represented by SEQ ID NO: 43, SEQ ID NO: 60, SEQ ID NO: 61 or SEQ ID NO: 62, there may be employed e.g. DNA comprising a base sequence having at least about 96% homology, preferably at least about 97% homology, more preferably at least about 98% homology, still more preferably at least about 99% homology to the base sequence represented by SEQ ID NO: 43, SEQ ID NO: 60, SEQ ID NO: 61 or SEQ ID NO: 62. As the DNA hybridizing under high stringent conditions with the base sequence represented by SEQ ID NO: 67 or SEQ ID NO: 103, there may be employed e.g. DNA comprising a base sequence having at least about 45% homology, preferably at least about 50% homology, more preferably at least about 70% homology, still more preferably at least about 80% homology, further more preferably at least about 90% homology still further more preferably at least about 95% homology to the base sequence represented by SEQ ID NO: 67 or SEQ ID NO: 103. The hybridization can be carried out by publicly known methods or by modifications of these methods, for example, according to the method described in Molecular Cloning, 2nd (J. Sambrook et al., Cold Spring Harbor Lab. Press, 1989). A commercially available library may also be used according to the instructions of the attached manufacturer's protocol. Preferably, the hybridization can be carried out under highly stringent conditions. The highly stringent conditions used herein are, for example, those in a sodium concentration at about 19 mM to about 40 mM, preferably about 19 mM to about 20 mM at a temperature of about 50° C. to about 70° C., preferably about 60° C. to about 65° C. In particular, hybridization conditions in a sodium concentration of about 19 mM at a temperature of about 65° C. are most preferred. More specifically, as the DNA encoding a protein comprising the amino acid sequence represented by SEQ ID NO: 1, there may be employed, e.g. DNA comprising the base sequence represented by SEQ ID NO: 2 or SEQ ID NO: 11; as the DNA encoding a protein comprising the amino acid sequence represented by SEQ ID NO: 14, there may be employed, e.g. DNA comprising the base sequence represented by SEQ ID NO: 13 or SEQ ID NO: 12; as the DNA encoding a protein comprising the amino acid sequence represented by SEQ ID NO: 104, there may be employed, e.g. DNA comprising the base sequence represented by SEQ ID NO: 105 or SEQ ID NO: 112; as the DNA encoding a protein comprising the amino acid sequence represented by SEQ ID NO: 18, there may be employed, e.g. DNA comprising the base sequence represented by SEQ ID NO: 19 or SEQ ID NO: 41; as the DNA encoding a protein comprising the amino acid sequence represented by SEQ ID NO: 42, there may be employed, e.g. DNA comprising the base sequence represented by SEQ ID NO: 43, SEQ ID NO: 60, SEQ ID NO: 61 or SEQ ID NO: 62; and as the DNA encoding a protein comprising the amino acid sequence represented by SEQ ID NO: 66, there may be employed, e.g. DNA comprising the base sequence represented by SEQ ID NO: 67 or SEQ ID NO: 103. The polynucleotide encoding the partial peptide of the present invention may be any polynucleotide so long as it comprises a base sequence encoding the partial peptide of the present invention described above. The polynucleotide is preferably DNA. The DNA may also be any of genomic DNA, genomic DNA library, cDNA derived from the cells and tissues described above, cDNA library derived from the cells and tissues described above and synthetic DNA. As the DNA encoding the partial peptide of the present invention, there may be employed, for example, DNA having a part of DNA having the base sequence represented by SEQ ID NO: 2, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 19, SEQ ID NO: 41, SEQ ID NO: 43, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 67, SEQ ID NO: 103, SEQ ID NO: 105 or SEQ ID NO: 112, or DNA comprising a base sequence hybridizing under stringent conditions with the base sequence represented by SEQ ID NO: 2, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 19, SEQ ID NO: 41, SEQ ID NO: 43, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 67, SEQ ID NO: 103, SEQ ID NO: 105 or SEQ ID NO: 112 and comprising a part of DNA encoding a protein having an activity substantially equivalent to that of the protein of the present invention. The DNA hybridizable with the base sequence represented by SEQ ID NO: 2, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 19, SEQ ID NO: 41, SEQ ID NO: 43, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 67, SEQ ID NO: 103, SEQ ID NO: 105 or SEQ ID NO: 112 has the same meaning as described above. As the hybridization method and high stringent conditions, those described above are used. For cloning of the DNA that completely encodes the protein of the present invention or its partial peptide (hereinafter sometimes merely referred to as the protein of the present invention), the DNA may be amplified by PCR using synthetic DNA primers comprising a part of the base sequence encoding the protein of the present invention, or the DNA inserted into an appropriate vector can be selected by hybridization with a labeled DNA fragment or synthetic DNA that encodes a part or entire region of the protein of the present invention. The hybridization can be carried out, for example, according to the method described in Molecular Cloning, 2nd, J. Sambrook et al., Cold Spring Harbor Lab. Press, 1989. The hybridization may also be performed using commercially available library in accordance with the protocol described in the attached instructions. Conversion of the base sequence of the DNA can be effected by publicly known methods such as the ODA-LA PCR method, the gapped duplex method or the Kunkel method or its modification using a publicly known kit available as Mutan™-G or Mutan™-K (both manufactured by Takara Shuzo Co., Ltd.). The cloned DNA encoding the protein can be used as it is, depending upon purpose or if desired after digestion with a restriction enzyme or after addition of a linker thereto. The DNA may have ATG as a translation initiation codon at the 5′ end thereof and may further have TAA, TGA or TAG as a translation termination codon at the 3′ end thereof. These translation initiation and termination codons may also be added by using an appropriate synthetic DNA adapter. The expression vector for the protein of the present invention can be manufactured, for example, by (a) excising the desired DNA fragment from the DNA encoding the protein of the present invention, and then (b) ligating the DNA fragment to an appropriate expression vector downstream from a promoter in the vector. Examples of the vector include plasmids derived form E. coli (e.g., pBR322, pBR325, pUC12, pUC13), plasmids derived from Bacillus subtilis (e.g., pUB110, pTP5, pC194), plasmids derived from yeast (e.g., pSH19, pSH15), bacteriophages such as λ phage, etc., animal viruses such as retrovirus, vaccinia virus, baculovirus, etc. as well as pA1-11, pXT1, pRc/CMV, pRc/RSV, pcDNAI/Neo, etc. The promoter used in the present invention may be any promoter if it matches well with a host to be used for gene expression. In the case of using animal cells as the host, examples of the promoter include SRα promoter, SV40 promoter, LTR promoter, CMV promoter, HSV-TK promoter, etc. Among them, CMV (cytomegalovirus) promoter or SRα promoter is preferably used. Where the host is bacteria of the genus Escherichia, preferred examples of the promoter include trp promoter, lac promoter, recA promoter, λPL promoter, lpp promoter, T7 promoter etc. In the case of using bacteria of the genus Bacillus as the host, preferred example of the promoter are SPO1 promoter, SPO2 promoter and penP promoter. When yeast is used as the host, preferred examples of the promoter are PHO5 promoter, PGK promoter, GAP promoter and ADH promoter. When insect cells are used as the host, preferred examples of the promoter include polyhedrin prompter and P10 promoter. In addition to the foregoing examples, the expression vector may further optionally contain an enhancer, a splicing signal, a polyA addition signal, a selection marker, SV40 replication origin (hereinafter sometimes abbreviated as SV40ori) etc. Examples of the selection marker include dihydrofolate reductase (hereinafter sometimes abbreviated as dhfr) gene [methotrexate (MTX) resistance], ampicillin resistant gene (hereinafter sometimes abbreviated as Ampr), neomycin resistant gene (hereinafter sometimes abbreviated as Neor, G418 resistance), etc. In particular, when dhfr gene is used as the selection marker in dhfr gene-deficient Chinese hamster's cells, selection can also be made on thymidine free media. If necessary and desired, a signal sequence that matches with a host is added to the N-terminus of the protein of the present invention. Examples of the signal sequence that can be used are PhoA signal sequence, OmpA signal sequence, etc. in the case of using bacteria of the genus Escherichia as the host; α-amylase signal sequence, subtilisin signal sequence, etc. in the case of using bacteria of the genus Bacillus as the host; MFα signal sequence, SUC2 signal sequence, etc. in the case of using yeast as the host; and insulin signal sequence, α-interferon signal sequence, antibody molecule signal sequence, etc. in the case of using animal cells as the host, respectively. Using the vector comprising the DNA encoding the protein of the present invention thus constructed, transformants can be manufactured. Examples of the host, which may be employed, are bacteria belonging to the genus Escherichia, bacteria belonging to the genus Bacillus, yeast, insect cells, insects and animal cells, etc. Specific examples of the bacteria belonging to the genus Escherichia include Escherichia coli K12 DH1 (Proc. Natl. Acad. Sci. U.S.A., 60, 160 (1968)), JM103 (Nucleic Acids Research, 9, 309 (1981)), JA221 (Journal of Molecular Biology, 120, 517 (1978)), HB101 (Journal of Molecular Biology, 41, 459 (1969)), C600 (Genetics, 39, 440 (1954)), etc. Examples of the bacteria belonging to the genus Bacillus include Bacillus subtilis MI114 (Gene, 24, 255 (1983)), 207-21 (Journal of Biochemistry, 95, 87 (1984)), etc. Examples of yeast include Saccharomyces cereviseae AH22, AH22R−, NA87-11A, DKD-5D, 20B-12, Schizosaccharomyces pombe NCYC1913, NCYC2036, Pichia pastoris KM71, etc. Examples of insect cells include, for the virus AcNPV, Spodoptera frugiperda cells (Sf cells), MG1 cells derived from mid-intestine of Trichoplusia ni, High Five™ cells derived from egg of Trichoplusia ni, cells derived from Mamestra brassicae, cells derived from Estigmena acrea, etc.; and for the virus BmNPV, Bombyx mori N cells (BmN cells), etc. are used. Examples of the Sf cell which can be used are Sf9 cells (ATCC CRL1711) and Sf21 cells (both cells are described in Vaughn, J. L. et al., In Vivo, 13, 213-217 (1977). As the insect, for example, a larva of Bombyx mori can be used (Maeda, et al., Nature, 315, 592 (1985)). Examples of animal cells include monkey cells COS-7, Vero, Chinese hamster cells CHO (hereinafter referred to as CHO cells), dhfr gene deficient Chinese hamster cells CHO (hereinafter simply referred to as CHO(dhfr−) cell), mouse L cells, mouse AtT-20, mouse myeloma cells, rat GH3, human FL cells, etc. Bacteria belonging to the genus Escherichia can be transformed, for example, by the method described in Proc. Natl. Acad. Sci. U.S.A., 69, 2110 (1972) or Gene, 17, 107 (1982). Bacteria belonging to the genus Bacillus can be transformed, for example, by the method described in Molecular & General Genetics, 168, 111 (1979). Yeast can be transformed, for example, by the method described in Methods in Enzymology, 194, 182-187 (1991), Proc. Natl. Acad. Sci. U.S.A., 75, 1929 (1978), etc. Insect cells or insects can be transformed, for example, according to the method described in Bio/Technology, 6, 47-55 (1988), etc. Animal cells can be transformed, for example, according to the method described in Saibo Kogaku (Cell Engineering), extra issue 8, Shin Saibo Kogaku Jikken Protocol (New Cell Engineering Experimental Protocol), 263-267 (1995), published by Shujunsha, or Virology, 52, 456 (1973). Thus, the transformant transformed with the expression vector comprising the DNA encoding the protein can be obtained. Where the host is bacteria belonging to the genus Escherichia or the genus Bacillus, the transformant can be appropriately incubated in a liquid medium which contains materials required for growth of the transformant such as carbon sources, nitrogen sources, inorganic materials, and so on. Examples of the carbon sources include glucose, dextrin, soluble starch, sucrose, etc. Examples of the nitrogen sources include inorganic or organic materials such as ammonium salts, nitrate salts, corn steep liquor, peptone, casein, meat extract, soybean cake, potato extract, etc. Examples of the inorganic materials are calcium chloride, sodium dihydrogenphosphate, magnesium chloride, etc. In addition, yeast extract, vitamins, growth promoting factors etc. may also be added to the medium. Preferably, pH of the medium is adjusted to about 5 to about 8. A preferred example of the medium for incubation of the bacteria belonging to the genus Escherichia is M9 medium supplemented with glucose and Casamino acids (Miller, Journal of Experiments in Molecular Genetics, 431-433, Cold Spring Harbor Laboratory, New York, 1972). If necessary and desired, a chemical such as 3β-indolylacrylic acid can be added to the medium to activate the promoter efficiently. Where the bacteria belonging to the genus Escherichia are used as the host, the transformant is usually cultivated at about 15° C. to about 43° C. for about 3 hours to about 24 hours. If necessary and desired, the culture may be aerated or agitated. Where the bacteria belonging to the genus Bacillus are used as the host, the transformant is cultivated generally at about 30° C. to about 40° C. for about 6 hours to about 24 hours. If necessary and desired, the culture can be aerated or agitated. Where yeast is used as the host, the transformant is cultivated, for example, in Burkholder's minimal medium (Bostian, K. L. et al., Proc. Natl. Acad. Sci. U.S.A., 77, 4505 (1980)) or in SD medium supplemented with 0.5% Casamino acids (Bitter, G A. et al., Proc. Natl. Acad. Sci. U.S.A., 81, 5330 (1984)). Preferably, pH of the medium is adjusted to about 5 to about 8. In general, the transformant is cultivated at about 20° C. to about 35° C. for about 24 hours to about 72 hours. If necessary and desired, the culture can be aerated or agitated. Where insect cells or insects are used as the host, the transformant is cultivated in, for example, Grace's Insect Medium (Grace, T. C. C., Nature, 195, 788 (1962)) to which an appropriate additive such as immobilized 10% bovine serum is added. Preferably, pH of the medium is adjusted to about 6.2 to about 6.4. Normally, the transformant is cultivated at about 27° C. for about 3 days to about 5 days and, if necessary and desired, the culture can be aerated or agitated. Where animal cells are employed as the host, the transformant is cultivated in, for example, MEM medium containing about 5% to about 20% fetal bovine serum (Science, 122, 501 (1952)), DMEM medium (Virology, 8, 396 (1959)), RPMI 1640 medium (The Journal of the American Medical Association, 199, 519 (1967)), 199 medium (Proceeding of the Society for the Biological Medicine, 73, 1 (1950)), etc. Preferably, pH of the medium is adjusted to about 6 to about 8. The transformant is usually cultivated at about 30° C. to about 40° C. for about 15 hours to about 60 hours and, if necessary and desired, the culture can be aerated or agitated As described above, the protein of the present invention can be produced in the cell, in the cell membrane or out of the cell of the transformant. The protein of the present invention can be separated and purified from the culture described above by the following procedures. When the protein of the present invention is extracted from the culture or cells after cultivation, the transformants or cells are collected by a publicly known method and suspended in an appropriate buffer. The transformants or cells are then disrupted by publicly known methods such as ultrasonication, a treatment with lysozyme and/or freeze-thaw cycling, followed by centrifugation, filtration, etc. Thus, the crude extract of the protein of the present invention can be obtained. The buffer used for the procedures may contain a protein modifier such as urea or guanidine hydrochloride, or a surfactant such as Triton X-100™, etc. When the protein is secreted in the culture, the supernatant after completion of the cultivation can be separated from the transformants or cells to collect the supernatant by a publicly known method. The protein contained in the supernatant or the extract thus obtained can be purified by appropriately combining the publicly known methods for separation and purification. Such publicly known methods for separation and purification include a method utilizing difference in solubility such as salting out, solvent precipitation, etc.; a method utilizing mainly difference in molecular weight such as dialysis, ultrafiltration, gel filtration, SDS-polyacrylamide gel electrophoresis, etc.; a method utilizing difference in electric charge such as ion exchange chromatography, etc.; a method utilizing difference in specific affinity such as affinity chromatography, etc.; a method utilizing difference in hydrophobicity such as reverse phase high performance liquid chromatography, etc.; a method utilizing difference in isoelectric point such as isoelectrofocusing electrophoresis; and the like. When the protein thus obtained is in a free form, it can be converted into the salt by publicly known methods or modifications thereof. On the other hand, when the protein is obtained in the form of a salt, it can be converted into the free form or in the form of a different salt by publicly known methods or modifications thereof. The protein produced by the recombinant can be treated, prior to or after the purification, with an appropriate protein-modifying enzyme so that the protein can be appropriately modified to partially remove a polypeptide. Examples of the protein-modifying enzyme include trypsin, chymotrypsin, arginyl endopeptidase, protein kinase, glycosidase or the like. The activity of the thus produced protein of the present invention or salts thereof can be determined by a test binding to a labeled ligand, by an enzyme immunoassay using a specific antibody, or the like. Antibodies to the protein of the present invention, its partial peptides, or salts thereof may be any of polyclonal antibodies and monoclonal antibodies as long as they are capable of recognizing the protein of the present invention, its partial peptides, or salts thereof. The antibodies to the protein of the present invention, its partial peptides, or salts thereof (hereinafter sometimes collectively referred to as the protein of the present invention) may be manufactured by publicly known methods for manufacturing antibodies or antisera, using as antigens the protein of the present invention. [Preparation of Monoclonal Antibody] (a) Preparation of Monoclonal Antibody-Producing Cells The protein of the present invention is administered to mammals either solely or together with carriers or diluents to the site where the production of antibody is possible by the administration. In order to potentiate the antibody productivity upon the administration, complete Freund's adjuvants or incomplete Freund's adjuvants may be administered. The administration is usually carried out once in every two to six weeks and 2 to 10 times in total. Examples of the applicable warm-blooded animals are monkeys, rabbits, dogs, guinea pigs, mice, rats, sheep, goats and chickens, with mice and rats being preferred. In the preparation of monoclonal antibody-producing cells, warm-blooded animals, e.g., mice, immunized with an antigen wherein the antibody titer is noted is selected, then the spleen or lymph node is collected after 2 to 5 days from the final immunization and antibody-producing cells contained therein are fused with myeloma cells from an animal of the same or different species to give monoclonal antibody-producing hybridomas. Measurement of the antibody titer in antisera may be made, for example, by reacting a labeled form of the protein, which will be described later, with the antiserum followed by assaying the binding activity of the labeling agent bound to the antibody. The fusion may be operated, for example, by the known Koehler and Milstein method (Nature, 256, 495, 1975). Examples of the fusion accelerator are polyethylene glycol (PEG), Sendai virus, etc., among which PEG is preferably employed. Examples of the myeloma cells are warm-blooded animal myeloma cells such as NS-1, P3U1, SP2/0, AP-1 etc., among which P3U1 is particularly preferably employed. A preferred ratio of the count of the antibody-producing cells used (spleen cells) to the count of myeloma cells is within a range of approximately 1:1 to 20:1. When PEG (preferably, PEG 1000 to PEG 6000) is added in a concentration of approximately 10 to 80% followed by incubation at about 20 to about 40° C., preferably at about 30 to about 37° C. for about 1 to about 10 minutes, an efficient cell fusion can be carried out. Various methods can be used for screening of a monoclonal antibody-producing hybridoma. Examples of such methods include a method which comprises adding the supernatant of hybridoma to a solid phase (e.g., microplate) adsorbed with the protein etc. as an antigen directly or together with a carrier, adding an anti-immunoglobulin antibody (when mouse cells are used for the cell fusion, anti-mouse immunoglobulin antibody is used) labeled with a radioactive substance or an enzyme, or Protein A and detecting the monoclonal antibody bound to the solid phase, and a method which comprises adding the supernatant of hybridoma to a solid phase adsorbed with an anti-immunoglobulin antibody or Protein A, adding the protein labeled with a radioactive substance or an enzyme and detecting the monoclonal antibody bound to the solid phase. The monoclonal antibody can be selected by publicly known methods or by modifications of these methods. In general, the selection can be effected in a medium for animal cells supplemented with HAT (hypoxanthine, aminopterin and thymidine). Any selection and growth medium can be employed as far as the hybridoma can grow therein. For example, RPMI 1640 medium containing 1% to 20%, preferably 10% to 20% fetal bovine serum, GIT medium (Wako Pure Chemical Industries, Ltd.) containing 1% to 10% fetal bovine serum, a serum free medium for cultivation of a hybridoma (SFM-101, Nissui Seiyaku Co., Ltd.) and the like can be used for the selection and growth medium. The cultivation is carried out generally at 20° C. to 40° C., preferably at about 37° C., for 5 days to 3 weeks, preferably 1 to 2 weeks. The cultivation can be conducted normally in 5% CO2. The antibody titer of the culture supernatant of hybridomas can be determined as in the assay for the antibody titer in antisera described above. (b) Purification of Monoclonal Antibody Separation and purification of a monoclonal antibody can be carried out by methods applied to conventional separation and purification of immunoglobulins, as in the conventional methods for separation and purification of polyclonal antibodies [e.g., salting-out, alcohol precipitation, isoelectric point precipitation, electrophoresis, adsorption and desorption with ion exchangers (e.g., DEAE), ultracentrifugation, gel filtration, or a specific purification method which comprises collecting only an antibody with an activated adsorbent such as an antigen-binding solid phase, Protein A, Protein Q etc. and dissociating the binding to obtain the antibody]. [Preparation of Polyclonal Antibody] The polyclonal antibody of the present invention can be manufactured by publicly known methods or modifications thereof. For example, an immunogen (antigen such as the protein) itself or a complex prepared from an immunogen and a carrier protein is used to immunize a warm-blooded animal a manner similar to the method described above for the manufacture of monoclonal antibodies. The product containing the antibody to the protein of the present invention is collected from the immunized animal followed by separation and purification of the antibody. In the complex of an immunogen and a carrier protein used to immunize a warm-blooded animal, the type of carrier protein and the mixing ratio of a carrier to hapten may be any type and in any ratio, as long as the antibody is efficiently produced to the hapten immunized by crosslinking to the carrier. For example, bovine serum albumin, bovine thyroglobulins, hemocyanin, etc. is coupled to hapten in a carrier-to-hapten weight ratio of approximately 0.1 to 20, preferably about 1 to about 5. A variety of condensing agents can be used for the coupling of a carrier to hapten. Glutaraldehyde, carbodiimide, maleimide-activated ester, activated ester reagents containing thiol group or dithiopyridyl group, etc. are used for the coupling. The condensation product is administered to warm-blooded animals either solely or together with carriers or diluents to the site in which the antibody can be produce by the administration. In order to potentiate the antibody productivity upon the administration, complete Freund's adjuvant or incomplete Freund's adjuvant may be administered. The administration is usually made once approximately in every 2 to 6 weeks and about 3 to about 10 times in total. The polyclonal antibody can be collected from the blood, ascites, etc., preferably from the blood of warm-blooded animals immunized by the method described above. The polyclonal antibody titer in antiserum can be assayed by the same procedure as that for the determination of serum antibody titer described above. The separation and purification of the polyclonal antibody can be carried out, following the method for the separation and purification of immunoglobulins performed as applied to the separation and purification of monoclonal antibodies described hereinabove. The antisense polynucleotide having a complementary or substantially complementary base sequence, or a part of thereof, to the DNA encoding the protein or partial peptide of the present invention (which in the following description of the antisense polynucleotide, is referred to sometimes as the DNA of the present invention) can be any antisense polynucleotide so long as it possesses a complementary or substantially complementary base sequence, or a part thereof, to that of the DNA of the present invention and capable of suppressing expression of the DNA. The antisense polynucleotide is preferably antisense DNA. The base sequence substantially complementary to the DNA of the present invention includes, for example, a base sequence having at least about 70% homology, preferably at least about 80% homology, more preferably at least about 90% homology and most preferably at least about 95% homology, to the full-length base sequence or partial base sequence of the base sequence complementary to the DNA of the present invention (i.e., complementary strand to the DNA of the present invention). The base sequence substantially complementary to the DNA of the present invention is particularly an antisense polynucleotide having at least about 70% homology, preferably at least about 80% homology, more preferably at least about 90% homology and most preferably at least about 95% homology to the complementary strand of the base sequence encoding the N-terminal site of the protein of the present invention (e.g., the base sequence around the initiation codon), in the entire base sequence of the complementary strand to the DNA of the present invention. Specifically, the base sequence substantially complementary to the DNA of the present invention is an antisense polynucleotide having a complementary or substantially complementary base sequence, or a part thereof, to the base sequence of DNA having the base sequence represented by SEQ ID NO: 2, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 19, SEQ ID NO: 41, SEQ ID NO: 43, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 67, SEQ ID NO: 103, SEQ ID NO: 105 or SEQ ID NO: 112, preferably an antisense polynucleotide having a complementary or substantially complementary base sequence, or a part thereof, to the base sequence of DNA having the base sequence represented by SEQ ID NO: 2, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 19, SEQ ID NO: 41, SEQ ID NO: 43, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 67, SEQ ID NO: 103, SEQ ID NO: 105 or SEQ ID NO: 112. The antisense polynucleotide is composed of usually about 10 to 40 bases, preferably about 15 to 30 bases. For preventing degradation by hydrolases such as nuclease etc., phosphoric acid residues (phosphates) of nucleotides constituting the antisense DNA may be substituted by chemically modified phosphoric acid residues such as phosphorothioate, methylphosphonate, phosphorodithionate etc. These antisense polynucleotides can be manufactured by a publicly known DNA synthesizer and the like. According to the present invention, antisense polynucleotides (nucleic acids) which can inhibit the replication or expression of the gene for the protein of the present invention and which correspond to the gene can be designed and synthesized based on the base sequence information of the cloned or determined DNA encoding the protein. Such antisense polynucleotide is capable of hybridizing with RNA of the protein gene of the present invention to inhibit the synthesis or function of said RNA or capable of modulating or controlling the expression of the protein gene of the invention via interaction with the protein-associated RNA of the invention. Polynucleotides complementary to the selected sequences of the protein-RNA of the invention, and polynucleotides specifically hybridizable with the protein-associated RNA of the invention, are useful in modulating or controlling the expression of the protein gene of the invention in vivo and in vitro, and useful for the treatment or diagnosis of diseases. The term “corresponding” is used to mean homologous to or complementary to a particular sequence of the nucleotide, base sequence or nucleic acid including the gene. The term “corresponding” between nucleotides, base sequences or nucleic acids and proteins usually refer to amino acids of a protein under the order derived from the sequence of nucleotides (nucleic acids) or their complements. In the protein genes, the 5′ end hairpin loop, 5′ end 6-base-pair repeats, 5′ end untranslated region, polypeptide translation initiation codon, protein coding region, ORF translation termination codon, 3′ end untranslated region, 3′ end palindrome region, and 3′ end hairpin loop, may be selected as preferred target regions, though any other region may be selected as a target in the protein genes. The relationship between the targeted nucleic acids and the polynucleotides complementary to at least a part of the target, or the relationship between the target and the polynucleotides hybridizable with the target, can be denoted to be “antisense”. Examples of the antisense polynucleotides include polydeoxynucleotides containing 2-deoxy-D-ribose, polynucleotides containing D-ribose, any other type of polynucleotides which are N-glycosides of a purine or pyrimidine base, or other polymers containing non-nucleotide backbones (e.g., protein nucleic acids and synthetic sequence-specific nucleic acid polymers commercially available) or other polymers containing nonstandard linkages (provided that the polymers contain nucleotides having such a configuration that allows base pairing or base stacking, as is found in DNA or RNA), etc. The antisense polynucleotides may be double-stranded DNA, single-stranded DNA, double-stranded RNA, single-stranded RNA or a DNA:RNA hybrid, and may further include unmodified polynucleotides (or unmodified oligonucleotides), those with publicly known types of modifications, for example, those with labels known in the art, those with caps, methylated polynucleotides, those with substitution of one or more naturally occurring nucleotides by their analogue, those with intramolecular modifications of nucleotides such as those with uncharged linkages (e.g., methyl phosphonates, phosphotriesters, phosphoramidates, carbamates, etc.) and those with charged linkages or sulfur-containing linkages (e.g., phosphorothioates, phosphorodithioates, etc.), those having side chain groups such as proteins (nucleases, nuclease inhibitors, toxins, antibodies, signal peptides, poly-L-lysine, etc.), saccharides (e.g., monosaccharides, etc.), those with intercalators (e.g., acridine, psoralen, etc.), those containing chelators (e.g., metals, radioactive metals, boron, oxidative metals, etc.), those containing alkylating agents, those with modified linkages (e.g., α anomeric nucleic acids, etc.), and the like. Herein the terms “nucleoside”, “nucleotide” and “nucleic acid” are used to refer to moieties that contain not only the purine and pyrimidine bases, but also other heterocyclic bases, which have been modified. Such modifications may include methylated purines and pyrimidines, acylated purines and pyrimidines and other heterocyclic rings. Modified nucleotides and modified nucleotides also include modifications on the sugar moiety, wherein, for example, one or more hydroxyl groups may optionally be substituted with a halogen atom(s), an aliphatic group(s), etc., or may be converted into the corresponding functional groups such as ethers, amines, or the like. The antisense polynucleotide of the present invention is RNA, DNA or a modified nucleic acid (RNA, DNA). Specific examples of the modified nucleic acid include, but are not limited to, sulfur and thiophosphate derivatives of nucleic acids and those resistant to degradation of polynucleoside amides or oligonucleoside amides. The antisense polynucleotides of the present invention can be modified preferably based on the following design, that is, by increasing the intracellular stability of the antisense polynucleotide, increasing the cellular permeability of the antisense polynucleotide, increasing the affinity of the polynucleotide to the targeted sense strand to a higher level, or minimizing the toxicity, if any, of the antisense polynucleotide. Many of such modifications are reported for example in Pharm. Tech. Japan, Vol. 8, p. 247 or 395, 1992, Antisense Research and Applications, CRC Press, 1993, etc. The antisense polynucleotide of the present invention may contain altered or modified sugars, bases or linkages. The antisense polynucleotide may also be provided in a specialized form such as liposomes, microspheres, or may be applied to gene therapy, or may be provided in combination with attached moieties. Such attached moieties include polycations such as polylysine that act as charge neutralizers of the phosphate backbone, or hydrophobic moieties such as lipids (e.g., phospholipids, cholesterols, etc.) that enhance the interaction with cell membranes or increase uptake of the nucleic acid. Preferred examples of the lipids to be attached are cholesterols or derivatives thereof (e.g., cholesteryl chloroformate, cholic acid, etc.). These moieties may be attached to the nucleic acid at the 3′ or 5′ ends thereof and may also be attached thereto through a base, sugar, or intramolecular nucleoside linkage. Other moieties may be capping groups specifically placed at the 3′ or 5′ ends of the nucleic acid to prevent degradation by nucleases such as exonuclease, RNase, etc. Such capping groups include, but are not limited to, hydroxyl protecting groups known in the art, including glycols such as polyethylene glycol, tetraethylene glycol and the like. The inhibitory action of the antisense polynucleotide can be examined using the transformant of the present invention, the gene expression system of the present invention in vivo and in vitro, or the translation system of the protein of the present invention in vivo and in vitro. Hereinafter, the protein of the present invention, its partial peptides, or salts thereof (hereinafter sometimes referred to as the protein of the present invention), the DNA encoding the protein of the present invention or its partial peptides (hereinafter sometimes referred to as the DNA of the present invention), the antibodies to the protein of the present invention, its partial peptides, or salts thereof (hereinafter sometimes referred to as the antibodies of the present invention) and the antisense polynucleotide of the DNA of the present invention (hereinafter sometimes referred to as the antisense polynucleotide of the present invention) are specifically described for the use or applications. The protein comprising an amino acid sequence identical or substantially identical with the amino acid sequence represented by SEQ ID NO: 1, SEQ ID NO: 14 or SEQ ID NO: 104 is sometimes referred to “protein A of the present invention”; the protein comprising an amino acid sequence identical or substantially identical with the amino acid sequence represented by SEQ ID NO: 18 is sometimes referred to “protein B of the present invention”; the protein comprising an amino acid sequence identical or substantially identical with the amino acid sequence represented by SEQ ID NO: 42 is sometimes referred to “protein C of the present invention”; and the protein comprising an amino acid sequence identical or substantially identical with the amino acid sequence represented by SEQ ID NO: 66 is sometimes referred to “protein D of the present invention”. [1] Prophylactic and/or Therapeutic Agents for Diseases Associated with the Protein of the Present Invention The protein A of the present invention contributes to transport of a substrate, and plays an important role in metabolism of the substrate, etc. Hereinafter, the substrate of the protein A of the present invention is referred to sometimes as “substrate A”. The substrate A includes, for example, steroid hormone, bile acid etc. The steroid hormone includes, for example, estrogen, progestogen, androgen, mineral corticoid, glucocorticoid, steroid chemicals or metabolites thereof (e.g., sulfate conjugates, glucuronide conjugates etc.) etc. In particular, steroid hormone or metabolites thereof are preferable. Estrogen or androgen or metabolites thereof (preferably sulfate conjugates etc.) are more preferable. Estrone, dehydroepiandrosterone or sulfate conjugates thereof are most preferable. The estrogen includes, for example, estrone, estradiol, estriol, estetrol etc. The progestogen includes, for example, progesterone, pregnanediol etc. The androgen includes, for example, dehydroepiandrosterone, testosterone, androstanedione, 5α-dihydrotestosterone, androsterone etc. The mineral corticoid includes, for example, aldosterone etc. The glucocorticoid includes, for example, cortisol, cortisone, corticosterone, dehydrocorticosterone etc. The steroid chemicals include, for example, dexamethasone, betamethasone, prednisolone, triamcinolone, fluorocortisone, clomiphene, tamoxifen, danazol etc. The bile acid includes, for example, taurocholic acid, glicocholic acid, cholic acid, lithocholic acid, deoxycholic acid, taurodeoxycholic acid, tauroursodeoxycholic acid, chenodeoxycholic acid, glicochenodeoxycholic acid, glicodeoxycholic acid etc. Accordingly, when DNA encoding the protein A of the present invention is abnormal or deficient or when the amount of the protein A of the invention expressed is reduced, there occur various diseases such as hyperlipemia, genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, bronchial asthma etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), diabetes, hypothyroidism, circulatory diseases (e.g., cardiac insufficiency, arrhythmia, long QT syndrome, arteriosclerosis, angina etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc. Accordingly, the protein A of the invention and the DNA encoding it can be used as safe medicines such as prophylactic/therapeutic agents for diseases such as hyperlipemia, genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, bronchial asthma etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), diabetes, hypothyroidism, circulatory diseases (e.g., cardiac insufficiency, arrhythmia, long QT syndrome, arteriosclerosis, angina etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably hyperlipemia, arteriosclerosis, genital diseases, digestive diseases etc. For example, when there is a patient who cannot sufficiently or normally exhibit an activity of transporting substrate A because of a decrease or deficiency in the protein A of the present invention in the living body, (i) DNA encoding the protein A of the invention is administered into the patient to express the protein A of the invention in the living body, (ii) the DNA is inserted into target cells to express the protein A of the invention and the cells are transplanted to the patient, or (iii) the protein A of the invention is administered into the patient, whereby the role of the protein of the invention can be exhibited sufficiently or normally in the patient. The protein B of the present invention has a cation (preferably monovalent cation such as Na+, K+, etc.)/H+ exchange transport activity, and plays an important role in regulation of intracellular pH, regulation of cell volume, and re-absorption of Na+ into the kidney and small intestine. Accordingly, when DNA encoding the protein B of the present invention is abnormal or deficient or when the amount of the protein B of the invention expressed is reduced, there occur various diseases such as renal diseases (e.g., renal insufficiency, uremia etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), spleen diseases, cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.), diabetes, hypertension, ischemia-reperfusion injury, central nerve diseases (e.g., Alzheimer's disease, Parkinson's syndrome, schizophrenia, cerebral vascular dementia, cerebral ischemia, epilepsy etc.) etc. Preferably, there occur many diseases such as respiratory diseases, renal diseases, digestive diseases etc. Accordingly, the protein B of the present invention and DNA encoding the same can be used as safe medicines such as prophylactic/therapeutic agents for renal diseases (e.g., renal insufficiency, uremia etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), spleen diseases, cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.), diabetes, hypertension, ischemia-reperfusion injury, central nerve diseases (e.g., Alzheimer's disease, Parkinson's syndrome, schizophrenia, cerebral vascular dementia, cerebral ischemia, epilepsy etc.) etc. The protein B of the present invention and DNA encoding the same are preferably prophylactic/therapeutic agents for respiratory diseases, renal diseases, digestive diseases etc. For example, when there is a patient who cannot sufficiently or normally exhibit a cation (preferably monovalent cation such as Na+, K+ etc.)/H+ exchange transport activity because of a decrease or deficiency in the protein B of the present invention in the living body, (i) DNA encoding the protein B of the invention is administered into the patient to express the protein B of the invention in the living body, (ii) the DNA is inserted into target cells to express the protein B of the invention and the cells are transplanted to the patient, or (iii) the protein B of the invention is administered into the patient, whereby the role of the protein B of the invention can be exhibited sufficiently or normally in the patient. The protein C of the present invention has an activity of transporting aminophospholipids, to contribute to transport of aminophospholipids, and simultaneously plays an important role in distributing lipids on a biomembrane. Accordingly, when DNA encoding the protein C of the invention is abnormal or deficient or when the amount of the protein C of the invention expressed is reduced, there occur various diseases such as pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), central nerve diseases (e.g., Alzheimer's disease, Parkinson's syndrome, schizophrenia, cerebral vascular dementia, cerebral ischemia, epilepsy etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), diabetes, hyperlipemia, cholestasis, or cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably pancreatic diseases, central nerve diseases, digestive diseases, respiratory diseases etc. Accordingly, the protein C of the invention and the DNA encoding it can be used as safe medicines such as prophylactic/therapeutic agents for pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), central nerve diseases (e.g., Alzheimer's disease, Parkinson's syndrome, schizophrenia, cerebral vascular dementia, cerebral ischemia, epilepsy etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), diabetes, hyperlipemia, cholestasis, or cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc. preferably pancreatic diseases, central nerve diseases, digestive diseases, respiratory diseases etc. For example, when there is a patient who cannot sufficiently or normally exhibit an activity of transporting aminophospholipids because of a decrease or deficiency in the protein C of the present invention in the living body, (i) DNA encoding the protein C of the invention is administered into the patient to express the protein C of the invention in the living body, (ii) the DNA is inserted into target cells to express the protein C of the invention and the cells are transplanted to the patient, or (iii) the protein C of the invention is administered into the patient, whereby the role of the protein of the invention can be exhibited sufficiently or normally in the patient. The protein D of the present invention has a cation channel activity, and plays an important role in recognition of stimuli such as pain. The protein D can also function as temperature-sensitive cation channel. Accordingly, when DNA encoding the protein D of the invention is abnormal or deficient or when the amount of the protein D of the invention expressed is reduced, there occur various diseases such as inflammatory diseases (e.g., septicemia, pneumonia, encephalitis, meningitis, hepatitis, myocarditis, pleurisy etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), diabetic neurosis, thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), circulatory diseases (e.g., cardiac insufficiency, arrhythmia, long QT syndrome, arteriosclerosis, angina etc.), hepatic diseases (e.g., hepatocirrhosis etc.), renal diseases (e.g., renal insufficiency, uremia etc.), muscular diseases (e.g., muscular dystrophy etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), burns, pain syndrome (e.g., cancerous sharp pain, referred pain etc.), cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably inflammatory diseases, rheumatoid diseases, diabetic neurosis etc. Accordingly, the protein D of the invention and the DNA encoding it can be used as safe medicines such as prophylactic/therapeutic agents for inflammatory diseases (e.g., septicemia, pneumonia, encephalitis, meningitis, hepatitis, myocarditis, pleurisy etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), diabetic neurosis, thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), circulatory diseases (e.g., cardiac insufficiency, arrhythmia, long QT syndrome, arteriosclerosis, angina etc.), hepatic diseases (e.g., hepatocirrhosis etc.), renal diseases (e.g., renal insufficiency, uremia etc.), muscular diseases (e.g., muscular dystrophy etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), burns, pain syndrome (e.g., cancerous sharp pain, referred pain etc.), cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc. The protein D of the invention and the DNA encoding it are preferably prophylactic/therapeutic agents for inflammatory diseases, rheumatoid diseases, diabetic neurosis etc. For example, when there is a patient who cannot sufficiently or normally exhibit a cation channel activity because of a decrease or deficiency in the protein D of the present invention in the living body, (i) DNA encoding the protein D of the invention is administered into the patient to express the protein D of the invention in the living body, (ii) the DNA is inserted into target cells to express the protein D of the invention and the cells are transplanted to the patient, or (iii) the protein D of the invention is administered into the patient, whereby the role of the protein of the invention can be exhibited sufficiently or normally in the patient. Where the DNA of the present invention is used as the prophylactic/therapeutic agents described above, the DNA itself is administered directly to human or other warm-blooded animal; alternatively, the DNA is inserted into an appropriate vector such as retrovirus vector, adenovirus vector, adenovirus-associated virus vector, etc. and then administered to human or other warm-blooded animal in a conventional manner. The DNA of the present invention may also be administered as an intact DNA, or prepared into medicines together with physiologically acceptable carriers such as adjuvants to assist its uptake, which are administered by gene gun or through a catheter such as a hydrogel catheter. Where the protein of the present invention is used as the aforesaid prophylactic/therapeutic agents, the protein is advantageously used on a purified level of at least 90%, preferably at least 95%, more preferably at least 98% and most preferably at least 99%. The protein of the present invention can be used orally, for example, in the form of tablets which may be sugar coated if necessary and desired, capsules, elixirs, microcapsules etc., or parenterally in the form of injectable preparations such as a sterile solution and a suspension in water or with other pharmaceutically acceptable liquid. These preparations can be manufactured by mixing the protein of the present invention with a physiologically acceptable known carrier, a flavoring agent, an excipient, a vehicle, an antiseptic agent, a stabilizer, a binder, etc. in a unit dosage form required in a generally accepted manner that is applied to making medicines. The active ingredient in the preparation is controlled in such a dose that an appropriate dose is obtained within the specified range given. Additives miscible with tablets, capsules, etc. include a binder such as gelatin, corn starch, tragacanth and gum arabic, an excipient such as crystalline cellulose, a swelling agent such as corn starch, gelatin, alginic acid, etc., a lubricant such as magnesium stearate, a sweetening agent such as sucrose, lactose or saccharin, and a flavoring agent such as peppermint, akamono oil or cherry. When the unit dosage is in the form of capsules, liquid carriers such as oils and fats may further be used together with the additives described above. A sterile composition for injection may be formulated according to a conventional manner used to make pharmaceutical compositions, e.g., by dissolving or suspending the active ingredient in a vehicle such as water for injection, with a naturally occurring vegetable oil such as sesame oil, coconut oil, etc. to prepare the pharmaceutical composition. Examples of an aqueous medium for injection include physiological saline and an isotonic solution containing glucose and other auxiliary agents (e.g., D-sorbitol, D-mannitol, sodium chloride, etc.) and may be used in combination with an appropriate dissolution aid such as an alcohol (e.g., ethanol or the like), a polyalcohol (e.g., propylene glycol and polyethylene glycol), a nonionic surfactant (e.g., polysorbate 80™ and HCO-50), etc. Examples of the oily medium include sesame oil, soybean oil, etc., which may also be used in combination with a dissolution aid such as benzyl benzoate, benzyl alcohol, etc. The protein of the present invention may further be formulated with a buffer (e.g., phosphate buffer, sodium acetate buffer, etc.), a soothing agent (e.g., benzalkonium chloride, procaine hydrochloride, etc.), a stabilizer (e.g., human serum albumin, polyethylene glycol, etc.), a preservative (e.g., benzyl alcohol, phenol, etc.), an antioxidant, etc. The thus prepared liquid for injection is normally filled in an appropriate ampoule. The vector in which the DNA of the present invention is inserted may also be prepared into medicines in a manner similar to the procedures above, and such preparations are generally used parenterally. Since the thus obtained medicine is safe and low toxic, and can be administered to, for example, warm-blooded animals (e.g., human, rat, mouse, guinea pig, rabbit, chicken, sheep, swine, bovine, horse, cat, dog, monkey, chimpanzee etc.). The dose of the protein A of the present invention may vary depending on target disease, subject to be administered, route for administration, etc. When the protein A of the present invention is orally administered for example for the purpose of treatment of hyperlipemia, the protein is administered to adult (as 60 kg) generally in a daily dose of approximately 0.1 mg to 100 mg, preferably approximately 1.0 mg to 50 mg, more preferably approximately 1.0 to 20 mg. When the protein is parenterally administered, a single dose of the protein of the present invention may vary depending on subject to be administered, target disease, etc. When the protein A of the present invention is administered to adult (as 60 kg body weight), it is convenient to administer the protein A by injection to the affected area, generally in a daily dose of approximately 0.01 to 30 mg, preferably approximately 0.1 to 20 mg, more preferably approximately 0.1 to 10 mg. For other animal species, the corresponding dose as converted per 60 kg weight can be administered. The dose of the protein B of the present invention may vary depending on target disease, subject to be administered, route for administration, etc. When the protein B of the present invention is orally administered for example for the purpose of treatment of renal insufficiency, the protein is administered to adult (as 60 kg) generally in a daily dose of approximately 0.1 mg to 100 mg, preferably approximately 1.0 mg to 50 mg, more preferably approximately 1.0 to 20 mg. When the protein is parenterally administered, a single dose of the protein may vary depending on subject to be administered, target disease, etc. When the protein B of the present invention is administered to adult (as 60 kg body weight) for the purpose of treatment of renal insufficiency, it is convenient to administer the protein by injection to the affected area, generally in a daily dose of approximately 0.01 to 30 mg, preferably approximately 0.1 to 20 mg, more preferably approximately 0.1 to 10 mg. For other animal species, the corresponding dose as converted per 60 kg weight can be administered. The dose of the protein C of the present invention may vary depending on target disease, subject to be administered, route for administration, etc. When the protein C of the present invention is orally administered for example for the purpose of treatment of diabetes, the protein of the present invention is administered to adult (as 60 kg) generally in a daily dose of approximately 0.1 mg to 100 mg, preferably approximately 1.0 mg to 50 mg, more preferably approximately 1.0 to 20 mg. When the protein is parenterally administered, a single dose of the protein may vary depending on subject to be administered, target disease, etc. When the protein C of the present invention is administered to adult (as 60 kg body weight) for the purpose of treatment of diabetes, it is convenient to administer the protein by injection to the affected area, generally in a daily dose of approximately 0.01 to 30 mg, preferably approximately 0.1 to 20 mg, more preferably approximately 0.1 to 10 mg. For other animal species, the corresponding dose as converted per 60 kg weight can be administered. The dose of the protein D of the present invention may vary depending on target disease, subject to be administered, route for administration, etc. When the protein D of the present invention is orally administered for example for the purpose of treatment of chronic articular rheumatism, the protein is administered to adult (as 60 kg) generally in a daily dose of approximately 0.1 mg to 100 mg, preferably approximately 1.0 mg to 50 mg, more preferably approximately 1.0 to 20 mg. When the protein is parenterally administered, a single dose may vary depending on subject to be administered, target disease, etc. When the protein D of the present invention is administered to adult (as 60 kg body weight) for the purpose of treatment of chronic articular rheumatism, it is convenient to administer the protein by injection to the affected area, generally in a daily dose of approximately 0.01 to 30 mg, preferably approximately 0.1 to 20 mg, more preferably approximately 0.1 to 10 mg. For other animal species, the corresponding dose as converted per 60 kg weight can be administered. [2] Screening of a Candidate Drug for Diseases The protein of the present invention is useful as a reagent for screening a compound or its salt that promotes or inhibits the activity of the protein of the present invention. The present invention provides (1) a method of screening a compound or a salt thereof (also referred to hereinafter as a promoter and inhibitor) that promotes or inhibits the activity (e.g., an activity of transporting substrate A etc.) of the protein A of the invention, which comprises using the protein A of the present invention. More specifically, the present invention provides, for example, (2) a method of screening a promoter or an inhibitor, which comprises comparing (i) the substrate A transport activity of a cell having an ability to produce the protein A of the present invention with (ii) the substrate A transport activity of a mixture of a test compound and a cell having an ability to produce the protein A of the present invention. Specifically, the amount of the substrate A in a labeled form incorporated into the cell is measured and compared between (i) and (ii) in the screening method described above. As the labeling agent, use is made of, for example, radioisotopes (for example, [3H], [125I], [14C], [32P], [33P], [35S], etc.), fluorescent substances (for example, cyanine fluorescent dyes (e.g., Cy2, Cy3, Cy5, Cy5.5, Cy7 (Amersham Bioscience) etc), fluorescein etc.), luminescent substances (for example, luminol etc.), enzymes (for example, peroxidase etc.) or lanthanide elements. As the labeled substrate A, use is made of, for example, [6,7-3H(N)]-estrone sulfate or [1,2,6,7-3H(N)]-dehydroepiandrosterone sulfate. Examples of the test compounds include peptides, proteins, non-peptide compounds, synthetic compounds, fermentation products, cell extracts, plant extracts, animal tissue extracts, etc. and these compounds may be novel compounds or publicly known compounds. To perform the screening method described above, a protein preparation is prepared by suspending cells having an ability to produce the protein A of the present invention, in a buffer appropriate for screening. A buffer such as a phosphate buffer or a borate buffer having a pH value of about 4 to 10 (preferably pH of about 6 to 8) can be used so long as it does not inhibit the activity of the protein A of the present invention. As the cells having an ability to produce the protein A of the present invention, for example a host (transformant) transformed with a vector comprising the DNA encoding the protein A of the present invention described above is used. As the host, animal cells such as CHO cells are preferably used. In the screening, for example a transformant expressing the protein A of the present invention on a cell membrane by culturing it by the method described above is preferably used. The substrate A transport activity can be measured according to known methods, for example a method described in Am. J. Physiol., 274, G157-169, 1998 or a modification thereto. For example, a compound or a salt thereof that promotes the substrate A transport activity in (ii) above by about at least 20%, preferably at least 30%, more preferably about at least 50% as compared with the activity in (i) above can be selected as a compound or a salt thereof that promotes the activity of the protein A of the present invention. For example, a compound or a salt thereof that inhibits the substrate A transport activity in (ii) above by about at least 20%, preferably at least 30%, more preferably about at least 50% as compared with the activity in (i) above can be selected as a compound or a salt thereof that inhibits (or suppresses) the activity of the protein A of the present invention. Specifically, the screening method is as follows: First, the cells are cultured in a multi-well plate etc. In screening, the medium is exchanged with a fresh buffer or a suitable buffer not toxic to the cells, and a given amount (5,000 cpm to 500,000 cpm) of a labeled form of the protein A is added to the cells, and at the same time, 10−10 to 10−7 M of a test compound is co-present. The reaction is carried out at 0° C. to 50° C., preferably about 4° C. to 37° C. for 20 minutes to 24 hours, preferably 30 minutes to 3 hours. After completion of the reaction, the medium or buffer is removed, and the cells are washed with an appropriate volume of a buffer (for example, PBS etc.), and then the residual radioactivity of the labeled substrate A incorporated into the cells is measured by means of a liquid scintillation counter. Assuming that the count in the absence of a test compound as an antagonizing compound is 100%, a test compound by which the count is reduced to e.g. 50% or less can be selected as a candidate compound capable of competitive inhibition. Alternatively, after a gene for secretory alkaline phosphatase, luciferase or the like is inserted into a region downstream from a promoter of the protein A gene of the present invention and the gene is expressed in the cells described above, a compound or a salt thereof that promotes or inhibits the expression of the protein A of the present invention (that is, a compound or a salt thereof that promotes or inhibits the activity of the protein A of the present invention) can be screened by examining whether a test compound when brought into contact with the cells activates or inhibits the enzyme activity. The present invention provides (1′) a method of screening a compound or a salt thereof (also referred to hereinafter as a promoter and inhibitor) that promotes or inhibits the activity [for example, cation (preferably monovalent cation such as Na+, K+ etc.)/H+ exchange transport activity] of the protein B of the invention, which comprises using the protein B of the present invention. More specifically, the present invention provides, for example: (2′) a method of screening a promoter or an inhibitor, which comprises comparing (i′) the cation (preferably monovalent cation such as Na+, K+ etc.)/H+ exchange transport activity of a cell having an ability to produce the protein B of the present invention with (ii′) the cation (preferably monovalent cation such as Na+, K+ etc.)/H+ exchange transport activity of a mixture of a test compound and a cell having an ability to produce the protein B of the present invention. Specifically, the screening method comprises, for example, measuring the cation (preferably monovalent cation such as Na+, K+ etc.)/H+ exchange transport activity as an indicator by a fluorescent dye and comparing the cation (preferably monovalent cation such as Na+, K+ etc.)/H+ exchange transport activity in (i′) above, with that in (ii′). Examples of the test compounds include peptides, proteins, non-peptide compounds, synthetic compounds, fermentation products, cell extracts, plant extracts, animal tissue extracts, etc. and these compounds may be novel compounds or publicly known compounds. To perform the screening method described above, a protein preparation is prepared by suspending cells having an ability to produce the protein B of the present invention, in a buffer appropriate for screening. A buffer such as a phosphate buffer or a borate buffer having a pH value of about 4 to 10 (preferably pH of about 6 to 8) can be used so long as it does not inhibit the cation (preferably monovalent cation such as Na+, K+, etc.)/H+ exchange transport activity of the protein B of the present invention. As the cells having an ability to produce the protein B of the present invention, for example a host (transformant) transformed with a vector comprising the DNA encoding the protein of the present invention described above is used. As the host, animal cells such as CHO cells are preferably used. In the screening, for example a transformant expressing the protein B of the present invention on a cell membrane by culturing it by the method described above is preferably used. The cation (preferably monovalent cation such as Na+, K+, etc.)/H+ exchange transport activity of the protein B of the present invention can be measured according to known methods, for example a method described in J. Biol. Chem. 274, 3978-3987, 1998 or a modification thereto. For example, a test compound that promotes the cation (preferably monovalent cation such as Na+, K+, etc.)/H+ exchange transport activity in (ii′) above by about at least 20%, preferably at least 30%, more preferably about at least 50% as compared with the activity in (i′) above can be selected as a compound or a salt thereof that promotes the activity of the protein B of the present invention. For example, a test compound that inhibits (or suppresses) the cation (preferably monovalent cation such as Na+, K+, etc.)/H+ exchange transport activity in (ii′) above by about at least 20%, preferably at least 30%, more preferably about at least 50% as compared with the activity in (i′) above can be selected as a compound or a salt thereof that inhibits the activity of the protein B of the present invention. Alternatively, after a gene for secretory alkaline phosphatase, luciferase or the like is inserted into a region downstream from a promoter of the protein B gene of the present invention and the gene is expressed in the cells described above, a compound or a salt thereof that promotes or inhibits the expression of the protein B of the present invention (that is, a compound or a salt thereof that promotes or inhibits the activity of the protein B of the present invention) can be screened by examining whether a test compound when brought into contact with the cells activates or inhibits the enzyme activity. The present invention provides (1″) a method of screening a compound or a salt thereof (also referred to hereinafter as a promoter and inhibitor) that promotes or inhibits the activity (for example, aminophospholipid transport etc.) of the protein C of the invention, which comprises using the protein C of the present invention. More specifically, the present invention provides, for example: (2″) a method of screening a promoter or an inhibitor, which comprises comparing (i″) the aminophospholipid transport activity of a cell having an ability to produce the protein C of the present invention with (ii″) the aminophospholipid transport activity of a mixture of a test compound and a cell having an ability to produce the protein C of the present invention. Specifically, the screening method comprises, for example, measuring aminophospholipid transport as an indicator by a radioisotope-labeled substrate or a fluorescent dye and comparing the aminophospholipid transport in (i″) with that in (ii″). Examples of the test compounds include peptides, proteins, non-peptide compounds, synthetic compounds, fermentation products, cell extracts, plant extracts, animal tissue extracts, etc. and these compounds may be novel compounds or publicly known compounds. To perform the screening method described above, a protein preparation is prepared by suspending cells having an ability to produce the protein C of the present invention, in a buffer appropriate for screening. A buffer such as a phosphate buffer or a borate buffer having a pH value of about 4 to 10 (preferably pH of about 6 to 8) can be used so long as it does not inhibit the aminophospholipid transport activity of the protein C of the present invention. As the cells having an ability to produce the protein C of the present invention, for example a host (transformant) transformed with a vector comprising the DNA encoding the protein C of the present invention described above is used. As the host, animal cells such as CHO cells are preferably used. In the screening, for example a transformant expressing the protein C of the present invention on a cell membrane by culturing it by the method described above is preferably used. The aminophospholipid transport activity of the protein C of the present invention can be measured according to known methods, for example a method described in J. Biol. Chem., 275, 23378-23386, 1998 or a modification thereto. For example, a test compound that promotes the aminophospholipid transport activity in (ii′) above by about at least 20%, preferably at least 30%, more preferably about at least 50% compared with the activity in (i′) above can be selected as a compound or a salt thereof that promotes the activity of the protein C of the present invention. For example, a test compound that inhibits (or suppresses) the aminophospholipid transport activity in (ii′) above by about at least 20%, preferably at least 30%, more preferably about at least 50% compared with the activity (i′) above can be selected as a compound or a salt thereof that inhibits the activity of the protein C of the present invention. Alternatively, after a gene for secretory alkaline phosphatase, luciferase or the like is inserted into a region downstream from a promoter of the protein C gene of the present invention and the gene is expressed in the cells described above, a compound or a salt thereof that promotes or inhibits the expression of the protein C of the present invention (that is, a compound or a salt thereof that promotes or inhibits the activity of the protein C of the present invention) can be screened by examining whether a test compound when brought into contact with the cells activates or inhibits the enzyme activity. The present invention provides (1′″) a method of screening a compound or a salt thereof (also referred to hereinafter as a promoter and inhibitor) that promotes or inhibits the activity (for example, cation channel activity) of the protein D of the invention, which comprises using the protein D of the present invention. More specifically, the present invention provides, for example: (2′″) a method of screening a promoter or an inhibitor, which comprises comparing (i′″) the cation channel activity of a cell having an ability to produce the protein D of the present invention with (ii′″) the cation channel activity of a mixture of a test compound and a cell having an ability to produce the protein D of the present invention. Specifically, the screening method comprises, for example, measuring the cation channel activity as an indicator by a patch clamp method and comparing the cation channel activity in (i′″) with that in (ii′″). Examples of the test compounds include peptides, proteins, non-peptide compounds, synthetic compounds, fermentation products, cell extracts, plant extracts, animal tissue extracts, etc. and these compounds may be novel compounds or publicly known compounds. To perform the screening method described above, a protein preparation is prepared by suspending cells having an ability to produce the protein D of the present invention, in a buffer appropriate for screening. A buffer such as a phosphate buffer or a borate buffer having a pH value of about 4 to 10 (preferably pH of about 6 to 8) can be used so long as it does not inhibit the cation channel activity of the protein D of the present invention. As the cells having an ability to produce the protein of the present invention, for example a host (transformant) transformed with a vector comprising the DNA encoding the protein of the present invention described above is used. As the host, animal cells such as CHO cells are preferably used. In the screening, for example a transformant expressing the protein of the present invention on a cell membrane by culturing it by the method described above is preferably used. The cation channel activity of the protein D of the present invention can be measured according to known methods, for example a method described in Nature, 389, 816, 1997 or a modification thereto. For example, a test compound that promotes the cation channel activity in (ii′″) above by about at least 20%, preferably at least 30%, more preferably about at least 50% as compared with the activity in (i′″) above can be selected as a compound or a salt thereof that promotes the activity of the protein D of the present invention. For example, a test compound that inhibits (or suppresses) the cation channel activity in (ii′″) above by about at least 20%, preferably at least 30%, more preferably about at least 50% as compared with the activity in (i′″) above can be selected as a compound or a salt thereof that inhibits the activity of the protein D of the present invention. Alternatively, after a gene for secretory alkaline phosphatase, luciferase or the like is inserted into a region downstream from a promoter of the protein D gene of the present invention and the gene is expressed in the cells described above, a compound or a salt thereof that promotes or inhibits the expression of the protein D of the present invention (that is, a compound or a salt thereof that promotes or inhibits the activity of the protein D of the present invention) can be screened by examining whether a test compound when brought into contact with the cells activates or inhibits the enzyme activity. Using the protein D of the present invention, or using the ligand binding assay system of the expression system constructed using a recombinant of the protein D of the present invention, compounds (e.g., peptides, proteins, non-peptide compounds, synthetic compounds, fermentation products, etc.) or salt forms thereof that alter the binding property between the protein D of the present invention and its ligand (hereinafter referred to as the ligand of the present invention) can be efficiently screened. Specifically, the case (i) where the ligand of the present invention is brought into contact with the protein D of the present invention is compared with the case (ii) where the ligand of the present invention and a test compound are brought into contact with the protein D of the present invention. In this comparison, for example the amount of the ligand of the present invention bound to the protein D of the present invention is measured. Specifically, the screening method of the present invention includes, for example: (a) a method of screening a compound or its salt that alters the binding property between the ligand of the present invention and the protein D of the present invention, which comprises measuring and comparing the amount of the ligand of the invention bound to the protein D of the invention in the case where the ligand of the invention is brought into contact with the protein D of the invention, with that in the case where the ligand of the invention and a test compound are brought into contact with the protein D of the invention, (b) a method of screening a compound or its salt that alters the binding property between the ligand of the present invention and the protein D of the present invention, which comprises measuring and comparing the amount of the ligand of the invention bound to cells containing the protein D of the invention or a membrane fraction of the cells in the case where the ligand of the invention is brought into contact with the cells or the cell membrane fraction, with that in the case where the ligand of the invention and a test compound are brought into contact with the cells or the cell membrane fraction, (c) the screening method according to the above-mentioned (b), wherein the protein D of the present invention is the protein D of the present invention which was expressed on a cell membrane by culturing a transformant comprising DNA encoding the protein D of the present invention, and (d) the screening method according to the above-mentioned (a) to (c), wherein the ligand of the present invention is a labeled ligand. The protein D of the present invention is preferably the one in membrane fractions from organs in humans or warm-blooded animals. However, acquisition of human-derived organs is extremely difficult, and thus the protein D used in screening is preferably the one expressed in a large amount by a transformant. For producing the protein D of the present invention, the above-described process for producing the protein D of the resent invention is used. When cells containing the protein D of the present invention or a membrane fraction of the cells is used in the screening method described above, a preparation method described later may be followed. Where cells containing the protein D of the present invention are used, the cells may be fixed using glutaraldehyde, formalin, etc. The fixation can be made by a publicly known method. The cells containing the protein D of the present invention are host cells that have expressed the protein D of the present invention, and the host cells include Escherichia coli, Bacillus subtilis, yeast, insect cells, animal cells, and the like. The method of producing the cells is the same as described above. The cell membrane fraction refers to a fraction abundant in cell membrane obtained by cell disruption and subsequent fractionation by a publicly known method. Useful cell disruption methods include cell squashing using a Potter-Elvehjem homogenizer, disruption using a Waring blender or Polytron (manufactured by Kinematica Inc.), disruption by ultrasonication, and disruption by cell spraying through thin nozzles under an increased pressure using a French press or the like. Cell membrane fractionation is effected mainly by fractionation using a centrifugal force, such as centrifugation for fractionation and density gradient centrifugation. For example, cell disruption fluid is centrifuged at a low speed (500 rpm to 3,000 rpm) for a short period of time (normally about 1 to about 10 minutes), the resulting supernatant is then centrifuged at a higher speed (15,000 rpm to 30,000 rpm) normally for 30 minutes to 2 hours. The precipitate thus obtained is used as the membrane fraction. The membrane fraction is rich in the protein D expressed and membrane components such as cell-derived phospholipids and membrane proteins. The amount of the protein D of the invention in the cells containing the protein D and in the membrane fraction of the cells is preferably 103 to 108 molecules per cell, more preferably 105 to 107 molecules per cell. As the amount of expression increases, the ligand binding activity per unit of membrane fraction (specific activity) increases so that not only the highly sensitive screening system can be constructed but also large quantities of samples can be assayed with the same lot. To carry out the screening method described above, for example a fraction of the protein D of the present invention and the ligand of the present invention (for example, the labeled ligand of the present invention) are used. The fraction of the protein D of the present invention is preferably a fraction of the naturally occurring protein D of the present invention or the recombinant protein D of the present invention having an activity equivalent to that of the natural protein. Herein, the equivalent activity is intended to mean a ligand binding activity etc. As the labeled ligand, use can be made of ligands labeled for example with radioisotopes (for example, [3H], [125I], [14C], [32P], [33P], [35S], etc.), fluorescent substances (for example, cyanine fluorescent dyes (e.g., Cy2, Cy3, Cy5, Cy5.5, Cy7 (Amersham Bioscience) etc), fluorescein etc.), luminescent substances (for example, luminol etc.), enzymes (for example, peroxidase etc.) or lanthanide elements. Specifically, to screen the compounds or salts thereof that alter the binding property between the ligand of the present invention and the protein D of the present invention, first, the receptor standard is prepared by suspending cells or cell membrane fraction containing the protein D of the present invention in a buffer appropriate for the screening. For the buffer, any buffer that does not interfere with the binding of the ligand to the protein is usable and examples of such a buffer are phosphate buffer, Tris-hydrochloride buffer, etc., having a pH value of 4 to 10 (preferably a pH value of 6 to 8). To minimize a non-specific binding, a surfactant such as CHAPS, Tween-80™ (Kao-Atlas Co.), digitonin, deoxycholate, etc. may be added to the buffer. To inhibit degradation of the protein D of the present invention by proteases, protease inhibitors such as PMSF, leupeptin, E-64 (manufactured by Peptide Research Laboratory, Co.), and pepstatin may be added. A predetermined amount (5,000 to 500,000 cpm) of the labeled ligand of the present invention is added to 0.01 to 10 ml solution of the protein in the coexistence of 10−10 to 10−7 M test compound. To examine non-specific binding (NSB), a reaction tube containing the unlabeled ligand of the present invention in large excess is also prepared. The reaction is carried out at approximately 0 to 50° C., preferably about 4 to 37° C. for about 20 minutes to about 24 hours, preferably about 30 minutes to about 3 hours. After completion of the reaction, the reaction mixture is filtrated through glass fiber filter paper, etc. and washed with an appropriate volume of the same buffer. The residual radioactivity on the glass fiber filter paper is then measured by means of a liquid scintillation counter or γ-counter. Assuming that the count (B0-NSB) obtained by subtracting the amount of non-specific binding (NSB) from the count obtained in the absence of any competitive substance (B0) is 100%, the test compound by which the amount of specific binding (B-NSB) is reduced for example to 50% or less can be selected as a candidate substance having a potential of competitive inhibition. The compounds or salts thereof obtained by using the screening method of the present invention are the compounds or salts thereof that alter the binding property between the protein D of the present invention and the ligand of the present invention. The polynucleotide encoding the protein of the present invention is useful as a reagent for screening a compound or its salt that promotes or inhibits the expression of the protein gene of the present invention. The present invention provides (3) a method of screening a compound or a salt thereof (also referred to hereinafter the promoter and inhibitor) that promotes or inhibits the expression of the gene for the protein of the invention, which comprises using a polynucleotide encoding the protein of the present invention. More specifically, the present invention provides, for example: (4) a method of screening the promoter and inhibitor, which comprises comparing the case (iii) where cells having an ability to produce the protein of the present invention are cultured, with the case (iv) where a mixture of a test compound and cells having an ability to produce the protein of the present invention is cultured. The screening method comprises, for example, measuring and comparing the expression level of the gene for the protein of the present invention (specifically, the amount of the protein of the present invention or the amount of mRNA encoding the protein) in the case (iii), with that in the case (iv). Examples of the test compounds include peptides, proteins, non-peptide compounds, synthetic compounds, fermentation products, cell extracts, plant extracts, animal tissue extracts etc. and these compounds may be novel compounds or publicly known compounds. To perform the screening method described above, a protein preparation is prepared by suspending cells having an ability to produce the protein of the present invention in a buffer appropriate for screening. A buffer such as a phosphate buffer or a borate buffer having a pH value of about 4 to 10 (preferably pH of about 6 to 8) can be used so long as it does not inhibit expression of the protein of the present invention. As the cells having an ability to produce the protein of the present invention, for example a host (transformant) transformed with a vector comprising the DNA encoding the protein of the present invention described above is used. As the host, animal cells such as CHO cells are preferably used. In the screening, for example a transformant expressing the protein of the present invention on a cell membrane by culturing it by the method described above is preferably used. In measuring the amount of the protein of the present invention, the protein present in a cellular extract or the like can be measured according to known methods, for example by Western analysis, ELISA or the like, or a modification thereof, with antibodies recognizing the protein of the present invention. The expression level of the protein gene of the present invention can be measured by known methods, for example Northern blotting, reverse transcription-polymerase chain reaction (RT-PCR), a real-time PCR analysis system (TaqMan polymerase chain reaction, Applied Biosystems) or by a modification thereof. For example, a test compound by which the expression level of the protein gene of the present invention in the case (iv) is promoted by at least about 20%, preferably at least about 30%, more preferably at least about 50%, as compared with the expression level in the case (iii), can be selected as a compound or its salt that promotes the expression level of the protein gene of the present invention. For example, a test compound by which the expression level of the protein gene of the present invention in the case (iv) is inhibited by at least about 20%, preferably at least about 30%, more preferably at least about 50%, as compared with the expression level in the case (iii), can be selected as a compound or its salt that inhibits the expression level of the protein gene of the present invention. The antibody of the present invention is useful as a reagent for screening a compound or a salt thereof that promotes or inhibits the expression of the protein of the present invention. The present invention provides (5) a method of screening a compound or a salt thereof (also referred to hereinafter as the promoter and inhibitor) that promotes or inhibits the expression of the protein of the present invention, which comprises using the antibody of the present invention. More specifically, the present invention provides, for example: (6) a method of screening the promoter or inhibitor, which comprises comparing the case (v) where cells having an ability to produce the protein of the present invention are cultured, with the case (vi) where a mixture of a test compound and cells having an ability to produce the protein of the present invention is cultured. The screening method comprises, for example, the measurement (e.g., detection of the expression of the protein of the present invention, quantification of the expressed protein of the present invention, etc.) of the expression level of the protein of the present invention (specifically, the amount of the protein of the present invention) by the antibody of the present invention and comparing the amount of the expressed protein in the case (v) with that in the case (vi). Examples of the test compounds include peptides, proteins, non-peptide compounds, synthetic compounds, fermentation products, cell extracts, plant extracts, animal tissue extracts, etc. and these compounds may be novel compounds or publicly known compounds. To perform the screening method described above, a protein preparation is prepared by suspending cells having an ability to produce the protein of the present invention in a buffer appropriate for screening. A buffer such as a phosphate buffer or a borate buffer having a pH value of about 4 to 10 (preferably pH of about 6 to 8) can be used so long as it does not inhibit the activity of the protein of the present invention. As the cells having an ability to produce the protein of the present invention, for example a host (transformant) transformed with a vector comprising the DNA encoding the protein of the present invention described above is used. As the host, animal cells such as CHO cells are preferably used. In the screening, for example a transformant expressing the protein of the present invention on a cell membrane by culturing it by the method described above is preferably used The amount of the protein of the present invention can determined by measuring the protein present in a cell extract with the antibody of the invention recognizing the protein by publicly known methods, for example, Western analysis, ELISA, or a modification of the known methods. For example, a test compound by which the expression of the protein of the invention in the case (vi) is promoted by at least about 20%, preferably at least about 30%, more preferably at least about 50%, as compared with the expression in the case (v) can be selected as a compound or its salt that promotes the expression of the protein of the present invention. For example, a test compound by which the expression of the protein of the invention in the case (vi) is inhibited by at least about 20%, preferably at least about 30%, more preferably at least about 50%, as compared with the expression in the case (v) can be selected as a compound or its salt that inhibits the expression of the protein of the present invention. The screening kit of the present invention comprises the protein of the present invention or its partial peptide or salts thereof, a cell having an ability to produce the protein or partial peptide of the present invention, the ligand of the present invention, the antibody of the present invention, etc. The compounds or salts thereof, which are obtainable using the screening method or screening kit of the present invention, are compounds (or salts thereof) selected from, e.g., peptides, proteins, non-peptide compounds, synthetic compounds, fermentation products, cell extracts, plant extracts, animal tissue extracts, blood plasma, and the like, and these compounds or salts thereof are compounds or their salts promoting or inhibiting the activity of the protein of the present invention, compounds or their salts promoting or inhibiting the expression of the protein gene of the present invention, compounds or their salts promoting or inhibiting the expression of the protein of the present invention, compounds or their salts altering the binding property between the protein A of the present invention and the ligand of the present invention, etc. For salts of these compounds, the same salts as those given for the protein of the present invention above may be used. The compound or its salt promoting the activity of the protein A of the present invention, the compound or its salt promoting the expression of the protein A gene of the present invention, and the compound or its salt promoting the expression of the protein A of the present invention are useful as safe and low toxic drugs such as prophylactic/therapeutic agents for diseases such as hyperlipemia, genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, bronchial asthma etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), diabetes, hypothyroidism, circulatory diseases (e.g., cardiac insufficiency, arrhythmia, long QT syndrome, arteriosclerosis, angina etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably hyperlipemia, arteriosclerosis, genital diseases, digestive diseases etc. The compound or its salt inhibiting the activity of the protein A of the present invention, the compound or its salt inhibiting the expression of the protein A gene of the present invention, and the compound or its salt inhibiting the expression of the protein A of the present invention are useful as safe and low toxic drugs such as prophylactic/therapeutic agents for diseases such as hyperlipemia, genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, bronchial asthma etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), diabetes, hypothyroidism, circulatory diseases (e.g., cardiac insufficiency, arrhythmia, long QT syndrome, arteriosclerosis, angina etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably hyperlipemia, arteriosclerosis, genital diseases, digestive diseases etc. The compound or its salt promoting the activity of the protein B of the present invention, the compound or its salt promoting the expression of the protein B gene of the present invention, and the compound or its salt promoting the expression of the protein B of the present invention are useful as safe and low toxic drugs such as prophylactic/therapeutic agents for diseases such as renal diseases (e.g., renal insufficiency, uremia etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), spleen diseases, cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.), diabetes, hypertension, ischemia-reperfusion injury, central nerve diseases (e.g., Alzheimer's disease, Parkinson's syndrome, schizophrenia, cerebral vascular dementia, cerebral ischemia, epilepsy etc.), preferably respiratory diseases, renal diseases, digestive diseases etc. The compound or its salt inhibiting the activity of the protein B of the present invention, the compound or its salt inhibiting the expression of the protein B gene of the present invention, and the compound or its salt inhibiting the expression of the protein B of the present invention are useful as safe and low toxic drugs such as prophylactic/therapeutic agents for diseases such as renal diseases (e.g., renal insufficiency, uremia etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), spleen diseases, cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.), diabetes, hypertension, ischemia-reperfusion injury, central nerve diseases (e.g., Alzheimer's disease, Parkinson's syndrome, schizophrenia, cerebral vascular dementia, cerebral ischemia, epilepsy etc.), preferably respiratory diseases, renal diseases, digestive diseases etc. The compound or its salt promoting the activity of the protein C of the present invention, the compound or its salt promoting the expression of the protein C gene of the present invention, and the compound or its salt promoting the expression of the protein C of the present invention are useful as safe and low toxic drugs such as prophylactic/therapeutic agents for diseases such as pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), central nerve diseases (e.g., Alzheimer's disease, Parkinson's syndrome, schizophrenia, cerebral vascular dementia, cerebral ischemia, epilepsy etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), diabetes, hyperlipemia, cholestasis, or cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably pancreatic diseases, central nerve diseases, digestive diseases, respiratory diseases etc. The compound or its salt inhibiting the activity of the protein C of the present invention, the compound or its salt inhibiting the expression of the protein C gene of the present invention, and the compound or its salt inhibiting the expression of the protein C of the present invention are useful as safe and low toxic drugs such as prophylactic/therapeutic agents for diseases such as pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), central nerve diseases (e.g., Alzheimer's disease, Parkinson's syndrome, schizophrenia, cerebral vascular dementia, cerebral ischemia, epilepsy etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), diabetes, hyperlipemia, cholestasis, or cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably pancreatic diseases, central nerve diseases, digestive diseases, respiratory diseases etc. The compound or its salt promoting the activity of the protein D of the present invention, the compound or its salt promoting the expression of the protein D gene of the present invention, and the compound or its salt promoting the expression of the protein D of the present invention are useful as safe and low toxic drugs such as prophylactic/therapeutic agents for diseases such as inflammatory diseases (e.g., septicemia, pneumonia, encephalitis, meningitis, hepatitis, myocarditis, pleurisy etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), diabetic neurosis, thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), circulatory diseases (e.g., cardiac insufficiency, arrhythmia, long QT syndrome, arteriosclerosis, angina etc.), hepatic diseases (e.g., hepatocirrhosis etc.), renal diseases (e.g., renal insufficiency, uremia etc.), muscular diseases (e.g., muscular dystrophy etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), burns, pain syndrome (e.g., cancerous sharp pain, referred pain etc.), cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably inflammatory diseases, rheumatoid diseases, diabetic neurosis etc. The compound or its salt inhibiting the activity of the protein D of the present invention, the compound or its salt inhibiting the expression of the protein D gene of the present invention, and the compound or its salt inhibiting the expression of the protein D of the present invention are useful as safe and low toxic drugs such as prophylactic/therapeutic agents for diseases such as inflammatory diseases (e.g., septicemia, pneumonia, encephalitis, meningitis, hepatitis, myocarditis, pleurisy etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), diabetic neurosis, thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), circulatory diseases (e.g., cardiac insufficiency, arrhythmia, long QT syndrome, arteriosclerosis, angina etc.), hepatic diseases (e.g., hepatocirrhosis etc.), renal diseases (e.g., renal insufficiency, uremia etc.), muscular diseases (e.g., muscular dystrophy etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), burns, pain syndrome (e.g., cancerous sharp pain, referred pain etc.), cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably inflammatory diseases, rheumatoid diseases, diabetic neurosis etc. The compound or its salt altering the binding property between the protein D of the present invention and the ligand of the present invention is useful as a safe and low toxic drug such as a prophylactic/therapeutic agent for diseases such as inflammatory diseases (e.g., septicemia, pneumonia, encephalitis, meningitis, hepatitis, myocarditis, pleurisy etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), diabetic neurosis, thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), circulatory diseases (e.g., cardiac insufficiency, arrhythmia, long QT syndrome, arteriosclerosis, angina etc.), hepatic diseases (e.g., hepatocirrhosis etc.), renal diseases (e.g., renal insufficiency, uremia etc.), muscular diseases (e.g., muscular dystrophy etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), burns, pain syndrome (e.g., cancerous sharp pain, referred pain etc.), cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably inflammatory diseases, rheumatoid diseases, diabetic neurosis etc. When the compounds obtainable using the screening method or screening kit of the present invention are used as the prophylactic/therapeutic agents described above, the compounds can be formulated by the conventional methods. The compounds may be prepared for example in the form of tablets, capsules, elixirs, microcapsules, sterile solutions, suspensions, etc. Since the thus obtained medicine is safe and low toxic, and can be administered to, for example, humans or warm-blooded animals (e.g., mouse, rat, rabbit, sheep, swine, bovine, horse, chicken, cat, dog, monkey, chimpanzee etc.). The dose of the above compound or its salt may vary depending on its action, target disease, subject to be administered, route for administration, etc. When the compound or its salt that promotes the activity or expression of the protein A of the present invention is orally administered for example for the purpose of treatment of hyperlipermia, the compound or its salt is administered to adult (as 60 kg) generally in a daily dose of approximately 0.1 mg to 100 mg, preferably approximately 1.0 mg to 50 mg, more preferably approximately 1.0 to 20 mg. When the compound or its salt is parenterally administered, a single dose of the compound or its salt may vary depending on subject to be administered, target disease, etc. When the compound or its salt is administered in the form of an injection to adult (as 60 kg body weight) for the purpose of treatment of hyperlipemia, it is convenient to administer the compound or its salt by intravenous injection generally in a daily dose of approximately 0.01 to 30 mg, preferably approximately 0.1 to 20 mg, more preferably approximately 0.1 to 10 mg. For other animal species, the corresponding dose as converted per 60 kg weight can be administered. The dose of the compound or its salt may vary depending on its action, target disease, subject to be administered, route for administration, etc. When the compound or its salt that promotes the activity or expression of the protein B of the present invention is orally administered for example for the purpose of treatment of renal insufficiency, the compound or its salt is administered to adult (as 60 kg) generally in a daily dose of approximately 0.1 mg to 100 mg, preferably approximately 1.0 mg to 50 mg, more preferably approximately 1.0 to 20 mg. When the compound or its salt is parenterally administered, a single dose of the compound or its salt may vary depending on subject to be administered, target disease, etc. When the compound or its salt is administered in the form of an injection to adult (as 60 kg body weight) for the purpose of treatment of renal insufficiency, it is convenient to administer the compound or its salt by intravenous injection generally in a daily dose of approximately 0.01 to 30 mg, preferably approximately 0.1 to 20 mg, more preferably approximately 0.1 to 10 mg. For other animal species, the corresponding dose as converted per 60 kg weight can be administered. The dose of the compound or its salt may vary depending on its action, target disease, subject to be administered, route for administration, etc. When the compound or its salt that promotes the activity or expression of the protein C of the present invention is orally administered for example for the purpose of treatment of diabetes, the compound or its salt is administered to adult (as 60 kg) generally in a daily dose of approximately 0.1 mg to 100 mg, preferably approximately 1.0 mg to 50 mg, more preferably approximately 1.0 to 20 mg. When the compound or its salt is parenterally administered, a single dose of the compound or its salt may vary depending on subject to be administered, target disease, etc. When the compound or its salt is administered in the form of an injection to adult (as 60 kg body weight) for the purpose of treatment of diabetes, it is convenient to administer the compound or its salt by intravenous injection generally in a daily dose of approximately 0.01 to 30 mg, preferably approximately 0.1 to 20 mg, more preferably approximately 0.1 to 10 mg. For other animal species, the corresponding dose as converted per 60 kg weight can be administered. The dose of the compound or its salt may vary depending on its action, target disease, subject to be administered, route for administration, etc. When the compound or its salt that promotes the activity or expression of the protein D of the present invention, or the compound or its salt that alters the binding property between the protein D of the present invention and the ligand of the present invention is orally administered for example for the purpose of treatment of chronic articular rheumatism, the compound or its salt is administered to adult (as 60 kg) generally in a daily dose of approximately 0.1 mg to 100 mg, preferably approximately 1.0 mg to 50 mg, more preferably approximately 1.0 to 20 mg. When the compound or its salt is parenterally administered, a single dose of the compound or its salt may vary depending on subject to be administered, target disease, etc. When the compound or its salt is administered in the form of an injection to adult (as 60 kg body weight) for the purpose of treatment of chronic articular rheumatism, it is convenient to administer the compound or its salt by intravenous injection generally in a daily dose of approximately 0.01 to 30 mg, preferably approximately 0.1 to 20 mg, more preferably approximately 0.1 to 10 mg. For other animal species, the corresponding dose as converted per 60 kg weight can be administered. [3] Quantification of the Protein of the Present Invention, its Partial Peptide, or its Salt The antibody of the present invention is capable of specifically recognizing the protein of the present invention and can thus be used for quantification of the protein of the present invention in a test sample fluid, in particular, for quantification by the sandwich immunoassay. That is, the present invention provides: (i) a method for quantification of the protein of the present invention in a test sample fluid, which comprises competitively reacting the antibody of the present invention, a test sample fluid and a labeled form of the protein of the present invention, and measuring the ratio of the labeled protein of the present invention bound to the antibody; and (ii) a method for quantification of the protein of the present invention in a test sample fluid, which comprises reacting the test sample fluid simultaneously or continuously with the antibody of the present invention immobilized on a carrier and a labeled form of the antibody of the present invention, and then measuring the activity of the labeling agent on the insoluble carrier. In the quantification method in the above-mentioned (ii), it is desirable that one antibody is an antibody recognizing the N-terminal region of the protein of the present invention, and the other antibody is an antibody reacting with the C-terminal region of the protein of the present invention. The monoclonal antibody to the protein of the present invention (hereinafter sometimes referred to as the monoclonal antibody of the present invention) may be used to quantify the protein of the present invention. Besides, the protein of the present invention may also be detected by means of tissue staining. For these purposes, the antibody molecule per se may be used or F(ab′)2, Fab′ or Fab fractions of the antibody molecule may be used as well. There is no particular limitation to the method of quantifying the protein of the present invention using the antibody of the present invention; any method may be used so far as it relates to a method in which the amount of antibody, antigen or antibody-antigen complex can be detected by a chemical or a physical means, depending on or corresponding to the amount of antigen (e.g., the amount of the protein) in a test sample fluid to be assayed, and then calculated using a standard curve prepared by a standard solution containing the known amount of antigen. Advantageously used are, for example, nephrometry, competitive method, immunometric method and sandwich method; in terms of sensitivity and specificity, the sandwich method, which will be later described, is particularly preferred. Examples of the labeling agent used in the assay method using the labeling substance are radioisotopes (for example, [125I], [131I], [3H], [14C] etc.), fluorescent substances [for example, cyanine fluorescent dyes (e.g., Cy2, Cy3, Cy5, Cy5.5, Cy7 (Amersham Bioscience) etc), fluorescamine, fluorescein isothiocyanate etc.], enzymes (for example, β-galactosidase, β-glucosidase, alkaline phosphatase, peroxidase, malate dehydrogenase etc), luminescent substances (for example, luminol, a luminol derivative, luciferin, lucigenin etc.), biotin, and lanthanide elements. Furthermore, the biotin-avidin system may also be used for binding of an antibody or antigen to a labeling agent. For immobilization of antigen or antibody, physical adsorption may be used. Chemical binding methods conventionally used for insolubilization or immobilization of proteins or enzymes may also be used. For the carrier, for example, insoluble polysaccharides such as agarose, dextran, cellulose, etc.; synthetic resin such as polystyrene, polyacrylamide, silicon, etc., and glass or the like. are used. In the sandwich method, the immobilized monoclonal antibody of the present invention is reacted with a test fluid (primary reaction), then with the labeled monoclonal antibody of the present invention (secondary reaction), and the activity of the label on the immobilizing carrier is measured, whereby the amount of the protein of the present invention in the test fluid can be quantified. The order of the primary and secondary reactions may be reversed, and the reactions may be performed simultaneously or with an interval. The methods of labeling and immobilization can be performed by the methods described above. In the immunoassay by the sandwich method, the antibody used for immobilized or labeled antibodies is not necessarily one species, but a mixture of two or more species of antibody may be used to increase the measurement sensitivity. In the method for assaying the protein of the present invention by the sandwich method according to the present invention, preferred monoclonal antibodies of the present invention used for the primary and the secondary reactions are antibodies whose binding sites to the protein of the present invention are different from one another. Thus, the antibodies used in the primary and the secondary reactions are those wherein, when the antibody used in the secondary reaction recognizes the C-terminal region of the protein of the present invention, the antibody recognizing the site other than the C-terminal region, e.g., recognizing the N-terminal region, is preferably used in the primary reaction. The monoclonal antibody of the present invention may be used in an assay system other than the sandwich method, such as a competitive method, an immunometric method, nephrometry, etc. In the competitive method, an antigen in a test sample fluid and a labeled antigen are competitively reacted with an antibody, then the unreacted labeled antigen (F) and the labeled antigen bound to the antibody (B) are separated (B/F separation) and the labeled amount of either B or F is measured to determine the amount of the antigen in the test sample fluid. In the reactions for such a method, there are a liquid phase method in which a soluble antibody is used as the antibody and the B/F separation is effected by polyethylene glycol while a second antibody to the antibody described above is used, and a solid phase method in which an immobilized antibody is used as the first antibody or a soluble antibody is used as the first antibody while an immobilized antibody is used as the second antibody. In the immunometric method, an antigen in a test sample fluid and an immobilized antigen are competitively reacted with a given amount of a labeled antibody followed by separating the solid phase from the liquid phase; or an antigen in a test sample fluid and an excess amount of labeled antibody are reacted, then an immobilized antigen is added to bind an unreacted labeled antibody to the solid phase, and the solid phase is separated from the liquid phase. Thereafter, the labeled amount of any of the phases is measured to determine the antigen amount in the test sample fluid. In the nephrometry, the amount of insoluble sediment, which is produced as a result of the antigen-antibody reaction in a gel or in a solution, is measured Even when the amount of an antigen in a test sample fluid is small and only a small amount of the sediment is obtained, laser nephrometry utilizing laser scattering can be suitably used. In applying each of those immunoassays to the quantification method of the present invention, any special conditions or operations are not required to set forth. The assay system for the protein of the present invention may be constructed in addition to conditions or operations conventionally used for each of the methods, taking the technical consideration by one skilled in the art into account. For the details of such conventional technical means, a variety of reviews, reference books, etc. may be referred to (for example, Hiroshi Irie (ed.): “Radioimmunoassay” (published by Kodansha, 1974); Hiroshi Irie (ed.): “Radioimmunoassay; Second Series” (published by Kodansha, 1979); Eiji Ishikawa, et al. (ed.): “Enzyme Immunoassay” (published by Igaku Shoin, 1978); Eiji Ishikawa, et al. (ed.): “Enzyme Immunoassay” (Second Edition) (published by Igaku Shoin, 1982); Eiji Ishikawa, et al. (ed.): “Enzyme Immunoassay” (Third Edition) (published by Igaku Shoin, 1987); “Methods in Enzymology” Vol. 70 (Immuochemical Techniques (Part A)); ibid., Vol. 73 (Immunochemical Techniques (Part B)); ibid., Vol. 74 (Immunochemical Techniques (Part C)); ibid., Vol. 84 (Immunochemical Techniques (Part D: Selected Immunoassays)); ibid., Vol. 92 (Immunochemical Techniques (Part E: Monoclonal Antibodies and General Immunoassay Methods)); ibid., Vol. 121 (Immunochemical Techniques (Part I: Hybridoma Technology and Monoclonal Antibodies)) (published by Academic Press); etc.) As described above, the protein of the present invention can be quantified with high sensitivity, using the antibody of the present invention. When a reduction in the concentration of the protein A of the present invention is detected by quantifying the concentration of the protein A of the invention with the antibody of the present invention, it can be diagnosed that there highly likely occur diseases such as hyperlipemia, genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, bronchial asthma etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), diabetes, hypothyroidism, circulatory diseases (e.g., cardiac insufficiency, arrhythmia, long QT syndrome, arteriosclerosis, angina etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably hyperlipemia, arteriosclerosis, genital diseases, digestive diseases etc. On the other hand, when an increase in the concentration of the protein A of the present invention is detected, it can be diagnosed that there highly likely occur diseases such as hyperlipemia, genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, bronchial asthma etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), diabetes, hypothyroidism, circulatory diseases (e.g., cardiac insufficiency, arrhythmia, long QT syndrome, arteriosclerosis, angina etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably hyperlipemia, arteriosclerosis, genital diseases, digestive diseases etc. When a reduction in the concentration of the protein B of the present invention is detected by quantifying the concentration of the protein B of the invention with the antibody of the present invention, it can be diagnosed that there highly likely occur diseases such as renal diseases (e.g., renal insufficiency, uremia etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), spleen diseases, cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.), diabetes, hypertension, ischemia-reperfusion injury, central nerve diseases (e.g., Alzheimer's disease, Parkinson's syndrome, schizophrenia, cerebral vascular dementia, cerebral ischemia, epilepsy etc.), preferably respiratory diseases, renal diseases, digestive diseases etc. On the other hand, when an increase in the concentration of the protein B of the present invention is detected, it can be diagnosed that there highly likely occur diseases such as renal diseases (e.g., renal insufficiency, uremia etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), spleen diseases, cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.), diabetes, hypertension, ischemia-reperfusion injury, central nerve diseases (e.g., Alzheimer's disease, Parkinson's syndrome, schizophrenia, cerebral vascular dementia, cerebral ischemia, epilepsy etc.) etc., preferably respiratory diseases, renal diseases, digestive diseases etc. When a reduction in the concentration of the protein C of the present invention is detected by quantifying the concentration of the protein D of the invention with the antibody of the present invention, it can be diagnosed that there highly likely occur diseases such as pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), central nerve diseases (e.g., Alzheimer's disease, Parkinson's syndrome, schizophrenia, cerebral vascular dementia, cerebral ischemia, epilepsy etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), diabetes, hyperlipemia, cholestasis, or cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably pancreatic diseases, central nerve diseases, digestive diseases, respiratory diseases etc. On the other hand, when an increase in the concentration of the protein C of the present invention is detected, it can be diagnosed that there highly likely occur diseases such as pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), central nerve diseases (e.g., Alzheimer's disease, Parkinson's syndrome, schizophrenia, cerebral vascular dementia, cerebral ischemia, epilepsy etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), diabetes, hyperlipemia, cholestasis, or cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably pancreatic diseases, central nerve diseases, digestive diseases, respiratory diseases etc. When a reduction in the concentration of the protein D of the present invention is detected by quantifying the concentration of the protein D of the invention with the antibody of the present invention, it can be diagnosed that there highly likely occur diseases such as inflammatory diseases (e.g., septicemia, pneumonia, encephalitis, meningitis, hepatitis, myocarditis, pleurisy etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), diabetic neurosis, thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), circulatory diseases (e.g., cardiac insufficiency, arrhythmia, long QT syndrome, arteriosclerosis, angina etc.), hepatic diseases (e.g., hepatocirrhosis etc.), renal diseases (e.g., renal insufficiency, uremia etc.), muscular diseases (e.g., muscular dystrophy etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), burns, pain syndrome (e.g., cancerous sharp pain, referred pain etc.), cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably inflammatory diseases, rheumatoid diseases and diabetic neurosis. On the other hand, when an increase in the concentration of the protein D of the present invention is detected, it can be diagnosed that there highly likely occur diseases such as inflammatory diseases (e.g., septicemia, pneumonia, encephalitis, meningitis, hepatitis, myocarditis, pleurisy etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), diabetic neurosis, thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), circulatory diseases (e.g., cardiac insufficiency, arrhythmia, long QT syndrome, arteriosclerosis, angina etc.), hepatic diseases (e.g., hepatocirrhosis etc.), renal diseases (e.g., renal insufficiency, uremia etc.), muscular diseases (e.g., muscular dystrophy etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), burns, pain syndrome (e.g., cancerous sharp pain, referred pain etc.), cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably inflammatory diseases, rheumatoid diseases, diabetic neurosis etc. The antibodies of the present invention can also be used for specifically detecting the protein of the present invention present in test samples such as body fluids or tissues. The antibodies may also be used for preparation of antibody columns for purification of the protein of the present invention, for detection of the protein of the present invention in each fraction upon purification, and for analysis of the behavior of the protein of the present invention in the test cells. [4] Gene Diagnostic Agent By using the DNA of the present invention as a probe, an abnormality (gene abnormality) of the DNA or mRNA encoding the protein of the present invention or its partial peptide in human or non-human warm-blooded animals (e.g., rat, mouse, guinea pig, rabbit, chicken, sheep, swine, bovine, horse, cat, dog, monkey, chimpanzee etc.) can be detected. Therefore, the DNA of the present invention is useful as a gene diagnostic agent for the damage against the DNA or mRNA, its mutation, or its decreased expression, or increased expression or over-expression of the DNA or mRNA. The gene diagnosis described above using the DNA of the present invention can be performed by, for example, the publicly known Northern hybridization assay or the PCR-SSCP assay (Genomics, 5, 874-879 (1989); Proceedings of the National Academy of Sciences of the United States of America, 86, 2766-2770 (1989)). For example, when the increased expression of the protein A gene of the present invention is detected by Northern hybridization, it can be diagnosed that there highly likely occur diseases such as hyperlipemia, genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, bronchial asthma etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), diabetes, hypothyroidism, circulatory diseases (e.g., cardiac insufficiency, arrhythmia, long QT syndrome, arteriosclerosis, angina etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably hyperlipemia, arteriosclerosis, genital diseases, digestive diseases etc. On the other hand, when a reduction in the expression is detected or when a mutation in the DNA is detected by PCR-SSCP, it can be diagnosed that there highly likely occur diseases such as hyperlipemia, genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, bronchial asthma etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), diabetes, hypothyroidism, circulatory diseases (e.g., cardiac insufficiency, arrhythmia, long QT syndrome, arteriosclerosis, angina etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably hyperlipemia, arteriosclerosis, genital diseases, digestive diseases etc. For example, when the increased expression of the protein B gene of the present invention is detected by Northern hybridization, it can be diagnosed that there highly likely occur diseases such as renal diseases (e.g., renal insufficiency, uremia etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), spleen diseases, cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.), diabetes, hypertension, ischemia-reperfusion injury, central nerve diseases (e.g., Alzheimer's disease, Parkinson's syndrome, schizophrenia, cerebral vascular dementia, cerebral ischemia, epilepsy etc.) etc., preferably respiratory diseases, renal diseases, digestive diseases etc. On the other hand, a reduction in the expression is detected or when a mutation in the DNA is detected by PCR-SSCP, it can be diagnosed that there highly likely occur diseases such as renal diseases (e.g., renal insufficiency, uremia etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), spleen diseases, cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.), diabetes, hypertension, ischemia-reperfusion injury, central nerve diseases (e.g., Alzheimer's disease, Parkinson's syndrome, schizophrenia, cerebral vascular dementia, cerebral ischemia, epilepsy etc.) etc., preferably respiratory diseases, renal diseases, digestive diseases etc. For example, when the increased expression of the protein C gene of the present invention is detected by Northern hybridization, it can be diagnosed that there highly likely occur diseases such as pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), central nerve diseases (e.g., Alzheimer's disease, Parkinson's syndrome, schizophrenia, cerebral vascular dementia, cerebral ischemia, epilepsy etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), diabetes, hyperlipemia, cholestasis, or cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably pancreatic diseases, central nerve diseases, digestive diseases, respiratory diseases etc. On the other hand, a reduction in the expression is detected or when a mutation in the DNA is detected by PCR-SSCP, it can be diagnosed that there highly likely occur diseases such as pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), central nerve diseases (e.g., Alzheimer's disease, Parkinson's syndrome, schizophrenia, cerebral vascular dementia, cerebral ischemia, epilepsy etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), diabetes, hyperlipemia, cholestasis, or cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably pancreatic diseases, central nerve diseases, digestive diseases, respiratory diseases etc. For example, when the increased expression of the protein D gene of the present invention is detected by Northern hybridization, it can be diagnosed that there highly likely occur diseases such as inflammatory diseases (e.g., septicemia, pneumonia, encephalitis, meningitis, hepatitis, myocarditis, pleurisy etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), diabetic neurosis, thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), circulatory diseases (e.g., cardiac insufficiency, arrhythmia, long QT syndrome, arteriosclerosis, angina etc.), hepatic diseases (e.g., hepatocirrhosis etc.), renal diseases (e.g., renal insufficiency, uremia etc.), muscular diseases (e.g., muscular dystrophy etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), burns, pain syndrome (e.g., cancerous sharp pain, referred pain etc.), cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably inflammatory diseases, rheumatoid diseases, diabetic neurosis etc. On the other hand, a reduction in the expression is detected or when a mutation in the DNA is detected by PCR-SSCP, it can be diagnosed that there highly likely occur diseases such as inflammatory diseases (e.g., septicemia, pneumonia, encephalitis, meningitis, hepatitis, myocarditis, pleurisy etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), diabetic neurosis, thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), circulatory diseases (e.g., cardiac insufficiency, arrhythmia, long QT syndrome, arteriosclerosis, angina etc.), hepatic diseases (e.g., hepatocirrhosis etc.), renal diseases (e.g., renal insufficiency, uremia etc.), muscular diseases (e.g., muscular dystrophy etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), burns, pain syndrome (e.g., cancerous sharp pain, referred pain etc.), cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably inflammatory diseases, rheumatoid diseases, diabetic neurosis etc. [5] Medicine Comprising the Antisense Polynucleotide The antisense polynucleotide of the present invention that binds complementarily to the DNA encoding the protein A of the present invention to inhibit expression of the DNA is low-toxic and can suppress the functions and activity of the protein or DNA in the body, and can thus be used as a medicine such as a prophylactic/therapeutic agent for diseases such as hyperlipemia, genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, bronchial asthma etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), diabetes, hypothyroidism, circulatory diseases (e.g., cardiac insufficiency, arrhythmia, long QT syndrome, arteriosclerosis, angina etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc, preferably hyperlipemia, arteriosclerosis, genital diseases, digestive diseases etc. The antisense polynucleotide of the present invention that binds complementarily to the DNA encoding the protein B of the present invention to inhibit expression of the DNA is low-toxic and can suppress the functions and activity of the protein or DNA in the body, and can thus be used as a medicine such as a prophylactic/therapeutic agent for diseases such as renal diseases (e.g., renal insufficiency, uremia etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), spleen diseases, cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.), diabetes, hypertension, ischemia-reperfusion injury, central nerve diseases (e.g., Alzheimer's disease, Parkinson's syndrome, schizophrenia, cerebral vascular dementia, cerebral ischemia, epilepsy etc.) etc., preferably respiratory diseases, renal diseases, digestive diseases etc. The antisense polynucleotide of the present invention that binds complementarily to the DNA encoding the protein C of the present invention to inhibit expression of the DNA is low-toxic and can suppress the functions and activity of the protein or DNA in the body, and can thus be used as a medicine such as a prophylactic/therapeutic agent for diseases such as pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), central nerve diseases (e.g., Alzheimer's disease, Parkinson's syndrome, schizophrenia, cerebral vascular dementia, cerebral ischemia, epilepsy etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), diabetes, hyperlipemia, cholestasis, or cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably pancreatic diseases, central nerve diseases, digestive diseases, respiratory diseases etc. The antisense polynucleotide of the present invention that binds complementarily to the DNA encoding the protein D of the present invention to inhibit expression of the DNA is low-toxic and can suppress the functions and activity of the protein or DNA in the body, and can thus be used as a medicine such as a prophylactic/therapeutic agent for diseases such as inflammatory diseases (e.g., septicemia, pneumonia, encephalitis, meningitis, hepatitis, myocarditis, pleurisy etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), diabetic neurosis, thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), circulatory diseases (e.g., cardiac insufficiency, arrhythmia, long QT syndrome, arteriosclerosis, angina etc.), hepatic diseases (e.g., hepatocirrhosis etc.), renal diseases (e.g., renal insufficiency, uremia etc.), muscular diseases (e.g., muscular dystrophy etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), burns, pain syndrome (e.g., cancerous sharp pain, referred pain etc.), cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably inflammatory diseases, rheumatoid diseases, diabetic neurosis etc. When the antisense polynucleotide is used as the aforesaid prophylactic/therapeutic agent, it can be formed into a medicine and administered in publicly known methods. For example, when the antisense polynucleotide is used, the antisense polynucleotide itself, or the antisense polynucleotide inserted into an appropriate vector such as retrovirus vector, adenovirus vector, adenovirus-associated virus vector, etc., is administered orally or parenterally to human or other warm-blooded animal (e.g., rat, rabbit, sheep, swine, bovine, cat, dog, monkey, etc.) in a conventional manner. The antisense polynucleotide may also be administered as it is, or prepared into medicines together with physiologically acceptable carriers such as adjuvants to assist its uptake, and such preparations are administered by gene gun or through a catheter like a hydrogel catheter. The dose of the antisense polynucleotide may vary depending upon target disease, subject to be administered, route for administration, etc. When the antisense nucleotide is administered topically to a specific digestive organ for the purpose of treatment of hyperlipemia, the antisense polynucleotide is administered to adult (60 kg body weight) usually in a daily dose of approximately 0.1 to 100 mg. In addition, the antisense polynucleotide may also be employed as an oligonucleotide probe for diagnosis to examine the presence of the DNA of the present invention in tissues or cells, or the states of its expression. Further, the present invention provides: (i) double-stranded RNA comprising a part of RNA encoding the protein of the present invention and RNA complementary thereto, (ii) a medicine comprising the double-stranded RNA, (iii) ribozyme comprising a part of RNA encoding the protein of the present invention, (iv) a medicine comprising the ribozyme, and (v) an expression vector comprising a gene (DNA) encoding the ribozyme. The double-stranded RNA or the ribozyme, similar to the antisense polynucleotide described above, can destroy RNA transcribed from the DNA of the present invention, or suppress the functions thereof. The double-stranded RNA or ribozyme which can suppress the functions of the protein A of the present invention or the DNA encoding it can be used as a prophylactic/therapeutic agent for diseases such as hyperlipemia, genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, bronchial asthma etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), diabetes, hypothyroidism, circulatory diseases (e.g., cardiac insufficiency, arrhythmia, long QT syndrome, arteriosclerosis, angina etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably hyperlipemia, arteriosclerosis, genital diseases, digestive diseases etc. The double-stranded RNA or ribozyme which can suppress the functions of the protein B of the present invention or the DNA encoding it can be used as a prophylactic/therapeutic agent for diseases such as renal diseases (e.g., renal insufficiency, uremia etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), spleen diseases, cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.), diabetes, hypertension, ischemia-reperfusion injury, central nerve diseases (e.g., Alzheimer's disease, Parkinson's syndrome, schizophrenia, cerebral vascular dementia, cerebral ischemia, epilepsy etc.) etc., preferably respiratory diseases, renal diseases, digestive diseases etc. The double-stranded RNA or ribozyme which can suppress the functions of the protein C of the present invention or the DNA encoding it can be used as a prophylactic/therapeutic agent for diseases such as pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), central nerve diseases (e.g., Alzheimer's disease, Parkinson's syndrome, schizophrenia, cerebral vascular dementia, cerebral ischemia, epilepsy etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), diabetes, hyperlipemia, cholestasis, or cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably pancreatic diseases, central nerve diseases, digestive diseases, respiratory diseases etc. The double-stranded RNA or ribozyme which can suppress the functions of the protein D of the present invention or the DNA encoding it can be used as a prophylactic/therapeutic agent for diseases such as inflammatory diseases (e.g., septicemia, pneumonia, encephalitis, meningitis, hepatitis, myocarditis, pleurisy etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), diabetic neurosis, thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), circulatory diseases (e.g., cardiac insufficiency, arrhythmia, long QT syndrome, arteriosclerosis, angina etc.), hepatic diseases (e.g., hepatocirrhosis etc.), renal diseases (e.g., renal insufficiency, uremia etc.), muscular diseases (e.g., muscular dystrophy etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), burns, pain syndrome (e.g., cancerous sharp pain, referred pain etc.), cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably inflammatory diseases, rheumatoid diseases, diabetic neurosis etc. According to known methods (for example, Nature, vol. 411, p. 494, 2001), the double-stranded RNA can be produced by designing it on the basis of the sequence of the polynucleotide of the present invention. According to known methods (for example, TRENDS in Molecular Medicine, vol. 7, p. 221, 2001), the ribozyme can be produced by designing it on the basis of the sequence of the polynucleotide of the present invention. For example, the ribozyme can be produced by partially replacing a known ribozyme sequence by a part of RNA encoding the protein of the present invention. The part of RNA encoding the protein of the present invention includes a sequence adjacent to a consensus sequence NUX (N represents any base, and X represents a base other than G) which can be cleaved with a known ribozyme. When the double-stranded RNA or the ribozyme is to be used as the aforesaid prophylactic/therapeutic agent, it can be formed into a medicine and administered in the same manner as for the antisense polynucleotide. The expression vector in (v) above is used as the aforesaid prophylactic/therapeutic agent in the same manner as in known gene therapy methods. [6] Creation of an Animal Having the DNA of the Present Invention The present invention provides a non-human mammal having the DNA encoding the protein of the present invention, which is exogenous (hereinafter simply referred to as the exogenous DNA of the present invention) or its mutant DNA (sometimes simply referred to as the exogenous mutant DNA of the present invention). Thus, the present invention provides: (1) a non-human mammal having the exogenous DNA of the present invention or its mutant DNA; (2) the mammal according to (1), wherein the non-human mammal is a rodent; (3) the mammal according to (2), wherein the rodent is mouse or rat; and (4) a recombinant vector comprising the exogenous DNA of the present invention or its mutant DNA and capable of expression in a mammal. The non-human mammal having the exogenous DNA of the present invention or its mutant DNA (hereinafter simply referred to as the DNA transgenic animal of the present invention) can be created by transfecting a desired DNA into an unfertilized egg, a fertilized egg, a spermatozoon, a germinal cell containing a primordial germinal cell thereof, or the like, preferably in the embryogenic stage in the development of a non-human mammal (more preferably in the single cell or fertilized cell stage and generally before the 8-cell phase) by standard means such as the calcium phosphate method, the electric pulse method, the lipofection method, the agglutination method, the microinjection method, the particle gun method, the DEAE-dextran method, etc. Also, it is possible to transfect the exogenous DNA of the present invention into a somatic cell, a living organ, a tissue cell or the like, by the DNA transfection methods, and utilize the transformant for cell culture, tissue culture, etc. In addition, these cells may be fused with the above-described germinal cell by a publicly known cell fusion method to create the transgenic animal of the present invention. Examples of the non-human mammal that can be used include bovine, swine, sheep, goat, rabbits, dogs, cats, guinea pigs, hamsters, mice, rats and the like. Above all, preferred are rodents, especially mice (e.g., C57BL/6 strain, DBA2 strain, etc. for a pure line and for a cross line, B6C3F1 strain, BDF1 strain, B6D2F1 strain, BALB/c strain, ICR strain, etc.) or rats (Wistar, SD, etc.) and the like, since they are relatively short in ontogeny and life cycle from a standpoint of creating model disease animals, and are easy in breeding. “Mammals” in a recombinant vector that can be expressed in mammals include human etc. in addition to the aforesaid non-human mammals. The exogenous DNA of the present invention refers to the DNA of the present invention that is once isolated and extracted from mammals, not the DNA of the present invention inherently possessed by the non-human mammals. The mutant DNA of the present invention includes mutants resulting from variation (e.g., mutation, etc.) in the base sequence of the original DNA of the present invention, specifically DNAs resulting from base addition, deletion, substitution with other bases, etc. and further including abnormal DNA. The abnormal DNA is intended to mean the DNA that expresses the abnormal protein of the present invention and exemplified by such a DNA that expresses a protein suppressing the functions of the normal protein of the present invention, or the like. The exogenous DNA of the present invention may be any one of those derived from a mammal of the same species as, or a different species from, the mammal as the target animal. In transfecting the DNA of the present invention to the target animal, it is generally advantageous to use the DNA as a DNA construct in which the DNA is ligated downstream a promoter capable of expressing the DNA in the target animal. For example, in the case of transfecting the human DNA of the present invention, a DNA transgenic mammal that expresses the DNA of the present invention to a high level can be prepared by microinjecting a DNA construct (e.g., vector, etc.) ligated with the human DNA of the present invention into a fertilized egg of the target mammal, e.g., a fertilized egg of mouse, downstream the various promoters capable of expressing the DNA derived from various mammals (e.g., rabbits, dogs, cats, guinea pigs, hamsters, rats, mice, etc.) having the DNA of the present invention highly homologous to the human DNA. As expression vectors for the protein of the present invention, there are Escherichia coli-derived plasmids, Bacillus subtilis-derived plasmids, yeast-derived plasmids, bacteriophages such as λ phage, etc., retroviruses such as Moloney leukemia virus, etc., animal viruses such as vaccinia virus, baculovirus, etc. Of these vectors, Escherichia coli-derived plasmids, Bacillus subtilis-derived plasmids, yeast-derived plasmids, etc. are preferably used. Examples of these promoters for regulating the DNA expression include (i) promoters for DNA derived from viruses (e.g., simian virus, cytomegalovirus, Moloney leukemia virus, JC virus, breast cancer virus, poliovirus, etc.), and (ii) promoters derived from various mammals (human, rabbits, dogs, cats, guinea pigs, hamsters, rats, mice, etc.), for example, promoters of albumin, insulin II, uroplakin II, elastase, erythropoietin, endothelin, muscular creatine kinase, glial fibrillary acidic protein glutathione S-transferase, platelet-derived growth factor β, keratins K1, K10 and K14, collagen types I and II, cyclic AMP-dependent protein kinase βI subunit, dystrophin, tartarate-resistant alkaline phosphatase, atrial natriuretic factor, endothelial receptor tyrosine kinase (generally abbreviated as Tie2), sodium-potassium adenosine triphosphorylase (Na, K-ATPase), neurofilament light chain, metallothioneins I and IIA, metalloproteinase 1 tissue inhibitor, MHC class I antigen (H-2L), H-ras, renin, dopamine β-hydroxylase, thyroid peroxidase (TPO), polypeptide chain elongation factor 1α (EF-1α), β actin, α and β myosin heavy chains, myosin light chains 1 and 2, myelin base protein, thyroglobulins, Thy-1, immunoglobulins, H-chain variable region (VNP), serum amyloid component P, myoglobin, troponin C, smooth muscle α actin, preproencephalin A, vasopressin, etc. Among them, cytomegalovirus promoters, human peptide elongation factor 1α (EF-1α) promoters, human and chicken β actin promoters etc., which can achieve high expression in the whole body, are preferred It is preferred that the vectors described above have a sequence for terminating the transcription of the desired messenger RNA in the DNA transgenic animal (generally called a terminator); for example, a sequence of each DNA derived from viruses and various mammals. SV40 terminator of the simian virus, etc. are preferably used. In addition, for the purpose of increasing the expression of the desired exogenous DNA to a higher level, the splicing signal and enhancer region of each DNA, a portion of the intron of an eukaryotic DNA may also be ligated at the 5′ upstream of the promoter region, or between the promoter region and the translational region, or at the 3′ downstream of the translational region, depending upon purposes. The normal translational region of the protein of the present invention can be prepared as the whole or a part of genomic DNA from DNA derived from liver, kidney, thyroid cells, fibroblasts etc. derived from humans or mammals (for example, rabbit, dog, cat, guinea pig, hamster, rat, mouse etc.) and a wide variety of commercial DNA libraries, or from complementary DNA as a starting material prepared by a known method from RNA derived from liver, kidney, thyroid cells, fibroblasts etc. As the extraneous abnormal DNA, a translational region can be prepared by point mutation of the normal translational region of the polypeptide obtained from the above cells or tissues. The translational region can be prepared, as a DNA construct capable of being expressed in the transgenic animal, by a conventional DNA engineering technique, in which the DNA is ligated downstream the aforesaid promoter and if desired, upstream the translation termination site. The exogenous DNA of the present invention is transfected at the fertilized egg cell stage in a manner such that the DNA is certainly present in all the germinal cells and somatic cells of the target mammal. The fact that the exogenous DNA of the present invention is present in the germinal cells of the animal prepared by DNA transfection means that all offspring of the prepared animal will maintain the exogenous DNA of the present invention in all of the germinal cells and somatic cells thereof. The offspring of the animal that inherits the exogenous DNA of the present invention also have the exogenous DNA of the present invention in all of the germinal cells and somatic cells thereof. The non-human mammal, in which the normal exogenous DNA of the present invention has been transfected can be passaged as the DNA-bearing animal under ordinary rearing environment, by confirming that the exogenous DNA is stably retained by mating. By the transfection of the exogenous DNA of the present invention at the fertilized egg cell stage, the DNA is retained to be excess in all of the germinal and somatic cells of the target mammal. The fact that the exogenous DNA of the present invention is excessively present in the germinal cells of the prepared animal after transfection means that all of the offspring of the animal prepared have the exogenous DNA of the present invention excessively in all of the germinal cells and somatic cells thereof. The offspring of the animal of this kind that inherits the exogenous DNA of the present invention excessively have the DNA of the present invention in all of the germinal cells and somatic cells thereof. By obtaining a homozygotic animal having the transfected DNA in both of homologous chromosomes and mating a male and female of the animal, all offspring can be passaged to excessively retain the DNA. In a non-human mammal bearing the normal DNA of the present invention, the normal DNA of the present invention is expressed to a high level, and may eventually develop the hyperfunction of the protein of the present invention by promoting the functions of endogenous normal DNA. Therefore, the animal can be utilized as a pathologic model animal for such a disease. Specifically, using the normal DNA transgenic animal of the present invention, it becomes possible to elucidate the hyperfunction of the protein of the present invention and to clarify the pathological mechanism of the disease associated with the protein of the present invention and to determine how to treat these diseases. Furthermore, since a mammal transfected with the exogenous normal DNA of the present invention exhibits an increasing symptom of the librated protein of the present invention, the animal is usable for screening of therapeutic agents agent for the disease associated with the protein of the present invention. On the other hand, non-human mammal having the exogenous abnormal DNA of the present invention can be passaged under normal breeding conditions as the DNA-bearing animal by confirming the stable retaining of the exogenous DNA via crossing. In addition, the objective exogenous DNA can be utilized as a starting material by inserting the objective exogenous DNA into the plasmid described above. The DNA construct with a promoter can be prepared using conventional DNA engineering techniques. The transfection of the abnormal DNA of the present invention at the fertilized egg cell stage is preserved to be present in all of the germinal and somatic cells of the mammals to be targeted. The fact that the abnormal DNA of the present invention is present in the germinal cells of the animal after DNA transfection means that all of the offspring of the prepared animal have the abnormal DNA of the present invention in all of the germinal and somatic cells. The offspring of such an animal that inherits the exogenous DNA of the present invention has the abnormal DNA of the present invention in all the germinal and somatic cells. A homozygous animal having the introduced DNA on both of homologous chromosomes can be acquired and then by mating these male and female animals, all the offspring can be bred to have the DNA. Since the non-human mammal having the abnormal DNA of the present invention expresses the abnormal DNA of the present invention at a high level, the animal may cause the function inactive type inadaptability of the protein of the present invention by inhibiting the functions of the endogenous normal DNA, and can be utilized as its disease model animal. For example, using the abnormal DNA-transferred animal of the present invention, it is possible to elucidate the mechanism of the function inactive type inadaptability of the protein of the present invention and to study a method for treatment of this disease. In its specific applicability, the transgenic animal of the present invention expressing the abnormal DNA of the present invention to a high level is also expected to serve as a model for the elucidation of the mechanism of the functional inhibition (dominant negative effect) of a normal protein by the abnormal protein of the present invention in the function inactive type inadaptability of the protein of the present invention. A mammal bearing the abnormal exogenous DNA of the present invention is also expected to serve for screening a candidate drug for the treatment of the function inactive type inadaptability of the protein of the present invention, since the protein of the present invention is increased in such an animal in its free form. Other potential applicability of the two kinds of the transgenic animals described above includes: (i) use as a cell source for tissue culture; (ii) elucidation of the association with a peptide that is specifically expressed or activated by the protein of the present invention, through direct analysis of DNA or RNA in tissue of the DNA transgenic animal of the present invention or by analysis of the peptide tissue expressed by the DNA; (iii) research in the function of cells derived from tissues that are cultured usually only with difficulty, using cells of tissue bearing the DNA cultured by a standard tissue culture technique; (iv) screening for a drug that enhances the functions of cells using the cells described in (iii) above; and, (v) isolation and purification of the variant protein of the present invention and preparation of an antibody thereto. Furthermore, clinical conditions of a disease associated with the protein of the present invention, including the function inactive type inadaptability of the protein of the present invention can be determined using the DNA transgenic animal of the present invention. Also, pathological findings on each organ in a disease model associated with the protein of the present invention can be obtained in more detail, leading to the development of a new method for treatment as well as the research and therapy of any secondary diseases associated with the disease. It is also possible to obtain a free DNA-transfected cell by withdrawing each organ from the DNA transgenic animal of the present invention, mincing the organ and degrading with a proteinase such as trypsin, etc., followed by establishing the line of culturing or cultured cells. Furthermore, the DNA transgenic animal of the present invention can serve as identification of cells capable of producing the protein of the present invention, and as studies on association with apoptosis, differentiation or propagation or on the mechanism of signal transduction in these properties to inspect any abnormality therein. Thus, the DNA transgenic animal of the present invention can provide an effective research material for the protein of the present invention and for elucidating the function and effect thereof. To develop pharmaceuticals for the treatment of diseases associated with the protein of the present invention, including the function inactive type inadaptability of the protein of the present invention, using the DNA transgenic animal of the present invention, an effective and rapid method for screening the pharmaceuticals for the treatment of diseases can be provided by using the method for inspection and the method for quantification, etc. described above. It is also possible to investigate and develop a method for DNA therapy for the treatment of diseases associated with the protein of the present invention, using the DNA transgenic animal of the present invention or a vector capable of expressing the exogenous DNA of the present invention. [7] Knockout Animal The present invention provides a non-human mammal embryonic stem cell bearing the DNA of the present invention inactivated and a non-human mammal deficient in expressing the DNA of the present invention. Thus, the present invention provides: (1) a non-human mammal embryonic stem cell in which the DNA of the present invention is inactivated; (2) the embryonic stem cell according to (1), wherein the DNA is inactivated by introducing a reporter gene (e.g., β-galactosidase gene derived from Escherichia coli); (3) the embryonic stem cell according to (1), which is resistant to neomycin; (4) the embryonic stem cell according to (1), wherein the non-human mammal is a rodent; (5) an embryonic stem cell according to (4), wherein the rodent is mouse; (6) a non-human mammal deficient in expressing the DNA of the present invention, wherein the DNA of the present invention is inactivated; (7) the non-human mammal according to (6), wherein the DNA is inactivated by inserting a reporter gene (e.g., β-galactosidase derived from Escherichia coli) therein and the reporter gene is capable of being expressed under the control of a promoter for the DNA of the present invention; (8) the non-human mammal according to (6), which is a rodent; (9) the non-human mammal according to (8), wherein the rodent is mouse; and (10) a method for screening a compound or its salt that promotes or inhibits the promoter activity for the DNA of the present invention, which comprises administering a test compound to the animal of (7) and detecting expression of the reporter gene. The non-human mammalian embryonic stem cell, in which the DNA of the present invention is inactivated, refers to a non-human mammalian embryonic stem cell that suppresses the ability of the non-human mammalian to express the DNA by artificially mutating the DNA of the present invention possessed in the non-human mammal, or the DNA has no substantial ability to express the protein of the present invention (hereinafter sometimes referred to as the knockout DNA of the present invention) by substantially inactivating the activities of the protein of the present invention encoded by the DNA (hereinafter merely referred to as ES cell). As the non-human mammalian, the same examples as described above apply. Techniques for artificially mutating the DNA of the present invention include deletion of a part or all of the DNA sequence and insertion of, or substitution with, other DNA, e.g., by genetic engineering. By these variations, the knockout DNA of the present invention may be prepared, for example, by shifting the reading frame of a codon or by disrupting the function of a promoter or exon. Specifically, the non-human mammalian embryonic stem cell, in which the DNA of the present invention is inactivated (hereinafter merely referred to as the ES cell with the DNA of the present invention inactivated or the knockout ES cell of the present invention), can be obtained by, for example, isolating the DNA of the present invention possessed by the target non-human mammal, inserting a DNA strand (hereinafter simply referred to as targeting vector) having a DNA sequence constructed so as to eventually destroy the gene by inserting into its exon site a chemical resistant gene such as a neomycin resistant gene or a hygromycin resistant gene, or a reporter gene such as lacZ (β-galactosidase gene) or cat (chloramphenicol acetyltransferase gene), etc. thereby destroying the functions of exon, or by inserting into the intron site between exons a DNA sequence which terminates gene transcription (e.g., polyA-added signal, etc.) thereby disabling the synthesis of complete messenger RNA, into a chromosome of the animal cells by, e.g., homologous recombination. The thus obtained ES cells are analyzed by the Southern hybridization using as a probe a DNA sequence on or near the DNA of the present invention, or by PCR using as primers a DNA sequence on the targeting vector and another DNA sequence near the DNA of the present invention which is not included in the targeting vector, and the knockout ES cell of the present invention is selected. The parent ES cells to inactivate the DNA of the present invention by homologous recombination, etc. may be of a strain already established as described above, or may be originally established in accordance with a modification of the known method by Evans and Kaufman supra. For example, in the case of mouse ES cells, currently it is common practice to use ES cells of the 129 strain. However, since their immunological background is obscure, the C57BL/6 mouse or the BDF1 mouse (F1 hybrid between C57BL/6 and DBA/2), wherein the low ovum collection per C57BL/6 mouse or C57BL/6 has been improved by crossing with DBA/2, may be preferably used, instead of obtaining a pure line of ES cells with the clear immunological genetic background. The BDF1 mouse is advantageous in that when a pathologic model mouse is generated using ES cells obtained therefrom, the genetic background can be changed to that of the C57BL/6 mouse by back-crossing with the C57BL/6 mouse, since its background is of the C57BL/6 mouse, as well as being advantageous in that ovum availability per animal is high and ova are robust. In establishing ES cells, blastocytes of 3.5 days after fertilization are commonly used. A large number of early stage embryos may be acquired more efficiently, by collecting the embryos of the 8-cell stage and using the same after culturing until the blastocyte stage. Although the ES cells used may be of either sex, male ES cells are generally more convenient for generation of a germ cell line chimera and are therefore preferred. It is desirable to identify sexes as soon as possible also in order to save painstaking culture time. As an example of the method for sex identification of the ES cell, mention may be made of a method in which a gene in the sex-determining region on the Y-chromosome is amplified by PCR and detected. When this method is used, ES cells (about 50 cells) corresponding to almost 1 colony are sufficient, whereas karyotype analysis hitherto required about 106 cells; therefore, the first selection of ES cells at the early stage of culture can be based on sex identification, and male cells can be selected early, which saves a significant amount of time at the early stage of culture. Second selection can be achieved by, for example, number of chromosome confirmation by the G-banding method. It is usually desirable that the chromosome number of the obtained ES cells be 100% of the normal number. However, when it is difficult to obtain the cells having the normal number of chromosomes due to physical operation etc. in cell establishment, it is desirable that the ES cell be again cloned to a normal cell (e.g., in mouse cells having the number of chromosomes being 2n=40) after the gene of the ES cells is rendered knockout. Although the embryonic stem cell line thus obtained shows a very high growth potential, it must be subcultured with great care, since it tends to lose its ontogenic capability. For example, the embryonic stem cell line is cultured at about 37° C. in a carbon dioxide incubator (preferably about 5% carbon dioxide and about 95% air, or about 5% oxygen, about 5% carbon dioxide and about 90% air) in the presence of LIF (1-10000 U/ml) on appropriate feeder cells such as STO fibroblasts, treated with a trypsin/EDTA solution (normally about 0.001 to about 0.5% trypsin/about 0.1 to 5 mM EDTA, preferably about 0.1% trypsin/about 1 mM EDTA) at the time of passage to obtain separate single cells, which are then seeded on freshly prepared feeder cells. This passage is normally conducted every 1 to 3 days; it is desirable that cells be observed at passage and cells found to be morphologically abnormal in culture, if any, be abandoned. By allowing ES cells to reach a high density in mono-layers or to form cell aggregates in suspension under appropriate conditions, it is possible to differentiate them to various cell types, for example, parietal and visceral muscles, cardiac muscle or the like [M. J. Evans and M. H. Kaufman, Nature, 292, 154, 1981; G R. Martin, Proc. Natl. Acad. Sci. U.S.A., 78, 7634, 1981; T. C. Doetschman et al., Journal of Embryology Experimental Morphology, 87, 27, 1985]. The cells deficient in expression of the DNA of the present invention, which are obtainable from the differentiated ES cells of the present invention, are useful for studying the functions of the protein of the present invention or the protein of the present invention in vitro cytologically or molecular biologically. The non-human mammal deficient in expression of the DNA of the present invention can be identified from a normal animal by measuring the amount of mRNA in the subject animal by a publicly known method, and indirectly comparing the levels of expression. As the non-human mammal, the same examples supra apply. With respect to the non-human mammal deficient in expression of the DNA of the present invention, the DNA of the present invention can be made knockout by transfecting a targeting vector, prepared as described above, to mouse embryonic stem cells or mouse oocytes thereof, and conducting homologous recombination in which a targeting vector DNA sequence, wherein the DNA of the present invention is inactivated by the transfection, is replaced with the DNA of the present invention on a chromosome of a mouse embryonic stem cell or mouse oocyte. The cells with the DNA of the present invention in which the DNA of the present invention is rendered knockout can be identified by the Southern hybridization analysis using as a probe a DNA sequence on or near the DNA of the present invention, or by PCR analysis using as primers a DNA sequence on the targeting vector and another DNA sequence which is not included in the DNA of the present invention derived from mouse, which is used as the targeting vector. When non-human mammalian embryonic stem cells are used, the cell line wherein the DNA of the present invention is inactivated is cloned by homologous recombination; the resulting cloned cell line is injected to, e.g., a non-human mammalian embryo or blastocyte, at an appropriate stage such as the 8-cell stage. The resulting chimeric embryos are transplanted to the uterus of the pseudo-pregnant non-human mammal. The resulting animal is a chimeric animal composed of both cells having the normal locus of the DNA of the present invention and those having an artificially mutated locus of the DNA of the present invention. When some germ cells of the chimeric animal have a mutated locus of the DNA of the present invention, an individual, in which all tissues are composed of cells having an artificially mutated locus of the DNA of the present invention, can be selected from a series of offspring obtained by crossing between such a chimeric animal and a normal animal, e.g., by coat color identification, etc. The individuals thus obtained are normally deficient in heterozygous expression of the protein of the present invention. The individuals deficient in homozygous expression of the protein of the present invention can be obtained from offspring of the intercross between the heterozygotes. When an oocyte is used, a DNA solution may be injected, e.g., to the prenucleus by microinjection thereby obtaining a transgenic non-human mammal having a targeting vector introduced into its chromosome. From such transgenic non-human mammals, those having a mutation at the locus of the DNA of the present invention can be obtained by selection based on homologous recombination. As described above, individuals wherein the DNA of the present invention is rendered knockout permit passage rearing under ordinary rearing conditions, after it is confirmed that in the animal individuals obtained by their crossing, the DNA has been knockout. Furthermore, the genital system may be obtained and maintained by conventional methods. That is, by crossing male and female animals each having the inactivated DNA, homozygote animals having the inactivated DNA in both loci can be obtained. The homozygotes thus obtained may be reared so that one normal animal and two or more homozygotes are produced from a mother animal to efficiently obtain such homozygotes. By crossing male and female heterozygotes, homozygotes and heterozygotes having the inactivated DNA are proliferated and passaged. The non-human mammalian embryonic stem cell, in which the DNA of the present invention is inactivated, is very useful for preparing a non-human mammal deficient in expression of the DNA of the present invention. Since the non-human mammal, in which the DNA of the present invention fails to express, lacks various biological activities induced by the protein of the present invention, such an animal can be a disease model suspected of inactivated biological activities of the protein of the present invention and thus, offers an effective study to investigate causes for and therapy for these diseases. [7a] Method for Screening of Compounds Having Therapeutic/Prophylactic Effects for Diseases Caused by Deficiency, Damages, Etc. of the DNA of the Present Invention The non-human mammal deficient in expression of the DNA of the present invention can be used to screen compounds having therapeutic/prophylactic effects for diseases caused by deficiency, damages, etc. of the DNA of the present invention. That is, the present invention provides a method for screening of a compound or its salt having therapeutic/prophylactic effects for diseases caused by deficiency, damages, etc. of the DNA of the present invention, which comprises administering a test compound to the non-human mammal deficient in expression of the DNA of the present invention, and observing and measuring a change having occurred in the animal. As the non-human mammal deficient in expression of the DNA of the present invention used for the screening method, the same examples as given hereinabove apply. Examples of the test compounds include peptides, proteins, non-peptide compounds, synthetic compounds, fermentation products, cell extracts, plant extracts, animal tissue extracts, blood plasma, etc. and these compounds may be novel compounds or publicly known compounds. Specifically, the non-human mammal deficient in the expression of the DNA of the present invention is treated with a test compound, comparison is made with an intact animal for control and a change in each organ, tissue, disease conditions, etc. of the animal is used as an indicator to assess the therapeutic/prophylactic effects of the test compound. For treating an animal to be tested with a test compound, for example, oral administration, intravenous injection, etc. are applied and the treatment is appropriately selected depending upon conditions of the test animal, properties of the test compound, etc. Furthermore, the amount of a test compound administered can be appropriately selected depending on administration route, nature of the test compound, or the like. For example, when a compound having a therapeutic effect on hyperlipemia is screened, a test compound is administered into a non-human mammalian animal deficient in expressing DNA encoding the protein A of the present invention, raised with common feed or cholesterol-containing common feed, and then the amount of total bile acid in feces or total serum cholesterol in the animal is measured with time. For example, when a compound having a prophylactic/therapeutic effect on renal insufficiency is screened, a test compound is administered into a non-human mammalian animal deficient in expressing DNA encoding the protein B of the present invention, and then the amount of blood creatine or urine protein in the animal is measured with time. For example, when a compound having a therapeutic effect on diabetics is screened, a non-human mammalian animal deficient in expressing DNA encoding the protein C of the present invention is subjected to a sugar loading treatment, a test compound is administered before or after the sugar loading treatment, and blood sugar level, body weight change, etc. of the animal are measured with time. For example, when a compound having a prophylactic/therapeutic effect on chronic articular rheumatism is screened, a test compound is administered into a non-human mammalian animal deficient in expressing DNA encoding the protein D of the present invention, and then the volume of a swelling in a joint in the animal is measured with time, or the damage in the joint is evaluated by X-ray, MRI. histological techniques etc. The compound obtained by the above screening is a compound selected from the test compounds described above, and has therapeutic/prophylactic effects on diseases caused by deficiency, damages, etc. of the protein of the present invention, and can thus be used as a safe and low toxic drug for the treatment/prevention, etc. for these diseases. A compound derived from the compound obtained by the screening can also be similarly used. The compound obtained by the screening method may form a salt, and as the salts of the compound, there may be used salts with physiologically acceptable acids (e.g., inorganic acids or organic acids) or bases (e.g., alkali metals), preferably physiologically acceptable acid addition salts. Examples of such salts are salts with inorganic acids (e.g., hydrochloric acid, phosphoric acid, hydrobromic acid, sulfuric acid), salts with organic acids (e.g., acetic acid, formic acid, propionic acid, fumaric acid, maleic acid, succinic acid, tartaric acid, citric acid, malic acid, oxalic acid, benzoic acid, methanesulfonic acid, benzenesulfonic acid) and the like. A medicine comprising the compound or salts thereof obtained by the above screening method may be manufactured in a manner similar to the method for preparing the medicine comprising the protein of the present invention described hereinabove. Since the medicine thus obtained is safe and low toxic, it can be administered to humans or other mammals (e.g., rat, mouse, guinea pig, rabbit, sheep, swine, bovine, horse, cat, dog, monkey, etc.). The dose of the above compound or its salt may vary depending on its action, target disease, subject to be administered, route for administration, etc. When the compound is orally administered, the compound is administered to adult (as 60 kg) as a patient with hyperlipemia generally in a daily dose of approximately 0.1 mg to 100 mg, preferably approximately 1.0 mg to 50 mg, more preferably approximately 1.0 to 20 mg. When the compound is parenterally administered, a single dose of the compound may vary depending on subject to be administered, target disease, etc. When the compound is administered in the form of an injection to adult (as 60 kg body weight) as a patient with hyperlipemia, it is convenient to administer the compound by intravenous injection generally in a daily dose of approximately 0.01 to 30 mg, preferably approximately 0.1 to 20 mg, more preferably approximately 0.1 to 10 mg. For other animal species, the corresponding dose as converted per 60 kg weight can be administered. [7b] Method of Screening a Compound that Promotes or Inhibits the Activities of a Promoter for the DNA of the Present Invention The present invention provides a method of screening a compound or its salt that promotes or inhibits the activities of a promoter for the DNA of the present invention, which comprises administering a test compound to a non-human mammal deficient in expression of the DNA of the present invention and detecting expression of the reporter gene. In the screening method described above, the non-human mammal deficient in expression of the DNA of the present invention is selected from the aforesaid non-human mammal deficient in expression of the DNA of the present invention for an animal, in which the DNA of the present invention is inactivated by introducing a reporter gene and the reporter gene can be expressed under the control of a promoter for the DNA of the present invention. The same examples given above for the test compound apply to the test compound. As the reporter gene, the same specific examples given above apply to the reporter gene, with β-galactosidase (lacZ), soluble alkaline phosphatase gene, luciferase gene, etc. being preferred. In the non-human mammal deficient in expression of the DNA of the present invention wherein the DNA of the present invention is substituted with a reporter gene, the reporter gene is present under the control of a promoter for the DNA of the present invention. Thus, the activity of the promoter can be detected by tracing the expression of a substance encoded by the reporter gene. For example, when a part of the DNA region encoding the protein of the present invention is substituted with, e.g., β-galactosidase gene (lacZ) derived from Escherichia coli, β-galactosidase is expressed in a tissue where the protein of the present invention should originally be expressed, in place of the protein of the present invention. Thus, the expression state of the protein of the present invention can be readily observed in vivo in an animal, by staining with a reagent, e.g., 5-bromo-4-chloro-3-indolyl-β-galactopyranoside (X-gal), which is a substrate for β-galactosidase. Specifically, a mouse deficient in the protein of the present invention, or its tissue section, is fixed with glutaraldehyde, etc. After washing with phosphate buffered saline (PBS), the system is reacted with a staining solution containing X-gal at room temperature or about 37° C. for approximately 30 minutes to 1 hour. After the β-galactosidase reaction is terminated by washing the tissue preparation with 1 mM EDTA/PBS solution, the color formed is observed. Alternatively, mRNA encoding lacZ may be detected in a conventional manner. The compound or salts thereof obtained using the screening methods supra are compounds selected from the test compounds described above, which promote or inhibit the promoter activity for the DNA of the present invention. The compound obtained by the screening methods may be in the form of salts. The salts of the compound used are salts with physiologically acceptable acids (e.g., inorganic acids) or bases (e.g., organic acids), and physiologically acceptable acid addition salts are preferred. Examples of such salts are salts with inorganic acids (e.g., hydrochloric acid, phosphoric acid, hydrobromic acid, sulfuric acid), salts with organic acids (e.g., acetic acid, formic acid, propionic acid, fumaric acid, maleic acid, succinic acid, tartaric acid, citric acid, malic acid, oxalic acid, benzoic acid, methanesulfonic acid, benzenesulfonic acid) and the like. The compound or its salt that promotes the activity of the promoter for the DNA encoding the protein A of the present invention can promote the expression of protein A of the present invention to promote the functions of the protein, and is thus useful as a medicine such as a prophylactic/therapeutic agent for diseases such as hyperlipemia, genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, bronchial asthma etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), diabetes, hypothyroidism, circulatory diseases (e.g., cardiac insufficiency, arrhythmia, long QT syndrome, arteriosclerosis, angina etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably hyperlipemia, arteriosclerosis, genital diseases, digestive diseases etc. The compound or its salt that inhibits the promoter activity for the DNA encoding the protein A of the present invention can inhibit the expression of the protein A of the present invention to inhibit the functions of the protein, and is thus useful as a medicine such as a prophylactic/therapeutic agent for diseases such as hyperlipemia, genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, bronchial asthma etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), diabetes, hypothyroidism, circulatory diseases (e.g., cardiac insufficiency, arrhythmia, long QT syndrome, arteriosclerosis, angina etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably hyperlipemia, arteriosclerosis, genital diseases, digestive diseases etc. The compound or its salt that promotes the promoter activity for the DNA encoding the protein B of the present invention can promote the expression of the protein B of the present invention to promote the functions of the protein, and is thus useful as a medicine such as a prophylactic/therapeutic agent for diseases such as renal diseases (e.g., renal insufficiency, uremia etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), spleen diseases, cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.), diabetes, hypertension, ischemia-reperfusion injury, central nerve diseases (e.g., Alzheimer's disease, Parkinson's syndrome, schizophrenia, cerebral vascular dementia, cerebral ischemia, epilepsy etc.) etc., preferably respiratory diseases, renal diseases, digestive diseases etc. The compound or its salt that inhibits the promoter activity for the DNA encoding the protein B of the present invention can inhibit the expression of the protein B of the present invention to inhibit the functions of the protein, and is thus useful as a medicine such as a prophylactic/therapeutic agent for diseases such as renal diseases (e.g., renal insufficiency, uremia etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), spleen diseases, cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.), diabetes, hypertension, ischemia-reperfusion injury, central nerve diseases (e.g., Alzheimer's disease, Parkinson's syndrome, schizophrenia, cerebral vascular dementia, cerebral ischemia, epilepsy etc.) etc., preferably respiratory diseases, renal diseases, digestive diseases etc. The compound or its salt that promotes the promoter activity for the DNA encoding the protein C of the present invention can promote the expression of the protein C of the present invention to promote the functions of the protein, and is thus useful as a medicine such as a prophylactic/therapeutic agent for diseases such as pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), central nerve diseases (e.g., Alzheimer's disease, Parkinson's syndrome, schizophrenia, cerebral vascular dementia, cerebral ischemia, epilepsy etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), diabetes, hyperlipemia, cholestasis, or cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably pancreatic diseases, central nerve diseases, digestive diseases, respiratory diseases etc. The compound or its salt that inhibits the promoter activity for the DNA encoding the protein C of the present invention can inhibit the expression of the protein C of the present invention to inhibit the functions of the protein, and is thus useful as a medicine such as a prophylactic/therapeutic agent for diseases such as pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), central nerve diseases (e.g., Alzheimer's disease, Parkinson's syndrome, schizophrenia, cerebral vascular dementia, cerebral ischemia, epilepsy etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), diabetes, hyperlipemia, cholestasis, or cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably pancreatic diseases, central nerve diseases, digestive diseases, respiratory diseases etc. The compound or its salt that promotes the promoter activity for the DNA encoding the protein D of the present invention can promote the expression of the protein D of the present invention to promote the functions of the protein, and is thus useful as a medicine such as a prophylactic/therapeutic agent for diseases such as inflammatory diseases (e.g., septicemia, pneumonia, encephalitis, meningitis, hepatitis, myocarditis, pleurisy etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), diabetic neurosis, thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), circulatory diseases (e.g., cardiac insufficiency, arrhythmia, long QT syndrome, arteriosclerosis, angina etc.), hepatic diseases (e.g., hepatocirrhosis etc.), renal diseases (e.g., renal insufficiency, uremia etc.), muscular diseases (e.g., muscular dystrophy etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), burns, pain syndrome (e.g., cancerous sharp pain, referred pain etc.), cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably inflammatory diseases, rheumatoid diseases, diabetic neurosis etc. The compound or its salt that inhibits the promoter activity for the DNA encoding the protein D of the present invention can inhibit the expression of the protein D of the present invention to inhibit the functions of the protein, and is thus useful as a medicine such as a prophylactic/therapeutic agent for diseases such as inflammatory diseases (e.g., septicemia, pneumonia, encephalitis, meningitis, hepatitis, myocarditis, pleurisy etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), diabetic neurosis, thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), circulatory diseases (e.g., cardiac insufficiency, arrhythmia, long QT syndrome, arteriosclerosis, angina etc.), hepatic diseases (e.g., hepatocirrhosis etc.), renal diseases (e.g., renal insufficiency, uremia etc.), muscular diseases (e.g., muscular dystrophy etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), burns, pain syndrome (e.g., cancerous sharp pain, referred pain etc.), cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably inflammatory diseases, rheumatoid diseases, diabetic neurosis etc. Further, a compound derived from the compound obtained in the above screening can also be used similarly. The medicine comprising the compound or its salt obtained by the screening method can be produced in a manner similar to the method for preparing the medicine comprising the protein of the present invention or its salt described hereinabove. Since the thus obtained medicine is safe and low toxic, and can be administered to, for example, human and warm-blooded animal (e.g., rat, mouse, guinea pig, rabbit, sheep, swine, bovine, horse, cat, dog, monkey, etc.). The dose of the compound or its salt may vary depending on target disease, subject to be administered, route for administration, etc. When the compound promoting the promoter activity for the DNA of the present invention is orally administered, the compound is administered to adult (as 60 kg) as a patient with hyperlipemia generally in a daily dose of approximately 0.1 mg to 100 mg, preferably approximately 1.0 mg to 50 mg, more preferably approximately 1.0 to 20 mg. When the compound is parenterally administered, a single dose of the compound may vary depending on subject to be administered, target disease, etc. When the compound promoting the promoter activity for the DNA of the present invention is administered in the form of an injection to adult (as 60 kg body weight) as a patient with hyperlipemia, it is convenient to administer the compound by intravenous injection in a daily dose of approximately 0.01 to 30 mg, preferably approximately 0.1 to 20 mg, more preferably approximately 0.1 to 10 mg. For other animal species, the corresponding dose as converted per 60 kg weight can be administered. On the other hand, when the compound inhibiting the promoter activity for the DNA of the present invention is orally administered, the compound is administered to adult (as 60 kg) as a patient with hyperlipemia generally in a daily dose of approximately 0.1 mg to 100 mg, preferably approximately 1.0 mg to 50 mg, more preferably approximately 1.0 to 20 mg. When the compound is parenterally administered, a single dose of the compound may vary depending on subject to be administered, target disease, etc. When the compound inhibiting the promoter activity for the DNA of the present invention is administered in the form of an injection to adult (as 60 kg body weight) as a patient with hyperlipemia, it is convenient to administer the compound by intravenous injection in a daily dose of approximately 0.01 to 30 mg, preferably approximately 0.1 to 20 mg, more preferably approximately 0.1 to 10 mg. For other animal species, the corresponding dose as converted per 60 kg weight can be administered. Thus, the non-human mammal deficient in expression of the DNA of the present invention is extremely useful in screening a compound or its salt that promotes or inhibits the activity of a promoter for the DNA of the present invention, and can contribute significantly to elucidation of causes for various diseases attributable to deficient expression of the DNA of the present invention or development of a prophylactic/therapeutic agent for the diseases. Further, genes encoding various proteins are ligated downstream DNA containing a promoter region for the protein of the present invention and injected into a fertilized egg of an animal to create a transgenic animal by which the protein of the present invention can be specifically synthesized and examined for its action in the living body. When a suitable reporter gene is ligated to the promoter region to establish a cell strain expressing the same, the cell strain can be used as a system of searching for a low-molecular compound having an action of specifically promoting or suppressing the ability of the cell strain to produce the protein of the present invention in vivo. [8] Determination of a Ligand to the Protein D of the Present Invention The protein D of the present invention or its partial peptide or its salts are useful as reagents for searching and determining ligands to the protein D of the present invention or its salts. That is, the present invention provides a method for determining a ligand to the protein D of the present invention, which comprises bringing the protein D of the present invention or its partial peptide or its salts, into contact with a test compound. Examples of the test compound include publicly known ligands (e.g., angiotensin, bombesin, canavinoid, cholecystokinin, glutamine, serotonin, melatonin, neuropeptide Y, opioid, purines, vasopressin, oxytocin, PACAP (e.g., PACAP27, PACAP38), secretin, glucagon, calcitonin, adrenomedulin, somatostatin, GHRH, CRF, ACTH, GRP, PTH, VIP (vasoactive intestinal and related polypeptide), somatostatin, dopamine, motilin, amylin, bradykinin, CGRP (calcitonin gene-related peptide), leukotrienes, pancreastatin, prostaglandins, thromboxane, adenosine, adrenaline, a chemokine superfamily (e.g., CXC chemokine subfamily such as IL-8, GROα, GROβ, GROγ, NAP-2, ENA-78, GCP-2, PF4, IP10, Mig, PBSF/SDF-1, etc.; CC chemokine subfamily such as MCAF/MCP-1, MCP-2, MCP-3, MCP-4, eotaxin, RANTES, MIP1-α, MIP-1β, HCC-1, MIP-3α/LARC, MIP-3β/ELC, I-309, TARC, MIPF-1, MIPF-2/eotaxin-2, MDC, DC-CK1/PARC, SLC, etc.; C chemokine subfamily such as lymphotactin; and CX3C chemokine subfamily such as fractalkine, etc.), endothelin, enterogastrin, histamine, neurotensin, TRH, pancreatic polypeptide, galanin, lysophosphatidic acid (LPA), sphingosine 1-phosphate, vanilloid, nucleotide, etc.) as well as other substances, for example, tissue extracts and cell culture supernatants from mammals (e.g., humans, mice, rats, swine, bovine, sheep, monkeys, etc.). For example, the tissue extract or cell culture supernatant is added to the protein D of the present invention and fractionated while assaying the cation channel activities, etc. to finally give a single ligand. In more detail, the method for determining ligands of the present invention comprises determining compounds (e.g., peptides, proteins, non-peptide compounds, synthetic compounds, fermentation products, nucleotides, etc.) or salts thereof that bind to the protein D of the present invention to provide cation channel activities (e.g., Ca2+ channel activity etc.), using the protein D of the present invention, or by the ligand binding assay using the constructed recombinant protein D expression system. The method for determining ligands according to the present invention is characterized, for example, by measurement of the amount of the test compound bound to the protein D or its partial peptide, or by assaying the cation channel activities, etc., when the test compound is brought into contact with the protein D of the present invention or its partial peptide. More specifically, the present invention provides: (i) A method for determining ligands to the protein D of the present invention or its salt, which comprises bringing a labeled test compound into contact with the protein D of the present invention or its salt or the partial peptide of the present invention or its salt and measuring the amount of the labeled test compound bound to the protein or its salt or to the partial peptide or its salt; (ii) A method for determining ligands to the protein D of the present invention or its salt, which comprises bringing a labeled test compound into contact with cells or cell membrane fraction containing the protein D of the present invention, and measuring the amount of the labeled test compound bound to the cells or the membrane fraction; (iii) A method for determining ligands to the protein D of the present invention, which comprises culturing a transformant containing the DNA encoding the protein D of the present invention, bringing a labeled test compound into contact with the protein D expressed on the cell membrane by said culturing, and measuring the amount of the labeled test compound bound to the protein D or its salt; and (iv) A method for determining ligands to the protein D of the present invention or its salt, which comprises bringing a test compound into contact with cells containing the protein D of the present invention and measuring the protein D-mediated cation channel activities (e.g., Ca2+ channel activity etc.). It is particularly preferred to perform the tests (i) to (iii) described above thereby confirming that the test compound can bind to the protein D of the present invention, followed by the test (iv) described above. As the protein D used in the method of determining ligands, any material comprising the protein D of the present invention or the partial peptide of the present invention may be used, but the protein produced in a large amount by animal cells is appropriate. The protein D of the present invention can be manufactured by the expression method described above, preferably by expressing DNA encoding the protein D in mammalian or insect cells. As DNA fragments encoding the desired portion of the protein, complementary DNA is generally used but not necessarily limited thereto. For example, gene fragments or synthetic DNA may also be used. For introducing a DNA fragment encoding the protein D of the present invention into host animal cells and efficiently expressing the same, it is preferred to insert the DNA fragment downstream a polyhedrin promoter of nuclear polyhedrosis virus (NPV), which is a baculovirus having insect hosts, an SV40-derived promoter, a retrovirus promoter, a metallothionein promoter, a human heat shock promoter, a cytomegalovirus promoter, an SRα promoter or the like. The amount and quality of the channel expressed can be determined by a publicly known method. For example, this determination can be made by the method described in the literature (Nambi, P., et al., J. Biol. Chem., 267, 19555-19559 (1992)). Accordingly, the subject containing the protein D of the present invention, its partial peptides or salts thereof in the method for determining the ligand according to the present invention may be the protein D, its partial peptides or salts thereof purified by publicly known methods, cells containing the protein D, or membrane fractions of such cells. In the ligand determination method of the present invention where cells containing the protein D of the present invention are used, the cells may be fixed with glutaraldehyde, formalin, etc. The cells can be fixed by publicly known methods. The cells containing the protein D of the present invention are host cells that have expressed the protein D. As the host cells, Escherichia coli, Bacillus subtilis, yeast, insect cells, animal cells and the like are used. The cell membrane fraction refers to a fraction abundant in cell membrane obtained by cell disruption and subsequent fractionation by a publicly known method. Cell disruption methods include cell squashing using a Potter-Elvehjem homogenizer, disruption using a Waring blender or Polytron (manufactured by Kinematica Inc.), disruption by ultrasonication, and disruption by cell spraying through thin nozzles under an increased pressure using a French press or the like. Cell membrane fractionation is effected mainly by fractionation using a centrifugal force, such as centrifugation for fractionation and density gradient centrifugation. For example, cell disruption fluid is centrifuged at a low speed (500 rpm to 3,000 rpm) for a short period of time (normally about 1 to about 10 minutes), and the resulting supernatant is then centrifuged at a higher speed (15,000 rpm to 30,000 rpm) normally for 30 minutes to 2 hours. The precipitate thus obtained is used as the membrane fraction. The membrane fraction is rich in the protein D expressed and membrane components such as cell-derived phospholipids and membrane proteins. The amount of the protein D in the protein D-containing cells or membrane fraction is preferably 103 to 108 molecules per cell, more preferably 105 to 107 molecules per cell. As the amount of expression increases, the ligand binding activity per unit of membrane fraction (specific activity) increases so that not only the highly sensitive screening system can be constructed but also large quantities of samples can be assayed with the same lot. To perform the methods (i) through (iii) supra for determination of a ligand to the protein D of the present invention or its salt, an appropriate protein D fraction and a labeled test compound are required. The protein D fraction is preferably a fraction of naturally occurring protein D or a recombinant channel fraction having an equivalent activity to that of the natural protein. Herein, the term “equivalent activity” is intended to mean a ligand binding activity, a cation channel activity or the like that is equivalent to that possessed by the naturally occurring protein. Preferred examples of labeled test compounds include angiotensin, bombesin, canavinoid, cholecystokinin, glutamine, serotonin, melatonin, neuropeptide Y, opioid, purines, vasopressin, oxytocin, PACAP (e.g., PACAP27, PACAP38), secretin, glucagon, calcitonin, adrenomedulin, somatostatin, GHRH, CRF, ACTH, GRP, PTH, VIP (vasoactive intestinal polypeptide), somatostatin, dopamine, motilin, amylin, bradykinin, CGRP (calcitonin gene-related peptide), leukotrienes, pancreastatin, prostaglandins, thromboxane, adenosine, adrenaline, a chemokine superfamily (e.g., CXC chemokine subfamily such as IL-8, GROα, GROβ, GROγ, NAP-2, ENA-78, GCP-2, PF4, IP10, Mig, PBSF/SDF-1, etc.; CC chemokine subfamily such as MCAF/MCP-1, MCP-2, MCP-3, MCP-4, eotaxin, RANTES, MIP1-α, MIP-1β, HCC-1, MIP-3α/LARC, MIP-3β/ELC, I-309, TARC, MIPF-1, MIPF-2/eotaxin-2, MDC, DC-CK1/PARC, SLC, etc.; C chemokine subfamily such as lymphotactin; and CX3C chemokine subfamily such as fractalkine, etc.), endothelin, enterogastrin, histamin, neurotensin, TRH, pancreatic polypeptide, galanin, lysophosphatidic acid (LPA) or sphingosine 1-phosphate, vanilloid, nucleotide etc.), which are labeled with [3H], [125I], [14C], [35S], etc. Specifically, the ligand to the protein D of the present invention or its salt is determined by the following procedures. First, a standard channel preparation is prepared by suspending cells containing the protein D of the present invention or the membrane fraction thereof in a buffer appropriate for use in the determination method. Any buffer can be used so long as it does not inhibit the ligand-protein D binding, such buffers including a phosphate buffer or a Tris-HCl buffer having pH of 4 to 10 (preferably pH of 6 to 8). For the purpose of minimizing non-specific binding, a surfactant such as CHAPS, Tween-80™ (manufactured by Kao-Atlas Inc.), digitonin or deoxycholate, and various proteins such as bovine serum albumin or gelatin, may optionally be added to the buffer. Further for the purpose of suppressing the degradation of the receptors or ligands by proteases, a protease inhibitor such as PMSF, leupeptin, E-64 (manufactured by Peptide Institute, Inc.) and pepstatin may also be added. A given amount (5,000 to 500,000 cpm) of the test compound labeled with [3H], [125I], [14C], [35S] or the like is added to 0.01 ml to 10 ml of the protein solution. To determine the amount of non-specific binding (NSB), a reaction tube containing an unlabeled test compound in large excess is also prepared. The reaction is carried out at approximately 0 to 50° C., preferably about 4 to 37° C. for about 20 minutes to about 24 hours, preferably about 30 minutes to about 3 hours. After completion of the reaction, the reaction mixture is filtrated through glass fiber filter paper, etc. and washed with an appropriate volume of the same buffer. The residual radioactivity on the glass fiber filter paper is then measured by means of a liquid scintillation counter or γ-counter. A test compound exceeding 0 cpm in count obtained by subtracting nonspecific binding (NSB) from the total binding (B) (B minus NSB) can be selected as a ligand to the protein D of the present invention or its salt. The method (iv) above for determination of a ligand to the protein D of the present invention or its salt can be performed as follows. The protein D-mediated cation channel activities (e.g., Ca2+ channel activity etc.) may be determined by a publicly known method, or using an assay kit commercially available. Specifically, cells containing the protein D are first cultured on a multi-well plate, etc. Prior to the ligand determination, the medium is replaced with fresh medium or with an appropriate non-cytotoxic buffer, followed by incorporation of a fluorescent Ca2+ probe (for example, Fura-2, Fuo-3 or the like) and subsequent measurement of fluorescence density by FLIPR (Molecular Devices, Ltd.) etc. for a given period of time in the presence of a test compound, etc. The kit of the present invention for determination of the ligand that binds to the protein D of the present invention or its salt comprises the protein D of the present invention or its salt, the partial peptide of the present invention or its salt, cells comprising the protein D of the present invention, or the membrane fraction of the cells containing the protein D of the present invention. In the specification and drawings, the codes of bases and amino acids are denoted in accordance with the IUPAC-TUB Commission on Biochemical Nomenclature or by the common codes in the art, examples of which are shown below. For amino acids that may have the optical isomer, L form is presented unless otherwise indicated. DNA deoxyribonucleic acid cDNA complementary deoxyribonucleic acid A adenine T thymine G guanine C cytosine RNA ribonucleic acid mRNA messenger ribonucleic acid dATP deoxyadenosine triphosphate dTTP deoxythymidine triphosphate dGTP deoxyguanosine triphosphate dCTP deoxycytidine triphosphate ATP adenosine triphosphate EDTA ethylenediaminetetraacetic acid SDS sodium dodecyl sulfate Gly glycine Ala alanine Val valine Leu leucine Ile isoleucine Ser serine Thr threonine Cys cysteine Met methionine Glu glutamic acid Asp aspartic acid Lys lysine Arg arginine His histidine Phe phenylalanine Tyr tyrosine Trp tryptophan Pro proline Asn asparagine Gln glutamine pGlu pyroglutamic acid The substituents, protective groups and reagents, which are frequently used throughout the specification, are shown by the following abbreviations. Me methyl Et ethyl Bu butyl Ph phenyl TC thiazolidine-4(R)-carboxamide Tos p-toluenesulfonyl CHO formyl Bzl benzyl Cl2Bzl 2,6-dichlorobenzyl Bom benzyloxymethyl Z benzyloxycarbonyl Cl-Z 2-chlorobenzyloxycarbonyl Br-Z 2-bromobenzyloxycarbonyl Boc t-butoxycarbonyl DNP dinitrophenyl Trt trityl Bum t-butoxymethyl Fmoc N-9-fluorenylmethoxycarbonyl HOBt 1-hydroxybenztriazole HOOBt 3,4-dihydro-3-hydroxy-4-oxo-1,2,3-benzotriazine HONB 1-hydroxy-5-norbornene-2,3-dicarboxyimide DCC N,N′-dicyclohexylcarbodiimide The sequence identification numbers in the sequence listing of the specification indicate the following sequences, respectively. [SEQ ID NO. 1] This shows the amino acid sequence of human TCH230 protein consisting of 377 amino acids, which was obtained in Example 1. [SEQ ID NO: 2] This shows the base sequence of DNA encoding human TCH230 protein having the amino acid sequence represented by SEQ ID NO. 1. [SEQ ID NO: 3] This shows the base sequence of primer OF used in Example 1. [SEQ ID NO: 4] This shows the base sequence of primer OR1 used in Example 1. [SEQ ID NO: 5] This shows the base sequence of primer OF1 used in Example 1. [SEQ ID NO: 6] This shows the base sequence of primer OR used in Example 1. [SEQ ID NO: 7] This shows the base sequence of primer SP6 used in Examples 1 and 13. [SEQ ID NO: 8] This shows the base sequence of primer T7 used in Examples 1, 13, 18, 25 and 33. [SEQ ID NO: 9] This shows the base sequence of primer B1 used in Examples 1 and 18. [SEQ ID NO. 10] This shows the base sequence of primer F1 used in Examples 1 and 18. [SEQ ID NO. 11] This shows the base sequence of cDNA derived from human small intestine cDNA comprising the full-length TCH230 gene obtained in Example 1. [SEQ ID NO. 12] This shows the base sequence of cDNA derived from human skeletal muscle cDNA comprising the full-length TCH230 gene obtained in Example 1. [SEQ ID NO. 13] This shows the base sequence of DNA encoding human TCH230 protein comprising the amino acid sequence represented by SEQ ID NO. 14. [SEQ ID NO. 14] This shows the amino acid sequence of human TCH230 protein comprising an amino acid sequence encoded by the base sequence represented by SEQ ID NO. 13. [SEQ ID NO. 15] This shows the base sequence of primer TF used in Examples 2, 19 and 38. [SEQ ID NO. 16] This shows the base sequence of primer TR used in Examples 2, 19 and 38. [SEQ ID NO. 17] This shows the base sequence of TaqMan probe T1 used in Examples 2, 19 and 38. [SEQ ID NO. 18] This shows the amino acid sequence of human TCH234 protein obtained in Example 1. [SEQ ID NO. 19] This shows the base sequence of DNA encoding human TCH234 protein having the amino acid sequence represented by SEQ ID NO. 19. [SEQ ID NO: 20] This shows the base sequence of primer AP1 used in Example 3. [SEQ ID NO: 21] This shows the base sequence of primer rr0 used in Example 3. [SEQ ID NO: 22] This shows the base sequence of primer AP2 used in Example 3. [SEQ ID NO: 23] This shows the base sequence of primer rr1 used in Example 3. [SEQ ID NO: 24] This shows the base sequence of primer ff1 used in Example 4. [SEQ ID NO: 25] This shows the base sequence of primer ff2 used in Examples 4, 5 and 25. [SEQ ID NO: 26] This shows the base sequence of primer ORFF1 used in Example 5. [SEQ ID NO: 27] This shows the base sequence of primer ORFR1 used in Example 5. [SEQ ID NO: 28] This shows the base sequence of primer ORFF2 used in Example 5. [SEQ ID NO: 29] This shows the base sequence of primer ORFR2 used in Example 5. [SEQ ID NO: 30] This shows the base sequence of primer M13F used in Example 5. [SEQ ID NO: 31] This shows the base sequence of primer M13R used in Example 5. [SEQ ID NO: 32] This shows the base sequence of primer TMF used in Examples 6, 27, 28 and 38. [SEQ ID NO: 33] This shows the base sequence of primer TMR used in Examples 6, 27, 28 and 38. [SEQ ID NO: 34] This shows the base sequence of primer F2 used in Example 5. [SEQ ID NO: 35] This shows the base sequence of primer F3 used in Examples 5 and 25. [SEQ ID NO: 36] This shows the base sequence of primer R1 used in Example 5. [SEQ ID NO: 37] This shows the base sequence of primer R2 used in Examples 5 and 25. [SEQ ID NO: 38] This shows the base sequence of TaqMan probe P1 used in Examples 6, 27, 28 and 38. [SEQ ID NO: 39] This shows the base sequence of cDNA obtained in Example 3. [SEQ ID NO: 40] This shows the base sequence of cDNA obtained in Example 4. [SEQ ID NO: 41] This shows the base sequence of cDNA obtained in Example 5. [SEQ ID NO: 42] This shows the amino acid sequence of human TCH212 protein obtained in Example 7. [SEQ ID NO: 43] This shows the base sequence of DNA encoding human TCH212 protein having the amino acid sequence represented by SEQ ID NO: 42. [SEQ ID NO: 44] This shows the base sequence of primer A3 used in Example 7. [SEQ ID NO: 45] This shows the base sequence of primer B3 used in Example 7. [SEQ ID NO: 46] This shows the base sequence of primer SP6 used in Example 7. [SEQ ID NO: 47] This shows the base sequence of primer T7 used in Example 7. [SEQ ID NO: 48] This shows the base sequence of primer A2 used in Examples 7 and 33. [SEQ ID NO: 49] This shows the base sequence of primer B1 used in Examples 7 and 33. [SEQ ID NO: 50] This shows the base sequence of primer B2 used in Examples 7 and 33. [SEQ ID NO: 51] This shows the base sequence of primer F1 used in Examples 7 and 33. [SEQ ID NO: 52] This shows the base sequence of primer F2 used in Examples 7 and 33. [SEQ ID NO: 53] This shows the base sequence of primer F3 used in Examples 7 and 33. [SEQ ID NO: 54] This shows the base sequence of primer F4 used in Examples 7 and 33. [SEQ ID NO: 55] This shows the base sequence of primer F5 used in Examples 7 and 33. [SEQ ID NO: 56] This shows the base sequence of primer R1 used in Examples 7 and 33. [SEQ ID NO: 57] This shows the base sequence of primer R2 used in Examples 7 and 33. [SEQ ID NO: 58] This shows the base sequence of primer R3 used in Examples 7 and 33. [SEQ ID NO: 59] This shows the base sequence of primer R4 used in Examples 7 and 33. [SEQ ID NO: 60] This shows the base sequence of cDNA comprising the full-length human TCH212 gene obtained in Example 7. [SEQ ID NO: 61] This shows the base sequence of cDNA comprising the full-length human TCH212 clone #2 obtained in Example 7. [SEQ ID NO: 62] This shows the base sequence of ORF in human TCH212 clone #2 obtained in Example 7. [SEQ ID NO: 63] This shows the base sequence of primer TF used in Examples 8 and 38. [SEQ ID NO: 64] This shows the base sequence of primer TR used in Examples 8 and 38. [SEQ ID NO: 65] This shows the base sequence of TaqMan probe T1 used in Examples 8 and 38. [SEQ ID NO: 66] This shows the amino acid sequence of human TCH200 protein. [SEQ ID NO: 67] This shows the base sequence of DNA encoding human TCH200 protein comprising the amino acid sequence represented by SEQ ID NO: 66. [SEQ ID NO: 68] This shows the base sequence of primer AP 1 used in Example 9. [SEQ ID NO: 69] This shows the base sequence of primer R1 used in Example 9. [SEQ ID NO: 70] This shows the base sequence of primer AP2 used in Example 9. [SEQ ID NO: 71] This shows the base sequence of primer rr2 used in Example 9. [SEQ ID NO: 72] This shows the base sequence of primer M13F used in Example 9. [SEQ ID NO: 73] This shows the base sequence of primer M13R used in Example 9. [SEQ ID NO: 74] This shows the base sequence of primer rr4 used in Example 9. [SEQ ID NO: 75] This shows the base sequence of primer rr6 used in Example 9. [SEQ ID NO: 76] This shows the base sequence of primer r1 used in Example 10. [SEQ ID NO: 77] This shows the base sequence of primer r2 used in Example 10. [SEQ ID NO: 78] This shows the base sequence of primer f1 used in Example 10. [SEQ ID NO: 79] This shows the base sequence of primer f2 used in Example 10. [SEQ ID NO: 80] This shows the base sequence of primer f4 used in Example 10. [SEQ ID NO: 81] This shows the base sequence of primer F0 used in Example 11. [SEQ ID NO: 82] This shows the base sequence of primer R7 used in Example 11. [SEQ ID NO: 83] This shows the base sequence of primer F00 used in Example 11. [SEQ ID NO: 84] This shows the base sequence of primer R00 used in Example 11. [SEQ ID NO: 85] This shows the base sequence of primer F1 used in Example 11. [SEQ ID NO: 86] This shows the base sequence of primer F2 used in Example 11. [SEQ ID NO: 87] This shows the base sequence of primer F5 used in Example 11. [SEQ ID NO: 88] This shows the base sequence of primer F7 used in Example 11. [SEQ ID NO: 89] This shows the base sequence of primer ff3 used in Example 11. [SEQ ID NO: 90] This shows the base sequence of primer ff4 used in Example 11. [SEQ ID NO: 91] This shows the base sequence of primer f3 used in Example 11. [SEQ ID NO: 92] This shows the base sequence of primer rr1 used in Example 11. [SEQ ID NO: 93] This shows the base sequence of primer rr3 used in Example 11. [SEQ ID NO: 94] This shows the base sequence of primer TMF used in Examples 12, 37 and 38. [SEQ ID NO: 95] This shows the base sequence of primer TMR used in Examples 12, 37 and 38. [SEQ ID NO: 96] This shows the base sequence of TaqMan probe P1 used in Examples 12, 37 and 38. [SEQ ID NO: 97] This shows the base sequence of cDNA obtained in Example 9. [SEQ ID NO: 98] This shows the base sequence of cDNA obtained in Example 9. [SEQ ID NO: 99] This shows the base sequence of cDNA obtained in Example 10. [SEQ ID NO. 100] This shows the base sequence of cDNA obtained in Example 10. [SEQ ID NO. 101] This shows the base sequence of cDNA obtained in Example 10. [SEQ ID NO. 102] This shows the base sequence of cDNA obtained in Example 11. [SEQ ID NO. 103] This shows the base sequence of DNA encoding human TCH200 protein comprising the amino acid sequence represented by SEQ ID NO: 66. [SEQ ID NO. 104] This shows the amino acid sequence of mouse TCH230 protein consisting of 373 amino acids, which was obtained in Example 13. [SEQ ID NO. 105] This shows the base sequence of DNA encoding mouse TCH230 protein having the amino acid sequence represented by SEQ ID NO. 104. [SEQ ID NO. 106] This shows the base sequence of primer m230A1 used in Example 13. [SEQ ID NO. 107] This shows the base sequence of primer m230B2 used in Example 13. [SEQ ID NO. 108] This shows the base sequence of primer m230F1 used in Example 13. [SEQ ID NO. 109] This shows the base sequence of primer m230F2 used in Example 13. [SEQ ID NO. 110] This shows the base sequence of primer m230R1 used in Example 13. [SEQ ID NO. 111] This shows the base sequence of primer m230R2 used in Example 13. [SEQ ID NO. 112] This shows the base sequence of cDNA comprising the full-length mouse TCH230 gene obtained in Example 13. [SEQ ID NO. 113] This shows the base sequence of primer m230TF used in Examples 14, 15 and 40. [SEQ ID NO. 114] This shows the base sequence of primer m230TR used in Examples 14, 15 and 40. [SEQ ID NO. 115] This shows the base sequence of TaqMan probe m230T1 used in Examples 14, 15 and 40. [SEQ ID NO. 116] This shows the base sequence of a partial sequence of rat TCH230 gene cDNA identified in Example 16. [SEQ ID NO. 117] This shows the base sequence of primer r230OF used in Example 16. [SEQ ID NO. 118] This shows the base sequence of primer r230OR used in Example 16. [SEQ ID NO. 119] This shows the base sequence of primer r230TF used in Example 17. [SEQ ID NO. 120] This shows the base sequence of primer r230TR used in Example 17. [SEQ ID NO. 121] This shows the base sequence of TaqMan probe r230T1 used in Example 17. [SEQ ID NO. 122] This shows the base sequence of primer 230OF2 used in Example 18. [SEQ ID NO. 123] This shows the base sequence of primer 230OF2 used in Example 18. [SEQ ID NO. 124] This shows the base sequence of primer BGHRV used in Example 18. [SEQ ID NO. 125] This shows the base sequence of a partial sequence of mouse TCH234 gene cDNA identified in Example 21. [SEQ ID NO. 126] This shows the base sequence of primer m234-1485F used in Example 21. [SEQ ID NO. 127] This shows the base sequence of primer m234-1801R used in Example 21. [SEQ ID NO. 128] This shows the base sequence of primer m234-TMF used in Examples 22 and 39. [SEQ ID NO. 129] This shows the base sequence of primer m234-TMR used in Examples 22 and 39. [SEQ ID NO. 130] This shows the base sequence of primer m234T1 used in Examples 22 and 39. [SEQ ID NO. 131] This shows the base sequence of a partial sequence of rat TCH234 gene cDNA identified in Example 23. [SEQ ID NO. 132] This shows the base sequence of primer r234-815F used in Example 23. [SEQ ID NO. 133] This shows the base sequence of primer r234-1177R used in Example 23. [SEQ ID NO. 134] This shows the base sequence of primer r234-TMF used in Example 24. [SEQ ID NO. 135] This shows the base sequence of primer r234-TMR used in Example 24. [SEQ ID NO. 136] This shows the base sequence of primer r234-P1 used in Example 24. [SEQ ID NO. 137] This shows the base sequence of primer 234OF used in Example 25. [SEQ ID NO. 138] This shows the base sequence of primer 234OR used in Example 25. [SEQ ID NO. 139] This shows the base sequence of primer 234F21 used in Example 25. [SEQ ID NO. 140] This shows the base sequence of primer 234F22 used in Example 25. [SEQ ID NO. 141] This shows the base sequence of primer 234F23 used in Example 25. [SEQ ID NO. 142] This shows the base sequence of primer 234R24 used in Example 25. [SEQ ID NO. 143] This shows the base sequence of a partial sequence of mouse TCH212 gene cDNA identified in Example 29. [SEQ ID NO. 144] This shows the base sequence of primer m212A1 used in Examples 29 and 31. [SEQ ID NO. 145] This shows the base sequence of primer m212B1 used in Examples 29 and 31. [SEQ ID NO. 146] This shows the base sequence of primer m212TF used in Example 30. [SEQ ID NO. 147] This shows the base sequence of primer m212TR used in Example 30. [SEQ ID NO. 148] This shows the base sequence of TaqMan probe m212T1 used in Example 30. [SEQ ID NO. 149] This shows the base sequence of a partial sequence of rat TCH212 gene cDNA identified in Example 31. [SEQ ID NO. 150] This shows the base sequence of primer r212TF used in Example 32. [SEQ ID NO. 151] This shows the base sequence of primer r212TR used in Example 32. [SEQ ID NO. 152] This shows the base sequence of primer r212T1 used in Example 32. [SEQ ID NO. 153] This shows the base sequence of primer 2120F used in Example 33. [SEQ ID NO. 154] This shows the base sequence of primer 2120R used in Example 33. [SEQ ID NO. 155] This shows the base sequence of a partial sequence of mouse TCH200 gene cDNA identified in Example 34. [SEQ ID NO. 156] This shows the base sequence of primer m200A1 used in Example 34. [SEQ ID NO. 157] This shows the base sequence of primer m200B1 used in Example 34. [SEQ ID NO. 158] This shows the base sequence of primer m200A2 used in Examples 34 and 35. [SEQ ID NO. 159] This shows the base sequence of primer m200B2 used in Examples 34 and 35. [SEQ ID NO. 160] This shows the base sequence of TaqMan probe m200T1 used in Example 35. [SEQ ID NO. 161] This shows the base sequence of primer TCH200F used in Example 36. [SEQ ID NO. 162] This shows the base sequence of primer TCH200R used in Example 36. [SEQ ID NO. 163] This shows the base sequence of primer T7 used in Example 36. [SEQ ID NO. 164] This shows the base sequence of primer AF used in Example 36. [SEQ ID NO. 165] This shows the base sequence of primer BF used in Example 36. [SEQ ID NO. 166] This shows the base sequence of primer CF used in Example 36. [SEQ ID NO. 167] This shows the base sequence of primer DF used in Example 36. [SEQ ID NO. 168] This shows the base sequence of primer BGH RV used in Example 36. [SEQ ID NO. 169] This shows the base sequence of primer DR used in Example 36. [SEQ ID NO. 170] This shows the base sequence of primer CR used in Example 36. [SEQ ID NO. 171] This shows the base sequence of primer BR used in Example 36. [SEQ ID NO. 172] This shows the base sequence of primer AR used in Example 36. Transformant Escherichia coli TOP10/PCR-BluntII-TCH230 obtained in Example 1 later described has been deposited with International Patent Organism Depositary (IPOD), National Institute of Advanced Industrial Science and Technology (AIST) at Central 6, 1-1-1, Higashi, Tsukuba, Ibaraki, Japan (zip code: 305-8566), under the Accession Number FERM BP-7869 since Jan. 17, 2002, and with Institute for Fermentation, Osaka (IFO) at 17-85, Juso-honmachi 2-chome, Yodogawa-ku, Osaka, Japan (zip code: 532-8686), under the Accession Number IFO 16749 since Jan. 17, 2002. Transformant Escherichia coli TOP10/PCR-BluntII-TCH234 obtained in Example 3 later described has been deposited with International Patent Organism Depositary (IPOD), National Institute of Advanced Industrial Science and Technology (AIST) at Central 6, 1-1-1, Higashi, Tsukuba, Ibaraki, Japan (zip code: 305-8566), under the Accession Number FERM BP-7906 since Feb. 18, 2002, and with Institute for Fermentation, Osaka (IFO) at 17-85, Juso-honmachi 2-chome, Yodogawa-ku, Osaka, Japan (zip code: 532-8686), under the Accession Number IFO 16758 since Feb. 7, 2002. Transformant Escherichia coli JM109/PCR-BluntII-TCH212 obtained in Example 7 later described has been deposited with International Patent Organism Depositary (IPOD), National Institute of Advanced Industrial Science and Technology (AIST) at Central 6, 1-1-1, Higashi, Tsukuba, Ibaraki, Japan (zip code: 305-8566), under the Accession Number FERM BP-7888 since Feb. 12, 2002, and with Institute for Fermentation, Osaka (IFO) at 17-85, Juso-honmachi 2-chome, Yodogawa-ku, Osaka, Japan (zip code: 532-8686), under the Accession Number IFO 16755 since Jan. 31, 2002. Transformant Escherichia coli TOP10/PCR-BluntII-TCH200 obtained in Example 9 later described has been deposited with International Patent Organism Depositary (IPOD), National Institute of Advanced Industrial Science and Technology (AIST) at Central 6, 1-1-1, Higashi, Tsukuba, Ibaraki, Japan (zip code: 305-8566), under the Accession Number FERM BP-7874 since Feb. 4, 2002, and with Institute for Fermentation, Osaka (IFO) at 17-85, Juso-honmachi 2-chome, Yodogawa-ku, Osaka, Japan (zip code: 532-8686), under the Accession Number IFO 16750 since Jan. 22, 2002. Hereinafter, the present invention will be specifically described by reference to the Examples, but is not limited thereto. The gene manipulation procedures using Escherichia coli were performed in accordance with the methods described in the Molecular Cloning. EXAMPLE 1 Cloning of Human TCH230 Gene cDNA Using two primer DNAs, i.e. primer OF (SEQ ID NO: 3) and primer OR1 (SEQ ID NO: 4), human small intestine Marathon-Ready cDNA and human skeletal muscle Marathon-Ready cDNA (both of which were manufactured by Clontech) were subjected to primary PCR with Pyrobest DNA Polymerase (Takara Shuzo Co., Ltd.) under the following conditions (1) to (3): (1) reaction at 94° C. for 2 minutes, (2) 30 cycles each consisting of reaction at 98° C. for 10 seconds, at 68° C. for 30 seconds and at 72° C. for 3 minutes, and (3) reaction at 72° C. for 10 minutes. Using the primary PCR product as a template, nested PCR was conducted with primer OF1 (SEQ ID NO: 5), primer OR (SEQ ID NO: 6) and Pyrobest DNA polymerase (Takara Shuzo Co., Ltd.) under the following conditions (4) to (6): (4) reaction at 94° C. for 2 minutes, (5) 35 cycles each consisting of reaction at 98° C. for 10 seconds, at 68° C. for 30 seconds, and at 72° C. for 3 minutes, (6) reaction at 72° C. for 10 minutes. The resulting amplification product was cloned by using the Zero Blunt TOPO Cloning Kit (Invitrogen, Inc.), to give plasmid pCR-BluntII-TCH230. This product was reacted with primer DNAs [primer SP6 (SEQ ID NO: 7), primer T7 (SEQ ID NO: 8), primer B1 (SEQ ID NO: 9), primer F1 (SEQ ID NO. 10)] and BigDye Terminator Cycle Sequencing Kit (Applied Biosystems), and the base sequence of the inserted cDNA fragment was determined by DNA sequencer ABI PRISM 3100 DNA analyzer (Applied Biosystems). The result indicated that the clone obtained from human small intestine cDNA had 1152-base sequence (SEQ ID NO. 11). The cDNA fragment (SEQ ID NO: 2) coded for a 377-amino acid sequence (SEQ ID NO. 1), and the protein having the amino acid sequence was designated human TCH230 protein. A transformant having a plasmid comprising the cDNA fragment was designated Escherichia coli TOP10/pCR-BluntII-TCH230. In the clone obtained from the human skeletal muscle cDNA, base substitution was recognized in one site (position 340 in the base sequence represented by SEQ ID NO. 11). This base substitution A340G is accompanied by amino acid substitution of Ile->Val, and it is considered that there is a possibility to be derived from single nucleotide polymorphisms (SNPs). The base sequence of the full-length cDNA possessed by this clone is shown in SEQ ID NO. 12, and the base sequence of ORF in this base sequence is shown in SEQ ID NO. 13. The amino acid sequence encoded by the base sequence represented by SEQ ID NO. 13 is shown in SEQ ID NO. 14. When homology with owl by using Blast P [Nucleic Acids Res., 25, 3389, 1997] was examined, the cDNA encoding human TCH230 protein was revealed to be a novel gene belonging to sodium-dependent bile acid transporter family (FIG. 1). This protein showed 46% homology at the base level and 44% homology at the amino acid level with reported human ileum sodium-dependent bile acid transporter ISBT [J. Biol. Chem., 270, 27228, 1995]. EXAMPLE 2 Analysis of Distribution of Human TCH230 Gene Product in Tissues Using two primer DNAs, i.e. primer TF (SEQ ID NO. 15) and primer TR (SEQ ID NO. 16), designed from the sequence of human TCH230, and TaqMan probe T1 (SEQ ID NO. 17), the expression level of human TCH230 by cDNA in each human tissue was measured by TaqMan PCR. The PCR reaction involved a reaction at 50° C. for 2 minutes and at 95° C. for 10 minutes and 40 cycles each consisting of a reaction at 95° C. for 15 seconds and at 60° C. for 1 minute by using TaqMan Universal PCR Master Mix (Applied Biosystems) in ABI PRISM 7900 sequence detection system (Applied Biosystems), and simultaneously detection was carried out. The cDNA in each tissue used in measurement is shown in Table 1. TABLE 1 cDNA (manufactured by Clontech) Tissues Human MTC panel I heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas Human MTC panel II spleen, thymus, prostate, testis, ovary, small intestine, colon, peripheral blood leukocyte Human digestive system liver, esophagus, stomach, duodenum, MTC panel jejunum, ileum, ileocecum, caecum, ascending colon, transverse colon, descending colon, rectum Human fetal MTC panel fetal brain, fetal lung, fetal liver, fetal kidney, fetal heart, fetal skeletal muscle, fetal spleen, fetal thymus Human tumor MTC breast cancer (GI-101), panel lung cancer (LX-1), colon cancer (CX-1), lung cancer (GI-117), prostate cancer (PC3), colon cancer (GI-112), ovarian cancer (GI-102), pancreatic cancer (GI-103) The results are shown in FIGS. 2, 3, 4 and 5. The human TCH230 gene product (mRNA) in human MTC panels I and II was slightly expressed in the heart, brain, liver, skeletal muscle, kidney, colon and peripheral blood leukocyte, expressed at a certain degree in the placenta, lung, pancreas, spleen, thymus, prostate and small intestine, and expressed strongly in the testis and ovary. In human digestive system MTC panel, strong expression was observed in every region from the stomach to rectum (particularly strong expression was observed in the esophagus). Strong expression was also observed in the liver. In human fetal MTC panel, slight expression was observed in the fetal heart, fetal skeletal muscle and fetal spleen, certain expression was observed in the fetal brain, fetal liver, fetal kidney and fetal lung, and strong expression was observed in the fetal thymus. In human tumor MTC panel, slight expression was observed in the lung cancer, colon cancer, prostate cancer and pancreatic cancer, certain expression was observed in the breast cancer, and strong expression was observed in the ovarian cancer. EXAMPLE 3 Cloning of the 5′-Upstream Terminus of cDNA Encoding Human TCH234 Protein The 5′-upstream base sequence of cDNA encoding human TCH234 protein was revealed by 5′RACE PCR cloning. Using two primer DNAs, i.e. primer AP1 (SEQ ID NO: 20) and primer rr0 (SEQ ID NO: 21), human pancreas Marathon-Ready cDNA (Clontech) was subjected to primary PCR with Advantage 2 DNA Polymerase (Clontech) under the following conditions (1) to (3): (1) reaction at 94° C. for 30 seconds, (2) 35 cycles each consisting of reaction at 94° C. for 10 seconds and at 68° C. for 2 minutes, and (3) reaction at 68° C. for 5 minutes. Using the primary PCR product as a template, nested PCR was conducted with primer AP2 (SEQ ID NO: 22), primer rr1 (SEQ ID NO: 23) and Advantage 2 DNA Polymerase (Clontech) under the following conditions (4) to (6): (4) reaction at 94° C. for 30 seconds, (5) 30 cycles each consisting of reaction at 94° C. for 10 seconds and at 68° C. for 2 minutes, and (6) reaction at 68° C. for 5 minutes. One (1) μl each of exonuclease I and shrimp alkaline phosphatase in PCR Product Pre-Sequencing Kit (USB) were added to 5 μl of the nested PCR reaction solution and reacted at 37° C. for 15 minutes and at 85° C. for 15 minutes. The solution was reacted by using primer rr1 (SEQ ID NO: 23) and BigDye Terminator Cycle Sequencing Kit (Applied Biosystems), and the base sequence of the amplified DNA fragment was determined by DNA sequencer ABI PRISM 3100 DNA analyzer (Applied Biosystems). As a result, the base sequence represented by SEQ ID NO: 39 was obtained. EXAMPLE 4 Cloning of the 3′-Downstream Terminus of cDNA Encoding Human TCH234 Protein The 3′-downstream base sequence of cDNA encoding human TCH234 protein was revealed by 3′RACE PCR cloning. Using two primer DNAs, i.e. primer AP1 (SEQ ID NO: 20) and primer ff1 (SEQ ID NO: 24), human pancreas Marathon-Ready cDNA (Clontech) was subjected to primary PCR with Advantage 2 DNA Polymerase (Clontech) under the following conditions (1) to (3): (1) reaction at 94° C. for 30 seconds, (2) 35 cycles each consisting of reaction at 94° C. for 10 seconds and at 68° C. for 2 minutes, and (3) reaction at 68° C. for 5 minutes. Using the primary PCR product as a template, nested PCR was conducted with primer AP2 (SEQ ID NO: 22), primer ff2 (SEQ ID NO: 25) and Advantage 2 DNA Polymerase (Clontech) under the following conditions (4) to (6): (4) reaction at 94° C. for 30 seconds, (5) 30 cycles each consisting of reaction at 94° C. for 10 seconds and at 68° C. for 2 minutes, and (6) reaction at 68° C. for 5 minutes. One (1) μl each of exonuclease I and shrimp alkaline phosphatase in PCR Product Pre-Sequencing Kit (USB) were added to 5 μl of the nested PCR reaction solution and reacted at 37° C. for 15 minutes and at 85° C. for 15 minutes. The solution was reacted by using primer ff2 (SEQ ID NO: 25) and BigDye Terminator Cycle Sequencing Kit (Applied Biosystems), and the base sequence of the amplified DNA fragment was determined by DNA sequencer ABI PRISM 3100 DNA analyzer (Applied Biosystems). As a result, the base sequence represented by SEQ ID NO: 40 was obtained. EXAMPLE 5 Cloning of cDNA Encoding Human TCH234 Protein Using two primer DNAs, i.e. primer ORFF1 (SEQ ID NO: 26) and primer ORFR1 (SEQ ID NO: 27), human pancreas Marathon-Ready cDNA (Clontech) was subjected to primary PCR with pfu turbo DNA Polymerase (Stratagene) under the following conditions (1) to (3): (1) reaction at 94° C. for 30 seconds, (2) 35 cycles each consisting of reaction at 94° C. for 10 seconds, at 54° C. for 5 seconds and at 72° C. for 2.5 minutes, and (3) reaction at 72° C. for 5 minutes. Using the primary PCR product as a template, nested PCR was conducted with primer ORFF2 (SEQ ID NO: 28), primer ORFR2 (SEQ ID NO: 29) and pfu turbo DNA Polymerase (Stratagene) under the following conditions (4) to (6): (4) reaction at 94° C. for 30 seconds, (5) 30 cycles each consisting of reaction at 94° C. for 10 seconds, at 55° C. for 5 seconds and at 72° C. for 2.5 minutes, and (6) reaction at 72° C. for 5 minutes. The nested PCR reaction solution was purified by QIAquick PCR Purification Kit (Qiagen). This DNA was cloned into pCR-Blunt II-TOPO vector according to a protocol of the Zero Blunt TOPO PCR Cloning Kit (Invitrogen, Inc.). The resulting product was transformed into Escherichia coli TOP10 competent cell (Invitrogen, Inc.), and clones having the cDNA insert fragment were selected in a kanamycin-containing LB agar medium to give transformants. The respective clones were cultured overnight in a kanamycin-containing LB medium, and plasmid DNAs were prepared by QIAwell 8 Plasmid Kit (Qiagen) to give pCR-BluntII-TCH234 plasmid clones #1, #2 and #3. These were reacted with primer DNAs [primer M13F (SEQ ID NO: 30), primer M13R (SEQ ID NO: 31), primer ORFF2 (SEQ ID NO: 28), primer ORFR2 (SEQ ID NO: 29), primer TMF (SEQ ID NO: 32), primer TMR (SEQ ID NO: 33), primer F2 (SEQ ID NO: 34), primer F3 (SEQ ID NO: 35), primer R1 (SEQ ID NO: 36), primer R2 (SEQ ID NO: 37), primer ff2 (SEQ ID NO: 25)] and BigDye Terminator Cycle Sequencing Kit (Applied Biosystems), and the base sequences of the inserted cDNA fragments were determined by a DNA sequencer ABI PRISM 3100 DNA analyzer (Applied Biosystems). As a result, the acquired 3 clones contained the same DNA fragment and had a 2426-base sequence (SEQ ID NO: 41). The fragment (SEQ ID NO. 19) encoded a 798-amino acid sequence (SEQ ID NO. 18), and the protein comprising the amino acid sequence represented by SEQ ID NO. 18 was designated human TCH234 protein. A transformant comprising the cDNA fragment was designated Escherichia coli TOP10/pCR-BluntII-TCH234. When homology with OWL was examined using Blast P [Nucleic Acids Res., 25, 3389, 1997], the cDNA was revealed to be a novel gene belonging to Na+/H+ exchange transporter (FIG. 6). Human TCH234 exhibited 53% homology at the amino acid level with Na+/H+ exchange transporter NHE2 [Genomics, 30, 25, 1995] and 84% homology at the amino acid level with rat NHE4 (J. Biol. Chem., 267, 9331, 1992), and the protein was estimated to have a 13-times transmembrane structure. EXAMPLE 6 Analysis of Distribution of Human TCH234 Gene Product in Tissues Using 2 primer DNAs, i.e. primer TMF (SEQ ID NO: 32) and primer TMR (SEQ ID NO: 33), designed from the sequence of human TCH234, and TaqMan probe P1 (SEQ ID NO: 38), the expression level of human TCH234 by cDNA (Human MTC panels I and II: Clontech) in each human tissue (heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis, ovary, small intestine, colon, peripheral blood leukocyte) was measured by TaqMan PCR. The reaction involved a reaction at 50° C. for 2 minutes and at 95° C. for 10 minutes and 40 cycles each consisting of a reaction at 95° C. for 15 seconds and at 60° C. for 1 minute by using TaqMan Universal PCR Master Mix (Applied Biosystems) in ABI PRISM 7900 sequence detection system (Applied Biosystems), and simultaneously detection was carried out. The results are shown in FIG. 7. The human TCH234 gene product (mRNA) was strongly expressed in the kidney. Certain expression was recognized in the prostate, pancreas, testis, spleen, thymus and ovary. EXAMPLE 7 Cloning of Human TCH212 Gene cDNA Using two primer DNAs, i.e. primer A3 (SEQ ID NO: 44) and primer OB3 (SEQ ID NO: 45), human testis Marathon-Ready cDNA (Clontech) was subjected to primary PCR with Pyrobest DNA Polymerase (Takara Shuzo Co., Ltd.) under the following conditions (1) to (3): (1) reaction at 94° C. for 2 minutes, (2) 35 cycles each consisting of reaction at 98° C. for 10 seconds, at 68° C. for 30 seconds and at 72° C. for 7 minutes, and (3) reaction at 72° C. for 10 minutes. The amplified product was cloned with the Zero Blunt TOPO Cloning Kit (Invitrogen, Inc.) to give plasmid pCR-BluntII-TCH212. This product was reacted with primer DNAs [primer SP6 (SEQ ID NO: 46), primer T7 (SEQ ID NO: 47), primer A2 (SEQ ID NO: 48), primer B1 (SEQ ID NO: 49), primer B2 (SEQ ID NO: 50), primer F1 (SEQ ID NO: 51), primer F2 (SEQ ID NO: 52), primer F3 (SEQ ID NO: 53), primer F4 (SEQ ID NO: 54), primer F5 (SEQ ID NO: 55), primer R1 (SEQ ID NO: 56), primer R2 (SEQ ID NO: 57), primer R3 (SEQ ID NO: 58), primer R4 (SEQ ID NO: 59)] and BigDye Terminator Cycle Sequencing Kit (Applied Biosystems), and the base sequence of the inserted cDNA fragment was determined by DNA sequencer ABI PRISM 3100 DNA analyzer (Applied Biosystems). The acquired clone had a 3643-base sequence (SEQ ID NO: 60). The cDNA fragment (SEQ ID NO: 43) coded for a 1148-amino acid sequence (SEQ ID NO: 42), and the protein having the amino acid sequence was designated human TCH212 protein. Base substitution was recognized at one site (position 1592 in the base sequence of SEQ ID NO: 60) in the acquired clone (designated clone #2). This base substitution C1592T was not accompanied by amino acid substitution and it is considered that the substitution is derived from single nucleotide polymorphisms (SNPs). The base sequence of the full-length cDNA possessed by this clone is shown in SEQ ID NO: 61, and the base sequence of ORF in this base sequence is shown in SEQ ID NO: 62. A transformant having a plasmid comprising cDNA comprising the base sequence represented by SEQ ID NO: 60 was designated Escherichia coli JM109/pCR-BluntII-TCH212. When homology with owl was examined using Blast P [Nucleic Acids Res., 25, 3389, 1997], the cDNA encoding human TCH212 was revealed to be a novel gene belonging to P-type ATPase family (FIGS. 8 to 10). The human TCH212 exhibited 60% homology at the base level and 67% homology at the amino acid level with reported human P-type ATPase 8A1 (ATP8A1) [Biochem. Biophys. Res. Commun., 257, 333-339, 1999] and 86% homology at the base level and 95% homology at the amino acid level with reported mouse P-type ATPase 8A2 [Physiol. Genomics (Online), 1, 139-150, 1999]. EXAMPLE 8 Analysis of Distribution of Human TCH212 Gene Product in Tissues Using two primer DNAs, i.e. primer TF (SEQ ID NO: 63) primer TR (SEQ ID NO: 64), designed from the sequence of human TCH212, and TaqMan probe T1 (SEQ ID NO: 65), the expression level of human TCH212 in each human tissue was measured by TaqMan PCR. The reaction involved a reaction at 50° C. for 2 minutes and at 95° C. for 10 minutes and 40 cycles each consisting of a reaction at 95° C. for 15 seconds and at 60° C. for 1 minute by using TaqMan Universal PCR Master Mix (Applied Biosystems) in ABI PRISM 7900 sequence detection system (Applied Biosystems), and simultaneously detection was carried out. The cDNA in each kind of tissue used in measurement is shown in Table 2. TABLE 2 cDNA (manufactured by Clontech) Tissues Human MTC panel I heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas Human MTC panel II spleen, thymus, prostate, testis, ovary, small intestine, colon, peripheral blood leukocyte Human fetal MTC panel fetal brain, fetal lung, fetal liver, fetal kidney, fetal heart, fetal skeletal muscle, fetal spleen, fetal thymus Human tumor MTC panel breast cancer (GI-101), lung cancer (LX-1), colon cancer (CX-1), lung cancer (GI-117), prostate cancer (PC3), colon cancer (GI-112), ovarian cancer (GI-102), pancreatic cancer (GI-103) The results are shown in FIGS. 11, 12 and 33. In human MTC panels I and II, the human TCH212 gene product (mRNA) was expressed at a certain degree in the brain and strongly expressed in the pancreas and testis. In human fetal MTC panel, certain expression was observed in the fetal kidney, and strong expression was observed in the fetal brain. In human tumor MTC panel, slight expression was observed in the colon cancer (GI-112). EXAMPLE 9 Cloning of the 5′-Upstream Terminus of cDNA Encoding Human TCH200 Protein The 5′-upstream base sequence of cDNA encoding human TCH200 protein was revealed by 5′RACE PCR cloning. Using human small intestine Marathon-Ready cDNA (Clontech) as a template, PCR reaction was carried out with primer AP1 (SEQ ID NO: 68) and primer R1 (SEQ ID NO: 69), and by using this PCR reaction solution as a template, PCR reaction was carried out with primer AP2 (SEQ ID NO: 70) and primer rr2 (SEQ ID NO: 71). The composition of the PCR reaction solution and reaction conditions are shown below. A reaction solution of 2.5 μl of human small intestine Marathon-Ready cDNA, 5 μM primer AP1, 5 μM primer R1, 0.4 mM dNTPs and 0.5 μl Advantage2 Polymerase mix (Clontech) was adjusted to 25 μl with a buffer attached to Advantage2 Polymerase mix (Clontech), and then heated at 94° C. for 30 seconds and subjected to 35 cycles of reaction each at 94° C. for 5 seconds and at 68° C. for 4 minutes in thermal cycler 9700 (Applied Biosystems). Then, a mixture consisting of 2.5 μl solution obtained by diluting the above PCR reaction solution (reacted with AP1/R1) 50-fold with tricine-EDTA buffer, 5 μM primer AP2, 5 μM primer rr2, 0.4 mM dNTPs and 0.5 μl Advantage2 Polymerase mix (Clontech) was adjusted to 25 μl with a buffer attached to Advantage2 Polymerase mix (Clontech), and then heated at 94° C. for 30 seconds and subjected to 30 cycles of reaction each at 94° C. for seconds and at 68° C. for 4 minutes in thermal cycler 9700 (Applied Biosystems). The amplified DNA was separated by 1.5% agarose gel electrophoresis, and DNA of about 700-base in length was cut off with a razor, and then the DNA was recovered with QIAquick Gel Extraction Kit (Qiagen). This DNA was cloned into PCR2.1-TOPO vector according to the protocol of TOPO TA Cloning Kit (Invitrogen, Inc.). The product was transformed into Escherichia coli TOP10 competent cell (Invitrogen, Inc.), and clones having the cDNA insert fragment were selected in an ampicillin-containing LB agar medium to give transformants. The respective clones were cultured overnight in an ampicillin-containing LB medium, and the plasmid DNA was prepared by QIAwell 8 Plasmid Kit (Qiagen). The plasmid DNA was reacted with primer DNAs [primer M13F (SEQ ID NO: 72), primer M13R (SEQ ID NO: 73), primer rr2 (SEQ ID NO: 71)] and BigDye Terminator Cycle Sequencing Kit (Applied Biosystems), and the base sequence of the inserted cDNA fragment was determined by DNA sequencer ABI PRISM 3100 DNA analyzer (Applied Biosystems). As a result, the base sequence shown in SEQ ID NO: 97 was obtained. Then, primer rr4 (SEQ ID NO: 74) and primer rr6 (SEQ ID NO: 75) were designed on the basis of the base sequence shown in SEQ ID NO: 97. To obtain further upstream base sequence, PCR reaction with primer AP1 (SEQ ID NO: 68) and primer rr4 (SEQ ID NO: 74) was conducted, and using this PCR reaction solution as a template, PCR reaction was conducted with primer AP2 (SEQ ID NO: 70) and primer rr6 (SEQ ID NO: 75). The composition of the PCR reaction solution and reaction conditions are shown below. A reaction solution of 2.5 μl of human small intestine Marathon-Ready cDNA, 5 μM primer AP1, 5 μM primer rr4, 0.4 mM dNTPs and 0.5 μl Advantage2 Polymerase mix (Clontech) was adjusted to 25 μl with a buffer attached to Advantage2 Polymerase mix (Clontech), and then heated at 94° C. for 30 seconds and subjected to 35 cycles of reaction each at 94° C. for 5 seconds and at 68° C. for 1.5 minutes in thermal cycler 9700 (Applied Biosystems). Then, a mixture consisting of 2.5 μl solution obtained by diluting the above PCR reaction solution (reacted with AP1/rr4) 50-fold with tricine-EDTA buffer, 0.5 μM primer AP2, 0.5 μM primer rr6, 0.4 mM dNTPs and 0.5 μl Advantage2 Polymerase mix (Clontech) was adjusted to 25 μl with a buffer attached to Advantage2 Polymerase mix (Clontech), and then heated at 94° C. for 30 seconds and subjected to 30 cycles of reaction each at 94° C. for 5 seconds and at 68° C. for 1.5 minutes in thermal cycler 9700 (Applied Biosystems). The amplified DNA of about 280-base in length was confirmed by 1.5% agarose gel electrophoresis, and 1 μl each of exonuclease I and shrimp alkaline phosphatase in PCR Product Pre-Sequencing Kit (USB) were added to 5 μl of the PCR reaction solution (reacted with AP2/rr6) and reacted at 37° C. for 15 minutes and at 85° C. for 15 minutes. This reaction solution was diluted 3-fold with ultrapure water, and reacted with primer rr6 (SEQ ID NO: 75) and BigDye Terminator Cycle Sequencing Kit (Applied Biosystems), and the base sequence of the amplified DNA fragment was determined by DNA sequencer ABI PRISM 3100 DNA analyzer (Applied Biosystems). As a result, the base sequence shown in SEQ ID NO: 98 was obtained. EXAMPLE 10 Cloning of the 3′-Downstream Terminus of cDNA Encoding Human TCH200 Protein For cloning of the 3′-downstream terminus, PCR reaction was carried out using human small intestine Marathon-Ready cDNA (Clontech) as a template with primer AP1 (SEQ ID NO: 68) and primer r1 (SEQ ID NO: 76), and by using this PCR reaction solution as a template, PCR reaction was carried out with primer AP2 (SEQ ID NO: 70) and primer r2 (SEQ ID NO: 77). The composition of the PCR reaction solution and reaction conditions are shown below. A reaction solution of 2.5 μl of human small intestine Marathon-Ready cDNA, 5 μM primer AP1, 5 μM primer r1, 0.4 mM dNTPs and 0.5 μl Advantage2 Polymerase mix (Clontech) was adjusted to 25 μl with a buffer attached to Advantage2 Polymerase mix (Clontech), and then heated at 94° C. for 30 seconds and subjected to 35 cycles of reaction each at 94° C. for 5 seconds and at 68° C. for 4 minutes in thermal cycler 9700 (Applied Biosystems). Then, a mixture consisting of 2.5 μl solution obtained by diluting the above PCR reaction solution (reacted with AP1/r1) 50-fold with tricine-EDTA buffer, 5 μM primer AP2, 5 μM primer r2, 0.4 mM dNTPs and 0.5 μl Advantage2 Polymerase mix (Clontech) was adjusted to 25 μl with a buffer attached to Advantage2 Polymerase mix (Clontech), and then heated at 94° C. for 30 seconds and subjected to 30 cycles of reaction each at 94° C. for 5 seconds and at 68° C. for 4 minutes in thermal cycler 9700 (Applied Biosystems). The amplified DNA was separated by 1.5% agarose gel electrophoresis, and DNA of about 600-base in length was cut off with a razor, and then the DNA was recovered with QIAquick Gel Extraction Kit (Qiagen). This DNA was cloned into PCR2.1-TOPO vector according to the protocol of TOPO TA Cloning Kit (Invitrogen, Inc.). The product was transformed into Escherichia coli TOP10 competent cell (Invitrogen, Inc.), and clones having the cDNA insert fragment were selected in an ampicillin-containing LB agar medium to give transformants. The respective clones were cultured overnight in an ampicillin-containing LB medium, and plasmid DNA was prepared by QIAwell 8 Plasmid Kit (Qiagen). The plasmid DNA was reacted with primer DNAs [primer M13F (SEQ ID NO: 72), primer M13R (SEQ ID NO: 73), primer r2 (SEQ ID NO: 77)] and BigDye Terminator Cycle Sequencing Kit (Applied Biosystems), and the base sequence of the inserted cDNA fragment was determined by DNA sequencer ABI PRISM 3100 DNA analyzer (Applied Biosystems). As a result, the base sequence shown in SEQ ID NO: 99 was obtained. To further obtain the base sequence of the 3′-downstream terminus, PCR reaction was conducted with primer AP1 (SEQ ID NO: 68) and primer f1 (SEQ ID NO: 78), and by using this PCR reaction solution as a template, PCR reaction was conducted with primer AP2 (SEQ ID NO: 70) and primer f2 (SEQ ID NO: 79). The composition of the PCR reaction solution and reaction conditions are shown below. A reaction solution consisting of 2.5 μl of human small intestine Marathon-Ready cDNA, 5 μM primer AP1, 5 μM primer f1, 0.4 mM dNTPs and 0.5 μl Advantage2 Polymerase mix (Clontech) was adjusted to 25 μl with a buffer attached to Advantage2 Polymerase mix (Clontech), and then heated at 94° C. for 30 seconds and subjected to 35 cycles of reaction each at 94° C. for 5 seconds and at 68° C. for 1.5 minutes in thermal cycler 9700 (Applied Biosystems). Then, a mixture consisting of 2.5 μl solution obtained by diluting the above PCR reaction solution (reacted with AP1/f1) 50-fold with tricine-EDTA buffer, 5 μM primer AP2, 5 μM primer f2, 0.4 mM dNTPs and 0.5 μl Advantage2 Polymerase mix (Clontech) was adjusted to 25 μl with a buffer attached to Advantage2 Polymerase mix (Clontech), and then heated at 94° C. for 30 seconds and subjected to 30 cycles of reaction each at 94° C. for 5 seconds and at 68° C. for 1.5 minutes in thermal cycler 9700 (Applied Biosystems). The amplified DNA of about 300-base in length was confirmed by 1.5% agarose gel electrophoresis, and 1 μl each of exonuclease I and shrimp alkaline phosphatase in PCR Product Pre-Sequencing Kit (USB) were added to 5 μl of the PCR reaction solution (reacted with AP2/f2) and reacted at 37° C. for 15 minutes and at 85° C. for 15 minutes. This reaction solution was diluted 3-fold with ultrapure water, and reacted with primer f2 (SEQ ID NO: 79) and BigDye Terminator Cycle Sequencing Kit (Applied Biosystems), and the base sequence of the amplified DNA fragment was determined by DNA sequencer ABI PRISM 3100 DNA analyzer (Applied Biosystems). As a result, the base sequence shown in SEQ ID NO. 100 was obtained. Then, primer f4 (SEQ ID NO: 80) was designed on the basis of the base sequence shown in SEQ ID NO. 100. To obtain further downstream base sequence, first PCR reaction was carried out with primer AP1 (SEQ ID NO: 68) and primer f2 (SEQ ID NO: 79), and by using this PCR reaction solution as a template, second PCR reaction was conducted with primer AP2 (SEQ ID NO: 70) and primer f4 (SEQ ID NO: 80). The composition of the PCR reaction solution and reaction conditions are shown below. A reaction solution consisting of 2.5 μl human testis Marathon-Ready cDNA, 5 μM primer AP1, 5 μM primer f2, 0.4 mM dNTPs and 0.5 μl Advantage2 Polymerase mix (Clontech) was adjusted to 25 μl with a buffer attached to Advantage2 Polymerase mix (Clontech), and then heated at 94° C. for 30 seconds and subjected to 35 cycles of reaction each at 94° C. for 5 seconds and at 68° C. for 1.5 minutes in thermal cycler 9700 (Applied Biosystems). Then, a mixture consisting of 2.5 μl solution obtained by diluting the above PCR reaction solution (reacted with AP1/f2) 50-fold with tricine-EDTA buffer, 5 μM primer AP2, 5 μM primer f4, 0.4 mM dNTPs and 0.5 μl Advantage2 Polymerase mix (Clontech) was adjusted to 25 μl with a buffer attached to Advantage2 Polymerase mix (Clontech), and then heated at 94° C. for 30 seconds and subjected to 30 cycles of reaction each at 94° C. for 5 seconds and at 68° C. for 1.5 minutes in thermal cycler 9700 (Applied Biosystems). The amplified DNA of about 150-base in length was confirmed by 1.5% agarose gel electrophoresis, and 1 μl each of exonuclease I and shrimp alkaline phosphatase in PCR Product Pre-Sequencing Kit (USB) were added to 5 μl of the PCR reaction solution (reacted with AP2/f4) and reacted at 37° C. for 15 minutes and at 85° C. for 15 minutes. This reaction solution was diluted 3-fold with ultrapure water, and reacted with primer DNAs [primer AP2 (SEQ ID NO: 70) and primer f4 (SEQ ID NO: 80)] and BigDye Terminator Cycle Sequencing Kit (Applied Biosystems), and the base sequence of the amplified DNA fragment was determined by DNA sequencer ABI PRISM 3100 DNA analyzer (Applied Biosystems). As a result, the base sequence shown in SEQ ID NO. 101 was obtained. EXAMPLE 11 Cloning of cDNA Encoding Human TCH200 Protein Cloning of cDNA encoding human TCH200 protein was conducted by nested PCR. For cloning of cDNA encoding human TCH200 protein, primer F0 (SEQ ID NO: 81), primer R7 (SEQ ID NO: 82), primer F00 (SEQ ID NO: 83) and primer R00 (SEQ ID NO: 84) were designed on the basis of the base sequences (SEQ ID NOS: 97, 98, 99, 100 and 101) obtained in Examples 1 and 2. First PCR reaction was carried out by using human small intestine Marathon-Ready cDNA (Clontech) as a template with primer F0 and primer R7. Using this PCR reaction solution as a template, second PCR reaction was conducted with primer F00 and primer R00. The composition of the PCR reaction solution and reaction conditions are shown below. A reaction solution consisting of 2.0 μl human small intestine Marathon-Ready cDNA, 12.5 μM primer F0, 12.5 μM primer R7, 0.4 mM dNTPs and 0.5 μl pfu turbo DNA Polymerase (Stratagene) was adjusted to 20 μl with a buffer attached to Advantage2 Polymerase mix (Clontech), and then heated at 94° C. for 30 seconds and subjected to 35 cycles of reaction each at 94° C. for 10 seconds, at 56° C. for 5 seconds and at 72° C. for 2.5 minutes in thermal cycler 9700 (Applied Biosystems). Then, a mixture consisting of 1 μl of this PCR reaction solution (reacted with R0/R7), 12.5 μM primer F00, 12.5 μM primer R00, 0.4 mM dNTPs and 0.5 μl Advantage2 Polymerase mix (Clontech) was adjusted to 20 μl with a buffer attached to Advantage2 Polymerase mix (Clontech), and then heated at 94° C. for 30 seconds and subjected to 30 cycles of reaction each at 94° C. for 10 seconds, 56° C. for 5 seconds and at 72° C. for 2.5 minutes in thermal cycler 9700 (Applied Biosystems). The amplified DNA was separated by 1.5% agarose gel electrophoresis, and DNA of about 2376-base in length was cut off with a razor, and then the DNA was recovered with QIAquick Gel Extraction Kit (Qiagen). This DNA was cloned into pCR-Blunt II-TOPO vector according to the protocol of the Zero Blunt TOPO PCR Cloning Kit (Invitrogen, Inc.). The product was transformed into Escherichia coli TOP10 competent cell (Invitrogen, Inc.), and clones having the cDNA insert fragment were selected in a kanamycin-containing LB agar medium to give transformants. The respective clones were cultured overnight in a kanamycin-containing LB medium, and plasmid DNAs were prepared by QIAwell 8 Plasmid Kit (Qiagen) to give pCR-BluntII-TCH200 plasmid clones #1, #2 and #3. These were reacted with primer DNAs [primer M13F (SEQ ID NO: 72), primer M13R (SEQ ID NO: 73), primer F00 (SEQ ID NO: 83), primer R00 (SEQ ID NO: 84), primer F1 (SEQ ID NO: 85), primer F2 (SEQ ID NO: 86), primer F5 (SEQ ID NO: 87), primer F7 (SEQ ID NO: 88), primer R1 (SEQ ID NO: 69), primer ff3 (SEQ ID NO: 89), primer ff4 (SEQ ID NO: 90), primer f2 (SEQ ID NO: 80), primer f3 (SEQ ID NO: 91), primer rr1 (SEQ ID NO: 92), primer rr2 (SEQ ID NO: 71) and primer rr3 (SEQ ID NO: 93)] and BigDye Terminator Cycle Sequencing Kit (Applied Biosystems), and the base sequences of the inserted cDNA fragments were determined by DNA sequencer ABI PRISM 3100 DNA analyzer (Applied Biosystems). As a result, the obtained 2 clones had the same DNA fragment and had a 2376-base sequence (SEQ ID NO. 102). The fragment (SEQ ID NO: 97) coded for a 791-amino acid sequence (SEQ ID NO: 66), and the protein comprising the amino acid sequence represented by SEQ ID NO: 66 was designated human TCH200 protein. A transformant having the plasmid comprising the cDNA fragment (SEQ ID NO. 102) was designated Escherichia coli TOP10/pCR-BluntII-TCH200. The obtained sequence (SEQ ID NO. 102) was examined for homology in a public genome database, and as a result, base substitution was recognized at one site (substitution of C with A at position 558 in the base sequence represented by SEQ ID NO: 67) (SEQ ID NO. 103). This base substitution C558A was not accompanied by amino acid substitution, and it is considered that the substitution is derived from single nucleotide polymorphisms (SNPs). When homology with GENEMBL was conducted by using Blast P [Nucleic Acids Res., 25, 3389, 1997], the cDNA comprising the base sequence represented by SEQ ID NO: 67 was revealed to be a novel gene belonging to human vanilloid receptor (FIG. 13). The TCH200 protein showed 58% homology at the base level and 43% homology at the amino acid level with reported human vanilloid receptor human VR1 [Biochemical and Biophysical Research Communications, 281, 1183, 2001], and the human TCH200 protein was estimated to have a 6-times transmembrane structure. EXAMPLE 12 Analysis of Distribution of Human TCH200 Gene Product in Tissues By using two primer DNAs, i.e. primer TMF (SEQ ID NO: 94) and primer TMR (SEQ ID NO: 95), designed from the sequence of human TCH200, and TaqMan probe P1 (SEQ ID NO: 96), the expression level of human TCH200 by cDNA (human MTC panels I and II: Clontech) in each human tissue (heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis, ovary, small intestine, large intestine, peripheral blood leukocyte) was measured by TaqMan PCR. The reaction involved a reaction at 50° C. for 2 minutes and at 95° C. for 10 minutes and 40 cycles each consisting of a reaction at 95° C. for 15 seconds and at 60° C. for 1 minute by using TaqMan Universal PCR Master Mix (Applied Biosystems) in ABI PRISM 7900 sequence detection system (Applied Biosystems), and simultaneously detection was carried out. The results are shown in FIG. 14. The human TCH200 gene product (mRNA) was strongly expressed in various tissues. Particularly in the thymus, testis, ovary, small intestine and colon, the human TCH200 gene product was expressed relatively strongly, but was hardly expressed in the placenta. EXAMPLE 13 Cloning of cDNA Encoding Mouse TCH230 Protein Using two primer DNAs, i.e. primer m230A1 (SEQ ID NO. 106) and primer m230B2 (SEQ ID NO. 107), mouse testis Marathon-Ready cDNA (Clontech) was subjected to primary PCR with Pyrobest DNA Polymerase (Takara Bio) under the following conditions (1) to (3): (1) reaction at 94° C. for 2 minutes, (2) 30 cycles each consisting of reaction at 98° C. for 10 seconds and at 72° C. for 2 minutes, and (3) reaction at 72° C. for 10 minutes. The resulting amplification product was cloned by Zero Blunt TOPO Cloning kit (Invitrogen, Inc.) to give plasmid pCR-BluntII-mTCH230. The product was reacted with primer DNAs [primer SP6 (SEQ ID NO: 7), primer T7 (SEQ ID NO: 8), primer m230F1 (SEQ ID NO. 108), primer m230F2 (SEQ ID NO. 109), primer m230R1 (SEQ ID NO. 110) and primer m230R2 (SEQ ID NO. 111)] and BigDye Terminator Cycle Sequencing Kit (Applied Biosystems), and the base sequence of the inserted cDNA fragment was determined by DNA sequencer ABI PRISM 3100 DNA analyzer (Applied Biosystems). As a result, the clone had a 1237-base sequence (SEQ ID NO. 112). The cDNA fragment (SEQ ID NO. 105) encoded a 373-amino acid sequence (SEQ ID NO. 104), and the protein having the amino acid sequence was designated mouse TCH230 protein. A transformant having the plasmid comprising the cDNA fragment was designated Escherichia coli TOP10/PCR-BluntII-mTCH230. The mouse TCH230 exhibited 74% homology at the base level and 70% homology at the amino acid level with human TCH230, and it was revealed that mouse TCH230 is a mouse ortholog of human TCH230 (FIG. 15). EXAMPLE 14 Analysis of Distribution of Mouse TCH230 Gene Product in Tissues Using two primer DNAs, i.e. primer m230TF (SEQ ID NO. 113) and primer m230TR (SEQ ID NO. 114), designed from the sequence of mouse TCH230, and TaqMan probe m230T1 (SEQ ID NO. 115), the expression level of mouse TCH230 by cDNA (mouse MTC panels I and II: Clontech) in each mouse tissue (bone marrow, eye, lymph node, smooth muscle, prostate, thymus, stomach, uterus, heart, brain, spleen, lung, liver, skeletal muscle, kidney, testis, embryo (7th day), embryo (11th day), embryo (15th day), embryo (17th day)) were measured by TaqMan PCR. The PCR reaction involved a reaction at 50° C. for 2 minutes and at 95° C. for 10 minutes and 40 cycles each consisting of a reaction at 95° C. for 15 seconds and at 60° C. for 1 minute by using TaqMan Universal PCR Master Mix (Applied Biosystems) in ABI PRISM 7900 sequence detection system (Applied Biosystems), and simultaneously detection was carried out. The results are shown in FIG. 16. In mouse MTC panels I and II, the mouse TCH230 gene product (mRNA) was expressed slightly in the eye, lymph node, prostate, thymus, uterus, spleen, liver, kidney and embryo (15th day), expressed at a certain degree in the stomach, skeletal muscle, testis, embryo (7th day) and embryo (17th day), expressed strongly in the heart, and expressed most strongly in the lung. EXAMPLE 15 Analysis of Distribution of Mouse TCH230 Gene Product in Tissues of 7-Week-Old BALB/c Mouse (1) Preparation of cDNA from Each Tissue in Normal Mouse Using ISOGEN (Nippon Gene) or RNeasy Mini Kit (Qiagen), total RNA was prepared from each kind of tissue in 7-week-old BALB/c mouse [cerebrum, cerebellum, hippocampus, medulla oblongata, spinal cord, ischiatic nerve, skin, skeletal muscle, eyeball, heart, lung, trachea, pancreas, kidney, liver, anterior stomach, pyloric stomach, duodenum, jejunoileum, caecum, colon, rectum, spleen, thymus, bone marrow, ovary, uterus, prostate, testis (ovary and uterus were collected from female mice, and other organs were from male mice, and each was collected from 1 to 10 mice)]. The prepared total RNA was subjected to reverse transcription reaction by using TaqMan Reverse Transcription Reagents (Applied Biosystems) to prepare cDNA. (2) Analysis of Distribution of Mouse TCH230 Gene Product in Tissues The expression level (copy number) of mouse TCH230 by cDNA in each kind of mouse tissue was measured by TaqMan PCR with two primer DNAs, i.e. primer m230TF (SEQ ID NO. 113) and primer m230TR (SEQ ID NO. 114) used in Example 14 and TaqMan probe m230T1 (SEQ ID NO. 115). The same cDNA was also measured for the expression level (copy number) of rodent glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by using TaqMan rodent GAPDH control reagents (Applied Biosystems). The reaction involved a reaction at 50° C. for 2 minutes and at 95° C. for 10 minutes and 40 cycles each consisting of a reaction at 95° C. for 15 seconds and at 60° C. for 1 minute by using TaqMan Universal PCR Master Mix (Applied Biosystems) in ABI PRISM 7900 sequence detection system (Applied Biosystems), and simultaneously detection was carried out. The results are shown in FIG. 17. In the tissues of 7-week-old BALB/c mice, the mouse TCH230 gene product (mRNA) was expressed slightly in the ovary, jejunoileum, caecum, colon, rectum, prostate, spleen, eyeball, pyloric stomach, pancreas and heart, expressed at a certain degree in the ischiatic nerve, trachea, testis and uterus, expressed highly in the skin and lung, and expressed at the highest degree in the anterior stomach. EXAMPLE 16 Identification of a Partial Sequence of Rat TCH230 Gene Using two primer DNAs, i.e. primer r230OF (SEQ ID NO. 117) and primer r230OR (SEQ ID NO. 118), rat testis Marathon-Ready cDNA (Clontech) was subjected to PCR with Advantage 2 DNA Polymerase (Clontech) under the following conditions (1) to (3): (1) reaction at 95° C. for 1 minute, (2) 35 cycles each consisting of reaction at 95° C. for 30 seconds and at 68° C. for 3 minutes, and (3) reaction at 68° C. for 3 minutes. The resulting amplification product was subjected to gel electrophoresis, and a fragment of about 1.0 kb was cut off, purified by QIAquick Gel Extraction Kit (Qiagen) and reacted by using primer r230OF (SEQ ID NO. 117), primer r230OR (SEQ ID NO. 118) and BigDye Terminator Cycle Sequencing Kit (Applied Biosystems), and the base sequence of the product amplified by PCR was determined by DNA sequencer ABI PRISM 3100 DNA analyzer (Applied Biosystems). As a result, a partial sequence of rat TCH230 gene cDNA having a 1046-base sequence represented by SEQ ID NO. 116 was identified. EXAMPLE 17 (1) Preparation of cDNA from Each Tissue in Normal Rat Using RNeasy Mini Kit (Qiagen), total RNA was prepared from each kind of tissue (cerebrum, cerebellum, liver, kidney, prostate, heart, lung, duodenum, jejunoileum, colon, skin, eyeball) in 12-week-old male Wistar rats. The prepared total RNA was subjected to reverse transcription reaction with TaqMan Reverse Transcription Reagents (Applied Biosystems) to prepare cDNA. (2) Analysis of Distribution of Rat TCH230 Gene Product in Tissues The expression level (copy number) of rat TCH230 by cDNA in each rat tissue was measured by TaqMan PCR with two primer DNAs, i.e. primer r230TF (SEQ ID NO. 119) and primer r230TR (SEQ ID NO. 120), designed from the sequence of SEQ ID NO. 116, and TaqMan probe r230T1 (SEQ ID NO. 121). The same cDNA was also measured for the expression level (copy number) of rodent glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by using TaqMan rodent GAPDH control reagents (Applied Biosystems). The PCR reaction involved a reaction at 50° C. for 2 minutes and at 95° C. for 10 minutes and 40 cycles each consisting of a reaction at 95° C. for 15 seconds and at 60° C. for 1 minute by using TaqMan Universal PCR Master Mix (Applied Biosystems) in ABI PRISM 7900 sequence detection system (Applied Biosystems), and simultaneously detection was carried out. The results are shown in FIG. 18. The TCH230 gene product (mRNA) was expressed in all tissues in the 12-week-old Wistar rats, and particularly in the cerebrum, prostate, jejunoileum, colon and skin, high expression was observed, and the highest expression was observed in the lung. EXAMPLE 18 Construction of Human TCH230 Expression Vector Human TCH230 (SEQ ID NO. 1) expression vector was constructed by the following method. Using 10 ng of plasmid obtained in Example 1 as a template, PCR was conducted with primer 230OF2 (SEQ ID NO. 122) and primer 230OR2 (SEQ ID NO. 123) and Pyrobest DNA Polymerase (Takara Bio) under the following conditions (1) to (3). The 5′-terminal side primer 230OF2 and the 3′-terminal side primer 230OR2 were designed such that Hind III site and Xba I site were added respectively to the 5′-terminal side for cloning into a vector. (1) reaction at 98° C. for 2 minutes, (2) 30 cycles each consisting of reaction at 98° C. for 10 seconds, at 65° C. for 30 seconds and at 72° C. for 3.5 minutes, and (3) reaction at 72° C. for 10 minutes. The PCR reaction solution was subjected to gel electrophoresis, and a major band was purified. The PCR fragment thus obtained was digested with restriction enzymes Hind III and Xba I at 37° C. for 1 hour, and the reaction solution was subjected to gel electrophoresis and purified. The product was ligated to Hind III site and Xba I site of an animal cell expression vector pcDNA3.1(+) (Invitrogen, Inc.) by Takara ligation kit ver. 2 (Takara Bio). This ligation reaction solution was precipitated with ethanol and used to transform a competent cell Escherichia coli TOP10 (Invitrogen, Inc.). From a plurality of colonies thus obtained, a plasmid was prepared, and this base sequence was reacted by using primer DNAs [primer BGH RV (SEQ ID NO. 124), primer T7 (SEQ ID NO: 8), primer B1 (SEQ ID NO: 9), primer F1 (SEQ ID NO. 10)] and BigDye Terminator Cycle Sequencing Kit (Applied Biosystems), and the base sequence was confirmed by DNA sequencer ABI PRISM 3100 DNA analyzer (Applied Biosystems). The transformant having this plasmid was designated Escherichia coli TOP10/pcDNA3.1(+)-TCH230. EXAMPLE 19 Preparation of Human TCH230 Expressing CHO Cell Strain and Measurement of the Expression Level of the Introduced Gene Escherichia coli TOP10/pCDNA3.1(+)-TCH230 was cultured, and from this Escherichia coli, plasmid DNA was prepared by EndoFree Plasmid Maxi Kit (Qiagen). This plasmid DNA was introduced into CHO dhfr− cells by using FuGENE 6 Transfection Reagent (Roche) according to its attached protocol. A mixture of 2 μg of plasmid DNA and transfection reagents was added to a 6 cm Petri dish on which 3×105 CHO dhfr− cells had been plated before 24 hours. The cells were cultured for 1 day in MEMα medium (Invitrogen, Inc.) containing 10% bovine fetal serum (JRH Bioscience), and peeled off by treatment with trypsin, and the recovered cells were plated on a 96-well plate at a density of 10-50 cells/well. After 24 hours, 0.5 mg/ml geneticine (Invitrogen, Inc.) was added to the medium, and then the TCH230 expression cells were selected in a medium containing 0.5-1.0 mg/ml geneticine. 22 wells wherein one to three colonies had grown per well were cultured in a 6-well plate, and from the grown cells, total RNA was prepared by RNeasy Mini Kit or RNeasy 96 Kit (both available from Qiagen). The prepared total RNA was subjected to reverse transcription reaction by TaqMan Reverse Transcription Reagents (Applied Biosystems) to prepare cDNA. This was examined for the expression level of TCH230 by TaqMan PCR with primer TF (SEQ ID NO. 15) and primer TR (SEQ ID NO. 16) used in Example 2 and TaqMan probe T1 (SEQ ID NO. 17). The reaction involved a reaction at 50° C. for 2 minutes and at 95° C. for 10 minutes and 40 cycles each consisting of a reaction at 95° C. for 15 seconds and at 60° C. for 1 minute by using TaqMan Universal PCR Master Mix (Applied Biosystems) in ABI PRISM 7900 sequence detection system (Applied Biosystems), and simultaneously detection was carried out. As cell strains (polyclonal) highly expressing human TCH230 gene, clone Nos. 19 and 26 were selected Each strain was inoculated into a 96-well plate at a density of 0.5 cell/well, and then cultured for 7 to 10 days in a medium containing geneticine, to give a monoclonal clone. Total RNA was prepared and the expression level of human TCH230 gene was measured by TaqMan PCR. As cell strains (monoclonal) expressing human TCH230, clone No. 19-6 were selected. EXAMPLE 20 Measurement of Incorporation of [6,7-3H(N)]-Estrone Sulfate and [1,2,6,7-3H(N)]-Dehydroepiandrosterone Sulfate into the Human TCH230-Expressing CHO Cell Strain Incorporation of [6,7-3H(N)]-estrone sulfate and [1,2,6,7-3H(N)]-dehydroepiandrosterone sulfate (hereinafter also referred to as [1,2,6,7-3H(N)]-DHEA-S) into the human TCH230-expressing CHO cell strain clone No. 19-6 obtained in Example 19 was measured. The human TCH230 expressing CHO cell strain clone No. 19-6 was inoculated at a density of 4×104 cells/well in a 96 well plate, and cultured at 37° C. for 24 hours in MEMα medium (Invitrogen, Inc.) containing 5 mM sodium butyrate. The medium was removed, and the cells were washed 3 times with 150 μL NMDG buffer (140 mM N-methyl-D(−)-glucamine, 5.4 mM KCl, 0.34 mM Na2HPO4, 0.44 mM KH2PO4, 1.26 mM CaCl2, 0.41 mM MgSO4, 0.49 mM MgCl2, 5.55 mM glucose, pH 7.4-7.6), and incubated in 150 μL NMDG buffer at 37° C. for 1 hour. The buffer was replaced with 90 μL NaCl buffer (140 mM NaCl, 5.4 mM KCl, 0.34 mM Na2HPO4, 0.44 mM KH2PO4, 1.26 mM CaCl2, 0.41 mM MgSO4, 0.49 mM MgCl2, 5.55 mM glucose, pH 7.4-7.6) or 90 μL NMDG buffer, followed by adding 10 μL of 2.5 μM estrone sulfate, ammonium salt, [6,7-3H(N)]- or 1.37 μM dehydroepiandrosterone sulfate, sodium salt, [1,2,6,7-3H(N)]- (all of which are available from Perkin-Elmer Life Science). The cells were incubated at 37° C. for 1 hour, and the buffer was removed, then washed 3 times with 200 μL PBS (Takara Bio) and lysed with 10 μL of 0.1N NaOH. 100 μL SuperMix scintillator (Perkin-Elmer Life Science) was added thereto and stirred, and the amount of [6,7-3H(N)]-estrone sulfate or [1,2,6,7-3H(N)]-DHEA-S incorporated into the cells was measured in terms of radioactivity. This measurement was carried out with 1450 MICROBETA PLUS LIQUID SCINTILLATION COUNTER (Perkin-Elmer Life Science). CHO dhfr− cells into which vector pcDNA3.1(+) had been introduced (also referred to hereinafter as Mock) was also subjected to the same procedure and measured for radioactivity. The result of [6,7-3H(N)]-estrone sulfate is shown in FIG. 19, and the result of [1,2,6,7-3H(N)]-DHEA-S is shown in FIG. 20. It was thereby revealed that the human TCH230 expressing CHO cells incorporate [6,7-3H(N)]-estrone sulfate and [1,2,6,7-3H(N)]-DHEA-S in the presence of 140 mM NaCl. EXAMPLE 21 Identification of a Partial Sequence of Mouse TCH234 Gene Using two primer DNAs, i.e. primer m234-1485F (SEQ ID NO. 126) and primer m234-1801R (SEQ ID NO. 127), mouse testis Marathon-Ready cDNA (Clontech) was subjected to PCR with Advantage 2 DNA Polymerase (Clontech) under the following conditions (1) to (5): (1) reaction at 94° C. for 30 seconds, (2) 35 cycles each consisting of reaction at 94° C. for 10 seconds, at 62° C. for 10 seconds and at 68° C. for 30-seconds, and (3) reaction at 68° C. for 3 minutes. The resulting amplification product was subjected to gel electrophoresis, and a fragment of about 0.3 kb was cut off, purified by QIAquick Gel Extraction Kit (Qiagen) and reacted by using primer m234-1485F (SEQ ID NO. 126), primer m234-1180R (SEQ ID NO. 127) and BigDye Terminator Cycle Sequencing Kit (Applied Biosystems), and the base sequence of the product amplified by PCR was determined by DNA sequencer ABI PRISM 3100 DNA analyzer (Applied Biosystems). As a result, a partial sequence of mouse TCH234 gene cDNA having a 317-base sequence represented by SEQ ID NO. 125 was identified. EXAMPLE 22 Analysis of Distribution of Mouse TCH234 Gene Product in Tissues The expression level (copy number) of mouse TCH234 by the cDNA prepared in Example 15 in each mouse tissue was measured by TaqMan PCR with two primer DNAs, i.e. primer m234-TMF (SEQ ID NO. 128) and primer m234-TMR (SEQ ID NO. 129), designed from the base sequence represented by SEQ ID NO. 125, and TaqMan probe m234T1 (SEQ ID NO. 130). The same cDNA was also measured for the expression level (copy number) of rodent glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by using TaqMan rodent GAPDH control reagents (Applied Biosystems). The reaction involved a reaction at 50° C. for 2 minutes and at 95° C. for 10 minutes and 40 cycles each consisting of a reaction at 95° C. for 15 seconds and at 60° C. for 1 minute by using TaqMan Universal PCR Master Mix (Applied Biosystems) in ABI PRISM 7900 sequence detection system (Applied Biosystems), and simultaneously detection was carried out. The results are shown in FIG. 21. In each kind of tissue of 7-week-old BALB/c mouse, the mouse TCH234 gene product (mRNA) was expressed slightly in the ischiatic nerve, ovary, skin, jejunoileum, colon, anterior stomach, prostate, kidney, uterus, thymus and cerebrum, expressed at a certain degree in the lung, hippocampus, duodenum, testis and trachea, and expressed particularly highly in the pyloric stomach. EXAMPLE 23 Identification of a Partial Sequence of Rat TCH234 Gene Using two primer DNAs, i.e. primer r234-815F (SEQ ID NO. 132) and primer r234-1177R (SEQ ID NO. 133), rat kidney Marathon-Ready cDNA (Clontech) was subjected to PCR with Advantage 2 DNA Polymerase (Clontech) under the following conditions (1) to (3): (1) reaction at 94° C. for 30 seconds, (2) 35 cycles each consisting of reaction at 94° C. for 10 seconds, at 62° C. for 10 seconds and at 68° C. for 30 seconds, and (3) reaction at 68° C. for 3 minutes. The resulting amplification product was subjected to gel electrophoresis, and a fragment of about 0.35 kb was cut off, purified by QIAquick Gel Extraction Kit (Qiagen) and reacted by using primer r234-815F (SEQ ID NO. 132), primer m234-1177R (SEQ ID NO. 133) and BigDye Terminator Cycle Sequencing Kit (Applied Biosystems), and the base sequence of the product amplified by PCR was determined by DNA sequencer ABI PRISM 3100 DNA analyzer (Applied Biosystems). As a result, a partial sequence of rat TCH234 gene cDNA having a 363-base sequence represented by SEQ ID NO. 131 was identified. EXAMPLE 24 Analysis of Distribution of Rat TCH234 Gene Product in Tissues The expression level (copy number) of rat TCH234 by the cDNA prepared in Example 17 in each rat tissue was measured by TaqMan PCR with two primer DNAs, i.e. primer r234-TMF (SEQ ID NO. 134) and primer r234-TMR (SEQ ID NO. 135), designed from the base sequence represented by SEQ ID NO. 131, and TaqMan probe r234-P1 (SEQ ID NO. 136). The same cDNA was also measured for the expression level (copy number) of rodent glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by using TaqMan rodent GAPDH control reagents (Applied Biosystems). The PCR reaction involved a reaction at 50° C. for 2 minutes and at 95° C. for 10 minutes and 40 cycles each consisting of a reaction at 95° C. for 15 seconds and at 60° C. for 1 minute by using TaqMan Universal PCR Master Mix (Applied Biosystems) in ABI PRISM 7900 sequence detection system (Applied Biosystems), and simultaneously detection was carried out. The results are shown in FIG. 22. In each kind of tissue of 12-week-old Wistar rat, the rat TCH234 gene product (mRNA) was expressed at a certain degree in the cerebellum, liver, jejunoileum and colon, expressed highly in the cerebrum, duodenum and eye and expressed most highly in the kidney. EXAMPLE 25 Construction of Human TCH234 Expression Vector Human TCH234 (SEQ ID NO. 18) expression vector was constructed by the following method. Using 10 ng plasmid obtained in Example 5 as a template, PCR was conducted with primer 2340OF (SEQ ID NO. 137) and primer 2340R (SEQ ID NO. 138) and Pyrobest DNA Polymerase (Takara Bio) under the following conditions (1) to (3). The 5′-terminal side primer 234OF and the 3′-terminal side primer 234OR were designed such that Hind III site and Xba I site were added respectively to the 5′-terminal side for cloning into a vector. (1) reaction at 94° C. for 1 minute, (2) 25 cycles each consisting of reaction at 94° C. for 30 seconds, at 55° C. for 30 seconds and at 72° C. for 3 minutes, and (3) reaction at 72° C. for 5 minutes. The PCR reaction solution was subjected to gel electrophoresis, and a major band was purified. The PCR fragment thus obtained was digested with restriction enzymes Hind III and Xba I at 37° C. for 1 hour, and the reaction solution was subjected to gel electrophoresis and purified. The product was ligated to Hind III site and Xba I site of an animal cell expression vector pcDNA3.1(+) (Invitrogen, Inc.) by using Takara ligation kit ver. 2 (Takara Bio). This ligation reaction solution was used to transform a competent cell Escherichia coli JM109 (Takara Bio). From a plurality of colonies thus obtained, a plasmid was prepared, and this base sequence was reacted by using primer DNAs [primer BGH RV (SEQ ID NO. 124), primer T7 (SEQ ID NO: 8), primer F3 (SEQ ID NO: 35), primer R2 (SEQ ID NO: 37), primer ff2 (SEQ ID NO: 25), primer 234F21 (SEQ ID NO. 139), primer 234F22 (SEQ ID NO. 140), primer 234F23 (SEQ ID NO. 141), primer 234R24 (SEQ ID NO. 142)] and BigDye Terminator Cycle Sequencing Kit (Applied Biosystems), and the base sequence was confirmed by DNA sequencer ABI PRISM 3100 DNA analyzer (Applied Biosystems). The transformant having this plasmid was designated Escherichia coli JM109/pCDNA3.1(+)-TCH234. EXAMPLE 26 Preparation of human TCH234-expressing CHO cell strain The Escherichia coli JM109/pcDNA3.1(+)-TCH234 was cultured, and from this Escherichia coli, plasmid DNA was prepared by EndoFree Plasmid Maxi Kit (Qiagen). This plasmid DNA was introduced into CHO dhfr− cells by using FuGENE 6 Transfection Reagent (Roche) according to its attached protocol. A mixture of 2 μg of plasmid DNA and transfection reagents was added to a Petri dish of 6 cm in diameter on which 3×105 CHO dhfr− cells had been plated before 24 hours. The cells were cultured for one (1) day in MEMα medium (Invitrogen, Inc.) containing 10% bovine fetal serum (JRH Bioscience), and peeled off by treatment with trypsin, and the recovered cells were suitably diluted and plated on a 10 cm Petri dish. After 24 hours, 0.5 mg/ml geneticine (Invitrogen, Inc.) was added to the medium, and for 10 days thereafter, human TCH234-expressing cells were selected in MEM medium containing 0.5-1.0 mg/ml geneticine. 104 grown colonies of monoclonal human TCH234-expressing cells were selected in the geneticine-containing selective medium. EXAMPLE 27 Measurement of the Expression Level of the Introduced Gene in the Human TCH234 Expressing CHO Cell Strain by TaqMan PCR The human TCH234 expressing CHO cell strain prepared in Example 26 was cultured in a 96-well plate, and from the grown cells, total RNA was prepared by using SV 96 Total RNA Isolation System (Promega). The prepared total RNA was subjected to reverse transcription reaction by TaqMan Reverse Transcription Reagents (Applied Biosystems) to prepare cDNA. This was measured for the expression level of human TCH234 by TaqMan PCR with primer TMF (SEQ ID NO: 32) and primer TMR (SEQ ID NO: 33), used in Example 6, and TaqMan probe P1 (SEQ ID NO: 38). The PCR reaction involved a reaction at 50° C. for 2 minutes and at 95° C. for 10 minutes and 40 cycles each consisting of a reaction at 95° C. for 15 seconds and at 60° C. for 1 minute by using TaqMan Universal PCR Master Mix (Applied Biosystems) in ABI PRISM 7900 sequence detection system (Applied Biosystems), and simultaneously detection was carried out. As a cell strain highly expressing human TCH234 gene, clone No. 104 was selected. EXAMPLE 28 Analysis of Tissue Distribution of Human TCH234 Gene Product in Human Digestive Tissues The expression level (copy number) of human TCH234 by cDNA (human digestive system MTC panel; Clontech) in each human digestive tract tissue (liver, esophagus, stomach, duodenum, jejunoileum, ileocecum, caecum, ascending colon, transverse colon, descending colon, rectum) was measured by TaqMan PCR with primer TMF (SEQ ID NO: 32) and primer TMR (SEQ ID NO: 33), used in Example 6, and TaqMan probe P1 (SEQ ID NO: 38). The same cDNA was also measured for the expression level (copy number) of rodent glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by using TaqMan rodent GAPDH control reagents (Applied Biosystems). The PCR reaction involved a reaction at 50° C. for 2 minutes and at 95° C. for 10 minutes and 40 cycles each consisting of a reaction at 95° C. for 15 seconds and at 60° C. for 1 minute by using TaqMan Universal PCR Master Mix (Applied Biosystems) in ABI PRISM 7900 sequence detection system (Applied Biosystems), and simultaneously detection was carried out. The results are shown in FIG. 23. In the digestive tract tissues, the human TCH234 gene product (mRNA) was expressed slightly in the ileocecum, expressed highly in the duodenum and expressed most highly in the stomach. EXAMPLE 29 Identification of a Partial Sequence of Mouse TCH212 Gene Using two primer DNAs, i.e. primer m212A1 (SEQ ID NO. 144) and primer m212B1 (SEQ ID NO. 145), mouse testis Marathon-Ready cDNA (Clontech) was subjected to PCR with Advantage 2 DNA Polymerase (Clontech) under the following conditions (1) to (3): (1) reaction at 95° C. for 1 minute, (2) 35 cycles each consisting of reaction at 95° C. for 30 seconds and at 68° C. for 3 minutes, and (3) reaction at 68° C. for 3 minutes. The resulting amplification product was subjected to gel electrophoresis, and a fragment of about 0.8 kb was cut off, purified by QIAquick Gel Extraction Kit (Qiagen) and reacted by using primer m212A 1 (SEQ ID NO. 144), primer m212B 1 (SEQ ID NO. 145) and BigDye Terminator Cycle Sequencing Kit (Applied Biosystems), and the base sequence of the product amplified by PCR was determined by DNA sequencer ABI PRISM 3100 DNA analyzer (Applied Biosystems). As a result, a partial sequence of mouse TCH212 gene cDNA having a 680-base sequence represented by SEQ ID NO. 143 was identified. EXAMPLE 30 Analysis of Distribution of Mouse TCH212 Gene Product in Tissues Using two primer DNAs, i.e. primer m212TF (SEQ ID NO: 146) and primer m212TR (SEQ ID NO: 147), designed from the base sequence represented by SEQ ID NO: 143, and TaqMan probe m212T1 (SEQ ID NO: 148), the expression level (copy number) of mouse TCH212 by the cDNA prepared in Example 15 in each mouse tissue was measured by TaqMan PCR. The same cDNA was also measured for the expression level (copy number) of rodent glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by using TaqMan rodent GAPDH control reagents (Applied Biosystems). The reaction involved a reaction at 50° C. for 2 minutes and at 95° C. for 10 minutes and 40 cycles each consisting of a reaction at 95° C. for 15 seconds and at 60° C. for 1 minute by using TaqMan Universal PCR Master Mix (Applied Biosystems) in ABI PRISM 7900 sequence detection system (Applied Biosystems), and simultaneously detection was carried out. The results are shown in FIG. 24. In each kind of tissue in 7-week-old BALB/c mouse, the mouse TCH212 gene product (mRNA) was expressed slightly in the trachea, anterior stomach, prostate, duodenum, uterus, spleen, eyeball, thymus, pyloric stomach, heart, lung, hippocampus and bone marrow, expressed at a certain degree in the ovary, skin, jejunoileum, caecum, rectum, pancreas, cerebellum and cerebrum, expressed highly in the ischiatic nerve, colon, medulla oblongata and spinal cord and expressed most highly in the testis. EXAMPLE 31 Identification of a Partial Sequence of Rat TCH212 Gene Using two primer DNAs, i.e. primer m212A1 (SEQ ID NO. 144) and primer m212B1 (SEQ ID NO. 145) used in Example 29, rat testis Marathon-Ready cDNA (Clontech) was subjected to PCR with Advantage 2 DNA Polymerase (Clontech) under the following conditions (1) to (3): (1) reaction at 95° C. for 1 minute, (2) 35 cycles each consisting of reaction at 95° C. for 30 seconds, at 60° C. for 30 seconds and at 68° C. for 3 minutes, and (3) reaction at 68° C. for 3 minutes. The resulting amplification product was subjected to gel electrophoresis, and a fragment of about 0.8 kb was excised, purified by QIAquick Gel Extraction Kit (Qiagen) and reacted by using primer m212A1 (SEQ ID NO. 144), primer m212B1 (SEQ ID NO. 145) and BigDye Terminator Cycle Sequencing Kit (Applied Biosystems), and the base sequence of the product amplified by PCR was determined by DNA sequencer ABI PRISM 3100 DNA analyzer (Applied Biosystems). As a result, a partial sequence of rat TCH212 gene cDNA having a 771-base sequence represented by SEQ ID NO. 149 was identified. EXAMPLE 32 Analysis of Distribution of Rat TCH212 Gene Product in Tissues Using two primer DNAs, i.e. primer r212TF (SEQ ID NO. 150) and primer r212TR (SEQ ID NO. 151), designed from the base sequence represented by SEQ ID NO: 149, and TaqMan probe r212T1 (SEQ ID NO. 152), the expression level (copy number) of rat TCH212 by the cDNA prepared in Example 17 in each rat tissue was measured by TaqMan PCR. The same cDNA was also measured for the expression level (copy number) of rodent glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by using TaqMan rodent GAPDH control reagents (Applied Biosystems). The reaction involved a reaction at 50° C. for 2 minutes and at 95° C. for 10 minutes and 40 cycles each consisting of a reaction at 95° C. for 15 seconds and at 60° C. for 1 minute by using TaqMan Universal PCR Master Mix (Applied Biosystems) in ABI PRISM 7900 sequence detection system (Applied Biosystems), and simultaneously detection was carried out. The results are shown in FIG. 25. In all tissues in 12-week-old Wistar rat, the rat TCH212 gene product (mRNA) was expressed; particularly in the lung, duodenum and jejunoileum, certain expression was observed, and in the cerebrum, cerebellum, prostate, colon and eyeball, high expression was observed. EXAMPLE 33 Construction of Human TCH212 Expression Vector Human TCH212 (SEQ ID NO: 42) expression vector was constructed by the following method. Using 10 ng of plasmid obtained in Example 7 as a template, PCR was conducted with primer 2120F (SEQ ID NO. 153) and primer 2120R (SEQ ID NO. 154) and KOD DNA Polymerase (Toyobo) under the following conditions (1) to (3). The 5′-terminal side primer 2120F and the 3′-terminal side primer 2120R were designed such that BamH I site and Not I site were added respectively to the 5′-terminal side for cloning into a vector. (1) reaction at 94° C. for 2 minutes, (2) 35 cycles each consisting of reaction at 94° C. for 15 seconds, at 60° C. for 30 seconds and at 68° C. for 3.5 minutes, and (3) reaction at 68° C. for 3 minutes. The PCR reaction solution was subjected to gel electrophoresis, and a major band was purified. The PCR fragment thus obtained was digested with restriction enzymes Bam HI and Not I at 37° C. for 1 hour, and the reaction solution was subjected to gel electrophoresis and purified. The product was ligated to Bam HI site and Not I site of an animal cell expression vector pcDNA3.1(+) (Invitrogen, Inc.) by using Takara ligation kit ver. 2 (Takara Bio). This ligation reaction solution was used to transform a competent cell Escherichia coli JM109 (Takara Bio). From a plurality of colonies thus obtained, a plasmid was prepared, and with respect to 2 clones wherein a fragment of about 3.5 kbp was confirmed to be inserted, the base sequence was reacted by using primer DNAs [primer BGH RV (SEQ ID NO. 124), primer T7 (SEQ ID NO: 8), primer A2 (SEQ ID NO: 48), primer B1 (SEQ ID NO: 49), primer B2 (SEQ ID NO: 50), primer F1 (SEQ ID NO: 51), primer F2 (SEQ ID NO: 52), primer F3 (SEQ ID NO: 53), primer F4 (SEQ ID NO: 54), primer F5 (SEQ ID NO: 55), primer R1 (SEQ ID NO: 56), primer R2 (SEQ ID NO: 57), primer R3 (SEQ ID NO: 58), primer R4 (SEQ ID NO: 59)] and BigDye Terminator Cycle Sequencing Kit (Applied Biosystems), and the base sequence was determined by DNA sequencer ABI PRISM 3100 DNA analyzer (Applied Biosystems). As a result, one-base substitution was observed in both the clones as compared with SEQ ID NO: 43. That is, in “clone 1”, Cat position 1185 in SEQ ID NO: 43 was changed into A, and in “clone 2”, A at position 2509 was changed into T, and the change in both cases was a change to a termination codon on the frame. Accordingly, the following correction was conducted. To introduce a termination codon on the same frame into an upstream from an initiation codon, the plasmid DNA in “clone 2” was cleaved with Nhe I, blunt-ended, re-cyclized by ligation and introduced into Escherichia coli JM109. The plasmid DNA in the resulting “modified clone 2” was cleaved with Bst EII and Not I, to remove a DNA fragment (about 1.1 kbp) having the one-base substitution at position 2509. Separately, the plasmid DNA in “clone 1” was cleaved with Bst EII and Not I to prepare a DNA fragment (about 1.1 kbp) of predetermined sequence. The above 2 DNA fragments were ligated and introduced into Escherichia coli JM109. After transformation, the transformant was cultured on agar medium at 30° C. for 2 days, and from a colony appearing on the second day, plasmid was extracted. This clone was determined for its base sequence in the same manner as described above, and confirmed to agree with SEQ ID NO: 43. The transformant having this plasmid was designated Escherichia coli JM109/pCDNA3.1(+)-NheBlunt-TCH212. EXAMPLE 34 Identification of a Partial Sequence of Mouse TCH 200 Gene Using two primer DNAs, i.e. primer m200A1 (SEQ ID NO. 156) and primer m200B1 (SEQ ID NO. 157), the mouse skin cDNA prepared in Example 15 was subjected to PCR with Advantage 2 DNA Polymerase (Clontech) under the following conditions (1) to (5): (1) reaction at 94° C. for 3 minutes, (2) 5 cycles each consisting of reaction at 94° C. for 5 seconds and at 72° C. for 1 minute, (3) 5 cycles each consisting of reaction at 94° C. for 5 seconds and at 70° C. for 1 minute, (4) 25 cycles each consisting of reaction at 94° C. for 5 seconds and at 68° C. for 1 minute, and (5) reaction at 70° C. for 10 minutes. The resulting amplification product was subjected to gel electrophoresis, and a fragment of about 1.1 kb was excised and purified by QIAquick Gel Extraction Kit (Qiagen). The purified product was reacted by using primer m200A1 (SEQ ID NO. 156), primer m200B 1 (SEQ ID NO. 157) and BigDye Terminator Cycle Sequencing Kit (Applied Biosystems), and the base sequence of the product amplified by PCR was determined by DNA sequencer ABI PRISM 3100 DNA analyzer (Applied Biosystems). From the determined sequence, two primer DNAs, i.e. primer m200A2 (SEQ ID NO. 158) and primer m200B2 (SEQ ID NO. 159) were designed and used in determination of the base sequence of the PCR amplification product. As a result, a partial sequence of mouse TCH200 gene cDNA having a 1064-base sequence represented by SEQ ID NO. 155 was identified. EXAMPLE 35 Analysis of Distribution of Mouse TCH200 Gene Product in Tissues The expression level (copy number) of mouse TCH200 by the cDNA prepared in Example 15 in each mouse tissue was measured by TaqMan PCR with TaqMan probe m200T1 (SEQ ID NO. 160) designed from the base sequence represented by SEQ ID NO. 155, and two primer DNAs, i.e. primer m200A2 (SEQ ID NO. 158) and primer m200B2 (SEQ ID NO. 159) used in Example 34. The same cDNA was also measured for the expression level (copy number) of rodent glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by using TaqMan rodent GAPDH control reagents (Applied Biosystems). The PCR reaction involved a reaction at 50° C. for 2 minutes and at 95° C. for 10 minutes and 40 cycles each consisting of a reaction at 95° C. for 15 seconds and at 60° C. for 1 minute by using TaqMan Universal PCR Master Mix (Applied Biosystems) in ABI PRISM 7900 sequence detection system (Applied Biosystems), and simultaneously detection was carried out. The results are shown in FIG. 26. In each tissue in 7-week-old BALB/c mouse, the mouse TCH200 gene product (mRNA) was expressed at a certain degree in the cerebrum, medulla oblongata, spinal cord, ischiatic nerve, duodenum, caecum, colon, ovary and uterus, expressed highly in the anterior stomach, jejunoileum and prostate and expressed most highly in the skin and rectum. EXAMPLE 36 Construction of Human TCH200 Expression Vector Human TCH200 (SEQ ID NO: 66) expression vector was constructed by the following method. Using the plasmid obtained in Example 11 as a template, PCR was conducted with primer TCH200F (SEQ ID NO. 161) and primer TCH200R (SEQ ID NO. 162) and Pyrobest DNA Polymerase (Takara Bio) under the following conditions (1) to (5). The 5′-terminal side primer TCH200F and the 3′-terminal side primer TCH200R were designed such that Kpn I site and Not I site were added respectively to the 5′-terminal side for cloning into a vector. (1) reaction at 98° C. for 5 seconds, (2) 2 cycles each consisting of reaction at 98° C. for 5 seconds and at 68° C. for 290 seconds, (3) 23 cycles each consisting of reaction at 98° C. for 5 seconds and at 66° C. for 290 seconds, (4) 3 cycles each consisting of reaction at 98° C. for 5 seconds and at 64° C. for 290 seconds, and (5) reaction at 72° C. for 7 minutes. The PCR reaction solution was subjected to gel electrophoresis, and a major band was purified. The PCR fragment thus obtained was digested with restriction enzymes KpnI and NotI at 37° C. for 1 hour, and the reaction solution was subjected to gel electrophoresis and purified. The product was ligated to KpnI site and NotI site of an animal cell expression vector pcDNA3.1(+) (Invitrogen, Inc.) by using Takara ligation kit ver. 2 (Takara Bio). This ligation reaction solution was used to transform Escherichia coli JM109 (Takara Bio) by the heat shock method. From a plurality of colonies thus obtained, plasmid was prepared, and this base sequence was reacted with primer DNAs [primer T7 (SEQ ID NO. 163), primer AF (SEQ ID NO. 164), primer BF (SEQ ID NO. 165), primer CF (SEQ ID NO. 166), primer DF (SEQ ID NO. 167), primer BGH RV (SEQ ID NO. 168), primer DR (SEQ ID NO. 169), primer CR (SEQ ID NO. 170), primer BR (SEQ ID NO. 171), primer AR (SEQ ID NO. 172)] and BigDye Terminator Cycle Sequencing Kit (Applied Biosystems), and the base sequence was confirmed by DNA sequencer ABI PRISM 3100 DNA analyzer (Applied Biosystems). The transformant having this plasmid was designated Escherichia coli JM109/pCDNA3.1(+)/TCH200. EXAMPLE 37 Preparation of Human TCH200-Expressing CHO Cell Strain and Measurement of the Expression Level of the Introduced Gene The Escherichia coli JM109/pCDNA3.1(+)/TCH200 was cultured, and from the Escherichia coli, plasmid DNA was prepared by using EndoFree Plasmid Maxi Kit (Qiagen). This plasmid DNA was introduced into CHO-K1 cell by Nucleofector (Amakusa) and Cell Line Nucleofector Kit T (Amakusa) according to their attached protocol. The CHO-K1 cells at a density of 1×106 were suspended at ordinary temperature in 100 μl of solution T to which supplements attached to the kit had been added, and then 2 μg of plasmid DNA was mixed with the resulting suspension and introduced into a cuvette and subjected to Nucleofetor program U-27. Immediately, 500 μl of RPMI1640 medium (Nikken Seibutsu Igaku Kenkyusho) containing 10% fetal bovine serum (ICN Biomedicals), which has been pre-warmed at 37° C., was added thereto, and 1 ml of Ham's F12 medium (Nikken Seibutsu Igaku Kenkyuisho) containing 10% fetal bovine serum was added thereto, and the suspension was dropped onto a 6-well plate, which has been pre-warmed at 37° C., and cultured. After 3 days, the medium was replaced with the medium containing 0.4 mg/ml geneticine (Invitrogen, Inc.) to initiate selection of human TCH200 expression cells. Four days after selection was initiated, the transfected cells were peeled off, and the recovered cells were inoculated at a density of 100 cells/well in FBS-Ham's F12 medium containing 10% bovine fetal serum in a 24-well plate. After 4 days, the number of colonies grown in each well and the approximate number of cells per colony were measured, whereby the number of cells per well was calculated, and on the basis of this number, the cells were inoculated such that one cell was put in one well on a 96-well plate, to order to produce a monoclonal cell expressing human TCH200. From the grown monoclonal cells expressing human TCH200, total RNA was prepared by RNeasy 96 Kit (Qiagen). The prepared total RNA was subjected to reverse transcription reaction by TaqMan Reverse Transcription Reagents (Applied Biosystems) to prepare cDNA. The cDNA was measured for the expression level of human TCH200 by TaqMan PCR with primer TMF (SEQ ID NO: 94) and primer TMR (SEQ ID NO: 95) used in Example 12 and TaqMan probe P1 (SEQ ID NO: 96). The reaction involved a reaction at 50° C. for 2 minutes and at 95° C. for 10 minutes and 40 cycles each consisting of a reaction at 95° C. for 15 seconds and at 60° C. for 1 minute by using TaqMan Universal PCR Master Mix (Applied Biosystems) in ABI PRISM 7900 sequence detection system (Applied Biosystems), and simultaneously detection was carried out. As a cell strain highly expressing human TCH200 gene, clone No. G10 was selected. EXAMPLE 38 Analysis of Expression of Human TCH230, Human TCH234, Human TCH212 and Human TCH200 Gene in Commercial Normal Human Cells (1) Preparation of Normal Human Cell cDNA Normal human cells were purchased from Cambrex BioScience Walkersvill and cultured according to a method attached to the product. The cells used in the experiment and the mediums used in culturing the cells are shown in Table 3. TABLE 3 No. Cell Medium 1 Umbilical cord vein endothelial cell C-2517 Bullet Kit EGM CC-3124 2 Main artery endothelial cell CC-2535 Bullet Kit EGM-2 CC-3162 3 Coronary artery endothelial cell CC-2585 Bullet Kit EGM-2MV CC-3202 4 Main artery smooth muscle cell CC-2571 Bullet Kit SmGM-2 CC-3182 5 Coronary artery smooth muscle cell CC-2583 Bullet Kit SmGM-2 CC-3182 6 Uterus smooth muscle cell CC-2562 Bullet Kit SmGM-2 CC-3182 7 Bronchial smooth muscle cell CC-2576 Bullet Kit SmGM-2 CC-3182 8 Skeletal muscle satellite cell CC-2561 Bullet Kit SkGM CC-3160 9 Mammary gland epithelial cell CC-2551 Bullet Kit MEGM CC-3150 10 Bronchial epithelial cell (with RA) CC-2540 Bullet Kit SAGM CC-3118 11 Bronchial epithelial cell (without RA) CC-2541 Bullet Kit SAGM CC-3118 12 Lung fibroblast CC-2512 Bullet Kit FGM-2 CC-3132 13 Kidney proximal urine tubule epithelial cell Bullet Kit REGM CC-3190 CC-2553 14 Mesangial cell CC-2559 Bullet Kit MsGM CC-3146 15 Kidney cortex epithelial cell CC-2554 Bullet Kit REGM CC-3190 16 Mesenchyme stem cell PT-2501 Bullet Kit MSCGM PT-3001 17 Knee joint cartilage cell CC-2550 Bullet Kit CGM CC-3216 18 Osteoblast CC-2538 Bullet Kit OGM CC-3207 Each cell was cultured in a 75 cm2 culture flask until the cell became subconfluent, and the cells were recovered by treatment with trypsin-EDTA. From the recovered cells, total RNA was prepared by using ISOGEN (Nippon Gene) or RNeasy Mini Kit (Qiagen) (in either case, contaminant DNA was removed by treatment with DNase). The prepared total RNA was subjected to reverse transcription reaction with TaqMan Reverse Transcription Reagents (Applied Biosystems) to prepare cDNA. (2) Analysis of Expression of Human TCH230, Human TCH234, Human TCH212 and Human TCH200 Genes in the Commercial Normal Human Cells The expression level (Ct value) of each cDNA was measured in the following manner by using TaqMan PCR. Primer TF (SEQ ID NO. 15) and primer TR (SEQ ID NO. 16) used in Example 2 and TaqMan probe T1 (SEQ ID NO. 17) were used for human TCH230; primer TMF (SEQ ID NO: 32) and primer TMR (SEQ ID NO: 33) used in Example 6 and TaqMan probe P1 (SEQ ID NO: 38) were used for human TCH234; primer TF (SEQ ID NO: 63) and primer TR (SEQ ID NO: 64) used in Example 8 and TaqMan probe T1 (SEQ ID NO: 65) were used for human TCH212; and primer TMF (SEQ ID NO: 94) and primer TMR (SEQ ID NO: 95) used in Example 12 and TaqMan probe P1 (SEQ ID NO: 96) were used for human TCH200. The same cDNA was also examined for the expression level (Ct value) of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by using TaqMan GAPDH control reagents (Applied Biosystems). The reaction involved a reaction at 50° C. for 2 minutes and at 95° C. for 10 minutes and 40 cycles each consisting of a reaction at 95° C. for 15 seconds and at 60° C. for 1 minute by using TaqMan Universal PCR Master Mix (Applied Biosystems) in ABI PRISM 7900 sequence detection system (Applied Biosystems), and simultaneously detection was carried out. On the basis of measurements obtained by the above method, the relative expression level of each TCH gene (human TCH230, human TCH234, human TCH212 and human TCH200) to GAPDH was calculated according to the following equation: Relative expression level=½A-B wherein A represents the Ct value of human TCH230 gene, human TCH234 gene, human TCH212 gene or human TCH200 gene, and B represents the Ct value of GAPDH gene. The result of human TCH230 gene is shown in FIG. 27. Human TCH230 was expressed at a certain degree in the main artery endothelial cell, coronary artery endothelial cell, main artery smooth muscle cell, coronary artery smooth muscle cell, uterus smooth muscle cell, mammary gland epithelial cell, lung fibroblast, kidney proximal urine tubule epithelial cell, mesangial cell, kidney cortex epithelial cell, knee joint cartilage cell and osteoblast and expressed strongly in the bronchial epithelial cell (with RA) and bronchial epithelial cell (without RA). The result of human TCH234 gene is shown in FIG. 28. Human TCH234 was expressed at a certain degree in the main artery endothelial cell, coronary artery endothelial cell and kidney proximal urine tubule epithelial cell and expressed particularly strongly in the kidney cortex epithelial cell. The result of human TCH200 gene is shown in FIG. 29. Human TCH200 was expressed at a certain degree in the main artery endothelial cell, coronary artery endothelial cell, main artery smooth muscle cell, skeletal muscle satellite cell and lung fibroblast, expressed strongly in the kidney cortex epithelial cell, and expressed particularly strongly in the mammary gland epithelial cell, bronchial epithelial cell (with RA) and bronchial epithelial cell (without RA). Human TCH212 was not expressed in any cells. EXAMPLE 39 Analysis of Expression of Mouse TCH234 and Mouse TCH212 Gene Products in the Lung of Chronic Obstructive Pulmonary Disease (COPD) Model Mouse (1) Preparation of COPD Model Mouse by Exposure to Cigarette Smoke and Preparation of Lung cDNA A COPD model was prepared by giving mainstream smoke generated from Kentucky Reference Cigarette 1R1 to C57BL/6N mice (6-week-old, Charles River Japan) for 1 to 4 hours/day at the interval of 5 days/week for 6 months in total. That is, Kentucky Reference Cigarette 1R1 was attached to a cigarette smoke generator (SG-200, Shibata Kagaku), and mainstream smoke was collected under the condition of 35 ml/puff, 10 puff/min, and 25 puff/cigarette. The obtained mainstream smoke was diluted to a density of 3% (V/V) with air, and then sent to an acrylic exposure chamber where mice were present, and the cigarette smoke was given to the mice under spontaneous respiration. As a control group, normal mice were used. On the day after final exposure was finished, the mice were killed under pentobarbital anesthesia, and after washing bronchial pulmonary alveoli, lungs were removed. The removed lungs were frozen in liquid nitrogen, then milled with a frozen-tissue milling device, and immersed in ISOGEN (Nippon Gene) in a 10-fold excess amount relative to the wet lungs. From a group exposed to cigarette smoke for 1 month (n=10), its control group (n=6), a group exposed to cigarette smoke for 3 months (n=8), its control group (n=8), a group exposed to cigarette smoke for 6 months (n=8), and its control group (n=8), total RNA was extracted by using ISOGEN according to its attached manual. Contaminant DNA was removed by using QIAGEN RNeasy Mini Kit (Qiagen) and RNase-Free DNAse set (Qiagen). The prepared total RNA was subjected to reverse transcription reaction with TaqMan Reverse Transcription Reagents (Applied Biosystems) to prepare cDNA. (2) Analysis of Expression of Mouse TCH234 Gene Product in COPD Model Mouse Lung Using two primer DNAs, i.e. primer m234-TMF (SEQ ID NO. 128) and primer m234-TMR (SEQ ID NO. 129) used in Example 22 and TaqMan probe m234T1 (SEQ ID NO. 130), the expression level (Ct value) of mouse TCH234 by the COPD model mouse lung cDNA prepared in (1) above was measured by TaqMan PCR. The same cDNA was also measured for the expression level (Ct value) of 18S rRNA by using Eukaryotic 18S rRNA Pre-Developed TaqMan Assay Reagents (Applied Biosystems). The reaction involved a reaction at 50° C. for 2 minutes and at 95° C. for 10 minutes and 40 cycles each consisting of a reaction at 95° C. for 15 seconds and at 60° C. for 1 minute by using TaqMan Universal PCR Master Mix (Applied Biosystems) in ABI PRISM 7900 sequence detection system (Applied Biosystems), and simultaneously detection was carried out. On the basis of measurements obtained by the above method, the relative expression level of mouse TCH234 to 18S rRNA was calculated according to the following equation: Relative expression level=½A-B wherein A represents the Ct value of mouse TCH234 gene, and B represents the Ct value of 18S rRNA gene. In statistical analysis, SAS software (manufactured by SAS) was used, and p<0.05 was regarded as significant in Student's t test. The result is shown in FIG. 30. In the lungs of COPD model mice in all the groups exposed to cigarette smoke for 1, 3 and 6 months, a significant increase in expression was observed (1 month, p=0.0415; 3 months, p=0.0058; 6 months, p=0.0001). From this result, TCH234 was considered to participate in respiratory diseases such as COPD. (3) Analysis of Expression of Mouse TCH212 Gene Product in COPD Model Mouse Lung Using two primer DNAs, i.e. primer m212TF (SEQ ID NO. 146) and primer m212TR (SEQ ID NO. 147) used in Example 30 and TaqMan probe m212T1 (SEQ ID NO. 148), the expression level (Ct value) of mouse TCH212 in the COPD model mouse lung cDNA prepared in (1) above was measured by TaqMan PCR, and the relative expression to 18S rRNA was calculated in the same manner as in (2) above. Statistical analysis was conducted in the same manner as in (2) above. The results are shown in FIG. 31. In the lungs of COPD model mice in all the groups exposed to cigarette smoke for 1, 3 and 6 months, a significant decrease in expression was observed (1 month, p=0.0014; 3 months, p=0.0004; 6 months, p=0.0001). From this result, TCH212 was considered to participate in respiratory diseases such as COPD. EXAMPLE 40 Analysis of Expression of Mouse TCH230 Gene Product in the Large Intestine in Colitis Model Mice (1) Preparation of Colitis Model Mice by Administration of DSS and Preparation of Large Intestine cDNA Colitis model mice were prepared by administering DSS (Dextran Sulfate Sodium 5000, Wako Pure Chemical Industries, Ltd.) into BALB/cA mice (male, 6-week-old, Nippon Clea). That is, the mice were allowed 5% DSS solution ad libitum, and on the second day when the symptom of diarrhea appeared and on the seventh day when bleeding also appeared, the animals were slaughtered in a carbon dioxide gas, and a part of the large intestine (5 cm from the anal verge) was excised. As a control group, normal mice were used. The removed large intestines from 3 mice were washed with physiological saline and extracted by using ISOGEN (Nippon Gene) according to its attached manual, to give total RNA. Contaminant DNA was removed by using QIAGEN RNeasy Mini kit and RNase-Free DNAse set (Qiagen). The prepared total RNA was subjected to reverse transcription reaction with TaqMan Reverse Transcription Reagents (Applied Biosystems) to prepare cDNA. (2) Analysis of Expression of Mouse TCH230 Gene Product in Colitis Model Mouse Large Intestine Using two primer DNAs, i.e. primer m230TF (SEQ ID NO. 113) and primer m230TR (SEQ ID NO. 114) used in Example 14 and TaqMan probe m230T1 (SEQ ID NO. 115), the expression level (Ct value) of mouse TCH230 by the colitis model mouse large intestine cDNA prepared in (1) above was measured by TaqMan PCR. The same cDNA was also measured for the expression level (Ct value) of 18S rRNA by using eukaryotic 18S rRNA Pre-Developed TaqMan Assay Reagents (Applied Biosystems). The reaction involved a reaction at 50° C. for 2 minutes and at 95° C. for 10 minutes and 40 cycles each consisting of a reaction at 95° C. for 15 seconds and at 60° C. for 1 minute by using TaqMan Universal PCR Master Mix (Applied Biosystems) in ABI PRISM 7900 sequence detection system (Applied Biosystems), and simultaneously detection was carried out. On the basis of measurements obtained by the above method, the relative expression level of mouse TCH230 to 18S rRNA was calculated according to the following equation: Relative expression level=½A-B wherein A represents the Ct value of mouse TCH230 gene, and B represents the Ct value of 18S rRNA gene. The result is shown in FIG. 32. An increase in expression of mouse TCH230 was observed on both the second and seventh days in the large intestines of colitis model mice given DSS. From this result, TCH230 was considered to participate in colitis such as ulcerous colitis, Crohn's disease and ischemic colitis. INDUSTRIAL APPLICABILITY The protein A of the present invention, the polynucleotide encoding the same, the antibody thereto, and the antisense polynucleotide are useful as diagnostic markers etc. for diseases such as hyperlipemia, genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, bronchial asthma etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), diabetes, hypothyroidism, circulatory diseases (e.g., cardiac insufficiency, arrhythmia, long QT syndrome, arteriosclerosis, angina etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably hyperlipemia, arteriosclerosis, genital diseases, digestive diseases etc. The protein A of the present invention, the polynucleotide encoding the same and the antibody thereto are useful for screening a compound or a salt thereof that promotes or inhibits the activity of the protein, a compound or a salt thereof that promotes or inhibits the expression of the gene for the protein, and a compound or a salt thereof that promotes or inhibits the expression of the protein. The compound or a salt thereof that promotes or inhibits the activity of the protein, the compound or a salt thereof that promotes or inhibits the expression of the gene for the protein, etc., can be used as prophylactic/therapeutic agents for diseases such as hyperlipemia, genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, bronchial asthma etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), diabetes, hypothyroidism, circulatory diseases (e.g., cardiac insufficiency, arrhythmia, long QT syndrome, arteriosclerosis, angina etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably hyperlipemia, arteriosclerosis, genital diseases, digestive diseases etc. The protein B of the present invention, the polynucleotide encoding the same, the antibody thereto, and the antisense polynucleotide are useful as diagnostic markers etc. for diseases such as renal diseases (e.g., renal insufficiency, uremia etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), spleen diseases, cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.), diabetes, hypertension, ischemia-reperfusion injury, central nerve diseases (e.g., Alzheimer's disease, Parkinson's syndrome, schizophrenia, cerebral vascular dementia, cerebral ischemia, epilepsy etc.) etc., preferably respiratory diseases, renal diseases, digestive diseases etc. The protein B of the present invention, the polynucleotide encoding the same and the antibody thereto are useful for screening a compound or a salt thereof that promotes or inhibits the activity of the protein, or a compound or a salt thereof that promotes or inhibits the expression of the protein. The compound or a salt thereof that promotes or inhibits the activity of the protein, the compound or a salt thereof that promotes or inhibits the expression of the gene for the protein or the compound or a salt thereof that promotes or inhibits the expression of the protein can be used as prophylactic/therapeutic agents for diseases such as renal diseases (e.g., renal insufficiency, uremia etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), spleen diseases, cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.), diabetes, hypertension, ischemia-reperfusion injury, central nerve diseases (e.g., Alzheimer's disease, Parkinson's syndrome, schizophrenia, cerebral vascular dementia, cerebral ischemia, epilepsy etc.) etc., preferably respiratory diseases, renal diseases, digestive diseases etc. The protein C of the present invention, the polynucleotide encoding the same, the antibody thereto, and the antisense polynucleotide are useful as diagnostic markers etc. for diseases such as pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), central nerve diseases (e.g., Alzheimer's disease, Parkinson's syndrome, schizophrenia, cerebral vascular dementia, cerebral ischemia, epilepsy etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), diabetes, hyperlipemia, cholestasis, or cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably pancreatic diseases, central nerve diseases, digestive diseases, respiratory diseases etc. The protein C of the present invention, the polynucleotide encoding the same and the antibody thereto are useful for screening a compound or a salt thereof that promotes or inhibits the activity of the protein, a compound or a salt thereof that promotes or inhibits the expression of the gene for the protein, or a compound or a salt thereof that promotes or inhibits the expression of the protein. The compound or a salt thereof that promotes or inhibits the activity of the protein, the compound or a salt thereof that promotes or inhibits the expression of the gene for the protein, or the compound or a salt thereof that promotes or inhibits the expression of the protein can be used as prophylactic/therapeutic agents for diseases such as pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), central nerve diseases (e.g., Alzheimer's disease, Parkinson's syndrome, schizophrenia, cerebral vascular dementia, cerebral ischemia, epilepsy etc.), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), diabetes, hyperlipemia, cholestasis, or cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably pancreatic diseases, central nerve diseases, digestive diseases, respiratory diseases etc. The protein D of the present invention, the polynucleotide encoding the same, the antibody to the same, and the antisense polynucleotide are useful as diagnostic markers for diseases such as inflammatory diseases (e.g., septicemia, pneumonia, encephalitis, meningitis, hepatitis, myocarditis, pleurisy etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), diabetic neurosis, thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), circulatory diseases (e.g., cardiac insufficiency, arrhythmia, long QT syndrome, arteriosclerosis, angina etc.), hepatic diseases (e.g., hepatocirrhosis etc.), renal diseases (e.g., renal insufficiency, uremia etc.), muscular diseases (e.g., muscular dystrophy etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), burns, pain syndrome (e.g., cancerous sharp pain, referred pain etc.), cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably inflammatory diseases, rheumatoid diseases, diabetic neurosis etc. The protein D of the present invention, the polynucleotide encoding the same and the antibody thereto are useful in screening a compound or a salt thereof that promotes or inhibits the activity of the protein, a compound or a salt thereof that promotes or inhibits the expression of the gene for the protein, a compound or a salt thereof that promotes or inhibits the expression of the protein, a compound or a salt thereof that alters the binding property between the protein and its ligand. The compound or a salt thereof that promotes or inhibits the activity of the protein, the compound or a salt thereof that promotes or inhibits the expression of the gene for the protein, the compound or a salt thereof that promotes or inhibits the expression of the protein, or the compound or a salt thereof that alters the binding property between the protein and its ligand can be used as prophylactic/therapeutic agents for diseases such as inflammatory diseases (e.g., septicemia, pneumonia, encephalitis, meningitis, hepatitis, myocarditis, pleurisy etc.), autoimmune diseases (e.g., myasthenia gravis, glomerulonephritis, multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus etc.), allergic diseases (e.g., pollinosis, allergic rhinitis, anaphylactic shock, atopic dermatitis etc.), rheumatoid diseases (e.g., chronic articular rheumatism, osteoarthritis, gout etc.), diabetic neurosis, thymic diseases, immune disorders (e.g., immune disorders accompanying leukocyte abnormalities, spleen function insufficiency or thymic abnormalities), digestive diseases (e.g., irritable bowel syndrome, ulcerous colitis, Crohn's disease, ischemic colitis, gastritis, digestive ulcer, rectitis, reflux esophagitis, duodenitis etc.), respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma etc.), circulatory diseases (e.g., cardiac insufficiency, arrhythmia, long QT syndrome, arteriosclerosis, angina etc.), hepatic diseases (e.g., hepatocirrhosis etc.), renal diseases (e.g., renal insufficiency, uremia etc.), muscular diseases (e.g., muscular dystrophy etc.), pancreatic diseases (e.g., pancreatic function insufficiency such as pancreatitis, pancreatic cystic fibrosis etc.), genital diseases (e.g., prostatic hypertrophy, prostatitis, testis neurosis, ovarian cystoma etc.), burns, pain syndrome (e.g., cancerous sharp pain, referred pain etc.), cancers (e.g., testis tumor, ovarian cancer, breast cancer, esophagus cancer, lung cancer, kidney cancer, hepatoma, non-small cell lung cancer, prostate cancer, stomach cancer, bladder cancer, uterine cervix cancer, colon cancer, rectum cancer, pancreatic cancer, thymoma, myoma etc.) etc., preferably inflammatory diseases, rheumatoid diseases, diabetic neurosis etc.

<SOH> BACKGROUND ART <EOH>Bile acid is synthesized in the liver and secreted into a small intestine, and plays an important role in promoting absorption of lipids, lipid-soluble vitamins and cholesterols in the small intestine. Bile acid is re-absorbed efficiently through the small intestine (ileum), returned via a portal vein to the liver and excreted again into bile (enterohepatic circulation). The cholesterol pool size in the body is subject to feedback regulation not only by cholesterol in a meal but also by bile acid in enterohepatic circulation, and thus hypercholesterolemia therapy is conducted by suppression of re-absorption of bile acid into intestines by using a bile acid adsorbent (anion exchange resin). The sodium-dependent bile acid transporter is considered to contribute to transport of bile acid. In humans, two isoforms of sodium-dependent bile acid transporter have been identified, and NTCP (Na + /taurocholate cotransporting polypeptide) is expressed mainly in the liver (J. Clin. Invest., 93, 1326-1331, 1994), while ISBT (ileal sodium/bile salt cotransporter) is expressed mainly in the ileum/kidney (J. Biol. Chem., 270, 27228-27234, 1995). With respect to ISBT, direct relationship between a gene mutation accompanied by amino acid substitution and insufficient absorption of bile acid is suggested (J. Clin. Invest., 99, 1880-1887, 1997). A Na + /H + exchange transporter (NHE) is a typical cation antiporter, which couples in animal cells with Na + inflow to discharge H + . NHE is divided into 2 major regions, that is, an amino terminal (N) region containing about 500 amino acids comprising a 10- to 13-times transmembrane region and a carboxyl terminal (C) region comprising about 300 amino acids, and its whole structure is common among isoforms. It is known that the former is an ion transport region comprising an amyloride-binding site, and the latter functions as an activity regulatory region. As isoforms of NHE in humans, 6 kinds of isoforms i.e. NHE1 to NHE3 and NHE5 to NHE7 are reported. NHE1 is distributed broadly in tissues, and involved in regulation of intracellular pH and cell volume. The activity of NHE1 is promoted by a growth factor or simulation with high osmotic pressure, resulting in an increase in intracellular pH. NHE3 is expressed in the kidney and small intestine, and plays an important role in absorption of Na + . It is thus known that the respective isoforms are different in their expression distribution, regulatory mechanism, and the effect of inhibitor. NHE1 is considered as one factor increasing intracellular Na + levels after ischemia and participating in causing myocardial difficulties. It is also reported that the activity of NHE1 in patients with hypertension is significantly higher than in healthy persons. In mice spontaneously developing epilepsy, it is confirmed that the disease is caused by a mutation in NHE (Cell, 91, 139-148, 1997). P-type ATPase is a membrane enzyme participating in transport of various substrates by utilizing energy upon hydrolysis of ATP. The P-type ATPase is divided into 3 classes, depending on its substrate. Type-1 utilizes heavy metals such as Cu 2+ ion and Cd 2+ ion as the substrate, possesses an N-terminal characteristic structure involved in binding to heavy metals, and has an 8-times transmembrane structure. Wilson's disease is a disease accompanying an abnormality in Cu 2+ -ATPase participating in excretion of copper in the liver. Type-2 utilizes alkali metals (K + ion, Na + ion), alkaline earth metals (Ca 2+ ion) or proton (H + ) as the substrate. In particular, H + , K + -ATPase (proton pump) in stomach acid-secreting cells is a target of chemicals such as proton pump inhibitors (omeplazole, lansoprazole etc.) that are therapeutic products for stomach ulcer/duodenum ulcer/reflux esophagitis. Further, Na + , K + -ATPase (sodium pump) is a target of chemicals such as cardiac glycosides used for cardiac diseases, and its activity is inhibited by ouabain. Type-3 is the latest determined type, and utilizes aminophospholipids as the substrate. It is also called aminophospholipid translocase (flippase), and reversely transfer phospholipids selectively from outer to inner layers by using energy generated upon hydrolysis of ATP. It is estimated that uneven distribution of lipids on the biomembrane is thereby maintained. No significant difference in structure is recognized between type-2 and type-3, both of which have a 10-times transmembrane structure (Biochemistry, 34, 15607-15613, 1995; Science, 272, 1495-1497, 1996). Up to now, 17 isoforms of P-type ATPase of type-3 have been identified in mammals. Among them, FIC1 is expressed in tissues such as the pancreas, small intestine, liver etc., and the relationship between an alteration in its gene and hereditary cholestasis is reported (Nature Genet., 18, 219-224, 1998). The P-type ATPase of type 3 is considered to play an important role in transport of aminophospholipids and in uneven distribution of lipids on the biomembrane, but the detailed functions and structure of each isoform and the relationship thereof with the disease are not so revealed. As a pain receptor, a vanilloid receptor subtype 1 (VR1) is a non-selective cation channel with high Ca 2+ permeability having outward rectification. It is known that VR1 has a 6-times transmembrane region, possesses an H5 region regarded as forming a pore between fifth and sixth transmembrane sites, and has 3 ankyrin repeat domains at the N-terminal thereof. In addition to VR1 (Biochemical and Biophysical Research Communications, 281, 1183, 2001), VRL (vanilloid receptor-like protein) 1 and VRL2 in humans have been cloned up to now, and have about 40% homology with VR1 respectively (Physiol Genomics 4, 165-174, 2001). Capsaicin has a vanillyl group and is thus called vanilloid, and is an extraneous ligand of vanilloid receptor. No intrinsic ligand has been revealed. Single electric current measurement revealed that VR1 is activated electrophysiologically directly by capsaicin. Further, VR1 is a receptor of multi-stimuli, which is activated not only by chemical stimulation with capsaicin or the like but also by heat stimulation regarded pain stimulation (at a temperature of higher than 43° C. that is a threshold temperature at which pain is induced in humans) and acid stimulation (tissues are acidified in inflammations and ischemia). VR1 is activated by stimuli (for example capsaicin, heat, proton) causing pain in the living body, and in a morbid state, these stimuli are considered to occur not singly but simultaneously. Receptiveness of every pain in the living body is not elucidated by only VR1, and the presence of other homologues and cofactors is also estimated. In the previously reported VR family, there are various expression sites and stimulation receptivity, and these are considered to function depending on one another, to transmit pain stimulation. The sodium-dependent bile acid transporter is considered to play an important role in transport of bile acid in the liver and small intestine, but its detailed mechanism and the relationship thereof with the disease are not so revealed. Full elucidation of the substrate specificity of the sodium-dependent bile acid transporter and its role in bile acid metabolism leads to development of therapeutic products for diseases associated with bile acid metabolism. As described above, NHE is involved in many morbid states, and elucidation of the mechanism of activation and regulation of each isoform of NHE leads to development of therapeutic products. Elucidation of detailed functions of P-type ATPase of type 3 leads to development of therapeutic products for diseases such as metabolic diseases, central nerve diseases, genital diseases and cancers associated with P-type ATPase of type 3. The above-mentioned capsaicin is used as an analgesic for relieving pains in diabetic neurosis and articular rheumatism, and thus elucidation of the structure, function and mutual relationship of VR family is considered to lead to development of therapeutic products for pains as a whole.

<SOH> BRIEF DESCRIPTION OF DRAWINGS <EOH>FIG. 1 shows comparison in amino acid sequence between human TCH230 and ileum sodium-dependent bile acid transporter (ISBT). In FIG. 1 , TCH230 shows an amino acid sequence of human TCH230; ISBT shows an amino acid sequence of ileum sodium-dependent bile acid transporter (ISBT); * shows the position of amino acid substitution (Ile->Val) derived from single nucleotide polymorphisms (SNPs). The symbol represented by opened square shows coincident amino acids between human TCH230 and ISBT. FIG. 2 shows the expression level of human TCH230 gene product in each tissue. The expression level is represented in terms of copy number per μl of cDNA solution. FIG. 3 shows the expression level of human TCH230 gene product in each tissue. The expression level is represented in terms of copy number per μl of cDNA solution. FIG. 4 shows the expression level of human TCH230 gene product in each tissue. The expression level is represented in terms of copy number per μl of cDNA solution. FIG. 5 shows the expression level of human TCH230 gene product in each tissue. The expression level is represented in terms of copy number per μl of cDNA solution. FIG. 6 shows comparisons in amino acid sequence among human TCH234, rat NHE4 and human NHE2. In FIG. 6 , TCH23 shows an amino acid sequence of human TCH234; rat NHE4 shows an amino acid sequence of rat NHE4; human NHE2 shows an amino acid sequence of human NHE2; the symbol “A” shows an amyloid-binding site; and TM1 to TM13 show a transmembrane region respectively. The symbol represented by opened square shows coincident amino acids with those in human TCH234. FIG. 7 shows the expression level of human TCH234 gene product in each tissue. The expression level is represented in terms of copy number per μl of cDNA solution. FIG. 8 shows comparisons in amino acid sequence among human TCH212, ATP8A1 and mATP8A2. In FIG. 8 , TCH212 shows an amino acid sequence of human TCH212; ATP8A1 shows an amino acid sequence of P-type ATPase 8A1; and mATP8A2 shows an amino acid sequence of mouse P-type ATPase 8A2. The symbol represented by opened square shows amino acids coincident with those in human TCH212. TM1 to 10 show a transmembrane region, respectively (continued to FIG. 9 ). FIG. 9 shows comparisons in amino acid sequence among human TCH212, ATP8A1 and mATP8A2. In FIG. 9 , TCH212 shows an amino acid sequence of human TCH212; ATP8A1 shows an amino acid sequence of P-type ATPase 8A1; and mATP8A2 shows an amino acid sequence of mouse P-type ATPase 8A2. The symbol represented by opened square shows coincident amino acids with those in human TCH212. TM1 to 10 show a transmembrane region, respectively (continued from FIG. 8 to FIG. 10 ). FIG. 10 shows comparison in amino acid sequence among human TCH212, ATP8A1 and mATP8A2. In FIG. 10 , TCH212 shows an amino acid sequence of human TCH212; ATP8A1 shows an amino acid sequence of P-type ATPase 8A1; and mATP8A2 shows an amino acid sequence of mouse P-type ATPase 8A2. The symbol represented by opened square shows coincident amino acids with those in human TCH212. TM1 to 10 show a transmembrane region, respectively (continued from FIG. 9 ). FIG. 11 shows the expression level of human TCH212 gene product in each tissue. The expression level is represented in terms of copy number per μl of cDNA solution. FIG. 12 shows the expression level of human TCH212 gene product in each tissue. The expression level is represented in terms of copy number per μl of cDNA solution. FIG. 13 shows comparison in amino acid sequence between human TCH200 and human VR1. In FIG. 13 , TCH200 shows an amino acid sequence of human TCH200; and hVR1 shows an amino acid sequence of humanVR1. TM1 to 6 show a transmembrane region, respectively. A1 to 3h show Ankyrin repeat sequence. The symbol represented by opened square shows coincident amino acids between two sequences. FIG. 14 shows the expression level of human TCH200 gene product in each tissue. The expression level is represented in terms of copy number per μl of cDNA solution. FIG. 15 shows comparison in amino acid sequence between mouse TCH230 (SEQ ID NO: 112) and human TCH230 (SEQ ID NO: 1). In FIG. 15 , hTCH230 shows an amino acid sequence of human TCH230; and mTCH230 shows an amino acid sequence of mouse TCH230. The symbol represented by opened square shows coincident amino acids between two sequences. FIG. 16 shows the expression level of mouse TCH230 gene product in each tissue cDNA. The expression level is represented in terms of copy number per μl of cDNA solution. FIG. 17 shows the expression level of mouse TCH230 gene product in each tissue. The expression level is represented as (copy number of mouse TCH230 per μl of cDNA solution/copy number of rodent GAPDH by equivalent amount of tissue cDNA). FIG. 18 shows the expression level of rat TCH230 gene product in each tissue. The expression level is represented as (copy number of rat TCH230 per μl of cDNA solution/copy number of rodent GAPDH by equivalent amount of tissue cDNA). FIG. 19 shows the result of measurement of incorporation of [6,7- 3 H(N)]-estrone sulfate into human TCH230-expressing CHO cell strain. The amount of the incorporated compound was expressed as count (cpm) upon incorporation of [6,7- 3 H(N)]-estrone sulfate for 1 hour. The amount was expressed as the average of the counts in 3 independent wells and standard deviation. In FIG. 19 , the cell having vector pcDNA3.1(+) introduced into it is represented as Mock, and human TCH230-expressing CHO cell is expressed as TCH230, and the cells incorporating [6,7- 3 H(N)]-estrone sulfate with NaCl buffer are represented as Mock/NaCl and TCH230/NaCl respectively, and the cells incorporating [6,7- 3 H(N)]-estrone sulfate with NMDG buffer are expressed as Mock/NMDG and TCH230/NMDG respectively. FIG. 20 shows the result of measurement of incorporation of [1,2,6,7- 3 H(N)]-DHEA-S into human TCH230-expressing CHO cell strain. The amount of the incorporated compound was represented as count (cpm) upon incorporation of [1,2,6,7- 3 H(N)]-DHEA-S for 1 hour. The amount was represented as the average of the counts in 3 independent wells and standard deviation. In FIG. 20 , the cell having vector pcDNA3.1(+) introduced into it is represented as Mock, and human TCH230-expressing CHO cell is represented as TCH230, and the cells incorporating [1,2,6,7- 3 H(N)]-DHEA-S with NaCl buffer are represented as Mock/NaCl and TCH230/NaCl respectively, and the cells incorporating [1,2,6,7- 3 H(N)]-DHEA-S with NMDG buffer are represented as Mock/NMDG and TCH230/NMDG respectively. FIG. 21 shows the expression level of mouse TCH234 gene product in each tissue. The expression level is represented as (copy number of mouse TCH234 per μl of cDNA solution/copy number of rodent GAPDH by equivalent amount of tissue cDNA). FIG. 22 shows the expression level of rat TCH234 gene product in each tissue. In the figure, the expression level shown on the ordinate is represented as ((copy number of rat TCH234 per μl of cDNA solution)/(copy number of rodent GAPDH by equivalent amount of tissue cDNA)×100,000)). FIG. 23 shows the amount of human TCH234 gene product expressed in each kind of tissue. In the figure, the expression level shown on the ordinate is represented as ((copy number of TCH234 per μl of cDNA solution)/(copy number of GAPDH by equivalent amount of tissue cDNA)×100,000)). FIG. 24 shows the expression level of mouse TCH212 gene product in each tissue. The expression level is represented as (copy number of mouse TCH212 per μl of cDNA solution)/(copy number of rodent GAPDH by equivalent amount of tissue cDNA). FIG. 25 shows the expression level of rat TCH212 gene product in each tissue. The expression level is represented as (copy number of rat TCH212 per μl of cDNA solution)/(copy number of rodent GAPDH by equivalent amount of tissue cDNA). FIG. 26 shows the expression level of mouse TCH200 gene product in each tissue. The expression level is represented as ((copy number of mouse TCH200 per μl of cDNA solution)/(copy number of rodent GAPDH by equivalent amount of tissue cDNA)×100,000)). FIG. 27 shows the expression level of human TCH230 gene product in normal cells. The expression level is represented as (relative expression amount×10,000). FIG. 28 shows the expression level of human TCH234 gene product in normal cells. The expression level is represented as (relative expression amount×10,000). FIG. 29 shows the expression level of human TCH200 gene product in normal cells. The expression level is represented as (relative expression amount×10,000). FIG. 30 shows the expression level of mouse TCH234 gene product in COPD model mouse lung. The expression level is represented as (relative expression amount×100,000,000). The result shows the average and standard error in each group. FIG. 31 shows the expression level of mouse TCH212 gene product in COPD model mouse lung. The expression level is represented as (relative expression amount×100,000,000). The result shows the average and standard error in each group. FIG. 32 shows the expression level of mouse TCH230 gene product in the large intestine of colitis model mouse. The expression level is represented as (relative expression amount×10,000,000). The result shows the average of duplicate measurements by independent TaqMan PCR. FIG. 33 shows the expression level of human TCH212 gene product in each tissue. The expression level is represented as copy number per μl of cDNA solution. detailed-description description="Detailed Description" end="lead"?

20040715

20100713

20061019

76635.0

A61K3817

LOCKARD, JON MCCLELLAND

HUMAN SODIUM-DEPENDENT BILE ACID TRANSPORTER PROTEINS

UNDISCOUNTED

ACCEPTED

A61K

ACCEPTED

Fin assembly

An integrally formed fibreglass fin assembly (1) including a base (2)—that is defined by broken lines (3,4)—for mounting the assembly to an object in the form of a surfboard (5). A primary fin (6) extends upwardly from base (2)—in that it extends upwardly from line (3)—and has a compound arcuate leading primary edge (7) and a compound arcuate trailing primary edge (8). A secondary fin (9) extends rearwardly and upwardly from base (2)—in that it extends from line (4)—and has a compound arcuate leading secondary edge (10) and a compound arcuate trailing secondary edge (11).

1. A fin assembly for a surf craft, the assembly including: a base for mounting the assembly to the surf craft; a primary fin extending from the base and having a leading primary edge and a trailing primary edge; and a secondary fin extending from the base and having a leading secondary edge and a trailing secondary edge. 2. An assembly according to claim 1 wherein the base and the fins are integrally formed. 3. An assembly according to claim 1 wherein the leading edges of the fins are aligned. 4. An assembly according to claim 1 wherein the leading and the trailing edges are aligned. 5. An assembly according to claim 1 wherein the base extends longitudinally between the leading primary edge and the trailing secondary edge. 6. An assembly according to claim 1 wherein the trailing primary edge and the leading secondary edge are joined by an intermediate arcuate edge defined by the base. 7. An assembly according to claim 6 wherein the arcuate edge is of varying radius. 8. An assembly according to claim 1 wherein the primary fin extends along a first plane that is normal to the base. 9. An assembly according to claim 8 wherein both the primary and secondary fins extend along the first plane. 10. An assembly according to claim 1 wherein the fins include respective pairs of opposite faces that extend between the leading and trailing edges. 11. An assembly according to claim 10 wherein one or more of the faces are substantially planar. 12. A fin assembly including: a base for mounting the assembly to an object; a primary fin extending from the base and having a leading primary edge and a trailing primary edge; and a secondary fin extending rearwardly from the base and having a leading secondary edge and a trailing secondary edge. 13. An assembly according to claim 12 wherein the leading primary edge is curved substantially complementarily to the leading secondary edge. 14. A fin assembly including: a base for mounting the assembly to an object; a larger fin extending from the base and having a leading primary edge and a trailing primary edge and a high rake; and a smaller fin extending rearwardly from the base and having a leading secondary edge and a trailing secondary edge. 15. An assembly according to claim 14 wherein the edges extend along a single plane. 16. An assembly according to claim 14 wherein the smaller fin is, in use, deformable in a direction normal to the plane. 17. A fin assembly for a surf craft, the assembly including: a base for mounting the assembly to the surf craft; a fin that extends from the base and which has a leading edge and a trailing edge that meet at a tip, where the edges lie substantially within a common plane; and a lobe extending rearwardly from the base, the lobe having a lobe edge that has a tangent that is parallel to the plane. 18. A fin assembly for a surf craft, the assembly including: a base having a substantially planar surface for mounting the assembly to the surf craft; a fin that extends from the base and which has a leading edge and a trailing edge that meet at a tip; and a lobe extending rearwardly from the base, the lobe having a lobe edge that has a tangent that is parallel to the surface. 19. An assembly according to claim 18 wherein the base, the fin and the lobe are integrally formed. 20. An assembly according to claim 18 wherein the base and the lobe extend longitudinally. 21. An assembly according to claim 20 wherein the base extends longitudinally between the leading edge and the trailing edge. 22. An assembly according to claim 21 wherein the lobe is directly underlying the leading and the trailing edge. 23. An assembly according to claim 22 wherein the lobe, the trailing edge and the leading edge extend in a common plane. 24. An assembly according to claim 18 wherein the trailing edge is feathered in an area intermediate of the lobe and the leading edge. 25. An assembly according to claim 24 wherein the trailing edge and the lobe are joined by an intermediate arcuate edge defined by the base. 26. An assembly according to claim 25 wherein the arcuate edge is of varying radius. 27. An assembly according to claim 18 wherein the fin extends along a first plane that is normal to the base. 28. An assembly according to claim 18 wherein each the fin includes a pair of opposite faces that extend between the leading and the trailing edges. 29. An assembly according to claim 28 wherein one or both of the faces are substantially planar. 30. An assembly according to claim 28 wherein one or both of the faces are substantially arcuate. 31. An assembly according to claim 18 wherein the lobe includes a leading secondary edge and a trailing secondary edge. 32. An assembly according to claim 18 wherein the fin assembly includes one or more mounting formations that extend from the surface for engaging with complementary locating formations extending from the surf craft. 33. An assembly according to claim 32 wherein the or each mounting formation is a protrusion, and the or each locating formation is a recess. 34. An assembly according to claim 33 wherein the assembly includes two spaced apart mounting formations and the surf craft includes at least two locating formations. 35. A fin assembly including: a base for mounting the assembly to an object; a primary fin extending from the base; a secondary fin extending from the base, wherein the base, the primary fin and the secondary fin include a combined total sectional area (Af); and a feathered portion between two or more of the primary fin, the secondary fin and the base, wherein the feathered portion includes a sectional area (Ap) where Ap>0.2.Af. 36. A surf craft including a fin assembly of any one of claim 1, claim 17 or claim 18. 37. A surf craft including a fin assembly of any one of claim 12, claim 14 or claim 35, where the object is the surf craft. 38. A method of manufacturing a fin assembly for a surf craft, the method including: forming a base for mounting the assembly to the surf craft; forming a primary fin that extends from the base and which has a leading primary edge and a trailing primary edge; and forming a secondary fin that extends from the base and which has a leading secondary edge and a trailing secondary edge. 39. A method according to claim 38 wherein the forming steps are performed simultaneously. 40. A method according to claim 38 wherein the base, the primary fin and the secondary fin are integrally formed. 41. A method according to claim 38 including the additional step of forming at least one mounting formation that extends from the base for engaging with a complementary locating formation that extends from the surf craft. 42. A fin assembly for a surf craft, the assembly, in use, providing a predetermined sectional water engaging area (A) and including: a base for mounting the assembly to extend from a surface of the surf craft; a primary fin extending from the base and away from the surface; and a secondary fin extending from the base, wherein a high proportion of A is near the surface. 43. An assembly according to claim 42 wherein the primary fin terminates in a point having a predetermined height (H) with respect to the surface, and at least 0.4.A is within 0.3.H of the surface. 44. An assembly according to claim 42 wherein at least 0.45.A is within 0.3.H of the surface. 45. An assembly according to claim 42 wherein at least 0.5.A is within 0.3.H of the surface. 46. An assembly according to claim 42 wherein at least 0.35.A is within 0.22H of the surface. 47. A fin assembly for a surf craft, the assembly including a sectional area of less than 95 cm2. 48. An assembly according to claim 47 wherein the sectional area is between about 90 cm2 and 95 cm2. 49. An assembly according to claim 48 wherein the assembly extends from the surf craft and the perimeter of the area, excluding any common perimeter with the surf craft, is greater than about 380 mm. 50. An assembly according to claim 49 wherein the perimeter is greater than about 400 mm. 51. A fin assembly for extending from a surface of a surf craft, the assembly extending longitudinally and having a longitudinal peripheral edge that terminates at two longitudinally spaced ends that are both disposed adjacent to the surface, the edge being at least 380 mm. 52. An assembly according to claim 51 wherein the edge is at least 400 mm. 53. An assembly according to claim 52 wherein the assembly includes a predetermined water engaging sectional area A that is bounded by the edge, where A is less than about 95 cm2. 54. A fin assembly for extending from a surface of a surf craft, the assembly extending longitudinally and having a longitudinal peripheral edge (PE) that terminates at two longitudinally spaced ends that are both disposed adjacent to the surface, the edge bounding a sectional area (A) of the assembly, wherein A/PE is less than 25. 55. An assembly according to claim 54 wherein A/PE is less than 24. 56. An assembly according to claim 54 wherein A/PE is less than 23.

BACKGROUND TO THE INVENTION The present invention relates to a fin and in particular to a fin assembly. The invention has been developed primarily for use with surf craft such as surfboards and will be described hereinafter with reference to that application. However, the invention is not limited to that particular field of use and is also applicable to other surf craft including surf skis and bogie boards and to water craft including kayaks, canoes, boats, sailboards and the like. DISCUSSION OF THE PRIOR ART Known fins or fin assemblies for surfboards have only incrementally advanced in the last forty years notwithstanding the reduction in size of boards and the use of modern manufacturing materials and techniques. An early style fin has been used with a board known as the Malabo board, while more recent boards typically make use of a fin known as the Simon Andersen fin. The latter was introduced in the 1980's and was developed into a triple fin arrangement that is mounted at the rear of the board. The centre one of the three fins included symmetric faces and is mounted along the centre line of the board. The other two fins include asymmetric faces and are mounted at an acute angle to the centre line and which are adjacent to but forward of the centre fin. This arrangement was reputed to provide the “Three Fin Thrust”. While the triple fin arrangement has significant advantages over the Malabo fin, it also has substantial limitations, such as increased drag and reduced manoeuvrability. Another innovation was an adaptation of the so-called Ben Lexcen fin—as disclosed in PCT application number PCT/AU85/00012—to surf craft. This fin design was the most radical deviation from the standard fin design known to date. However, as presently understood, it has enjoyed neither significant commercial success nor acceptance within the surfing community. Fins are now modular and generally bought separately to a surfboard or other surf craft, as illustrated by the disclosure in the following U.S. Pat. Nos. 5,328,397, 5,464,359 and 5,672,081. While this allows fin design to occur separately from that of the board, replacement fins are typically similar to those originally fitted. It is understood that this is a result of replacement fins needing to be received within the same retaining formations as the original fins, and also due to the limitations imposed by the highly image conscious nature of the users of the surfboards. Any discussion of the prior art throughout the specification should in no way be considered as an admission that such prior art is widely known or forms part of common general knowledge in the field. SUMMARY OF THE INVENTION It is an object of the present invention to ameliorate one or more of the deficiencies of the prior art or at least to provide a useful alternative. According to a first aspect of the invention there is provided a fin assembly for a surf craft, the assembly including: a base for mounting the assembly to the surf craft; a primary fin extending from the base and having a leading primary edge and a trailing primary edge; and a secondary fin extending from the base and having a leading secondary edge and a trailing secondary edge. Preferably, the base and the fins are integrally formed. Preferably also, the leading edges of the fins are aligned. More preferably, the leading and the trailing edges are aligned. Even more preferably, the base extends longitudinally between the leading primary edge and the trailing secondary edge. In a preferred form, the trailing primary edge and the leading secondary edge are joined by an intermediate arcuate edge defined by the base. More preferably, the arcuate edge is of varying radius. Preferably, the primary fin extends along a first plane that is normal to the base. More preferably, both the primary and secondary fins extend along the first plane. Preferably also, the fins include respective pairs of opposite faces that extend between the leading and trailing edges. More preferably, one or more of the faces are substantially planar. In other embodiments, however, one or more of the faces are substantially arcuate. In a preferred form, the fins are longitudinally spaced apart. In some embodiments, the fins are transversely spaced apart. According to a second aspect of the invention there is provided a fin assembly including: a base for mounting the assembly to an object; a primary fin extending from the base and having a leading primary edge and a trailing primary edge; and a secondary fin extending rearwardly from the base and having a leading secondary edge and a trailing secondary edge. Preferably the leading primary edge is curved substantially complementarily to the leading secondary edge. According to a third aspect of the invention there is provided a fin assembly including: a base for mounting the assembly to an object; a larger fin extending from the base and having a leading primary edge and a trailing primary edge and a high rake; and a smaller fin extending rearwardly from the base and having a leading secondary edge and a trailing secondary edge. Preferably, the edges extend along a single plane. More preferably, smaller fin is, in use, deformable in a direction normal to the plane. According to a fourth aspect of the invention there is provided a fin assembly for a surf craft, the assembly including: a base for mounting the assembly to the surf craft; a fin that extends from the base and which has a leading edge and a trailing edge that meet at a tip, where the edges lie substantially within a common plane; and a lobe extending rearwardly from the base, the lobe having a lobe edge that has a tangent that is parallel to the plane. According to a fifth aspect of the invention there is provided a fin assembly for a surf craft, the assembly including: a base having a substantially planar surface for mounting the assembly to the surf craft; a fin that extends from the base and which has a leading edge and a trailing edge that meet at a tip; and a lobe extending rearwardly from the base, the lobe having a lobe edge that has a tangent that is parallel to the surface. Preferably, the base, the fin and the lobe are integrally formed. More preferably, the base and the lobe extend longitudinally. Even more preferably, the base extends longitudinally between the leading edge and the trailing edge. Preferably also, the lobe is directly underlying the leading and the trailing edge. More preferably, the lobe, the trailing edge and the leading edge extend in a common plane. Preferably also, the trailing edge is feathered in an area intermediate of the lobe and the leading edge. In a preferred form, the trailing edge and the lobe are joined by an intermediate arcuate edge defined by the base. More preferably, the arcuate edge is of varying radius. Preferably, the fin extends along a first plane that is normal to the base. Preferably also, the fin includes a pair of opposite faces that extend between the leading and the trailing edge. More preferably, one or both of the faces are substantially planar. In other embodiments, however, one or both of the faces are substantially arcuate. Preferably, the edges extend along a common plane. In a preferred form, the lobe includes a leading secondary edge and a trailing secondary edge. More preferably, the lobe is a secondary fin. Preferably also, the fin assembly includes one or more mounting formations that extend from the surface for engaging with complementary locating formations extending from the surf craft. More preferably, the or each mounting formation is a protrusion, and the or each locating formation is a recess. Even more preferably the assembly includes two spaced apart mounting formations and the surf craft includes at least two locating formations. According to a sixth aspect of the invention there is provided a fin assembly including: a base for mounting the assembly to an object; a primary fin extending from the base; a secondary fin extending from the base, wherein the base, the primary fin and the secondary fin include a combined total sectional area (Af); and a feathered portion between two or more of the primary fin, the secondary fin and the base, wherein the feathered portion includes a sectional area (Ap) where Ap>0.2.Af. Preferably, Ap>0.24.Af. More preferably, Ap>0.35.Af. According to a seventh aspect of the invention there is provided a surf craft including a fin assembly of one of the first, second, fourth or fifth aspects of the invention. According to an eighth aspect of the invention there is provided a surf craft including a fin assembly of one of the third, fourth or sixth aspects of the invention, where the object is the surf craft. According to a ninth aspect of the invention there is provided a method of manufacturing a fin assembly for a surf craft, the method including: forming a base for mounting the assembly to the surf craft; forming a primary fin that extends from the base and which has a leading primary edge and a trailing primary edge; and forming a secondary fin that extends from the base and which has a leading secondary edge and a trailing secondary edge. Preferably, the forming steps are performed simultaneously. More preferably, the base, the primary fin and the secondary fin are integrally formed. Preferably also, the method includes forming at least one mounting formation that extends from the base for engaging with a complementary locating formation that extends from the surf craft. According to a tenth aspect of the invention there is provided a fin assembly for a surf craft, the assembly, in use, providing a predetermined sectional water engaging area (A) and including: a base for mounting the assembly to extend from a surface of the surf craft; a primary fin extending from the base and away from the surface; and a secondary fin extending from the base, wherein a high proportion of A is near the surface. Preferably, the primary fin terminates in a point having a predetermined height (H) with respect to the surface, and at least 0.4.A is within 0.3.H of the surface. More preferably, at least 0.45.A is within 0.3.H of the surface. Even more preferably, at least 0.5.A is within 0.3.H of the surface. In other embodiments, at least 0.35.A is within 0.22H of the surface. According to an eleventh aspect of the invention there is provided a fin assembly for a surf craft, the assembly including a sectional area of less than 95 cm2. Preferably, the sectional area is between about 90 cm2 and 95 cm2. More preferably, the assembly extends from the surf craft and the perimeter of the area, excluding any common perimeter with the surf craft, is greater than about 380 mm. More preferably, it is greater than about 400 mm. According to a twelfth aspect of the invention there is provided a fin assembly for extending from a surface of a surf craft, the assembly extending longitudinally and having a longitudinal peripheral edge that terminates at two longitudinally spaced ends that are both disposed adjacent to the surface, the edge being at least 380 mm. Preferably, the edge is at least 400 mm. More preferably, the assembly includes a predetermined water engaging sectional area A that is bounded by the edge, where A is less than about 95 cm2. According to a thirteenth aspect of the invention there is provided a fin assembly for extending from a surface of a surf craft, the assembly extending longitudinally and having a longitudinal peripheral edge (PE) that terminates at two longitudinally spaced ends that are both disposed adjacent to the surface, the edge bounding a sectional area (A) of the assembly, wherein A/PE is less than 25. Preferably, A/PE is less than 24. More preferably, A/PE is less than 23. BRIEF DESCRIPTION OF THE DRAWINGS Preferred embodiments of the invention will now be described, by way of example only, with reference to the accompanying drawings in which: FIG. 1 is a side view of a fin assembly according to a first embodiment of the invention that is mounted to a surfboard; FIG. 2 is a rear view of the fin of FIG. 1 when not mounted to the surfboard; FIG. 3 is a side view of a fin assembly according to a second embodiment of the invention; FIG. 4 is a side view of a fin assembly according to a third embodiment of the invention; FIG. 5 is a side view of a fin assembly according to a fourth embodiment of the invention; FIG. 6 is a rear view of a fin assembly according to another aspect of the invention; FIG. 7 is a rear view of an alternative embodiment of the invention; and FIG. 9 is a side view of a further fin assembly according to the invention. DESCRIPTION OF THE PREFERRED EMBODIMENTS Referring to FIG. 1, there is illustrated an integrally formed fibreglass fin assembly 1 including a base 2—that is defined by broken lines 3 and 4—for mounting the assembly to an object in the form of a surfboard 5. A primary fin 6 extends upwardly from base 2—in that it extends upwardly from line 3—and has a compound arcuate leading primary edge 7 and a compound arcuate trailing primary edge 8. A secondary fin 9 extends rearwardly and upwardly from base 2—in that it extends from line 4—and has a compound arcuate leading secondary edge 10 and a compound arcuate trailing secondary edge 11. In this embodiment, the arcuate form of the leading primary edge 7 and leading secondary edge 10 are substantially the same, although scaled for the different heights of fins 6 and 9. It will be appreciated that for surf craft, the height of the fin is referred to as its depth. It will be appreciated that the assembly, as represented in FIG. 1, and the assemblies as represented in the other Figures, are illustrative only of the preferred embodiments and all the proportions may not be absolutely true to scale. When interpreting the drawings, use should be made of the accompanying description. Base 2 includes a bottom surface 15 that is substantially planar and which is abutted with an adjacent and opposed substantially planar surface 16 of board 5. Surface 15 extends longitudinally along board 5 from a leading end 13 to a trailing end 14. Two longitudinally spaced apart mounting formations, in the form of prismatic protrusions 17 and 18, extend downwardly from the bottom surface and into complementary locating formations, in the form of prismatic recesses (not shown). Protrusion 17, protrusion 18, fin 6 and fin 9 are all integrally formed with base 2. In other embodiments alternative means of connection between assembly 1 and board 5 are used. For example, in some embodiments, assembly 1 and board 5 are integrally formed, while in other embodiments, use is made of adhesive or other bonding materials to affect a fixed mounting of the components. Alternatively, assembly 1 is able to be removeably mounted to board 5 by means such as disclosed in U.S. Pat. No. 5,328,397. While assembly 1 is illustrated in an inverted configuration, this is for illustration purposes only. In use, assembly 1 extends downwardly from board 5 for protruding into the water in which board 5 is disposed. All of edges 7, 8, 10 and 11 are aligned, in that they lie within a common longitudinally extending plane 19. In this embodiment, and as best shown in FIG. 2, plane 19 is normal to surface 16 of board 5. Edges 7 and 8 intersect to define a primary fin tip 20, while edges 10 and 11 intersect to define a secondary fin tip 21. Tip 20 is an inflection point of edges 7 and 8, while tip 21 is an inflection point of edges 10 and 11. As shown in FIG. 1, fin 6 includes an uppermost point 23, while fin 9 includes an uppermost point 24. It will be appreciated that, in use, points 23 and 24 will typically define the lowermost points of the respective fins. The height of point 23 from base 2—that is, the depth of fin 6—is greater than that of tip 20, while the height of point 24 from base 2—that is, the depth of fin 9—is greater than that of tip 21. This results in edge 7 over wrapping the adjacent portion of edge 8. This is referred to as a feathering of edge 8. Edge 8 and edge 10 are joined by an intermediate arcuate edge 25 that is defined by base 2. Edge 25 is of varying radius such that edges 8, 10 and 25 are continuous and co-planar. Moreover, base 2 includes a leading edge 26 that is continuous with edge 7. Edges 26, 7, 8, 25, 10 and 11 are continuous and have a collective total length of about 430 mm. This is substantially longer than prior art assemblies of the same height as assembly 1. Tips 20 and 21, and points 23 and 24 also lie in plane 19. In this embodiment, the fins are longitudinally spaced apart. However, in other embodiments, the fins are transversely and/or longitudinally spaced apart. Fin 6 includes a pair of opposite faces 31 and 32 that extend between the leading and trailing edge and line 3. Similarly, fin 9 includes a pair of opposite faces 33 and 34 that extend between edges 10 and 11 and line 4. Base 2 includes opposed surfaces that extend continuously from the other adjacent surfaces. In this embodiment, all of faces 31, 32, 33 and 34 are non-planar. However, in other embodiments, faces 31 and 33 are substantially planar, or faces 32 and 34 are substantially planar. That is, corresponding sides of a fin assembly are planar or non-planar, as the case may be. In other embodiments, any one or more of the faces 31, 32, 33 and 34 are planar. In all cases, the faces of base 2 are shaped to provide a smooth and continuous transition between the fins. Preferably, any non-planar faces are substantially arcuate. The transverse thickness of assembly 1 varies to provide for low drag. Additionally, assembly 1 is of a reduced transverse thickness at or adjacent to line 4, that being the connection or boundary between base 2 and fin 9. This reduced thickness allows for a preferential transverse deformation of fin 9 about an axis that lies substantially along line 4. This typically slight accommodation of flex provides for an increased drive through and out of turns. That is, when a turn is commenced and underway, the transverse forces exerted upon assembly 1 flex fin 9 inwardly toward the centre of the arc, while fin 6 remains substantially unmoved from the centre line—in that it remains approximately tangential to the arc. However, as the board begins to straighten when coming out of a turn, the deformed portion quickly returns resiliently to the unbiased position and thereby contributes to the so-called “drive” out of the turn. In other embodiments, the flexing is accommodated by other forms of structural weakness. For example, through the use of a less rigid material in the region of line 4, or the inclusion of apertures or recesses in base 2 and fin 9 adjacent to or overlying line 4. The distance between point 23 and the bottom of base 2 is the depth of assembly 1 with respect to surface 16. This depth is indicated in FIG. 1 as H and is, in this embodiment, about 115 mm. The effective sectional area of assembly 1 that is available to engage the water and resist transverse movement of board 5 is best shown in the side view of FIG. 1. This sectional area is referred to, in this specification, as the predetermined sectional water engaging area A and includes the sectional area of base 2, fin 6 and fin 9. As formations 17 and 18 are contained within board 5 they do not contribute to A. For this embodiment, A is about 97 cm2. In the event that assembly 1 is mounted at an angle to the longitudinal axis of board 5, the effective area will be reduced. However, this is typical for fin assemblies. One of the features of assembly 1 is that, in use, a high proportion of A is near surface 16. This is quantified by calculating the proportion of A that is within a given proportion of H from surface 16. In this embodiment, about 51.4 cm2 lies within 0.3.H from surface 16. That is, about 53% of the total effective water engaging area of assembly 1—0.53.A—is provided by the bottom 30% of the assembly illustrated in FIG. 1. Again, it will be appreciated that, in use, assembly 1 will be inverted from the FIG. 1 configuration and, as such, it will be the top 30% of the assembly that provides the high proportion of the effective water engaging surface area. Another feature of assembly 1 is that, adjacent to surface 16, it is long in comparison to prior art fins relative to its height. By way of example, assembly 1 has a longitudinal length of about 170 mm, and a depth of about 100 mm. Some more common prior art fin assemblies have a corresponding length dimension of less than about 130 mm. Notwithstanding, the preferred embodiments have similar sectional areas to the prior art fin assemblies. For example, a prior art fin assembly sold by Fin Control Systems Pty Ltd under the designation K2.1, includes a depth of about 115 mm, a sectional area of about 99 cm2, a length adjacent to surface 16 of about 110 mm, and a water engaging peripheral edge of about 340 mm. Another prior art fin assembly, the Simon Andersen fin, includes a sectional area of about 101.5 cm2, a longitudinal length adjacent to surface 16 of about 130 mm, and a water engaging peripheral edge of about 350 mm. A further feature of assembly 1 is that it has a relatively long water engaging peripheral edge that is defined collectively by edges 26, 7, 8, 25, 10 and 11. These edges are continuous and have a collective length of about 430 mm. The prior art fins mentioned above have a far smaller corresponding dimension. The water engaging peripheral edge referred to above is the perimeter of assembly 1 when viewed from the side, excluding the perimeter that is adjacent to surface 16. This perimeter bounds the water engaging area A. These features of the embodiment of FIG. 1—that is, the larger proportion of the total surface area at or near the surface of the surf craft, the greater longitudinal length, and the longer peripheral edge—allows assembly 1 to provide the surfer or other surf craft user greater turning potential, without having to compromise control. In comparison to prior art fin assemblies, assembly 1 allows the surf craft to undertake turns about a smaller arc—or about the same arc, but with less input required from the surfer. In effect, assembly 1 allows the surf craft to be more manoeuvrable. The extended length of the fin assembly adjacent to the surf craft provides sufficient sectional area to allow the surface to gain sufficient purchase against the water when executing a turn. However, fin assembly 1 also has a depth sufficient to provide for good straight-line stability, without contributing overly to drag due to the relatively small sectional area in the portion of the assembly that is distal from the surf craft. A summary of the dimensions for assembly 1, four different prior art fins, and two other specific embodiments of the invention are provided in Table 1. TABLE 1 Peripheral Sectional 0.3.H Fin Depth Length Edge Area Area Area/PE Assembly (mm) (mm) (mm) (cm2) (%) (mm) FCS K2.1 115 110 330 99 35 30.0 (Prior Art) Simon 115 130 345 101.5 38 29.4 Anderson (Prior Art) FCS G5 115 109 340 95 35 27.9 (Prior Art) FCS G3000 111 107 320 90 36 28.1 (Prior Art) Assembly 1 100 190 430 97 53 22.6 Assembly 41 113 122 400 93.4 41 23.4 Assembly 51 118 146 380 91.5 46 24.1 A second embodiment of the invention, in the form of a fin assembly 41, is illustrated in FIG. 3, where corresponding features are denoted by corresponding reference numerals. Assembly 41 is not as longitudinally elongate as assembly 1, and intermediate edge 25 is very short. For comparison purposed, some key dimensions of assembly 41 are provided in Table 1. Relative to assembly 1, assembly 41 has a greater depth, a smaller length adjacent to surface 16, a smaller sectional area A, and a lower percentage of the total area in the 0.3.H zone. The difference in performance between assembly 1 and assembly 41 is that the latter is even more manoeuvrable than the former, in that is will turn with less force being exerted by the surfer (or turn more when exposed to the same force). A third embodiment of the invention, in the form of a fin assembly 51, is illustrated in FIG. 4, where corresponding features are denoted by corresponding reference numerals. Assembly 51 is not as elongate as assembly 1, but more elongate than assembly 41. The key dimensions of assembly 51 are provided in Table 1 for ease of comparison with the prior art and the other embodiments of the invention. While the 0.3.H area and the longitudinal length of fin assembly 51 adjacent to surface 16 are greater than for assembly 41, the peripheral edge and the sectional area of assembly 51 are both less than the corresponding dimensions for assembly 41. Moreover, 36% the sectional area of assembly 51 is in the bottom 22% of the height of fin 6. That is, the 0.22.H area is 36%. The effect of this on the performance of assembly 51 is far smoother in use, in that it offers a more progressive feel to the surfer over assemblies 1 and 41. The trade off is slightly less “initial bite” when entering turns. While such a fin assembly, being more forgiving, is typically best applied to a less experienced surfer, it is also extremely advantageously useable by a more experienced surfer in conditions that dictate gentler inputs. A significant distinction between assemblies 1 and 41, on the one hand, and assembly 51 on the other, is the form of the secondary fin. In the FIG. 4 embodiment, leading edge 10 of fin 9 is minimal as there is only a slight rise from the low point of edge 25 to point 24. In other embodiments, such as the assembly 61 illustrated in FIG. 5, fin 9 is a lobe 62, in that it does not include a leading edge, but only trailing edge 11. In this embodiment, the portion of edge 11 adjacent to edge 25 is parallel with surface 16. In other embodiments (not shown) a tangent from any point on edge 11 is non-parallel with the plane of surface 16. All of the fin assemblies of the above embodiments extend normally away from surface 16 and the respective continuous water engaging edges lie within a plane that is also normal to surface 16. In other embodiments, the assembly extends from surface 16 at an angle other than 90°. Additionally, in some embodiments, the water engaging edge is not uni-planar as fins 6 and 9 are disposed in different, but parallel, planes. For example, reference is made to FIG. 6 that illustrates a fin assembly 71 where corresponding features are denoted by corresponding reference numerals. It will be appreciated that fin 6 and fin 9 are transversely spaced apart, although edges 7 and 8 are substantially coplanar, and edges 10 and 11 are substantially coplanar, and those planes are substantially parallel. Base 2 and edge 25 create a smooth transition between the fins and the respective edges. In the FIGS. 3, 4 and 5 embodiments, fin 9 wholly underlies fin 6, in that fin 6- or lobe 62, as the case may be—extends further rearwardly than fin 9. Additionally, as the continuous water engaging edges for each of the fin assemblies lies within a single plane, edge 10 and 11 underlies both edges 7 and 8. In a further embodiment of the invention, there is provided a fin assembly 81, as best illustrated in FIG. 7, and where corresponding features are denoted by corresponding reference numerals. It will be noted that fin 6 of assembly 81 extends along plane 19, while fin 9 extends at an angle to that plane. This arrangement provides slightly more drag while board 5 is progressing in a straight line, but allows for an increased initial turn in for the board rider. Faces 31 and 33 are substantially planar, while faces 32 and 34 are arcuate. Face 31 extends along plane 19. In use, and as shown in FIG. 8, assembly 81 is mounted to board 5 opposite to a further fin assembly 82 that is a reflection of assembly 81 about plane 19. The inclination of fins 9 from respective planes 19 is such that the plane containing respective pairs of edges 10 and 11 intersect at the tip of the board (not shown). In other embodiments, such as where fin 9 is parallel with fin 6, the assembly as a whole is mounted such the assembly is inclined with respect to the longitudinal axis of board 5. As also shown in FIG. 8, use is made of a centrally disposed symmetrical fin assembly 83. Typically, assembly 83 is mounted to board 5 rearwardly of assemblies 81 and 82. The preferred embodiments have been developed to provide surf craft with an increased degree of manoeuvrability. This, in turn, enables the surfer to perform turns on the wave while maintaining proper momentum when progressing down the face of the wave. Turns are achieved by applying weight and/or pressure to the board at various locations so as to cause the edges and surfaces of the board to attack the water surface at different angles and thereby produce turning forces. The fins of the preferred embodiments improve the board's turning ability without unduly affecting forward speed through the water. In some embodiments the forward speed is increased. The improvement in performance of the fin assemblies of the preferred embodiments is presently understood to arise at least in part from the ability of those embodiments to allow the rake of the primary fin to be increased beyond what would be acceptable for a prior art fin while also providing an increased base length. This, in turn, allows a fin assembly of less height to be used without having to compromise on the straight-line stability of the board. The last column in Table 1 provides for each of the fin assemblies a quotient having as the numerator the sectional area of the assembly (in mm2) and, as a denominator, the length of the water engaging peripheral edge (in mm). It is apparent that, relative to the prior art, the embodiments of the invention provide low quotients. So, notwithstanding that the embodiments of the invention, in absolute terms, offer a long water engaging peripheral edge, this is done with proportionally less surface area. While conventional wisdom is more concerned with the absolute surface area provided as the critical determinant of performance, the inventors have appreciated that while this is a consideration, it is also important to ensure that the area is distributed advantageously. A further fin assembly 91, in accordance with another embodiment of the invention, is illustrated in FIG. 9 and has corresponding features denoted by corresponding reference numerals. As with all the other embodiments of the invention illustrated above, assembly 91 includes a feathering or cut-away portion 92 that is bounded by fin 6, fin 9 and base 2. The other boundary for portion 92 is defined by a straight line 93 which extends between the respective rears of fins 6 and 9. In this embodiment, the area of portion 92 is 24% of the total sectional area A of assembly 91. The corresponding characteristics for other fin assemblies are provided in Table 2. TABLE 2 Feathered Area as a Fin Assembly % of assembly area A FCS K2.1 10.6% (Prior Art) Simon Anderson 15.2% (Prior Art) FCS G5 16.2% (Prior Art) FCS G3000 17.6% (Prior Art) Assembly 41 25% Assembly 51 36% That is, the embodiments of the invention mentioned in Table 2 provide a large degree of feathering, in this case greater than 20%, and more preferably, greater than 24%. Moreover, for those embodiments making use of a lobe or small rear fin, the feathering is typically greater than 30%, and more preferably greater than 35%. Without wishing to be bound by theory, it is presently understood that at least some of the performance benefits of the preferred embodiments are derived from the increased feathering of the embodiments. In comparison to prior art assemblies, the surface area of the preferred embodiments has been, in effect, “removed” from the fin assembly to create the feathering, and in part “redistributed” to a point closer to board 5. Line 93 lies at a tangent to the respective rears of fins 6 and 9, and intersects surface 16 at an acute angle R, which is referred to as the rake of fin assembly 91. In the FIG. 9 embodiment, R is about 750. The corresponding characteristic for assemblies 1, 41 and 51 are 145°, 76° and 86° respectively. Relatively small amounts of rake have been traditionally used to create drag and holding power through the second half of the turn. The embodiments of the invention, however, use either a high rake or a low rake, although in combination with feathering to achieve the same or a similar affect. In addition, the use of a relatively long length adjacent to surface 16 ensures that the embodiments also provide stability. In this context, the prior art offers rake in the range of about 80° to 90°, while some of the embodiments of the invention have a rake of far greater than 90°, while others have a rake of less than 80°. The embodiments illustrated in the drawings include a longitudinal extent that is greater than that offered by the prior art due to the rearward extent of the secondary fin or lobe. The inclusion of the secondary fin or lobe allows the depth of the primary fin to be reduced, and the undercut or feathering of the primary fin to be increased, while adding to the stability of the assembly in use. That is, the embodiments of the invention are able to provide both manoeuvrability and stability, two factors that have traditionally had to be traded off against each other when designing a fin assembly. Board 5 or the other surf craft to which the fin assembly of the invention is mounted typically includes a substantially planar surface 16 in the region of engagement between the assembly and the surface. In other embodiments, surface 15 is other than planar, and surface 15 is complementarily shaped. As mentioned above, three fin assemblies are mounted to a single board, and this is often done in the known three-fin configuration. This involves having the centre fin assembly disposed along the centre line of the board and adjacent to the rear of the board. The other two fin assemblies are mounted to the board forward of and transversely spaced apart from the centre assembly. Typically, the two assemblies are inclined with respect to the centre line of the board such that the planes passing through the respective assemblies intersect at the leading point of the board. As the fin assemblies of the invention are able to be mounted in existing mounting formations of a board, it will be appreciated that the relatively long longitudinal extent of the assemblies will reduce the longitudinal distance between the trailing edge of the side pair of assemblies and the leading edge of the centre assembly. This will also improve the turning ability of the board. It is preferred, however, that there remains a longitudinal spacing between the leading edge of the centre assembly and the respective trailing edges of the other assemblies. If required, the longitudinally gap is able to match that offered by the prior art through appropriate location of formations 17 and 18 on surface 15. However, preferably, when the invention is applied to a pre-existing board, the longitudinal gap is reduced in comparison to what it would be for a prior art board. By way of example, the longitudinal gap for a prior art board using the Simon Anderson fin assembly is about 75 mm to 90 mm, although this is dependent upon the placement of the specific locating formations on the particular board. The corresponding longitudinal gap for the invention is at least 15 mm less than it is for the Simon Anderson fin. Preferably, however, the gap is at least 25 mm less. Surprisingly, and unlike prior art fins, the manoeuvrability of the preferred embodiments are not compromised by the increased base length. This is due to the greater undercut or feathering of the primary fin. That is, the combination of features offered by the preferred embodiments provide improved grip and hold against the water—both at the wave face and at the trough—greater ease of manoeuvrability and a substantial improvement in speed. In colloquial terms, the fin assembly provides greater drive due to the ability to trap more water. While not wishing to be bound by theory, it is thought that the improved performance is also due, at least in part, to the emphasised curvature toward the fin tips of the longitudinally viewed fin profiles, as well as the increased sectional area in the portion of the assembly that is adjacent to surface 16. The assemblies of the preferred embodiments include a sectional area, when viewed from the side, that is substantially equivalent to or less than the corresponding sectional area provided by a prior art Three Fin arrangement. However, the area provided by the embodiments is distributed far differently than that of the prior art, in that the primary fin is undercut to a greater extent, and the secondary fin extends rearwardly. As the primary fin has a sectional area that is substantially less than a prior art fin, it allows the surfer to perform smaller radius turns. This then allows the surfer to carve the wave face with a greater frequency. However, the directional stability to not degraded due to the presence of the secondary fin. In those embodiments where the secondary fin is designed to accommodate flex in a direction normal to the plane of the fin, the surfer is able to gain additional acceleration out of turns. Although it is usual to include a set of three fin assemblies of the invention together on a single surf craft—such as the arrangement illustrated in FIG. 8—in other embodiments, use is made of a single fin assembly that is centrally mounted to the rear of a surfboard. Where the fin assemblies are applied to surf craft larger than surfboards, the dimensions are scaled accordingly. The term “fin assembly” is used as a collective label for the various component parts of the preferred embodiments. All those component parts are typically integrally formed in a fixed predetermined relative spatial relationship to define the assembly. In some embodiments, however, some components are designed for relative resilient flexing movement with respect to each other, although still being integrally formed. In still further embodiments, one or more of the component parts are separate but attached to the other parts. Although the invention has been described with reference to specific examples, it will be appreciated by those skilled in the art that the invention may be embodied in many other forms.

<SOH> BACKGROUND TO THE INVENTION <EOH>The present invention relates to a fin and in particular to a fin assembly. The invention has been developed primarily for use with surf craft such as surfboards and will be described hereinafter with reference to that application. However, the invention is not limited to that particular field of use and is also applicable to other surf craft including surf skis and bogie boards and to water craft including kayaks, canoes, boats, sailboards and the like.

<SOH> SUMMARY OF THE INVENTION <EOH>It is an object of the present invention to ameliorate one or more of the deficiencies of the prior art or at least to provide a useful alternative. According to a first aspect of the invention there is provided a fin assembly for a surf craft, the assembly including: a base for mounting the assembly to the surf craft; a primary fin extending from the base and having a leading primary edge and a trailing primary edge; and a secondary fin extending from the base and having a leading secondary edge and a trailing secondary edge. Preferably, the base and the fins are integrally formed. Preferably also, the leading edges of the fins are aligned. More preferably, the leading and the trailing edges are aligned. Even more preferably, the base extends longitudinally between the leading primary edge and the trailing secondary edge. In a preferred form, the trailing primary edge and the leading secondary edge are joined by an intermediate arcuate edge defined by the base. More preferably, the arcuate edge is of varying radius. Preferably, the primary fin extends along a first plane that is normal to the base. More preferably, both the primary and secondary fins extend along the first plane. Preferably also, the fins include respective pairs of opposite faces that extend between the leading and trailing edges. More preferably, one or more of the faces are substantially planar. In other embodiments, however, one or more of the faces are substantially arcuate. In a preferred form, the fins are longitudinally spaced apart. In some embodiments, the fins are transversely spaced apart. According to a second aspect of the invention there is provided a fin assembly including: a base for mounting the assembly to an object; a primary fin extending from the base and having a leading primary edge and a trailing primary edge; and a secondary fin extending rearwardly from the base and having a leading secondary edge and a trailing secondary edge. Preferably the leading primary edge is curved substantially complementarily to the leading secondary edge. According to a third aspect of the invention there is provided a fin assembly including: a base for mounting the assembly to an object; a larger fin extending from the base and having a leading primary edge and a trailing primary edge and a high rake; and a smaller fin extending rearwardly from the base and having a leading secondary edge and a trailing secondary edge. Preferably, the edges extend along a single plane. More preferably, smaller fin is, in use, deformable in a direction normal to the plane. According to a fourth aspect of the invention there is provided a fin assembly for a surf craft, the assembly including: a base for mounting the assembly to the surf craft; a fin that extends from the base and which has a leading edge and a trailing edge that meet at a tip, where the edges lie substantially within a common plane; and a lobe extending rearwardly from the base, the lobe having a lobe edge that has a tangent that is parallel to the plane. According to a fifth aspect of the invention there is provided a fin assembly for a surf craft, the assembly including: a base having a substantially planar surface for mounting the assembly to the surf craft; a fin that extends from the base and which has a leading edge and a trailing edge that meet at a tip; and a lobe extending rearwardly from the base, the lobe having a lobe edge that has a tangent that is parallel to the surface. Preferably, the base, the fin and the lobe are integrally formed. More preferably, the base and the lobe extend longitudinally. Even more preferably, the base extends longitudinally between the leading edge and the trailing edge. Preferably also, the lobe is directly underlying the leading and the trailing edge. More preferably, the lobe, the trailing edge and the leading edge extend in a common plane. Preferably also, the trailing edge is feathered in an area intermediate of the lobe and the leading edge. In a preferred form, the trailing edge and the lobe are joined by an intermediate arcuate edge defined by the base. More preferably, the arcuate edge is of varying radius. Preferably, the fin extends along a first plane that is normal to the base. Preferably also, the fin includes a pair of opposite faces that extend between the leading and the trailing edge. More preferably, one or both of the faces are substantially planar. In other embodiments, however, one or both of the faces are substantially arcuate. Preferably, the edges extend along a common plane. In a preferred form, the lobe includes a leading secondary edge and a trailing secondary edge. More preferably, the lobe is a secondary fin. Preferably also, the fin assembly includes one or more mounting formations that extend from the surface for engaging with complementary locating formations extending from the surf craft. More preferably, the or each mounting formation is a protrusion, and the or each locating formation is a recess. Even more preferably the assembly includes two spaced apart mounting formations and the surf craft includes at least two locating formations. According to a sixth aspect of the invention there is provided a fin assembly including: a base for mounting the assembly to an object; a primary fin extending from the base; a secondary fin extending from the base, wherein the base, the primary fin and the secondary fin include a combined total sectional area (A f ); and a feathered portion between two or more of the primary fin, the secondary fin and the base, wherein the feathered portion includes a sectional area (A p ) where A p >0.2.A f . Preferably, A p >0.24.A f . More preferably, A p >0.35.A f . According to a seventh aspect of the invention there is provided a surf craft including a fin assembly of one of the first, second, fourth or fifth aspects of the invention. According to an eighth aspect of the invention there is provided a surf craft including a fin assembly of one of the third, fourth or sixth aspects of the invention, where the object is the surf craft. According to a ninth aspect of the invention there is provided a method of manufacturing a fin assembly for a surf craft, the method including: forming a base for mounting the assembly to the surf craft; forming a primary fin that extends from the base and which has a leading primary edge and a trailing primary edge; and forming a secondary fin that extends from the base and which has a leading secondary edge and a trailing secondary edge. Preferably, the forming steps are performed simultaneously. More preferably, the base, the primary fin and the secondary fin are integrally formed. Preferably also, the method includes forming at least one mounting formation that extends from the base for engaging with a complementary locating formation that extends from the surf craft. According to a tenth aspect of the invention there is provided a fin assembly for a surf craft, the assembly, in use, providing a predetermined sectional water engaging area (A) and including: a base for mounting the assembly to extend from a surface of the surf craft; a primary fin extending from the base and away from the surface; and a secondary fin extending from the base, wherein a high proportion of A is near the surface. Preferably, the primary fin terminates in a point having a predetermined height (H) with respect to the surface, and at least 0.4.A is within 0.3.H of the surface. More preferably, at least 0.45.A is within 0.3.H of the surface. Even more preferably, at least 0.5.A is within 0.3.H of the surface. In other embodiments, at least 0.35.A is within 0.22H of the surface. According to an eleventh aspect of the invention there is provided a fin assembly for a surf craft, the assembly including a sectional area of less than 95 cm 2 . Preferably, the sectional area is between about 90 cm 2 and 95 cm 2 . More preferably, the assembly extends from the surf craft and the perimeter of the area, excluding any common perimeter with the surf craft, is greater than about 380 mm. More preferably, it is greater than about 400 mm. According to a twelfth aspect of the invention there is provided a fin assembly for extending from a surface of a surf craft, the assembly extending longitudinally and having a longitudinal peripheral edge that terminates at two longitudinally spaced ends that are both disposed adjacent to the surface, the edge being at least 380 mm. Preferably, the edge is at least 400 mm. More preferably, the assembly includes a predetermined water engaging sectional area A that is bounded by the edge, where A is less than about 95 cm 2 . According to a thirteenth aspect of the invention there is provided a fin assembly for extending from a surface of a surf craft, the assembly extending longitudinally and having a longitudinal peripheral edge (PE) that terminates at two longitudinally spaced ends that are both disposed adjacent to the surface, the edge bounding a sectional area (A) of the assembly, wherein A/PE is less than 25. Preferably, A/PE is less than 24. More preferably, A/PE is less than 23.

20040714

20080701

20050609

97908.0

VASUDEVA, AJAY

FIN ASSEMBLY

MICRO

ACCEPTED

ACCEPTED

Novel fluorescent protein from aequorea coerulscens and methods for using the same

The present invention provides nucleic acid compositions encoding a novel colorless GFP-like protein, acGFP, from Aequorea coerulscens and fluorescent and non-fluorescent mutants and derivatives thereof, as well as peptides and proteins encoded by these nucleic acid compositions. The subject protein and nucleic acid compositions of the present invention are colored and/or fluorescent and/or can be photoactivated, and can be used in a variety of different biological applications, particularly for labeling. Finally, kits for use in such biological applications are provided.

1. A nucleic acid molecule present in other than its natural environment, wherein said nucleic acid encodes a fluorescent protein from Aequorea coerulescens. 2. The nucleic acid of claim 1, wherein said nucleic acid is isolated. 3. The nucleic acid of claim 1, wherein said fluorescent protein has an amino acid sequence selected from the group consisting of: SEQ ID NO: 02, 04, 06, 08, 10, 12, 14, 16, 18, 20, 22, or 24. 4. The nucleic acid of claim 3, wherein said nucleic acid has a sequence similarity of at least about 70% with a sequence of at least 10 residues in length taken form the group of sequences consisting of SEQ ID NO: 01, 03, 05, 07, 09, 11, 13, 15, 17, 19, 21, or 23. 5. The nucleic acid of claim 1, encoding a mutant fluorescent protein. 6. The nucleic acid of claim 5, wherein said mutant protein comprises at least one point mutation as compared to a wild type protein. 7. The nucleic acid of claim 5, wherein said mutant protein comprises at least one deletion mutation as compared to a wild type protein. 8. A nucleic acid molecule having a sequence that is substantially similar to or identical to a nucleotide sequence of at least 10 residues in length taken from SEQ ID NO: 01, 03, 05, 07, 09, 11, 13, 15, 17, 19, 21, or 23. 9. An isolated nucleic acid or mimetic thereof that hybridizes under stringent conditions to a nucleic acid selected from the group consisting of: (a) an isolated nucleic acid encoding a fluorescent protein from Aequorea coerulescens; (b) a nucleic acid having a sequence that is substantially similar to or identical to a nucleotide sequence of at least 10 residues in length from SEQ ID NO: 01, 03, 05, 07, 09, 11, 13, 15, 17, 19, 21, or 23; (c) an isolated nucleic acid that encodes a mutant fluorescent protein from a Aequorea coerulescens; (d) complements of nucleic acids (a)-(c); or (e) fragments of nucleic acids (a)-(c). 10. A construct comprising a vector and the nucleic acid of claim 9. 11. An expression cassette comprising: (a) a transcriptional initiation region functional in an expression host; (b) the nucleic acid of claim 9; and (c) and a transcriptional termination region functional in the expression host. 12. A cell, or progeny thereof, comprising the expression cassette of claim 11. 13. A method of producing a chromo- or fluorescent protein, said method comprising growing the cell of claim 12 under conditions where the chromo- or fluorescent protein is expressed. 14. The method of claim 13 further including the step of isolating the chromo- or fluorescent protein substantially free of other proteins. 15. A protein or fragment thereof encoded by the nucleic acid of claim 9. 16. A protein or fragment thereof having a sequence similarity of at least about 95% to the protein or fragment of claim 15. 17. A fusion protein incorporating the protein or fragment of claim 15. 18. An antibody binding specifically to the protein of claim 15. 19. A transgenic organism comprising the nucleic acid of claim 9. 20. A kit comprising the nucleic acid of claim 9 and instructions for using the nucleic acid.

FIELD OF THE INVENTION This invention relates to fluorescent proteins. BACKGROUND OF THE INVENTION Labeling is a tool for marking a protein, cell, or organism of interest and plays a prominent role in many biochemical, molecular biological and medical diagnostic applications. A variety of different labels have been developed and used in the art, including radiolabels, chromolabels, fluorescent labels, chemiluminescent labels, and the like, with varying properties and optimal uses. However, there is continued interest in the development of new labels. Of particular interest is the development of new protein labels, including fluorescent protein labels. RELEVANT LITERATURE U.S. patents of interest include: U.S. Pat. Nos. 6,066,476; 6,020,192; 5,985,577; 5,976,796; 5,968,750; 5,968,738; 5,958,713; 5,919,445; 5,874,304; and 5,491,084. International Patent Publications of interest include: WO 00/46233; WO 99/49019; and DE 197 18 640 A. Also of interest are: Anderluh et al., Biochemical and Biophysical Research Communications (1996) 220:437-442; Dove et al., Biological Bulletin (1995) 189:288-297; Fradkov et al., FEBS Lett. (2000) 479(3):127-30; Gurskaya et al., FEBS Lett., (2001) 507(1):16-20; Gurskaya et al., BMC Biochem. (2001) 2:6; Lukyanov, K., et al. (2000) J. Biol. Chemistry 275(34):25879-25882: Macek et al., Eur. J. Biochem. (1995) 234:329-335; Martynov et al., J. Biol. Chem. (2001) 276:21012-6; Matz, M. V., et al. (1999) Nature Biotechnol., 17:969-973; Terskikh et al., Science (2000) 290:1585-8; Tsien, Annual Rev. of Biochemistry (1998) 67:509-544; Tsien, Nat. Biotech. (1999) 17:956-957; Ward et al., J. Biol. Chem. (1979) 254:781-788; Wiedermann et al., Jarhrestagung der Deutschen Gesellschact fur Tropenokologie-qto. Ulm. Feb. 17-19, 1999. Poster P4.20; Yarbrough et al., Proceedings of the National Academy of Sciences (2001) 98:462-7. SUMMARY OF THE INVENTION The present invention provides nucleic acid compositions encoding a unique colorless protein from Aequorea coerulscens and fluorescent and non-fluorescent mutants thereof, as well as the proteins and peptides encoded by the nucleic acids. The proteins of the present invention are proteins that are colored and/or fluorescent and/or can be photoactivated, where this optical feature arises from the interaction of two or more amino acid residues of the protein. Also of interest are proteins that are substantially similar to, or derivatives or mutants of, the above-referenced specific proteins including fusion proteins incorporating peptides of the present invention, as well as antibodies to these proteins. The subject protein and nucleic acid compositions find use in a variety of different applications. Finally, the present invention provides kits for use in labeling applications. DESCRIPTION OF THE FIGURES FIG. 1 is the amino acid sequence and the nucleic acid sequence encoding the wild type GFP-like protein from Aequorea coerulescens, herein referred to as acGFP. FIG. 2 is the comparison of Aequorea victoria GFP and Aequorea coerulescens acGFP amino acid sequences. FIG. 3 is the amino acid sequence and the nucleic acid sequence encoding the acGFP mutant, Z1. FIG. 4 is the excitation-emission spectra for mutant Z1. FIG. 5 is the amino acid sequence and the nucleic acid sequence the acGFP sequence mutant, Z2. FIG. 6 is the amino acid sequence and the nucleic acid sequence encoding the acGFP mutant, G1. FIG. 7 is the amino acid sequence and the nucleic acid encoding the acGFP mutant, G2. FIG. 8 is the excitation-emission spectra for mutant G2. FIG. 9 is the amino acid sequence and the nucleic acid sequence encoding the acGFP mutant, G22. FIG. 10 is the excitation-emission spectra for mutant G22. FIG. 11 is a protein gel-electrophoresis analysis of wildtype acGFP and acGFP mutants. FIG. 12 is the amino acid sequence and the nucleic acid sequence encoding the acGFP mutant, G22-G222E. FIG. 13 is the absorption and excitation-emission spectra for mutant G22-G222E. FIG. 14 provides the spectra for UV-induced photoconversion of G22-G222E. FIG. 15 is the amino acid sequence and the nucleic acid sequence encoding the acGFP mutant, G22-G222E/Y220L. FIG. 16 is the excitation-emission spectra for mutant G22-G222E/Y220L. FIG. 17 is the amino acid sequence and the nucleic acid sequence encoding the acGFP mutant, 220-II-5. FIG. 18 provides spectral properties of mutant 220-II-5. FIG. 19 is the amino acid sequence and the nucleic acid sequence encoding the acGFP mutant, CFP-rand3. FIG. 20 is the excitation-emission spectra for mutant CFP-rand3. FIG. 21 is the amino acid sequence and the nucleic acid sequence encoding acGFP mutant, CFP-3. FIG. 22 provides spectral properties of mutant CFP-3. FIG. 23 is the amino acid and nucleic acid sequences for a humanized version of mutant G22. FIG. 24 shows microphotographs of mammalian cells expressing mutant G22. FIG. 25 shows the photoactivation of mutant 220-II-5 in E. coli colonies. DESCRIPTION OF THE INVENTION The subject invention provides a nucleic acid, wherein the nucleic acid encodes a fluorescent protein, acGFP, or a mutant or derivative thereof. In certain embodiments, the nucleic acid is isolated, or has been engineered or is present in an environment other than its natural environment. In certain embodiments, the nucleic acid has a sequence of residues that is substantially the same as, or identical to, a nucleotide sequence of at least 10 residues in length from SEQ ID NO: 01, 03, 05, 07, 09, 11, 13, 15, 17, 19, 21, or 23. In certain embodiments, the nucleic acid of the present invention has a sequence similarity of at least about 60% with a sequence of SEQ ID NO: 01, 03, 05, 07, 09, 11, 13, 15, 17, 19, 21, or 23, and is at least 10 residues in length. In certain embodiments, the nucleic acid of the present invention encodes a protein that has an amino acid sequence selected from the group consisting of SEQ ID NO: 02, 04, 06, 08, 10, 12, 14, 16, 18, 20, 22, or 24, encoding a mutant or derivative protein of a Aequorea coerulscens fluorescent protein. Also provided are fragments of the nucleic acids of the present invention. Additionally, nucleic acids or mimetics thereof that hybridize under stringent conditions to the nucleic acids of the present invention are provided. Also provided are constructs comprising a vector and a nucleic acid of the present invention. In addition, the present invention provides expression cassettes that include: a transcriptional initiation region functional in a expression host, a nucleic acid of the present invention, and a transcriptional termination region functional in the expression cassette as part of an extrachromosomal element or integrated into the genome of the cell as a result of introduction of said expression cassette into the cell. Also provided are methods of producing a chromogenic and/or fluorescent protein including growing a cell of the present invention, expressing the protein in the cell, and isolating the protein substantially free of other proteins. In addition, proteins or fragments or peptides encoded by a nucleic acid of the present invention are provided, as are antibodies that bind specifically to the proteins or peptides of the present invention. Additionally, transgenic cells (or their progeny) that include a nucleic acid of the present invention are provided, as are transgenic organisms that include a nucleic acid of the present invention. Also provided are methods that employ a chromo- or fluorescent protein of the present invention, or that employ a nucleic acid encoding a chromogenic or fluorescent protein of the present invention. Additionally, kits that include a nucleic acid or protein according to the subject invention and instructions of use therefor, are provided. In accordance with the present invention there may be employed conventional molecular biology, microbiology, and recombinant DNA techniques within the sill of the art. Such techniques are explained fully in the literature. See, e.g., Maniatis, Fritsch & Sambrook, Molecular Cloning: A Laboratory Manual (1982); DNA Cloning: A Practical Approach. Volumes I and II (D. N. Glover, ed. 1985); Oligonucleotide Synthesis (M. J. Gait, ed. 1984); Nucleic Acid Hybridization (B. D. Hames & S. J. Higgins, eds. (1984)); Animal Cell Culture (R. I. Freshney, ed. (1986)); Immobilized Cells and Enzymes (IRL Press (1986)); and B. Perbal, A Practical Guide to Molecular Cloning (1984). A “vector” is a replicon, such as plasmid, phage or cosmid, to which another DNA segment may be attached. A “DNA molecule” refers to the polymeric form of deoxyribonucleotides (adenine, guanine, thymine, or cytosine) in either single-stranded form or a double-stranded helix. This term refers only to the primary and secondary structure of the molecule, and does not limit it to any particular tertiary forms. Thus, “DNA molecule” includes double-stranded DNA found, inter alia, in linear DNA molecules (e.g., restriction fragments), viruses, plasmids, and chromosomes. A DNA “coding sequence” is a DNA sequence which is transcribed and translated into a polypeptide in vivo when placed under the control of appropriate regulatory sequences. The boundaries of the coding sequence are determined by a start codon at the 5′ (amino) terminus and a translation stop codon at the 3′ (carboxyl)terminus. A coding sequence can include, but is not limited to, prokaryotic sequences, cDNA from eukaryotic mRNA, genomic DNA sequences from eukaryotic (e.g., mammalian) DNA, and synthetic DNA sequences. A polyadenylation signal and transcription termination sequence may be located 3′ of the coding sequence. As used herein, the term “hybridization” refers to the process of association of two nucleic acid strands to form an antiparallel duplex stabilized by means of hydrogen bonding between residues of the opposite nucleic acid strands. The term “oligonucleotide” refers to a short (under 100 bases in length) nucleic acid molecule. “DNA regulatory sequences”, as used herein, are transcriptional and translational control sequences, such as promoters, enhancers, polyadenylation signals, terminators, and the like, that provide for and/or regulate expression of a coding sequence in a host cell. A “promoter sequence” is a DNA regulatory region capable of binding RNA polymerase in a cell and initiating transcription of a coding sequence. For example, the promoter sequence may be bounded at its 3′ terminus by the transcription initiation site and extend upstream (5′ direction) to include the minimum number of bases or elements necessary to initiate transcription at levels detectable above background. Within the promoter sequence may be found a transcription initiation site, as well as protein binding domains responsible for the binding of RNA polymerase. Eukaryotic promoters will often, but not always, contain “TATA” boxes and “CAT” boxes. Various promoters, including inducible promoters, may be used to drive the various vectors of the present invention. As used herein, the terms “restriction endonucleases” and “restriction enzymes” refer to bacterial enzymes, each of which cut double-stranded DNA at or near a specific nucleotide sequence. A cell has been “transformed” or “transfected” by exogenous or heterologous DNA when such DNA has been introduced inside the cell. The transforming DNA may or may not be integrated (covalently linked) into the genome of the cell. In prokaryotes, yeast, and mammalian cells for example, the transforming DNA may be maintained on an episomal element such as a plasmid. With respect to eukaryotic cells, a stably transformed cell is one in which the transforming DNA has become integrated into a host cell chromosome or is maintained extra-chromosomally so that the transforming DNA inherited by daughter cells during cell replication. Such a stably transformed eukaryotic cell is able to establish cell lines or clones comprised of a population of daughter cells containing the transforming DNA. A “clone” is a population of cells derived from a single cell or common ancestor by mitosis. A “cell line” is a clone or a cell that is capable of stable growth in vitro for many generations. A “heterologous” region of a DNA construct is an identifiable segment of DNA within a larger DNA molecule that is not found in association with the larger molecule in nature; for example, when the heterologous region encodes a mammalian genomic DNA in the genome of a non-mammlian organism. In another example, heterologous DNA includes coding sequences in a construct where portions of genes from two different sources have been brought together so as to produce a fusion protein product. As used herein, the term “reporter gene” refers to a coding sequence attached to heterologous promoter or enhancer elements and whose product may be assayed easily and quantifiably when the construct is introduced into tissues or cells. The amino acids described herein are preferred to be in the “L” isomeric form. The amino acid sequences are given in one-letter code (A: alanine; C; cysteine; D: aspartic acid; E: glutamic acid; F: phenylalanine; G: glycine; H: histidine; I: isoleucine; K: lysine; L: leucine; M: methionine; N: asparagine; P: proline; Q: glutamine; R: arginine; S: serine; T: threonine; V: valine; W: tryptophan; Y: tyrosine; X: any residue). NH2 refers to the free amino group present at the amino terminus of a polypeptide. COOH refers to the free carboxy group present at the carboxy terminus of a polypeptide. Standard polypeptide nomenclature, see J. Biol. Chem., 243, 3552-59 (1969), is used. The term “immunologically active” defines the capability of the natural, recombinant or synthetic chromogenic or fluorescent protein, or any oligopeptide thereof, to induce a specific immune response in appropriate animals or cells and to bind with specific antibodies. As used herein, “antigenic amino acid sequence” means an amino acid sequence that, either alone or in association with a carrier molecule, can elicit an antibody response in a mammal. The term “specific binding,” in the context of antibody binding to an antigen, is a term well understood in the art and refers to binding of an antibody to the antigen to which the antibody was raised, but not other, unrelated antigens. As used herein the term “isolated” is meant to describe a polynucleotide, a polypeptide, an antibody, or a host cell that is an environment different from that in which the polynucleotide, the polypeptide, and antibody, or the host cell naturally occurs. Bioluminescence is emission of light by living organisms that is visible in the dark. (See, e.g., Harvey, Bioluminescence, New York: Academic Press (1952); Hastings, “Bioluminescence” in: Cell Physiology (ed. by Speralakis), New York Academic Press pp. 651-81 (1995); Wilson and Hastings, “Bioluminescence”, Annu. Rev. Cell. Dev. Biol. 14, pp. 197-230 (1998)). Bioluninescence does not include so-called ultra-weak light emission, that can be detected in virtually all living structures using sensitive luminometric equipment (Murphy and Sies, “Visible-range low-level chemiluminescence in biological systems”, Meth. Enzymol. 186, pp. 595-610 (1990); Radotic, et al., “Spontaneous ultra-weak bioluminescence in plants: origin, mechanisms and properties”, Gen. Physiol. Biophys. 17, pp. 289-308 (1998)), nor does bioluminescence emanate from weak light emission which most probably does not play an ecological role, such as the glowing of a bamboo growth cone (Totsune, et al., “Cemiluminescence from bamboo shoot cut”, Biochem. Biophys. Res. Comm. 194, pp. 1025-1029 (1993)), or emission of light during the fertilization of animal eggs (Klebanoff, et al., “Metabolic similarities between fertilization and phagocytosis”, J. Exp. Med. 149, pp. 938-53 (1979); Schomer and Epel, “Redox changes during fertilization and maturation of marine invertebrate eggs”, Dev. Biol. 2003, pp. 1-11 (1998)). As used herein, the term “GFP-like proteins” is meant to describe proteins similar to the green fluorescent protein (GFP) from Aequorea victoria. Nucleic acid compositions encoding a colorless GFP-like protein, acGFP, from Aequorea coerulscens, and fluorescent and non-fluorescent derivatives or mutants thereof, as well as proteins and peptides encoded by these nucleic acid composites are provided. The proteins of interest are proteins that are colored and/or fluorescent and/or can be photoactivated, where the color, fluorescent, or photoactivation feature arises from the interaction of two or more amino acid residues of the protein. Also of interest are proteins that are substantially similar to, or derivatives or mutants of, the above-referenced specific proteins. Also provided are fragments of the nucleic acids and the peptides encoded thereby, as well as antibodies to the subject proteins and peptides. In addition, transgenic cells and organisms are provided. The subject protein and nucleic acid compositions find use in a variety of different applications and methods, particularly protein labeling applications. Finally, kits for use in such methods and applications are provided. Before the subject invention is described further, it is to be understood that the invention is not limited to the particular embodiments of the invention described below, as variations of the particular embodiments may be made and still fall within the scope of the invention. It is also to be understood that the terminology employed is for the purposed of describing particular embodiments, and is not intended to be limiting. In this specification, the singular forms “a”, “an” and “the” include plural references unless the context clearly dictates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which this invention belongs. Although any methods, devices and materials similar or equivalent to those described herein can be used in the practice or testing of the invention, the preferred methods, devices and materials are now described. All publications mentioned herein are incorporated herein by reference for the purpose of describing and disclosing the invention. In describing the present invention, nucleic acid compositions will be described first, followed by a discussion of protein compositions, antibody compositions and transgenic cells and organisms. Next a review of exemplary methods in which the proteins of the present invention find use is provided. Nucleic Acid Compositions As summarized above, the present invention provides nucleic acid compositions encoding a colorless protein, acGFP, from Aequorea coerulescens, or fluorescent and non-fluorescent mutants or derivatives of acGFP, as well as fragments and homologs of the nucleic acid compositions. The phrase “fluorescent protein” means a protein that is fluorescent; e.g., it may exhibit low, medium or intense fluorescence upon irradiation with light of the appropriate excitation wavelength. The proteins of the present invention are those in which the fluorescent characteristic is one that arises from the interaction of two or more amino acid residues of the protein, and not from a single amino acid residue. As such, the fluorescent proteins of the present invention do not include proteins that exhibit fluorescence only from residues that act by themselves as intrinsic fluors, i.e., tryptophan, tyrosine and phenylalanine. The fluorescent proteins of the subject invention thus are fluorescent proteins whose fluorescence arises from some structure in. the protein other than the above-specified single amino acid resides; e.g., it arises from an interaction of two or more amino acid residues. One nucleic acid composition of the present invention is a composition comprising a sequence of DNA having an open reading frame that encodes a polypeptide of the subject invention; i.e., a fluoroprotein gene. Such a nucleic acid composition is capable, under appropriate conditions, of being expressed as a fluoroprotein. Also encompassed in the term nucleic acid composition are nucleic acids that are homologous to, substantially similar to, identical to, or mimetics of the nucleic acids of the present invention. The subject nucleic acids are present in an environment other than their natural environment; e.g., they are isolated, present in enriched amounts, or are present or expressed in vitro or in a cell or organism other than their naturally occurring environment. In another embodiment of the present invention, the nucleic acids may be encoded by SEQ ID NO: 01, 03, 05, 07, 09, 11, 13, 15, 17, 19, 21 or 23, or are nucleic acids derived from, or are homologs of such nucleic acids. In addition to the above-described specific nucleic acid compositions, also of interest are homologs of the above sequences. With respect to homologs of the subject nucleic acids, the source of homologous genes may be any species of plant or animal or the sequence may be wholly or partially synthetic including sequences incorporating nucleic acid mimetics. In certain embodiments, sequence similarity between homologs is at least about 40%, and maybe 50%, 60%, 70% or higher, including 75%, 80%, 85%, 90% and 95% or higher. Sequence similarity is calculated based on a reference sequence, which may be a subset of a larger sequence, such as a conserved motif, coding region, flanking region, etc. A reference sequence will usually be at least about 18 nucleotides long, more usually at least about 30 nucleotides long, and may extend to the complete sequence that is being compared. Algorithms for sequence analysis are known in the art, such as BLAST, described in Altschul et al., J. Mol. Biol., 215, pp. 403-10 (1990) (for example, using default settings, i.e., parameters w=4 and T=17). Homologs are identified by any of a number of methods. A fragment of a cDNA of the present invention may be used as a hybridization probe against a cDNA library from a target organism of interest, where low stringency conditions are used. The probe may be a large fragment, or one or more short degenerate primers. Nucleic acids having sequence similarity are detected by hybridization under low stringency conditions, for example, at 50° C. and 6×SSC (0.9 M sodium chloride/0.09 M sodium citrate) and remain bound when subjected to washing at 55° C. in 1×SSC (0I.15 M sodium chloride/0.015 M sodium citrate). Sequence identity may be determined by hybridization under stringent conditions, for example, at 50° C. or higher and 0.1×SSC (15 mM sodium chloride/1.5 mM sodium citrate). Nucleic acids having a region of substantial identity to the provided sequences, e.g., allelic variants, genetically-altered versions of the gene, etc., bind to the provided sequences under stringent hybridization conditions. By using probes, particularly labeled probes of DNA sequences, one can isolate homologous or related genes. Or particular interest in certain embodiments of the present invention are nucleic acids of substantially the same length as the nucleic acids identified as SEQ ID NO: 01, 03, 05, 07, 09, 11, 13, 15, 17, 19, 21, or 23, where “substantially the same length” means that any difference in length does not exceed about 20%, usually does not exceed about 10% and more usually does not exceed about 5%. In preferred embodiments nucleotides of substantially the same length will have a sequence identity to SEQ ID NO: 01, 03, 05, 07, 09, 11, 13,15, 17, 19, 21 or 23, of at least about 90% (e.g., at least about 92%, 93%, 94%), usually at least about 95%, 96%, 97% or 98% or even about 99% over the entire length of the nucleic acid. “Substantially similar” means that sequence identity will generally be at least about 60%, usually at least about 75% and often at least about 80, 85, 90 (e.g., 92%, 93%, 94%), or even 95%, e.g., 96%, 98%, 98%, 99%, 99.5% or higher. In addition, the present invention includes nucleic acids that encode the proteins encoded by the previously-described nucleic acids, but differ in sequence from the previously-described nucleic acids due to the degeneracy of the genetic code. Also provided are nucleic acids that hybridize to the above-described nucleic acids under stringent conditions (i.e., complements of the previously-described nucleic acids). An example of stringent hybridization conditions is hybridization at 50° C. or higher and 0.1×SSC (15 mM sodium chloride/1.5 mM sodium citrate). Another example of stringent hybridization conditions is overnight incubation at 42° C. in a solution of 50% formamide, 5×SSC (150 mM NaCl, 15 mM trisodium citrate), 50 mM sodium phosphate (pH7.6), 5× Denhardt's solution, 10% destran sulfate, and 20 μg/ml denatured, sheared salmon sperm DNA, followed by washing in 0.1×SSC at about 65° C. Stringent hybridization conditions are hybridization conditions that are at least 80% as stringent as the above-representative conditions. Other stringent hybridization conditions are known in the art and may also be employed to identify nucleic acids of this particular embodiment of the invention. Nucleic acids encoding mutants or derivatives of the proteins of the invention also are provided. Mutant nucleic acids can be generated by random mutagenesis or targeted mutagenesis, using techniques well known in the art. Mutations of interest include deletions, additions and substitutions. In some embodiments, fluorescent proteins encoded by nucleic acids encoding homologs or mutants have the same fluorescent properties as the wild type fluorescent protein. In other embodiments, homolog or mutant nucleic acids encode fluorescent proteins with altered spectral properties, as described in more detail for mutant acGFP proteins herein. Nucleic acids of the subject invention may be cDNA or genomic DNA or a fragment thereof. In certain embodiments, the nucleic acids of the subject invention include one or more of the open reading frames encoding specific fluorescent proteins and polypeptides, and introns, as well as adjacent 5′ and 3′ non-coding nucleotide sequences involved in the regulation of expression, including sequences up to about 20 kb beyond the coding region, but possibly further, in either direction. The subject nucleic acids may be introduced into an appropriate vector for extrachromosomal maintenance or for integration into a host genome, as described in greater detail below. The term “cDNA” as used herein is intended to include nucleic acids that share the arrangement of sequence elements found in native mature mRNA species, where sequence elements are exons and 5′ and 3′ non-coding regions. Normally mRNA species have contiguous exons, with the intervening introns, when present, being removed by nuclear RNA splicing, to create a continuous open reading frame encoding the protein. A genomic sequence of interest may comprise the nucleic acid present between the initiation codon and the stop codon, as defined in the listed sequences, including all of the introns that are normally present in a native chromosome. The genomic sequence of interest further may include 5′ an 3′ un-translated regions found in the mature mRNA, as well as specific transcriptional and translational regulatory sequences, such as promoters, enhancers, etc., including about 1 kb, but possibly more, of flanking genomic DNA at either the 5′ or 3′ end of the transcribed region. The genomic DNA may be isolated as a fragment of 100 kb or smaller; and substantially free of flanking chromosomal sequence. Genomic DNA flanking the coding region, either 3′ or 5′, or internal regulatory sequences as sometimes found in introns, may contain sequences required for proper tissue- and stage-specific expression. The nucleic acid compositions of the subject invention may encode all or a part of the subject proteins. Double- or single-stranded fragments may be obtained from the DNA sequence by chemically synthesizing oligonucleotides in accordance with conventional methods, by restriction enzyme digestion, by PCR amplification, etc. For the most part, DNA fragments will be at least about 15 nucleotides in length, usually at least about 18 nucleotides in length or about 25 nucleotides in length, and may be at least about 50 nucleotides in length. In some embodiments, the subject nucleotide acid molecules may be about 100, about 200, about 300, about 400, about 500, about 600, about 700 nucleotides or greater in length. The subject nucleic acids may encode fragments of the subject proteins or the full-length proteins; e.g., the subject nucleic acids may encode polypeptides of about 25 amino acids, about 50, about 75, about 100, about 125, about 150, about 200 amino acids up to the full length protein. The subject nucleic acids may be isolated and obtained in substantial purity, generally as other than as an intact chromosome. Usually, the DNA will be obtained substantially free of nucleic acid sequences that do not include a nucleic acid of the subject invention or a fragment thereof. Substantial purity means that the nucleic acids are at least about 50% pure, usually at least about 90% pure and are typically “recombinant”, i.e., flanked by one ore more nucleotides with which it is not normally associated on a naturally-occurring chromosome in its natural host organism. The polynucleotides of the present invention, e.g., polynucleotides having the sequence of SEQ ID NO: 01, 03, 05, 07, 09, 11, 13, 15, 17, 19, 21 or 23, the corresponding cDNAs, full-length genes and constructs can be generated synthetically by a number of different protocols known to those of skill in the art. Appropriate polynucleotide constructs are purified using standard recombinant DNA techniques as described in, for example, Sambrook et al., Molecular Cloning: A Laboratory Manual, 2nd Ed., Cold Spring Harbor Press, Cold Spring Harbor, N.Y. (1989), and under regulations described in, e.g., United States Dept. of HHS, National Institute of Health (NIH) Guidelines for Recombinant DNA Research. Also provided are nucleic acids that encode fusion proteins of the subject protein or peptides of the present invention, or fragments thereof, fused to a second peptide or protein. The second protein may be, for example, a degradation sequence, a signal peptide, or any protein of interest. Fusion proteins may comprise for example, an acGFP or mutant acGFP polypeptide and a second polypeptide (“the fusion partner”) fused in-frame at the N-terminus and/or C-terminus of the acGFP polypeptide. Fusion partners include, but are not limited to, polypeptides that can bind antibodies specific to the fusion partner (e.g., epitope tags), antibodies or binding fragments thereof, polypeptides that provide a catalytic function or induce a cellular response, ligands or receptors or mimetics thereof, and the like. In such fusion proteins, the fusion partner is generally not naturally associated with the acGFP portion of the fusion protein, and is typically not an Aequorea coerulescens protein or derivative/fragment thereof; i.e., it is not found in Aequorea species. Also provided are vector and other nucleic acid constructs comprising the subject nucleic acids, where such constructs may be used for a number of applications, including propagation, protein production, etc. Viral and non-viral vectors may be prepared and used, including plasmids. The choice of vector will depend on the type of cell in which propagation is desired and the purpose of propagation. Certain vectors are useful for amplifying and making large amounts of the desired DNA sequence. Other vectors are suitable for expression in cells in culture. Still other vectors are suitable for transfer and expression in cells in a whole animal. The choice of appropriate vector is well within the skill of the art, and many such vectors are available commercially. To prepare the constructs, the partial or full-length polynucleotide is inserted into a vector typically by means of DNA ligase attachment to a cleaved restriction enzyme site in the vector. Alternatively, the desired nucleotide sequence can be inserted by homologous recombination in vivo, typically by attaching regions of homology to the vector on the flanks of the desired nucleotide sequence. Regions of homology are added by ligation of oligonucleotides, or by polymerase chain reaction using primers comprising both the region of homology and a portion of the desired nucleotide sequence, for example. Also provided are expression cassettes or systems that find use in, among other applications, the synthesis of the subject chromogenic or fluorescent proteins or fusion proteins thereof. For expression, the gene product encoded by a polynucleotide of the invention is expressed in any convenient expression system, including, for example, bacterial, yeast, insect, amphibian and mammalian systems. Such vectors and host cells are described in U.S. Pat. No. 5,654,173. In the expression vector, a subject polynucleotide—e.g., as set forth in SEQ ID NO: 01, 03, 05, 07, 09, 11, 13, 15, 17, 19, 21 or 23—is linked to a regulatory sequence as appropriate to obtain the desired expression properties. These regulatory sequences can include promoters (attached either at the 5′ end of the sense strand or at the 3′ end of the antisense strand), enhancers, terminators, operators, repressors and inducers. The promoters can be regulated or constitutive. In some situations it may be desirable to use conditionally active promoters, such as tissue-specific or developmental stage-specific promoters. These are linked to the desired nucleotide sequences using the techniques described above for linkage to vectors. Any techniques known in the art can be used. In other words, the expression vector will provide a transcriptional and translational initiation region, which may be inducible or constitutive, where the coding region is operably linked under the transcriptional control of the transcriptional initiation region, and a transcriptional and translational termination region. These control regions may be native to the subject species from which the subject nucleic acid is obtained, or may be derived from exogenous sources. Expression vectors generally have convenient restriction sites located near the promoter sequence to provide for the insertion of nucleic acid sequences encoding heterologous proteins. A selectable marker operative in the expression host may be present. Expression vectors may be used for, among other things, the production of fusion proteins, as described above. Expression cassettes may be prepared comprising a transcription initiation region, the gene or fragment thereof, and a transcriptional termination region. Of particular interest is the use of sequences that allow for the expression of functional epitopes or domains, usually at least about 8 amino acids in length, more usually at least about 15 amino acids in length, to about 25 amino acids, and up to the complete open reading frame of the gene. After introduction of the DNA, the cells containing the construct may be selected by means of a selectable marker, the cells expanded, then used for expression. The above-described expression systems may be employed with prokaryotes or eukaryotes in accordance with conventional methods, depending upon the purpose for expression. For large-scale production of the protein, a unicellular organism, such as E. coli, B. subtilis, S. cerevisiae, insect cells in combination with baculovirus vectors, or cells of a higher organism such as vertebrates, e.g., COS 7 cells, HEK 293, CHO, Xenopus oocytes, etc., may be used as the expression host cells. In some situations, it is desirable to express the gene in eukaryotic cells, where the expressed protein will benefit from native folding and post-transitional modifications. Small peptides also can be synthesized in the laboratory. Polypeptides that are subsets of the complete protein sequence may be used to identify and investigate parts of the protein important for function. Specific expression systems of interest include bacterial-, yeast-, insect cell- and mammalian cell-derived expression systems. References drawn to representative systems from each of these categories are provided below. Expression systems in bacteria include those described in Chang et al., Nature 275:615 (1978); Goeddel et al., Nature 281:544 (1979); Goeddel et al., Nucleic Acids Res. 8:4057 (1980); EP 0 036,776; U.S. Pat. No. 4,551,433; DeBoer et al., Proc. Natl. Acad. Sci. (USA) 80:21-25 (1983); and Siebenlist et al., Cell 20:269 (1980). Expression systems in yeast include those described in Hinnen et al., Proc. Natl. Acad. Sci. (USA) 75:1929 (1978); Ito et al., J. Bacteriol. 153:163 (1983); Kurtz et al., Mol. Cell Biol. 6:142 (1986); Kunze et al., J. Basic Microbiol. 25:141 (1985); Gleeson et al., J. Gen. Microbiol. 132:3459 (1986); Roggenkamp et al., Mol. Gen. Genet. 202:302; (1986); Das et al., J. Bacteriol. 158:1165 (1984); De Louvencourt et al., J. Bacteriol. 154:737 (1983); Van den Berg et al., Bio/Technology 8:135 (1990); Kunze et al., J. Basic Microbiol. 25:141 (1985); Cregg et al., Mol. Cell. Biol. 5:3376 (1985); U.S. Pat. Nos. 4,837,148 and 4,929,555; Beach and Nurse, Nature 300:706 (1981); Davidow et al., Curr. Genet. 10:380 (1985); Gaillardin et al., Curr. Genet. 10:49 (1985); Ballance et al., Biochem. Biophvs. Res. Commun. 112:284-289 (1983); Tilburn et al., Gene 26:205-221 (1983); Yelton et al., Proc. Nati. Acad. Sci. (81:1470-1474 (1984); Kelly and Hynes, EMBO J. 4:475479 (1985); EP 0 244, 234: and WO 91/00357. Expression of heterologous genes in insects is accomplished as described in U.S. Pat. No. 4,745,051; Friesen et al., “The Regulation of Baculovirus Gene Expression”, in: The Molecular Biology of Baculoviruses (W. Doerfler, ed.) (1986); EP 0 127,839; EP 0 155,476; and VIak et al., J. Gen. Virol. 69:765-776 (1988); Miller et al., Ann. Rev. Microbiol. 42:177 (1988); Carbonell et al., Gene 73:409 (1988); Maeda et al., Nature 315:592-594 (1985); Labacq-Verheyden et al., Mol. Cell. Biol. 8:3129 (1988); Smith et al., Proc. Natl. Acad. Sci. 82:8844 (1985); Miyajima et al., Gene 58:273 (1987); and Martin et al., DNA 7:99 (1988). Numerous baculoviral strains and variants and corresponding permissive insect host cells from hosts are described in Luckow et al., Bio/Technology 6:47-55 (1988); Miller et al., Genetic Engineering 8:277-279 (1986); and Maeda et al., Nature 315:592-594 (1985). Mammalian expression is accomplished as described in Dijkema et al., EMBO J. 4:761 (1985), Gorman et al., Proc. Natl. Acad. Sci. (USA) 79:6777 (1982); Boshart et al., Cell 41:521 (1985); and U.S. Pat. No. 4,399,216. Other features of mammalian expression are facilitated as described in Hamm and Wallace, Meth. Enz. 58:44 (1979); Barnes and Sata, Anal. Biochem. 102:255 (1980); U.S. Pat. Nos. 4,767,704; 4,657,866; 4,927,762; 4,560,655; WO 90/103430; WO 87/00195, and U.S. Pat. RE No. 30,985. When any of the above-referenced host cells, or other appropriate host cells or organisms are used to replicate and/or express the polynucleotides or nucleic acids of the invention, the resulting replicated nucleic acid, RNA, expressed protein or polypeptide is within the scope of the invention as a product of the host cell or organism. The product may be recovered by an appropriate means known in the art. Once the gene corresponding to a selected polynucleotide is identified, its expression can be regulated in the cell to which the gene is native. For example, an endogenous gene of a cell can be regulated by an exogenous regulatory sequence inserted into the genonie of the cell at location sufficient to at least enhance expression of the gene in the cell. The regulatory sequence may be designed to integrate into the genome via homologous recombination, as disclosed in U.S. Pat. Nos. 5,641,670 and 5,733,761, the disclosures of which are herein incorporated by reference, or may be designed to integrate into the genome via non-homologous recombination, as described in WO 99/15650, the disclosure of which also is herein incorporated by reference. As such, also encompassed in the present invention is the production of proteins without manipulation of the encoding nucleic acid itself, but instead through integration of a regulatory sequence into the genome of cell that already includes a gene encoding the desired protein. Also of interest are promoter sequences of the genomic sequences of the present invention, where the sequence of the 5′ flanking region may be utilized for promoter elements, including enhancer binding sites, that, for example, provide for regulation of expression in cells/tissues where the subject proteins gene are expressed. Also provided are small DNA fragments of the subject nucleic acids, that are useful as primers for PCR, hybridization screening probes, etc. Larger DNA fragments are useful for production of the encoded polypeptide, as described previously. However, for use in geometric amplification reactions, such as geometric PCR, a pair of small DNA fragments, i.e., primers, will be used. The exact composition of the primer sequences is not critical to the invention, but for most applications, the primers will hybridize to the subject sequence under stringent conditions, as is known in the art. It is preferable to choose a pair of primers that will generate an amplification product of at least about 50 nucleotides, preferably at least about 100 nucleotides. Algorithms for the selection of primer sequences are generally known, and are available in commercial software packages. Amplification primers hybridize to complementary strands of DNA and will prime toward each other. The nucleic acid compositions of the present invention also may be used to identify expression of a gene in a biological specimen. The manner in which one probes cells for the presence of particular nucleotide sequences, such as genomic DNA or RNA, is well established in the art. Briefly, DNA or mRNA is isolated from a cell sample. The mRNA may be amplified by RT-PCR, using reverse transcriptase to form a complementary DNA strand, followed by polymerase chain reaction amplification using primers specific for the subject DNA sequences. Alternatively, the mRNA sample is separated by gel electrophoresis, transferred to a suitable support, e.g., nitrocellulose, nylon, etc., and then probed with a fragment of the subject DNA as a probe. Other techniques, such as oligonucleotide ligation assays, in situ hybridizations, and hybridization to DNA probes arrayed on a solid chip may also be used. Detection of mRNA hybridizing to the subject sequence is indicative of gene expression in the sample. The subject nucleic acids, including flanking promoter regions and coding regions, may be mutated in various ways known in the art to generate targeted changes in promoter strength or to vary the sequence of the encoded protein or properties of the encoded protein, including the fluorescent properties of the encoded protein. The DNA sequence or protein product of such a mutation will be substantially similar to SEQ ID NOS. 1-24 provided herein. The sequence changes of these sequences may be substitutions, insertions, deletions, or a combination thereof. Deletions may further include large changes, such as deletions of a domain or exon, e.g., of stretches of 10, 20, 50, 75, 100, 150 or more amino acid residues. Techniques for in vitro mutagenesis may be found in Gustin et al., Biotechniques 14;22 (1993); Barany, Gene 37:111-23 (1985); and Colicelli et al., Mol. Gen. Genet. 199:537-9 (1985). Methods for site-specific mutagenesis can be found in Sambrook et al., Molecular Cloning: A Laboratory Manual, CSH Press, pp. 15.3-15.108 (1989). Such mutated nucleic acid derivatives may be used to study structure-function relationships of a particular chromogenic fluorescent protein, or to alter properties of the protein that affect its function or regulation. Also of interest are humanized versions of the subject nucleic acids such as the hG22 mutant of acGFP described herein. As used herein, the term “humanized” refers to changes made to the nucleic acid sequence to optimize the codons for expression of the protein in human cells (Yang et al., Nucleic Acids Research 24:4592-93 (1996)). See also U.S. Pat. No. 5,795,737 which describes humanization of proteins, the disclosure of which is herein incorporated by reference. Peptide Compositions The subject invention provides fluorescent protein acGFP and derivatives thereof, as well as related polypeptide fragments. As used herein, the term fluorescent protein refers to any protein that fluoresces when irradiated with light, e.g., white light or light of a specific wavelength (or a narrow band of wavelengths such as an excitation wavelength). The term polypeptide as used herein refers to both full-length proteins, as well as portions or fragments of proteins. Also included in this term are variations of a naturally occurring protein, where such variations are homologous or substantially similar to the naturally occurring protein, and mutants of the naturally occurring proteins, as described in greater detail below. The subject polypeptides are present in environments other than their natural environment. In many embodiments, the subject proteins have an absorbance maximum ranging from about 300 nm to 700 nm, usually from about 350 nm to 550 nm and more usually from about 400 to 500 nm, and often from about 450 to 490 nm, e.g., 470 to 490 nm while the emission spectra of the subject proteins typically ranges from about 400 nm to 700 nm, usually from about 450 nm to 650 nm and more usually from about 500 to 600 nm while in many embodiments the emission spectra ranges from about 500 to 550 nm, e.g., 500 to 525 nm, or 500 to 510 nm. The subject proteins generally have a maximum extinction coefficient that ranges from about 25,000 to 150,000 and usually from about 45,000 to 120,000, e.g., 50,000 to 100,000. The subject proteins typically range in length from about 150 to 300 amino acids and usually from about 200 to 300 amino acid residues, and generally have a molecular weight ranging from about 15 to 35 kDa, usually from about 17.5 to 32.5 kDa. In certain embodiments, the subject proteins are bright, where “bright” is meant that the chromoproteins and their fluorescent derivatives can be detected by common methods (e.g., visual screening, spectrophotometry, spectrofluorometry, fluorescent microscopy, by FACS instrumentation, etc.). Fluorescence brightness of a particular fluorescent protein is determined by its quantum yield multiplied by maximal extinction coefficient. Brightness of a chromoprotein may be expressed by its maximal extinction coefficient. In certain embodiments, the subject proteins fold rapidly following expression in the host cell. “Rapidly folding” means that the proteins achieve the tertiary structure that gives rise to their chromogenic or fluorescent quality in a short period of time. In these embodiments, the proteins fold in a period of time that generally does not exceed about 3 days, usually does not exceed about 2 days and more usually does not exceed about 1 day. Specific proteins of interest include the wild type acGFP fluorescent protein and mutants thereof, as provided, for example, in SEQ ID NO: 02, 04, 06, 08, 10, 12, 14, 16, 18, 20, 22, or 24 coding for acGFP, Z1, Z2, G1, G2, G22, G22-G22E, G22-G22E/Y220L, 220-II-5, CFP-rand3 and CFP-3 and humanized G22. Homologs of proteins (or fragments thereof) that vary in sequence from the above-provided specific amino acid sequences, i.e., SEQ ID NO: 02, 04, 06, 08, 10, 12, 14, 16, 18, 20, 22, or 24, are also provided. “Homolog” means a protein having at least about 35%, usually at least about 40% and more usually at least about 60% amino acid sequence identity to amino acid sequences SEQ ID NO: 02, 04, 06, 08, 10, 12, 14, 16, 18, 20, 22, or 24, as determined using MegAlign, DNAstar clustal algorithm as described in D. G. Higgins and P. M. Sharp, “Fast and Sensitive multiple Sequence Alignments on a Microcomputer,” CABIOS, 5 pp. 151-3 (1989) (using parameters ktuple 1, gap penalty 3, window 5 and diagonals saved 5). In many embodiments, homologs of interest have much higher sequence identity e.g., 65%, 70%, 75%, 80%, 85%, 90% (e.g., 92%, 93%, 94%) or higher, e.g., 95%, 96%, 97%, 98%, 99%, 99.5%, particularly for the sequence of the amino acids that provide the functional regions of the protein. Also provided are proteins that are substantially identical to the wild type protein, where “substantially identical” means that the protein has an amino acid sequence identity to the sequence of wild type protein of at least about 60%, usually at least about 65%, and more usually at least about 70%, and in some instances the identity may be much higher, e.g., 75%, 80%, 85%, 90% (e.g., 92%, 93%, 94%), 95% or higher, e.g., 95%, 96%, 97%, 98%, 99%, 99.5%. Proteins that are derivatives or mutants of the above-described naturally occurring proteins are also provided. Mutants may retain biological properties of the wild type (e.g., naturally occurring) proteins, or may have biological properties which differ from the wild type proteins. The term “biological property” of the proteins of the present invention refers to, but is not limited to, spectral properties, such as absorbance maximum, emission maximum, maximum extinction coefficient, brightness (e.g., as compared to the wild type protein or another reference protein such as green fluorescent protein (GFP) from A. Victoria), and the like; in vivo and/or in vitro stability (e.g., half-life); and other such properties. Mutations include single amino acid changes, deletions of one or more amino acids, N-terminal truncations, C-terminal truncations, insertions, and the like. Mutant proteins can be generated using standard techniques of molecular biology, e.g., random mutagenesis, and targeted mutagenesis as described earlier. Several mutants are described herein. Given the guidance provided in the Example, and using standard techniques, those skilled in the art can readily generate a wide variety of additional mutants and test whether a biological property has been altered. For example, fluorescence intensity can be measured using a spectrophotometer at various excitation wavelengths. Those proteins of the subject invention that are naturally-occurring proteins are present in a non-naturally occurring environment, e.g., are separated from their naturally-occurring environment. In certain embodiments, the subject proteins are present in a composition that is enriched for the subject protein as compared to its naturally-occurring environment. For example, purified protein is provided, where “purified” means that the protein is present in a composition that is substantially free of non-chromogenic or fluorescent proteins of interest, where “substantially free” means that less than 90%, usually less than 60% and more usually less than 50% of the composition is made up of non-chromogenic or fluorescent proteins or mutants thereof. The proteins of the present invention also may be present as an isolate, by which is meant that the protein is substantially free of other proteins and other naturally-occurring biological molecules, such as oligosaccharides, polynucleotides and fragments thereof, and the like, where the term “substantially free” in this instance means that less than 70%, usually less than 60% and more usually less than 50% of the composition containing the isolated protein is some other natural occurring biological molecule. In certain embodiments, the proteins are present in substantially pure form, where by “substantially pure form” means at least 95%, usually at least 97% and more usually at least 99% pure. In addition to the naturally-occurring proteins, polypeptides that vary from the naturally occurring proteins, e.g., the mutant proteins described above, are also provided. Generally such polypeptides include an amino acid sequence encoded by an open reading frame (ORF) of the gene encoding the subject wild type protein, including the full length protein and fragments thereof, particularly biologically active fragments and/or fragments corresponding to functional domains, and the like; including fusions of the subject polypeptides to other proteins or peptides. Fragments of interest will typically be at least about 10 amino acids in length, usually at least about 50 amino acids in length, and may be as long as 300 amino acids in length or longer, but will usually not exceed about 250 amino acids in length, where the fragment will have a stretch of amino acids that is identical to the subject protein of at least about 10 amino acids, and usually at least about 15 amino acids, and in many embodiments at least about 50 amino acids in length. In some embodiments, the subject polypeptides are about 25 amino acids, about 50, about 75, about 100, about 125, about 150, about 200, or about 250 amino acids in length, up to the entire length of the protein. In some embodiments, a protein fragment retains all or substantially all of the specific property of the wild type protein. The subject proteins and polypeptides may be obtained from naturally-occurring sources or synthetically produced. For example, wild type proteins may be derived from biological sources which express the proteins, e.g., Aequorea coerulescens the subject proteins may also be derived from synthetic means, for example, by expressing a recombinant gene or nucleic acid coding sequence encoding the protein of interest in a suitable host, as described above. Any convenient protein purification procedures may be employed, where suitable protein purification methodologies are described in Guide to Protein Purification, (Deuthser ed.) (Academic Press, 1990). For example, a lysate may be prepared from the original source and purified using HPLC, exclusion chromatography, gel electrophoresis, affinity chromatography, and the like. Antibody Compositions Also provided are antibodies that bind specifically to the fluorescent proteins of the present invention. Suitable antibodies are obtained by immunizing a host animal with peptides comprising all or a portion of the protein. Suitable host animals include mice, rats, sheep, goats, hamsters, rabbits, and others. The immunogen may comprise the complete protein, or fragments and derivatives thereof. Preferred immunogens comprise all or a part of the protein, where the protein includes post-translation modifications found on the native target protein. Immunogens are produced in a variety of ways known in the art, for example, expression of cloned genes using conventional recombinant methods, or isolation directly from Aequorea coerulscens. For preparation of polyclonal antibodies, the first step involves immunization of the host animal with the peptide immunogen, where the peptide protein immunogen preferably will be in substantially pure form, comprising less than about 1% contaminant. The immunogen may comprise a complete protein, or fragments or derivatives thereof. To increase the immune response of the host animal, the target protein may be combined with an adjuvant, where suitable adjuvants include alum, dextran, sulfate, large polymeric anions, oil and water emulsions, Freund's adjuvant, Freund's complete adjuvant, and the like. The peptide immunogen also may be conjugated to synthetic carrier proteins or synthetic antigens. The peptide immunogen is administered to the host, usually intradermally, with an initial dosage followed by one or more, usually at least two, additional booster dosages. Following immunization, the blood from the host will be collected where the blood serum is separated from the blood cells. The immunoglobulin present in the resultant antiserum may be purified using known methods, such as ammonium salt fractionation, DEAE chromatography, and the like. Alternatively, monoclonal antibodies may be produced by conventional techniques. Generally, the spleen and/or lymph nodes of an immunized host animal provide a source of plasma cells. The plasma cells are immortalized by fusion with myeloma cells to produce hybridoma cells. Culture supernatant from individual hybridomas is screened using standard techniques to identify those producing antibodies with the desired specificity. Suitable animals for production of monoclonal antibodies to the human protein include mice, rats, hamsters and the like. To raise antibodies against the mouse protein, the animal will generally be a hamster, guinea pig, or rabbit. The antibody may be purified from the hybridoma cell supernatants or ascites fluid by conventional techniques, such as affinity chromatography using protein bound to an insoluble support like protein A sepharose. The antibody may be produced as a single chain, instead of the normal multimeric structure. Single chain antibodies are described in Jost et al., J.B.C. 269:26267-73 (1994), and others. DNA sequences encoding the variable region of the heavy chain and the variable region of the light chain may be ligated to a spacer encoding at least about 4 amino acids of small neutral amino acids, including glycine and/or serine. The protein encoded by this fusion allows assembly of a functional variable region that retains the specificity and affinity of the original antibody. Also of interest in certain embodiments are humanized antibodies. Methods of humanizing antibodies are known in the art. The humanized antibody may be the product of an animal having transgenic human immunoglobulin constant region genes (see for example International Patent Applications WO 90/10077 and WO 90/04036). Alternatively, the antibody of interest may be engineered by recombinant DNA techniques to substitute the CH1, CH2, CH3, hinge domains, and/or the framework domain with the corresponding human sequence (see WO 92/02190). The use of immunoglobulin cDNA for construction of chimeric immunoglobulin genes is known in the art (Liu et al., Proceedings of the National Academy of Sciences 84:3439 (1987) and J. Immunol. 139:3521 (1987)). Essentially, mRNA is isolated from a hybridoma or other cell producing the antibody and used to produce cDNA. The cDNA of interest may be amplified by the polymerase chain reaction using specific primers (U.S. Pat. Nos. 4,683,195 and 4,683,202). Alternatively, a library is made and screened to isolate the sequence of interest. The DNA sequence encoding the variable region of the antibody is then fused to human constant region sequences. The sequences of human constant regions genes may be found in Kabat et al., “Sequences of Proteins of Immunological Interest”, N.I.H. publication no. 91-3242 (1991). Human C region genes are readily available from known clones. The choice of isotype will be guided by the desired effector functions, such as complement fixation, or activity in antibody-dependent cellular cytotoxicity. Preferred isotopes are IgG1, IgG3 and IgG4. Either of the human light chain constant regions, kappa or lambda, may be used. The chimeric, humanized antibody is then expressed by conventional methods. Antibody fragments, such as Fv, F(ab′)2 and Fab may be prepared by cleavage of the intact protein, for example, by a protease or lay chemical cleavage. Alternatively, a truncated gene may be designed. For example, a chimeric gene encoding a portion of the F(ab′)2 fragment would indicate DNA sequences encoding the CH1 domain and hinge region of the H chain, followed by a translational stop codon to yield the truncated molecule. Consensus sequences of H and L J regions may be used to design oligonucleotides for use as primers to introduce useful restriction sites into the J region for subsequent linkage of V region segments to human C region segments. C region cDNA can be modified by site directed mutagenesis to place a restriction site at the analogous position in the human sequence. Expression vectors include plasmids, retroviruses, YACs, EBV-derived episomes, and the like. A convenient vector is one that encodes a functionally complete human CH or CL immunoglobulin sequence, with appropriate restriction sites engineered so that any VH or VL sequence can be easily inserted and expressed. In such vectors, splicing usually occurs between the splice donor site in the inserted J region and the splice acceptor site preceding the human C region, and also at the splice regions that occur within the human CH exons. Polyadenylation and transcription termination occur at native chromosomal sites downstream of the coding regions. The resulting chimeric antibody may be joined to any strong promoter, including retroviral LTRs, such as the SV40 early promoter, (Okayama et al., Mol. Cell. Bio. 3:280 (1983)); Rous sarcoma virus LTR (Gorman et al., Proceedings of the National Academy of Sciences. 79:6777 (1982)); or moloney murine leukemia virus LTR (Grosschedl et al., Cell 41:885 (1985)); or native lg promoters etc. Transgenics The nucleic acids of the present invention can be used to generate transgenic, non-human plants or animals or site-specific gene modifications in cell lines. Transgenic cells of the subject invention include one or more nucleic acids according to the subject invention present as a transgene, where included within this definition are the parent cells transformed to include the transgene and the progeny thereof. In many embodiments, the transgenic cells are cells that do not normally harbor or contain a nucleic acid according to the present invention. In those embodiments where the transgenic cells do naturally contain the subject nucleic acids, the nucleic acid will be present in the cell in a position other than its natural location, such as being integrated into the genomic material of the cell at a non-natural location. Transgenic animals may be made through homologous recombination, where the endogenous locus is altered. Alternatively, a nucleic acid construct is randomly integrated into the genome. Vectors for stable integration include plasmids, retroviruses and other animal viruses, YACs, and the like. Transgenic organisms of interest include cells and multicellular organisms, both plants and animals, in which the protein or variants thereof is expressed in cells or tissues where it is not normally expressed and/or at levels not normally present in such cells or tissues. DNA constructs for homologous recombination will comprise at least a portion of a nucleic acid of the present invention, wherein the gene has the desired genetic modification(s), and includes regions of homology to the target locus. DNA constructs for random integration need not include regions of homology to mediate recombination. Conveniently, markers for positive and negative selection may be included. Methods for generating cells having targeted gene modifications through homologous recombination are known in the art. For various techniques for transfecting mammalian cells, see Keown et al., Meth. Enzymol. 185:527-37 (1990). For embryonic stem (ES) cells, an ES cell line may be employed, or embryonic cells may be obtained freshly from a host, such as a mouse, rat, guinea pig, etc. Such cells are grown on an appropriate fibroblast-feeder layer or grown in the presence of leukemia inhibiting factor (LIF). When ES or embryonic cells have been transformed, they may be used to produce transgenic animals. After transformation, the cells are plated onto a feeder layer in an appropriate medium. Cells containing the construct may be detected by employing a selective medium. After sufficient time is given for colonies to grow, the colonies are picked and analyzed for the occurrence of homologous recombination or integration of the construct. Those colonies that are positive may then be used for embryo manipulation and blastocyst injection. Blastocysts are obtained from 4- to 6-week old superovulated females. The ES cells are trypsinized, and the modified cells are injected into the blastocoel of the blastocyst. After injection, the blastocysts are returned to each uterine horn of pseudopregnant females. Females are then allowed to go to term and the resulting offspring are screened for the construct. Chimeric progeny can be readily detected if the phenotype of transformed cells differs in some way from the naturally occurring cells (such as exhibiting fluroescence). The chimeric animals are screened for the presence of the modified gene and males and females having the modification are mated to produce homozygous progeny. If the gene alterations cause lethality at some point in development, as is possible particularly with the fusion proteins of the present invention, tissues or organs can be maintained as allogeneic or congenic grafts or transplants, or in in vitro culture. The transgenic animals may be any non-human mammal, such as laboratory animals, domestic animals, etc., and used in functional studies, drug screening and the like. Representative examples of the use of transgenic animals include those described infra. Transgenic plants also may be produced. Methods of preparing transgenic plant cells and plants are described in U.S. Pat. Nos. 5,767,367; 5,750,870; 5,739,409; 5,689,049; 5,689,045; 5,674,731; 5,656,466; 5,633,155; 5,629,470; 5,595,896; 5,576,198; 5,538,879; 5,484,956; the disclosures of which are herein incorporated by reference. Methods of producing transgenic plants also are reviewed in Plant Biochemistry and Molecular Biology (eds. Lea and Leegood, John Wiley & Sons) pp. 275-295 (1993). In brief, a suitable plant cell or tissue is harvested, depending on the nature of the plant species. As such, in certain instances, protoplasts will be isolated, where such protoplasts may be isolated from a variety of different plant tissues, e.g., leaf, hypocotyl, root, etc. For protoplast isolation, the harvested cells are incubated in the presence of cellulases in order to remove the cell wall, where exact incubation conditions will vary depending on the type of plant and/or tissue from which the cell is derived. The resultant protoplasts are then separated from the resultant cellular debris by sieving and centrifugation. Alternatively, embryogenic explants comprising somatic cells may be used for preparation of the transgenic host. Following cell or tissue harvesting, exogenous DNA of interest is introduced into the plant cells, where a variety of different techniques is available for such introduction. With isolated protoplasts, the opportunity arises for introduction via DNA-mediated gene transfer protocols, including incubation of the protoplasts with naked DNA, such as plasmids comprising the exogenous coding sequence of interest in the presence of polyvalent cations (for example, PEG or PLO); or electroporation of the protoplasts in the presence of naked DNA comprising the exogenous sequence of interest. Protoplasts that have successfully taken up the exogenous DNA are then selected, grown into a callus, and ultimately into a transgenic plant through contact with the appropriate amounts and ratios of stimulatory factors, such as auxins and cytokinins. With embryonic explants, a convenient method of introducing the exogenous DNA in to the target somatic cells is through the use of particle acceleration or “gene-gun” protocols. The resultant explants are then allowed to grow into chimeric plants, are cross-bred, and transgenic progeny are then obtained. Instead of the naked DNA approaches described above, another method of producing transgenic plants is via Agrobacterium-mediated transformation. With Agrobacterium-mediated transformation, co-integrative or binary vectors comprising the exogenous DNA are prepared and then introduced into an appropriate Agrobacterium strain, e.g., A. tumefaciens. The resultant bacteria are then incubated with prepared protoplasts or tissue explants, such as a leaf disk, and a callus is produced. The callus is then grown under selective conditions, selected and subjected to growth media to induce root and shoot growth to ultimately produce a transgenic plant. Methods of Use The fluorescent proteins and peptides of the present invention find use in a variety of different applications. Representative uses for each of these types of proteins will be described below, where the uses described herein are merely exemplary and are in no way meant to limit the use of the proteins of the present invention to those described. The first application of interest is the use of the subject proteins in fluorescence resonance energy transfer (FRET) methods. In these methods, the subject proteins serve as donor and/or acceptors in combination with a second fluorescent protein or dye, for example, a fluorescent protein as described in Matz et al., Nature Biotechnology 17:969-973 (1999); a green fluorescent protein from Aequorea victoria or fluorescent mutant thereof, for example, as described in U.S. Pat. Nos. 6,066,476; 6,020,192; 5,985,577; 5,976,796; 5,968,750; 5,968,738; 5,958,713; 5,919,445; 5,874,304, the disclosures of which are herein incorporated by reference; other fluorescent dyes such as coumarin and its derivatives, 7-amino-4-methylcoumarin and aminocoumarin; bodipy dyes; cascade blue; or fluorescein and its derivatives, such as fluorescein isothiocyanate and Oregon green; rhodamine dyes such as Texas red, tetramethylrhodamine, eosins and erythrosins; cyanine dyes such as Cy3 and Cy5; macrocyclic chealates of lenthaninde ions, such as quantum dye; and chemilumescent dyes such as luciferases, including those described in U.S. Pat. Nos. 5,843,746; 5,700,673; 5,674,713; 5,618,722; 5,418,155; 5,330,906; 5,229,285; 5,221,623; 5,182,202; the disclosures of which are herein incorporated by reference. Specific examples of where FRET assays employing the subject fluorescent proteins may be used include, but are not limited to, the detection of protein-protein interactions, such as in a mammalian two-hybrid system, transcription factor dimerization, membrane protein multimerization, multiprotein complex formation; as a biosensor for a number of different events, where a peptide or protein covalently links a FRET fluorescent combination including the subject fluorescent proteins and the linking peptide or protein is, for example, a protease-specific substrate for caspase-mediated cleavage, a peptide that undergoes conformational change upon receiving a signal which increases or decreases FRET, such as a PKA regulatory domain (cAMP-sensor), a phosphorylation site (for example, where there is a phosphorylation site in the peptide or the peptide has binding specificity to phosphorylated/dephosphorylated domain of another protein), or the peptide has Ca2+ binding domain. In addition, fluorescence resonance energy transfer or FRET applications in which the proteins of the present invention find use include, but are not limited to, those described in: U.S. Pat. Nos. 6,008,373; 5,998,146; 5,981,200; 5,945,526; 5,945,283; 5,911,952; 5,869,255; 5,866,336; 5,863,727; 5,728,528; 5,707,804; 5,688,648; 5,439,797; the disclosures of which are herein incorporated by reference. The subject fluorescent proteins also find use as biosensors in prokaryotic and eukaryotic cells, such as a Ca2+ ion indicator; a pH indicator; a phorphorylation indicator; or as an indicator of other ions, such as magnesium, sodium, potassium, chloride and halides. For example, for detection of Ca2+ ions, proteins containing an EF-hand motif are known to translocate from the cytosol to membranes upon Ca2+ binding. These proteins contain a myristoyl group that is buried within the molecule by hydrophobic interactions with other regions of the protein. Binding of Ca2+ induces a conformational change exposing the myristoyl group which then is available for the insertion into the lipid bilayer (called a “Ca2+ myristoyl switch”). Fusion of such a EF-hand containing protein to fluorescent proteins would make it an indicator of intracellular Ca2+ by monitoring the translocation from the cytosol to the plasma membrane by confocal microscopy. EF-hand proteins suitable for use in this system include, but are not limited to: recoverin, calcineurin B, troponin C, visinin, neurocalcin, calmodulin, parvalbumin, and the like. For indicating pH, a system based on hisactophilins may be employed. Hisactophilins are myristoylated histidine-rich proteins known to exist in Dictyostelium. Their binding to actinand acidic lipids is sharply pH-dependent within the range of cytoplasmic pH variations. In living cells, membrane binding seems to override the interaction of isactophilins with actin filaments. At pH≦6.5 they locate to the plasma membrane and nucleus. In contrast, at pH 7.5 they evenly distribute throughout the cytoplasmic space. This change of distribution is reversible and is attributed to histidine clusters exposed in loops on the surface of the molecule. The reversion of intracellular distribution in the range of cytoplasmic pH variations is in accord with a pK of 6.5 of histidine residues. The cellular distribution is independent of myristoylation of the protein. By fusing fluorescent proteins to hisactophilin, the intracellular distribution of the fusion protein can be followed by laser scanning, confocal microscopy or standard fluorescence microscopy. For such studies, quantitive fluorescence analysis can be done by performing line scans through cells (laser scanning confocal microscopy) or other electronic data analysis (e.g., using metamorph software (Universal Imaging Corp)) and averaging of data collected in a population of cells. Substantial pH-dependent redistribution of hisactophilin/fluorescent protein from the cytosol to the plasma membrane occurs within 1-2 minutes and reaches a steady state level after 5-10 minutes. The reverse reaction takes place on a similar time scale. As such, a hisactophilin-fluorescent protein fusion protein that acts in an analogous fashion can be used to monitor cytosolic pH changes in real time in live mammalian cells. Such methods have use in high throughput applications, for example, in the measurement of pH changes as a consequence of growth factor receptor activation (e.g., epithelial or platelet-derived growth factor), chemotactic stimulation/cell locomotion, in the detection of intracellular pH changes as second messenger, in the monitoring of intracellular pH in pH manipulating experiments, and the like. For detection of PKC activity, the reporter system exploits the fact that a molecule called MARCKS (myristoylated alanine-rich C kinase substrate) is a PKC substrate. MARCKS is anchored to the plasma membrane via myristoylation and a stretch of positively charged amino acids (ED-domain) that bind to the negatively-charged plasma membrane via electrostatic interactions. Upon PKC activation, the ED-domain becomes phosphorylated by PKC, thereby becoming negatively charged, and as a consequence of electrostatic repulsion MARCKS translocates from the plasma membrane to the cytoplasm (called the “myristoyl-electrostatic switch”). Fusion of the N-terminus of MARCKS from the the myristoylation motif to the ED-domain of MARCKS to the fluorescent proteins of the present invention provides a detector system for PKC activity. When phosphorylated by PKC, the fusion protein translocates from the plasma membrane to the cytosol. This translocation may be tracked by standard fluorescence microscopy or confocal microscopy, for example, by using Cellomics Inc., technology or other high content screening systems (such as those from Universal Imaging Corp., or Becton Dickinson). The above reporter system has application in high content screening for PKC inhibitors, and as an indicator for PKC activity inscreening assays for potential reagents that interfere with this signal tansduction pathway. Methods of using fluorescent proteins as biosensors also include those described in U.S. Pat. Nos. 5,972,638; 5,824,485 and 5,650,135 (as well as the references cited therein) the disclosures of which are herein incorporated by reference. The fluorescent proteins of the present invention also find use in applications involving the automated screening of arrays of cells expressing fluorescent reporting groups by using microscopic imaging and electronic analysis. Screening can be used for drug discovery and in the field of functional genomics where the subject proteins are used as markers of whole cells to detect changes in multicellular reorganization and migration, for example in the formation of multicellular tubules (blood vessel formation) by endothelial cells, migration of cells through the Fluoroblok Insert system (Becton Dickinson Co.), wound healing, or neurite outgrowth. Screening can also be employed where the proteins of the present invention are used as markers fused to peptides (such as targeting sequences) or proteins that detect changes in intracellular location as an indicator for cellular activity, for example in signal transduction, such as kinase and transcription factor translocation upon stimuli. Examples include protein kinase C, protein kinase A, transcription factor NFkB, and NFAT; cell cycle proteins, such as cyclin A, cyclin B1 and cyclin E; protease cleavage with subsequent movement of cleaved substrate; phospholipids, with markers for intracellular structures such as the endoplasmic reticulum, Golgi apparatus, mitochondria, peroxisomes, nucleus, nucleoli, plasma membrane, histones, endosomes, lysosomes, or microtubules. The proteins of the present invention also can be used in high content screening to detect co-localization of other fluorescent fusion proteins with localization markers as indicators of movements of intracellular fluorescent proteins/peptides or as markers alone. Examples of applications involving the automated screening of arrays of cells in which the subject fluorescent proteins find use include U.S. Pat. No. 5,989,835; as well as WO 0017624; WO 00/26408; WO 00/17643; and WO 00/03246; the disclosures of which are herein incorporated by reference. The fluorescent proteins of the present invention also find use in high throughput screening assays. The subject fluorescent proteins are stable proteins with half-lives of more than 24 hours. Also provided are destabilized versions of the subject fluorescent proteins with decreased half-lives that can be used as transcription reporters for drug discovery. For example, a protein according to the subject invention can be fused with a putative proteolytic signal sequence derived from a protein with shorter half-life, such as a PEST sequence from the mouse ornithine decarboxylase gene, a mouse cyclin B1 destruction box or ubiquitin, etc. For a description of destabilized proteins and vectors that can be employed to produce the same, see e.g., U.S. Pat. No. 6,130,313; the disclosure of which is herein incorporated by reference. Promoters in signal transduction pathways can be detected using destabilized versions of the subject fluorescent proteins for drug screening such as, for example, AP1, NFAT, NFkB, Smad, STAT, p53, E2F, Rb, myc, CRE, ER, GR and TRE, and the like. The proteins of the present invention can be used as photoactivated labels for precise in vivo photolabeling and following trafficking of proteins, organelles or cells as described in, for example, Patterson and Lippincoft-Scott, Science, 13:1873-77 (2002) and Ando, et al., Proc. Natl. Acad. Sci. USA, 99:12651-56 (2002). Additionally, the subject proteins can be used as second messenger detectors by fusing the subject proteins to specific domains such as the PKCgamma Ca binding domain, PKCgamma DAG binding domain, SH2 domain or SH3 domain, etc. Secreted forms of the subject proteins can be prepared by fusing secreted leading sequences to the subject proteins to construct secreted forms of the subject proteins, which in turn can be used in a variety of different applications. The subject proteins also find use in fluorescence activated cell sorting (FACS) applications. In such applications, the subject fluorescent protein is used as a label to mark a poplulation of cells and the resulting labeled population of cells is then sorted with a fluorescent activated cell sorting device, as is known in the art. FACS methods are described in U.S. Pat. Nos. 5,968,738 and 5,804,387; the disclosures of which are herein incorporated by reference. The subject proteins also find use as in vivo markers in transgenic animals. For example, expression of the subject protein can be driven by tissue-specific promoters, where such methods find use in research for gene therapy, such as testing efficiency of transgenic expression, among other applications. A representative application of fluorescent proteins in transgenic animals that illustrates such applications is found in WO 00/02997, the disclosure of which is herein incorporated by reference. Additional applications of the proteins of the present invention include use as markers following injection into cells or animals and in calibration for quantitative measurements; as markers or reporters in oxygen biosensor devices for monitoring cell viability; as markers or labels for animals, pets, toys, food, and the like. The subject fluorescent proteins also find use in protease cleavage assays. For example, cleavage-inactivated fluorescence assays can be developed using the subject proteins, where the subject proteins are engineered to include a protease-specific cleavage sequence without destroying the fluorescent character of the protein. Upon cleavage of the fluorescent protein by an activated protease, fluorescence would sharply decrease due to the destruction of the functional chromophore. Alternatively, cleavage-activated fluorescence can be developed using the proteins of the present invention where the proteins are engineered to contain an additional spacer sequence in close proximity/or inside the chromophore. This variant is significantly decreased in its fluorescent activity, because parts of the functional chromophore are divided by the spacer. The spacer is framed by two identical protease-specific cleavage sites. Upon cleavage via the activated protease, the spacer would be cut out and the two residual “subunits” of the fluorescent protein would be able to reassemble to generate a functional fluorescent protein. Both of the above applications could be developed in assays for a variety of different types of proteases, such as caspases and others. The subject proteins also can be used in assays to determine the phospholipid composition in biological membranes. For example, fusion proteins of the subject proteins (or any other kind of covalent or non-covalent modification of the subject proteins) that allows binding to specific phospholipids to localize/visualize patterns of phospholipid distribution in biological membranes, while allowing co-localization of membrane proteins in specific phospholipid rafts, can be accomplished with the subject proteins. For example, the PH domain of GRP1 has a high affinity to phosphatidyl-inositol tri-phosphate (PIP3) but not to PIP2. As such, a fusion protein between the PH domain of GRP1 and the subject proteins can be constructed to specifically label PIP3-rich areas in biological membranes. Yet another application of the subject proteins is as a fluorescent timer, in which the switch of one fluorescent color to another (e.g., green to red) concomitant with the aging of the fluorescent protein is used to determine the activation/deactivation of gene expression, such as developmental gene expression, cell cycle-dependent gene expression, circadian rhythm-specific gene expression, and the like. The antibodies of the subject invention, described above, also find use in a number of applications, including the differentiation of the subject proteins from other fluorescent proteins. Kits Also provided by the present invention are kits for use in practicing one or more of the above-described applications, where the kits typically include elements for expressing the subject proteins, for example, a construct comprising a vector that includes a coding region for the subject protein. The kit components are typically present in a suitable storage medium, such as a buffered solution, typically in a suitable container. Also present in the kits may be antibodies to the provided protein. In certain embodiments, the kit comprises a plurality of different vectors each encoding the subject protein, where the vectors are designed for expression in different environments and/or under different conditions, for example, constitutive expression where the vector includes a strong promoter for expression in mammalian cells or a promoterless vector with a multiple cloning site for custom insertion of a promoter and tailored expression, etc. In addition to the above components, the subject kits will further include instructions for practicing the subject methods. These instructions may be present in the subject kits in a variety of forms, one or more of which may be present in the kit. One form in which these instructions may be present is as printed information included in the packaging of the kit, such as a package insert. Yet another means would be a computer readable medium, e.g., diskette, CD, etc., on which the information has been recorded. Yet another means that may be present is a website address which may be used to access the information at a removed site via the internet. Any convenient means may be present in the kits. The following example is offered by way of illustration and not by way of limitation. EXAMPLE Several specimens of large hydromedusa were collected at the Russian coast of the Japan Sea near Vladivostok in August 2001. A set of characteristic features permits identification of these medusae as Aequorea coerulescens (Kramp, Dana Rept.,72:201-202 (1968); Pogodin and Yakovlev, Rus. J. Mar. Biol., 25:417-419 (1999)). Although A. coerulecens and A. Victoria (synonyms of A. forscalea, A. aequorea) are similar, some of their features are very different. The most obvious difference is the number of tentacles: A. victoria carries only one tentacle per radial channel while A. coeruilescens possesses 4-6 tentacles between each pair of adjacent radial channels. The A. coerulescens specimens caught were bioluminescent. In contrast to A. Victoria, they displayed a blue rather than green luminescence. No detectable fluorescence was observed in the A. coerulescens medusae in UV light or when using a fluorescent microscope. Nevertheless, a monoclonal antibody against A. Victoria GFP detected a GFP-like protein in the protein extract from A. coerulescens. FIG. 11 shows a protein gel-electrophoresis analysis of acGFP. FIG. 11 a is a Western blot analysis of soluble protein extract from A. coerulescens using antibodies against A. victoria GFP. Lane 1 is purified recombinant A. Victoria GFP, Lane 2 is the A. coerulescens extract. To clone the GFP-like protein, PCR was performed with degenerative primers corresponding to conservative amino acid sequences. A cDNA encoding a GFP-like protein was cloned. The nucleotide and amino acid sequence of the wildtype acGFP protein is shown in FIG. 1. The acGFP protein demonstrated very high similarity to GFP, having a 92% amino acid sequence similarity; see FIG. 2. All known key residues, including the chromophore-forming Ser65, Tyr66 and Gly67, the evolutionary invariant Arg96 and Glu222, and the residues spatially proximate to the chromophore, His148, Phe165, Ile167 and Thr203 were found unchanged in acGFP. Only three interior amino acids differed between these proteins. Taking into account the very high sequence similarity, it was expected that the spectral properties of acGFP would be very similar to that of GFP. Nevertheless, E. coli colonies expressing acGFP showed neither fluorescence nor coloration. The most simple explanation of this fact—unsatisfactory acGFP folding in E. coli—was only partially correct, as was demonstrated in further experiments. The presence of acGFP cDNA in various parts of the medusa was tested by PCR using specific primers. Three cDNA samples corresponding to the umbrella border, radial channel, and oral disc of the medusa were tested. AcGFP cDNA was clearly detected in the umbrella border but was absent in two other samples. Thus, distribution of acGFP within the A. coerulescens is similar to the distribution of GFP in A. victoria, which forms a fluorescent ring in A. victoria umbrella border. Random mutagenesis of acGFP produced many green fluorescent clones, some of which were characterized. Their properties and possible applications are similar to those for the enhanced GFP (EGFP) mutant of A. victoria. Mutant Z1 contained one amino acid substitution, E222G (a glycine for a glutamic acid at position 222), as seen in FIG. 3. The mutant Z1 protein possessed low brightness, very slow folding and required a temperature of less than 20° C. for maturation. After growth at 30° C., E. coli colonies expressing Z1 must be stored for 3-5 days at room temperature or at 4° C. for the fluorescence to become visible. Excitation and emission spectra for the Z1 mutant have maxima at 480 and 504 nm, respectively (see FIG. 4). Mutant Z2 contained two amino acid substitutions, specifically, N19D (an aspartic acid for an asparagine at position 19) and E222G (a glycine for a glutamic acid at position 222) as seen in FIG. 5. The mutant Z2 possessed low brightness, very slow folding efficiency and required a temperature of less than 20° C. for maturation. After overnight growth at 37° C., E. coli colonies expressing Z2 must be stored for 3-5 days at room temperature or at 4° C. for the fluorescence to become visible. Excitation and emission spectra for the Z2 mutant are very similar to those of the mutant Z1. Mutant G1 has substitutions V11I (an isoleucine for a valine at position 11), K101E (a glutamic acid for a lysine at position 101), and E222G (a glycine for a glutamic acid at position 222) as seen in FIG. 6. Mutant G1 was generated in an independent round of random mutagenesis. Since substitution E222G was found in three of the mutants, it seemed likely that this mutation was important for the green fluorescence of these mutants. Mutant G1 possesses rather low brightness. Fluorescence of this mutant becomes visible on the first day after overnight growth of the E. coli. The excitation and emission spectra of mutant G1 are very similar to those of the mutant Z1. Mutant G2 has substitutions V11I (an isoleucine for a valine at position 11), F64L (a leucine for a phenylalamine at position 6A), K101E (a glutamic acid for a lysine at position 101), and E222G (a glycine for a glutamic acid at position 222) as seen in FIG. 7. Mutant G2 was generated based on mutant G1 using a second round of random mutagenesis. In comparison to G1, the G2 mutant protein possesses improved brightness and protein folding rate characteristics. Interestingly, G2 contains the substitution F64L that is also characteristic for enhanced GFP (EGFP) (Cormack et al., Gene, 173:33-38 (1996); Yang et al., Nuc. Acids Res., 24:45924593 (1996)). Spectral properties of G2 are shown in Table 1, infra. The excitation-emission spectra for G2 are shown in FIG. 8. Mutant G22 has substitutions V11I (an isoleucine for a valine at position 11), F64L (a leucine for phenylalmine at position 64), K101E (a glutamic acid for a lysine at position 101), T206A (an alanine for a threonine at position 206), and E222G (a glycine for a glutamic acid at position 222) as seen in FIG. 9. Mutant G22 was generated from mutant G2 using a third round of random mutagenesis. In comparison to G2, G22 possesses even greater improved brightness. The spectral properties of G22 are reported in Table 1. The excitation-emission spectra for G22 are shown in FIG. 10. An extinction coefficient of 50,000 M−1 cm−1 and a quantum yield of 0.55 make this protein nearly as bright as the widely used enhanced GFP. Gel-filtration tests as well as SDS-PAGE of the non-heated mutant G22 protein demonstrated that G22 is monomeric. FIG. 11B compares the mobility of heated (lanes 1-3) versus non-heated (lanes 4-6) protein samples. Lanes 1 and 4 are A. victoria GFP, lanes 2 and 5 are the G22 mutant, and lanes 3 and 6 are the G22-G222E mutant. Coomassie blue staining is shown on the left and fluorescence of the non-heated proteins under UV light is shown on the right. All of the fluorescent mutants of acGFP mentioned above have similar excitation and emission spectra, peaking at 470-480 nm and 500-510 nm, respectively. The shape of their excitation spectra are similar to that of enhanced GFP, but not wild type A. victoria GFP. It is likely that the fluorophore of the acGFP mutants is always in a deprotonated form, as it has been shown to be for enhanced GFP. A possible explanation is absence of Glu222, which may likely be important for proton transfer (Ehrig et al., FEBS Lett., 367:163-166 (1995)). To clarify the importance of the E222G substitution for fluorescence, a reverse G222E substitution was made to the mutant G22 (substitutions V11I, F64L, K101E, T206A). The nucleic acid and amino acid sequences of this reverse mutant G22-E222G is shown in FIG. 12. The reverse mutation readily transformed the G22-E222G mutant protein into a colorless state. E. coli colonies expressing G22-G222E displayed neither coloration nor detectable fluorescence. G22-G222E was expressed and folded in E. coli at 37° C. without a problem, as evidenced by the high yield of the soluble recombinant protein (about 20% of total proteins). Purified G22-G222E displayed an absorption spectrum with a major peak at 280 nm and a minor peak at 390 nm (see FIG. 13A). Alkali-denatured G22-G222E protein showed absorption peak at 446 nm that apparently corresponds to the anionic form of the GFP chromophore. Assuming an extinction coefficient 44,000 M−1 cm−1 for the chromophore, the extinction of native G22-G222E at 390 nm was estimated to be 33,000 M−1 cm−1. The observed ratio between the 280-nm and 390-nm peaks (molar extinction coefficient at 280 nm was calculated to be 23,500 M−1 cm−1) showed that only about 3% of soluble G22-G222E existed in a mature form. Excitation at 390 nm led to a weak dual-color fluorescence peaking at 460 nm and 505 nm with a quantum yield of 0.07 (see FIG. 13B). It is well-known that GFP-like proteins retain their spectral properties and oligomerization state under conditions of common SDS-PAGE as long as the protein samples are not heated before being loading onto the gel. This test was used to examine the folding state of G22-G222E. Gel-electrophoresis demonstrated a clear difference in the mobility of non-denatured and denatured proteins (see FIG. 11). In addition, the non-heated G22-G222E protein band produced very weak fluorescence under UV light (again, see FIG. 11). As about 97% of this protein is present in a non-absorbing form, these results indicate that the conformation of this non-absorbing form is close to the native state, but not to the denatured state. Encouraged by these results, the attempts to obtain and characterize the recombinant wild type acGFP were repeated. Growth of E. coli expressing acGFP at room temperature without induction, followed by a several days incubation at 4° C., resulted in the appearance of a small fraction of soluble acGFP (about 5% of total acGFP). Shapes of the absorption and fluorescence spectra for the soluble wild type acGFP were very similar to that of G22-G222E. It was concluded that G22-G222E mutant mirrors the properties of the natural acGFP but possesses improved protein folding and temperature stability when expressed in E. coli. These data showed that soluble G22-G222E as well as the wild type acGFP exists in two forms. The majority of these proteins are present in a folded but immature form without a spectrally-detectable chromophore. The minor 390 nm-absorbing form contains a GFP-like chromophore in a neutral state and possesses weak dual-color fluorescence. A novel type of photoconversion was observed in mutant G22-G222E. Irradiation of a G22-G222E protein sample with 250-300 nm UV light resulted in the appearance of a 480 nm peak in the absorption/excitation spectra. Note in FIG. 14 the excitation spectrum of G22-G222E before irradiation (line1) and the gradual change of the curve due to irradiation of the protein sample with light at 250-300 nm. The unnumbered line represents the emission spectrum after photoconversion (excitation at 480 nm). This may originate from an immature, spectrally undetectable form of the protein, as the 390 nm absorption peak did not decrease during this photoconversion. Excitation at the 480 nm peak produced green fluorescence at 505 nm with a high quantum yield (0.45). A greater than 1000-fold UV-induced enhancement of green fluorescence intensity was achieved (excitation at 480 nm). Mutant G22-G222E/Y220L has substitutions V11I (an isoleucine for a valine at Position 11), F64L (a leucine for a phenylalanine at position 64), Vg8A (an alanine for a valine at position 68) K101E (a glutamic acid for a lysine at position 101), T206A (an alanine for a threonine at position 206), and Y220L (a leucine for a tyrosine at position 220) compared to the wild type acGFP, as seen in FIG. 15. This mutant demonstrated protein folding at 37° C. and possessed clear green fluorescence at 508 nm. The excitation spectrum for the G22-G222E/Y220L had a major peak at 396 nm and a minor peak at 493 nm (ratio 10:1) (see FIG. 16 where the excitation spectra is the dotted line and the emission spectra is the solid line). Spectral properties of this mutant were very similar to that of wild type GFP from Aequorea victoria. Using mutant G22-G222E/Y220L as a basis, mutant 220-II-5 was obtained having substitutions V11I (an isoleucine for a valine at Position 11), F64L (a leucine for a phenylalanine at position 64), K101E (a glutamic acid for a lysine at position 101), E115K (a lysine for a glutamic acid at position 115), H148Q (a glutamine for a histidine at position 148), T206A (an alanine for a threonine at position 206), Y220L (a leucine for a tyrosine at position 220), F221L (a leucine for aphenylalanine at position 221), and K238Q (a glutamine for a lysine at position 238). The nucleic acid and amino acid sequences for this mutant are in FIG. 17. Thus mutant has a major excitation peak at 395 nm, and no excitation peak at about 480 nm, with the emission peak at 512 nm (see FIG. 18A). It is likely that the suppression of the longer-wavelength excitation peak can be explained by the substitution H148Q that results in a disappearance of the fraction of charged chromophore. After several minutes of relatively intense irradiation with light at approximately 400 nm under a fluorescent microscope, the excitation spectrum of mutant G22-G222E/Y220L changed. There was a simultaneous decrease of the 395 nm peak and appearance of the 480 nm excitation peak (see FIG. 18B). As a result, a more than 100-fold contrast in the fluorescent brightness of the 510 nm emission can be obtained in the 480 nm excitation light, as compared to before and after irradiation of intense light of 400 nm wavelength. FIG. 25 shows two E. coli colonies expressing mutant 220-II-5 under a fluorescent microscope. The two areas in the upper colony were photoactivated preliminarily by an intense 400 nm light. As such, the G22-G22E/Y220L mutants can be used as a photoactivated fluorescent marker for photo-labeling living organisms similar to the recently published methods for use of PA-GFP mutant in Patterson and Lippincott-Schwartz, Science, 13:1873-1877 (2002). Cyan fluorescent protein mutant CFP-rand3 has substitutions at V11I (isoleucine for valine at position 11), T62A (alanine for threonine at position 62), F64L (leucine for phenylalanine at position 64), K101E (glutamic acid for lysine at position 101), N121S (serine for asparagine at position 121), H148T (threonine for histidine at position 148), E172K (lysine for glutamic acid at position 172), and T206A (alanine for threonine at position 206). The amino and nucleic acid sequences for the CFP-rand3 mutant are shown in FIG. 19. This mutant has an excitation peak at 402 nm, with a single emission peak at 467 nm (see FIG. 20). Another mutant cyan fluorescent protein, CFP-3, was generated having substitutions V11I (isoleucine for valine at position 11), F64L (a leucine for a phenylalanine at position 64), K101E (glutamic acid for lysine at position 101), H148S (serine for histidine at position 148), F165L (leucine for phenylalanine at position 165), E172A (alanine for glutamic acid at position 172), and T206A (alanine for threonine at position 206). The amino and nucleic acid sequences for this mutant are shown in FIG. 21. This mutant has an excitation peak at 390 nm, with a single emission peak at 470 nm FIG. 22A. After several minutes of relatively intense irradiation with light at 400 nm, the following changes of excitation and emission spectra were observed: (i) considerable decrease in the 390-nm excitation peak, and (ii) appearance of a 480 nm excitation peak with emission at 505 nm (see FIG. 22B). As a result, a more than 30-fold contrast in the fluorescent brightness of the 505 nm emission may be obtained using excitation light at 480 nm, comparing the spectra before and after intense irradiation at 405 nm. Simultaneous change of the excitation and emission parameters transforms the cyan mutant CFP-3 to a green fluorescent protein in response to intense 400 nm irradiation. Therefore, the CFP-3 mutant can be used as a photoactivated or “photo-switched” fluorescent marker for photo-labeling of living organisms. In one exemplary experiment, the G22 mutant was used as a fluorescent tag to test protein expression in mammalian cells. Unexpectedly, however, mutant G22 produced a very low fluorescent signal in human cell lines. This likely can be explained by either non-optimal codon usage or by presence of a cryptic intron in the G22 mutant gene. To overcome both these problems, a G22-h mutant gene was synthesized incorporating mammalian-optimized codon usage. The amino and nucleic acid sequences for this humanized mutant are shown in FIG. 23. Transient expression of G22-h in different cell lines showed a bright green signal without aggregation. FIG. 24 shows transient expression of the G22-h mutant (panels A-E), and a G22-β-actin fusion protein (panel F) in different mammalian cell lines. Panel A-293T; panel B-vero; panel C-3T3; panel D-L929; panel E-COS1; panel F-3T3. Fluorescence was clearly detectable 24 hours post-transfection. No toxicity was observed. The ability of G22-h to tag proteins was demonstrated by constructing a fusion protein with cytoplasmic β-actin. Transient expression of this fusion in 3T3 cells showed bright and accurate actin labeling (see FIG. 24F). Stress fibers, focal contacts and cell possesses were clearly visible. There was no observed detriment to cell adhesion or vitality, nor was any non-specific protein aggregation observed. Methods: Total RNA was isolated using a NucleoSpin RNA II kit (Clontech) from a small vivsection of an Aequorea coerulescens organism that included umbrella border and radial channel. cDNA was synthesized and amplified with a SMART PCR cDNA Synthesis kit (Clontech). A fragment of the novel fluorescent protein gene was obtained by PCR with degenerated primers. A step-out PCR RACE method was used to clone the 5′-end fragment of the target cDNA. The nucleotide sequence of the cDNA encoding the novel fluoresent protein, acGFP, has been submitted to GenBank with accession number AY151052. For bacterial expression of acGFP, the full-length coding region was amplified using specific primers and cloned into the pQE30 vector (Qiagen). A Diversity PCR Random Mutagenesis kit (CLONTECH) was used for random mutagenesis of acGFP, in conditions optimal for 5-6 mutations per 1000 basepairs. E. coli colonies expressing mutant proteins were screened visually with a fluorescent stereomicroscope SZX-12 (Olympus). The brightest variants were selected and subjected an additional round of random mutagenesis. Site-directed mutagenesis was performed by PCR using the overlap extension method, with primers containing appropriate target substitutions (see, for example, Ho et al., Gene, 77:51-59 (1989). Proteins fused to an N-terminal six-histidine tag were expressed in E. coli XL1 blue strain (Invitrogen) and purified using TALON metal-affinity resin (Clontech). Absorption spectra were recorded with a Beckman DU520 UV/VIS Spectrophotometer. A Varian Cary Eclipse Fluorescence Spectrophotometer was used for measuring excitation-emission spectra. For molar extinction coefficient determination, estimation of mature chromophore concentration was used. Proteins were alkali-denatured with an equal volume of 2M NaOH. Under these conditions, the A. victona GFP chromophore absorbs at 446 nm and its molar extinction coefficient equals 44,000 M−1cm−1 (Ward et al., Photochem. Photobiol., 31:611-615 (1980)). Absorption spectra for native and alkali-denatured proteins were measured. The molar extinction coefficients for the native state were estimated using the absorption of denatured proteins as a basis. For quantum yield determination, the fluorescence of the mutants was compared to that of enhanced GFP (quantum yield 0.60). UV-induced photoconversion of acGFP-G222E was performed using a Cary Eclipse Fluorescence Spectrophotometer. The protein sample was irradiated for several hours with 250-300 nm wavelength light in scanning mode (excitation slit 20 nm, scan rate 30 nm/min, averaging time 1 second, cycle mode). Purified protein samples (˜1 mg/ml) were loaded onto a Sephadex-100 column (0.7×60 cm) and eluted with 50 mM phosphate buffer (pH 7.0) with 100 mM NaCl. EGFP, HcRed1, and DsRed2 (Clontech) were used as monomer, dimer and tetramer standards, respectively. For protein gel analysis, heated and unheated samples were loaded onto a common 12% SDS-PAGE, and electrophoresis was carried out at 15 mA/gel. For Western blotting, proteins were transferred onto a Hybond C membrane (Amersham) using standard procedures. Membranes were probed with mouse antibodies (Clontech) against GFP (1:2500), and then with HRP-conjugated anti-mouse antibodies (Amersham) at 1:2500. To develop the staining pattern, an ECL Western blotting analysis system (Amersham Pharmacia Biotech) was used, including detection reagents 1, 2 and Hyperfilm ECL. For expression in eukaryotic cells, acGFP was cloned into pEGFP-C1 and pEGFP-Actin vectors (CLONTECH) between AgeI and BglI restriction sites (in lieu of the EGFP coding region). The following cell lines were used: human kidney epithelial cells 293T, mouse embryo fibroblasts 3T3, murine subcutaneous fibroblasts L929, African green monkey kidney epithelial cells Vero, and African green monkey kidney fibroblasts COS1. Cells were transfected with LipofectAMINE reagent (Invitrogen) and were tested 20 hours after transfection. An Olympus CK40 fluorescent microscope equipped with CCD camera DP-50 (Olympus) was used for cell imaging. TABLE 1 Spectral properties of acGFP mutants in comparison with EGFP. Maximal extinction Protein Absorption Emission coefficient, Quantum Relative Species name max, nm max, nm M−1cm−1 yield brightness** Aequorea EGFP* 488 509 53,000 0.60 1 victoria Aequorea Wild type 390 460, 505 nt nt nt coerulescens acGFP Mutant G2 475 504 58,000 0.38 0.69 Mutant G22 480 505 50,000 0.55 0.86 Mutant 390 460, 505 33,000 0.07 0.07 G22- G222E*** Mutant 402 467 35,000 0.30 0.33 CFP-rand3 *Data from reference: Patterson, G., Day, R. N., and Piston, D. (2001) Fluorescent protein spectra. J. Cell. Sci. 114, 837-838 **As compared to the brightness (extinction coefficient multiplied by quantum yield) of EGFP. ***Data on mature fraction of the mutant (about 3% from the total protein) All publications and patent applications cited in this specification are herein incorporated by reference as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference. The citation of any publication is for its disclosure prior to the filing date and should not be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, it is readily apparent to those of ordinary skill in the art in light of the teachings of this invention that certain changes and modifications may be made thereto without departing from the spirit or scope of the appended claims.

<SOH> BACKGROUND OF THE INVENTION <EOH>Labeling is a tool for marking a protein, cell, or organism of interest and plays a prominent role in many biochemical, molecular biological and medical diagnostic applications. A variety of different labels have been developed and used in the art, including radiolabels, chromolabels, fluorescent labels, chemiluminescent labels, and the like, with varying properties and optimal uses. However, there is continued interest in the development of new labels. Of particular interest is the development of new protein labels, including fluorescent protein labels.

<SOH> SUMMARY OF THE INVENTION <EOH>The present invention provides nucleic acid compositions encoding a unique colorless protein from Aequorea coerulscens and fluorescent and non-fluorescent mutants thereof, as well as the proteins and peptides encoded by the nucleic acids. The proteins of the present invention are proteins that are colored and/or fluorescent and/or can be photoactivated, where this optical feature arises from the interaction of two or more amino acid residues of the protein. Also of interest are proteins that are substantially similar to, or derivatives or mutants of, the above-referenced specific proteins including fusion proteins incorporating peptides of the present invention, as well as antibodies to these proteins. The subject protein and nucleic acid compositions find use in a variety of different applications. Finally, the present invention provides kits for use in labeling applications.

20040715

20081007

20060727

85733.0

C07K14435

MONSHIPOURI, MARYAM

NOVEL FLUORESCENT PROTEIN FROM AEQUOREA COERULSCENS AND METHODS FOR USING THE SAME

UNDISCOUNTED

ACCEPTED

C07K

ACCEPTED

Biodegradable auricular prosthetic device

A biodegradable auricular prosthetic device is described, particularly but not exclusively devised for the treatment of otitis media, comprising a tubular body having axially opposed ends and flanged at least at one of the opposed ends and at least a portion of which is produced from a material subject to biological degradation in the presence of organic liquids, wherein at least the portion made of material subject to biological degradation is produced from a polymeric material selected from the group of polyphosphazenes.

1. A biodegradable auricular prosthetic device, particularly but not exclusively devised for the treatment of otitis media, comprising a tubular body having axially opposed ends and flanged at least at one of said opposed ends and at least a portion of which is produced from a material subject to biological degradation in the presence of organic liquids, characterized in that at least said portion made of material subject to biological degradation is produced from a polymeric material selected from the group of polyphosphazenes. 2. A prosthetic device according to claim 1, wherein at least said portion made of material subject to biological degradation has variable biodegradability characteristics along the axial extension of said tubular body. 3. A prosthetic device according to claim 1 or 2, wherein said tubular body has a cylindrical configuration. 4. A prosthetic device according to claim 3, wherein said tubular body, in an intermediate portion thereof comprised between said ends, has a greater biodegradability with respect to the biodegradability of said flange(s). 5. A prosthetic device according to one or more of the preceding claims, wherein said body is flanged at both said opposed ends in a bobbin shape. 6. A prosthetic device according to one or more of the preceding claims, wherein there are incorporated into said polymeric material substances selected from drugs, growth factors, bacteriostatic substances and/or bactericides, singly or in admixture with one another.

TECHNICAL FIELD The subject of the present invention is a biodegradable auricular prosthetic device, particularly but not exclusively devised for the treatment of otitis media. TECHNOLOGICAL BACKGROUND The treatment of otitis media provides for a tubular ventilation device to be surgically implanted in the tympanic membrane to balance a pressure difference established between the middle ear and the outer ear. At one time such implants had to be surgically removed at the end of the treatment. Nowadays there have been devised, but hitherto never produced on an industrial scale, devices produced from biodegradable materials, such as polylactides, subject to biological degradation in the presence of organic liquids. An example of such devices (otherwise known as reabsorbable auricular ventilation tubes) is described in U.S. Pat. No. 4,650,488. The device described therein has a tapered body, of substantially frustoconical configuration, traversed axially by a hole and having a flanged end at the minor base. The device, or at least the flanged portion thereof, is produced from a biodegradable material based on polymers of lactic acid. Such a device has not hitherto been applied in the field inasmuch as it is potentially susceptible to exposing the patients in which it is implanted to numerous risks. Firstly, the polylactides involve the risk of growth of granulation tissues consequent upon their imperfect absorption by the tissues. The formation of granulation tissues is particularly risky in auricular treatments. Moreover, both through the typical degradation of the material used and through the frustoconical configuration of the tapered body it involves the risk that the epithelial growth with which the hole for application of the prosthesis tends to close itself up again develops with invagination of the keratinized squamous epithelium, of the actual outer ear, along the conical portion and towards the middle ear, where mucous epithelium is present. There is in practice a risk of migration of the keratinized squamous epithelium towards the middle ear which is a possible cause of cholesteatoma. All the problems in question have hitherto led to delays in the marketing of devices of the aforesaid type. Moreover, up to now there have not been reabsorbable auricular ventilation tubes approved by the FDA (Federal Drug Administration) of the United States. DESCRIPTION OF THE INVENTION The problem underlying the present invention is therefore that of making available a prosthetic device structurally and functionally designed to remedy all the drawbacks mentioned with reference to the prior art cited. This problem is confronted and solved by the invention by means of a prosthetic device, such as an auricular ventilation tube, produced in accordance with the following claims. BRIEF DESCRIPTION OF THE DRAWINGS The characteristics and advantages of the invention will become clear from the description of a preferred exemplary embodiment thereof illustrated, by way of non-limiting example, with reference to the appended drawings, in which: FIG. 1 is a view in longitudinal section of a prosthetic device according to the invention implanted in a tympanic membrane; FIG. 2 is a perspective view of the device of FIG. 1; FIGS. 3 to 5 are views in elevation of the device of the present invention produced in three further configurations. PREFERRED EMBODIMENT OF THE INVENTION In the drawings, the reference 1 indicates as a whole an auricular prosthetic device according to the invention, surgically implanted through a hole 2a made in the tympanic membrane 2 which sub-divides the ear into outer ear 3 and middle ear 4. The epithelial tissues of the outer ear 3 and middle ear 4 are respectively of the squamous type (cutis) and the mucous type. The device 1 comprises a tubular body having a cylindrical portion 10 of circular cross-section having two axially opposed ends with each of which there is associated, for example provided integrally, a respective flange 11, 12. The flange 11, in use as an implant, is located on the middle ear side with respect to the tympanic membrane, while the flange 12 is on the outer ear side. The tubular body is traversed by a through duct 14 which serves to ventilate the middle ear for the treatment of otitis (for example seromucosa). At least the cylindrical portion 10 of the tubular body and the flange 11, but preferably the entire prosthetic device, is produced from a reabsorbable biodegradable material selected from the group of polyphosphazenes and relative polymeric compounds. The use of such materials and the relative formulation are described in U.S. Pat. No. 6,077,916, the content of which is considered as forming an integral part of the present description. The production of the entire device (or of both the flanges) from biodegradable material renders it reversible, preventing the possibility of errors of orientation thereof in the implant site. Preferably, the characteristics of biodegradability of the tubular body (understood as inclusive of the flanges) are variable along the axial extension thereof. For example, it has proved preferable for the speed of degradation of the cylindrical portion 10 to be greater than the speed of degradation of the flanges 11, 12. In this way the degradation of the cylindrical portion occurs with regular reduction of its cross-section and the occlusion of the implant hole occurs with regular regrowth of the tissues on both sides of the tympanic membrane, avoiding different mechanical stresses on the tissues, as well as the risk of invagination and consequent cholesteatoma. The variation of the degree of bioabsorption or biodegradability is obtained by means of irradiation (for example with gamma rays), since the areas subjected to greater irradiation generally assume a lesser molecular weight and an increase in the speed of degradation, or by producing the tubular body from different materials. Once the cylindrical portion 10 is severed, the inner flange 11 falls into the middle ear and is reabsorbed without giving rise to the growth of granulation tissue, while the outer flange 12 and the relative portion of cylindrical body fall into the outer ear and are expelled or reabsorbed without consequence. Moreover, the possibility is provided of incorporating into the structure of the polymer drugs, growth factors, bacteriostatic substances and/or bactericides. As has been emphasized, a first embodiment of the invention provides for the tubular body to be flanged at both the opposed ends in a bobbin configuration. Alternatively (FIG. 3) it is arranged for the flange 11 to be provided with a pointed appendage 20, for perforating the tympanic membrane at the implant site, or for the tubular body to be flanged at only one end (FIG. 4—in this case only the inner end 11) and further for said end flange to be oblique with respect to the axis of the cylindrical portion (FIG. 5). The oblique flange 11 serves in such a case as an “arrowhead” to facilitate the perforation of the tympanic membrane at the implant site. The invention thus solves the problem posed, also providing numerous advantages, among which are: the possibility of establishing a priori, beforehand, the duration of permanence of the implant based on the therapeutic requirements; the abolition of the need for removal with a consequent second surgical procedure (and the need for anaesthesia in children); the reduction of the risk of residual permanent tympanic perforation; the possibility of incorporating into the structure of the polymer drugs, growth factors, bacteriostatic substances and/or bactericides.

<SOH> TECHNOLOGICAL BACKGROUND <EOH>The treatment of otitis media provides for a tubular ventilation device to be surgically implanted in the tympanic membrane to balance a pressure difference established between the middle ear and the outer ear. At one time such implants had to be surgically removed at the end of the treatment. Nowadays there have been devised, but hitherto never produced on an industrial scale, devices produced from biodegradable materials, such as polylactides, subject to biological degradation in the presence of organic liquids. An example of such devices (otherwise known as reabsorbable auricular ventilation tubes) is described in U.S. Pat. No. 4,650,488. The device described therein has a tapered body, of substantially frustoconical configuration, traversed axially by a hole and having a flanged end at the minor base. The device, or at least the flanged portion thereof, is produced from a biodegradable material based on polymers of lactic acid. Such a device has not hitherto been applied in the field inasmuch as it is potentially susceptible to exposing the patients in which it is implanted to numerous risks. Firstly, the polylactides involve the risk of growth of granulation tissues consequent upon their imperfect absorption by the tissues. The formation of granulation tissues is particularly risky in auricular treatments. Moreover, both through the typical degradation of the material used and through the frustoconical configuration of the tapered body it involves the risk that the epithelial growth with which the hole for application of the prosthesis tends to close itself up again develops with invagination of the keratinized squamous epithelium, of the actual outer ear, along the conical portion and towards the middle ear, where mucous epithelium is present. There is in practice a risk of migration of the keratinized squamous epithelium towards the middle ear which is a possible cause of cholesteatoma. All the problems in question have hitherto led to delays in the marketing of devices of the aforesaid type. Moreover, up to now there have not been reabsorbable auricular ventilation tubes approved by the FDA (Federal Drug Administration) of the United States.

<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>The characteristics and advantages of the invention will become clear from the description of a preferred exemplary embodiment thereof illustrated, by way of non-limiting example, with reference to the appended drawings, in which: FIG. 1 is a view in longitudinal section of a prosthetic device according to the invention implanted in a tympanic membrane; FIG. 2 is a perspective view of the device of FIG. 1 ; FIGS. 3 to 5 are views in elevation of the device of the present invention produced in three further configurations. detailed-description description="Detailed Description" end="lead"?

20040715

20070116

20050407

70949.0

ISABELLA, DAVID J

BIODEGRADABLE AURICULAR PROSTHETIC DEVICE

SMALL

ACCEPTED

ACCEPTED

Ceramic membrane based on a substrate containing polymer or natural fibres, method for the production and use thereof

The present invention relates to membranes and to a process for making them. The membranes according to the invention comprise a sheetlike flexible substrate having a multiplicity of openings and having a coating on and in said substrate, the material of said substrate being selected from nonwovens of polymeric fibers, said nonwovens having a porosity of more than 50% and said coating being a porous ceramic coating, said substrate preferably being from 10 to 200 μm in thickness. Such membranes provide a distinctly higher flux than conventional membranes. The membranes are useful as separators for batteries or as a microfiltration membrane.

1. A membrane comprising a sheetlike flexible substrate having a multiplicity of openings and having a porous coating on and in said substrate, said coating comprising inorganic components, wherein the material of said substrate is selected from the group consisting of nonwovens of a polymeric fiber, nonwovens of a natural fiber and mixtures thereof, said nonwovens having a porosity of more than 50%, said substrate being from 10 to 200 μm in thickness and said coating being a porous ceramic coating. 2. The membrane of claim 1, wherein said polymeric fiber is selected from the group consisting of poly-acrylonitrile, polyamides, polyimides, poly-acrylates, polytetrafluoroethylene, polyesters polyolefin and mixtures thereof. 3. The membrane of claim 1, wherein said polymeric fiber is from 1 to 25 μm in diameter. 4. The membrane of claim 1, wherein the porosity of said substrate is in the range from 50 to 97%. 5. The membrane of claim 1, wherein said coating on and in said substrate comprises an oxide of a metal selected from the group consisting of Al, Zr, Si, Ti, Y and mixtures thereof. 6. The membrane of claim 1, wherein the porosity of said membrane is in the range from 10 to 70%. 7. The membrane of claim 1, wherein said membrane has an average pore size in the range of from 10 to 2000 nm. 8. The membrane of claim 1, wherein said membrane has a tensile strength of more than 1 N/cm. 9. The membrane of claim 1, wherein said membrane is bendable around a radius down to 100 m without damage. 10. The membrane of claim 1, wherein said membrane is bendable around a radius down to 2 mm without damage. 11. A process for producing a membrane as claimed in claim 1 comprising providing a substrate from 10 to 200 μm in thickness, selected from the group consisting of nonwovens of polymeric fiber, natural fiber and mixtures thereof having a porosity of more than 50%, with a coating, said coating being a porous ceramic coating which is brought onto and into said substrate by applying a suspension and heating one or more times to solidify said suspension on and in said substrate, said suspension comprising at least one oxide of a metal selected from the group consisting of Al, Zr, Si, Ti, Y and mixtures thereof and a sol. 12. The process of claim 11, wherein said suspension is brought onto and into said substrate by printing on, pressing on, pressing in, rolling on, knifecoating on, spreadcoating on, dipping, spraying or pouring on. 13. The process of claim 11, wherein said polymeric fibers are selected from the group consisting of polyacrylonitrile, polyamides, polyimides, poly-acrylates, polytetrafluoroethylene, polyester, polyolefin and mixtures thereof. 14. The process of claim 11, wherein said suspension comprises at least one metal oxide sol, at least one semimetal oxide sol or at least one mixed metal oxide sol or a mixture thereof and is prepared by suspending at least one inorganic component in at least one of these sols. 15. The process of claim 14, wherein said sols are obtained by hydrolyzing at least one metal compound, at least one semimetal compound or at least one mixed metal compound using water or an acid or a combination thereof. 16. The process of claim 14, wherein said sol comprises less than 50% by weight of water and/or acid. 17. The process of claim 15, wherein said metal compound hydrolyzed is at least one metal alkoxide compound or at least one semimetal alkoxide compound selected from alkoxide compounds of the elements selected from the group consisting of Zr, Al, Si, Ti, Y and mixtures thereof or at least one metal nitrate, metal carbonate or metal halide selected from metal salts of the elements selected from the group consisting of Zr, Al, Si, Ti, Y and mixtures thereof. 18. The process of claim 14, wherein said inorganic component suspended is at least one oxide selected from the oxides of the elements selected from the group consisting of Y, Zr, Al, Si, Ti and mixtures thereof. 19. The process of claim 11, wherein the mass fraction of said suspended component is from 0.1 to 500 times that of the sol used. 20. The process of claim 11, further comprising adding an adhesion promoter to said suspension. 21. The process of claim 11, further comprising adding an adhesion promoter on said fibers prior to said applying of said suspension. 22. The process of claim 20, wherein said adhesion promoter is selected from the organofunctional silanes and/or the oxides of the elements selected from the group consisting of Zr, Al, Si, Ti and mixtures thereof. 23. The process of claim 22, wherein said adhesion promoter is selected from the group consisting of 3-aminopropyltriethoxysilane, 2-aminoethyl-3-aminopropyltrimethoxysilane, 3-glycidyloxytrimethoxysilane, 3-methacryloyloxypropyltrimethoxysilane, vinyltriethoxysilane, vinyltrimethoxysilane, and vinyltris(2-methoxyethoxy)silane and mixtures thereof. 24. The process of claim 11, wherein said suspension present on and in the support is solidified by heating at from 50 to 350° C. 25. The process of claim 24, wherein said heating is effected at from 110 to 280° C. for from 0.5 to 10 minutes. 26. A method for producing batteries comprising placing a membrane as claimed in claim 1 in a battery as a separator. 27. A method comprising utilizing a membrane as claimed in claim 1 as a carrier for ultra-filtration, nanofiltration, reverse osmosis, gas separation or pervaporation membranes. 28. A method for microfiltration comprising placing a membrane as claimed in claim 1 in a microfiltration device. 29. The process of claim 12, wherein said polymeric fibers are selected from the group consisting of polyacrylonitrile, polyamides, polyimides, poly-acrylates, polytetrafluoroethylene, polyester, polyolefin and mixtures thereof. 30. The process of claim 15, wherein said sol comprises less than 50% by weight of water and/or acid. 31. The process of claim 21, wherein said adhesion promoter is selected from the organofunctional silanes and/or the oxides of the elements selected from the group consisting of Zr, Al, Si, Ti and mixtures thereof.

The present invention relates to a membrane, especially a microfiltration membrane, comprising a substrate based on polymeric or natural fibers and a ceramic coating, a process for making the membrane and the use of the membrane. Various applications are known for ceramic composites. The advantage of ceramic composites is that the ceramic coatings are chemically inert to most chemical substances, for example organic solvents, and also predominantly resistant to acids or alkalis. Accordingly, metals are often coated with ceramics to protect the metal against chemical influences. The porous surface of a ceramic-coated composite, moreover, enhances the abrasion resistance of subsequently applied paints or protective coatings. Ceramics themselves, having a porous surface, are also very useful as membranes or filters. The disadvantage of ceramics or ceramic composites is the brittleness of the ceramic. Ceramic-coated metals are therefore very impact-sensitive and the ceramic coating hardly survives any mechanical exposure without the surface of the ceramic being damaged. Since, moreover, the bending of such a ceramic composite leads to a damaged ceramic layer, the areas in which such ceramic composites can be used are still limited at present. Notwithstanding their disadvantages, ceramic composites are frequently also used in filtration engineering or membrane engineering. EP 0 358 338 describes a method which comprises applying to a surface, preferably a smooth metal surface, an aqueous solution comprising a metal oxide sol and solidifying this solution to form a protective ceramic coat on the surface. The aqueous solution may include a metal oxide powder and/or an adhesion promoter to improve the adhesion of the ceramic layer to the surface to be protected. The application of layers to pervious carrier materials is not described. WO 96/00198 teaches the production of ceramic layers on surfaces of various materials. These coated materials can be used as membranes for nanofiltration. In this process, titanium dioxide sol is dispersed with alumina powder using hydrochloric acid for peptization. U.S. Pat. No. 4,934,139 teaches a process for producing ceramic membranes for ultrafiltration and microfiltration. A sol or a particle suspension is applied to a porous metal carrier and sintered to produce such ceramic membranes. The porous carrier can be stainless steel sintered metal or woven stainless steel fabric having metal particles sintered into its interstices. Woven metal fabrics having interstices above 100 μm cannot be produced by this process without sintering in metal particles. The process avoids suspension or sol penetrating into the interstices of the carrier material. U.S. Pat. No. 5,376,442 and U.S. Pat. No. 5,605,628 have an organic binder being incorporated into the coating solution to bridge interstices in the carrier material. This binder has to be removed again in the solidifying step, and this can lead to irregularities in the ceramic surface and/or structure. Similarly, DE 42 10 413 has the inorganic powder being fixed by means of a polymeric resin. This resin likewise has to be removed again in the solidifying step, and this can lead to irregularities in the ceramic surface and/or structure. WO 99/15262 describes the production of a flexible pervious composite based on a perforate carrier material. The carrier here can consist of various materials, including polymeric apertured films, wovens composed of polymer, natural fiber, glass and steel or metal nonwovens. The coating is effected using a sol very largely consisting of water, or of aqueous solutions of strong acids, into which particles of the oxides of aluminum, titanium, zirconium or silicon have been stirred. The sol may further contain organosilyl compounds such as methyltriethoxysilane. These pervious composite materials are useful inter alia as membranes in filtration. All microfiltration membranes described hitherto have a fairly low transmembrane flux. In addition, the ceramic coatings are brittle and are easily detached from the carrier in the use of such membranes when adhesion is too low. Such membranes are then inutile. It is an object of the present invention to provide a flexible membrane which has a high transmembrane flux and is more durable than prior art membranes. It has been found that this object is achieved, surprisingly, by using polymeric nonwoven materials instead of apertured films to provide a distinct increase in the transmembrane flux. This is due to the greater porosity of the nonwoven. It has further been determined that, surprisingly, membranes comprising nonwoven materials based on polymers are distinctly more durable and flexible than membranes comprising ceramic coatings on glass or metal wovens or nonwovens or on polymer films. The present invention accordingly provides a membrane comprising a sheetlike flexible substrate having a multiplicity of openings and having a porous coating on and in said substrate, said coating comprising inorganic components, characterized in that the material of said substrate is selected from nonwovens of polymeric or natural fibers, said nonwovens having a porosity of more than 50% and said coating being a porous ceramic coating. The present invention further provides a process for producing a membrane according to the invention, which comprises providing a sheetlike flexible substrate having a multiplicity of openings with a coating in and on said substrate, the material of said substrate being selected from nonwovens of polymeric fibers, and said coating being a porous ceramic coating which is brought onto and into said substrate by applying a suspension, comprising at least one oxide of the metals Al, Zr, Si, Sn, Ti and/or Y and a sol, onto the substrate and heating one or more times to solidify said suspension on and in said substrate. The present invention similarly provides for the use of a membrane according to the invention as a separator in batteries, as a carrier for ultrafiltration, nano-filtration, reverse osmosis, gas separation or pervaporation membranes or as a microfiltration membrane. One advantage of the membranes according to the invention is that the transmembrane flux is distinctly higher than for conventional membranes. The increase in the transmembrane flux over membranes based on apertured polymer films is about 150%. This is attributable to the fact that the nonwoven materials themselves have a distinctly larger porosity than the films used. Therefore, the open filter area of the resulting materials on nonwovens is likewise distinctly larger. This, as a result of the enlarged effective filtration area, also brings about a distinct increase in the filtration performance or flux. The membranes according to the invention are also distinctly more durable than membranes, especially composite membranes, available to date. It is believed that this is due to the irregular structure of the nonwoven used as a carrier. Woven fabrics contain a regularly spaced arrangement of knurls, ie. locations where the fibers are superposed. These regular knurls are locations for breakages or kinks, since the ceramic coating is not as thick in these locations as between the knurls. The regularity of the knurls in the case of membranes based on woven fabrics can have a perforation effect and cause the membrane to crack in this location. This problem can be remedied by the use of a nonwoven as a substrate or carrier because the arrangement of the knurls in a nonwoven is not regular. A further advantage of the polymeric nonwoven supported membranes according to the invention is that they are much less costly than alternative materials which might be used for high-flux membranes. A metal nonwoven costs about ε1250/m2, but a polymeric nonwoven less than ε 15/m2. Composite membranes are therefore now obtainable that can be produced so economically that they open up new markets which were previously inaccessible because of the high cost. These markets are particularly located in the field of the filtration of drinking and waste water, where membranes costing more than ε500/m2 cannot be used. The membrane according to the invention will now be described without the invention being limited thereto. The membrane according to the invention, comprising a sheetlike flexible substrate having a multiplicity of openings and having a porous coating on and in the substrate, the coating comprising inorganic components, is notable for the material of the substrate being selected from nonwovens of polymeric or natural fibers, the nonwovens having a porosity of more than 50%, and the coating being a porous ceramic coating. The substrate preferably has a porosity of 50 to 97%, more preferably of from 60 to 90% and most preferably of from 70 to 90%. Porosity in this context is defined as the volume of the nonwoven 100% minus the volume of the fibers of the nonwoven, ie. the fraction of the nonwoven volume which is not filled up by material. The volume of the nonwoven can be calculated from the dimensions of the nonwoven. The volume of the fibers is calculated from the measured weight of the nonwoven in question and the density of the polymeric fibers. The large porosity of the substrate also means a higher porosity for the membrane according to the invention, which is why higher transmembrane fluxes are obtainable with the membrane according to the invention. The membrane according to the invention also preferably comprises a substrate which is from 10 to 200 μm in thickness. It can be particularly advantageous for the membrane according to the invention to comprise a substrate which is from 30 to 100 μm, preferably from 25 to 50 μm and particularly preferably from 30 to 40 μm in thickness. The low thickness of the substrate used is another reason why the transmembrane flux through the membrane is higher than in the case of conventional membranes. The polymeric fibers are preferably selected from a polyacrylonitrile, polyamides, polyimides, polyacrylates, polytetrafluoroethylene, polyester, for example polyethylene terephthalate, and/or polyolefins, for example polypropylene or polyethylene, or mixtures thereof. But all other known polymeric fibers and many natural fibers such as for example flax fibers, cotton or hemp fibers are conceivable as well. The membrane according to the invention preferably comprises polymeric fibers which have a softening temperature of more than 100° C. and a melting temperature of more than 110° C. The range of possible uses is smaller in the case of polymeric fibers having lower temperature limits. Preferred membranes can be used up to a temperature of up to 150° C., preferably up to a temperature of from 120 to 150° C. and most preferably up to a temperature of 121° C. It can be advantageous for the polymeric fibers to be from 1 to 25 μm and preferably from 2 to 15 μm in diameter. Were the polymeric fibers to be distinctly thicker than the ranges mentioned, the flexibility of the substrate and hence also of the membrane would suffer. Polymeric fibers for the purposes of the present invention also comprehend the fibers of polymers which have been partially changed chemically or structurally by a thermal treatment, for example partially carbonized polymeric fibers. The ceramic coating on and in the substrate preferably comprises an oxide of the metals Al, Zr, Si, Sn, Ti and/or Y. Preferably the coating on and in the substrate comprises an oxide of the metals Al, Zr, Ti and/or Si as an inorganic component. It can be advantageous for the ceramic coating or the inorganic components which make up the coating to be attached to the substrate, especially to the polymeric fibers, via adhesion promoters. Typical adhesion promoters include organofunctional silanes as available for example from Degussa under the trade name Dynasilane, but also pure oxides such as ZrO2, TiO2, SiO2 or Al2O3 can be suitable adhesion promoters for some fiber materials. Depending on manufacturing conditions and adhesion promoter used, the adhesion promoters can still be detectable in the membrane according to the invention. It can be advantageous for the nonwoven or woven to have been first precoated with an adhesion promoter. Accordingly, such a membrane will then include in its interior a nonwoven, preferably a polymeric nonwoven, whose fibers bear a thin layer of an adhesion promoter, as of a metal oxide or of an organosilane compound. The porous ceramic material is present in and on the precoated polymeric carrier. The coating preferably includes at least one inorganic component in a particle size fraction having an average particle size of from 1 to 250 nm or having an average particle size of from 251 to 10 000 nm or from 1000 to 10 000 nm and particularly preferably from 250 to 1750 nm. It can be advantageous for the membrane according to the invention to comprise a coating which comprises at least two particle size fractions of at least one inorganic component. It can similarly be advantageous for the coating to comprise at least two particle size fractions of at least two inorganic components. The particle size ratio can be from 1 to 1 to 1 to 10 000 and preferably from 1 to 1 to 1 to 100. The amount ratio of the particle size fractions of the composite material can preferably be from 0.01 to 1 to 1 to 0.01. One of the factors which limits the perviousness and the porosity and hence also the transmembrane flux of the membrane according to the invention is the particle size of the inorganic components used. The membrane according to the invention preferably has a porosity of from 10% to 70%, more preferably of from 20% to 60% and most preferably of from 30% to 50%. Porosity as understood here relates to the accessible, ie. open, pores. The porosity can be determined via the known method of mercury porosimetry or can be calculated from the volume and the density of the materials used on the assumption that open pores are present exclusively. The average pore size of the membrane according to the invention is preferably in the range from 10 to 2000 nm and most preferably in the range from 50 to 800 nm. The membranes according to the invention have a tensile strength of at least 1 N/cm, preferably of 3 N/cm and most preferably of more than 6 N/cm. The membranes according to the invention are preferably flexible and are preferably bendable around a radius down to 100 m, more preferably down to 50 mm and most preferably down to 2 mm without damage. The good bendability of the membrane according to the invention has the advantage that the membrane is easily able to withstand sudden pressure fluctuations without damage when used in microfiltration. The membrane according to the invention is preferably obtainable by a process for producing a membrane, which comprises providing a sheetlike flexible substrate having a multiplicity of openings with a coating in and on said substrate, the material of said substrate being selected from nonwovens of polymeric or natural fibers, said nonwovens preferably having a porosity of more than 50%, and said coating being a porous ceramic coating which is brought onto said substrate by applying a suspension, comprising at least one oxide of the metals Al, Zr, Si, Sn, Ti and/or Y and a sol, onto the substrate and heating one or more times to solidify said suspension on and in said substrate. The suspension may include further inorganic components, especially inorganic components as already described above as inorganic components. The suspension may be brought onto and into a substrate by, for example, printing on, pressing on, pressing in, rolling on, knifecoating on, spreadcoating on, dipping, spraying or pouring on. The material of the substrate is preferably selected from polymeric fiber nonwovens from 10 to 200 μm in thickness. It can be advantageous for the membrane according to the invention to comprise a substrate from 30 to 100 μm and preferably from 25 to 50 μm in thickness. The polymeric fibers are preferably selected from a polyacrylonitrile, polyamides, polyimides, polyacrylates, polytetrafluoroethylene, polyester, for example polyethylene terephthalate, and/or polyolefins. But all other known polymeric fibers and many natural fibers can be used as well. The membrane according to the invention preferably comprises polymeric fibers which have a softening temperature of more than 100° C. and a melting temperature of more than 110° C. The range of possible uses is smaller in the case of polymeric fibers having lower temperature limits. Preferred membranes can be used up to a temperature of up to 150° C., preferably up to a temperature of from 120 to 150° C. and most preferably up to a temperature of 121° C. It can be advantageous for the polymeric fibers to be from 1 to 25 μm and preferably from 2 to 15 μm in diameter. Were the polymeric fibers to be distinctly thicker than the ranges mentioned, the flexibility of the substrate and hence also of the membrane would suffer. The suspension used for preparing the coating preferably comprises at least one inorganic oxide of aluminum, of titanium, of silicon and/or of zirconium and at least one sol, at least one semimetal oxide sol or at least one mixed metal oxide sol or a mixture thereof, and is prepared by suspending at least one inorganic component in at least one of these sols. The sols are obtained by hydrolyzing at least one compound, preferably at least one metal compound, at least one semimetal compound or at least one mixed metal compound. The compound to be hydrolyzed is preferably at least one metal nitrate, a metal chloride, a metal carbonate, a metal alkoxide compound or at least one semimetal alkoxide compound, particularly preferably at least one metal alkoxide compound. The metal alkoxide compound or semimetal alkoxide compound hydrolyzed is preferably an alkoxide compound of the elements Zr, Al, Si, Ti, Sn and Y or at least one metal nitrate, metal carbonate or metal halide selected from the metal salts of the elements Zr, Al, Ti, Si, Sn and Y as a metal compound. The hydrolysis is preferably carried out in the presence of liquid water, water vapor, ice or an acid or a combination thereof. One embodiment of the process according to the invention comprises preparing particulate sols by hydrolysis of the compounds to be hydrolyzed. These particulate sols are notable for the compounds formed by hydrolysis being present in the sol in particulate form. The particulate sols can be prepared as described above or as in WO 99/15262. These sols customarily have a very high water content, which is preferably above 50% by weight. It can be advantageous for the compound to be hydrolyzed to be introduced into alcohol or an acid or a combination thereof prior to hydrolysis. The hydrolyzed compound may be peptized by treatment with at least one organic or inorganic acid, preferably with a 10-60% organic or inorganic acid, particularly preferably with a mineral acid selected from sulfuric acid, hydrochloric acid, perchloric acid, phosphoric acid and nitric acid or a mixture thereof. The particulate sols thus prepared can subsequently be used for preparing suspensions, in which case it is preferable to prepare suspensions for application to natural fiber nonwovens or to polymeric sol pretreated polymeric fiber nonwovens. In a further embodiment of the process according to the invention, hydrolysis of the compounds to be hydrolyzed is used to prepare polymeric sols. These polymeric sols are notable for the fact that the compounds formed by hydrolysis are present in the sol in polymeric form, ie. in the form of chains crosslinked across a relatively large space. The polymeric sols customarily include less than 50% by weight and preferably much less than 20% by weight of water and/or aqueous acid. To obtain the preferred fraction of water and/or aqueous acid, the hydrolysis is preferably carried out in such a way that the compound to be hydrolyzed is hydrolyzed with from 0.5 to 10 times the molar ratio and preferably with half the molar ratio of liquid water, water vapor or ice, based on the hydrolyzable group of the hydrolyzable compound. The amount of water used can be up to 10 times in the case of compounds which are very slow to hydrolyze, such as tetraethoxysilane. Compounds which are very fast to hydrolyze, such as zirconium tetraethoxide, are perfectly capable under these conditions of forming particulate sols as it is, which is why it is preferable to use 0.5 times the amount of water to hydrolyze such compounds. A hydrolysis with less than the preferred amount of liquid water, water vapor or ice likewise leads to good results, although using more than 50% less than the preferred amount of half the -molar ratio is possible but not very sensible, since hydrolysis would no longer be complete and coatings based on such sols not very stable using an amount below this value. To prepare these polymeric sols having the desired, very low fraction of water and/or acid in the sol, it can be advantageous for the compound to be hydrolyzed to be dissolved in an organic solvent, especially ethanol, isopropanol, butanol, amyl alcohol, hexane, cyclohexane, ethyl acetate and or mixtures thereof, before the actual hydrolysis is carried out. A sol thus prepared can be used for preparing the suspension according to the invention or as an adhesion promoter in a pretreatment step. Both the particulate sols and the polymeric sols can be used as a sol to prepare the suspension in the process according to the invention. Not just sols which are obtainable as just described can be used, but in principle also commercially available sols, for example zirconium nitrate sol or silica sol. The process of preparing membranes by applying a suspension to and solidifying it on a carrier is known per se from WO 99/15262, but not all the parameters and input materials are applicable to the preparation of the membrane according to the invention. More particularly, the operation described in WO 99/15262 is not fully applicable to polymeric nonwoven materials in this form, since the very watery sol systems described therein frequently did not provide complete, in-depth wetting of the customarily hydrophobic polymeric nonwovens, since the most polymeric nonwovens are only badly wetted by the very watery sol systems, if at all. It has been determined that even the minutest unwetted areas in the nonwoven material can lead to membranes being obtained that have defects and hence are inutile. It has now been found, surprisingly, that a sol system or suspension whose wetting behavior has been adapted to the polymers will completely penetrate the nonwoven materials and so provide defect-free coatings. In the process according to the invention, it is therefore preferable to adapt the wetting behavior of the sol or suspension. This is preferably done by preparing polymeric sols or suspensions from polymeric sols, these sols comprising one or more alcohols, for example methanol, ethanol or propanol or mixtures comprising one or more alcohols and also preferably aliphatic hydrocarbons. But other solvent mixtures are also conceivable for addition to the sol or suspension to adapt the wetting behavior thereof to the substrate used. It has been determined that the fundamental change in the sol system and of the suspension resulting therefrom leads to a distinct improvement in the adhesion properties of the ceramic components on the and in a polymeric nonwoven material. Such good adhesion strengths are normally not obtainable with particulate sol systems. Preference is therefore given to coating substrates comprising polymeric fibers using suspensions which are based on polymeric sols or were finished with an adhesion promoter in a preceding step by treatment with a polymeric sol. It can be advantageous for the suspension to be prepared by using an inorganic component comprising at least one oxide selected from the oxides of the elements Y, Zr, Al, Si, Sn and Ti and suspended in a sol. Preference is given to suspending an inorganic component which comprises at least one compound selected from aluminum oxide, titanium dioxide, zirconium oxide and/or silicon dioxide. The mass fraction of the suspended component is preferably from 0.1 to 500 times, more preferably from 1 to 50 times and most preferably from 5 to 25 times that of the sol used. It can be advantageous to suspend in at least one sol at least one inorganic component having an average particle size of from 1 to 10 000 nm, preferably from 1 to 10 nm, from 10 to 100 nm, from 100 to 1000 nm or from 1000 to 10 000 nm, more preferably from 250 to 1750 nm and most preferably from 300 to 1250 nm. The use of inorganic components having an average particle size of from 250 to 1250 nm confers a particularly highly suitable bendability and porosity on the membrane. To improve the adhesion of the inorganic components to polymeric fibers as a substrate, it can be advantageous for the suspensions used to be admixed with adhesion promoters, for example organofunctional silanes or else pure oxides such as ZrO2, TiO2, SiO2 or Al2O3, in which case it is preferable to admix the adhesion promoters especially to suspensions based on polymeric sols. Useful adhesion promoters include in particular compounds selected from the octylsilanes, the fluorinated octylsilanes, the vinylsilanes, the amine-functionalized silanes and/or the glycidyl-functionalized silanes, for example the Dynasilanes from Degussa. Particularly preferred adhesion promoters for polytetrafluoroethylene (PTFE) include for example fluorinated octylsilanes, for polyethylene (PE) and polypropylene (PP) they are vinyl-, methyl- and octylsilanes, although an exclusive use of methylsilanes is not optimal, for polyamides and polyamines they are amine-functional silanes, for polyacrylates and polyesters they are glycidyl-functionalized silanes and for polyacrylonitrile it is also possible to use glycidyl-functionalized silanes. Other adhesion promoters can be used as well, but they have to be adapted to the respective polymers. The WO 99/15262 addition of methyltriethoxysilane to the sol system in the coating of polymeric carrier materials is a comparatively bad solution to the adhesivity problem of ceramics on polymeric fibers. Furthermore, the drying time of from 30 to 120 min at from 60 to 100° C. in the case of the sol systems described is not sufficient to obtain hydrolysis-resistant ceramic materials. This means that these materials will dissolve or become damaged in the course of prolonged storage in aqueous media. On the other hand, the thermal treatment at above 350° C. that is described in WO 99/15262 would lead to an incineration of the polymeric nonwoven used here and hence to the destruction of the membrane. The adhesion promoters accordingly have to be selected so that the solidification temperature is below the melting or softening temperature of the polymer and below its decomposition temperature. Suspensions according to the invention preferably include distinctly less than 25% by weight and more preferably less than 10% by weight of compounds capable of acting as adhesion promoters. An optimal fraction of adhesion promoter results from coating the fibers and/or particles with a monomolecular layer of the adhesion promoter. The amount in grams of adhesion promoter required for this purpose can be obtained by multiplying the amount in g of the oxides or fibers used by the specific surface area of the materials in m2 g-1 and then dividing by the specific area required by the adhesion promoter in m2g−1, the specific area required frequently being on the order of from 300 to 400 m2 g−1. The table which follows contains an illustrative overview over usable adhesion promoters based on organofunctional silicon compounds for typical nonwoven material polymers. Polymer Organofunction type Adhesion Promoter PAN Glycidyl GLYMO Methacryloyl MEMO PA Amino AMEO, DAMO PET Methacryloyl MEMO Vinyl VTMO, VTEO, VTMOEO PE, PP Amino AMEO, AMMO Vinyl VTMO, VTEO, Silfin Methacryloyl MEMO where: AMEO = 3-aminopropyltriethoxysilane DAMO = 2-aminoethyl-3-aminopropyltrimethoxysilane GLYMO = 3-glycidyloxytrimethoxysilane MEMO = 3-methacryloyloxypropyltrimethoxysilane Silfin = vinylsilane + initiator + catalyst VTEO = vinyltriethoxysilane VTMO = vinyltrimethoxysilane VTMOEO = vinyltris(2-methoxyethoxy)silane The coatings according to the invention are applied to the substrate by solidifying the suspension in and on the substrate. According to the invention, the suspension present on and in the substrate can be solidified by heating at from 50 to 350° C. Since the maximum temperature is dictated by the substrate when polymeric substrate materials are used, the maximum temperature must be adapted accordingly. Depending upon the embodiment of the process according to the invention, the suspension present on and in the substrate is solidified by heating at from 100 to 350° C. and most preferably by heating at from 110 to 280° C. It can be advantageous for the heating to take place at from 100 to 350° C. for from 1 second to 60 minutes. It is more preferable to solidify the suspension by heating at from 110 to 300° C. and most preferably at from 110 to 280° C. and preferably for from 0.5 to 10 min. Depending on the temperature level chosen to solidify the membrane, some polymer materials may undergo changes in their chemical structure under the thermal influence, so that the polymers are subsequently no longer present in their original state or original modification. For instance, polyimides may partially carbonize and polyacrylonitrile may form so-called ladder polymers which subsequently undergo a partial carbonization. These effects will always lead to a change in the properties of the carrier materials. This can also be specifically intended, depending on the intended application, since, for example, the solvent, acid and alkali resistance may be enhanced as a result. The degree of transformation involved can be affected via the temperature and the time. The assembly may be heated according to the invention by means of heated air, hot air, infrared radiation or by other heating methods according to the prior art. In a particular embodiment of the process according to the invention, the abovementioned adhesion promoters are applied to the substrate, especially to the polymeric nonwoven, in a preceding step. To this end, the adhesion promoters are dissolved in a suitable solvent, for example ethanol. This solution may additionally include a small amount of water, preferably from 0.5 to 10 times the molar amount of the hydrolyzable group, and small amounts of an acid, for example HCl or HNO3, as a catalyst for the hydrolysis and condensation of the Si—OR groups. This solution is applied to the substrate by the known techniques, for example spraying on, printing on, pressing on, pressing in, rolling on, knifecoating on, spreadcoating on, dipping, spraying or pouring on, and the adhesion promoter is fixed on the substrate by a thermal treatment at from 50 to not more than 350° C. It is only after the adhesion promoter has been applied that this embodiment of the process according to the invention has the suspension being applied and solidified. In another embodiment of the process according to the invention, adhesion-promoting layers are applied in a pretreatment step in which a polymeric sol is applied and solidified. The polymeric sol is preferably applied and solidified in the same way as the suspensions are applied and solidified. Application of these polymeric sols renders the substrates, especially the polymeric nonwovens, finished with an oxide of Al, Ti, Zr or Si as an adhesion promoter and so renders the substrate hydrophilic. Thus rendered substrates can then be given a porous coating as described in WO 99/15262 or as described above, and this coating would be observed to possess distinctly better adhesion, especially to polymeric nonwovens, as a result of the pretreatment. A typical polymeric sol for a pretreatment is an approximately 2-10% by weight alcoholic solution of a metal alkoxide (eg. titanium ethoxide or zirconium propoxide) which may additionally include from 0.5 to 10 mol fractions of water and also small amounts of an acid as a catalyst. After such a sol has been applied to the substrate, the substrates, preferably polymeric nonwovens, are treated at a temperature of not more than 350° C. This will cause a dense film of a metal oxide to form around the substrate fibers, making it possible to infiltrate the substrate with a suspension or slip based on a commercial zirconium nitrate sol or silica sol without wetting problems. Since polymeric sols are more likely to form dense films than particulate sols and, what is more, particulate sols always have relatively large amounts of water in the pore microstructure of the void volumes, it is simpler to dry polymeric sols than particulate sols. Nevertheless, the membranes have to be dried at temperatures of above 150° C. in order that the ceramic material may acquire sufficiently good adhesion to the carrier. Particularly good adhesions are obtainable at a temperature of at least 200° C. and very particularly good adhesions at a temperature of at least 250° C. However, in that case, it is absolutely vital to use polymers of appropriate thermal stability, for example polyethylene terephthalate (PET), polyacrylonitrile (PAN), polytetrafluoroethylene (PTFE), polyvinylidene fluoride (PVDF) or polyamide (PA). If the carrier does not possess sufficient thermal stability, the membrane can initially be preconsolidated by predrying it at a lower temperature (up to 100° C.). When the supplementary consolidation is then carried out at an elevated temperature, the ceramic layer acts as a prop for the support, so that the substrate can no longer simply melt away. These process parameters hold not only for the application and solidification of a polymeric sol, for example as an adhesion promoter, but also for the application and solidification of suspensions based on polymeric sols. Both forms of applying an adhesion promoter prior to the actual application of the suspension provide improved adhesivity of the substrates especially with regard to aqueous particulate sols, which is why especially thus pretreated substrates can be coated according to the invention with suspensions based on commercially available sols, for example zirconium nitrate sol or silica sol. But this way of applying an adhesion promoter also means that the production process of the membrane according to the invention has to be extended to include an intervening or preliminary treatment step. This is feasible albeit more costly than the use of adapted sols to which adhesion promoters have been added, but also has the advantage that better results are obtained on using suspensions based on commercially available sols. The process according to the invention can be carried out for example by unrolling the substrate off a roll, passing it at a speed of from 1 m/h to 2 m/s, preferably at a speed of from 0.5 m/min to 20 m/min and most preferably at a speed of from 1 m/min to 5 m/min through at least one apparatus which applies the suspension atop and into the support and at least one further apparatus whereby the suspension is solidified on and in the support by heating, for example an electrically heated furnace, and rolling the membrane thus produced up on a second roll. This makes it possible to produce the membrane according to the invention in a continuous process. Similarly, the pretreatment steps can be carried out on a continuous basis by observing the parameters mentioned. The membranes according to the invention can be used as a separator in batteries, as a carrier for ultrafiltration, nanofiltration, reverse osmosis, gas separation or pervaporation membranes or simply as a microfiltration membrane. The nonlimiting examples which follow illustrate the present invention. EXAMPLE 1 Preparation of an S450PET Membrane To 160 g of ethanol are initially added 15 g of a 5% by weight aqueous HCl solution, 10 g of tetraethoxysilane, 2.5 g of methyltriethoxysilane and 7.5 g of GLYMO Dynasilane (Degussa AG). This sol, which was initially stirred for some hours, is then used to suspend 125 g each of Martoxid MZS-1 and Martoxid MZS-3 aluminas from Martinswerke. This suspension (slip) is homogenized with a magnetic stirrer for at least a further 24 h, during which the stirred vessel has to be covered over in order that solvent may not escape. This slip is then used to coat a PET nonwoven about 30 μm in thickness and about 20 g/m2 in basis weight in a continuous roll coating process at a belt speed of about 8 m/h and T 200° C. In this roll coating process, the slip is coated onto the nonwoven using a roll turning opposite to the belt direction (the direction of movement of the nonwoven). The nonwoven subsequently passes through an oven at the stated temperature. The same method and apparatus is employed in the runs which follow. The end result obtained is a microfiltration membrane having an average pore size of 450 nm. EXAMPLE 2 Preparation of an S240PAN Membrane To 160 g of ethanol are initially added 15 g of a 5% by weight aqueous HCl solution, 10 g of tetraethoxysilane, 2.5 g of methyltriethoxysilane and 7.5 g of GLYMO Dynasilane. This sol, which was initially stirred for some hours, is then used to suspend 280 g of AlCoA CT1200 SG alumina. This slip (suspension) is homogenized with a magnetic stirrer for at least a further 24 h, during which the stirred vessel has to be covered over in order that solvent may not escape. This slip is then used to coat a PAN nonwoven (Viledon 1773 from Freudenberg) about 100 μm in thickness and 22 g/m2 in basis weight in a continuous roll coating process at a belt speed of about 8 m/h and T=250° C. The end result is a microfiltration membrane having an average pore size of 240 nm. EXAMPLE 3 Preparation of an S450PO Membrane To 160 g of ethanol are initially added 15 g of a 5% by weight aqueous HCl solution, 10 g of tetraethoxysilane, 2.5 g of methyltriethoxysilane and 7.5 g of GLYMO Dynasilane. This sol, which was initially stirred for some hours, is then used to suspend 125 g each of Martoxid MZS-1 and Martoxid MZS-3 aluminas from Martinswerke. This suspension is homogenized with a magnetic stirrer for at least a further 24 h, during which the stirred vessel has to be covered over in order that solvent may not escape. A polyolefin nonwoven composed of polyethylene and polypropylene fibers (FS 2202-03 from Freudenberg) about 30 μm in thickness is coated with the above suspension in a continuous roll coating process at a belt speed of about 8 m/h and T=110° C. The end result is a microfiltration membrane having an average pore size of 450 nm. EXAMPLE 4 Preparation of an S100PET Membrane To 160 g of ethanol are initially added 15 g of a 5% by weight aqueous HCl solution, 10 g of tetraethoxysilane, 2.5 g of methyltriethoxysilane and 7.5 g of GLYMO Dynasilane. This sol, which was initially stirred for some hours, is then used to suspend 280 g of AlCoA CT3000 alumina. This suspension is homogenized with a magnetic stirrer for at least a further 24 h, during which the stirred vessel has to be covered over in order that solvent may not escape. The above suspension is then used to coat a PET nonwoven about 30 μm in thickness and about 20 g/m2 in basis weight in a continuous roll coating process at a belt speed of about 8 m/h and T=200° C. The end result is a microfiltration membrane having an average pore size of 100 nm. EXAMPLE 5 Preparation of an S100PAN Membrane To 160 g of ethanol are initially added 15 g of a 5% by weight aqueous HCl solution, 10 g of tetraethoxysilane, 2.5 g of methyltriethoxysilane and 7.5 g of GLYMO Dynasilane. This sol, which was initially stirred for some hours, is then used to suspend 300 g of AlCoA CT3000 alumina. This slip is homogenized with a magnetic stirrer for at least a further 24 h, during which the stirred vessel has to be covered over in order that solvent may not escape. The above slip is then used to coat a PAN nonwoven (Viledon 1773 from Freudenberg) about 100 μm in thickness and 22 g/m2 in basis weight in a continuous roll coating process at a belt speed of about 8 m/h and T=250° C. The end result is a microfiltration membrane having an average pore size of 100 nm. EXAMPLE 6 Preparation of an S450PAN Membrane To 160 g of ethanol are initially added 15 g of a 5% by weight aqueous HCl solution, 10 g of tetraethoxysilane, 2.5 g of methyltriethoxysilane and 7.5 g of MEMO Dynasilane. This sol, which was initially stirred for some hours, is then used to suspend 140 g each of Martoxid MZS-1 and Martoxid MZS-3 aluminas. This slip is homogenized with a magnetic stirrer for at least a further 24 h, during which the stirred vessel has to be covered over in order that solvent may not escape. The above slip is then used to coat a PAN nonwoven (Viledon 1773 from Freudenberg) about 100 μm in thickness and 22 g/m2 in basis weight in a continuous roll coating process at a belt speed of about 8 m/h and T=250° C. The end result is a microfiltration membrane having an average pore size of 450 nm possessing better adhesivity than described in Example 2. EXAMPLE 7 Preparation of an S450PET Membrane To 160 g of ethanol are initially added 15 g of a 5% by weight aqueous HCl solution, 10 g of tetraethoxysilane, 2.5 g of methyltriethoxysilane and 7.5 g of MEMO Dynasilane. This sol, which was initially stirred for some hours, is then used to suspend 130 g each of Martoxid MZS-1 and Martoxid MZS-3 aluminas from Martinswerke. This slip is homogenized with a magnetic stirrer for at least a further 24 h, during which the stirred vessel has to be covered over in order that solvent may not escape. The above slip is used to coat a PET nonwoven about 30 μm in thickness and about 20 g/m2 in basis weight in a continuous roll coating process at a belt speed of about 8 m/h and T=200° C. The end result is a microfiltration membrane having an average pore size of 450 nm possessing better adhesivity than described in Example 1. EXAMPLE 8 Preparation of a Z450PAN Membrane 10 g of a 70% by weight solution of zirconium propoxide in propanol are dissolved in 340 g of propanol. This solution is admixed with 0.72 g of water and 0.04 g of concentrated hydrochloric acid by vigorous stirring. Stirring of this sol is continued for some hours. This sol is then used to coat a PAN nonwoven (Viledon 1773 from Freudenberg) about 100 μm in thickness and 22 g/m2 in basis weight in a continuous roll coating process at a belt speed of about 8 m/h and T=200° C. 1.4 g of zirconium acetylacetonate are dissolved in a mixture of 150 g of deionized water and 22.5 g of ethanol. 140 g each of MZS-1 and MZS-3 are suspended in this solution and the slip is stirred for at least 24 h. About 1 hour prior to the coating step, a further 75 g of a commercial 30% by weight zirconium nitrate sol from MEL Chemicals are added to the slip. The precoated PAN nonwoven is then coated with this slip in a second continuous roll coating process at a belt speed of about 8 m/h and T=250° C. The end result is a microfiltration membrane having an average pore size of 450 nm, possessing very good adhesivity and excellent resistance even in very alkaline media (pH>10).

20040719

20121225

20050331

77615.0

IMANI, ELIZABETH MARY COLE

CERAMIC MEMBRANE BASED ON A SUBSTRATE CONTAINING POLYMER OR NATURAL FIBRES, METHOD FOR THE PRODUCTION AND USE THEREOF

UNDISCOUNTED

ACCEPTED

ACCEPTED

MOORING ARRANGEMENT

Arrangement for mooring, loading and unloading of a vessel, comprising: a stationary inner tower with a lower end fixedly anchored to the seabed, from where the inner tower extends upwards through the sea to an upper end over the sea level, which inner tower at level close to the seabed has through connections for hoses and cables for transfer of load and signals, which hoses and cables are brought further up through the inner tower and out of its upper end; a yoke that in one end is rotatably fastened to the inner tower, wherefrom the yoke extends further outwards to at least one outer ballastable end wherefrom moorings are arranged to keep the vessel anchored, on which vessel devices are provided to connect the vessel with the moorings and said hoses and cables for transfer of load and signals. The mooring arrangement is distinguished in that it further is comprising an outer tower with rotatable fastening to the inner tower, which outer tower from the fastening to the inner tower extends upwards outside the inner tower to a level over the upper end of the inner tower, wherein the rotatable fastening is placed below sea level and also is comprising the fastening of the yoke, such that the outer tower and the yoke as one unit is freely rotatable over and around the inner tower that is stationary anchored to the seabed; and a swivel provided between the upper end of the inner tower and the upper end of the outer tower, for rotatable transfer of load and signals with said hoses and cables between the inner and the outer tower and therefrom further to the vessel.

1. An arrangement for mooring, loading and unloading of a vessel, comprising: a stationary inner tower with a lower end fixedly anchored to the seabed, from where the inner tower extends upwards through the sea to an upper end over the sea level, which inner tower at level close to the seabed has through connections for hoses and cables for transfer of load and signals, the hoses and cables brought further up through the inner tower and out the upper end, a yoke having one end rotatably fastened to the inner tower, wherefrom the yoke extends further outwards to at least one outer ballastable end wherefrom moorings are arranged to keep the vessel anchored, on which vessel devices are provided to connect the vessel with the moorings and said hoses and cables for transfer of load and signals, an outer tower having a rotatable fastening to the inner tower, the outer tower from the fastening to the inner tower extending upwards outside the inner tower to a level over the upper end of the inner tower, the rotatable fastening placed below sea level and further comprising the fastening of the yoke, such that the outer tower and yoke as one unit is freely rotatable over and around the inner tower that is stationary anchored to the seabed, and a swivel provided between the upper end of the inner tower and the upper end of the outer tower for rotatable transfer of load and signals with the hoses and cables between the inner tower, the outer tower and the vessel. 2. The mooring arrangement according to claim 1 further comprising the rotatable fastening of the outer tower and the yoke located at a depth level deeper than the largest draught for the vessel proximate the lower end of the inner tower and a short distance over the seabed. 3. The mooring arrangement according to claim 1 further comprising the rotatable fastening of the outer tower and the yoke, the placement thereof, the length of the yoke and the length of the moorings with the vessel anchored for loading and unloading, dimensioned such that an extension of the longitudinal axis of the yoke penetrates the stationary anchoring in the seabed. 4. The mooring arrangement according to claim 1 wherein, the rotatable fastening of the outer tower and the yoke further comprises a rotatable disc with fixed self lubricating bearings having a main radial bearing, an upper axial bearing and a lower axial bearing. 5. The mooring arrangement according to claim 1 further comprising the yoke formed as a triangle with a top point fastened to the inner tower and two outer ends between which outer ends ballast chambers are provided and from which two outer end moorings are provided to hold the vessel anchored. 6. The mooring arrangement according to claim 1, further comprising the yoke fastened to a protrusion in a rotatable disc that is rotatable around the inner tower, the yoke rotatably bolted to the protrusion with a fastening bolt with a longitudinal axis parallel with the plane of the rotatable disc and tangential to the rotation axis of the rotatable disc, and wherein the yoke includes a rotatable pin provided outside the rotatable disc in the longitudinal axis of the yoke for rotation around the longitudinal axis, such that the yoke is moveable around three axes.

FIELD OF THE INVENTION The present invention regards arrangements for mooring, loading and unloading of a vessel. The vessel is for example a FPSO-vessel (“Floating Production Storage and Offloading”), but can be a tanker or another type of vessel. The load is preferably comprising hydrocarbons in form of oil or gas, but can be any fluid or for example powder that can be transported through pipes. The invention is in particular relevant for mooring, loading and unloading of a vessel of the FPSO-type at shallow waters. BACKGROUND OF THE INVENTION AND PRIOR ART For mooring, loading and unloading of a vessel at shallow waters, for example a vessel of the FPSO-type, it has proved difficult to arrange anchor chains with sufficient slack such that a suitable resilience is achieved in the mooring system. At too low resilience in the mooring system, sudden vessel movements may result in too large forces. Another crucial factor regarding mooring is to achieve a position restoring force in the mooring, such that the vessel as moored can lay in a stable position during loading and unloading without occurrence of too strong forces. Regarding conventional single anchoring systems with a floating buoy connected with a chain or a connection arm to a foundation structure fastened to the seabed, it has proved that the position restoring forces are insufficient. Completely submerged systems for mooring and transfer of load and signals are possible, but significant problems appear in that critical components are submerged in the sea. This shortens the lifetime significantly and results in severe problems with respect to repair and maintenance. In view of the above, mooring, loading and unloading at shallow waters are preferably undertaken by use of a mooring tower that extends from the seabed and up to above sea level, with a sufficiently resilient anchoring of the vessel to the top of the mooring tower. Patent publication U.S. Pat. No. 4,516,942 contains description of a mooring tower that extends from the anchoring at the seabed to over the sea level, where the tower is provided with a triaxial rotatable yoke in the top in the mooring tower, for mooring and transfer of fluid and signals. The yoke's fastening in the top of the mooring tower results in that the mooring tower is subject to a very large momentum from the mooring forces, and the dimensioning of the mooring tower is therefore very powerful. Also the vessel that is to be moored to the mooring tower according to U.S. Pat. No. 4,516,942 must have a powerful dimensioning in order to handle the forces involved, in particular since the main structure of the vessel has to take up forces from the yoke from above deck level. The volume of the mooring tower and the yoke above the water line and down to the deepest draught for vessels in the waters is very significant, resulting in risk for collision and heavy impact from ice, current, waves and wind. As apparent from the above a number of disadvantages are associated with the mooring tower according to U.S. Pat. No. 4,516,942. The objective of the present invention is to provide an arrangement for mooring without the disadvantages associated with the mooring tower according to patent U.S. Pat. No. 4,516,942 and other relevant prior art, as referred to above. SUMMARY OF THE INVENTION The objective of the present invention is met in that a mooring arrangement is provided, having design and distinguishing features as apparent from claim 1. With the arrangement for mooring according to the present invention the mooring forces providing momentum on the mooring tower are significantly reduced, with resulting consequences for the dimensioning of the mooring tower and the anchoring to the seabed. The momentum of the mooring forces on the mooring tower can be zero at particularly preferred embodiments involving that the resultant of the mooring forces is in line through the anchoring in the seabed. With the arrangement for mooring according to the present invention also the risk for collision with the vessel that is to be moored is reduced, in particular by placing the yoke lower than the maximum draught of the vessel. The reduced dimensions of the mooring tower are reducing the impact from ice, current, waves and wind. DRAWINGS FIG. 1 shows a side view of the arrangement for mooring according to the invention, with a FPSO-vessel as moored. FIG. 2 shows a top view of FIG. 1, FIG. 3 shows an enlarged section of the mooring tower illustrated on FIG. 1, FIG. 4 is a process diagram for the mooring arrangement. DETAILED DESCRIPTION In the following a particular embodiment is further described with reference to the drawings. In this connection only mooring, loading and unloading with a typical FPSO-vessel is considered. FIG. 1 illustrates an embodiment of the arrangement according to the invention, with a FPSO-vessel as anchored, whereby the arrangement is illustrated for a water depth of 25 m and with a FPSO with storage capacity of about 1000000 bbl (160000 m3). The draught of the vessel is 8.0 m with ballast and 15.0 m fully loaded, the length is 265 m and the breadth is 42.5 m. This is of course only for illustration and scaling to other dimensions or vessels can be undertaken according to demand. The arrangement according to the invention is in general most useful for water depths from 20 m to 50 m, but the limits are not fixed. The arrangement is completely making use of known components that all are well proven and have exhibited long service life without need for maintenance. Yet the arrangement and all critical components are designed such that inspection is simple and replacement of critical components is possible. The design life will be chosen to a minimum of 15 years for the illustrated embodiment. FIG. 1 shows, as mentioned, a typical FPSO laying moored to the arrangement according to the invention, with hoses and moorings connected to the buoy of the vessel. The hoses for transfer of load, including cables for transfer of signals, extend out from the vessel via a bending restrictor and hang as catenary lines towards a corresponding bending restrictor at the top of the outer tower of the arrangement according to the invention. The vessel is connected via a mooring fastening structure in the buoy with moorings to the ends of a yoke that is placed submerged under water. As illustrated on the figure the yoke is fastened to the inner tower at a height of 7.0 m over the seabed. The vessel can rotate freely around the inner tower with the yoke, the outer tower, the moorings, hoses and cables. The position restoring effect of the mooring arrangement is increased by ballast provided between the outer arms of the yoke. In the illustrated embodiment the ballast is a 25 m long cylinder of diameter 3 m, divided into three compartments. After installation the central compartment of the ballast cylinder is water filled while the two side compartments are filled with heavy slurry to provide suitable pretensioning of the moorings. Between the top of the outer tower and top of the inner tower a swivel connection is provided to achieve rotatable transfer of load and signals. The swivel deck on FIG. 1 is at elevation 14 m. The swivel comprises a process swivel, a swivel for electrical power and electrical and optical signals, and a swivel for the hydraulics. All seals are designed as double barrier seals. Means will be provided for inert gas purging or similar for rooms with swivels, for pressure monitoring and pressure control. Also emergency shut-down systems for fluids and electrical signals will be provided. The number of hoses and cables is in principle without any particular limit. When the expression hoses here is used it is considered to mean both stiff pipes and flexible pipes, except from the distance between the top of the outer tower and the vessel where hoses or pipes have to be flexible because they are hanging as catenary lines above the water level. A typical tower will for example comprise two 12 inch hoses or pipes for loading of crude oil, a 12 inch flexible pipe for water injection, and an additional reserve pipe of 12 inch. The number, the types and dimension of pipes, hoses or cables can of course be varied according to the demand. As illustrated on FIG. 1, and appearing more clearly on FIG. 3, the inner of the mooring tower is open to the atmosphere and is dry for personnel access. The view of FIG. 1 and FIG. 2 as combined illustrates both the design of the yoke and the inner tower. The inner tower is fixedly fastened to the seabed. Three suction anchors are illustrated in triangular configuration with 15 m between each suction anchor, wherein each suction anchor, having a diameter of 8 m, is to penetrate 8 m into the seabed. The design as illustrated is considered to be sufficiently powerful to hold a FPSO of the specified size passively anchored in a 100 years condition of harsh weather, whereby the vessel is without available motor power. However, it is possible to use other types of anchoring to the seabed, provided that the dimensioning is according to the acting forces. Suction anchors are preferable with respect to installation, fastening force with respect to volume, difficult soil conditions and possible removal after use. Suction anchors can relatively easy be installed and later be removed. The outer tower with all connected equipment and the yoke can weathervane freely with the vessel around the stationary inner tower fixedly anchored to the seabed, under all weather conditions. The arrangement according to the present invention further comprises equipment over the sea-line or placed dry within the tower, which equipment is easily accessible for inspection and maintenance, and said equipment is preferably of known type for rotatable communication of fluid and signals, and mechanical transfer. The tower structure provides dry placement of said equipment and supports the connections for load transfer and signal transfer, which are hanging as catenary lines about 20 m over the sea level. With the arrangement according to the present invention the anchoring forces are transferred via the yoke to the seabed via the rotatable fastening, which in the illustrated embodiment is a rotatable disc. The rotatable fastening of the yoke and the outer tower is the only critical component that is not placed dry in the arrangement according to the present invention. Some further details regarding some of the components are as follows: The inner tower with mounted rotatable disc over a fast anchoring to the seabed represents the stationary part of the arrangement according to the invention and supports all the equipment above. The inner tower takes up the forces acting on the outer tower because of ice, wind, current, the hanged-up hoses, etc., which forces are transferred from the outer tower via bearings along the length between the towers. The bearings can be designed with sliding surfaces manufactured from Inconel cladded steel. The diameter on the lower part of the inner tower below the rotatable disc is according to the illustrated embodiment 3.7 m, while the diameter of the upper part of the inner tower is 3.1 m. On the outside of the outer tower, at the water-line level, an ice-breaking device is installed. Disconnection of the whole mooring arrangement is possible within 48 hours, for example at very severe ice conditions. The arrangement is, however, designed to withstand the worst 100 years conditions of ice. A footbridge can be installed between the vessel and the tower structure, for use at moderate or better weather conditions. The rotatable disc has the outer tower mounted with bolts. The rotatable disc has a protrusion to which the yoke is fastened The rotatable disc is preferably of a well known type according to the so called “STL/STP-system”. The bearing means comprises a main radial bearing encompassing the inner tower and an upper axial bearing and a lower axial bearing. Preferably a self lubricating bearing system of the type Oiles 500 is used, with bronze alloy bearings with PTFE-lubrication, chosen for long service life. The bearings are fixed to the rotatable disc. The upper bearing ring supporting the upper axial bearing is locked to the stationary inner tower by use of a segment locking system fastened in a circular groove on the centre shaft. This is a well proven solution used with good results for swivels subsea, according to the SAL-systems. The fluid transfer system is also illustrated on FIG. 4 where a typical process flow diagram is indicated. As apparent, means are also provided for pigging of the load transferring lines and the water injection hose. Installation and deinstallation is relatively simple because of the suction anchors and large compartments that can be filled with air or ballasted in a controlled way, and by installing the yoke after installation of the tower structure. Then pipes and hoses are installed. It is estimated that 7-8 m water depth is required in order to tow a tower structure as the one illustrated, when it is floating by use of suitable air filling. Preferably a crane vessel, divers and remotely operated vehicles are used in connection with installation and deinstallation.

<SOH> BACKGROUND OF THE INVENTION AND PRIOR ART <EOH>For mooring, loading and unloading of a vessel at shallow waters, for example a vessel of the FPSO-type, it has proved difficult to arrange anchor chains with sufficient slack such that a suitable resilience is achieved in the mooring system. At too low resilience in the mooring system, sudden vessel movements may result in too large forces. Another crucial factor regarding mooring is to achieve a position restoring force in the mooring, such that the vessel as moored can lay in a stable position during loading and unloading without occurrence of too strong forces. Regarding conventional single anchoring systems with a floating buoy connected with a chain or a connection arm to a foundation structure fastened to the seabed, it has proved that the position restoring forces are insufficient. Completely submerged systems for mooring and transfer of load and signals are possible, but significant problems appear in that critical components are submerged in the sea. This shortens the lifetime significantly and results in severe problems with respect to repair and maintenance. In view of the above, mooring, loading and unloading at shallow waters are preferably undertaken by use of a mooring tower that extends from the seabed and up to above sea level, with a sufficiently resilient anchoring of the vessel to the top of the mooring tower. Patent publication U.S. Pat. No. 4,516,942 contains description of a mooring tower that extends from the anchoring at the seabed to over the sea level, where the tower is provided with a triaxial rotatable yoke in the top in the mooring tower, for mooring and transfer of fluid and signals. The yoke's fastening in the top of the mooring tower results in that the mooring tower is subject to a very large momentum from the mooring forces, and the dimensioning of the mooring tower is therefore very powerful. Also the vessel that is to be moored to the mooring tower according to U.S. Pat. No. 4,516,942 must have a powerful dimensioning in order to handle the forces involved, in particular since the main structure of the vessel has to take up forces from the yoke from above deck level. The volume of the mooring tower and the yoke above the water line and down to the deepest draught for vessels in the waters is very significant, resulting in risk for collision and heavy impact from ice, current, waves and wind. As apparent from the above a number of disadvantages are associated with the mooring tower according to U.S. Pat. No. 4,516,942. The objective of the present invention is to provide an arrangement for mooring without the disadvantages associated with the mooring tower according to patent U.S. Pat. No. 4,516,942 and other relevant prior art, as referred to above.

<SOH> SUMMARY OF THE INVENTION <EOH>The objective of the present invention is met in that a mooring arrangement is provided, having design and distinguishing features as apparent from claim 1 . With the arrangement for mooring according to the present invention the mooring forces providing momentum on the mooring tower are significantly reduced, with resulting consequences for the dimensioning of the mooring tower and the anchoring to the seabed. The momentum of the mooring forces on the mooring tower can be zero at particularly preferred embodiments involving that the resultant of the mooring forces is in line through the anchoring in the seabed. With the arrangement for mooring according to the present invention also the risk for collision with the vessel that is to be moored is reduced, in particular by placing the yoke lower than the maximum draught of the vessel. The reduced dimensions of the mooring tower are reducing the impact from ice, current, waves and wind.

20041203

20050823

20050519

62104.0

SOTELO, JESUS D

MOORING ARRANGEMENT

UNDISCOUNTED

ACCEPTED

ACCEPTED

Method of encoding and decoding

The invention relates to a method of encoding user data into codevectors and to a corresponding method of decoding codevectors into user data. In order to be able to use the same ECC decoder for decoding of more than one type of data a method of encoding is proposed comprising the steps of: a) generating a first block of a fixed first number of data symbols by taking a fixed second number, being smaller than said first number, of user data symbols, and a fixed third number of dummy data symbols, and by arranging said user data symbols and said dummy data symbols in a predetermined order, b) encoding said first block of data symbols using an ECC encoder (2) to obtain a codeword having a fixed number of symbols, said codeword comprising said first block of data symbols and a second block of a fixed forth number of parity symbols, and (c) generating a codevector by selecting a fifth predetermined number of user data symbols and a sixth predetermined number of parity symbols from said codeword, the sum of said fifth and sixth number being predetermined and smaller than the sum of said second and forth number.

1. A method of encoding user data into codevectors (C) of an error correcting code (ECC), comprising the steps of: generating a first block (B) of a fixed first number (Z1) of data symbols by taking a fixed second number (Z2), being smaller than said first number (Z1), of user data symbols (U), and a fixed third number (Z3) of dummy data symbols (D), and by arranging said user data symbols (U) and said dummy data symbols (D) in a predetermined order, encoding said first block (B) of data symbols using an ECC encoder (2) to obtain a codeword (E) having a fixed number of symbols, said codeword (E) comprising said first block (B) of data symbols and a second block of a fixed forth number (Z4) of parity symbols (P), and generating a codevector (C) by selecting a fifth predetermined number (Z5) of user data symbols (U2) and a sixth predetermined number (Z6) of parity symbols (P1) from said codeword (E), the sum of said fifth and sixth number being predetermined and smaller than the sum of said second and forth number. 2. A method of decoding codevectors of an error correcting code (ECC) into user data, said codevectors (C) being encoded by a method as claimed in claim 1 and comprising a fifth predetermined number (Z5) of user data symbols (U2) and a sixth predetermined number (Z6) of parity symbols (P1), comprising the steps of: generating a codeword (E) comprising said fixed third number (Z3) of dummy data symbols (D), a codevector (C) and a seventh number (Z71, Z72) of filling symbols (F1, F2), arranged in a predetermined order, the sum of said third, fifth, sixth and seventh number being equal to said the sum of said first and forth number, decoding said codeword (E) using an ECC decoder (8) to obtain said user data symbols (U) embedded in said codevector (C). 3. The method as claimed in claim 2, further comprising the step of providing an erasure flag to said ECC decoder (8) before decoding said codeword (E) indicating that said codeword (E) contains filling symbols (F1, F2) to be corrected by said ECC decoder (8). 4. The method as claimed in claim 3, said erasure flag indicating the position and/or the number of said filling symbols (F1, F2) in said codeword (E) to said ECC decoder (8). 5. The method as claimed in claim 2, wherein the generation of said codeword (E) is controlled such that the order of said dummy data symbols (D), said codevectors (C) and said filling symbols (F1, F2) corresponds to the order of the codeword (E) encoded by the encoder (2), wherein said filling symbols (F1, F2) are arranged at positions of user data symbols (Ul) and/or parity symbols (P2) of said codeword (E) encoded by said encoder (2), which are not included in said codevector (C). 6. The method as claimed in claim 1, said method being used for encoding or decoding, respectively, user data to be recorded on an optical record carrier (5), particularly a CD, a DVD or a DVR disc. 7. The method as claimed in claim 1, said method being used for encoding or decoding, respectively, user data to be stored on a DVR disc in a special purpose zone (SPZ) or a burst cutting area (BCA) and to be decoded by an ECC decoder used for decoding codevectors (C) of a long distance codeword (LDC) or a Burst Indicator Subcode (BIS) codeword. 8. The method as claimed in claim 1, wherein said error correcting code (ECC) is a (32, 16, 17) code and said ECC encoder (2) and decoder are adapted for encoding or decoding, respectively, of a (248, 216, 33) RS code or a (62, 30, 33) RS code. 9. The method as claimed in claim 2, wherein a priori known user data symbols are used by the decoder during decoding of the codeword (E). 10. A device for encoding user data into codevectors (C) of an error correcting code (ECC), comprising: means for generating a first block (B) of a fixed first number (Z1) of data symbols by taking a fixed second number (Z2), being smaller than said first number (Z1), of user data symbols (U), and a fixed third number (Z3) of dummy data symbols (D), and by arranging said user data symbols (U)and said dummy data symbols (D) in a predetermined order, an ECC encoder (2) for encoding said first block (B) of data symbols to obtain a codeword (E) having a fixed number of information symbols, said codeword (E) comprising said first block (B) of data symbols and a second block of a fixed forth number (Z4) of s, and means for generating a codevector (C) by selecting a fifth predetermined number of user data symbols (U) and a sixth predetermined number of parity symbols (P) from said codeword (E), the sum of said fifth and sixth number being predetermined and smaller than the sum of said second and forth number. 11. A device for decoding codevectors (C) of an error correcting code (ECC) into user data, said codevectors (C) being encoded by a method as claimed in claim 1 and comprising a fifth predetermined number of user data symbols (U) and a sixth predetermined number of parity symbols (P), comprising: means for generating a codeword (E) comprising said fixed third number (Z3) of dummy data symbols (D), a codevector (C) and a seventh number of filling symbols, arranged in a predetermined order, the sum of said third, fifth, sixth and seventh number being equal to said the sum of said first and forth number (Z4), an ECC decoder for decoding said codeword (E) to obtain said user data symbols (U) embedded in said codevector (C). 12. Information carrier, in particular optical recording medium, storing codevectors (C) of an error correcting code encoded by a method as claimed in claim 1. 13. Information carrier storing codevector (C) of an error correction code encoded by the method claimed in claim 1 for one type of information and also storing codeword (E) for another type of information. 14. Computer program product comprising program code means for performing the steps of the method as claimed in claim 1 if said computer program runs on a computer.

The invention relates to a method of encoding user data into code words of an error correcting code (ECC), to a corresponding method of decoding code words of an error correcting code into user data, to corresponding devices for encoding or decoding, to an information carrier and to a computer program product. Information carriers like rewritable optical discs, such as a CD−RW, a DVD+RW or a DVR information carrier, contain different kinds of data. For example, a rewritable optical record carrier comprises written user data like video or audio information in the phase change material and address information, for example specifying the position of the user data in each field, the track number, the frame number, the field number or the line number, in the wobble channel. To protect this information parities are added to the information in such a way that errors during read out can be corrected. A well-known method to calculate and correct data with parities are error correcting codes, particularly Reed Solomon Codes (RS codes). In a reading device for reading information from an information carrier particularly the costs for the hardware of the decoder, i.e. the error correcting unit, are high. When due to careful design of the error correcting code used for storing data on the information carrier, however, it will be possible to use the same decoder for more than one type of data so that hardware costs for different types of decoders in one reading device can be saved. However, different types of data almost always imply different types of constraints such as block length and parity length of the decoder which issues have to be solved. The issue of different block length is already addressed in WO 01/04895 A1. Therein a device for reading an information carrier carrying an identification information and user information is disclosed. The identification information is arranged so as to be spread over the information carrier. Organization means are provided for organizing the information in such a way that both the identification information and the user information can be processed by the error correction means. It is an object of the present invention to provide methods of encoding and decoding as well as corresponding devices which enable the use of the same decoder for different types of data, particularly error correcting codes having different numbers of parities. This object is achieved according to the present invention by a method of encoding as claimed in claim 1, comprising the steps of: generating a first block of a fixed first number of data symbols by taking a fixed second number, being smaller than said first number, of user data symbols, and a fixed third number of dummy data symbols, and by arranging said user data symbols and said dummy data symbols in a predetermined order, encoding said first block of data symbols using an ECC encoder to obtain a codeword having a fixed number of symbols, said codeword comprising said first block of data symbols and a second block of a fixed forth number of parity symbols, and generating a codevector by selecting a fifth predetermined number of user data symbols and a sixth predetermined number of parity symbols from said codeword, the sum of said fifth and sixth number being predetermined and smaller than the sum of said second and forth number. A corresponding method of decoding codevectors according to the present invention is claimed in claim 2, comprising the steps of: generating a codeword comprising said fixed third number of dummy data symbols, a codevector and a seventh number of filling symbols, arranged in a predetermined order, the sum of said third, fifth, sixth and seventh number being equal to said the sum of said first and forth number, decoding said codeword using an ECC decoder to obtain said user data symbols embedded in said codevector. The present invention is based inter alia on the idea to define a first block having a fixed block length, to fill in user data to be encoded in one portion and to fill up the remaining portion with dummy data symbols. The block length is chosen such that it is consistent with the block length expected by an ECC encoder already present and used for encoding other data. After encoding of said block, however, not the complete obtained codeword is used as codevector and, e.g. stored on an information carrier or transmitted over a network, but only a certain part thereof, particularly a predetermined number of user data symbols and parity symbols included in said codeword in order to save storage and/or to comply with given storage requirements. Correspondingly, during decoding the same codeword is formed, filled in with the received codevector, the same dummy data symbols and, in remaining empty portions, with filling symbols. Said filling is controlled such that the order of the symbols is the same as in the codeword obtained during encoding. Thus, an ECC decoder already present and used for decoding codevectors of other codes can be used for decoding said codevectors to obtain the user data embedded in said codevectors. This simplifies devices for recording and/or reading of information carriers storing different types of data because, generally, only one type of error correcting means has to be included reducing the production costs of such devices. It should be noted that it is not relevant for the invention which user data symbols and which parity symbols of a codeword are taken and used as a codevector. Further, the position of the dummy data symbols and the user data symbols in a codeword are arbitrary; the only requirement is that the positions of the dummy data symbols and the user data symbols are known and that the values of the dummy data symbols are known. Preferred embodiments of the invention are defined in the dependent claims. In accordance with a preferred aspect of the invention an erasure flag is used indicating to the decoder that the codeword contains filling symbols to be corrected by said ECC decoder, in particular indicating the position and/or the number of filling symbols in said codeword to said ECC decoder. This has the advantage that the number of parities necessary to correct errors by an ECC decoder can be reduced, if the decoder already knows that there are errors and in which positions these errors are. E.g., when the decoder already knows that the codeword comprises 16 errors, i.e. comprises 16 filling symbols marked as erasures by erasure flags, only 16 parities are required to correct these errors, leaving 16 parities for correcting additional errors in the written codevector. Without such erasure flags, 32 parities would be necessary to correct 16 errors. The method according to the invention is preferably used for encoding or decoding, respectively, user data to be recorded on an optical record carrier, particularly a CD, a CD-ROM, a DVD or a DVR disc of, preferably, a rewritable or recordable type. Particularly in the field of DVR user data are stored in a special purpose zone (SPZ) or a Burst Cutting Area (BCA). In said zone, which is located at the most inner side of the disc, a “barcode” is written. The data in this barcode is protected by an ECC. Since the bit density of the barcode is very low only 32 bytes can be stored therein. In order to protect these bytes with an ECC which has a Hamming distance of 17, i.e. which uses 16 parities, the same decoder as used for decoding codewords of a long distance codeword (LDC) or for decoding Burst Indicator Subcode (BIS) words is preferably used. Corresponding devices for encoding and decoding, respectively, are defined in claims 10 and 11. The invention relates also to an information carrier, in particular an optical recording medium, storing codevectors of an error correcting code encoded by a method as claimed in claim 1. Still further, the invention relates to a computer program product comprising program code means for performing the steps of the method as claimed in claim 1 or 2 if said computer program runs on a computer. The invention will now be explained in more detail with reference to the drawings, in which FIG. 1 shows a block diagram illustrating the methods of encoding and decoding according to the present invention, FIG. 2 shows the generation of a codeword and a codevector used according to the present invention, FIG. 3 shows an embodiment of an encoding apparatus illustrating code puncturing, FIG. 4 shows an embodiment of a decoding apparatus illustrating code puncturing, FIG. 5 shows another codevector according to the invention, and FIG. 6 shows still another codevector according to the invention. The block diagram shown in FIG. 1 illustrates the methods of encoding and decoding according to the present invention. In a block generation unit 1 a first block B of a fixed first number of data symbols is generated. Said block generation unit 1 receives as input a number of user data symbols U and a number of dummy data symbols D which are arranged in a predetermined order to form said block B. Said block B of data symbols is thereafter encoded by an ECC encoder 2 to obtain a codeword E, i.e. to obtain parity symbols for error correction. While conventionally said codewords E are completely used as codevectors, according to the present invention only a fixed portion of said codewords E is used as codevectors C which are stored on an information carrier 5 by a write unit 3 under control of a control unit 4. Said control unit 4 controls the generation of said codevectors C from said codewords E, i.e. selects according to a fixed rule which symbols of said codewords E are used as codevectors C. These blocks and symbols can be seen in FIG. 2 showing a complete codeword E and the different portions thereof. As explained, said codeword E comprises a first block B of a first fixed number Z1 of data symbols. Said data symbols comprise a fixed second number Z2 of user data symbols U (J1, U2) and a third fixed number Z3 of dummy data symbols D. These dummy data symbols D are filled in, to achieve the fixed block length of said block B and can, in general, be freely chosen. Preferably they are chosen as non-zero values, particularly having the value FF in hexadecimal notation. The ECC encoder 2 calculates a fourth fixed number Z4 of parity symbols P (P1, P2) resulting in an encoded codeword E having in total Z1+Z4 symbols. Therefrom codevectors C are generated by selecting a fifth fixed number Z5 of data symbols U2 and a fixed sixth number Z6 of parity symbols P1. Said codevectors C are then stored on the record carrier 5. To give a more detailed example which may be applied for storing data on a DVR information carrier, particularly to protect data to be stored in a barcode of the burst cutting area (BCA) of a DVR information carrier the first block B will be formed by 16 user data symbols U and 14 dummy data symbols D, thus coming to 30 data symbols of the first block B. The PIC and main data of a DVR information carrier include so-called BIS (Burst Indicator Subcode) data which are protected by a RS code with 32 parities and having a codeword length of 62, i.e. being protected by a (62, 30, 33) RS code. In order to be able to use an ECC decoder to be built for said code also for decoding the user data stored in the barcode of the BCA the first block B having 30 data symbols is encoded by a corresponding ECC encoder, i.e. an encoder for a [62, 30, 33] code, generating 32 parity symbols, resulting in a block length of 62 symbols of the codeword E. Since the bit density of the barcode in the BCA is very low only 32 symbols (bytes) can be stored therein. Thus, according to the present invention, from said codeword E the 16 user data symbols U and 16 parity symbols P are used as codevector C and stored on the information carrier. However, in general the method according to the invention will also work if less user data symbols and more parity symbols are combined to form a codevector C as long as the sum of said symbols is 32. In the embodiment shown in FIG. 2 a number Z5 of user data symbols U2, e.g. 12 user data symbols U2, and a number Z6 of parity symbols P1, e.g. 20 parity symbols P1, are combined into one codevector. It should be noted that it does not matter which symbols of the U and P portions of the codeword E are taken and used as codevector C. Further, the position of the D and U portions in the codevector C are arbitrary. The positions can be swapped (first U and then D); the only requirement is that the positions for the U and D portions are known and that the values of the D symbols are known. During decoding the codevectors C are read from the information carrier 5 by a reading unit 6 and further inputted into a codeword generation unit 7. Therein the codeword E will be regenerated so that it has the same number and arrangement of symbols as during encoding. Therefore, the codeword E is filled with said third number Z3 of dummy data symbols D having the same value as the dummy data symbols D used during encoding. Thereafter the codevector C including said fifth number Z5 of user data symbols U2 and said sixth number Z6 of parity symbols P1 are inserted at the same positions as they have been in the codeword during encoding. Finally, remaining portions are filled with filling symbols F1, F2, i.e. a seventh number (Z71+Z72) of filling symbols F1, F2 is filled in at positions where in the codeword E during encoding user data symbols U1 and parity symbols P2 had been located, but had not been stored on the information carrier 5. The filling of said codeword can preferably be achieved by sending the data thereof in the correct order to an ECC decoder 8 adapted to decode such codewords E to obtain the original user data U comprising the user data symbols U1 and U2. To enable the codeword generation unit 7 to reconstruct the codeword E it must be known to said unit 7 how the codeword E had been constructed during encoding, i.e. the number of dummy data symbols D, user data symbols U and parity symbols P, their positions in the codeword E as well as the length of the codevector including the positions of symbols selected to form said codevector C have to be known to the codeword generation unit 7, e.g. have to be fixed by a corresponding standard. Also the value of the dummy data symbols D have to be fixed in advance. Reverting to the above described example for storing data in the barcode on an DVR information carrier, where the codevector C comprises 12 user data symbols U2 and 20 parity symbols P1, it will be clear that 4 (Z71) filling symbols F1 and 12 (Z72) filling symbols F2 are filled into the remaining portions during decoding to form the codeword E. Preferably, the filling symbols are flagged as erasures so that the ECC decoder only requires Z71+Z72 parities to correct these errors. In the example, only 16 parities are needed to correct said 16 errors (filling symbols), similar to a conventional 16 parity code which leaves 16 parities to correct errors in the written codevector which is similar to a conventional 16 parity RS code, while without such erasure flags twice as many parities would be needed for a correction. As already mentioned above the number Z5 of user data symbols U2 and the number Z6 of parity symbols P1 used to form the codevector C are not fixed, but only the sum Z5+Z6 of said numbers is fixed. Thus it may also be possible to use no user data symbols U and all parity symbols P, i.e. Z4 parity symbols, as codevector C. During decoding, at first Z3 dummy data symbols D, thereafter Z2 filling symbols F and finally Z4 parity symbols would then be sent as codeword E to the ECC decoder to obtain the Z2 user data symbols U, which have originally been located at the positions of the filling symbols F. Also in this case the Z2 user data symbols (erasures) can be calculated using Z2 (being smaller than Z4) parity symbols and using the remaining Z4−Z2 parity symbols to correct errors from the information carrier. If a conventional 16 parity RS code is used 16 data symbols and 16 parities are usually written on a disc. In this codeword of 32 symbols a maximum of 16 errors can be corrected. According to the present invention a 32 parity RS code is used which will offer the same performance of the 16 parity RS code. It is important to note that according to the invention the codevector, e.g. the symbols written on disc, belong to a 32 parity RS codeword and can not be decoded by a 16 parity RS decoder. When applying the invention in DVR, on the encoding side a 248 symbols codeword is formed which comprises 200 dummy data symbols, 16 user data symbols and 32 parity symbols, i.e. a (248, 216, 33) RS code is used, called LDC or Long Distance Code in DVR. From the 16 user symbols and 32 parity symbols 32 symbols are written to disc as codevector. Again, it is important to mention that is does not matter which 32 from these 48 symbols are written to disc. On the decoding side the same 248 symbol codeword is formed. The 200 known dummy data symbols are placed on the correct positions in the codeword. The 32 symbols written to disc are also placed in the codeword and the 16 non written (and unknown) symbols are passed to the decoder as erasures. The decoder uses 16 of the 32 parities to calculate the 16 unknown symbols which leaves 16 parities to correct errors in the 32 symbol written codevector. Thus, a performance can be achieved as if a 16 parity RS code was used. The general use of code puncturing, as particularly described in European patent application EP 01201841.2, the description of which is herein incorporated by reference, shall now be explained with reference to FIGS. 3 and 4. FIG. 3 illustrates the method of encoding an information word m into a codeword c and FIG. 4 illustrates the method of decoding a possibly mutilated codeword r into an information word m. As shown in FIG. 3 the information word m comprising k information symbols is encoded by an encoding unit 41 of an encoding apparatus 40 using an intermediate generator matrix G″. Said intermediate generator matrix G″ derives from a generator matrix G which has been selected by a selection unit 42 as particularly explained in European patent application EP 01201841.2. The intermediate generator matrix G″ is larger than the generator matrix G in that it comprises at least one more column than the generator matrix G. In general, the generator matrix G has k rows and n columns while the intermediate generator matrix G″ has k rows and n+k columns and comprises k columns with a single non-zero entry at mutually different positions. When using said intermediate generator matrix G″ for encoding the information word m, intermediate codewords having k+n symbols are obtained. From said intermediate codeword the codeword c is obtained from a codeword generating unit 44 by omitting a number of symbols of said intermediate codeword t. Therein the number of symbols to omit corresponds to the difference between the number of columns of said intermediate generator matrix G″ and said generator matrix G. Thus, the obtained codeword c comprises n symbols. However, it is to be noted that also G can be used directly for encoding in the encoding apparatus instead of G″. During decoding a possibly multilated codeword r comprising a symbols is received by a decoder as shown in FIG. 4. In a first step the received word r is extended into a first pseudo codeword r′ by an extension unit 50. Therein said intermediate generator matrix G″ which has already been used in the encoder is used to determine the length of said pseudo codeword r′, i.e. the number of symbols of said pseudo codeword r′ corresponds to the number of columns of said intermediate generator matrix G″, i.e. to the n symbols of the received word r k erasures are added to obtain the pseudo codeword r′. If G has been used directly for encoding instead of G″, the pseudo codeword r′ equals the n symbols of the received word r to which k erasures are added. Thereafter, in a replacement umit 51 a priori known information symbols, e.g. m1, m5, m6, are replaced in said pseudo codeword r′ at positions of the erasures which correspond to the positions of said a priori known information symbols. This means that the erasures 1, 5 and 6 are replaced by the a priori known information symbols m1, m5, m6. The obtained second pseudo codeword r″ is thereafter inputted to a decoder unit 52 which is preferably a known error and erasure decoder decoding said second pseudo codeword r″ by use of said intermediate generator matrix G″ into the information word m comprising k symbols. According to this embodiment a larger intermediate generator matrix G″ is used compared to the standard generator matrix G. However, the advantage of this embodiment is that the information symbols do not need to be known a priori in successive order but any additional information symbol known a priori irrespective of the position of the information symbol within the information word generally leads to an enhanced minimum Hamming distance compared to the code used if no information symbols are known a priori. The embodiment based on code puncturing shall now be illustrated differently. Considered is an [8, 3, 6] extended Reed-Solomon Code C over a Galois Field GF (8) defined as follows. The vector c=(c−1, c0, c1. . . , c6) is in C if and only if c - 1 = ∑ i = 0 6 ⁢ ⁢ c i ⁢ ⁢ and ⁢ ⁢ ∑ i = 0 6 ⁢ ⁢ c i ⁢ α ij = 0 ⁢ ⁢ ⁢ for ⁢ ⁢ 1 ≤ j ≤ 4. Herein, α is an element of GF(8) satisfying α3=1+α. It can be seen that the following intermediate generator matrix G″ generates the code C G ″ = ( 1 0 0 α 2 1 α 6 α 2 α 6 0 1 0 α 3 1 α 3 α α 0 0 1 α 4 1 α 5 α 5 α 4 ) . The rightmost 5 columns of the intermediate generator matrix G″ are used as a generator matrix G, i. e. the generator matrix G is G = ( α 2 1 α 6 α 2 α 6 α 3 1 α 3 α α α 4 1 α 5 α 5 α 4 ) . The code generated by the generator matrix G has minimum Hamming distance 3. Knowledge of any j information symbols effectively increases the minimum Hamming distance from 3 to 3+j. Coming back to the present invention, in a first embodiment for use in DVR, as explained above with reference to FIG. 2 and as shown in FIG. 5, the codevector C may comprise Z5=16 user data symbols U (Z71=0) and Z6=16 parity symbols P1. In a second embodiment for use in DVR, as shown in FIG. 6, the codevector C may comprise Z4=32 parity symbols P but no user data symbols U. For decoding of the codevector C of the first embodiment (FIG. 5) 16 erasures are put on the locations of the parity symbols P2 by the decoder to reconstruct the codeword E, leaving Hamming distance 17 available for correcting errors and erasures in the locations of the user data symbols U and the parity symbols P in the codeword E. For decoding of the codevector C of the second embodiment (FIG. 6) 16 erasures are put on the locations of the user data symbols U by the decoder to reconstruct the codeword E, again leaving at least Hamming distance 17 available for correcting errors and erasures in the locations of the user data symbols U and the parity symbols P in the codeword E. However, if a number x of user data symbols are known a priori to the decoder, these need not be erased by the decoder enhancing the remaining Hamming distance. Thus, the decoder decoding the reconstructed codeword E has Hamming distance 17+x available for correcting errors and erasures in the locations of the user data symbols U and the parity symbols P in the codeword E. User data symbols can, as an example described in European patent application EP 01201841.2, be known a priori to the decoder if much of the header information of a current sector can be inferred from the previously read sectors and the table of contents, or from the knowledge where the reading or writing head will approximately land. A possible application is thus in the field of address retrieval on optical media. It should be noted hat the encoding procedure of said second embodiment is similar to the embodiment described above with reference to FIGS. 3 and 4. Therein a kx(n+k) matrix G″=(I,G) is used, where I is the kxk identity matrix, and G a kxn generator matrix. Since the standard [62,30,33] RS code used according to the present invention is a systematic code, its 30×62 generator matrix Gstandard can be written as Gstandard=(I,P′), where the 30×32 matrix P′ denotes the parity part of the matrix Gstandard Encoding of the dummy data symbols D corresponds to using the upper 14 rows of Gstandard, while encoding of the user data symbols U corresponds to using the lower 16 rows of Gstandard. Because the dummy data symbols D are known at the decoder, it can be reconstructed free of errors at the decoder. Conceptually, the contribution of the dummy data symbols D to the parities P is also known at the decoder and can be subtracted from the parity symbols P to obtain intermediate parity symbols P″, which then only depend on the user data symbols U. The bottom 16 rows of Gstandard form a 16×62 matrix of which the first 14 columns are all-zero. G standard = ( I 14 0 P 14 × 32 ′ 0 I 16 P 16 × 32 ′ ) The matrix I16 corresponds to the systematic reproduction of the user data symbols U in the codeword E which is not transmitted. The matrix P′16×32 corresponds to the part of the parity part P′ of Gstandard that effectively generates the parities corresponding to the user data symbols U. In terms of the embodiment shown in FIGS. 3 and 4, the equivalence is given by (I,G)=(I16, P′16×32). It should be noted that the advantageous effect of using a number of a priori known user data symbols by the decoder can also be applied if the codevector C is not formed exclusively by parity symbols as shown in FIG. 6, but also if the codevector C consists of a number of user data symbols, but not all user data symbols, and a number of parity symbols. It should be noted that the present invention is not limited to the above-described embodiment or to encoding or decoding of data to be stored on a DVR information carrier. The invention is generally applicable in any kind of technical field where different kinds of data shall be encoded using more than one error correcting code having different numbers of parities, particularly in any new optical, magnetic or mobile communication standard. The invention can also be applied to any kind of information carrier, be it a read-only, recordable or rewritable information carrier for storing any kind of data in any area of such an information carrier. In addition, the codevectors need not necessarily be stored but can also be transmitted over a network or a transmission line.

20040719

20070403

20050210

99379.0

CHAUDRY, MUJTABA M

METHOD OF ENCODING AND DECODING

UNDISCOUNTED

ACCEPTED

ACCEPTED

Method for manufacturing cellulose carbamate

The invention relates to a method for manufacturing cellulose carbamate. In the method, an auxiliary agent and urea in solution form and possibly in solid form are absorbed into cellulose, and a reaction between cellulose and urea is carried out in a mixture containing cellulose, a liquid, the auxiliary agent, and urea The absorption of the auxiliary agent and urea into cellulose, and the reaction between the cellulose and the auxiliary agent at least partly are carried out in a working device. According to the invention, it is possible to manufacture cellulose carbamate without ammonia, organic solvents or other auxiliary agents, by using only a small quantity of water as a medium.

1. A method for manufacturing cellulose carbamate, in which method an auxiliary agent and urea are absorbed into cellulose, and a reaction between cellulose and urea is carried out in a mixture containing cellulose, a liquid, the auxiliary agent, and urea, wherein the liquid content in the mixture is less than 40%. 2. The method according to claim 1, wherein the auxiliary agent is an alkalizing agent. 3. The method according to claim 1, wherein the auxiliary agent is hydrogen peroxide. 4. The method according to claim 1, wherein the absorption of the auxiliary agent and urea up to the core of the cellulose fiber is enhanced and/or the reaction between cellulose and urea is performed at least partly by subjecting the mixture to mechanical working. 5. The method according to claim 4, wherein the mixture is subjected to the working between two surfaces moving in relation to each other. 6. The method according to claim 5, wherein in the working, the mixture is pressed through openings in one of the surfaces. 7. The method according to claim 5, wherein the working is performed by running the mixture through a nip formed by two rolls. 8. The method according to claim 7, wherein the surface of at least one of the rolls is provided with a grooving. 9. The method according to claim 5, wherein the same mixture is recirculated several times between the two surfaces moving in relation to each other. 10. The method according to claim 1, wherein more than 50% of the liquid is water. 11. The method according to claim 1, wherein the auxiliary agent and an aqueous solution of urea, and possibly dry, powdery urea, are premixed into cellulose in such a way that the liquid substances are added in atomized form. 12. The method according to claim 11, wherein the premixing is performed in a fluidized bed mixer. 13. The method according to claim 1, wherein the processing time is less than 30 min. 14. The method according to claim 1 wherein the cellulose is wood cellulose or dissolving pulp or cotton linters. 15. The method according to claim 1, wherein the cellulose is finely ground to a grain size of <2 mm. 16. The method according to claim 1, wherein during the working, the temperature of the mixture is adjusted by the circulation of an external heating or cooling medium. 17. The method according to claim 1, wherein the liquid content in the mixture is less than 30%. 18. The method according to claim 1, wherein the liquid content in the mixture is less than 25%. 19. The method according to claim 1, wherein the liquid content in the mixture is less than 22%. 20. The method according to claim 2, wherein the alkalizing agent is sodium hydroxide. 21. The method according to claim 4, wherein the mixture is subjected to a mechanical working in such a way that the components of the mixture are subjected to working repeatedly. 22. The method according to claim 6, wherein the working is performed in a sieve press. 23. The method according to claim 10, more than 70% of the liquid is water. 24. The method according to claim 10, wherein more than 90% of the liquid is water. 25. The method according to claim 10, wherein all of the liquid is water. 26. The method according to claim 13, wherein the processing time is less than 20 min. 27. The method according to claim 13, wherein the processing time is less than 15 min. 28. The method according to claim 13, wherein the processing time is less than 10 mm. 29. The method according to claim 15, wherein the cellulose is ground to a grain size of less than 1 mm. 30. The method according to claim 15, wherein the cellulose is ground to a grain size of less than 0.7 mm.

FIELD OF THE INVENTION The invention relates to a method for manufacturing cellulose carbamate, in which method cellulose is allowed to react with an auxiliary agent and urea. Carbamate cellulose can be used further as an alkaline solution, in the same way as viscose cellulose, for example in the manufacture of fibres and films and for reinforcing paper products, by regenerating the solution back to cellulose fibres, as is done in a viscose process. Another possibility is to use it only by precipitating as carbamate fibres or films. TECHNICAL BACKGROUND The manufacture of fibres and films from cellulose by the viscose process has been known for more than a hundred years. Even today, almost all cellulose-based fibres are manufactured by the viscose method. It is a known method, by which various properties of the final product are achieved by varying the material and process parameters. However, the viscose method involves significant drawbacks: the preparation of the spinning solution includes laborious work stages, the carbon disulphide used for the dissolution is toxic, inflammable and combustible, and it is difficult to recover. Furthermore, some of the carbon disulphide is decomposed to hydrogen sulphide, which is also toxic and explosive. In addition, the viscose solution is an unstable product, whereby it cannot be stored as an intermediate product, but all the steps of the manufacture must be taken without a delay from the beginning to the end, keeping the mass at a low temperature. Several attempts are known to replace the viscose method with a more ecological method. The most promising one has been the conversion of cellulose to cellulose carbamate by means of urea (see, for example, D. Klemm et al., Comprehensive Cellulose Chemistry, Wiley-VCH 1998). In spite of its obvious advantages and several known attempts, this method has, however, remained on the laboratory scale. Reasons have included problems in the homogeneity of the product, the recovery and residues of organic auxiliary agents (e.g. hydrocarbon) and/or solvents (normally ammonia) used, the properties of the final products (primarily fibres), which have been not more than satisfactory, and the operation costs of the methods developed. Known attempts to provide a method for manufacturing cellulose carbamate have been based on the soaking of pulp sheets in an alkaline solution (mercerization), which has, in some cases, included an addition of ammonia and/or other solvents or accelerators. After the mercerization, the pulp, partly dried by compressing, is treated in a urea solution, which may include an addition of an alkalizing agent, normally also ammonia and possible solvents or salts. Finally, the reaction between urea and the pulp is carried out in an oven at a temperature of about 130° C. The methods have required the best viscose cellulose whose DP level has been reduced, for example, by long-term curing in a mercerization solution or by irradiation in advance. Examples of the above-described processes are presented in patents FI 61033, EP 0 402 606 and WO 00/08060. One of the first attempts to manufacture cellulose carbamate is presented in U.S. Pat. No. 2,134,825. It uses the aqueous solution of urea and sodium hydroxide, with which the pulp sheets are first impregnated. After the impregnation, settling and compression, the mass is dried and heated in the oven to achieve a reaction between the cellulose and urea. The patent presents a number of chemicals to improve the absorption and to reduce the gelling tendency of the solution. This patent also presents the use of hydrogen peroxide for the purpose of reducing the viscosity of the solution. However, pulps manufactured on the basis of the patent have been only partly soluble in such a way that a large quantity of unreacted fibres is left in the solution, jamming the spinning nozzle. This is probably due to the unevenness of the substitution. In all known methods for manufacturing cellulose carbamate, an alkaline solution (aqueous sodium hydroxide) is used for activating (swelling) the pulp, as in conventional mercerization of pulp. An exception to this, U.S. Pat. No. 2,134,825 experiments the use of hydrogen peroxide with and without sodium hydroxide to activate the pulp for the purpose of reducing the viscosity of the solution. Cellulose carbamate is alkali soluble at a substitution degree of 0.2 to 0.3. The formation of cellulose carbamate begins when the mixture of cellulose and urea is heated to a temperature exceeding the melting point of the latter (133° C.). When heated, urea is decomposed to isocyanic acid and ammonia according to the following reaction formula: NH2—CO—NH2→HN═C═O+NH3 Isocyanic acid is very reactive and it forms carbamates with the hydroxy groups of cellulose as follows: Cell-OH+H—N═C═O→Cell-O—C—NH2 Possible side reactions include the reaction of urea and isocyanic acid to a biuret, or the formation of cyanuric acid and other polymerization products of isocyanic acid. GENERAL DESCRIPTION OF THE INVENTION The purpose of the invention is to start from the starting points of said U.S. Pat. No. 2,134,825 but to apply a new processing technique to eliminate the problems involved in the quality of the product and to provide several parameters for the control of the properties of the final product. The aim of the invention is also to present a method by which it is possible to prepare solutions and final products of high quality also when starting from ordinary and inexpensive wood pulp. To achieve these aims, the invention is characterized in what will be presented in claim 1. In the method according to the invention, cellulose is allowed to react with the auxiliary agent and urea at a high dry matter content and without an organic solvent or other auxiliary agents. In the method, the penetration of the chemicals into the fibre, the homogenization of the pulp, the reduction of the crystallinity of the pulp, the DP adjustment of the product, and partly also the reaction are caused by mechanical working. The reaction is completed in an oven. Some preferred embodiments of the invention will be described in the other claims. The auxiliary agent used in the reaction is an alkalization agent, such as an alkali metal hydroxide, or hydrogen peroxide. When hydrogen peroxide is used, it can replace the alkali metal hydroxide partly or entirely in the pretreatment of the pulp before the addition of liquid urea. In the method according to the invention, the penetration of the auxiliary agent and urea in the cellulose can be enhanced in a mechanical working device. Under mechanical working, the fibre bundles are disintegrated, the pores in the fibre are opened and the liquid penetrates into the fibre. The auxiliary agent activates the fibre and contributes to the penetration of urea. The mechanical working is also used for homogenization of the mixture of pulp and chemicals. The mechanical working device is particularly a sieve press, a roll mixer, or an extruder. The reaction is carried out in a mixture containing a liquid. Its content in the mixture is, for example, less than 40%, advantageously less than 30%, preferably less than 25%, and most preferably less than 22%. For example, more than 50%, advantageously more than 70%, preferably more than 90%, and most preferably all of the liquid is water. The cellulose used can be, for example, wood pulp, dissolving pulp, or linters. The cellulose used as the basic material is preferably fine ground cellulose (particle size e.g. less than 0.7 mm). The particle size is indicated as the mesh size of the sieve which the particles pass in the grinding. The processing device is a mechanical working device, in which the mixture is compressed, rubbed and stretched several times. In particular, the working device may be a sieve press, a continuously operating roll mixer, or an extruder. Thanks to the thermal energy produced during the mechanical working and/or introduced in the system from the outside, the temperature of the mixture can be raised to such a level that the actual reaction can also be started and performed, at least partly, already in the mechanical working device. It is typical of the mechanical working method that the cellulose fibres, together with the other ingredients in the mixture, must go several times through the same working event, when the migration of a single fibre is examined. The alkalization agent used as the auxiliary agent may be, particularly, an alkali metal hydroxide, such as sodium hydroxide. The alkalization agent can be added in the reaction mixture, for example, in an aqueous solution and/or in the dry state. The alkalization agent can be added before urea, or partly or wholly simultaneously with urea. The urea can be added in dry state and/or in an aqueous solution. The feeds of liquid substances can be performed in an atomized form in a pre-mixing device, for example a fluidized bed mixer, followed by the reaction in the mechanical working device. The liquid, the urea and the auxiliary agent are dosed into the cellulose in such a proportion that the liquid content of the mixture is raised to the aforementioned relatively low starting level at which the absorption takes place. A part of the urea can also be added in solid form. Surprisingly, the alkali metal hydroxide, such as sodium hydroxide, can be replaced wholly or entirely by hydrogen peroxide (H2O2) in the pretreatment of the pulp before the addition of liquid urea. The manufacture of cellulose carbamate is not successful with the urea solution alone. In particular, it has been surprising that when H2O2 is used, the optimal quantity of urea is lower than in a corresponding process based on NaOH. Furthermore, the quantity of hydrogen peroxide in relation to the pulp is smaller than the corresponding quantity of NaOH. From what has been said above, it follows that the efficiency is higher, the consumption of chemicals is lower, and the quantity of material to be circulated in the wash is smaller. In combination, these will compensate for the higher price of H2O2 so that the total costs of the manufacturing process will remain lower than in a corresponding process based on NaOH. NMR and IR analyses of cellulose carbamate made by the method show that cellulose carbamate is the same as in the case of pulp treated with NaOH. Hydrogen peroxide works, as in known cellulose processing techniques (primarily bleaching), by reducing the DP level of the pulp. The DP level is now controlled in two ways: on one hand, by the quantity of H2O2 and, on the other hand, by the degree of mechanical working. In the method according to the invention, in which the alkalizing agent is wholly replaced with hydrogen peroxide, the penetration of chemicals into the fibres can be enhanced in the mechanical working device as in the case of sodium hydroxide. The solutions thus obtained are of at least as high quality as in the case of sodium hydroxide. Surprisingly, we have found that the pulp activated by means of the peroxide can, after the dosage of the chemicals, be directly introduced in the reaction oven, without mechanical working, still resulting in applicable solutions. Solutions prepared by this method can be used in applications which allow a small quantity of remaining fibres. The hydrogen peroxide can be added before the urea, partly or wholly simultaneously with the urea. It can be added in the form of an aqueous solution. The dosages of liquid substances into the cellulose can be provided in atomized form in a mixing device, for example a fluidized bed mixer, followed, if necessary, by mechanical working and the partial reaction in the mechanical working device. The liquid content achieved in the dosage is low in the same way as when an alkalizing agent is used; that is, the liquid content in the mixture is less than 40%, advantageously less than 30%, preferably less than 25%, and most preferably less than 22%. For example, more than 50%, advantageously more than 70%, preferably more than 90%, and most preferably all of the liquid is water. The cellulose used can be, for example, wood cellulose, dissolving pulp, or cotton linters. The cellulose used as the starting material is preferably fine ground cellulose (particle size e.g. less than 0.7 mm). The content of hydrogen peroxide in relation to the dry weight of the cellulose is normally at least 1%, preferably 1 to 12%. In one aspect of the invention, the mechanical working device is a sieve press or a roll mixer, which are reliable in use and which are not jammed as easily as extruders. In a sieve press, the pulp is pressed through channels. Normally, rotating rolls are used for the pressing. The pressing efficiency depends on the diameter and length of the channels, the number of channels per area, as well as the press load on the pulp over the channel matrix. There is a variety of such devices. The channel matrix may be rotating, placed underneath a press roll mounted on a fixed axle. There may also be several rolls. The press rolls may also be inside a cylindrical rotating matrix. If necessary, the matrix or the rolls can be heated or cooled. A roll mixer comprises two rolls rotating opposite to each other. The pulp to be mixed is fed into a nip formed by the rolls, in which the pulp adheres as a mat on the surface of one roll and is compressed several times in the nip. In a continuously operating roll mixer, the pulp is fed into one end of the nip, and the mat is conveyed to the opposite end of the nip. To facilitate the conveying, the rolls may be provided with shallow screw thread grooves or low screw thread ridges, the rolls may tilted towards the outlet end, or there may be a speed difference between the rolls. The surface material of the rolls is selected so that the pulp adheres as a uniform mat to the desired roll. If necessary, one or both of the rolls can be heated or cooled. In one aspect of the invention, when mechanical working is used, the pulp is run several times, for example 2 to 10 times, such as 4 to 6 times, through the mechanical working device. At the sieve press, this may involve the change of the sieve plate after a few compression times, or the use of two different presses one after the other. In an aspect of the invention, the total processing time is less than 30 min, advantageously less than 20 min, preferably less than 15 min, and most preferably less than 10 min. The pre-mixing time is for example less than 30 min, preferably less than 15 min, and most preferably less than 10 min. The drying and reaction time will depend on the temperature in that the time can be reduced at a higher temperature. In the method according to the invention, for example ammonia, organic solvents or other auxiliary agents will not be needed. Water, needed as the medium is supplied together with the chemicals to be added in the system. Because of the high dry matter content, the mixture can, after the mechanical working, be transferred directly to the reaction step to an oven or the like to elevated temperature, without drying in an intermediate step. When hydrogen peroxide is used as the auxiliary agent, mechanical working is not necessarily needed, depending on the use. In this case it is essential that the liquid content (water content) of the reaction mixture is low, as mentioned above. After absorption for a given time at a low liquid content, the mixture which has not been worked mechanically, is transferred to the reaction step into the oven. DESCRIPTION OF THE DRAWINGS In the following, some embodiments of the invention will be described in detail. The appended drawings are part of the description. In the drawings, FIG. 1 shows, in three cross-sectional views, a sieve press in which the reaction according to the invention can be carried out, and FIG. 2 shows, in top and side views, a continuously operating roll mixer in which the reaction according to the invention can be carried out. DETAILED DESCRIPTION OF SOME EMBODIMENTS OF THE INVENTION In FIG. 1, a sieve press 1 is provided with a drive shaft 3 placed in a stationary vat 2, a horizontal roll axle being mounted on the shaft and rolls 4 being journalled at the ends of the axle. The bottom of the vat is a sieve plate matrix 5, against which the rolls roll when the drive shaft is rotated. The sieve plate matrix is exchangeable. The side walls of the vat and the matrix form a jacket, through which a heat transfer medium can be led. The rolls can also be equipped with heat transfer devices. The rotating rolls press the pulp supplied into the vat through openings in the sieve plate matrix, whereupon the pulp is compressed into pellets. The pressing efficiency depends on the diameter and length of the channels, the number of channels per area, as well as the press load caused by the rolls on the pulp over the matrix. The roll mixer 6 shown in FIG. 2 comprises two adjacent rolls rotating in opposite directions: a rubbing roller 7 and a pulp roll 8. The material to be pressed adheres to the surface of the pulp roll, being pressed several times in the nip between the rolls, when the rolls are rotated. The rolls are provided with a screw thread grooving for conveying the material to the other end of the nip. The rolls are equipped with heat transfer devices. In the following examples, various formulations will be used, and a sieve press will be used as the mechanical working method. It will be common to them all that the chemical dosage is made in batches in a fluidized bed mixer. Depending on the chemicals used during and after the dosage, cooling of the pulp may be needed. Also the working devices are coolable or heatable. The sieve plate press is used for homogenizing the pulp and partly for the reaction by running the pulp several times through the press. This is optimized in relation to the quality aimed at (DP, viscosity, filtration residue). The quality of the process was evaluated by analyzing the alkali-dissolved carbamate cellulose solution by various methods. Some or all of the following methods will be used here according to the case: 1) Degree of polymerization (DP), which gives an estimate of the mechanical and physical properties of the final product (fibres and films) and which is used as a measure for the quality control in the process. The higher the DP level, the more diluted solutions must be used, if the level of viscosity is limited because of application. The optimal DP level and cellulose content must be found separately in each case. Normally, in the manufacture of viscose fibres, the desired DP level is in the range from 200 to 400. For determining the DP, the method according to the standard SCAN-CM 15:99 is used here. In the method, the viscosity ratio is determined to evaluate the DP on the empirical basis (see e.g. J. Gullichsen, H. Paulapuro, Papermaking Science and Technology, Fapet 2000). 2) Clogging indicator Kw (filtration residue) represents the content of insoluble matter in the solution. This is a common measurement for the quality of a solution, and particularly a measure for the clogging tendency of a fibre nozzle. This analysis is made according to the article by H. Sihtola in Paperi ja puu 44 (1962):5, pp. 295-300. It should be noted that the result will, to some extent, depend on the filter cloth type used. The filter mentioned in the article is no longer available, but a corresponding type has been sought here. After a number of tests, we decided to use the paper-based filter type 520B manufactured by Schleicher & Schnell. Normally, a solution with Kw<2000 is considered good in view of fibre applications. 3) The nitrogen content of the solution indicates the degree of substitution. The degree of substitution refers to the average number of substituents attached to one glucose unit. In this context, the Kjeltek device by VTT BEL (supplied by Tecator) is used for determining the nitrogen content. If the carbamate cellulose is not regenerated but only precipitated, the nitrogen is also left in the final product. The obtained product is thus different in its properties, for example biodegradability, than viscose-based products. 4) The degree of purity of the carbamate pulp is analyzed by washing and by measuring the content of residues. 5) The viscosity of the solution is measured by the conventional ball method (see said article by Sihtola) and/or by a Brookfield viscometer. The control of viscosity is essential in view of the processing (nozzle flows and pulp transfer in general), as was already mentioned in connection with the DP analysis. Furthermore, the viscosity has an influence on the operation of the dissolving mixer: the higher the viscosity formed in the solution, the higher the mixer efficiency and/or the better the mixer configuration needed to achieve a good dispersion. 6) The fibre residue of the solution is also evaluated microscopically by using a subjective scale from 1 to 5 in such a way that 1: clear solution with no fibres and 5: turbid solution containing a lot of whole fibres, fibre bundles and/or gel-like structures. The percentages given in this application are weight percentages, unless otherwise indicated. EXAMPLES 2 TO 5 In Examples 1 to 7, three different pulp types were used with various NaOH quantities and urea contents. The mechanical working was carried out by means of a sieve plate press with several runs through. The dosage of chemicals is carried out in a fluidized bed type mixer in such a way that during the dosage, the pulp is moving all the time and the chemicals are added in atomized form to achieve as high a homogeneity as possible. Both of the chemicals (alkalizing agent and urea) are dozed separately one after the other. The urea is dosed in an aqueous solution in such a way that the total moisture content remains as shown in the table. NaOH is dosed in an aqueous solution. The cellulose is finely ground wood pulp. The sieve plate working is carried out with a continuously operating sieve plate device, in which the feeding is performed by a double-screw feeder. The feed rate is selected so that no material will be accumulated in front, on top or on the sides of the wheels, but all the fed material is pressed through the holes in the matrix. On the outflow side of the matrix, the material is cut with a cutter to granules. The jacket can be cooled by an external water circulation. Process and Running Parameters for Sieve Plate Pressing: Hole diameter and length D/H mm 3/40 Number of holes 120 Inner/outer diameter of hole distribution d/D mm 160/190 Number and diameter of press rolls D1 mm 2/150 Rotational speed of roll rpm 10-20 Temperature set for cooling the jacket T° C. −5 . . . +100 Number of times to run through 1-20 The following table 1 includes the pulp types of different test runs (DP of starting pulp), dosage quantities (chemicals in relation to the dry weight of pulp), the calculated total water content, and the number of times to run through the sieve plate working. TABLE 1 The manufacture of cellulose carbamate with an alkali metal hydroxide as the auxiliary agent. NaOH Water % No. of Test % on Urea % in total working No. Pulp type pulp on pulp mass cycles 1 Birch pulp, DP 950 7 62 21.2 14 2 Birch pulp, DP 950 7 22 22.2 8 3 Birch pulp, DP 950 7 70 20.4 14 4 Eucalyptus dissolving 7 42 18.1 4 pulp, DP 600 5 Eucalyptus dissolving 11 50 20.7 7 pulp, DP 600 6 Eucalyptus dissolving 5 70 22.4 14 pulp, DP 600 7 Softwood dissolving 7 70 22.5 10 pulp, DP 1400 After the processing, the reaction is completed in an oven, in which T=140° C. and the retention time t=4 h, followed by refining with a disc refiner. After the refining, the powder is dissolved in an aqueous NaOH solution in such a way that the final concentration of the solution will be 9.6 wt-% of NaOH. The properties of the cellulose carbamates thus obtained are presented in table 2 below. TABLE 2 Properties of cellulose carbamates obtained by the manufacturing methods of examples 1 to 7. Degree of Clogging Viscosity of the Ball viscosity Test polymerization indicator solution (cP)/ s/CCA Nitrogen Degree Quality of No. DP Kw concentration % concentration N % of purity % solution 1 220 2740/6 52/6 1.96 63.2 2 2 600 0.15 76.9 5 3 100 596/5.5 2.52 61.2 3 4 250 37500 5500/6 36/9 1.13 76.4 4 5 69 934 265/6 102/10 3.16 67.5 1 6 240 2177 60/7 73.0 1 7 315 1945 38/5 73.0 1 In the examples 8 to 15, the same dissolving pulp type is always used, and formulations based on NaOH and H2O2 are compared with each other. Various quantities of NaOH and H2O2 and urea contents are used. The mechanical working is performed with a sieve plate press whose running parameters are the same as in the examples 1 to 7 but in which 10 run-through times are used. The dosage of chemicals is carried out in a batch type fluidized bed mixer in such a way that during the dosage, the pulp is moving all the time and the chemicals are added in atomized form to achieve as high a homogeneity as possible. Both chemicals are dosed one after the other, first H2O2 or NaOH and then urea, in aqueous solutions of different concentrations to achieve the total moisture content given in the table. The cellulose is finely ground to the mesh size of 0.3 mm. The following table 3 shows the formulations for the different test runs. The pulp type is the same for all (softwood dissolving pulp, DP 1900, finely ground to the size of 0.3 mm). The table shows the quantities for dosing the chemicals (in relation to the dry weight of pulp alone) and the total water content calculated on the total mass of the mixture: TABLE 3 Dosage ratios of example test runs with alkali metal hydroxide or hydrogen peroxide as auxiliary agent. The examples 8 to 11 are with the NaOH formulation and the examples 12 to 15 with the H2O2 formulation. H2O2 % NaOH % Urea % Water % in Test No. on pulp on pulp on pulp total mass 8 — 7 72 24 9 — 7 72 24 10 — 7 72 24 11 — 9.2 91 26.1 12 10.8 — 72.0 25.8 13 7.0 — 42.0 21.3 14 3.8 — 30.8 24.0 15 3.0 — 30.0 20.4 After the working, the reaction is completed in an oven, in which T=135° C. and the retention time t=4 h, and finally the pulp is refined with a disc refiner. The properties of the cellulose carbamates thus obtained are presented in the following table 4. TABLE 4 Analysis results of example test runs. Degree of Clogging Test Polymerization indicator Concentration Nitrogen Degree Quality of No. DP Kw of solution % Ball viscosity S N % of purity % solution 8 230 1900 5 12 1 9 700 6400 3 10 200 400 7 40 69.7 1 11 160 553 2.5 51 66.2 1 12 130 627 8 199 2.4 69.1 1 13 160 1489 7 58 2.5 79.6 1 14 400 5 140 1.5 84.5 3 15 300 570 7 18 82.6 1 The invention is not restricted to the examples of the above description, but it can be modified within the scope of the inventive idea presented in the claims.

<SOH> TECHNICAL BACKGROUND <EOH>The manufacture of fibres and films from cellulose by the viscose process has been known for more than a hundred years. Even today, almost all cellulose-based fibres are manufactured by the viscose method. It is a known method, by which various properties of the final product are achieved by varying the material and process parameters. However, the viscose method involves significant drawbacks: the preparation of the spinning solution includes laborious work stages, the carbon disulphide used for the dissolution is toxic, inflammable and combustible, and it is difficult to recover. Furthermore, some of the carbon disulphide is decomposed to hydrogen sulphide, which is also toxic and explosive. In addition, the viscose solution is an unstable product, whereby it cannot be stored as an intermediate product, but all the steps of the manufacture must be taken without a delay from the beginning to the end, keeping the mass at a low temperature. Several attempts are known to replace the viscose method with a more ecological method. The most promising one has been the conversion of cellulose to cellulose carbamate by means of urea (see, for example, D. Klemm et al., Comprehensive Cellulose Chemistry, Wiley-VCH 1998). In spite of its obvious advantages and several known attempts, this method has, however, remained on the laboratory scale. Reasons have included problems in the homogeneity of the product, the recovery and residues of organic auxiliary agents (e.g. hydrocarbon) and/or solvents (normally ammonia) used, the properties of the final products (primarily fibres), which have been not more than satisfactory, and the operation costs of the methods developed. Known attempts to provide a method for manufacturing cellulose carbamate have been based on the soaking of pulp sheets in an alkaline solution (mercerization), which has, in some cases, included an addition of ammonia and/or other solvents or accelerators. After the mercerization, the pulp, partly dried by compressing, is treated in a urea solution, which may include an addition of an alkalizing agent, normally also ammonia and possible solvents or salts. Finally, the reaction between urea and the pulp is carried out in an oven at a temperature of about 130° C. The methods have required the best viscose cellulose whose DP level has been reduced, for example, by long-term curing in a mercerization solution or by irradiation in advance. Examples of the above-described processes are presented in patents FI 61033, EP 0 402 606 and WO 00/08060. One of the first attempts to manufacture cellulose carbamate is presented in U.S. Pat. No. 2,134,825. It uses the aqueous solution of urea and sodium hydroxide, with which the pulp sheets are first impregnated. After the impregnation, settling and compression, the mass is dried and heated in the oven to achieve a reaction between the cellulose and urea. The patent presents a number of chemicals to improve the absorption and to reduce the gelling tendency of the solution. This patent also presents the use of hydrogen peroxide for the purpose of reducing the viscosity of the solution. However, pulps manufactured on the basis of the patent have been only partly soluble in such a way that a large quantity of unreacted fibres is left in the solution, jamming the spinning nozzle. This is probably due to the unevenness of the substitution. In all known methods for manufacturing cellulose carbamate, an alkaline solution (aqueous sodium hydroxide) is used for activating (swelling) the pulp, as in conventional mercerization of pulp. An exception to this, U.S. Pat. No. 2,134,825 experiments the use of hydrogen peroxide with and without sodium hydroxide to activate the pulp for the purpose of reducing the viscosity of the solution. Cellulose carbamate is alkali soluble at a substitution degree of 0.2 to 0.3. The formation of cellulose carbamate begins when the mixture of cellulose and urea is heated to a temperature exceeding the melting point of the latter (133° C.). When heated, urea is decomposed to isocyanic acid and ammonia according to the following reaction formula: in-line-formulae description="In-line Formulae" end="lead"? NH 2 —CO—NH 2 →HN═C═O+NH 3 in-line-formulae description="In-line Formulae" end="tail"? Isocyanic acid is very reactive and it forms carbamates with the hydroxy groups of cellulose as follows: in-line-formulae description="In-line Formulae" end="lead"? Cell-OH+H—N═C═O→Cell-O—C—NH 2 in-line-formulae description="In-line Formulae" end="tail"? Possible side reactions include the reaction of urea and isocyanic acid to a biuret, or the formation of cyanuric acid and other polymerization products of isocyanic acid.

20040721

20100216

20050310

97324.0

WHITE, EVERETT

METHOD FOR MANUFACTURING CELLULOSE CARBAMATE

SMALL

ACCEPTED

ACCEPTED

Polyolefin membrane with integrally asymmetrical tructure and process for producing such a membrane

Process for producing an integrally asymmetrical hydrophobic polyolefinic membrane with a sponge-like, open-pored, microporous support structure and a separation layer with a denser structure, using a thermally induced liquid-liquid phase separation process. A solution of at least one polyolefin is extruded to form a shaped object. The solvent used is one for which the demixing temperature of a solution of 25% by weight of the polyolefin in this solvent is 10 to 70° C. above the solidification temperature. After leaving the die, the shaped object is cooled using a liquid cooling medium that does not dissolve the polymer up to the die temperature, until the phase separation and solidification of the high-polymer-content phase take place. The integrally asymmetrical membrane producible in this manner has a porosity of greater than 30% to 75% by volume, a sponge-like, open-pored, microporous support layer without macrovoids and with on average isotropic pores, and on at least one of its surfaces a separation layer with pores <100 nm, if any. The membrane is preferably used for gas separation or gas transfer processes, in particular for oxygenation of blood.

1. Process for producing an integrally asymmetrical hydrophobic membrane having a sponge-like, open-pored, microporous support structure and a separation layer with a denser structure compared to the support structure, the process comprising at least the steps of: a) preparing a homogeneous solution from a system comprising 20-90% by weight of a polymer component comprising at least one polyolefin and 80-10% by weight of a solvent for the polymer component, wherein the system at elevated temperatures has a range in which it is present as a homogeneous solution on cooling has a critical demixing temperature, below the critical demixing temperature in the liquid state of aggregation has a miscibility gap, and has a solidification temperature, b) rendering the solution to form a shaped object, with first and second surfaces, in a die at a die temperature above the critical demixing temperature, c) cooling the shaped object by contacting the shaped object with a liquid cooling medium that does not dissolve or react chemically with the polymer component at temperatures up to the die temperature, the liquid cooling medium being conditioned to a cooling temperature below the solidification temperature, at such a rate that a thermodynamic non-equilibrium liquid-liquid phase separation into a high-polymer-content phase and a low-polymer-content phase takes place and solidification of the high-polymer-content phase subsequently occurs when the temperature of the shaped object falls below the solidification temperature, and d) optionally removing the low-polymer-content phase from the shaped object, wherein a solvent for the polymer component is selected for which, on cooling at a rate of 1° C./min, the demixing temperature of a solution of 25% by weight of the polymer component in the solvent is 10 to 70° C. above the solidification temperature. 2. Process for producing a membrane according to claim 1, wherein the solvent for the at least one polymer is one for which, for a solution of 25% by weight of the polymer component in the solvent and a cooling rate of 1° C./min, the critical demixing temperature is 20 to 50° C. above the solidification temperature. 3. Process for producing a membrane according to claim 1, wherein the solvent for the at least one polymer is one for which, for a solution of 25% by weight of the polymer component in this solvent and a cooling rate of 1° C./min, the critical demixing temperature is 25 to 45° C. above the solidification temperature. 4. Process for producing a membrane according to claim 1, wherein the polymer component has a density of ≦910 kg/m3. 5. Process for producing a membrane according to claim 1, wherein the liquid cooling medium is a non-solvent for the polymer component that, on heating up to a boiling point of the non-solvent, does not dissolve the polymer component to form a homogeneous solution. 6. Process for producing a membrane according to claim 1 wherein the liquid cooling medium is a liquid that is a strong non-solvent for the polymer component and is homogeneously miscible with the solvent at the cooling temperature. 7. Process for producing a membrane according to claim 1, wherein the liquid cooling medium has a temperature that is at least 100° C. below the critical demixing temperature. 8. Process for producing a membrane according to claim 1, wherein 30-60% by weight of the polymer component is dissolved in 70-40% by weight of the solvent. 9. Process for producing a membrane according to claim 1, wherein the at least one polyolefin contained in the polymer component consists exclusively of carbon and hydrogen. 10. Process for producing a membrane according to claim 9, wherein the at least one polyolefin is a poly(4-methyl-1-pentene). 11. Process for producing a membrane according to claim 9, wherein the at least one polyolefin is a polypropylene. 12. Process for producing a membrane according to claim 9, wherein the at least one polyolefin is a mixture of a poly(4-methyl-1-pentene) and a polypropylene. 13. Process for producing a membrane according to claim 10, wherein the solvent is palm nut oil, dibutyl phthalate, dioctyl phthalate, dibenzyl ether, coconut oil, or a mixture thereof. 14. Process for producing a membrane according to claim 11, wherein the solvent is N,N-bis(2-hydroxyethyl)tallow amine, dioctyl phthalate, or a mixture thereof. 15. Process for producing a membrane according to claim 1, wherein the membrane is a hollow-fiber membrane. 16. Hydrophobic integrally asymmetrical membrane made by a process according to claim 1, wherein the membrane consists essentially of at least one polyolefin, has first and second surfaces and an intermediate support layer with a sponge-like, open-pored, microporous structure and adjacent to this support layer on at least one of the surfaces a separation layer, where the separation layer is dense or has pores with an average diameter ≦100 nm, the support layer is free of macrovoids, the pores in the support layer are on average substantially isotropic, and the membrane has a porosity in the range from greater than 30% to less than 75% by volume. 17. A gas separation process, comprising contacting a gas to be separated with the membrane made by the process of claim 1. 18. A gas transfer process, comprising contacting a gas with the membrane made by the process of claim 1. 19. An oxygenation of blood process, comprising contacting blood with the membrane made by the process of claim 1. 20. An oxygenation of blood process, comprising contacting blood with the membrane of claim 16.

CROSS-REFERENCE TO RELATED APPLICATION The present application is a U.S. national stage application of International Application No. PCT/EP03/00084, filed on Jan. 8, 2003. BACKGROUND OF THE INVENTION 1. Field of Invention The invention relates to a process for producing a hydrophobic membrane using a thermally induced phase separation process in accordance with the preamble of claim 1, the membrane having a sponge-like, open-pored, microporous structure, and to the use of the membrane for gas exchange processes, in particular oxygenation of blood, and for gas separation processes. 2. Description of Related Art In a multitude of applications in the fields of chemistry, biochemistry, or medicine, the problem arises of separating gaseous components from liquids or adding such components to the liquids. For such gas exchange processes, there is increasing use of membranes that serve as a separation membrane between the respective liquid, from which a gaseous component is to be separated or to which a gaseous component is to be added, and a fluid that serves to absorb or release this gaseous component. The fluid in this case can be either a gas or a liquid containing the gas component to be exchanged or capable of absorbing it. Using such membranes, a large surface can be provided for gas exchange and, if required, direct contact between the liquid and fluid can be avoided. Membranes are also used in many different ways to separate individual gas components from a mixture of different gases. In such membrane-based gas separation processes, the gas mixture to be separated is directed over the surface of a membrane usable for gas separation. Sorption and diffusion mechanisms result in a transport of the gas components through the membrane wall, with the transport of the individual gas components of the mixture occurring at different rates. This causes an enrichment of the permeate stream passing through the membrane by the most rapidly permeating gas component, while the retentate stream is enriched by the components that permeate less readily. This ability to separate individual gas components from a gas mixture using membranes finds numerous applications. For example, membrane-based gas separation systems can be used to enrich the oxygen content of air to increase combustion efficiency or to enrich nitrogen in the air for applications requiring an inert atmosphere. An important application of membrane-based gas exchange processes in the medical field is for oxygenators, also called artificial lungs. In these oxygenators, which are used in open-heart operations, for example, oxygenation of blood and removal of carbon dioxide from the blood take place. Generally, bundles of hollow-fiber membranes are used for such oxygenators. Venous blood flows in this case in the exterior space around the hollow-fiber membranes, while air, oxygen-enriched air, or even pure oxygen, i.e., a gas, is passed through the lumen of the hollow-fiber membranes. Via the membranes, there is contact between the blood and the gas, enabling transport of oxygen into the blood and simultaneously transport of carbon dioxide from the blood into the gas. In order to provide the blood with sufficient oxygen and at the same time to remove carbon dioxide from the blood to a sufficient extent, the membranes must ensure a high degree of gas transport: a sufficient amount of oxygen must be transferred from the gas side of the membrane to the blood side and, conversely, a sufficient amount of carbon dioxide from the blood side of the membrane to the gas side, i.e., the gas flow or gas transfer rates, expressed as the gas volume transported per unit of time and membrane surface area from one membrane side to the other, must be high. A decisive influence on the transfer rates is exerted by the porosity of the membrane, since only in the case of sufficiently high porosity can adequate transfer rates be attained. A number of oxygenators are in use that contain hollow-fiber membranes with open-pored, microporous structure. One way to produce this type of membrane for gas exchange, such as for oxygenation, is described in DE-A-28 33 493. Using the process in accordance with this specification, membranes with up to 90% by volume of interconnected pores can be produced from meltable thermoplastic polymers. The process is based on a thermally induced phase separation process with liquid-liquid phase separation. In this process, a homogeneous single-phase solution is first prepared from the thermoplastic polymer and a compatible component that forms a binary system with the polymer, the system in the liquid state of aggregation having a range of full miscibility and a range with a miscibility gap, and this solution is then extruded into a bath that is substantially chemically inert with respect to, i.e., does not substantially react chemically with, the polymer and has a temperature lower than the demixing temperature. In this way, a liquid-liquid phase separation is initiated and, on further cooling, the thermoplastic polymer solidified to form the membrane structure. The membranes in accordance with DE-A-28 33 493 have an open-pored, microporous structure and also open-pored, microporous surfaces. On the one hand, this has the result that, in gas exchange processes, gaseous substances such as oxygen (O2) or carbon dioxide (CO2) can pass through the membrane relatively unrestricted and the transport of a gas takes place as a “Knudsen flow” combined with relatively high transfer rates for gases or high gas flow rates through the membrane. Such membranes with gas flow rates for CO2 exceeding 1 ml/(cm2*min*bar) and for O2 at approximately the same level have gas flow rates that are sufficiently high for oxygenation of blood. On the other hand, in extended-duration use of these membranes in blood oxygenation or generally in gas exchange processes with aqueous liquids, blood plasma or a portion of the liquid can penetrate into the membrane and, in the extreme case, exit on the gas side of the membrane, even if in these cases the membranes are produced from hydrophobic polymers, in particular polyolefins. This results in a drastic decrease in gas transfer rates. In medical applications for blood oxygenation, this is termed plasma breakthrough. The plasma breakthrough time of such membranes as producible in accordance with DE-A-28 33 493 is sufficient in most cases of conventional blood oxygenation to oxygenate a patient in a normal open-heart operation. However, these membranes are not suitable for so-called extended-duration oxygenation due to their relatively short plasma breakthrough times. Such membranes also cannot be used for gas separation tasks due to their consistent open-pored structure. However, in the field of oxygenation, the desire exists for membranes with higher plasma breakthrough times in order to attain higher levels of safety in extended-duration heart operations and to rule out the possibility of a plasma breakthrough that would require immediate replacement of the oxygenator. The aim is also to be able to oxygenate premature infants or in general patients with temporarily restricted lung function long enough until the lung function is restored, i.e., to be able to conduct extended-duration oxygenation. A prerequisite for this is appropriately long plasma breakthrough times. A frequently demanded minimum value for the plasma breakthrough time in this connection is 20 hours. From EP-A-299 381, hollow-fiber membranes for oxygenation are known that have plasma breakthrough times of more than 20 hours, i.e., there is no plasma breakthrough even under extended use. This is achieved with the otherwise porous membranes by using a barrier layer with an average thickness not exceeding 2 μm and substantially impermeable to ethanol. According to the disclosed examples, the membranes in accordance with EP-A-299 381 have a porosity of at most 31% by volume, since at higher porosity values the pores are interconnected via the membrane wall and communication occurs between the sides of the hollow-fiber membranes, resulting in plasma breakthrough. The production of these membranes is conducted via a melt-drawing process, i.e., the polymer is first melt-extruded to form a hollow fiber and then hot- and cold-drawn. In this case, only relatively low porosity values are obtained, which means that, in conjunction with the transport occurring in the barrier layer via solution diffusion, the attainable transfer rates for oxygen and carbon dioxide remain relatively low. Moreover, while the hollow-fiber membranes in accordance with EP-A-299 381 exhibit sufficient tensile strength as a result of the pronounced drawing in conjunction with manufacture, they have only a small elongation at break. In subsequent textile processing steps, such as producing hollow-fiber mats, which have proven excellent in the production of oxygenators with good exchange capacity and as are described in EP-A-285 812, for example, these hollow-fiber membranes are therefore difficult to process. U.S. Pat. No. 4,664,681 discloses polyolefin membranes in particular for gas separation, with a microporous layer and a non-porous separation layer, the membranes also being produced using a melt-drawing process. The properties of these membranes are similar to those described in EP-A-299 381. Typically, in melt-drawing processes, membranes are formed with slit-shaped pores with pronounced anisotropy, the first main extension of which is perpendicular to the drawing direction and the second main extension perpendicular to the membrane surface, i.e., in the case of hollow-fiber membranes runs between the exterior and interior surfaces of the membrane, so that the channels formed by the pores run in a relatively straight line between the surfaces. In the case in which, for example, mechanical damage in the spinning process causes leaks in the barrier layer, a preferred direction then exists for the flow of a liquid between the interior and exterior surfaces or vice versa, thereby promoting plasma breakthrough. DE-C-27 37 745 relates to microporous bodies likewise produced using a process with thermally induced liquid-liquid phase separation. During production of the microporous bodies, when the polymer solution is cast onto a substrate, such as a metal plate, the microporous bodies according to DE-C-27 37 745 can also exhibit a surface skin with a structure not having a cellular form, the thickness of the skin being in most cases approximately the thickness of an individual cell wall. DE-C-27 37 745, however, does not state that such microporous bodies with a surface skin are usable for gas exchange processes, in particular extended-duration oxygenation, or for gas separation processes. Moreover, hollow-fiber membranes cannot be produced using the procedure described in DE-C-27 37 745. In WO 00/43113 and WO 00/43114, integrally asymmetrical polyolefin membranes are disclosed, and processes for producing them described, that are usable for gas exchange, in particular extended-duration oxygenation, or also for gas separation. The processes are likewise based on a thermally induced phase separation process with liquid-liquid phase separation. The membranes according to WO 00/43113 or WO 00/43114 have a support layer with a sponge-like, open-pored, microporous structure and, adjacent to on this support layer on at least one of the surfaces a separation layer with a denser structure. To produce this membrane structure, and in particular the separation layer, the cited specifications for producing the polyolefin solutions employed start with solvent systems consisting of a mixture of a solvent with a non-solvent for the polyolefin, where the properties of the solvent and non-solvent must meet specific requirements. A disadvantage of the processes disclosed in these specifications is that solvent systems must always be used that are mixtures of several components. Such solvent systems are, from experience, complex with respect to the elements of the process that are aimed at reusing the individual components. SUMMARY OF THE INVENTION It is therefore an object of the invention to provide a simplified process for producing integrally asymmetrical membranes with a microporous support structure and a separation layer with a denser structure, also in the form of hollow-fiber membranes, that are suited for gas exchange and at high gas exchange levels are impervious over extended periods of time to a breakthrough of hydrophilic liquids, in particular blood plasma, or that are suited for gas separation, the membranes having good qualities for further processing. The object is achieved by a process for producing an integrally asymmetrical hydrophobic membrane having a sponge-like, open-pored, microporous support structure and a separation layer with a denser structure compared to the support structure, the process comprising at least the steps of: a) preparing a homogeneous solution from a system comprising 20-90% by weight of a polymer component consisting of at least one polyolefin and 80-10% by weight of a solvent for the polymer component, wherein the system at elevated temperatures has a range in which it is present as a homogeneous solution and on cooling a critical demixing temperature, below the critical demixing temperature in the liquid state of aggregation a miscibility gap, and a solidification temperature, b) rendering the solution to form a shaped object, with first and second surfaces, in a die having a temperature above the critical demixing temperature, c) cooling the shaped object using a cooling medium, conditioned to a cooling temperature below the solidification temperature, at such a rate that a thermodynamic non-equilibrium liquid-liquid phase separation into a high-polymer-content phase and a low-polymer-content phase takes place and solidification of the high-polymer-content phase subsequently occurs when the temperature falls below the solidification temperature, d) possibly removing the low-polymer-content phase from the shaped object, characterized in that a solvent for the polymer component is selected for which, on cooling at a rate of 1° C./min, the demixing temperature of a solution of 25% by weight of the polymer component in this solvent is 10 to 70° C. above the solidification temperature and that, for cooling, the shaped object is brought into contact with a liquid cooling medium that does not dissolve or react chemically with the polymer component at temperatures up to the die temperature. Surprisingly, it has been shown that, by adhering to these process conditions, integrally asymmetrical membranes are obtained in which at least one surface is formed as a separation layer that covers the adjacent sponge-like, open-pored, microporous support layer and has a denser structure compared to the support layer. The process according to the invention allows the realization of very thin separation layers, whose structure can be adjusted from dense to nanoporous, with pores having an average size of less than 100 nm and in individual cases beyond that. At the same time, the support layer of the membranes produced in this manner has a high volume porosity. Preferably, the process according to the invention is used to produce integrally asymmetrical membranes with a dense separation layer. In this context, a dense separation layer or dense structure is understood to be one for which no pores are evident based on an examination by scanning electron microscope at 60000× magnification. The process according to the invention thus permits the production of integrally asymmetrical membranes with a separation layer that is impervious over long periods of time to liquid breakthrough but at the same time gas permeable, and with a support layer with high volume porosity, resulting at the same time in high gas transfer levels for these membranes in gas transfer processes. These membranes find excellent application for extended-duration blood oxygenation, the separation layer of these membranes being responsible for making them impervious over extended periods of time to the breakthrough of blood plasma. At the same time, membranes with a dense separation layer can be produced that allow high gas separation factors to be attained and can be used for gas separation. BRIEF DESCRIPTION OF FIGURES FIG. 1 shows a scanning electron microscope (SEM) image of the exterior surface of a hollow-fiber membrane according to example 1 at 60000× magnification; FIG. 2 shows an SEM image of the interior surface of a hollow-fiber membrane according to example 1 at 13500× magnification; FIG. 3 shows an SEM image of the surface of fracture perpendicular to the longitudinal axis of a hollow-fiber membrane according to example 1 in the vicinity of the exterior surface at 13500× magnification; FIG. 4 shows an SEM image of the surface of fracture perpendicular to the longitudinal axis of a hollow-fiber membrane according to example 1 in the vicinity of the interior surface at 13500× magnification; FIG. 5 shows an SEM image of the exterior surface of a hollow-fiber membrane according to example 2 at 60000× magnification; FIG. 6 shows an SEM image of the interior surface of a hollow-fiber membrane according to example 2 at 13500× magnification; FIG. 7 shows an SEM image of the surface of fracture perpendicular to the longitudinal axis of a hollow-fiber membrane according to example 2 in the vicinity of the exterior surface at 13500× magnification; FIG. 8 shows an SEM image of the exterior surface of a hollow-fiber membrane according to example 3 at 60000× magnification; FIG. 9 shows an SEM image of the interior surface of a hollow-fiber membrane according to example 3 at 13500× magnification; FIG. 10 shows an SEM image of the surface of fracture perpendicular to the longitudinal axis of a hollow-fiber membrane according to example 3 in the vicinity of the exterior surface at 13500× magnification; FIG. 11 shows an SEM image of the exterior surface of a hollow-fiber membrane according to example 4 at 60000× magnification; FIG. 12 shows an SEM image of the interior surface of a hollow-fiber membrane according to example 4 at 13500× magnification; FIG. 13 shows an SEM image of the surface of fracture perpendicular to the longitudinal axis of a hollow-fiber membrane according to example 4 in the vicinity of the exterior surface at 13500× magnification; FIG. 14 shows an SEM image of the exterior surface of a hollow-fiber membrane according to comparative example 1 at 60000× magnification; FIG. 15 shows an SEM image of the interior surface of a hollow-fiber membrane according to comparative example 1 at 4500× magnification; FIG. 16 shows an SEM image of the surface of fracture perpendicular to the longitudinal axis of a hollow-fiber membrane according to comparative example 1 in the vicinity of the exterior surface at 13500× magnification; and FIG. 17 shows an SEM image of the surface of fracture perpendicular to the longitudinal axis of a hollow-fiber membrane according to comparative example 1 in the vicinity of the interior surface at 13500× magnification. DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS Within the context of the present invention, an integrally asymmetrical membrane is understood to be one in which the separation and support layers consist of the same material and were formed together directly during membrane production, resulting in both layers being integrally joined with each other. In the transition from the separation layer to the support layer, there is merely a change with respect to the membrane structure. Contrasting with this are composite membranes, for example, which have a multilayer structure formed by applying, in a separate process step, a dense layer as a separation layer on a porous, often microporous support layer or support membrane. The result is that the materials constituting the support and separation layers also have different properties in the case of composite membranes. The process according to the invention is based on a thermally induced phase separation process with liquid-liquid phase separation. According to the invention, the polymer component and the solvent form a binary system, which in the liquid state of aggregation has a range in which the system is present as a homogeneous solution and a range in which it exhibits a miscibility gap in the liquid state of aggregation. If such a system is cooled, from the range in which it is present as a homogenous solution, below the critical demixing or phase separation temperature, liquid-liquid demixing or phase separation into two liquid phases, namely one with a high polymer content and the other with a low polymer content, initially takes place. On further cooling, below the solidification temperature, the high-polymer-content phase solidifies to form a three-dimensional membrane structure. The cooling rate in this case has a substantial influence on the pore structure being created. If the cooling rate is high enough that the liquid-liquid phase separation cannot take place under thermodynamic equilibrium conditions but rather under thermodynamic non-equilibrium conditions and on the other hand still relatively slowly, the liquid-liquid phase separation occurs approximately concurrently with the formation of a large number of droplets of liquid that are of substantially the same size. The resulting polymer object then has a sponge-like cellular and open-pored microstructure. If the cooling rate is significantly higher, the polymer solidifies before most of the droplets of liquid can form. In this case, sponge-like structures with network- or coral-like microstructures are formed. The variety of such sponge-like microporous structures formed via processes with thermally induced liquid-liquid phase separation are described in detail in DE-C-27 37 745, reference to the disclosure of which is hereby explicitly made, and depicted for example in R. E. Kesting, “Synthetic Polymeric Membranes”, John Wiley & Sons, 1985, pp. 261-264. Generally speaking, the solvent is to be seen as a compound in which the polymer component is completely dissolved to form a homogeneous solution when heated to at most the boiling point of this compound. In the context of the present invention, a solvent for the at least one polymer is to be used for which, for a solution of 25% by weight of the polymer component in this solvent and a cooling rate of 1° C./min, the demixing temperature is 10 to 70° C. above the solidification temperature. Such solvents can be categorized as weak solvents for the polymer component. A strong solvent would then be one for which, for a solution of 25% by weight of the polymer component in this solvent and a cooling rate of 1° C./min, the demixing temperature is no more than 5° C. above the solidification temperature. It has been observed that the use of an overly strong solvent, for which the difference between the demixing and solidification temperatures is less than 10° C. and which results in comparatively low solidification temperatures, promotes the formation of spherulitic or particle-shaped structures and in part defective separation layers. These structures, which are outside the scope of the invention, have a structure consisting of particle-shaped structure elements with in part rosette or laminar construction, where the structure elements are interconnected via laminar or fibrillar links. The membranes produced using the cited solvents, which are outside the scope of the invention, then do not have a sponge-like, open-pored, microporous support structure and furthermore lack sufficient mechanical stability for practical application. On the other hand, the use of overly weak solvents can result in a separation layer that is not free of defects but rather exhibits relatively large holes or splits. The demixing temperature is preferably 20 to 50° C., and especially preferably 25 to 45° C., above the solidification temperature. The demixing, or phase separation, temperature and the solidification temperature in this case can be determined in a simple manner by initially preparing a homogeneous solution of 25% by weight of the polymer component in the solvent under investigation and then heating this solution to a temperature approximately 20° C. above the dissolving temperature. This solution is stirred and maintained at this temperature for about 0.5 hours, in order to achieve sufficient homogeneity. Subsequently, the solution is cooled at a rate of 1° C./min while stirring. The phase separation temperature is determined as the temperature at which clouding becomes visible. On further cooling, solidification of the high-polymer-content phase begins with the appearance of individual polymer particles. The solidification temperature is then the temperature at which substantially all of the high-polymer-content phase has solidified. The formation of spherulitic or particle-shaped structures has also been observed in particular when high-density polyolefins were used. Apparently, when carrying out the process according to the invention, high-density polyolefins have an increased tendency to form spherulitic or particle-shaped structures. It is presumed that the crystallization behavior, such as the crystallization rate, then has an increased effect on the formation of the membrane structure. Preferably, therefore, a polymer component with a density of ≦910 kg/m3 is employed. According to the invention, the polymer component used is at least one polyolefin. In this case, the polymer component can be a single polyolefin or a mixture of several polyolefins, where the polyolefins also include polyolefin copolymers or modified polyolefins. Mixtures of different polyolefins are interesting in that various properties such as permeability or mechanical characteristics can be optimized thereby. For example, by adding just slight amounts of a polyolefin with an ultrahigh molecular weight, for example exceeding 106 daltons, a strong influence can be exerted on the mechanical properties. A prerequisite for this, of course, is that the polyolefins employed in this case together be soluble in the solvent used. In the case that mixtures of several polyolefins-are used for the polymer component, in an especially preferred embodiment each polyolefin contained in the mixture has a density of ≦910 kg/m3. The at least one polyolefin contained in the polymer component preferably consists exclusively of carbon and hydrogen. Especially preferred polyolefins are polypropylene and poly(4-methyl-1-pentene) or mixtures of these polyolefins among themselves. Of particular advantage is the use of poly(4-methyl-1-pentene). Particularly dense separation layers and high gas transfer rates can be realized thereby, while maintaining good mechanical properties for the membranes. For the solvent, compounds are to be used that fulfill the stated conditions. In case of the especially preferred use of polypropylene as the polymer component, N,N-bis(2-hydroxyethyl)tallow amine, dioctyl phthalate, or a mixture thereof are preferably used as solvents. In the especially preferred use of poly(4-methyl-1-pentene) as a polyolefin, preferred solvents are palm nut oil, dibutyl phthalate, dioctyl phthalate, dibenzyl ether, coconut oil, or a mixture thereof. Especially dense separation layers are obtained using dibutyl phthalate or dibenzyl ether. The fractions of polymer component and solvent required for membrane production can be determined by generating phase diagrams in simple experiments. Such phase diagrams can be developed using known methods, such as are described in C. A. Smolders, J. J. van Aartsen, A. Steenbergen, Kolloid-Z. und Z. Polymere, 243 (1971), pp. 14-20. The polymer fraction of the system from which the solution is formed is preferably 30-60% by weight, and the fraction of the solvent is 70-40% by weight. The polymer fraction is especially preferred to be 35-50% by weight and the fraction of the solvent 65-50% by weight. If necessary, additional substances such as antioxidants, nucleating agents, fillers, components to improve biocompatibility, i.e., blood tolerance when using the membrane in oxygenation, such as vitamin E, and similar substances can be employed as additives to the polymer component, solvent, or polymer solution. The polymer solution formed from the polymer component and the solvent is given shape using suitable dies. The shaped object preferably has the form of a film or hollow filament, and the membrane ultimately produced therefrom is a flat or hollow-fiber membrane. Conventional dies such as sheeting dies, casting molds, doctor blades, profiled dies, annular-slit dies, or hollow-filament dies can be employed. In a preferred embodiment, hollow-fiber membranes are produced by the process according to the invention. In this case, the polymer solution is extruded through the annular gap of the corresponding hollow-filament die to form a shaped object, i.e., a hollow filament. A fluid is metered through the central bore of the hollow-filament die that acts as an interior filler that shapes and stabilizes the lumen of the hollow-fiber membrane. The extruded hollow filament or resulting hollow-fiber membrane then exhibits a surface facing the lumen, the interior surface, and a surface facing away from the lumen, the exterior surface, separated from the interior surface by the wall of the hollow filament or hollow-fiber membrane. After shaping, the shaped object is cooled using the liquid cooling medium employed in accordance with the invention, so that a thermodynamic non-equilibrium liquid-liquid phase separation occurs in the shaped object, i.e., in the shaped polymer solution, and the polymer structure subsequently solidifies and hardens. In this process, the cooling medium has been conditioned to a temperature below the solidification temperature. According to the invention, in order to produce the desired integrally asymmetrical membrane with separation layer, a liquid cooling medium is to be used that does not dissolve or react chemically with the polymer component, even when the medium is heated to the die temperature. The use of such a cooling medium plays a primary role in the formation of a separation layer with a denser structure. Such a requirement placed on the cooling medium rules out, for example, the use as a cooling medium of the solvent employed according to the invention. Although the latter would not dissolve the polymer component at the cooling temperature, this solvent forms a homogeneous solution with the polymer component at the die temperature, as previously noted. It is especially preferred for the liquid used as the cooling medium to be a non-solvent for the polymer component, i.e., it does not dissolve the polymer component to form a homogeneous solution when heated up to the boiling point of the cooling medium. The liquid used as the cooling medium can also contain a component that is a solvent for the polymer component, or it can also be a mixture of different non-solvents, as long as it overall does not dissolve the polymer component at temperatures up to at least the die temperature. It is observed in this case that the degree of non-solvent character of the cooling medium influences the tightness of the separation layer being formed. In an especially preferred embodiment of the process according to the invention, therefore, a liquid is used as a cooling medium that is a strong non-solvent for the polymer component. In the scope of the present invention, the strength of a non-solvent is assessed on the basis of the difference between the demixing temperature of a solution consisting of the polymer component and a strong solvent and the demixing temperature of a solution containing as a solvent the same solvent and 10% by weight of the non-solvent under investigation. The polymer component concentration in each case is 25% by weight. A strong non-solvent is then understood to be one that leads to an increase in the demixing temperature of at least 10% relative to the demixing temperature of the corresponding solution consisting of only the solvent and the polymer component. Preferably, the cooling medium at the cooling temperature is a homogeneous, single-phase liquid. This ensures production of membranes with especially homogeneous surface structures. The liquid cooling medium used can be one that is miscible with the solvent to form a homogeneous solution or one that does not dissolve the solvent. The cooling medium is advantageously a liquid that is a strong non-solvent for the polymer component and is homogeneously miscible with the solvent at the cooling temperature, i.e., in which the solvent dissolves at the cooling temperature. To initiate a thermodynamic non-equilibrium liquid-liquid phase separation, the temperature of the cooling medium must be significantly below the critical demixing temperature or phase separation temperature of the system used, consisting of the polymer component and solvent, and, in order to solidify the high-polymer-content phase, below the solidification temperature. In this case, the formation of the separation layer is promoted when there is as great a difference as possible between the demixing temperature and the temperature of the cooling medium. The cooling medium preferably has a temperature at least 100° C. below the phase separation temperature, and especially preferably a temperature that is at least 150° C. below the phase separation temperature. It is particularly advantageous if the temperature of the cooling medium in this case is under 50° C. In individual cases, cooling to temperatures below ambient temperature can be required. It is also possible for cooling to be performed in several steps. The liquid cooling medium in which the shaped object is immersed for cooling and through which it is normally passed, can be located in a tub-shaped container, for example. The liquid cooling medium is preferably in a shaft or spinning tube which the shaped object passes through for cooling purposes. In this case, the cooling medium and shaped object are generally fed in the same direction through the shaft or spinning tube. The shaped object and cooling medium can be fed at the same or different linear speeds through the spinning tube, where, depending on the requirement, either the shaped object or the cooling medium can have the higher linear speed. Such process variants are described in DE-A-28 33 493 or EP-A-133 882, for example. The interior filler employed in extrusion of hollow filaments can be in gaseous or liquid form. When using a liquid as the interior filler, a liquid must be selected that substantially does not dissolve the polymer component in the shaped polymer solution below the critical demixing temperature of the polymer solution. In other respects, the same liquids can be used as can also be used as the cooling medium. In this manner, hollow-fiber membranes can also be produced that have a separation layer on both their outside and inside, or also hollow-fiber membranes that have a separation layer only on their inside. Preferably, the interior filler is then a non-solvent for the polymer component and especially preferably a strong non-solvent for the polymer component. The interior filler in this case can be miscible with the solvent to form a homogeneous, single-phase solution. In case the interior filler is gaseous, it can be air, a vaporous material, or preferably nitrogen or other inert gases. It is advantageous if the exit surface of the die and the surface of the cooling medium are spatially separated by a gap, which is transited by the shaped object prior to contact with the cooling medium. The gap can be an air gap, or it can also be filled with another gaseous atmosphere, and it can also be heated or cooled. The polymer solution, however, can also be brought directly into contact with the cooling medium after exiting from the die. In an advantageous embodiment of the process according to the invention, at least one of the surfaces of the shaped object leaving the die, preferably the surface on which the separation layer is to be formed, is subjected prior to cooling to a gaseous atmosphere promoting the evaporation of the solvent, i.e., to an atmosphere in which the evaporation of the solvent is possible. Preferably, air is used to form the gaseous atmosphere. Likewise preferred are nitrogen or other inert gases or also vaporous media. The gaseous atmosphere is advantageously conditioned and generally has a temperature below that of the die. To evaporate a sufficient fraction of the solvent, at least one of the surfaces of the shaped object is preferably subjected to the gaseous atmosphere for at least 0.5 s. To provide the gaseous atmosphere promoting the evaporation of the solvent, it is often sufficient to spatially separate the die and cooling medium so that a gap is formed between them that contains the gaseous atmosphere and through which the shaped object passes. In producing flat membranes, for example, the polymer solution extruded through a sheeting die, for example, can, as a flat sheet, initially be passed through a gap, such as an air gap, before being cooled. In this case, the flat sheet is enveloped on all sides, i.e., the two surfaces and the edges, by the gaseous atmosphere, influencing the formation of the separation layer on both surfaces of the resulting flat membrane. In the case of producing hollow-fiber membranes, the hollow filament leaving the die can likewise be directed through a gap formed between the die and cooling medium and containing the gaseous atmosphere. In individual cases, the structure of the separation layer can also be influenced by drawing the shaped polymer solution after exiting the die, i.e., particularly in the air gap, the drawing being effected by establishing a difference between the exit speed of the polymer solution from the die and the speed of the first withdrawal device for the cooled shaped object. After cooling and hardening of the polymer structure, the solvent or low-polymer-content phase is usually removed from the shaped object. Removal can be performed, for example, by extraction. Preferably, extraction agents are used that do not dissolve the polymer or polymers but are miscible with the solvent. Subsequent drying at elevated temperatures can be necessary to remove the extraction agent from the membrane. Suitable extraction agents are acetone, methanol, ethanol, and preferably isopropanol. In some cases, it can also be practical to retain the solvent at least in part in the shaped object. Other components added to the solvent as additives can remain in the membrane structure as well and thus serve as functional active liquids, for example. Various examples of microporous polymers containing functional active liquids are described in DE-C 27 37 745. Before or after the removal of at least a substantial portion of the solvent, a slight stretching of the membrane can take place in particular to modify the properties of the separation layer in a specific manner. For example, in a substantially dense separation layer, stretching can be used to create pores or the size of pores in the separation layer can be adapted to the size required by the specific application for the resulting membrane. In producing membranes for extended-duration oxygenation, however, it must be ensured that the average pore size does not exceed 100 nm, so that premature breakthrough of liquid can be avoided. For this reason, the stretching should generally not exceed 10% when producing the membranes of the invention. The stretching can, as required, also be performed in several directions and is advantageously performed at elevated temperatures. For example, such stretching can also be conducted during drying of the membrane that might be necessary after extraction. By adjusting the pore size of the separation layer, such as in a downstream stretching step, membranes for nanofiltration or ultrafiltration can therefore also be produced by the process according to the invention. The process according to the invention is preferably used to produce a hydrophobic integrally asymmetrical membrane, in particular for gas separation or gas exchange, wherein the membrane is composed primarily of at least one polyolefin, has first and second surfaces, and has an intermediate support layer with a sponge-like, open-pored, microporous structure and adjacent to this support layer on at least one of the surfaces a separation layer with a denser structure, where the separation layer is dense or has pores with an average diameter ≦100 nm, the support layer is free of macrovoids, the pores in the support layer are on average substantially isotropic, and the membrane has a porosity in the range from greater than 30% to less than 75% by volume. For this reason, the invention further relates to such a membrane producible by the process according to the invention. It is especially preferable for the membrane produced by the process according to the invention to have a dense separation layer. The average pore diameter in the separation layer is understood to be the mean of the diameters of the pores in the surface formed as the separation layer, where an image of a scanning electron microscope at 60000× magnification is used as a basis. In the image-analysis evaluation, the pores are assumed to have a circular cross-section. The average pore diameter is the arithmetic mean of all visible pores on a membrane surface of approx. 8 μm×6 μm at 60000× magnification. In the membranes according to the invention and those produced by the process according to the invention, existing pores in the surface exhibiting the separation layer are uniformly, i.e., homogeneously, distributed over this surface. Due to their structure, these membranes, when used for gas transfer, are distinguished by high gas flow rates and high gas transfer rates while maintaining high levels of safety with respect to a breakthrough of the liquid from which a gaseous component is to be separated or to which a gaseous component is to be added, and also by good mechanical properties. To achieve this, the membrane has a high volume porosity, where the latter is determined substantially by the structure of the support layer, and a defined separation layer with minimal thickness. The support layer of the membranes produced by the process according to the invention, or the membranes according to the invention, can, as previously discussed, have different structures. In one embodiment, the support layer has a sponge-like, cellular, and open-pored structure, in which the pores can be described as enveloped microcells that are interconnected by channels, smaller pores, or passages. In another embodiment, the support layer has a non-cellular structure, in which the polymer phase and the pores form interpenetrating network structures, which can also be described as coral-shaped structures. In any case, however, the support layer is free of macrovoids, i.e., free of such pores often referred to in the literature as finger pores or caverns. The pores of the support layer can have any geometry and be, for example, of elongated, cylindrical, rounded shape, or also have a more or less irregular shape. In the membranes according to the invention or those produced by the process according to the invention, the pores in the support layer are on average substantially isotropic. This is understood to mean that, although the individual pores can also have an elongated shape, the pores on average in all spatial directions have substantially the same extension, where deviations of up to 20% can exist between the extensions in the individual spatial directions. With an insufficiently low volume porosity, i.e. an insufficient pore fraction compared to the total volume of the membrane, the attainable gas flows and gas transfer rates are too low. On the other hand, an excessive pore fraction in the membrane leads to deficient mechanical properties, and the membrane cannot be readily processed in subsequent processing steps. Using the process according to the invention, preferably membranes can be produced that have a volume porosity in the range of greater than 30% to less than 75% by volume and especially preferably greater than 50% to less than 65% by volume. Furthermore, the membranes can have a separation layer on only one of their surfaces, or they can have a separation layer on both surfaces. The separation layer influences on the one hand the gas flows and gas transfer rates but on the other hand the breakthrough time, i.e., the time the membrane is protected from a breakthrough of the liquid from which, when using the membrane according to the invention, a gaseous component is to be separated or to which a gaseous component is to be added, or from a breakthrough of components contained in the liquid. It also influences whether and how well various gases in a gas mixture can be separated from one another, i.e., the gas separation factor α(CO2/N2), for example. With a non-porous, dense separation layer, very long breakthrough times are the result, but the transfer rates and gas flows are limited in size, since in non-porous membrane layers the gas transfer or gas flow takes place solely via a comparatively slow solution diffusion, in contrast to the considerably greater “Knudsen flow” in porous structures. In the case of a nanoporous separation layer, on the other hand, the gas transfer rates and gas flows are higher than those with a dense separation layer, but reduced breakthrough times can result due to the pores. The tightness of the separation layer and its suitability in particular for gas separation or gas transfer can often not be evaluated with sufficient reliability solely on the basis of visual inspection, using a scanning electron microscope for example. In this case, not only the size of existing pores or in general structural defects such as fissures but also their number play a role. However, the absence or presence of pores and/or defects, as well as their number, can be evaluated by examining the gas permeation and gas flows through the membrane as well as the gas separation factors. It is well known that the general principles of gas transport in polymer membranes depend on the pore size in the membrane. In membranes in which the separation layer has pores at most approx. 2-3 nm in size, the gas permeates through this membrane via solution diffusion mechanisms. The permeability coefficient P0 of a gas then depends solely on the polymer material of the membrane and on the gas itself, and the gas flow Q0, i.e., the permeability coefficient divided by the membrane thickness, depends, for a given gas, only on the thickness of the separation layer. The gas separation factor α, which specifies the ratio of the permeability coefficients or the gas flows Q of two gases in this membrane, therefore depends likewise solely on the polymer material and not, for example, on the thickness of the separation layer. For example, the gas separation factor for CO2 and N2 is then α0(CO2/N2)=P0(CO2)/P0(N2). For polymers in general use, resulting α0(CO2/N2) values are at least 1 and generally at least 3. In porous membranes with pores between 2 nm and about 10 μm in size, the transport of gases takes place primarily via “Knudsen flow”. The calculated gas separation factors α1, as the ratio of the measured apparent permeability coefficients, are then inversely proportional to the square root of the ratio of the molecular weights of the gases. For α1(CO2/N2), therefore, the result is {square root}28/44=0.798, for example. If a gas permeates the membranes of the present invention, which have a microporous support structure and compared with it a denser separation layer with pores not exceeding 100 nm on average, the permeation through the separation layer is the step that determines the rate. If this separation layer has a significant number of pores or defects, on the one hand the apparent permeability coefficients increase, but on the other hand the gas separation factor decreases. For this reason, the presence or absence of pores and/or defects in the separation layer of the membranes of the invention can be determined on the basis of the measured gas separation factors for CO2 and N2, α(CO2/N2). If the CO2/N2 gas separation factor α(CO2/N2) is significantly less than 1, the membrane has an excessive number of pores or defects in the separation layer. If the number of pores or defects in the separation layer is too high, however, a premature liquid breakthrough or plasma breakthrough can no longer be ruled out with adequate certainty, and the membranes are not suitable for extended-duration use in blood oxygenation. Such membranes are likewise unsuitable for gas separation applications. The membranes of the invention, therefore, preferably have a gas separation factor α(CO2/N2) of at least 1, and especially preferably at least 2. The separation layer must not be too thin, since this increases the risk of defects and thus of breakthrough, and the resulting α(CO2/N2) values are too low. However, the time to actual breakthrough is still relatively long in this case, since with the membranes of the invention there is no preferred direction for the flow of a liquid; rather, the course of the liquid is tortuous due to the pore structure. Contrasting with this are membranes produced according to the aforementioned melt-drawing process, in which, due to the pronounced anisotropy of the pores, a preferred direction for the flow of the liquids from one surface to the other results. While an excessively thin separation layer makes-the risk of defects too great, an excessive separation layer thickness makes the transfer rates and gas flow rates too low. Preferably, therefore, the thickness of the separation layer is between 0.01 μm and 5 μm, especially preferably between 0.1 μm and 2 μm. Membranes of the invention with a separation layer thickness between 0.1 μm and 0.6 μm are excellently suited. The thickness of the separation layer can be determined for the membranes of the invention in a simple manner by measuring the layer using fracture images generated by scanning electron microscopy or by ultrathin-section characterizations using transmission electron microscopy. In conjunction with the high porosity of the membranes, this permits the attainment of a sufficiently high permeability of the membranes for use in blood oxygenation and thus sufficiently high gas flows. Preferably, therefore, the membranes of the invention have a gas flow Q for CO2, Q(CO2), of at least 1 ml/(cm2*min*bar). An important application of the membranes producible by the process according to the invention is the oxygenation of blood. In these applications, as previously noted, the plasma breakthrough time plays a role, i.e., the time in which the membrane is stable against a breakthrough of blood plasma. It must be emphasized that plasma breakthrough is a considerably more complex process than the mere penetration of a hydrophobic membrane by a hydrophilic liquid. According to accepted opinion, plasma breakthrough is induced by the fact that initially proteins and phospholipids in the blood effect a hydrophilation of the pore system of the membrane, and in a subsequent step a sudden penetration of blood plasma into the hydrophilated pore system takes place. The critical variable for a liquid breakthrough is therefore considered to be the plasma breakthrough time. The membranes of the invention preferably exhibit a plasma breakthrough time of at least 20 hours, and especially preferably a plasma breakthrough time of at least 48 hours. In general, in the membranes of the present invention, the transition from the porous support layer to the separation layer takes place in a narrow region of the membrane wall. In a preferred embodiment, the membrane structure changes abruptly in the transition from the separation layer to the support layer, i.e., the membrane structure changes substantially transition-free and step-like from the microporous support structure to the separation layer. Membranes with such a structure have, in comparison to membranes with a gradual transition from the separation layer to the support layer, the advantage of higher permeability of the support layer for gases to be transferred, since the support layer is less compact in its area adjacent to the separation layer. In a preferred embodiment, the membranes of the invention or those produced by the process according to the invention are flat membranes, which preferably have a thickness between 10 and 300 μm, especially preferably between 30 and 150 μm. In a likewise preferred embodiment, the membranes are hollow-fiber membranes. Depending on the embodiment, they can have a separation layer only on their interior surface, i.e. on the surface facing the lumen, or only on their exterior surface, i.e. the surface facing away from the lumen, or on both the interior and exterior surfaces. The separation layer is preferably on the exterior surface. The hollow-fiber membranes preferably have an outside diameter between 30 and 3000 μm, especially preferably between 50 and 500 μm. A wall thickness of the hollow-fiber membrane between 5 and 150 μm is advantageous, and a thickness between 10 and 100 μm is especially advantageous. The hollow-fiber membranes have outstanding mechanical properties, in particular a breaking force of at least 70 cN and an elongation at break of at least 75%, readily enabling processing in subsequent textile processing steps. When using hollow-fiber membranes, it has proven beneficial for the hollow-fiber membranes, with respect to the performance characteristics of membrane modules made therefrom, to be initially formed, for example, by appropriate knitting processes into mats of hollow-fiber membranes substantially parallel to each other, which are then fashioned into appropriate bundles. The associated textile processes impose stringent demands on the mechanical properties of the membranes, in particular on the tensile strength and elongation. These requirements are fulfilled by the membranes of the invention and those produced by the process according to the invention. The membranes of the invention or those produced according to the invention can be used in numerous applications in which a membrane is required with a separation layer. Preferred applications are processes for gas separation, in which, for example, a single gas component is selectively separated from a mixture of at least two gases, or for gas enrichment, in which one or more gas components in a mixture of different gases is enriched. Furthermore, the membranes of the invention or those produced according to the invention can be used for gas transfer processes, in which a gas dissolved in a liquid is selectively removed from this liquid, and/or a gas from a mixture of gases, for example, is dissolved in a liquid. Due to their high impermeability for plasma, i.e. to their long plasma breakthrough times, and their high gas transfer capacity for O2 and CO2, the membranes of the invention are excellently suited for use in oxygenators, i.e., for the oxygenation of blood and in particular for the extended-duration oxygenation of blood. On the other hand, in the process according to the invention, adjustment of the pore size of the separation layer, for example in a downstream stretching step, also preferably permits production of membranes for nanofiltration, such as for separating low-molecular substances chiefly from non-aqueous media, or for ultrafiltration, such as for treating fresh water, sewage, or process water, as well as for applications in the food, beverage, and dairy industries. The membranes of the invention and those produced using the process of the invention can moreover also be used advantageously for separation or recovery of anesthesia gases, which have a considerably greater molecular diameter compared to the gases contained in respiratory air. In the examples, the following methods were employed to characterize the membranes obtained: Determination of the Plasma Breakthrough Time: To determine the plasma breakthrough time, a phospholipid solution maintained at 37° C. (1.5 g L-α-Phosphatidy-LCholine dissolved in 500 ml physiological saline solution) is directed with a flow of 6 l/(min*2m2) at a pressure of 1.0 bar along one surface of a membrane sample. Air is allowed to flow along the other surface of the membrane sample, the air after exiting the membrane sample being fed through a cooling trap. The weight of the liquid accumulated in the cooling trap is measured as a function of time. The time until the occurrence of a significant increase in the weight, i.e., to the first significant accumulation of liquid in the cooling trap, is designated as the plasma breakthrough time. Determination of the Volume Porosity: A sample of at least 0.5 g of the membrane to be examined is weighed in a dry state. The membrane sample is then placed for 24 hours into a liquid that wets the membrane material but does not cause it to swell, so that the liquid penetrates into all pores. This can be detected visually in that the membrane sample is transformed from an opaque to a glassy, transparent state. The membrane sample is then removed from the liquid, liquid adhering to the sample removed by centrifugation at about 1800 g, and the mass of the thus pretreated wet, i.e., liquid-filled, membrane sample determined. The volume porosity in % is determined according to the following formula: Volume ⁢ ⁢ porosity ⁢ [ % ] = 100 * ( m wet - m dry ) / ρ liq . ( m wet - m dry ) / ρ liq . + m dry / ρ polymer where mdry=weight of the dry membrane sample mwet=weight of the wet, liquid-filled membrane sample pliq.=density of the liquid used ppolymer=density of the membrane polymer Determination of the Gas Flow: To determine the gas flows, one of the sides of a membrane sample is subjected to the gas to be measured, under a constant test pressure of 2 bar. In the case of hollow-fiber membranes, the gas is introduced into the lumen of the hollow-fiber membrane for this purpose. The volume stream of the gas penetrating through the wall of the membrane sample is determined and standardized with respect to the test pressure and area of the membrane sample penetrated by the gas stream. For hollow-fiber membranes, the interior surface of the membrane enclosing the lumen is employed for this. Determination of the Average Diameter of the Pores in the Separation Layer: The determination of the average diameter of the pores in the separation layer is performed using an image-analysis technique. For this purpose, the pores are assumed to have a circular cross-section. The average pore diameter is then the arithmetic mean of all visible pores on a membrane surface of approx. 8 μm×6 μm at 60000× magnification. EXAMPLE 1 Poly(4-methyl-1-pentene) was melted stepwise in an extruder at increasing temperatures ranging from 265° C. to 300° C. and fed continuously to a dynamic mixer using a gear pump. The solvent used, dibutyl phthalate (Palatinol C); was also fed, via a metering pump, to the mixer, in which the polymer and solvent were processed together at a temperature of 290° C. to form a homogeneous solution with a polymer concentration of 35% by weight and a solvent concentration of 65% by weight. This solution was fed to a hollow-filament die with an outside diameter of the annular gap of 1.2 mm and extruded above the phase separation temperature at 240° C. to form a hollow filament. Nitrogen was used as the interior filler. After an air section of 20 mm, the hollow filament passed through an approx. 1 m long spinning tube, through which the cooling medium, conditioned to ambient temperature, flowed. The cooling medium used was glycerin triacetate. The hollow filament, solidified as a result of the cooling process in the spinning tube, was drawn off from the spinning tube at a rate of 72 m/min, wound onto a spool, subsequently extracted with isopropanol, and then dried at 120° C. A hollow-fiber membrane was obtained with an outside diameter of approx. 415 μm, a wall thickness of approx. 90 μm, and a porosity of 57% by volume. The outside of the membrane had an approx. 0.3 μm thick separation layer, and the SEM examination of the exterior surface at 60000× magnification indicated no pores (FIGS. 1 to 4). For the membrane according to this example, a CO2 flow of 4.65 ml/(cm2*min*bar), an N2 flow of 0.54 ml/(cm2*min*bar), and thus a gas separation factor α(CO2/N2) of approx. 8.6 were determined. The membrane exhibited a plasma breakthrough time of more than 72 hours. After this time, the measurement was discontinued. EXAMPLE 2 The procedure of example 1 was followed using dibenzyl ether as the solvent. The hollow-fiber membrane obtained thereby had an outside diameter of approx. 400 μm, a wall thickness of approx. 95 μm, and a porosity of approx. 56% by volume. The membrane likewise had a sponge-like, microporous support structure and a 0.1 to 0.3 μm thick separation layer on its outside, and the SEM examination of the exterior surface at 60000× magnification indicated no pores (FIGS. 5 to 7). For the membrane according to this example, on average, a CO2 flow of 2.58 ml/(cm2*min*bar), an N2 flow of 0.83 ml/(cm2*min*bar), and a gas separation factor α(CO2/N2) of 3.1 were determined. A plasma breakthrough time of more than 72 hours was determined for the membrane. EXAMPLE 3 The procedure of example 1 was followed using coconut oil as the solvent. The mixer temperature was 285° C. The resulting hollow-fiber membrane had dimensions similar to those in example 2. On its outside, it had a thin separation layer with individual pores up to approx. 100 nm (FIGS. 8 to 10). The CO2 and N2 flows for the membrane of this example were on the same order of magnitude, from 64 to 76 ml/(cm2*min*bar). EXAMPLE 4 The membrane was produced as for that in example 1. The solvent used, however, was palm nut oil. For cooling, a glycerin/water mixture in a ratio of 65:35 was employed. The mixer temperature was set to 265° C. The hollow-fiber membrane produced thereby had an outside diameter of 406 μm and a wall thickness of 96 μm. The membrane porosity exceeded 55% by volume. The membrane had a sponge-like, microporous support structure and an approx. 0.2 μm thick separation layer on its outside. In the SEM examination, numerous pores up to approx. 80 nm in size were observable in the exterior surface of the membrane, i.e., in the separation layer (FIGS. 11 to 13). The CO2 and N2 flows were 179 and 202 ml/(cm2*min*bar), respectively, yielding a gas separation factor α(CO2N2) of 0.89. COMPARATIVE EXAMPLE 1 The procedure of example 1 was followed. Dioctyl adipate was used as the solvent. For dioctyl adipate, the demixing temperature of a solution of 25% by weight of the poly(4-methyl-1-pentene) employed as the polymer component was only approx. 5° C. above the solidification temperature and thus below the minimum level of 10° C. required by the invention. Glycerin triacetate was used as the cooling medium and was maintained at ambient temperature. The hollow-fiber membranes produced thereby had an integrally asymmetrical structure with a dense separation layer, although the separation layer was relatively thick at approx 3 μm. The support structure adjacent to the separation layer was not sponge-like but rather consisted of particle-shaped structure elements, with the structure elements interconnected via laminar or fibrillar links (FIGS. 14. to 17). Moreover, these membranes, which are outside the scope of the invention, had only a slight mechanical stability. COMPARATIVE EXAMPLE 2 The membrane was produced using the process of comparative example 1. Instead of dioctyl adipate, isopropyl myristate was used as the solvent. For isopropyl myristate as well, the demixing temperature of a solution of 25% by weight of the poly(4-methyl-1-pentene) employed as the polymer component was only approx. 5° C. above the solidification temperature and thus below the minimum level of 10° C. required by the invention. The hollow-fiber membranes produced thereby were similar to those for comparative example 1 and had an integrally asymmetrical structure with a compact, approx. 2 μm thick separation layer. The support structure adjacent to this separation layer likewise consisted of particle-shaped structure elements interconnected via laminar or fibrillar links. Moreover, these membranes, which are outside the scope of the invention, had only a slight mechanical stability.

<SOH> BACKGROUND OF THE INVENTION <EOH>1. Field of Invention The invention relates to a process for producing a hydrophobic membrane using a thermally induced phase separation process in accordance with the preamble of claim 1 , the membrane having a sponge-like, open-pored, microporous structure, and to the use of the membrane for gas exchange processes, in particular oxygenation of blood, and for gas separation processes. 2. Description of Related Art In a multitude of applications in the fields of chemistry, biochemistry, or medicine, the problem arises of separating gaseous components from liquids or adding such components to the liquids. For such gas exchange processes, there is increasing use of membranes that serve as a separation membrane between the respective liquid, from which a gaseous component is to be separated or to which a gaseous component is to be added, and a fluid that serves to absorb or release this gaseous component. The fluid in this case can be either a gas or a liquid containing the gas component to be exchanged or capable of absorbing it. Using such membranes, a large surface can be provided for gas exchange and, if required, direct contact between the liquid and fluid can be avoided. Membranes are also used in many different ways to separate individual gas components from a mixture of different gases. In such membrane-based gas separation processes, the gas mixture to be separated is directed over the surface of a membrane usable for gas separation. Sorption and diffusion mechanisms result in a transport of the gas components through the membrane wall, with the transport of the individual gas components of the mixture occurring at different rates. This causes an enrichment of the permeate stream passing through the membrane by the most rapidly permeating gas component, while the retentate stream is enriched by the components that permeate less readily. This ability to separate individual gas components from a gas mixture using membranes finds numerous applications. For example, membrane-based gas separation systems can be used to enrich the oxygen content of air to increase combustion efficiency or to enrich nitrogen in the air for applications requiring an inert atmosphere. An important application of membrane-based gas exchange processes in the medical field is for oxygenators, also called artificial lungs. In these oxygenators, which are used in open-heart operations, for example, oxygenation of blood and removal of carbon dioxide from the blood take place. Generally, bundles of hollow-fiber membranes are used for such oxygenators. Venous blood flows in this case in the exterior space around the hollow-fiber membranes, while air, oxygen-enriched air, or even pure oxygen, i.e., a gas, is passed through the lumen of the hollow-fiber membranes. Via the membranes, there is contact between the blood and the gas, enabling transport of oxygen into the blood and simultaneously transport of carbon dioxide from the blood into the gas. In order to provide the blood with sufficient oxygen and at the same time to remove carbon dioxide from the blood to a sufficient extent, the membranes must ensure a high degree of gas transport: a sufficient amount of oxygen must be transferred from the gas side of the membrane to the blood side and, conversely, a sufficient amount of carbon dioxide from the blood side of the membrane to the gas side, i.e., the gas flow or gas transfer rates, expressed as the gas volume transported per unit of time and membrane surface area from one membrane side to the other, must be high. A decisive influence on the transfer rates is exerted by the porosity of the membrane, since only in the case of sufficiently high porosity can adequate transfer rates be attained. A number of oxygenators are in use that contain hollow-fiber membranes with open-pored, microporous structure. One way to produce this type of membrane for gas exchange, such as for oxygenation, is described in DE-A-28 33 493. Using the process in accordance with this specification, membranes with up to 90% by volume of interconnected pores can be produced from meltable thermoplastic polymers. The process is based on a thermally induced phase separation process with liquid-liquid phase separation. In this process, a homogeneous single-phase solution is first prepared from the thermoplastic polymer and a compatible component that forms a binary system with the polymer, the system in the liquid state of aggregation having a range of full miscibility and a range with a miscibility gap, and this solution is then extruded into a bath that is substantially chemically inert with respect to, i.e., does not substantially react chemically with, the polymer and has a temperature lower than the demixing temperature. In this way, a liquid-liquid phase separation is initiated and, on further cooling, the thermoplastic polymer solidified to form the membrane structure. The membranes in accordance with DE-A-28 33 493 have an open-pored, microporous structure and also open-pored, microporous surfaces. On the one hand, this has the result that, in gas exchange processes, gaseous substances such as oxygen (O 2 ) or carbon dioxide (CO 2 ) can pass through the membrane relatively unrestricted and the transport of a gas takes place as a “Knudsen flow” combined with relatively high transfer rates for gases or high gas flow rates through the membrane. Such membranes with gas flow rates for CO 2 exceeding 1 ml/(cm 2 *min*bar) and for O 2 at approximately the same level have gas flow rates that are sufficiently high for oxygenation of blood. On the other hand, in extended-duration use of these membranes in blood oxygenation or generally in gas exchange processes with aqueous liquids, blood plasma or a portion of the liquid can penetrate into the membrane and, in the extreme case, exit on the gas side of the membrane, even if in these cases the membranes are produced from hydrophobic polymers, in particular polyolefins. This results in a drastic decrease in gas transfer rates. In medical applications for blood oxygenation, this is termed plasma breakthrough. The plasma breakthrough time of such membranes as producible in accordance with DE-A-28 33 493 is sufficient in most cases of conventional blood oxygenation to oxygenate a patient in a normal open-heart operation. However, these membranes are not suitable for so-called extended-duration oxygenation due to their relatively short plasma breakthrough times. Such membranes also cannot be used for gas separation tasks due to their consistent open-pored structure. However, in the field of oxygenation, the desire exists for membranes with higher plasma breakthrough times in order to attain higher levels of safety in extended-duration heart operations and to rule out the possibility of a plasma breakthrough that would require immediate replacement of the oxygenator. The aim is also to be able to oxygenate premature infants or in general patients with temporarily restricted lung function long enough until the lung function is restored, i.e., to be able to conduct extended-duration oxygenation. A prerequisite for this is appropriately long plasma breakthrough times. A frequently demanded minimum value for the plasma breakthrough time in this connection is 20 hours. From EP-A-299 381, hollow-fiber membranes for oxygenation are known that have plasma breakthrough times of more than 20 hours, i.e., there is no plasma breakthrough even under extended use. This is achieved with the otherwise porous membranes by using a barrier layer with an average thickness not exceeding 2 μm and substantially impermeable to ethanol. According to the disclosed examples, the membranes in accordance with EP-A-299 381 have a porosity of at most 31% by volume, since at higher porosity values the pores are interconnected via the membrane wall and communication occurs between the sides of the hollow-fiber membranes, resulting in plasma breakthrough. The production of these membranes is conducted via a melt-drawing process, i.e., the polymer is first melt-extruded to form a hollow fiber and then hot- and cold-drawn. In this case, only relatively low porosity values are obtained, which means that, in conjunction with the transport occurring in the barrier layer via solution diffusion, the attainable transfer rates for oxygen and carbon dioxide remain relatively low. Moreover, while the hollow-fiber membranes in accordance with EP-A-299 381 exhibit sufficient tensile strength as a result of the pronounced drawing in conjunction with manufacture, they have only a small elongation at break. In subsequent textile processing steps, such as producing hollow-fiber mats, which have proven excellent in the production of oxygenators with good exchange capacity and as are described in EP-A-285 812, for example, these hollow-fiber membranes are therefore difficult to process. U.S. Pat. No. 4,664,681 discloses polyolefin membranes in particular for gas separation, with a microporous layer and a non-porous separation layer, the membranes also being produced using a melt-drawing process. The properties of these membranes are similar to those described in EP-A-299 381. Typically, in melt-drawing processes, membranes are formed with slit-shaped pores with pronounced anisotropy, the first main extension of which is perpendicular to the drawing direction and the second main extension perpendicular to the membrane surface, i.e., in the case of hollow-fiber membranes runs between the exterior and interior surfaces of the membrane, so that the channels formed by the pores run in a relatively straight line between the surfaces. In the case in which, for example, mechanical damage in the spinning process causes leaks in the barrier layer, a preferred direction then exists for the flow of a liquid between the interior and exterior surfaces or vice versa, thereby promoting plasma breakthrough. DE-C-27 37 745 relates to microporous bodies likewise produced using a process with thermally induced liquid-liquid phase separation. During production of the microporous bodies, when the polymer solution is cast onto a substrate, such as a metal plate, the microporous bodies according to DE-C-27 37 745 can also exhibit a surface skin with a structure not having a cellular form, the thickness of the skin being in most cases approximately the thickness of an individual cell wall. DE-C-27 37 745, however, does not state that such microporous bodies with a surface skin are usable for gas exchange processes, in particular extended-duration oxygenation, or for gas separation processes. Moreover, hollow-fiber membranes cannot be produced using the procedure described in DE-C-27 37 745. In WO 00/43113 and WO 00/43114, integrally asymmetrical polyolefin membranes are disclosed, and processes for producing them described, that are usable for gas exchange, in particular extended-duration oxygenation, or also for gas separation. The processes are likewise based on a thermally induced phase separation process with liquid-liquid phase separation. The membranes according to WO 00/43113 or WO 00/43114 have a support layer with a sponge-like, open-pored, microporous structure and, adjacent to on this support layer on at least one of the surfaces a separation layer with a denser structure. To produce this membrane structure, and in particular the separation layer, the cited specifications for producing the polyolefin solutions employed start with solvent systems consisting of a mixture of a solvent with a non-solvent for the polyolefin, where the properties of the solvent and non-solvent must meet specific requirements. A disadvantage of the processes disclosed in these specifications is that solvent systems must always be used that are mixtures of several components. Such solvent systems are, from experience, complex with respect to the elements of the process that are aimed at reusing the individual components.

<SOH> SUMMARY OF THE INVENTION <EOH>It is therefore an object of the invention to provide a simplified process for producing integrally asymmetrical membranes with a microporous support structure and a separation layer with a denser structure, also in the form of hollow-fiber membranes, that are suited for gas exchange and at high gas exchange levels are impervious over extended periods of time to a breakthrough of hydrophilic liquids, in particular blood plasma, or that are suited for gas separation, the membranes having good qualities for further processing. The object is achieved by a process for producing an integrally asymmetrical hydrophobic membrane having a sponge-like, open-pored, microporous support structure and a separation layer with a denser structure compared to the support structure, the process comprising at least the steps of: a) preparing a homogeneous solution from a system comprising 20-90% by weight of a polymer component consisting of at least one polyolefin and 80-10% by weight of a solvent for the polymer component, wherein the system at elevated temperatures has a range in which it is present as a homogeneous solution and on cooling a critical demixing temperature, below the critical demixing temperature in the liquid state of aggregation a miscibility gap, and a solidification temperature, b) rendering the solution to form a shaped object, with first and second surfaces, in a die having a temperature above the critical demixing temperature, c) cooling the shaped object using a cooling medium, conditioned to a cooling temperature below the solidification temperature, at such a rate that a thermodynamic non-equilibrium liquid-liquid phase separation into a high-polymer-content phase and a low-polymer-content phase takes place and solidification of the high-polymer-content phase subsequently occurs when the temperature falls below the solidification temperature, d) possibly removing the low-polymer-content phase from the shaped object, characterized in that a solvent for the polymer component is selected for which, on cooling at a rate of 1° C./min, the demixing temperature of a solution of 25% by weight of the polymer component in this solvent is 10 to 70° C. above the solidification temperature and that, for cooling, the shaped object is brought into contact with a liquid cooling medium that does not dissolve or react chemically with the polymer component at temperatures up to the die temperature. Surprisingly, it has been shown that, by adhering to these process conditions, integrally asymmetrical membranes are obtained in which at least one surface is formed as a separation layer that covers the adjacent sponge-like, open-pored, microporous support layer and has a denser structure compared to the support layer. The process according to the invention allows the realization of very thin separation layers, whose structure can be adjusted from dense to nanoporous, with pores having an average size of less than 100 nm and in individual cases beyond that. At the same time, the support layer of the membranes produced in this manner has a high volume porosity. Preferably, the process according to the invention is used to produce integrally asymmetrical membranes with a dense separation layer. In this context, a dense separation layer or dense structure is understood to be one for which no pores are evident based on an examination by scanning electron microscope at 60000× magnification. The process according to the invention thus permits the production of integrally asymmetrical membranes with a separation layer that is impervious over long periods of time to liquid breakthrough but at the same time gas permeable, and with a support layer with high volume porosity, resulting at the same time in high gas transfer levels for these membranes in gas transfer processes. These membranes find excellent application for extended-duration blood oxygenation, the separation layer of these membranes being responsible for making them impervious over extended periods of time to the breakthrough of blood plasma. At the same time, membranes with a dense separation layer can be produced that allow high gas separation factors to be attained and can be used for gas separation.

20040915

20080930

20050707

69857.0

HEITBRINK, JILL LYNNE

PROCESS FOR PRODUCING POLYOLEFIN MEMBRANE WITH INTEGRALLY ASYMMETRICAL STRUCTURE

UNDISCOUNTED

ACCEPTED

ACCEPTED

Venous pulse oximetry

A method of non-invasively measuring venous oxygen saturation, comprising: applying a pressure transducer at a first site on a body, applying a drive signal to the external pressure transducer at a predetermined frequency, to cause a series of pulsations of a predetermined magnitude in the venous blood volume in the vicinity of said first site, applying an oximeter device at a second site on the body, measuring output signals received from said oximeter device, said output signals containing a component representative of the modulation of venous blood volume due to said pulsations, deriving a measure of venous oxygen saturation from the frequency response of said output signals.

1. A method of non-invasively measuring venous oxygen saturation, comprising applying a pressure transducer at a first site on a body, applying a drive signal to the external pressure transducer at a predetermined frequency, to cause a series of pulsations of a predetermined magnitude in the venous blood volume in the vicinity of said first site, applying an oximeter device at a second site on the body, measuring output signals received from said oximeter device, said output signals containing a component representative of the modulation of venous blood volume due to said pulsations, deriving a measure of venous oxygen saturation from the frequency response of said output signals. 2. A method according to claim 1 wherein the relationship between the distance between the first and second sites on the one hand, and the magnitude of the pulsations on the other hand, is such that a multiplicative term in the frequency spectrum of the measured signals, indicative of a disturbance to the arterial system, is minimised. 3. A method according to claim 1 wherein the frequency of the drive signal is chosen such that the pulsations are distinguishable from the heart rate. 4. A method according to claim 1 wherein the relationship between the frequency ωm of the pulsations caused by said drive signal and the heart rate ωHR is chosen to comply with the following conditions: ωm≠n(ωHR±ΔωHR) and ωm±(ωHR±ΔωHR)≠n(ωHR±ΔωHR) where n>1 5. A method according to claim 3 wherein the frequency of the drive signal is determined iteratively on the basis of a real time measurement of the heart rate. 6. A method according to claim 1 wherein the magnitude the pulsations is controlled such that the arterial system is minimally disturbed. 7. A method according to claim 1 wherein the magnitude of the pulsations is controlled such as to cause a variation of less than 1% in the DC level of the received signal. 8. A method according to claim 7 wherein the magnitude of the pulsations is such as to cause a variation of approximately 0.1% in the DC level of the received signal. 9. A method according to claim 1 wherein the oximeter is placed on a digit and a further pressure transducer is placed away from a distal end of a limb, and arranged to occlude the supply of blood to and from said limb, and the measurement is performed during the period of occlusion. 10. A method according to claim 2 wherein the magnitude of the pulsations is determined by progressively increasing the pulsation magnitude and observing a frequency response of the output signals; the appearance of a multiplicative term in the frequency spectrum being indicative of the maximum permissible magnitude having been reached. 11. A method according to claim 10, wherein, upon reaching the point where said multiplicative term appears, the pulsation magnitude is subsequently reduced to a point where the multiplicative term becomes insignificant. 12. A method according to claim 1, further including a calibration step, during which the spacing between the first and second sites is varied while the pulsation magnitude is held constant, in order to derive an optimum spacing. 13. A method according to claim 12, wherein the calibration step includes a further step of varying the pulsation magnitude while the spacing of the first and second sites is held constant. 14. A method according to claim 1, wherein a measure of arterial oxygen saturation is derived from the frequency response of said output signals, and the difference is levels of said arterial and venous oxygen saturation is representative of tissue oxygen consumption. 15. Apparatus for non-invasively measuring venous oxygen saturation comprising: A pressure transducer for applying a series of pulsations to a first site on a body, a pulse oximeter, control means for controlling the frequency and/or magnitude of said pulsations, such that the venous blood volume is modulated, signal processing means for extracting a value for venous oxygen saturation from signals received from said oximeter, said signals containing a component representative of a modulation of venous blood volume due to said pulsations. 16. A device according to claim 15 wherein said control means operates to control the relationship between the frequency ωm of the pulsations caused by said drive signal and the heart rate ωHR according to the following conditions: ωm≠n(ωHR±ΔωHR) and ωm±(ωHR±ΔωHR)≠n(ωHR±ΔωHR) where n>1 17. A device according to claim 15 wherein the pressure transducer comprises an inflatable digit cuff supplied with air from an air pump. 18. A device according to claim 17 wherein said pressure transducer and said pulse oximeter are formed as an integral device.

FIELD OF THE INVENTION This invention relates to a means of inducing regular modulations of the venous blood volume and the associated measurement of those modulations using sensors. By illuminating vascular tissue and detecting the light that has passed through the tissue, changes in blood volume due to differential absorption of the light intensity can be registered. This finds particular application in the measurement of venous blood oxygen saturation, achieved by the use of at least two separate wavelengths of illumination and subsequent detection. BACKGROUND OF THE INVENTION The monitoring of venous blood oxygen saturation (SvO2) is called venous oximetry. The method is often used in Intensive Care Units (ICU) to monitor the patient's overall oxygen supply and consumption. Current invasive methods have resulted in its under-utilization although SvO2 is unquestionably a valuable assessment tool in the evaluation of oxygenation. All venous oximetry techniques can be categorised into two areas, methods that are invasive and those that are non-invasive. A discussion of the various known invasive and non-invasive techniques follows. Oxygen saturation can be measured invasively by employing a variation of the standard Swan-Ganz Pulmonary Artery Catheter (PAC) in which two fiberoptic bundles were inserted in the PAC. The modified PAC used the principle of reflection spectrophotometry to make quantitative measurement of oxygen transport. Due to its invasive nature and the cost of the modified PAC, the method is not employed extensively for venous oximetry. U.S. Pat. No. 5,673,694 is representative of this background art. The majority of non-invasive, continuous peripheral venous oximetry techniques are based on Near InfraRed Spectroscopy (NIRS) or a combination of NIRS and various exercise protocols such as over-systolic venous occlusion. NIRS is hindered from supplanting the current invasive, continuous method utilizing SvO2 or central venous catheter mainly due to the difficulty in determining certain critical parameters without which calibration for venous oximetry would not be possible. Prior art approaches based upon NIPS are disclosed in U.S. Pat. Nos. 6,015,969 and 5,661,302. Pulse oximetry is one of the main applications of photoplethysmography (PPG), and is widely used for the measurement of arterial oxygen saturation, SpO2. The PPG waveform contains two components, one which is attributable to the pulsatile component in the vessels, i.e. the arterial pulse, is caused by the heartbeat and gives a rapidly alternating signal (AC component), and the other is due to the blood volume and its change in the skin and gives a steady signal that only changes slowly (DC component). Two wavelengths of light are used in Pulse oximetry, one in the red band (660 nm) and one in the infrared band (940 nm). Since at 660 nm reduced hemoglobin absorbs more light than oxyhemoglobin and at 940 nm, oxyhemoglobin absorbs more light than its reduced form, pulse oximetry relates this differential measurement to the arterial oxygen saturation. In pulse oximetry, light is first being transmitted through the tissues and the intensity of the transmitted light is then measured by a photo detector on the other side. The pulse oximeter first determines the AC component of the absorbance at each wavelength and then divides it by the corresponding DC component to obtain ratio that is independent of the incident light intensity. The ratio of ratios is then constructed as: R = AC 660 / DC 660 AC 940 / DC 940 The pulse oximeter is then calibrated by measuring the ratio of ratios and simultaneously sampling arterial blood for in vitro saturation measurements. Whilst the use of these techniques is effective for the measurement of arterial blood oxygen saturation, it relies upon the presence of pulsations of the arterial blood which is generated by the heart. No such measurable pulsations are present in venous blood. Venous Occlusion Plethymography (VOP) is the measurement of changes in tissue volume in response to temporary obstruction of venous return. It is used clinically to measure certain physiological conditions of blood vessels such as venous capacitance. VOP relies on the principle that occlusion of venous return causes slight swelling of distal portion of the tissue under test due to continued arterial inflow. The step response of venous blood volume over time during VOP can be used to measure arterial blood flow, venous outflow and venous compliance. M. Nitzal et al (Journal of Biomedical Optics 5(2), 155-162, April 2000) employed the principle of VOP to the measurement of SvO2, by applying pressure to the forearm sufficient to completely occlude venous flow, but leave arterial flow unaffected. Light absorption at 2 wavelengths is compared before and after occlusion. However, the approach does not appear to yield separate determination of venous and arterial oxygen saturation. PCT publication WO99/62399 and U.S. Pat. No. 5,638,816 relate to methods of venous oximetry where a cyclical active pulse is applied via an external cuff. However, the level of modulation (10% of the DC signal) is large, and will require a cuff-sensor spacing so close that the optical coupling will be affected, or if further away, pulsations will be at a level which will cause perturbations in the arterial system, and hence lead to inaccuracies in venous oxygen saturation measurements. As indicated above, prior art techniques for measuring venous oxygen saturation by non-invasive means do not yield the requisite accuracy. The aim of the invention is to achieve an improved measure of venous oxygen saturation. The principles of arterial pulse oximetry are well known (see above). The crucial element of the method that enables specific calibration of the oxygen carrying hemoglobin depends upon the presence of blood volume pulsations in the arterial system. These pulsations are of course naturally present throughout the circulation system. If one could induce pulsations in the venous system and properly isolate them from those of the arterial system, a similar calibration method could be employed to measure venous oxygen saturation. According to the invention, there is provided a method of non-invasively measuring venous oxygen saturation, comprising applying a pressure transducer at a first site on a body, applying a drive signal to the external pressure transducer at a predetermined frequency, to cause a series of pulsations of a predetermined magnitude in the venous blood volume in the vicinity of said first site, applying an oximeter device at a second site on the body, measuring output signals received from said oximeter device, said output signals containing a component representative of the modulation of venous blood volume due to said pulsations, deriving a measure of venous oxygen saturation from the frequency response of said output signals. The term oximeter device is intended to encompass any device which uses light of different frequencies to determine tissue oxygen content. It may encompass both transmission and reflection mode devices. The relationship between the distance between the first and second sites on the one hand, and the magnitude of the pulsations on the other hand, may be arranged such that a multiplicative term in the frequency spectrum of the measured signals, indicative of a disturbance to the arterial system, is minimised. Preferably the frequency of the drive signal is chosen such that the pulsations are distinguishable from the heart rate. The relationship between the frequency ωm of the pulsations caused by said drive signal and the heart rate ωHR can be chosen to comply with the following conditions: ωm≠n(ωHR±ΔωHR) and ωm±(ωHR±ΔωHR)≠n(ωHR±ΔωHR) where n>1 The frequency of the drive signal can be determined iteratively on the basis of a real time measurement of the heart rate. Ideally the magnitude of the pulsations is controlled such that the venous blood system is modulated without disturbing the arterial system. The magnitude of the pulsations can be controlled such as to cause a variation of less than 1% in the DC level of the received signal, or more preferably a variation of approximately 0.1% in the DC level of the received signal. In an alternative embodiment the oximeter is placed on a digit and a further pressure transducer is placed away from a distal end of a limb, and arranged to occlude the supply of blood to and from said limb, and the measurement is performed during the period of occlusion. Advantageously, the optimum magnitude of the pulsations can be determined by progressively increasing the pulsation magnitude and observing a frequency response of the output signals; the appearance of a multiplicative term in the frequency spectrum being indicative of the maximum permissible magnitude having been reached. Upon reaching the point where a multiplicative term appears, the pulsation magnitude can be subsequently reduced to a point where the multiplicative term becomes insignificant. The method may further include a calibration step, during which the spacing between the first and second sites is varied while the pulsation magnitude is held constant, in order to derive an optimum spacing. The calibration step may include a further step of varying the pulsation magnitude while the spacing of the first and second sites is held constant. In a further embodiment the method may include the measurement of arterial oxygen saturation derived from the frequency response of the output signals, such that the difference in levels of the arterial and venous oxygen saturation being representative of tissue oxygen consumption. The invention also provides an apparatus for non-invasively measuring venous oxygen saturation comprising a pressure transducer for applying a series of pulsations to a first site on a body, a pulse oximeter, control means for controlling the frequency and/or magnitude of said pulsations, such that the venous blood volume is modulated, signal processing means for extracting a value for venous oxygen saturation from signals received from said oximeter, said signals containing a component representative of a modulation of venous blood volume due to said pulsations. Advantageously, the control means operates to control the relationship between the frequency ωm of the pulsations caused by said drive signal and the heart rate ωHR according to the following conditions: ωm≠n(ωHR±ΔωHR) and ωm±(ωHR±ΔωHR)≠n(ωHR±ΔωHR) when n>1 Preferably the pressure transducer comprises an inflatable digit cuff supplied with air from an air pump; the pressure transducer and the pulse oximeter may be formed as an integral device. In order that the invention may be more fully understood an embodiment thereof will now be described by way of example with reference to the accompanying drawings in which: FIG. 1 illustrates the general principle by which the invention operates. FIG. 2 shows a block diagram of the operation of an embodiment of the invention. FIG. 3 shows an example of output waveforms from the oximeter device without venous blood volume modulation. FIG. 4 shows the waveforms generated according to the invention. FIG. 5 shows the frequency spectrum at the two frequencies of the PPG signals. FIG. 6 illustrates the correlation between the arterial blood oxygen saturation and the venous oxygen saturation. FIGS. 7a to 7e show graphs of the effect of variation of the modulation frequency on the power spectrum of the received signals from the oximeter device. FIG. 8 shows the relationship between the received signal amplitude and the modulation pressure for a range of cuff to oximeter probe spacings. With reference to FIG. 1, the principle of the invention will now be described. In its simplest form, the invention involves some means for inducing changes in venous blood volume and a corresponding means for measuring the changes induced. The signals extracted are processed to yield at least a separate value for venous oxygen saturation, and where necessary, a value for arterial oxygen saturation. The generalized theory underlying the invention will now be explained. Extending the lowest order conventional description of arterial pulse oximetry can make a zeroth order theoretical description of venous pulse oximetry. The Beer-Lambert law, which couples physical path length and effective absorbance into a single definition of optical density, is commonly used in arterial pulse oximetry to assign physical significance to changes in the optical path length. According to this model, we can write the received intensity due to a particular illuminating wavelength, λ, in terms of the proportion of arterial hemoglobin that is chemically combined with oxygen, S, I(t,λ)=I0(λ)exp{−[SεHbO2(λ)+(1−S)εHb(λ)]z(t)−μstaticd}, (1) where εHbO2(λ), εHb(λ) are the millimolar extinction coefficients of oxygenated and de-oxygenated hemoglobin respectively, z(t) is a function of both the dynamic physical path length through arterial blood and the total hemoglobin concentration, and μstaticd is the optical density of the non-pulsatile tissue and other anatomical components. By distinguishing optical paths through venous zv(t) and arterial za(t)blood we may generalize the model equation (1) to I(t,λ)=I0(λ)exp{−μaza(t)−μvzv(t)−μstaticd}, (2) where we have made the substitutions μa(λ)=└SaεHbO2(λ)+(1−Sa)εHb(λ)┘ μv(λ)=[SvεHbO2(λ)+(1−Sv)εHb(λ)] We now explore small changes in the received intensity resulting from small changes in the optical paths (resulting from the presence of low amplitude venous and arterial modulations) and consider the resultant changes (AC) normalized by the quasi-static (DC) intensity, namely Δ ⁢ ⁢ I ⁡ ( t , λ ) I ⁡ ( t , λ ) ≅ - μ a ⁢ Δ ⁢ ⁢ z a ⁡ ( t ) - μ v ⁢ Δ ⁢ ⁢ z v ⁡ ( t ) . ( 3 ) The quantities expressed in equation (3) can be separated by electronic (or other signal processing methods) since the induced venous modulations are of known origin. One method of separation is to induce a frequency modulation of the venous system in a band that is distinct from the arterial pulsations. Once isolation of the arterial and venous dynamics is achieved the process of calibration can be applied. Inversion of the classical Beer-Lambert model of pulse oximetry is usually achieved by generating two instances of equation (3) at two different wavelengths. These equations are then solved for a quantity known as the ratio of ratios, R, which is defined as the ratio of the total extinction of blood at the two wavelengths used. Assuming each term in equation (3) has been isolated, we may form two “ratio of ratios”: R a = [ I ⁡ ( t , λ 2 ) ⁢ Δ ⁢ ⁢ I ⁡ ( t , λ 1 ) I ⁡ ( t , λ 1 ) ⁢ Δ ⁢ ⁢ I ⁡ ( t , λ 2 ) ] a = μ a ⁡ ( λ 1 ) μ a ⁡ ( λ 2 ) ⁢ ⁢ R v = [ I ⁡ ( t , λ 2 ) ⁢ Δ ⁢ ⁢ I ⁡ ( t , λ 1 ) I ⁡ ( t , λ 1 ) ⁢ Δ ⁢ ⁢ I ⁡ ( t , λ 2 ) ] v = μ v ⁡ ( λ 1 ) μ v ⁡ ( λ 2 ) . ( 4 ) Knowledge of the extinction coefficients of oxygenated and deoxygenated hemoglobin at the two wavelengths can then be used to estimate Sa,Sv from the calculated R using the formulae S a = R a ⁢ ɛ Hb ⁡ ( λ 2 ) - ɛ Hb ⁡ ( λ 1 ) R a ⁡ [ ɛ Hb ⁡ ( λ 2 ) - ɛ HbO 2 ⁡ ( λ 2 ) ] - [ ɛ Hb ⁡ ( λ 1 ) - ɛ HbO 2 ⁡ ( λ 1 ) ] ⁢ ⁢ S v = R v ⁢ ɛ Hb ⁡ ( λ 2 ) - ɛ Hb ⁡ ( λ 1 ) R v ⁡ [ ɛ Hb ⁡ ( λ 2 ) - ɛ HbO 2 ⁡ ( λ 2 ) ] - [ ɛ Hb ⁡ ( λ 1 ) - ɛ HbO 2 ⁡ ( λ 1 ) ] ( 5 ) The invention will now be illustrated by way of example by description of a specific embodiment, involving the modulation of venous blood volume in the index finger to thereby inject a pulsatile signal into the venous blood. The methods of achieving the modulation, recording of the signal and extraction of the modulated signal will be outlined below. A digit cuff measuring 90 mm long and 16 mm wide was obtained from Hokanson®. Modulation of the venous blood volume within the index finger is achieved by continuously inflating and deflating the digit cuff which is wrapped around the base of the index finger. The high modulating frequency (six to seven Hertz) can be achieved mainly because the volume of air needed to inflate the digit cuff in order to cause a partial occlusion of the digit and hence a significant fractional blood volume change is small. In the same way, the time to deflate the cuff is short as the volume of air within the cuff is small. A micro pressure air pump from Sensidyne® was obtained as an air source for the digit cuff. It is able to maintain an air flow of 6.1 LPM and a minimum pressure of 4.9 psig. These specifications are suitable for the application of inflating the digit cuff to a suitable pressure in order to cause a significant fractional blood volume change and cause a pulsatile signal that is comparable to the arterial pulsation. A solenoid operated pinch valve was obtained from BioChem Valve® in order to modulate the digit cuff. The three-way pinch valve has one normally closed valve and one normally open valve. When the solenoid is energised, the configuration changes over. One valve is used to control the tube leading from the micro air pump to the digit cuff and the other is used to control the outlet from the digit cuff. During inflation, the tube leading from the micro air pump is opened in order to allow air to enter the digit cuff and the tube that is used as an air outlet from the digit cuff is closed. During deflation, the tube leading from the air pump into the digit cuff is ‘pinched’ and therefore closed and at the same time the tube leading from the digit cuff which is used as an air outlet is opened to allow air within the digit cuff to escape. By controlling the three-way pinch valve, modulation of the digit cuff at a certain frequency can be achieved. The new method of non-invasive venous oximetry works in conjunction with a standard pulse oximeter finger probe attached to a PPG system. The digit cuff is wrapped around the base of the index finger and the finger probe is also mounted to record the modulated venous blood volume signal. The probe to cuff spacing is selected to yield a suitable level of modulation in the received signal, as will be discussed in more detail later in this specification. As the finger probe used comes equipped with two light sources, red and infrared, two different signals of the modulated venous blood volume are recorded. These signals are in turn used to formulate the ratio of ratios which is related to the oxygen saturation of the venous blood (SvO2). The recorded signal will consist of two signals of different frequencies. One signal is the PPG signal that is related to the arterial pulsation which frequency is the subject's heart rate. The second signal is the modulated venous blood volume signal, that may be modulated at a frequency set away from the arterial pulsation so as to aid extraction of it through filtering techniques. FIG. 2 illustrates the operation of this embodiment in schematic form. A discussion of the results obtained with this embodiment now follows. The diagram in FIG. 3 shows the PPG signals (AC components) recorded without any venous blood volume modulation. The signal sources used to obtain the top waveform and bottom waveform were IR and Red respectively. The diagram in FIG. 4 shows the waveforms that were recorded when the venous blood volume was modulated at a frequency higher than the PPG signal and at a pressure that was below systole. By performing a Fast Fourier Transform (FFT) on the modulated waveforms, the power spectrum density of the two wavelengths can be obtained. FIG. 5 shows the power spectrum density at the two wavelengths. It can be seen from the power spectrums that the modulation of venous blood was at seven Hertz and at a pressure lower than the systolic pressure. The modulated venous blood volume can be easily extracted through band-pass filtering method and the ratio of ratios can be formulated in the same way as described earlier in the background discussion of the pulse oximeter. This can then be calibrated in the same manner with measurement of the oxygen saturation of blood samples by co-oximeter drawn from the pulmonary artery. In this way, a non-invasive mixed venous blood oximetry can be achieved. A preliminary calibration of uncalibrated SaO2 to uncalibrated SvO2 is shown in FIG. 6. The graph clearly shows a correlation between arterial oxygen saturation and venous oxygen saturation. As mentioned above, it is important that the signal due to modulation of the venous blood can be separated from the PPG signal. One way of achieving this is to ensure that the frequency with which the pulsations are applied is chosen such that is distinct from the PPG signal. In order to optimise the modulation frequency, both the modulation fundamental frequency and the multiplicative term if any should be set away from the second harmonic of the PPG signal. The frequency of the multiplicative term not only depends on the modulation frequency but also on the PPG fundamental frequency, that is, the heart rate. Since the normal heart rate at rest can vary, an optimisation phase can be introduced just before any actual measurement during operation. The purpose of the optimisation phase is to first gauge the heart rate of the subject and then position the modulation frequency in such a way that both the 1st and 2nd harmonics of the PPG signal are not obscured by the modulation fundamental frequency or the multiplicative term. An optimisation phase may be needed since the variability of the heart rate and the perceived modulation depth at the measurement site depends on the physiological profile of the subject. The upper limit of the modulation frequency is a function of the frequency response of the vascular system. Therefore too high a modulation frequency will cause the modulating signal to fail to register completely. During this optimisation phase, the modulation depth can be adjusted according to the magnitude of the multiplicative term, as will be described in more detail later. In this way both the modulation frequency and modulation depth could be optimised before any actual measurement during operation. The optimisation phase can also be made adaptable throughout the operation, so that real time changes in heart rate could be compensated for by adapting the modulation frequency to the changes. There are two conditions that need to be satisfied during modulation frequency optimnisation. In order to illustrate these two conditions, it helps to use a mathematical model each to represent the PPG signal and the modulating signal. The PPG signal can be represented by the equation: f HR ⁡ ( t ) = ∑ n = 1 ⁢ f n ⁢ sin ⁡ ( n ⁢ ⁢ ω HR ⁢ t + ϕ HR ) ( 1 ) Where ƒn is the coefficient and ωHR is the PPG fundamental frequency and n represent the harmonics (n=1 is the fundamental frequency), and φHR is the phase involved. The modulating signal can be represented by the equation: ƒm(t)=g0 sin(ωmt+φm) (2) Where g0 is the coefficient ωm is the modulation frequency and φm is the phase in the model. To illustrate the variability of the heart rate the equation (1) can be rewritten as: f HR ⁡ ( t ) = ∑ n = 1 ⁢ f n ⁢ sin ⁡ ( n ⁡ ( ω HR ± Δω HR ) ⁢ t + ϕ HR ) ( 3 ) The two conditions which need to be met for optimisation of the measurement are: ωm≠n(ωHR±ΔωHR) (4) and ωm±(ωHR±ΔωHR) ≠n(ωHR±ΔωHR) (5) where n>1 In this way, a table can be constructed to identify the forbidden frequencies. Assuming a heart rate is 70 and the variability is ±10 Forbidden frequency bands ωm for condition ωm for at (4) condition at (5) 2 Hz to 2.7 Hz 1 Hz to 4 Hz 3 Hz to 4.05 Hz 2 Hz to 2.7 Hz Therefore ωm should be at least greater than 4 Hz but less than the filter upper cut-off frequency for signal detection (typically 3 Hz to 6 Hz). Most commercial SpO2 devices use low cut-off frequencies. Thus ωm must be set in a narrow range of optimised band. The graphs shown in FIGS. 7a to 7e are the power spectrums of the PPG signal with venous modulation at various frequencies. A relatively high modulation depth of 160 mmHg was chosen such that the multiplicative term could be significantly registered. In the first graph shown in FIG. 7a, the first harmonic (n=2) of the PPG signal overlapped with the multiplicative term and the modulation fundamental overlapped with the 2nd harmonic. Thus the modulation frequency of 4 Hz failed both the conditions. This would pose a problem when it comes to spectrally separating the two signals. Furthermore, in optimising the modulation depth, the magnitude of the multiplicative term is important in determining the degree of coupling between the two signals, the overlapping of the multiplicative terms with PPG harmonics would cause erroneous measurement of the magnitude. In the second graph (FIG. 7b), at 4.5 Hz, the multiplicative term started to move away from the first harmonic but the modulation frequency remained dangerously close to the 2nd harmonic. The third graph illustrates the situation when the heart rate was increased. Although the modulation frequency has increased to 5 Hz, the multiplicative term and modulation fundamental still overlap with the 1st and 2nd harmonics respectively. This demonstrates that the optimisation depends on the heart rate variability as well. The fourth graph (FIG. 7d) illustrates the situation where the modulation frequency was set at 5.5 Hz. The multiplicative term overlapped the 2nd harmonic. The last graph (FIG. 7e) shows an optimised modulation frequency. Both the multiplicative term and the modulation fundamental were beyond the 3rd harmonic region. This was done to cater for the variability of the heart rate. Due to the proximity of the multiplicative term with the harmonics and the variability of the heart rate, the optimisation would result in a fairly narrow frequency band. As mentioned earlier above, the modulation pressure can be adjusted according to the magnitude of the multiplicative term. The modulation pressure must be high enough to cause artificial pulsations in the venous blood system and yet not too strong as to affect the arterial system. The indicator of too great a pressure is the appearance of the multiplicative term in the frequency spectrum of the detected signal. Since the multiplicative term is an indication of the degree to which the underlying arterial system is being disturbed, it is important the term is minimised. The graph shown in FIG. 8 illustrates the effect of modulation pressure and cuff to oximeter spacing on the level of the detected signal. Each of the curves plots the measured signal level against the modulation pressure, and the black dot indicates the point at which the multiplicative term becomes significant. By moving the modulation site closer to the site of measurement, the multiplicative term can be kept small, and the detected signal of a measurable level even with a relatively low pressure modulation. Typically the modulation pressure is set to result in approximately 0.1% variation in the DC level of the detected signal. The ideal balance between modulation pressure and modulation/measurement site spacing is represented by the space denoted “ideal design window”. Typically a spacing of 30 to 50 mm is appropriate, depending on the pressure applied via the cuff. If the spacing is too small, the pulsations from the transducer will be coupled to the oximeter probe and cause a motion artefact in the received signal. It is to be appreciated that in addition to the cuff and air pump arrangement, other ways of modulating pressure to generate a venous pulsatile signal are envisaged. This could for example be achieved by direct mechanical means or by applying electrical or thermal impulses to the site of modulation. Further, whilst the embodiment described applies positive pressure to the subject, a similar effect can be achieved by the application of negative pressure, for example by providing a vacuum pump to generate the perturbations to the system. Whilst the oximeter probe and pressure transducer will generally be separate devices, they may also be formed as an integral device, provided that mechanical coupling between the transducer and the probe is avoided. The specific embodiment described has employed the pulse oximeter probe in a transmission mode (in other words, the light passing through the digit, light source and sensor lying on opposite sides of the digit) but a probe operating in reflection mode could also be used. Since the veins lie close to the surface of the skin, if a reflection mode probe is used, the position of the probe could be used at a wide range of locations on the body, and is not limited to those regions where light is transmissible through the body tissue (digits, ear lobes etc). In the event that both arterial and venous oxygen saturation are measured, this can be achieved simultaneously as described above. Alternatively, should the external pressure modulations disturb the calibration of the arterial oxygenation measurement, the measurement of these two quantities can be separated either physically (by measuring arterial and venous saturation at different sites) or temporally (e.g. by multiplexing the arterial and venous measurements over time). Where the measurement sites are separated physically, the probe may be either integrally formed, e.g. incorporating an arterial oximeter, and a venous oximeter and cuff, arranged to measure from two adjacent fingers, or may be formed of separate arterial and venous monitor devices. A non-invasive method of determining venous oxygen content has been described which will allow accurate real time monitoring at lower risk to patients. This is of particular relevance during surgical recovery and management of therapy. A number of areas where the invention will find application are outlined below. When patients are suffering from severe illness of either the cardiovascular system or the lungs their survival depends on the ability to optimise the delivery of oxygen to their tissues. Tailoring of oxygen delivery to match a patient's requirements is very difficult, even in an intensive care unit. It relies upon a combination of clinical assessment, laboratory blood tests, haemodynamic data and oximetry. These data are obtained from the insertion of catheters into the radial/femoral arteries and pulmonary artery and can take 1-2 hours to complete. The insertion of these lines carries a significant morbidity and mortality. The integration of the data needed to tailor the patient's oxygen delivery can take several hours to achieve. As such it is not suited to rapidly changing physiological situations. A rapidly applicable, non-invasive, measure of tissue oxygen delivery would benefit all critically ill patients in intensive care units. It would also be useful for patients in High Dependency Units and ordinary hospital wards. Perhaps its most useful potential application, however, would be in the resuscitation of patients. Non-invasive venous oximetry would allow resuscitation to be more focused; since the survival of patients suffering out-of-hospital cardiac arrest is <5%, this would be a great breakthrough. In addition, non-invasive venous oximetry would prove an invaluable aid to the safe transfer of critically ill patients between intensive care units. Indeed, studies performed by the inventors have shown that there is a close correlation between SvO2 and cardiac output (CO), and therefore the method can also serve as a non-invasive indicator of Cardiac Output based on measurement of SvO2. Cardio-Pulmonary Bypass (CPB) and Extracorporeal Membrance Oxygenation (ECMO) involve the temporary replacement of cardio-vascular and lung function by use of a pump-oxygenator. CPB is used in the operating theatre, whilst ECMO is used in the Intensive Care unit to support patients who are suffering from potentially reversible heart/lungs failure. Blood flow from the pump is non-pulsatile, and this means that conventional oxime try is ineffective. The ability to track oxygen delivery non-invasively with a device which does not rely on naturally pulsatile flow would have wide application. Since Coronary Artery Bypass Grafting (CABG) is the most commonly performed operation in the USA today this represents a significant potential application. The diagnosis and monitoring of vascular disease and circulatory function will be enhanced by the availability of SvO2 measurement. Elevated SvO2 measures at rest may indicate reduced tissue perfusion due to impaired blood flow. Monitoring venous oxygen saturation will therefore allow the severity of injury and functional compromise resulting from trauma to be examined more easily. Depressed SvO2 measures may suggest tissue dysfunction and monitoring will allow judgements to be made about the viability of tissue during trauma or disease. As the PaO2 drops below about 40 Torr, even small changes in the partial pressure of inspired oxygen result in large decreases in SaO2. SvO2 measurement will enhance the monitoring of hypoxia in a range of conditions. Physical training evokes peripheral adaptations to allow for effective utilisation of the increase in O2 delivery resulting in higher O2 diffusional conductance in muscle. The effect of endurance training can be observed as a greater capillary density allowing for a longer transit time at a given blood flow and also a higher a {overscore (v)}O2 difference. The invention would be a valuable tool in performing exercise/stress tests and examining the effects of heat and cold, micro-gravity and dehydration. It would also support numerous other medical and physiological research themes.

<SOH> BACKGROUND OF THE INVENTION <EOH>The monitoring of venous blood oxygen saturation (SvO 2 ) is called venous oximetry. The method is often used in Intensive Care Units (ICU) to monitor the patient's overall oxygen supply and consumption. Current invasive methods have resulted in its under-utilization although SvO 2 is unquestionably a valuable assessment tool in the evaluation of oxygenation. All venous oximetry techniques can be categorised into two areas, methods that are invasive and those that are non-invasive. A discussion of the various known invasive and non-invasive techniques follows. Oxygen saturation can be measured invasively by employing a variation of the standard Swan-Ganz Pulmonary Artery Catheter (PAC) in which two fiberoptic bundles were inserted in the PAC. The modified PAC used the principle of reflection spectrophotometry to make quantitative measurement of oxygen transport. Due to its invasive nature and the cost of the modified PAC, the method is not employed extensively for venous oximetry. U.S. Pat. No. 5,673,694 is representative of this background art. The majority of non-invasive, continuous peripheral venous oximetry techniques are based on Near InfraRed Spectroscopy (NIRS) or a combination of NIRS and various exercise protocols such as over-systolic venous occlusion. NIRS is hindered from supplanting the current invasive, continuous method utilizing SvO 2 or central venous catheter mainly due to the difficulty in determining certain critical parameters without which calibration for venous oximetry would not be possible. Prior art approaches based upon NIPS are disclosed in U.S. Pat. Nos. 6,015,969 and 5,661,302. Pulse oximetry is one of the main applications of photoplethysmography (PPG), and is widely used for the measurement of arterial oxygen saturation, SpO 2 . The PPG waveform contains two components, one which is attributable to the pulsatile component in the vessels, i.e. the arterial pulse, is caused by the heartbeat and gives a rapidly alternating signal (AC component), and the other is due to the blood volume and its change in the skin and gives a steady signal that only changes slowly (DC component). Two wavelengths of light are used in Pulse oximetry, one in the red band (660 nm) and one in the infrared band (940 nm). Since at 660 nm reduced hemoglobin absorbs more light than oxyhemoglobin and at 940 nm, oxyhemoglobin absorbs more light than its reduced form, pulse oximetry relates this differential measurement to the arterial oxygen saturation. In pulse oximetry, light is first being transmitted through the tissues and the intensity of the transmitted light is then measured by a photo detector on the other side. The pulse oximeter first determines the AC component of the absorbance at each wavelength and then divides it by the corresponding DC component to obtain ratio that is independent of the incident light intensity. The ratio of ratios is then constructed as: R = AC 660 / DC 660 AC 940 / DC 940 The pulse oximeter is then calibrated by measuring the ratio of ratios and simultaneously sampling arterial blood for in vitro saturation measurements. Whilst the use of these techniques is effective for the measurement of arterial blood oxygen saturation, it relies upon the presence of pulsations of the arterial blood which is generated by the heart. No such measurable pulsations are present in venous blood. Venous Occlusion Plethymography (VOP) is the measurement of changes in tissue volume in response to temporary obstruction of venous return. It is used clinically to measure certain physiological conditions of blood vessels such as venous capacitance. VOP relies on the principle that occlusion of venous return causes slight swelling of distal portion of the tissue under test due to continued arterial inflow. The step response of venous blood volume over time during VOP can be used to measure arterial blood flow, venous outflow and venous compliance. M. Nitzal et al (Journal of Biomedical Optics 5(2), 155-162, April 2000) employed the principle of VOP to the measurement of SvO 2 , by applying pressure to the forearm sufficient to completely occlude venous flow, but leave arterial flow unaffected. Light absorption at 2 wavelengths is compared before and after occlusion. However, the approach does not appear to yield separate determination of venous and arterial oxygen saturation. PCT publication WO99/62399 and U.S. Pat. No. 5,638,816 relate to methods of venous oximetry where a cyclical active pulse is applied via an external cuff. However, the level of modulation (10% of the DC signal) is large, and will require a cuff-sensor spacing so close that the optical coupling will be affected, or if further away, pulsations will be at a level which will cause perturbations in the arterial system, and hence lead to inaccuracies in venous oxygen saturation measurements. As indicated above, prior art techniques for measuring venous oxygen saturation by non-invasive means do not yield the requisite accuracy. The aim of the invention is to achieve an improved measure of venous oxygen saturation. The principles of arterial pulse oximetry are well known (see above). The crucial element of the method that enables specific calibration of the oxygen carrying hemoglobin depends upon the presence of blood volume pulsations in the arterial system. These pulsations are of course naturally present throughout the circulation system. If one could induce pulsations in the venous system and properly isolate them from those of the arterial system, a similar calibration method could be employed to measure venous oxygen saturation. According to the invention, there is provided a method of non-invasively measuring venous oxygen saturation, comprising applying a pressure transducer at a first site on a body, applying a drive signal to the external pressure transducer at a predetermined frequency, to cause a series of pulsations of a predetermined magnitude in the venous blood volume in the vicinity of said first site, applying an oximeter device at a second site on the body, measuring output signals received from said oximeter device, said output signals containing a component representative of the modulation of venous blood volume due to said pulsations, deriving a measure of venous oxygen saturation from the frequency response of said output signals. The term oximeter device is intended to encompass any device which uses light of different frequencies to determine tissue oxygen content. It may encompass both transmission and reflection mode devices. The relationship between the distance between the first and second sites on the one hand, and the magnitude of the pulsations on the other hand, may be arranged such that a multiplicative term in the frequency spectrum of the measured signals, indicative of a disturbance to the arterial system, is minimised. Preferably the frequency of the drive signal is chosen such that the pulsations are distinguishable from the heart rate. The relationship between the frequency ω m of the pulsations caused by said drive signal and the heart rate ω HR can be chosen to comply with the following conditions: in-line-formulae description="In-line Formulae" end="lead"? ω m ≠n(ω HR ±Δω HR ) in-line-formulae description="In-line Formulae" end="tail"? in-line-formulae description="In-line Formulae" end="lead"? and in-line-formulae description="In-line Formulae" end="tail"? in-line-formulae description="In-line Formulae" end="lead"? ω m ±(ω HR ±Δω HR )≠n(ω HR ±Δω HR ) in-line-formulae description="In-line Formulae" end="tail"? where n>1 The frequency of the drive signal can be determined iteratively on the basis of a real time measurement of the heart rate. Ideally the magnitude of the pulsations is controlled such that the venous blood system is modulated without disturbing the arterial system. The magnitude of the pulsations can be controlled such as to cause a variation of less than 1% in the DC level of the received signal, or more preferably a variation of approximately 0.1% in the DC level of the received signal. In an alternative embodiment the oximeter is placed on a digit and a further pressure transducer is placed away from a distal end of a limb, and arranged to occlude the supply of blood to and from said limb, and the measurement is performed during the period of occlusion. Advantageously, the optimum magnitude of the pulsations can be determined by progressively increasing the pulsation magnitude and observing a frequency response of the output signals; the appearance of a multiplicative term in the frequency spectrum being indicative of the maximum permissible magnitude having been reached. Upon reaching the point where a multiplicative term appears, the pulsation magnitude can be subsequently reduced to a point where the multiplicative term becomes insignificant. The method may further include a calibration step, during which the spacing between the first and second sites is varied while the pulsation magnitude is held constant, in order to derive an optimum spacing. The calibration step may include a further step of varying the pulsation magnitude while the spacing of the first and second sites is held constant. In a further embodiment the method may include the measurement of arterial oxygen saturation derived from the frequency response of the output signals, such that the difference in levels of the arterial and venous oxygen saturation being representative of tissue oxygen consumption. The invention also provides an apparatus for non-invasively measuring venous oxygen saturation comprising a pressure transducer for applying a series of pulsations to a first site on a body, a pulse oximeter, control means for controlling the frequency and/or magnitude of said pulsations, such that the venous blood volume is modulated, signal processing means for extracting a value for venous oxygen saturation from signals received from said oximeter, said signals containing a component representative of a modulation of venous blood volume due to said pulsations. Advantageously, the control means operates to control the relationship between the frequency ω m of the pulsations caused by said drive signal and the heart rate ω HR according to the following conditions: in-line-formulae description="In-line Formulae" end="lead"? ω m ≠n(ω HR ±Δω HR ) in-line-formulae description="In-line Formulae" end="tail"? in-line-formulae description="In-line Formulae" end="lead"? and in-line-formulae description="In-line Formulae" end="tail"? in-line-formulae description="In-line Formulae" end="lead"? ω m ±(ω HR ±Δω HR )≠n(ω HR ±Δω HR ) in-line-formulae description="In-line Formulae" end="tail"? when n>1 Preferably the pressure transducer comprises an inflatable digit cuff supplied with air from an air pump; the pressure transducer and the pulse oximeter may be formed as an integral device. In order that the invention may be more fully understood an embodiment thereof will now be described by way of example with reference to the accompanying drawings in which: FIG. 1 illustrates the general principle by which the invention operates. FIG. 2 shows a block diagram of the operation of an embodiment of the invention. FIG. 3 shows an example of output waveforms from the oximeter device without venous blood volume modulation. FIG. 4 shows the waveforms generated according to the invention. FIG. 5 shows the frequency spectrum at the two frequencies of the PPG signals. FIG. 6 illustrates the correlation between the arterial blood oxygen saturation and the venous oxygen saturation. FIGS. 7 a to 7 e show graphs of the effect of variation of the modulation frequency on the power spectrum of the received signals from the oximeter device. FIG. 8 shows the relationship between the received signal amplitude and the modulation pressure for a range of cuff to oximeter probe spacings. detailed-description description="Detailed Description" end="lead"? With reference to FIG. 1 , the principle of the invention will now be described. In its simplest form, the invention involves some means for inducing changes in venous blood volume and a corresponding means for measuring the changes induced. The signals extracted are processed to yield at least a separate value for venous oxygen saturation, and where necessary, a value for arterial oxygen saturation. The generalized theory underlying the invention will now be explained. Extending the lowest order conventional description of arterial pulse oximetry can make a zeroth order theoretical description of venous pulse oximetry. The Beer-Lambert law, which couples physical path length and effective absorbance into a single definition of optical density, is commonly used in arterial pulse oximetry to assign physical significance to changes in the optical path length. According to this model, we can write the received intensity due to a particular illuminating wavelength, λ, in terms of the proportion of arterial hemoglobin that is chemically combined with oxygen, S, in-line-formulae description="In-line Formulae" end="lead"? I ( t, λ)= I 0 (λ)exp{−[ S ε HbO 2 (λ)+(1 −S )ε Hb (λ)] z ( t )−μ static d}, (1) in-line-formulae description="In-line Formulae" end="tail"? where ε HbO 2 (λ), ε Hb (λ) are the millimolar extinction coefficients of oxygenated and de-oxygenated hemoglobin respectively, z(t) is a function of both the dynamic physical path length through arterial blood and the total hemoglobin concentration, and μ static d is the optical density of the non-pulsatile tissue and other anatomical components. By distinguishing optical paths through venous z v (t) and arterial z a (t)blood we may generalize the model equation (1) to in-line-formulae description="In-line Formulae" end="lead"? I ( t ,λ)= I 0 (λ)exp{−μ a z a ( t )−μ v z v ( t )−μ static d}, (2) in-line-formulae description="In-line Formulae" end="tail"? where we have made the substitutions in-line-formulae description="In-line Formulae" end="lead"? μ a (λ)=└ S a ε HbO 2 (λ)+(1 −S a )ε Hb (λ)┘ in-line-formulae description="In-line Formulae" end="tail"? in-line-formulae description="In-line Formulae" end="lead"? μ v (λ)=[ S v ε HbO 2 (λ)+(1 −S v )ε Hb (λ)] in-line-formulae description="In-line Formulae" end="tail"? We now explore small changes in the received intensity resulting from small changes in the optical paths (resulting from the presence of low amplitude venous and arterial modulations) and consider the resultant changes (AC) normalized by the quasi-static (DC) intensity, namely Δ ⁢ ⁢ I ⁡ ( t , λ ) I ⁡ ( t , λ ) ≅ - μ a ⁢ Δ ⁢ ⁢ z a ⁡ ( t ) - μ v ⁢ Δ ⁢ ⁢ z v ⁡ ( t ) . ( 3 ) The quantities expressed in equation (3) can be separated by electronic (or other signal processing methods) since the induced venous modulations are of known origin. One method of separation is to induce a frequency modulation of the venous system in a band that is distinct from the arterial pulsations. Once isolation of the arterial and venous dynamics is achieved the process of calibration can be applied. Inversion of the classical Beer-Lambert model of pulse oximetry is usually achieved by generating two instances of equation (3) at two different wavelengths. These equations are then solved for a quantity known as the ratio of ratios, R, which is defined as the ratio of the total extinction of blood at the two wavelengths used. Assuming each term in equation (3) has been isolated, we may form two “ratio of ratios”: R a = [ I ⁡ ( t , λ 2 ) ⁢ Δ ⁢ ⁢ I ⁡ ( t , λ 1 ) I ⁡ ( t , λ 1 ) ⁢ Δ ⁢ ⁢ I ⁡ ( t , λ 2 ) ] a = μ a ⁡ ( λ 1 ) μ a ⁡ ( λ 2 ) ⁢ ⁢ R v = [ I ⁡ ( t , λ 2 ) ⁢ Δ ⁢ ⁢ I ⁡ ( t , λ 1 ) I ⁡ ( t , λ 1 ) ⁢ Δ ⁢ ⁢ I ⁡ ( t , λ 2 ) ] v = μ v ⁡ ( λ 1 ) μ v ⁡ ( λ 2 ) . ( 4 ) Knowledge of the extinction coefficients of oxygenated and deoxygenated hemoglobin at the two wavelengths can then be used to estimate S a ,S v from the calculated R using the formulae S a = R a ⁢ ɛ Hb ⁡ ( λ 2 ) - ɛ Hb ⁡ ( λ 1 ) R a ⁡ [ ɛ Hb ⁡ ( λ 2 ) - ɛ HbO 2 ⁡ ( λ 2 ) ] - [ ɛ Hb ⁡ ( λ 1 ) - ɛ HbO 2 ⁡ ( λ 1 ) ] ⁢ ⁢ S v = R v ⁢ ɛ Hb ⁡ ( λ 2 ) - ɛ Hb ⁡ ( λ 1 ) R v ⁡ [ ɛ Hb ⁡ ( λ 2 ) - ɛ HbO 2 ⁡ ( λ 2 ) ] - [ ɛ Hb ⁡ ( λ 1 ) - ɛ HbO 2 ⁡ ( λ 1 ) ] ( 5 ) The invention will now be illustrated by way of example by description of a specific embodiment, involving the modulation of venous blood volume in the index finger to thereby inject a pulsatile signal into the venous blood. The methods of achieving the modulation, recording of the signal and extraction of the modulated signal will be outlined below. A digit cuff measuring 90 mm long and 16 mm wide was obtained from Hokanson®. Modulation of the venous blood volume within the index finger is achieved by continuously inflating and deflating the digit cuff which is wrapped around the base of the index finger. The high modulating frequency (six to seven Hertz) can be achieved mainly because the volume of air needed to inflate the digit cuff in order to cause a partial occlusion of the digit and hence a significant fractional blood volume change is small. In the same way, the time to deflate the cuff is short as the volume of air within the cuff is small. A micro pressure air pump from Sensidyne® was obtained as an air source for the digit cuff. It is able to maintain an air flow of 6.1 LPM and a minimum pressure of 4.9 psig. These specifications are suitable for the application of inflating the digit cuff to a suitable pressure in order to cause a significant fractional blood volume change and cause a pulsatile signal that is comparable to the arterial pulsation. A solenoid operated pinch valve was obtained from BioChem Valve® in order to modulate the digit cuff. The three-way pinch valve has one normally closed valve and one normally open valve. When the solenoid is energised, the configuration changes over. One valve is used to control the tube leading from the micro air pump to the digit cuff and the other is used to control the outlet from the digit cuff. During inflation, the tube leading from the micro air pump is opened in order to allow air to enter the digit cuff and the tube that is used as an air outlet from the digit cuff is closed. During deflation, the tube leading from the air pump into the digit cuff is ‘pinched’ and therefore closed and at the same time the tube leading from the digit cuff which is used as an air outlet is opened to allow air within the digit cuff to escape. By controlling the three-way pinch valve, modulation of the digit cuff at a certain frequency can be achieved. The new method of non-invasive venous oximetry works in conjunction with a standard pulse oximeter finger probe attached to a PPG system. The digit cuff is wrapped around the base of the index finger and the finger probe is also mounted to record the modulated venous blood volume signal. The probe to cuff spacing is selected to yield a suitable level of modulation in the received signal, as will be discussed in more detail later in this specification. As the finger probe used comes equipped with two light sources, red and infrared, two different signals of the modulated venous blood volume are recorded. These signals are in turn used to formulate the ratio of ratios which is related to the oxygen saturation of the venous blood (SvO 2 ). The recorded signal will consist of two signals of different frequencies. One signal is the PPG signal that is related to the arterial pulsation which frequency is the subject's heart rate. The second signal is the modulated venous blood volume signal, that may be modulated at a frequency set away from the arterial pulsation so as to aid extraction of it through filtering techniques. FIG. 2 illustrates the operation of this embodiment in schematic form. A discussion of the results obtained with this embodiment now follows. The diagram in FIG. 3 shows the PPG signals (AC components) recorded without any venous blood volume modulation. The signal sources used to obtain the top waveform and bottom waveform were IR and Red respectively. The diagram in FIG. 4 shows the waveforms that were recorded when the venous blood volume was modulated at a frequency higher than the PPG signal and at a pressure that was below systole. By performing a Fast Fourier Transform (FFT) on the modulated waveforms, the power spectrum density of the two wavelengths can be obtained. FIG. 5 shows the power spectrum density at the two wavelengths. It can be seen from the power spectrums that the modulation of venous blood was at seven Hertz and at a pressure lower than the systolic pressure. The modulated venous blood volume can be easily extracted through band-pass filtering method and the ratio of ratios can be formulated in the same way as described earlier in the background discussion of the pulse oximeter. This can then be calibrated in the same manner with measurement of the oxygen saturation of blood samples by co-oximeter drawn from the pulmonary artery. In this way, a non-invasive mixed venous blood oximetry can be achieved. A preliminary calibration of uncalibrated SaO 2 to uncalibrated SvO 2 is shown in FIG. 6 . The graph clearly shows a correlation between arterial oxygen saturation and venous oxygen saturation. As mentioned above, it is important that the signal due to modulation of the venous blood can be separated from the PPG signal. One way of achieving this is to ensure that the frequency with which the pulsations are applied is chosen such that is distinct from the PPG signal. In order to optimise the modulation frequency, both the modulation fundamental frequency and the multiplicative term if any should be set away from the second harmonic of the PPG signal. The frequency of the multiplicative term not only depends on the modulation frequency but also on the PPG fundamental frequency, that is, the heart rate. Since the normal heart rate at rest can vary, an optimisation phase can be introduced just before any actual measurement during operation. The purpose of the optimisation phase is to first gauge the heart rate of the subject and then position the modulation frequency in such a way that both the 1 st and 2 nd harmonics of the PPG signal are not obscured by the modulation fundamental frequency or the multiplicative term. An optimisation phase may be needed since the variability of the heart rate and the perceived modulation depth at the measurement site depends on the physiological profile of the subject. The upper limit of the modulation frequency is a function of the frequency response of the vascular system. Therefore too high a modulation frequency will cause the modulating signal to fail to register completely. During this optimisation phase, the modulation depth can be adjusted according to the magnitude of the multiplicative term, as will be described in more detail later. In this way both the modulation frequency and modulation depth could be optimised before any actual measurement during operation. The optimisation phase can also be made adaptable throughout the operation, so that real time changes in heart rate could be compensated for by adapting the modulation frequency to the changes. There are two conditions that need to be satisfied during modulation frequency optimnisation. In order to illustrate these two conditions, it helps to use a mathematical model each to represent the PPG signal and the modulating signal. The PPG signal can be represented by the equation: f HR ⁡ ( t ) = ∑ n = 1 ⁢ f n ⁢ sin ⁡ ( n ⁢ ⁢ ω HR ⁢ t + ϕ HR ) ( 1 ) Where ƒ n is the coefficient and ω HR is the PPG fundamental frequency and n represent the harmonics (n=1 is the fundamental frequency), and φ HR is the phase involved. The modulating signal can be represented by the equation: in-line-formulae description="In-line Formulae" end="lead"? ƒ m ( t )= g 0 sin(ω m t+φ m )   (2) in-line-formulae description="In-line Formulae" end="tail"? Where g 0 is the coefficient ω m is the modulation frequency and φ m is the phase in the model. To illustrate the variability of the heart rate the equation (1) can be rewritten as: f HR ⁡ ( t ) = ∑ n = 1 ⁢ f n ⁢ sin ⁡ ( n ⁡ ( ω HR ± Δω HR ) ⁢ t + ϕ HR ) ( 3 ) The two conditions which need to be met for optimisation of the measurement are: in-line-formulae description="In-line Formulae" end="lead"? ω m ≠n(ω HR ±Δω HR )   (4) in-line-formulae description="In-line Formulae" end="tail"? in-line-formulae description="In-line Formulae" end="lead"? and in-line-formulae description="In-line Formulae" end="tail"? in-line-formulae description="In-line Formulae" end="lead"? ω m ±(ω HR ±Δω HR ) ≠n(ω HR ±Δω HR )   (5) in-line-formulae description="In-line Formulae" end="tail"? where n>1 In this way, a table can be constructed to identify the forbidden frequencies. Assuming a heart rate is 70 and the variability is ±10 Forbidden frequency bands ω m for condition ω m for at (4) condition at (5) 2 Hz to 2.7 Hz 1 Hz to 4 Hz 3 Hz to 4.05 Hz 2 Hz to 2.7 Hz Therefore ω m should be at least greater than 4 Hz but less than the filter upper cut-off frequency for signal detection (typically 3 Hz to 6 Hz). Most commercial SpO 2 devices use low cut-off frequencies. Thus ω m must be set in a narrow range of optimised band. The graphs shown in FIGS. 7 a to 7 e are the power spectrums of the PPG signal with venous modulation at various frequencies. A relatively high modulation depth of 160 mmHg was chosen such that the multiplicative term could be significantly registered. In the first graph shown in FIG. 7 a, the first harmonic (n=2) of the PPG signal overlapped with the multiplicative term and the modulation fundamental overlapped with the 2 nd harmonic. Thus the modulation frequency of 4 Hz failed both the conditions. This would pose a problem when it comes to spectrally separating the two signals. Furthermore, in optimising the modulation depth, the magnitude of the multiplicative term is important in determining the degree of coupling between the two signals, the overlapping of the multiplicative terms with PPG harmonics would cause erroneous measurement of the magnitude. In the second graph ( FIG. 7 b ), at 4.5 Hz, the multiplicative term started to move away from the first harmonic but the modulation frequency remained dangerously close to the 2 nd harmonic. The third graph illustrates the situation when the heart rate was increased. Although the modulation frequency has increased to 5 Hz, the multiplicative term and modulation fundamental still overlap with the 1 st and 2 nd harmonics respectively. This demonstrates that the optimisation depends on the heart rate variability as well. The fourth graph ( FIG. 7 d ) illustrates the situation where the modulation frequency was set at 5.5 Hz. The multiplicative term overlapped the 2 nd harmonic. The last graph ( FIG. 7 e ) shows an optimised modulation frequency. Both the multiplicative term and the modulation fundamental were beyond the 3 rd harmonic region. This was done to cater for the variability of the heart rate. Due to the proximity of the multiplicative term with the harmonics and the variability of the heart rate, the optimisation would result in a fairly narrow frequency band. As mentioned earlier above, the modulation pressure can be adjusted according to the magnitude of the multiplicative term. The modulation pressure must be high enough to cause artificial pulsations in the venous blood system and yet not too strong as to affect the arterial system. The indicator of too great a pressure is the appearance of the multiplicative term in the frequency spectrum of the detected signal. Since the multiplicative term is an indication of the degree to which the underlying arterial system is being disturbed, it is important the term is minimised. The graph shown in FIG. 8 illustrates the effect of modulation pressure and cuff to oximeter spacing on the level of the detected signal. Each of the curves plots the measured signal level against the modulation pressure, and the black dot indicates the point at which the multiplicative term becomes significant. By moving the modulation site closer to the site of measurement, the multiplicative term can be kept small, and the detected signal of a measurable level even with a relatively low pressure modulation. Typically the modulation pressure is set to result in approximately 0.1% variation in the DC level of the detected signal. The ideal balance between modulation pressure and modulation/measurement site spacing is represented by the space denoted “ideal design window”. Typically a spacing of 30 to 50 mm is appropriate, depending on the pressure applied via the cuff. If the spacing is too small, the pulsations from the transducer will be coupled to the oximeter probe and cause a motion artefact in the received signal. It is to be appreciated that in addition to the cuff and air pump arrangement, other ways of modulating pressure to generate a venous pulsatile signal are envisaged. This could for example be achieved by direct mechanical means or by applying electrical or thermal impulses to the site of modulation. Further, whilst the embodiment described applies positive pressure to the subject, a similar effect can be achieved by the application of negative pressure, for example by providing a vacuum pump to generate the perturbations to the system. Whilst the oximeter probe and pressure transducer will generally be separate devices, they may also be formed as an integral device, provided that mechanical coupling between the transducer and the probe is avoided. The specific embodiment described has employed the pulse oximeter probe in a transmission mode (in other words, the light passing through the digit, light source and sensor lying on opposite sides of the digit) but a probe operating in reflection mode could also be used. Since the veins lie close to the surface of the skin, if a reflection mode probe is used, the position of the probe could be used at a wide range of locations on the body, and is not limited to those regions where light is transmissible through the body tissue (digits, ear lobes etc). In the event that both arterial and venous oxygen saturation are measured, this can be achieved simultaneously as described above. Alternatively, should the external pressure modulations disturb the calibration of the arterial oxygenation measurement, the measurement of these two quantities can be separated either physically (by measuring arterial and venous saturation at different sites) or temporally (e.g. by multiplexing the arterial and venous measurements over time). Where the measurement sites are separated physically, the probe may be either integrally formed, e.g. incorporating an arterial oximeter, and a venous oximeter and cuff, arranged to measure from two adjacent fingers, or may be formed of separate arterial and venous monitor devices. A non-invasive method of determining venous oxygen content has been described which will allow accurate real time monitoring at lower risk to patients. This is of particular relevance during surgical recovery and management of therapy. A number of areas where the invention will find application are outlined below. When patients are suffering from severe illness of either the cardiovascular system or the lungs their survival depends on the ability to optimise the delivery of oxygen to their tissues. Tailoring of oxygen delivery to match a patient's requirements is very difficult, even in an intensive care unit. It relies upon a combination of clinical assessment, laboratory blood tests, haemodynamic data and oximetry. These data are obtained from the insertion of catheters into the radial/femoral arteries and pulmonary artery and can take 1-2 hours to complete. The insertion of these lines carries a significant morbidity and mortality. The integration of the data needed to tailor the patient's oxygen delivery can take several hours to achieve. As such it is not suited to rapidly changing physiological situations. A rapidly applicable, non-invasive, measure of tissue oxygen delivery would benefit all critically ill patients in intensive care units. It would also be useful for patients in High Dependency Units and ordinary hospital wards. Perhaps its most useful potential application, however, would be in the resuscitation of patients. Non-invasive venous oximetry would allow resuscitation to be more focused; since the survival of patients suffering out-of-hospital cardiac arrest is <5%, this would be a great breakthrough. In addition, non-invasive venous oximetry would prove an invaluable aid to the safe transfer of critically ill patients between intensive care units. Indeed, studies performed by the inventors have shown that there is a close correlation between SvO 2 and cardiac output (CO), and therefore the method can also serve as a non-invasive indicator of Cardiac Output based on measurement of SvO2. Cardio-Pulmonary Bypass (CPB) and Extracorporeal Membrance Oxygenation (ECMO) involve the temporary replacement of cardio-vascular and lung function by use of a pump-oxygenator. CPB is used in the operating theatre, whilst ECMO is used in the Intensive Care unit to support patients who are suffering from potentially reversible heart/lungs failure. Blood flow from the pump is non-pulsatile, and this means that conventional oxime try is ineffective. The ability to track oxygen delivery non-invasively with a device which does not rely on naturally pulsatile flow would have wide application. Since Coronary Artery Bypass Grafting (CABG) is the most commonly performed operation in the USA today this represents a significant potential application. The diagnosis and monitoring of vascular disease and circulatory function will be enhanced by the availability of SvO 2 measurement. Elevated SvO 2 measures at rest may indicate reduced tissue perfusion due to impaired blood flow. Monitoring venous oxygen saturation will therefore allow the severity of injury and functional compromise resulting from trauma to be examined more easily. Depressed SvO 2 measures may suggest tissue dysfunction and monitoring will allow judgements to be made about the viability of tissue during trauma or disease. As the PaO 2 drops below about 40 Torr, even small changes in the partial pressure of inspired oxygen result in large decreases in SaO 2 . SvO 2 measurement will enhance the monitoring of hypoxia in a range of conditions. Physical training evokes peripheral adaptations to allow for effective utilisation of the increase in O 2 delivery resulting in higher O 2 diffusional conductance in muscle. The effect of endurance training can be observed as a greater capillary density allowing for a longer transit time at a given blood flow and also a higher a {overscore (v)}O 2 difference. The invention would be a valuable tool in performing exercise/stress tests and examining the effects of heat and cold, micro-gravity and dehydration. It would also support numerous other medical and physiological research themes. detailed-description description="Detailed Description" end="tail"?

20050503

20070828

20051117

95746.0

WINAKUR, ERIC FRANK

VENOUS PULSE OXIMETRY

SMALL

ACCEPTED

ACCEPTED

Refrigerated merchandising storage unit with sliding door covers

A cover for a merchandising display unit (1) disclosed. The cover of the rectangular top opening of the storage compartment includes displaceable lids (9) arranged in two rows along opposing longer sides (2,4) of the storage unit so that access is provided to the storage compartment from both sides of the storage unit. The cover has a stationary cover plate (6) along a mid section of the storage unit and a rail system (5) with a number of parallel transverse rails between the two longer sides, and the lids (9) mounted between separate tracks in adjacent rails and are displaceable in a direction perpendicular to the longer sides (2,4).

1. A cover for a merchandising storage unit for display of goods including a storage compartment having an essentially rectangular top opening, the cover comprising: displaceable lids arranged in two rows along opposing longer sides of the storage unit so that access is provided to the storage compartment from both sides of the storage unit; a stationary cover plate extending parallel to said sides along a mid section of the storage unit; and a rail system with a number of parallel transverse rails between the two longer sides; wherein the lids are displaceably mounted between two adjacent rails of the rail system, said rails comprising separate tracks for the lids in each of the rows, whereby the lids in the rows are displaceable in a direction perpendicular to the longer sides. 2. A cover according to claim 1, wherein the rails have three tracks and the cover plate is arranged in a separate track comprising the uppermost of the three tracks. 3. A cover according to any of the preceding claims 1, wherein each of the lids covers approximately {fraction (1/3)} of a width of the top opening. 4. A cover according to any of the preceding claims 1, wherein the cover is planar. 5. A cover according to claim 1, wherein the cover is provided with a curved shape along a width of the opening. 6. A merchandising storage unit for display of goods comprising a storage compartment having an essentially rectangular top opening which provides access to the storage compartment from both longer sides of the storage unit and a cover comprising: displaceable lids arranged in two rows along opposing longer sides of the storage unit so that access is provided to the storage compartment from both sides of the storage unit; a stationary cover plate extending parallel to said sides along a mid section of the storage unit, and a rail system with a number of parallel transverse rails between the two longer sides, wherein the lids are displaceably mounted between two adjacent rails of the rail system, said rails comprising separate tracks for the lids in each of the rows, whereby the lids in the rows are displaceable in a direction perpendicular to the longer sides. 7. A merchandising storage unit according to claim 6, wherein the storage compartment is divided into two sections by a wall member arranged parallel to the longer sides. 8. A merchandising storage unit according to claim 6, wherein an end storage unit is arranged at an end section of the merchandising storage unit, the end storage unit comprising a number of displaceable lids, which may be displaced away from an outer side of the end storage unit and towards an inner side of the end storage unit for opening thereof.

The present invention relates to a cover for a merchandising display unit, in particular a refrigerated merchandising display unit, for display of goods. The cover of the rectangular top opening of the storage compartment includes displaceable lids arranged in two rows along opposing longer sides of the storage unit so that access is provided to the storage compartment from both sides of the storage unit. BACKGROUND For many years, grocery stores have commonly used refrigerating or freezing storage units of the above-mentioned kind, which are accessible from the top along both sides of the unit to allow for an overview of the contents of the storage unit and for free and unhindered access from the top by the customers and the staff. The refrigerating or freezing merchandising storage unit may be covered with insulation mats during periods in which the grocery store or a similar store is closed in order to reduce energy consumption when storing the goods in the storage unit. The use of open refrigerating and freezing merchandising storage unit results in extensive losses of energy and it may therefore be provided with an essentially transparent cover. Several examples of covers are known which may be used during opening hours. Thus, refrigerating and freezing storage units provided with a cover by the manufacturer are known. Alternatively, the cover may be retrofitted onto an existing storage unit. Known covers for refrigerating and freezing merchandising storage units may be divided into two different types. A sliding lid type and a “lift-up” type. The sliding lid type is of the kind where a cover in the longitudinal direction of the storage unit is typically divided into an appropriate number of plane plates, typically approx. 62.5 cm of width. The individual plates are arranged in two planes so that they may be displaced in the longitudinal direction of the storage unit over, respectively under each other. Examples hereof are known from EP 0 769 262 A2. The plates are transparent which provides for the possibility of examining the goods in the storage unit without having to open it. However, this design only allows for access to the storage compartment in a maximum of half of the longitudinal direction, which limits access to the goods in the storage unit and makes refilling and cleaning of the storage unit difficult since it cannot be opened in the entire longitudinal direction at the same time. U.S. Pat. No. 2,793,925 discloses a cover with sliding lids that are arranged in two planes and may be displaced in the transversal direction of the storage unit over, respectively under each other. However, the access to the storage compartment is similarly limited to a maximum of half of the top opening area. The “lift-up” type is of the kind where a cover in the longitudinal direction of the storage unit is divided into an appropriate number of plates, typically 62.5 cm in width. In the width, the lift-up type is divided into two plane plates hinged to a centre console extending in the longitudinal direction so that the individual parts of the 24-hour cover along the longer side of the storage unit may be lifted up and thereby opened. However, operating this type is difficult for little people such as for example children. In addition, a pumping effect is created during opening and closing so that when opened, warm air from the surroundings is sucked into the storage unit and cool air is pumped out into the surroundings when it is closed. This results in an undesirable energy loss. On this background, it is the object of the invention is to create a cover for a merchandising storage unit of the initially mentioned kind which provides for simultaneous or unhindered access to the storage compartment of the merchandising unit in its entire longitudinal direction along both longer sides without the disadvantages mentioned above, and in particular, it is an object of the invention to avoid unnecessary energy loss when operating the cover of a refrigerated storage unit. Moreover, it is an object of the invention to provide a cover for a merchandising unit, which ensures good access to the contents of the merchandising unit from the top on both sides and which allows the customers and staff to examine the contents of the storage unit without having their vision compromised. The invention comprises a cover of the initially mentioned kind, said cover has a stationary cover plate extending parallel to said sides along a mid section of the storage unit and a rail system with a number of parallel transverse rails between the two longer sides, and that the lids are displaceable mounted between two adjacent rails of the rail system, said rails comprising separate tracks for the lids in each of the rows, whereby the lids in the rows are displaceable in a direction perpendicular to the longer sides. The lids are preferably essentially transparent. Hereby, the objects of the invention are obtained since the lids of a cover according to the invention may be opened by displacement towards the centre of the merchandising unit under or over the stationary cover plate. Hereby, access may be provided along the entire length at both sides without creating a pump effect by operating the lids. In addition, good visual access is provided for easy examination of the contents of the merchandising unit, since the cover according to the invention provides for the possibility of simultaneous opening of a large percentage of the total top of the merchandising unit. By transparent lids, a good possibility of immediate visual examination of the contents is also ensured without having to open the cover and thereby initiate the unavoidable extra energy loss which this inevitably causes. In the preferred embodiment of the invention, the rails are provided with three tracks, where the cover plate is arranged in a separate track, which is preferably the uppermost of the three tracks. By using three tracks and having the centre plate stationary arranged in the middle of the uppermost track, a cover is provided with each of the lids covering approx. ⅓ of the width of the top opening. Hereby, a total potential opening area of up to ⅔ of the entire opening of the merchandising unit offers unhindered access to the contents of the storage unit. By designing the rails as profiles with three tracks, arrangement of the cover in three parallelly extending planes is allowed for. The two rows of lids are placed in the lower and the middle track, respectively, of the profiles. Hereby, the lids may be displaced independently of each other, not just in relation to the other lids in the same row, but also independently of the lids in the opposite row. In a preferred embodiment of a cover according to the invention, the cover is plane. In this embodiment, the rails are straight. In another preferred embodiment of the invention, the covers is provided with a curved shape as the rails are designed with a convex curvature whereby “free space” is provided above the goods in the storage compartment of the merchandising unit. The lids may be designed in an easily bendable plate material whereby the curvature does not necessarily have to be a circular curvature since the lids hereby would be able to adjust to the curvature of the rail sections which they at any given time are present in, once they are displaced back and forth between open and closed position. The invention also refers to a merchandising storage unit for display of goods comprising a storage compartment having an essentially rectangular top opening which provides access to the storage compartment from both longer sides of the storage unit and a cover according to the first aspect described above. The storage compartment may be divided into two sections by means of a wall member arranged parallel to the longer sides, whereby the merchandising unit may be used for several groups of goods separated so that there is access to the groups of goods from both sides of the merchandising unit. The invention is described in detail in the following with reference to the accompanying drawings, in which FIG. 1 is a perspective drawing of a merchandising unit displaying goods with a cover according to a first preferred embodiment of the invention, FIG. 2 is a perspective drawing of a merchandising unit displaying goods with a cover according to a second preferred embodiment of the invention, FIG. 3 is a cross-section of a merchandising unit displaying goods with a cover according to a preferred embodiment of the invention, and FIG. 4 is a detailed drawing of the embodiment of a cover in a corresponding end storage unit. In FIGS. 1 to 3 are shown a merchandising unit for display and sale of refrigerated or frozen goods in a supermarket store or a similar store. As it is shown, the contents of the merchandising unit for display of goods are accessible from both longer sides 2, 4. These two longer sides, a first side 2 and a second side 4, respectively, are parallel and the merchandising unit 1 has an essentially rectangular basic shape. The merchandising unit 1 has a storage compartment 8, which may be divided into two sections by a partition wall 3 as shown in FIG. 3. The storage compartment 8 has a top opening 7 over which the cover in mounted. The cover comprises a number of rails 5 arranged in parallel between the first and the second longer sides 2, 4 at a certain predetermined and preferably equal distance. The rails 5 have three substantially parallel tracks, in which the cover plates 6, 9, 10 are displaceably arranged. In the upper track, a centre plate 6 is permanently arranged. In each of the other tracks, a number of displaceable lids 9 are arranged so that they cover the opening between the centre plate 6 and the side edge 2, and in the third track on the rails 5 a number of displaceable lids 10 for covering the opening between the centre plate 6 and the second side 4 are correspondingly arranged. The lids 9, 10 are arranged in two rows in such a way that they may be shifted between an open position, where they are completely or partially shifted in underneath the centre plate 6 from each side, and a closed position, where the lids 9, 10 abut the first and the second side edges of the sides 2, 4, respectively. The width of the two sets of lids 9, 10 is preferably substantially the same as the width of the centre plate 6. Hereby, the possibility of simultaneous opening of approx. ⅔ of the top opening 7 of the storage unit 1 is achieved. As is apparent from FIGS. 2 and 3, the lids 9, 10 and the centre plate 6 are transparent so that there is unhindered access for visual orientation of the kinds of goods and their location in the merchandising unit 1. On the centre plate 6, a display device 11 may be mounted, on which signs with e.g. price tags, special offers, etc. relating to the goods in the storage unit may be displayed. As shown in FIG. 1, the cover of the storage unit 1 may be designed as a flat cover according to a first embodiment of the invention, since the rails 5 are straight and the cover plates 6, 9, 10 are plane. In a second embodiment of the invention, the cover is designed with a curvature as shown in FIG. 2. The rails 5 are curved, so that the two rows of lids 9, 10 along both longer sides 2, 4 of the merchandising unit 1 and the centre plate 6 have a convex cover of the merchandising unit 1. In FIG. 4 is shown an embodiment of the cover in an accompanying end storage unit which is located at the end of a merchandising unit of the type shown in FIGS. 1 and 2. The cover of the end storage unit is also divided into three sections so that a simultaneous opening of ⅔ of the top is possible. A fixed plate 6a is arranged at the back. Two displaceable plates 10a and 10b are arranged in a track 5a in front of the plate. The outermost plate 10a may be provided with a handle for operation of the cover. The invention is described above with reference to two preferred embodiments. However, it is realised by the invention that the cover may be carried out in other variants than these without departing from the scope of the invention as specified in the accompanying claims.

<SOH> BACKGROUND <EOH>For many years, grocery stores have commonly used refrigerating or freezing storage units of the above-mentioned kind, which are accessible from the top along both sides of the unit to allow for an overview of the contents of the storage unit and for free and unhindered access from the top by the customers and the staff. The refrigerating or freezing merchandising storage unit may be covered with insulation mats during periods in which the grocery store or a similar store is closed in order to reduce energy consumption when storing the goods in the storage unit. The use of open refrigerating and freezing merchandising storage unit results in extensive losses of energy and it may therefore be provided with an essentially transparent cover. Several examples of covers are known which may be used during opening hours. Thus, refrigerating and freezing storage units provided with a cover by the manufacturer are known. Alternatively, the cover may be retrofitted onto an existing storage unit. Known covers for refrigerating and freezing merchandising storage units may be divided into two different types. A sliding lid type and a “lift-up” type. The sliding lid type is of the kind where a cover in the longitudinal direction of the storage unit is typically divided into an appropriate number of plane plates, typically approx. 62.5 cm of width. The individual plates are arranged in two planes so that they may be displaced in the longitudinal direction of the storage unit over, respectively under each other. Examples hereof are known from EP 0 769 262 A2. The plates are transparent which provides for the possibility of examining the goods in the storage unit without having to open it. However, this design only allows for access to the storage compartment in a maximum of half of the longitudinal direction, which limits access to the goods in the storage unit and makes refilling and cleaning of the storage unit difficult since it cannot be opened in the entire longitudinal direction at the same time. U.S. Pat. No. 2,793,925 discloses a cover with sliding lids that are arranged in two planes and may be displaced in the transversal direction of the storage unit over, respectively under each other. However, the access to the storage compartment is similarly limited to a maximum of half of the top opening area. The “lift-up” type is of the kind where a cover in the longitudinal direction of the storage unit is divided into an appropriate number of plates, typically 62.5 cm in width. In the width, the lift-up type is divided into two plane plates hinged to a centre console extending in the longitudinal direction so that the individual parts of the 24-hour cover along the longer side of the storage unit may be lifted up and thereby opened. However, operating this type is difficult for little people such as for example children. In addition, a pumping effect is created during opening and closing so that when opened, warm air from the surroundings is sucked into the storage unit and cool air is pumped out into the surroundings when it is closed. This results in an undesirable energy loss. On this background, it is the object of the invention is to create a cover for a merchandising storage unit of the initially mentioned kind which provides for simultaneous or unhindered access to the storage compartment of the merchandising unit in its entire longitudinal direction along both longer sides without the disadvantages mentioned above, and in particular, it is an object of the invention to avoid unnecessary energy loss when operating the cover of a refrigerated storage unit. Moreover, it is an object of the invention to provide a cover for a merchandising unit, which ensures good access to the contents of the merchandising unit from the top on both sides and which allows the customers and staff to examine the contents of the storage unit without having their vision compromised. The invention comprises a cover of the initially mentioned kind, said cover has a stationary cover plate extending parallel to said sides along a mid section of the storage unit and a rail system with a number of parallel transverse rails between the two longer sides, and that the lids are displaceable mounted between two adjacent rails of the rail system, said rails comprising separate tracks for the lids in each of the rows, whereby the lids in the rows are displaceable in a direction perpendicular to the longer sides. The lids are preferably essentially transparent. Hereby, the objects of the invention are obtained since the lids of a cover according to the invention may be opened by displacement towards the centre of the merchandising unit under or over the stationary cover plate. Hereby, access may be provided along the entire length at both sides without creating a pump effect by operating the lids. In addition, good visual access is provided for easy examination of the contents of the merchandising unit, since the cover according to the invention provides for the possibility of simultaneous opening of a large percentage of the total top of the merchandising unit. By transparent lids, a good possibility of immediate visual examination of the contents is also ensured without having to open the cover and thereby initiate the unavoidable extra energy loss which this inevitably causes. In the preferred embodiment of the invention, the rails are provided with three tracks, where the cover plate is arranged in a separate track, which is preferably the uppermost of the three tracks. By using three tracks and having the centre plate stationary arranged in the middle of the uppermost track, a cover is provided with each of the lids covering approx. ⅓ of the width of the top opening. Hereby, a total potential opening area of up to ⅔ of the entire opening of the merchandising unit offers unhindered access to the contents of the storage unit. By designing the rails as profiles with three tracks, arrangement of the cover in three parallelly extending planes is allowed for. The two rows of lids are placed in the lower and the middle track, respectively, of the profiles. Hereby, the lids may be displaced independently of each other, not just in relation to the other lids in the same row, but also independently of the lids in the opposite row. In a preferred embodiment of a cover according to the invention, the cover is plane. In this embodiment, the rails are straight. In another preferred embodiment of the invention, the covers is provided with a curved shape as the rails are designed with a convex curvature whereby “free space” is provided above the goods in the storage compartment of the merchandising unit. The lids may be designed in an easily bendable plate material whereby the curvature does not necessarily have to be a circular curvature since the lids hereby would be able to adjust to the curvature of the rail sections which they at any given time are present in, once they are displaced back and forth between open and closed position. The invention also refers to a merchandising storage unit for display of goods comprising a storage compartment having an essentially rectangular top opening which provides access to the storage compartment from both longer sides of the storage unit and a cover according to the first aspect described above. The storage compartment may be divided into two sections by means of a wall member arranged parallel to the longer sides, whereby the merchandising unit may be used for several groups of goods separated so that there is access to the groups of goods from both sides of the merchandising unit. The invention is described in detail in the following with reference to the accompanying drawings, in which FIG. 1 is a perspective drawing of a merchandising unit displaying goods with a cover according to a first preferred embodiment of the invention, FIG. 2 is a perspective drawing of a merchandising unit displaying goods with a cover according to a second preferred embodiment of the invention, FIG. 3 is a cross-section of a merchandising unit displaying goods with a cover according to a preferred embodiment of the invention, and FIG. 4 is a detailed drawing of the embodiment of a cover in a corresponding end storage unit. detailed-description description="Detailed Description" end="lead"? In FIGS. 1 to 3 are shown a merchandising unit for display and sale of refrigerated or frozen goods in a supermarket store or a similar store. As it is shown, the contents of the merchandising unit for display of goods are accessible from both longer sides 2 , 4 . These two longer sides, a first side 2 and a second side 4 , respectively, are parallel and the merchandising unit 1 has an essentially rectangular basic shape. The merchandising unit 1 has a storage compartment 8 , which may be divided into two sections by a partition wall 3 as shown in FIG. 3 . The storage compartment 8 has a top opening 7 over which the cover in mounted. The cover comprises a number of rails 5 arranged in parallel between the first and the second longer sides 2 , 4 at a certain predetermined and preferably equal distance. The rails 5 have three substantially parallel tracks, in which the cover plates 6 , 9 , 10 are displaceably arranged. In the upper track, a centre plate 6 is permanently arranged. In each of the other tracks, a number of displaceable lids 9 are arranged so that they cover the opening between the centre plate 6 and the side edge 2 , and in the third track on the rails 5 a number of displaceable lids 10 for covering the opening between the centre plate 6 and the second side 4 are correspondingly arranged. The lids 9 , 10 are arranged in two rows in such a way that they may be shifted between an open position, where they are completely or partially shifted in underneath the centre plate 6 from each side, and a closed position, where the lids 9 , 10 abut the first and the second side edges of the sides 2 , 4 , respectively. The width of the two sets of lids 9 , 10 is preferably substantially the same as the width of the centre plate 6 . Hereby, the possibility of simultaneous opening of approx. ⅔ of the top opening 7 of the storage unit 1 is achieved. As is apparent from FIGS. 2 and 3 , the lids 9 , 10 and the centre plate 6 are transparent so that there is unhindered access for visual orientation of the kinds of goods and their location in the merchandising unit 1 . On the centre plate 6 , a display device 11 may be mounted, on which signs with e.g. price tags, special offers, etc. relating to the goods in the storage unit may be displayed. As shown in FIG. 1 , the cover of the storage unit 1 may be designed as a flat cover according to a first embodiment of the invention, since the rails 5 are straight and the cover plates 6 , 9 , 10 are plane. In a second embodiment of the invention, the cover is designed with a curvature as shown in FIG. 2 . The rails 5 are curved, so that the two rows of lids 9 , 10 along both longer sides 2 , 4 of the merchandising unit 1 and the centre plate 6 have a convex cover of the merchandising unit 1 . In FIG. 4 is shown an embodiment of the cover in an accompanying end storage unit which is located at the end of a merchandising unit of the type shown in FIGS. 1 and 2 . The cover of the end storage unit is also divided into three sections so that a simultaneous opening of ⅔ of the top is possible. A fixed plate 6 a is arranged at the back. Two displaceable plates 10 a and 10 b are arranged in a track 5 a in front of the plate. The outermost plate 10 a may be provided with a handle for operation of the cover. The invention is described above with reference to two preferred embodiments. However, it is realised by the invention that the cover may be carried out in other variants than these without departing from the scope of the invention as specified in the accompanying claims. detailed-description description="Detailed Description" end="tail"?

20040728

20120424

20050310

64229.0

WILKENS, JANET MARIE

Cover for a refrigerated merchandising unit and a merchandising unit with the same

SMALL

ACCEPTED

ACCEPTED

Frequency modulator for digital transmissions

The invention relates to a method of transmitting digital data exhibiting a rate T by means of a frequency modulator able to modulate as a function of the data, a central carrier frequency f0 at a first frequency value f0+¼T and/or a second frequency value f0−¼T. It comprises the step consisting in modulating the carrier frequency from one of the frequency values to the other during a time interval T, via successive frequency stages.

1. A method of transmitting digital data exhibiting a rate T by means of a frequency modulator able to modulate as a function of the data, a central carrier frequency f0 at a first frequency value f0+¼T and/or a second frequency value f0−¼T, method including the step of: modulating the central carrier frequency f0 from one of the frequency values to the other during a time interval T, via successive frequency stages. 2. The method as claimed in claim 1, wherein the number of frequency stages for going from f0−¼T to f0+¼T is the same as for going from f0+¼T to f0−¼T. 3. The method as claimed in claim 2, wherein the frequency stages for going from f0−¼T to f0+¼T are the same in absolute value as the frequency stages for going from f0+¼T to f0−¼T. 4. The method as claimed in, claim 1 wherein the number of frequency stages for going from one of the frequency values to the other is equal to 16. 5. The method as claimed in, claim 1 wherein the digital data are transmitted between a reference station and a mobile of a satellite-based positioning system. 6. A device able to implement a frequency modulation at a rate T according to two predetermined frequencies, comprising: a device for shaping the said modulation as several frequency stages during a time interval T. 7. The device as claimed in claim 6, comprising a microprocessor able to program the frequency stages. 8. The device as claimed in claim 7, furthermore comprising, linked to the microprocessor, a device of “FPGA” type able to shape the modulation as a function of data to be transmitted and of the programmed stages. 9. A frequency modulator, comprising a device able to shape a frequency modulation according to claim 6 and, linked to it, a device for generating instantaneous frequencies using a “DDS” function. 10. The method as claimed in claim 2, wherein the number of frequency stages for going from one of the frequency values to the other is equal to 16. 11. The method as claimed in claim 3, wherein the number of frequency stages for going from one of the frequency values to the other is equal to 16. 12. The method as claimed in claim 2, wherein the digital data are transmitted between a reference station and a mobile of a satellite-based positioning system. 13. The method as claimed in claim 3, wherein the digital data are transmitted between a reference station and a mobile of a satellite-based positioning system. 14. The method as claimed in claim 4, wherein the digital data are transmitted between a reference station and a mobile of a satellite-based positioning system.

The invention relates to a method of transmitting digital data by means of a frequency modulator based on a frequency modulation of minimum phase gradient or “Minimum Shift Keying” (MSK) type. The subject of the invention is also the corresponding device. The invention applies to all digital data transmissions using MSK-type frequency modulation. It applies in particular to the accurate determination of the position of a mobile on the basis of necessary data transmitted between a reference station and the mobile, both receiving satellite-based positioning signals. For the determination of the absolute position of a mobile, use is commonly made of satellite-based position measurement means, using for example the radio signals emitted by the satellites of the GPS (Global Positioning System) or of other similar systems (GLONASS system, future GALILEO system). The accuracy obtained goes from a few meters to a few tens of meters. In the GPS system, the signal emitted by a satellite is coded and the time taken by the signal to reach the point to be located is used to determine the distance between this satellite and this point, preferably called the pseudo-distance so as to take account of synchronization errors between the clock of the satellite and that of the station. These synchronization errors are conventionally eliminated by calculation when the signals are received from at least four different satellites. The determination of the distance between the point to be located and several satellites makes it possible, knowing the geographical coordinates of the satellites, to calculate the coordinates of the point to be located, usually coordinates expressed as latitude, longitude and altitude in a fixed terrestrial reference frame. To determine the precise position of a mobile (accuracy of from a centimeter to a meter, as the case may be), a so-called “differential GPS” procedure is used, which consists in using, at the level of the mobile, for the calculation of its position, the errors noted with regard to each pseudo-distance at the level of a so-called reference station of known position. This procedure makes it possible to correct the position calculation errors due in particular to trajectory deformations and to propagation. These errors are corrected, for example, by comparing for the reference station its known position and its calculated position arising from the measurement of the propagation time between the satellite and the reference station. The digital data corresponding to these errors are transmitted by the reference station to the mobile. Traditionally, these digital data are transmitted by radio using MSK-type frequency modulation, well-suited to an information bit rate that may be as much as 200 baud (bits per second). For greater information bit rates, such as 400 baud, the MSK-type frequency modulation is no longer suitable since it exhibits too wide a frequency spectrum that decreases too slowly. It is in fact recalled that the narrower the spectra of the reference stations and the faster they decrease, the more they can be juxtaposed on the same frequency band without them encroaching on one another and thus the more reference stations there can be. Now, it is noted that curve a), representing in FIG. 1 the frequency spectrum of an MSK modulation at 400 baud, exhibits at 1000 Hz a sidelobe situated at around −38 dB from the central lobe, whereas one wants it to be situated at around −50 dB. One solution consists in preceding the MSK frequency modulation by a Gaussian low-pass filtering. One is then dealing with a Gaussian minimum phase gradient, or “GMSK” (Gaussian minimum shift keying) modulation, whose frequency spectrum is represented by curve b) of FIG. 1. The spectral occupancy is better adapted than in the case of “MSK” modulation, but the GMSK modulation introduces undesirable inter-symbol crosstalk. It is recalled that inter-symbol crosstalk consists in the reception of the data (also termed symbols) being scrambled through the simultaneous reception of the correct data and of a tailoff of the previous data item or even of the previous but one. An important aim of the invention is therefore to propose a method and a device exhibiting spectral occupancy equivalent to that exhibited by GMSK modulation, without introducing inter-symbol crosstalk. Another aim of the invention is to propose a method that is easy to implement. To achieve these aims, the invention proposes a method of transmitting digital data exhibiting a rate T by means of a frequency modulator able to modulate as a function of the data, a central carrier frequency f0 at a first frequency value f0+¼T and/or a second frequency value f0−¼T, this process being characterized in that it comprises the step consisting in modulating the central carrier frequency f0 from one of the frequency values to the other during a time interval T, via successive frequency stages. Thus, instead of going directly from a first frequency value corresponding to a first value of a data item, to a second frequency value corresponding to a second value of a data item, one goes from the first frequency to the second through successive frequency stages. The frequency spectrum corresponding to these staged changes of frequency exhibits a faster decrease than the spectrum of an “MSK” modulation. This staged change of frequency furthermore exhibits the advantage of consuming less energy at high frequency than during instantaneous changes of frequency such as in the case of “MSK” modulation, this energy gain then being in part carried over to the central lobe of the spectrum, thus giving it a slightly wider useful band than in the case of “MSK” modulation and resulting in a gain in the signal/noise ratio with respect to “MSK”, for identical conditions. According to a characteristic of the invention, the frequency stages for going from f0−¼T to f0+¼T are the same in absolute value as the frequency stages for going from f0+¼T to f0−¼T. The number of frequency stages for going from one of the frequency values to the other is preferably equal to 16. The method applies in particular when the digital data are transmitted between a reference station and a mobile of a satellite-based positioning system. Also, the subject of the invention is not only the method of transmitting data, the gist of which has just be described, but also a device able to implement a frequency modulation at a rate T according to two predetermined frequencies. This device comprises means for shaping the said modulation as several frequency stages during a time interval T. This device comprises a microprocessor able to program the frequency stages and preferably, linked to the microprocessor, a device able to shape the modulation as a function of data to be transmitted and of the programmed stages. Finally, a subject of the invention is a frequency modulator, characterized in that it comprises a device able to shape a frequency modulation as described and a device for generating instantaneous frequencies. Other characteristics and advantages of the invention will become apparent on reading the detailed description which follows and which is given with reference to the appended drawings in which: the curves represented diagrammatically in FIG. 1 illustrate the variation of the frequency spectrum of a modulator of “MSK” type (curve a) and “GMSK” type (curve b); FIGS. 2a), 2b) and 2c) diagrammatically represent, as a function of time t, respectively an example of binary data to be transmitted, and the corresponding frequency and phase modulations; FIG. 3 diagrammatically represents as a function of time t, the frequency modulations corresponding to an input signal comprising the data −1, 1, −1 for a conventional “MSK” modulation (curve a) and for an exemplary modulation according to the invention designated “MSK16” (curve b); FIG. 4 diagrammatically represents as a function of time t, the “MSK” modulation (curve a) and “MSK16” modulation (curve b) for an input signal comprising the data −1, 1, 1, −1, 1, 1, −1, 1, −1, 1; FIG. 5 diagrammatically represents as a function of time, the phase variations corresponding to the said “MSK” modulation (curve a) and “MSK16” modulation (curve b) for an input signal comprising the data −1, 1, 1, −1, 1, 1, −1, 1, −1, 1; FIG. 6 diagrammatically represents the frequency spectra of an “MSK” modulation at 400 baud (curve a) and of an “MSK16” modulation at 400 baud (curve b); FIG. 7 diagrammatically represents an exemplary device able to implement the method according to the invention. The frequency modulation according to the invention is based on an “MSK”-type modulation. The features of the frequency modulation of “MSK” type are briefly recalled on the basis of an example described in conjunction with FIGS. 2a), 2b) and 2c). This is of course a constant-amplitude modulation. The binary data to be transmitted, represented in FIG. 2a), each have a duration T also referred to as the data rate. As represented in FIG. 2b), each data item is transmitted as a frequency, for a duration T according to the following characteristics: a) +1 is represented by the first frequency f0+¼T, b) −1 is represented by the second frequency f0−¼T, f0 being the central carrier frequency. With this frequency modulation may be associated over the duration T, a variation of the phase according to the following formula: φ = ∫ 0 T ⁢ 2 ⁢ π ⁢ ⁢ f ⁡ ( t ) ⁢ ⅆ t ( 1 ) The deviation ¼T is chosen in such a way that the corresponding phase (φ, represented in FIG. 2c), varies linearly between −π/2 and π/2. On reception, phase demodulation is often preferred to frequency demodulation. The method according to the invention consists in going from one frequency to the other according to successive stages in such a way as to attain the desired frequency (f0±¼T) at the end of the duration T. Thus, at the end of a time T, the corresponding phase φ attains the same value (±π/2) as in the case of “MSK” modulation; this makes it possible on reception to phase-demodulate the data received whether they have been modulated according to conventional “MSK” modulation or according to the invention. In what follows, consideration is given to an example of frequency modulation with 16 frequency stages, the carrier frequency f0 taking values between 1.6 and 3.5 MHz, in particular 1.8146 MHz, the rate T corresponding to 400 Hz and ¼T being equal to 100 Hz. The data thus modulated in this HF (high frequency) range are transmitted by means of a suitable antenna, in this instance a large antenna. The number of stages may take other values such as, for example, 8 or 32. Illustrated in FIG. 3 is this example of frequency modulation for an input signal comprising the data −1, 1, −1. Curve a) corresponds to conventional “MSK” modulation and exhibits two frequency states; curve b) corresponds to the modulation according to the invention referred to as “MSK16” since the modulation is shaped as 16 frequency stages. As regards the “MSK16” curve (b), the frequency f0+¼T normalized in the figure to +1 is attained at the 16th stage; likewise, the frequency f0−¼T normalized in the figure to −1 is attained at the 16th stage. In order for a receiver able to demodulate data modulated according to an “MSK” modulation to be compatible with a modulation according to the invention, “MSK16” for example, it is necessary for the phase to be equal to ±π/2 at the end of the time T. This is why, having regard to relation (1), certain frequency stages exceed (in absolute value) the frequency to be attained. The “MSK16” curve (b) which, in order to go from the frequency −1 to the frequency +1 with a phase variation equal to ±π/2, exhibits 16 frequency stages of the form ki×(¼T), i varying from 1 to 16, was obtained with the following coefficients ki: −0.703 −0.413 −0.12 +0.173 +0.466 +0.76 +1.053 +1.346 +1.64 +1.933 +2.226 +2.053 +1.791 +1.528 +1.266 +1 Likewise, the 16 frequency stages for going from +1 to −1 were obtained with the opposite coefficients: +0.703 +0.413 +0.12 −0.173 −0.466 −0.76 −1.053 −1.346 −1.64 −1.933 −2.226 −2.053 −1.791 −1.528 −1.266 −1 Of course, as in the case of “MSK”, the frequency remains stable when the data do not change; illustrated in FIG. 4 are the “MSK” modulation (curve a) and “MSK16” modulation (curve b) for an input signal comprising the data −1, 1, 1, −1, 1, 1, −1, 1, −1, 1. The differences between these two curves appear only at the changes of frequency. The phase variations of this input signal are illustrated in FIG. 5: curves a and b corresponding respectively to the “MSK” and “MSK16” modulations. The phases vary by ±π/2 over T in both cases, the phase of curve b) first lagging slightly behind that of curve a) and subsequently catching it up. The frequency spectrum of an “MSK16” modulation at 400 baud exhibits, as illustrated in FIG. 6, curve b a faster decrease than the spectrum of an “MSK” modulation at 400 baud also, illustrated by curve a. At 1000 Hz, one clearly obtains a sidelobe situated at around −50 dB of the central lobe and the sidelobes are much less marked. This staged change of frequency furthermore exhibits the advantage of consuming less energy at high frequency than during instantaneous changes of frequency, as in the case of “MSK” modulation, this energy gain then being in part carried over to the central lobe of the spectrum which is flatter in the case of “MSK16” modulation than in that of “MSK” modulation and thus gives it a slightly wider useful band and therefore a signal/noise ratio higher by around 2 dB, for identical conditions. As has been seen, as far as reception is concerned, conventional phase or frequency demodulation corresponding to “MSK” modulation may be performed. As represented in FIG. 7, the method according to the invention is implemented by a modulator comprising a device 1 for shaping the modulation as 16 stages, which is linked to a device 2 able to generate the instantaneous frequency using, for example, a “DDS” function, the acronym standing for “Direct Digital Synthesis”, this device itself being linked to a power amplifier 3. When the carrier frequency lies in a frequency range other than the HF range, a frequency transposition circuit may possibly be added between the device 2 and the amplifier 3. The device 1 for shaping the modulation as 16 frequency stages comprises means 10 for programming the 16 stages, included for example in a microprocessor, these means 10 being linked to means 20 for shaping the modulation as a function of the data to be transmitted and of the frequency stages such as programmed. These means 20 for shaping the modulation may be included in the microprocessor. These means 20 for shaping the modulation preferably comprise an “FPGA”, the acronym standing for “Field Programmable Gate Array”, linked to the microprocessor. The “FPGA” comprises, on the one hand and traditionally, means 21 for temporally adapting the data to be transmitted and, on the other hand, means 22 for providing the “DDS” type device with the instructions for generating the frequencies corresponding to the data modulated according to an “MSK16” modulation. Such a modulator which makes it possible to obtain a frequency spectrum exhibiting the same advantages as that obtained by a “GMSK”-type modulator, is however of simpler design insofar as it does not use any Gaussian filter. Moreover, by eliminating the Gaussian filter, it eliminates the corresponding part of the analog processing (filtering) of the data, thereby simplifying overall the management and the reliability of the modulator. Furthermore, it exhibits no inter-symbol crosstalk.

20040803

20100601

20050526

60240.0

BOCURE, TESFALDET

FREQUENCY MODULATOR FOR DIGITAL TRANSMISSIONS

UNDISCOUNTED

ACCEPTED

ACCEPTED

Solid preparation containing single crystal form

There are provided a solid preparation containing a single crystal of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxyl ic acid, an excipient and a disintegrating agent, and a method for producing the same.

1. A solid composition comprising a single crystal of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxyl ic acid, an excipient, and a disintegrating agent. 2. A solid composition according to claim 1, wherein said single crystal shows a solid 15N-NMR spectrum having specific signals at 226 ppm, 230 ppm, 275 ppm and 282 ppm. 3. A solid composition according to claim 1, wherein said single crystal shows an X-ray powder diffraction pattern having specific peaks at a reflection angle 2θ, of 6.62°, 7.18°, 12.80°, 13.26°, 16.48°, 19.58°, 21.92°, 22.68°, 25.84°, 26.70°, 29.16° and 36.70°. 4. A solid composition according to claim 1, wherein said excipient is one or more selected from the group consisting of lactose, lactose anhydride, crystalline cellulose, cornstarch, pregelatinized starch, partly pregelatinized starch, D-mannitol and dibasic calcium phosphate. 5. A solid composition according to claim 1 or 4, which contains the excipient in an amount 50 to 98 parts by weight based on 100 parts by weight of the solid preparation. 6. A solid composition according to claim 1, wherein said disintegrating agent is one or more selected from the group consisting of carmellose sodium, carmellose calcium, low-substituted hydroxypropyl cellulose, crosscarmellose sodium, carboxymethyl starch sodium and crosspovidone. 7. A solid composition according to claim 1 or 6, which contains the disintegrating agent in an amount 1 to 25 parts by weight based on 100 parts by weight of the solid preparation. 8. A solid composition according to claim 1, which contains further a binder. 9. A solid composition according to claim 8, wherein said binder is one or more selected from the group consisting of hydroxypropyl cellulose, hydroxy propylmethyl cellulose, and polyvinyl pyrrolidone. 10. A solid composition according to claim 1, which contains said single crystal in an, amount of 1 to 50 parts by weight based on 100 parts by weight of the solid preparation. 11. A solid composition according to claim 1, wherein the average particle size of said single crystal is 3 μm or greater and 50 μm or less. 12. A solid composition according to claim 1, wherein said solid preparation is in a form of tablets. 13. A method for producing a solid composition comprising a single crystal of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxyl ic acid, an excipient, and a disintegrating agent. 14. A method for producing a solid preparation according to claim 13, wherein said single crystal shows a solid=15N-NMR spectrum having specific signals at 226 ppm, 230 ppm, 275 ppm and 282 ppm. 15. A method for producing a solid preparation according to claim 13, wherein said single crystal shows an X-ray powder diffraction pattern having specific peaks at a reflection angle 2θ, of 6.62°, 7.18°, 12.80°, 13.26°, 16.48°, 19.58°, 21.92°, 22.68°, 25.84°, 26.70°, 29.16° and 36.70°. 16. A method for producing a solid composition according to claim 13, wherein said excipient is one or more selected from the group consisting of lactose, lactose anhydride, crystalline cellulose, corn starch, pregelatinized starch, partly pregelatinized starch, D-mannitol and dibasic calcium phosphate. 17. A method for producing a solid composition according to claim 13 or 16, wherein said solid preparation contains the excipient in an amount of 50 to 98 parts by weight based on 100 parts by weight of the solid preparation. 18. A method for producing a solid composition according to claim 13, wherein said disintegrating agent is one or more selected from the group consisting of carmellose sodium, carmellose calcium, low-substituted hydroxypropyl cellulose, crosscarmellose sodium, carboxymethyl starch sodium and crosspovidone. 19. A method for producing a solid composition according to claim 13 or 18, wherein said solid preparation contains the disintegrating agent in an amount of 1 to 25 parts by weight based on 100 parts by weight of the solid composition. 20. A method for producing a solid composition according to claim 13, wherein said solid preparation contains further a binder. 21. A method for producing a solid composition according to claim 20, wherein said binder is one or more selected from the group consisting of hydroxypropyl cellulose, hydroxy propylmethyl cellulose, and polyvinyl pyrrolidone. 22. A method for producing a solid preparation according to claim 13, wherein said solid preparation contains said single crystal in an amount of 1 to 50 parts by weight based on 100 parts by weight of the solid preparation. 23. A method for producing a solid preparation according to claim 13, wherein the average particle size of said single, crystal is 3 μm or more and 50 μm or less. 24. A method for producing a solid preparation according to claim 13, wherein said solid preparation is in a form of tablets.

TECHNICAL FIELD The present invention relates to a solid preparation of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazole carboxylic acid for oral administration. More particularly, it relates to a solid preparation comprising 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazole carboxylic acid as a single crystal form, and a method for producing the same. BACKGROUND ART 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid has a strong activity for inhibiting xanthine oxidase or a uric acid decreasing action, and it is expected to be a therapeutic agent for gout or hyperuricemia, as has been described in International Publication WO92/09279. In International Publication WO99/65885, there are described following six crystal polymorphs of 2-(3-cyano-4-isobutyloxyphehyl)-4-methyl-5-thiazole carboxylic acid, i.e., a polymorph which shows an X-ray powder diffraction pattern having specific peaks at a reflection angle 2θ, of about 6.62°, 7.18°, 12.80°, 13.26°, 16.48°, 19.58°, 21.92°, 22.68°, 25.84°, 26.70°, 29.16° and 36.70° (crystal A).; a polymorph which has specific peaks at a reflection angle 2θ of about 6.76°, 8.08°, 9.74°, 11.50°, 12.22°, 13.56°, 15.76°, 16.20°, 17.32°, 19.38°, 21.14°, 21.56°, 23.16°, 24.78°, 25.14°, 25.72°, 26.12°, 26.68°, 27.68° and 29.36° (crystal B); a polymorph which has specific peaks at a reflection angle 2θ of about 6.62°, 10.82°, 13.36°, 15.52°, 16.74°, 17.40°, 18.00°, 18.70°, 20.16°, 20.62°, 21.90°, 23.50°, 24.78°, 25.18°, 34.08°, 36.72° and 38.04° (crystal C); a polymorph which has specific peaks at a reflection angle 2θ of about 8.32°, 9.68°, 12.92°, 16.06°, 17.34°, 19.38°, 21.56°, 24.06°, 26.00°, 30.06°, 33.60° and 40.34° (crystal D).; and a polymorph which has specific peaks at a reflection angle 2θ of about 6.86°, 8.36°, 9.60°, 11.76°, 13.74°, 14.60°, 15.94°, 16.74°, 17.56°, 20.00°, 21.26°, 23.72°, 24.78°, 25.14°, 25.74°, 26.06°, 26.64°, 27.92°, 28.60°, 29.66° and 29.98° (crystal G), and an amorphous (also referred to as crystal E). In said International Publication WO99/65885, it is described that crystals A, C and G are useful in view of retention of a crystal form in long term storage. Among them, crystal A is preferred in view of industrial superiority. However, the publication is silent about what the industrial superiority means. Further, the publication has no evidence (data) supporting the fact that the crystal A is preferred in view of industrial superiority. The present inventors investigated this matter and found that, in formulating 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazole carboxylic acid, it is not possible to obtain preparations having no variation in the dissolution profiles of drugs, even if such a crystal form is used as is thought to be most stable in a physical stability test. Further, they found that there is a crystal form that is suitable for preparing preparations, independently from the characteristics of the crystals (including amorphous) of drug substances and have reached the invention. An object of the invention is, therefore, to provide solid preparations of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid which is stable and which is little variation in the dissolution profiles. DISCLOSURE OF THE INVENTION The invention provides solid preparations containing a single crystal form of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid, excipients and disintegrating agents. Further, the invention provides a process for producing solid preparations containing a single crystal form of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid, excipients and disintegrating agents. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is an X-ray powder diffraction pattern showing the transformation of crystal B in Reference Example 1. FIG. 2 is an X-ray powder diffraction pattern showing the transformation of crystal D in Reference Example 1. FIG. 3 is an X-ray powder diffraction pattern showing the transformation of crystal E in Reference Example 1. FIG. 4 is a data showing the transformation speed of crystal B in Reference Example 1 (unsealed state at 40° C./75% RH). FIG. 5 is a data showing the transformation speed of crystal D in Reference Example 1 (unsealed at 40° C./75% RH). FIG. 6 is a data showing the transformation speed of crystal E in Reference example 1 (unsealed at 40° C./75% RH). FIG. 7 shows dissolution profiles of tablets containing crystal A (particles 1 to 4) in Example 4 each having a different average particle size. BEST MODE FOR CARRYING OUT THE INVENTION The single crystal of the 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid (also referred to as the drug substance of the invention) of the invention is that which has a characteristic spectrum when the drug substance is analyzed by a solid NMR or that having specific peaks when analyzed by an X-ray powder diffraction. The crystal of the invention, i.e., the crystal A of the drug substance of the invention has, when analyzed by a solid 15N-NMR a, a spectrum having specific signals at 226 ppm, 228 ppm, 276 ppm, and 282 ppm. When analyzed by a solid 13C-NMR, the crystal A has approximately equivalent doublet peak at 20 ppm. Further, the crystal of the drug substance of the invention shows an X-ray powder diffraction pattern having specific peaks at a reflection angle 2θ, of about 6.62°, 7.18°, 12.80°, 13.26°, 16.48°, 19.58°, 21.92°, 22.68°, 25.84°, 26.70°, 29.16° and 36.70°. The crystal of the drug substance of the invention can be produced by the method shown in, for example, International Publication WO 92/09279 and WO 99/65885. The crystal of the drug substance of the invention is contained in the solid preparation of the invention preferably in an amount of 1 to 50 parts by weight based on 100 parts by weight of the solid preparation. There are no particular restrictions to the average particle size of the crystal of the drug substance of the invention contained in the solid preparation of the invention. The average particle size is preferably 3 μm or greater and 50 μm or less, when it is determined by an image analysis. Examples of the excipients for the solid preparation of the invention include lactose, lactose anhydride, crystalline cellulose, corn starch, pregelatinized starch, partly pregelatinized starch, D-mannitol and dibasic calcium phosphate. Particularly the lactose, crystalline cellulose, starches or their combination are preferable. The excipients are contained in an amount of 50 to 98 parts by weight, and more preferably 60 to 95 parts by weight, based on 100 parts by weight of the solid preparation. Examples of the disintegrating agent for the solid preparation of the invention include carmellose sodium, carmellose calcium, low-substituted hydroxypropyl cellulose, crosscarmellose sodium, carboxymethyl starch sodium and crosspovidone. Particularly the crosscarmellose sodium and partly pregelatinized starch are preferable. The disintegrating agent is contained in an amount of 1 to 25 parts by weight, preferably 1.5 to 20 parts by weight, based on 100 parts by weight of the solid preparation. There may be added known binders, lubricants, coating agents, plasticizers, diluents, colorants, preservatives, antiseptics or fragrance agents to the solid preparation of the invention to improve the physical properties, appearance, odor, etc. of the preparation. The binders for the solid preparation of the invention may be those known to the persons in the art. Particularly preferable binders are hydroxypropyl cellulose, hydroxy propylmethyl cellulose, and polyvinyl pyrrolidone. The binder is contained in an amount of 0.5 to 25 parts by weight, and preferably 1 to 20 parts by weight, based on 100 parts by weight of the solid preparation of the invention. The solid preparations of the invention can be produced by compressing a mixture of the crystals of the drug substance of the invention with excipients and disintegrating agents. For example, one method for the production includes mixing the crystals of the drug substance of the invention with the materials for the preparation by a suitable mixer, and directly compressing the mixture to tablets. Other methods include a dry granulating step to produce granules for tablets using dry granulating machines or roller compacters, and a wet granulating step to produce granules for tablets using water, ethanol and solutions containing binders when necessary. There is no limitation to the dosage form of the solid preparation of the invention. An example is a tablet. When the solid preparation is made in a form of a tablet, the tablet can be produced, for example, through granulating, sieving, mixing and tableting steps. Further, it is possible to coat the surface of the tablet by adding a coating step-to the production steps mentioned above. Concrete examples of producing the tablet are as follows; (1) Granulating Step To a known granulating machine there are charged crystals of the drug substance of the invention, excipients, disintegrating agents and binders, and water is sprayed to the charged mixture, followed by granulating the mixture to obtain granules. Otherwise, there may be charged crystals of the drug substance of the invention, excipients and disintegrating agents excluding binders, to a known granulating machine, and water in which binders are dissolved is sprayed to the charged mixture, followed by granulating the mixture to obtain granules. In the former case, the granules at the end of spraying contains moisture (determined by the loss on drying method) in an amount of 17 to 26% by weight while in the latter case, the granules at the end of spraying contains moisture in an amount of about 10 to 16% by weight. That is, it is possible in the latter case to produce granules with a lesser amount of water, enabling to shorten the production time. The loss on drying method is carried out by drying powder under heat by emission of infrared rays and determining the percentage (%) of the moisture in the powder based on the weight change caused by the evaporation of water. In the latter case, there is a tendency that the content ratio of drug substance at each particle size group (the content of drug substance in granules classified by the particle size) becomes constant. (2) Sieving Step The obtained granules are sieved through a desired sieve to remove coarse particles, for example, particles of 710 μm or larger. (3) Mixing Step The sieved granules are mixed with disintegrating agents and lubricants to obtain lubricated granules to be tableted. (4) Tableting Step The lubricated granules are tableted by a conventionally known, rotary tableting machine to obtain plain tablets. In this step, conditions for the tableting may be those known to persons in the art. A preferred tableting pressure, for example, is 1,300 kgf/cm2 or more and 5,200 kgf/cm2 or less. (5) Coating Step A coating solution is prepared by dissolving a coating agent in water. Subsequently, the plain tablets are coated with the coating solution by a known coating machine to obtain the tablets of the invention. The crystal of the drug substance of the invention is not limited to a particular particle size. Preferred average particle size is in the range from 3 μm to 50 μm (measured by an image analysis). When the size is less than 3 μm, the particle tends to be dispersed at weighing, or care should be taken at weighing and at the time the starting material is charged into a manufacturing equipment. However, the solid preparations of the invention can be produced even if the average particle size is out of the range. When the average particle size is over 50 μm, the produced solid preparations vary in the dissolution profile. According to the invention, there are provided solid preparations that have less variation in the dissolution profile by using a single crystal form (the crystal form of the drug substance of the invention) and a method for producing the same. When the particle size of the crystal of the drug substance is controlled to be in a predetermined range, it is possible to provide solid preparations having a uniform dissolution profile and a method for producing the same. According to the invention, it is possible to provide solid preparations having an improved content uniformity by using a single crystal form (the crystal form of the drug substance of the invention) and a method for producing the same. When the particle size of the crystal of the drug substance is controlled to be in a predetermined range, it is possible to provide solid preparations having a still more improved content uniformity (i.e., small CV valued preparations) and a method for producing the same. According to the invention, it is possible to provide stable solid preparations wherein no transformation of effective ingredients is occurred during the process of formulating to tablets, etc., by using a single crystal form (the crystal form of the drug substance of the invention) and a method for producing the same. The drug substance of the invention is preferably administered 1 to 3 times a day in an amount of 0.8 to 50 mg/day. The solid preparation and a method for producing the same can be used for producing an inhibitor of xanthine oxidase, uric acid reducing agent, gout therapeutic agent or hyperuricemia therapeutic agent and a method for production of these agents. The gout or hyperuricemia can be treated by administrating the solid preparations of the invention to patients. That is, the invention provides a method for treating the gout or hyperuricemia, and a method for producing the therapeutic agent for treating the gout or hyperuricemia. Further, the invention provides a method for administering a sole crystal form (crystal A) of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxyl ic acid in a form of a solid preparation. The invention is explained by reference to working examples. It should naturally be understood that the invention is not limited by these examples. EXAMPLES The stability, dissolution rate, solid 13N-NMR and 13C-NMR of each crystal form of drug substances (crystals A, B, C, D, E and G) of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxyl ic acid were measured as reference examples. The drug substances (crystals A, B, C, D, E and G) of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxyl ic acid can be produced, for example, by the methods shown in International Publication WO 92/09279 and WO 99/65885. Reference Example 1 Physical Stability Each of the drug substances (crystals A, B, C, D, E and G) of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxyl ic acid was tested in bottles with and without closure under the conditions of 40° C./75% RH. Any degradant was detected by a HPLC. Their transformation was detected by an X-ray powder diffraction pattern and by a thermal mass measurement method, and the 50% transform time was determined. The results are shown in Table 1. There was no degradant for all of the six crystal forms. Crystals A, C and G were stable even after storage for three months while transformation of crystals B, D and E was detected. <50% Transform time> 40° C./75% RH without 40° C./75% RH Analysis type closure with closure Crystal A XRD (Not changed) (Not changed) Crystal B TG 14 hours 5 days Crystal C XRD (Not changed) (Not changed) Crystal D XRD 0.25 hours 17 days Crystal E XRD 19 days 55 days Crystal G XRD (Not changed) (Not changed) For the above HPLC, Model 2690 produced by Waters was adopted, using an ODS column with a measured wave length of 217 nm at a predetermined temperature around 40° C. For the above X-ray powder diffraction, Model XRD-6000 of Shimadzu Corp. was used. For the above heat mass measurement, Model TGA7, Pyrisl produced by Perkin Elmer was used at a temperature rising speed of 40° C./min. Reference Example 2 Dissolution Rate The dissolution rate was measured according to USP 24, <1087>Intrinsic Dissolution. Specifically, the measurement was carried out as follows: 50 mg each of crystals powdered lightly in an agate mortar was set between plates, and a pressure of 754 kgf/cm2 was applied thereto for one minute to produce pellets. As the testing solution, 900 mL of the second fluid of the disintegration test of Japanese Pharmacopoeia was used and the test was carried out at 50 rpm using the dissolution apparatus produced by Vankel. Subsequently, the testing liquid was filtered through a filter and the resultant, used as the sample solution, was tested with respect to a standard solution by a spectrophotometry (wavelength of 317 nm). The results are shown in Table 2, in which the order of the dissolution rate of the six crystals is as follows: E>A>B>D>G>C. Intrinsic rate (mg/cm2/min) Crystal A 0.1434 Crystal B 0.1242 Crystal C 0.0694 Crystal D 0.1092 Crystal E 0.1874 Crystal G 0.0967 Reference Example 3 Solid NMR Data of Crystal Forms The analysis of the drug substance contained in the preparations is limited only to solid NMR. Therefore, Crystals A, B, C, D, E and G of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxyl ic acid was analyzed in advance by the solid NMR. The crystals show the following spectrums: Solid 15N-NMR Crystal A: Sharp peaks at 226 ppm, 228 ppm, 276 ppm and 282 ppm; Crystal B: Broad peaks at 216 ppm, 222 ppm and 284 ppm; Crystal C: Sharp single peaks at 210 ppm and 282 ppm; Crystal D: Sharp single peaks at 229 ppm and 264 ppm; Crystal E: Broad peaks at 223 ppm and 281 ppm; Crystal G: Sharp single peaks at 216 ppm and 222 ppm, and a doublet peak at 283 ppm. Solid 13C-NMR(specific peak at 20 ppm) Crystal A: approximately equivalent doublet peaks; Crystal B: non-equivalent doublet peaks; Crystal C: approximately equivalent triplet peaks; Crystal D: two single peaks; Crystal E: Broad peaks; Crystal G: non-equivalent triplet peaks. In the following examples, each of the crystal forms was determined using the spectrum data described above. Example 1 82.05 g of crystal A of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxyl ic acid, 328.61 g of lactose (Pharmatose 200M, produced by DMV), 77.03 g of partly pregelatinized starch (PC-10, produced by Asahi Kasei Corp.), 12.31 g of hydroxypropyl cellulose (HPC-SL, produced by Nippon Soda Co.) were charged into a fluidized-bed granulator with agitator (New Marumerizer NQ-125, produced by Fuji Paudal) and were fluidized at a heater temperature of 60° C. with a air amount of 0.7 m3/min. Subsequently, ion exchanged water was sprayed thereto at a spraying speed of 16 g/min, and dried at 60° C. to obtain granules containing about 12% by weight of the drug substance. The produced granules were sieved through a vibrating screen for removing particles having a size of 710 μm or greater to obtain sieved granules. 1,200 g of the sieved granules were mixed with 24.6 g of cross carmellose sodium (Ac-Di-Sol, produced by Asahi Kasei Corp.) and 6.15 g of magnesium stearate (produced by Sakai Chemical Ind.) in a cross rotary mixer (CM-10-S, produced by Tsukasa Ind.) to obtain the lubricated granules. The lubricated granules was tableted with a rotary type tableting machine (HT-P18, produced by Hata Tekkosho, tablet size: 7 mmφ, tableting pressure: 2,500 kgf/cm3) The obtained preparations were analyzed by a solid 15N-NMR, with the result that there were sharp peaks at 226 ppm, 228 ppm, 276 ppm and 282 ppm. When the preparations were analyzed by a solid 13C-NMR,-the peak at 20 ppm was an approximately equivalent doublet peak and, accordingly, it was confirmed that crystal form of the drug substance in the preparations is all crystal A. Comparative Example 1 Tablets were prepared by a method same as that of Example 1 except that crystal C of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxyl ic acid was used. The obtained preparations were analyzed by a solid 15N-NMR, with the result that the peaks at 210 ppm and 282 ppm were broadened, an sharp peak was shown at 284 ppm and the peak at 20 ppm showed an broad peak when they were analyzed by a solid 13C-NMR. Accordingly, it was confirmed that crystals C and E were contained in the preparations. Comparative Example 2 Tablets were prepared by a method same as that of Example 1 except that crystal B of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxyl ic acid was used. The obtained preparations were analyzed by a solid 15N-NMR, with the result that the peaks at 216 ppm and 222 ppm were broadened, and the peak at 20 ppm showed an broad peak when they were analyzed by a solid 13C-NMR. Accordingly, it was confirmed that crystals B, G and E were contained in the preparations. Comparative Example 3 Tablets were prepared by a method same as that of Example 1 except that crystal D of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxyl ic acid was used. The obtained preparations were analyzed by a solid 15N-NMR, with the result that the peaks at 216 ppm, 222 ppm, 229 ppm and 264 ppm were broadened, and a broad peak was shown at 284 ppm. Further, the peak at 20 ppm showed a broad peak when they were analyzed by a solid 13C-NMR. Accordingly, it was confirmed that crystals D, G and E were contained in the preparations. Comparative Example 4 Tablets were prepared by a method same as that of Example 1 except that crystal G of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxyl ic acid was used. The obtained preparations were analyzed by a solid 15N-NMR, with the result that the peaks at 216 ppm and 222 ppm were broadened, and a broad peak was shown at 284 ppm. Further, the peak at 20 ppm showed a broad peak when the preparations were analyzed by a solid 13C-NMR. Accordingly, it was confirmed that crystals G and E were contained in the preparations. Example 2 The tablets prepared by the method shown in Example 1 were tested for six months under the conditions of 40° C./75% RH. Then the uniformity of content (the ratio of the amount of the drug substance contained in actual tablets to the amount charged) and the crystal form of the tablets just after produced and after six months storage were studied. The content in tablets just after produced was 99.72% and the CV value (coefficient of variation) showing the variation in content was 1.37%. The content after storage for six months was 99.5%, and the CV value showing the variation in content is 1.55%, which demonstrates a superior uniformity. The crystal form of the tablets was analyzed by a solid 15N-NMR, just as the case with immediately after produced. The result showed that sharp peaks were shown at 226 ppm, 228 ppm, 276 ppm and 282 ppm. Further, the results of the analysis by a solid=13C-NMR showed that the peak at 20 ppm was an approximately equivalent doublet peak and, accordingly, it was confirmed that the preparations contains crystal A. Comparative Example 5 Tablets prepared in Comparative Examples 1 through 4 were tested for six months under the conditions of 40° C./75% RH, and the uniformity in content of the drug substance in tablets and the crystal form of the tablets just after produced and after six months were checked. The content of the drug substance in tablets just after produced in Comparative Example 1 was 100.37% and the CV value (coefficient of variation) showing the variation in content was 1.11%. The content after storage for six months is 99.5% or greater, and the variation in content shown by a CV value showed an improved value of 1.68%. But it was confirmed that the preparations comprise crystals C and E according to the solid NMR. The analysis of preparations after storage showed that a part of crystal E was transformed to crystal G. For the preparations produced in Comparative Example 2, the content in tablets immediately after produced was 99.75% and the CV value showing the variation in content was 1.11%. The content after storage was 99.5% or greater and the variation expressed by a CV value showed an improved uniformity of 1.90%. But it was confirmed that the preparations comprise crystals B, G and E according to the solid NMR. Further, it was confirmed that the ratio of crystal E was reduced and that of crystal G was increased after storage For the preparations produced in Comparative Example 3, the content in tablets immediately after produced was 100.01% and the variation shown by a CV value was 1.39%. The content in tablets after storage maintained 99.5% or more and the CV value showed an improved uniformity of 1.54%. But it was confirmed that the preparations comprise crystals D, G and E according to the solid NMR. Further, it was confirmed that the ratio of crystal E was reduced and that of crystal G was increased after storage. For the preparations produced in Comparative Example 4, the content in tablets immediately after produced was 93.5% and the variation shown by a CV value was 4.5%, which facts show that the content of the drug substance contained in tablets to the amount charged is very low and that there is a considerable variation. Therefore, the tablets did not reach the level of being brought to a market and, thus, no stability test has been carried out. Example 3 The tablets prepared by the method shown in Example 1 were tested for six months under the conditions of 40° C./75% RH. Then the dissolution profiles of the tablets just after produced and after six months were compared. The dissolution test was carried out by a Paddle method using a Mcllvaine buffer solution of pH 5.5 as a testing solution. Three lots (n=3), i.e., 9 test examples in total, were produced by a same method and were tested. The results are shown in Table 3. It was confirmed, as shown in Table 3, that there is little variation or difference in dissolution ratio between points and uniform dissolution profiles are maintained even after storage of six months. TABLE 3 Immediately Six months after produced after storage Average Average Dissolution dissolution dissolution time (min) ratio (%) CV value (%) ratio (%) CV value (%) 15 69.8 2.8 71.6 3.1 60 90.1 2.8 91.7 2.9 Comparative Example 6 For the preparations produced in Comparative Examples 1 through 3 comparisons were made between the dissolution profiles of those immediately after produced and those having been tested for six months under the conditions of 40° C./75% RH. The dissolution test was carried out by a Paddle method using a Mcllvaine buffer solution of pH 5.5 as a testing solution. Three lots (n=3), i.e., 9 test examples in total, were produced by a same method and were tested. The results are shown in Tables 4 through 6. The preparations of Comparative Example 3 after storage showed a slower dissolution profile than those immediately after produced, as shown in Table 4. Further, there is some variation or difference in dissolution ratio between points for the preparations after storage. This is thought to be caused by that crystal E was transformed, by the storage, into crystal G having low solubility. The variation or difference in dissolution ratio between points are thought to be caused by that the ratio of crystals C and E is uneven between lots and that the transformed amount of crystal G from crystal E is not uniform. The preparations of Comparative Example 2 after storage showed a slower dissolution profile than those immediately after produced, as shown in Table 5. Further, there is some variation or difference in dissolution ratio between points for the preparations after storage. This is thought to be caused by that crystals B and E were transformed, by the storage, into crystal G having low solubility. The variation or difference in dissolution ratio between points are thought to be caused by that the ratio of crystals B and E is uneven between lots and that the transformed amount of crystal G from crystals B and E is not uniform. The preparations of Comparative Example 3 after storage showed a slower dissolution profile than those immediately after produced, as shown in Table 6. Further, there is some variation or difference in dissolution ratio between points for the preparations after storage. This is thought to be caused by that crystals D and E were transformed, by the storage, into crystal G having low solubility. The variation or difference in dissolution ratio between points are thought to be caused by that the ratio of crystals D and E is uneven between lots and that the transformed amount of crystal G from crystals D and E is not uniform. Table 4 Dissolution Profile of the Preparations Produced by Comparative Example 1 Immediately Six months after produced after storage Average Average Dissolution dissolution dissolution time (min) ratio (%) CV value (%) ratio (%) CV value (%) 15 54.8 18.5 46.2 19.8 60 75.1 15.7 62.1 16.4 Table 5 Dissolution Profile of the Preparations Produced by Comparative Example 2 Immediately Six months after produced after storage Average Average Dissolution dissolution dissolution time (min) ratio (%) CV value (%) ratio (%) CV value (%) 15 55.1 10.8 48.3 20.4 60 72.1 18.4 63.5 30.2 Table 6 Dissolution Profile of the Preparations Produced by Comparative Dissolution Profile of the Preparations Produced by Comparative Example 3 Immediately Six months after produced after storage Average Average Dissolution dissolution dissolution time (min) ratio (%) CV value (%) ratio (%) CV value (%) 15 53.3 18.1 47.3 19.4 60 60.4 10.9 56.1 22.0 Example 4 Plain tablets were prepared by the method same as that of Example 1 except that particles (Particles 1˜4) shown in Table 7, with crystal A and with four different kinds of average particle sizes, were used as 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid. The obtained plain tablets were coated with coating liquid comprising purified water, polyethylene glycol and hydroxypropylmethyl cellulose by a coating machine (High Coater HCT-30, Freund Ind.). Dissolution tests were carried out for the four types of the obtained coated tablets by a Paddle method using a Mcllvaine buffer solution with pH 5.5, as a testing liquid. The results are shown in Table 7. TABLE 7 Pulverized particle size (μm)1) Average 95% Pulverizing particle cumulative Pulverizer conditions diameter diameter Particle 1 Jet mill Feeding speed: 3.5 5.6 (Dalton, 5.0 kg/hr PJM-100SP) Pulverizing pressure: 0.65 MPa Particle 2 Sample mill Screen 2.0 mmΦ 12.9 29.5 (Dalton, KII 12,000 rpm WG-1) Particle 3 Impact mill Screen 1.0 mmΦ 26.2 74.7 (Dalton, DS-2) 6,120 rpm Particle 4 Power mill Screen 2 Hmm 48.6 140.8 (Dalton, P-3) 4,000 rpm 1)Results measured by an image analysis Measuring instruments (image analysis system, digital camera for microscope and biological microscope)

<SOH> BACKGROUND ART <EOH>2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid has a strong activity for inhibiting xanthine oxidase or a uric acid decreasing action, and it is expected to be a therapeutic agent for gout or hyperuricemia, as has been described in International Publication WO92/09279. In International Publication WO99/65885, there are described following six crystal polymorphs of 2-(3-cyano-4-isobutyloxyphehyl)-4-methyl-5-thiazole carboxylic acid, i.e., a polymorph which shows an X-ray powder diffraction pattern having specific peaks at a reflection angle 2θ, of about 6.62°, 7.18°, 12.80°, 13.26°, 16.48°, 19.58°, 21.92°, 22.68°, 25.84°, 26.70°, 29.16° and 36.70° (crystal A).; a polymorph which has specific peaks at a reflection angle 2θ of about 6.76°, 8.08°, 9.74°, 11.50°, 12.22°, 13.56°, 15.76°, 16.20°, 17.32°, 19.38°, 21.14°, 21.56°, 23.16°, 24.78°, 25.14°, 25.72°, 26.12°, 26.68°, 27.68° and 29.36° (crystal B); a polymorph which has specific peaks at a reflection angle 2θ of about 6.62°, 10.82°, 13.36°, 15.52°, 16.74°, 17.40°, 18.00°, 18.70°, 20.16°, 20.62°, 21.90°, 23.50°, 24.78°, 25.18°, 34.08°, 36.72° and 38.04° (crystal C); a polymorph which has specific peaks at a reflection angle 2θ of about 8.32°, 9.68°, 12.92°, 16.06°, 17.34°, 19.38°, 21.56°, 24.06°, 26.00°, 30.06°, 33.60° and 40.34° (crystal D).; and a polymorph which has specific peaks at a reflection angle 2θ of about 6.86°, 8.36°, 9.60°, 11.76°, 13.74°, 14.60°, 15.94°, 16.74°, 17.56°, 20.00°, 21.26°, 23.72°, 24.78°, 25.14°, 25.74°, 26.06°, 26.64°, 27.92°, 28.60°, 29.66° and 29.98° (crystal G), and an amorphous (also referred to as crystal E). In said International Publication WO99/65885, it is described that crystals A, C and G are useful in view of retention of a crystal form in long term storage. Among them, crystal A is preferred in view of industrial superiority. However, the publication is silent about what the industrial superiority means. Further, the publication has no evidence (data) supporting the fact that the crystal A is preferred in view of industrial superiority. The present inventors investigated this matter and found that, in formulating 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazole carboxylic acid, it is not possible to obtain preparations having no variation in the dissolution profiles of drugs, even if such a crystal form is used as is thought to be most stable in a physical stability test. Further, they found that there is a crystal form that is suitable for preparing preparations, independently from the characteristics of the crystals (including amorphous) of drug substances and have reached the invention. An object of the invention is, therefore, to provide solid preparations of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid which is stable and which is little variation in the dissolution profiles.

<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>FIG. 1 is an X-ray powder diffraction pattern showing the transformation of crystal B in Reference Example 1. FIG. 2 is an X-ray powder diffraction pattern showing the transformation of crystal D in Reference Example 1. FIG. 3 is an X-ray powder diffraction pattern showing the transformation of crystal E in Reference Example 1. FIG. 4 is a data showing the transformation speed of crystal B in Reference Example 1 (unsealed state at 40° C./75% RH). FIG. 5 is a data showing the transformation speed of crystal D in Reference Example 1 (unsealed at 40° C./75% RH). FIG. 6 is a data showing the transformation speed of crystal E in Reference example 1 (unsealed at 40° C./75% RH). FIG. 7 shows dissolution profiles of tablets containing crystal A (particles 1 to 4) in Example 4 each having a different average particle size. detailed-description description="Detailed Description" end="lead"?

20040803

20080422

20050224

62164.0

SHIAO, REI TSANG

SOLID PREPARATION CONTAINING SINGLE CRYSTAL FORM

UNDISCOUNTED

ACCEPTED

ACCEPTED

Vanilloid receptor modulators

Certain compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R1, R2, R3, P, X, Y, q, r ans s are as defined in the specification, a process for preparing such compounds, a pharmaceutical composition comprising such compounds and the use of such compounds in medicine.

1. A compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein, P is selected from phenyl, heteroaryl or heterocyclyl; R1 and R2 are independently selected from halo, alkyl, alkoxy, cycloalkyl, aralkyl, aralkoxy, cycloalkylalkyl, cycloalkylalkoxy, —CN, —NO2, —OH, ═O, —OCF3, —CF3, —NR4R5, —S(O)mR6, —S(O)2NR4R5, —OS(O)2R6, —OS(O)2CF3, —O(CH2)nNR4R5, —C(O)CF3, —C(O)alkyl, —C(O)cycloalkyl, —C(O)aralkyl, —C(O)Ar, —C(O)(CH2)nOR6, —C(O)(CH2)nNR4R5, —C(O)alkoxy, —C(O)NR4R5, —(CH2)nC(O)alkoxy, —(CH2)nOC(O)R6, —O(CH2)nOR6, —(CH2)nOR6, —(CH2)nR4R5, —(CH2)nC(O)NR4R5, —(CH2)nN(R4)C(O)R6, —(CH2)nS(O)2NR4R5, —(CH2)nN(R4)S(O)2R6, -ZAr, —(CH2)nS(O)2R6, —(OCH2)nS(O)2R6, —N(R4)S(O)2R6, —N(R4)C(O)R6, —(CH2)nN(R4)S(O)2R6, —(CH2)nN(R4)C(O)R6 or —(CH2)nC(O)alkyl; R3 is selected from alkyl, alkoxy, —CF3, halo, —O(CH2)nOR6, —O(CH2)nNR4R5, phenyl, cyclohexyl, benzo[1,3]dioxolyl, morpholinyl, pyridyl, pyrimidinyl, pyrazinyl, piperazinyl, piperidinyl, pyridizinyl, thienyl, furyl, pyrazolyl, pyrrolyl, triazolyl, indanyl, imidazolyl, oxazolyl, thiazolyl, oxadiazolyl, isothiazolyl, isoxazolyl or thiadiazolyl; wherein said alkyl, alkoxy, phenyl, cyclohexyl, benzo[1,3]dioxolyl, morpholinyl, pyridyl, pyrimidinyl, pyrazinyl, piperazinyl, piperidinyl, pyridizinyl, thienyl, furyl, pyrazolyl, pyrrolyl, triazolyl, indanyl, imidazolyl, oxazolyl, thiazolyl, oxadiazolyl, isothiazolyl, isoxazolyl and thiadiazolyl groups may be optionally substituted by one or more groups, which may be the same or different, selected from R2; R4 and R5 may be the same or different and represent —H or alkyl or R4 and R5 together with the nitrogen atom to which they are attached form a heterocyclic ring; R6 is —H, alkyl or aryl; R7 is —H, alkyl or aryl; R8 is selected from —H, alkyl, hydroxyalkyl, cycloalkyl, aralkyl, alkoxyalkyl, cycloalkylalkyl, heterocyclylalkyl, —S(O)mR6, —C(O)CF3, —C(O)alkyl, —C(O)cycloalkyl, —C(O)aralkyl, —C(O)Ar, —C(O)(CH2)nOR6, —C(O)(CH2)nNR4R5, —C(O)alkoxy, —C(O)NR4R5, —(CH2)nC(O)alkoxy, —(CH2)nOC(O)R6, —(CH2)nOR6, —(CH2)nR4R5, —(CH2)nC(O)NR4R5, —(CH2)nN(R4)C(O)R6, —(CH2)nS(O)2NR4R5, —(CH2)nN(R4)S(O)2R6, —(CH2)nS(O)2R6, —(CH2)nN(R4)S(O)2R6, —(CH2)nN(R4)C(O)R6 or —(CH2)nC(O)alkyl; or where X is NR8 and Y is C(R9)2, R8 may combine with R1 to form a benzoquinuclidine group; R9 is —H or R1; Ar is aryl or heteroaryl, each of which may be optionally substituted by R2; Z is a bond, O, S, NR7 or CH2; m is 0, 1 or 2; n is an integer value from 1 to 6; q and r are independently selected from 0, 1, 2 or 3; s is 0, 1, 2 or 3; and X and Y are selected such that: when X is N, Y is CR9; when X is NR8, Y is C(R9)2; when X is CR9, Y is N; when X is C(R9)2, Y is NR8; with the proviso that said compound of formula (I) is not a compound selected from: N-{3-[(N,N-Dimethylamino)methyl]-1,2,3,4-tetrahydro-7-quinolinyl}-4-biphenylcarboxamide; N-{3-[(N,N-Dimethylamino)methyl]-1-formyl-1,2,3,4-tetrahydro-7-quinolinyl}-4-biphenylcarboxamide; N-{1-Acetyl-3-[(N,N-dimethylamino)methyl]-1,2,3,4-tetrahydro-7-quinolinyl}-4-biphenylcarboxamide; N-{3-[(N,N-Dimethylamino)methyl]-1-methylsulfonyl-1,2,3,4-tetrahydro-7-quinolinyl}-4-biphenylcarboxamide; 5-amino-N-isoquinolin-5-yl-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide; 5-methyl-N-quinolin-8-yl-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide, 5-methyl-N-quinolin-7-yl-1-[3-trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide, 5-methyl-N-quinolin-3-yl-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide, N-isoquinolin-5-yl-5-methyl-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide, 5-methyl-N-quinolin-5-yl-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide, 1-(3-chlorophenyl)-N-isoquinolin-5-yl-5-methyl-1H-pyrazole-3-carboxamide, N-isoquinolin-5-yl-1-(3-methoxyphenyl)-5-methyl-1H-pyrazole-3-carboxamide, 1-(3-fuorophenyl)-N-isoquinolin-5-yl-5-methyl-1H-pyrazole-3-carboxamide, 1-(2-chloro-5-trifluoromethylphenyl)-N-isoquinolin-5-yl-5-methyl-1H-pyrazole-3-carboxamide, 5-methyl-N-(3-methylisoquinolin-5-yl)-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide, and 5-methyl-N-(1,2,3,4-tetrahydroisoquinolin-5-yl)-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide. 2. A compound of formula (i), as claimed in claim 1, of formula (IA), or a pharmaceutically acceptable salt or solvate thereof, wherein, P is selected from phenyl, heteroaryl or heterocyclyl; R1 and R2 are independently selected from halo, alkyl, alkoxy, cycloalkyl, aralkyl, aralkoxy, cycloalkylalkyl, cycloalkylalkoxy, —CN, —NO2, —OH, ═O, —OCF3, —CF3, —NR4R5, —S(O)mR6, —S(O)2NR4R5, —OS(O)2R6, —OS(O)2CF3, —O(CH2)nNR4R5, —C(O)CF3, —C(O)alkyl, —C(O)cycloalkyl, —C(O)aralkyl, —C(O)Ar, —C(O)(CH2)nOR6, —C(O)(CH2)nNR4R5, —C(O)alkoxy, —C(O)NR4R5, —(CH2)nC(O)alkoxy, —(CH2)nOC(O)R6, —O(CH2)nOR6, —(CH2)nOR6, —(CH2)nR4R5, —(CH2)nC(O)NR4R5, —(CH2)nN(R4)C(O)R6, —(CH2)nS(O)2NR4R5, —(CH2)nN(R4)S(O)2R6, -ZAr, —(CH2)nS(O)2R6, —(OCH2)nS(O)2R6, —N(R4)S(O)2R6, —N(R4)C(O)R6, —(CH2)nN(R4)S(O)2R6, —(CH2)nN(R4)C(O)R6 or —(CH2)nC(O)alkyl; R3 is selected from alkyl, —CF3, halo, phenyl, cyclohexyl, benzo[1,3]dioxolyl morpholinyl, pyridyl, pyrimidinyl, pyrazinyl, piperazinyl piperidinyl, pyridizinyl, thienyl, furyl, pyrazolyl, pyrrolyl, triazolyl, indanyl, imidazolyl, oxazolyl, thiazolyl, oxadiazolyl, isothiazolyl, isoxazolyl or thiadiazolyl; wherein said alkyl, alkoxy, phenyl, cyclohexyl, benzo[1,3]dioxolyl, morpholinyl, pyridyl, pyrimidinyl, pyrazinyl, piperazinyl, piperidinyl, pyridizinyl, thienyl, furyl, pyrazolyl, pyrrolyl, triazolyl, indanyl, imidazolyl, oxazolyl, thiazolyl, oxadiazolyl, isothiazolyl, isoxazolyl and thiadiazolyl groups may be optionally substituted by one or more groups, which may be the same or different, selected from R2; R4 and R5 may be the same or different and represent —H or alkyl or R4 and R5 together with the nitrogen atom to which they are attached form a heterocyclic ring; R6 is —H, alkyl or aryl; R7 is —H, alkyl or aryl; R8 is selected from —H, alkyl, hydroxyalkyl, cycloalkyl, aralkyl, alkoxyalkyl, cycloalkylalkyl, heterocyclylalkyl, —S(O)mR6, —C(O)CF3, —C(O)alkyl, —C(O)cycloalkyl, —C(O)aralkyl, —C(O)Ar, —C(O)(CH2)nOR6, —C(O)(CH2)nNR4R5, —C(O)alkoxy, —C(O)NR4R5, —(CH2)nC(O)alkoxy, —(CH2)nOC(O)R6, —(CH2)nOR6, —(CH2)nR4R5, —(CH2)nC(O)NR4R5, —(CH2)nN(R4)C(O)R6, —(CH2)nS(O)2NR4R5, —(CH2)nN(R4)S(O)2R6, —(CH2)nS(O)2R6, —(CH2)nN(R4)S(O)2R6, —(CH2)nN(R4)C(O)R6 or —(CH2)nC(O)alkyl; or where X is NR8 and Y is C(R9)2, R8 may combine with R1 to form a benzoquinuclidine group; R9 is —H or R1. Ar is aryl or heteroaryl, each of which may be optionally substituted by R2; Z is a bond, O, S, NR7 or CH2; m is 0, 1 or 2; n is an integer value from 1 to 6; q and r are independently selected from 0, 1, 2 or 3; s is 0, 1, 2 or 3; and X is C(R9)2 and Y is NR8 or X is NR8 and Y is C(R9)2; with the proviso that said compound of formula (I) is not a compound selected from: N-{3-[(N,N-Dimethylamino)methyl]-1,2,3,4-tetrahydro-7-quinolinyl}-4-biphenylcarboxamide; N-{3-[(N,N-Dimethylamino)methyl]-1-formyl-1,2,3,4-tetrahydro-7-quinolinyl}-4-biphenylcarboxamide; N-{1-Acetyl-3-[(N,N-dimethylamino)methyl]-1,2,3,4-tetrahydro-7-quinolinyl}-4-biphenylcarboxamide; N-{3-[(N,N-Dimethylamino)methyl]-1-methylsulfonyl-1,2,3,4-tetrahydro-7-quinolinyl}-4-biphenylcarboxamide; and 5-methyl-N-(1,2,3,4-tetrahydroisoquinoliN-5-yl)-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide. 3. A compound of formula (I), as claimed in claim 1, of formula (IB), or a pharmaceutically acceptable salt or solvate thereof, wherein, P is selected from phenyl, heteroaryl or heterocyclyl; R1 and R2 are independently selected from halo, alkyl, alkoxy, cycloalkyl, aralkyl, aralkoxy, cycloalkylalkyl, cycloalkylalkoxy, —CN, —NO2, —OH, —OCF3, —CF3, —NR4R5, —S(O)mR6, —S(O)2NR4R5, —OS(O)2R6, —OS(O)2CF3, —O(CH2)nNR4R5, —C(O)CF3, —C(O)alkyl, —C(O)cycloalkyl, —C(O)aralkyl, —C(O)Ar, —C(O)(CH2)nOR6, —C(O)(CH2)nNR4R5, —C(O)alkoxy, —C(O)NR4R5, —(CH2)nC(O)alkoxy, —(CH2)nOC(O)R6, —(CH2)nOR6, —(CH2)nR4R5, —(CH2)nC(O)NR4R5, —(CH2)nN(R4)C(O)R6, —(CH2)nS(O)2NR4R5, —(CH2)nN(R4)S(O)2R6, -ZAr, —(CH2)nS(O)2R6, —(OCH2)nS(O)2R6, —N(R4)S(O)2R6, —N(R4)C(O)R6, —(CH2)nN(R4)S(O)2R6, —(CH2)nN(R4)C(O)R6 or —(CH2)nC(O)alkyl; R3 is selected from halo, —CF3, alkyl, alkoxy, —O(CH2)nOR6, —O(CH2)nNR4R5, phenyl, cyclohexyl, benzo[1,3]dioxolyl, morpholinyl, pyridyl, pyrimidinyl, pyrazinyl, piperazinyl, piperidinyl, pyridizinyl, thienyl, furyl, pyrazolyl, pyrrolyl, triazolyl, imidazolyl, oxazolyl, thiazolyl, oxadiazolyl, isothiazolyl, isoxazolyl or thiadiazolyl; which alkyl, alkoxy, phenyl, cyclohexyl, benzo[1,3]dioxolyl, morpholinyl, pyridyl; pyrimidinyl, pyrazinyl, piperazinyl, piperidinyl, pyridizinyl, thienyl, furyl, pyrazolyl; pyrrolyl, triazolyl, imidazolyl, oxazolyl, thiazolyl, oxadiazolyl, isothiazolyl, isoxazolyl and thiadiazolyl groups may be optionally substituted by one or more groups, which may be the same or different, selected from R2; R4 and R5 may be the same or different and represent —H or alkyl or R4 and R5 together with the nitrogen atom to which they are attached form a heterocyclic ring; R6 is —H, alkyl or aryl; R7 is —H, alkyl or aryl; Ar is aryl or heteroaryl; each of which may be optionally substituted by R2; X and Y are selected from CR9 and N with the proviso that X and Y may not be the same; Z is a bond, O, S, NR7 or CH2; m is 0, 1 or 2; n is an integer value from 1 to 6; q and r are independently selected from 0, 1, 2 or 3; and s is 0, 1, 2 or 3; with the proviso that said compound of formula (IB) is not a compound selected from: 5-amino-N-isoquinolin-5-yl-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide; 5-methyl-N-quinolin-8-yl-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide, 5-methyl-N-quinolin-7-yl-1-[3-trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide, 5-methyl-N-quinolin-3-yl-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide, N-isoquinolin-5-yl-5-methyl-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide, 5-methyl-N-quinolin-5-yl-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide, 1-(3-chlorophenyl)-N-isoquinolin-5-yl-5-methyl-1H-pyrazole-3-carboxamide, N-isoquinolin-5-yl-1-(3-methoxyphenyl)-5-methyl-1H-pyrazole-3-carboxamide, 1-(3-fuorophenyl)-N-isoquinolin-5-yl-5-methyl-1H-pyrazole-3-carboxamide, 1-(2-chloro-5-trifluoromethylphenyl)-N-isoquinolin-5-yl-5-methyl-1H-pyrazole-3-carboxamide, 5-methyl-N-(3-methylisoquinolin-5-yl)-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide; and N-[3-[2-(diethylamino)ethyl]-1,2-dihydro-4-methyl-2-oxo-7-quinolinyl]-4-phenyl-1-piperazinecarboxamide. 4. A compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, as claimed in claim 1, substantially as hereinbefore described with reference to any one of the Examples. 5. A process for the preparation of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, which process comprises: (a) reacting a compound of formula (II): wherein, R1, R2, q, r, X and Y are as defined in relation to formula (I), with a compound of formula (III): wherein, P, R3 and s are as defined in relation to formula (I) and thereafter, as necessary, carrying out one or more of the following reactions: (i) converting one compound of formula (I) into another compound of formula (I); (ii) removing any protecting group; (iii) preparing a salt or a solvate of the compound so formed. 6. A compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, as claimed in claim 1, for use as an active therapeutic substance. 7. A method for the treatment or prophylaxis of disorders in which antagonism of the Vanilloid (VR1) receptor is beneficial in mammals including humans, which method comprises administering to a mammal in need thereof a therapeutically effective amount of a compound of formula (i) or a pharmaceutically acceptable salt or solvate thereof, as claimed in claim 1. 8. (canceled) 9. A pharmaceutical composition, which comprises a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, as claimed in claim 1, and a pharmaceutically acceptable carrier or excipient therefor.

This invention relates to novel amide derivatives having pharmacological activity, processes for their preparation, to compositions containing them and to their use in medicine, especially in the treatment of various disorders. Vanilloids are a class of natural and synthetic compounds that are characterised by the presence of a vanillyl (4-hydroxy 3-methoxybenzyl) group or a functionally equivalent group. Vanilloid Receptor (VR-1), whose function is modulated by such compounds, has been widely studied and is extensively reviewed by Szallasi and Blumberg (The American Society for Pharmacology and Experimental Therapeutics, 1999, Vol. 51, No. 2.). A wide variety of Vanilloid compounds of different structures are known in the art, for example those disclosed in European Patent Application Numbers, EP 0 347 000 and EP 0 401 903, UK Patent Application Number GB 2226313 and International Patent Application, Publication Number WO 92/09285. Particularly notable examples of vanilloid compounds or vanilloid receptor modulators are capsaicin or trans 8-methyl-N-vanillyl-6-nonenamide which is isolated from the pepper plant, capsazepine (Tetrahedron, 53, 1997, 4791) and olvanil or —N-(4-hydroxy-3-methoxybenzyl)oleamide (J. Med. Chem., 36, 1993, 2595). International Patent Application, Publication Number WO 02/08221 discloses diaryl piperazine and related compounds which bind with high selectivity and high affinity to vanilloid receptors, especially Type I Vanilloid receptors, also known as capsaicin or VR1 receptors. The compounds are said to be useful in the treatment of chronic and acute pain conditions, itch and urinary incontinence. International Patent Application, Publication Numbers WO 02/16317, WO 02/16318 and WO 02/16319 suggest that compounds having a high affinity for the vanilloid receptor are useful for treating stomach-duodenal ulcers. U.S. Pat. No. 3,424,760 and U.S. Pat. No. 3,424,761 both describe a series of 3-Ureidopyrrolidines that are said to exhibit analgesic, central nervous system, and pyschopharmacologic activities. These patents specifically disclose the compounds 1-(1-phenyl-3-pyrrolidinyl)-3-phenyl urea and 1-(1-phenyl-3-pyrrolidinyl)-3-(4-methoxyphenyl)urea respectively. International Patent Applications, Publication Numbers WO 01/62737 and WO 00/69849 disclose a series of pyrazole derivatives which are stated to be useful in the treatment of disorders and diseases associated with the NPY receptor subtype Y5, such as obesity. WO 01/62737 specifically discloses the compound 5-amino-N-isoquinolin-5-yl-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide. WO 00/69849 specifically discloses the compounds 5-methyl-N-quinolin-8-yl-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide, 5-methyl-N-quinolin-7-yl-1-[3-trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide, 5-methyl-N-quinolin-3-yl-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide, N-isoquinolin-5-yl-5-methyl-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide, 5-methyl-N-quinolin-5-yl-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide, 1-(3-chlorophenyl)-N-isoquinolin-5-yl-5-methyl-1H-pyrazole-3-carboxamide, N-isoquinolin-5-yl-1-(3-methoxyphenyl)-5-methyl-1H-pyrazole-3-carboxamide, 1-(3-fuorophenyl)-N-isoquinolin-5-yl-5-methyl-1H-pyrazole-3-carboxamide, 1-(2-chloro-5-trifluoromethylphenyl)-N-isoquinolin-5-yl-5-methyl-1H-pyrazole-3-carboxamide, 5-methyl-N-(3-methylisoquinolin-5-yl)-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide, 5-methyl-N-(1,2,3,4-tetrahydroisoquinolin-5-yl)-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide. German Patent Application Number 2502588 describes a series of piperazine derivatives. This application specifically discloses the compound N-[3-[2-(diethylamino)ethyl]-1,2-dihydro-4-methyl-2-oxo-7-quinolinyl]-4-phenyl-1-piperazinecarboxamide. We have now discovered that certain compounds falling within the scope of International Patent Application, Publication Number WO 02/08221 have surprising potency and selectivity as VR-1 antagonists. The compounds of the present invention are considered to be particularly beneficial as VR-1 antagonists as certain compounds exhibit improved aqueous solubility and metabolic stability relative to the compounds disclosed in WO 02/08221. According to a first aspect of the present invention, there is provided a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein, P is selected from phenyl, heteroaryl or heterocyclyl; R1 and R2 are independently selected from halo, alkyl, alkoxy, cycloalkyl, aralkyl, aralkoxy, cycloalkylalkyl, cycloalkylalkoxy, —CN, —NO2, —OH, ═O, —OCF3, —CF3, —NR4R5, —S(O)mR6, —S(O)2NR4R5, —OS(O)2R6, —OS(O)2CF3, —O(CH2)nNR4R5, —C(O)CF3, —C(O)alkyl, —C(O)cycloalkyl, —C(O)aralkyl, —C(O)Ar, —C(O)(CH2)nOR6, —C(O)(CH2)nNR4R5, —C(O)alkoxy, —C(O)NR4R5, —(CH2)nC(O)alkoxy, —(CH2)nOC(O)R6, —O(CH2)nOR6, —(CH2)nOR6, —(CH2)nR4R5, —(CH2)nC(O)NR4R5, —(CH2)nN(R4)C(O)R6, —(CH2)nS(O)2NR4R5, —(CH2)nN(R4)S(O)2R6, -ZAr, —(CH2)nS(O)2R6, —(OCH2)nS(O)2R6, —N(R4)S(O)2R6, —N(R4)C(O)R6, —(CH2)nN(R4)S(O)2R6, —(CH2)nN(R4)C(O)R6 or —(CH2)nC(O)alkyl; R3 is selected from alkyl, alkoxy, —CF3, halo, —O(CH2)nOR6, —O(CH2)nNR4R5, phenyl, cyclohexyl, benzo[1,3]dioxolyl, morpholinyl, pyridyl, pyrimidinyl, pyrazinyl, piperazinyl, piperidinyl, pyridizinyl, thienyl, furyl, pyrazolyl, pyrrolyl, triazolyl, indanyl, imidazolyl, oxazolyl, thiazolyl, oxadiazolyl, isothiazolyl, isoxazolyl or thiadiazolyl; wherein said alkyl, alkoxy, phenyl, cyclohexyl, benzo[1,3]dioxolyl, morpholinyl, pyridyl, pyrimidinyl, pyrazinyl, piperazinyl, piperidinyl, pyridizinyl, thienyl, furyl, pyrazolyl, pyrrolyl, triazolyl, indanyl, imidazolyl, oxazolyl, thiazolyl, oxadiazolyl, isothiazolyl, isoxazolyl and thiadiazolyl groups may be optionally substituted by one or more groups, which may be the same or different, selected from R2; R4 and R5 may be the same or different and represent —H or alkyl or R4 and R5 together with the nitrogen atom to which they are attached form a heterocyclic ring; R6 is —H, alkyl or aryl; R7 is —H, alkyl or aryl; R8 is selected from —H, alkyl, hydroxyalkyl, cycloalkyl, aralkyl, alkoxyalkyl, cycloalkylalkyl, heterocyclylalkyl, —S(O)mR6, —C(O)CF3, —C(O)alkyl, —C(O)cycloalkyl, —C(O)aralkyl, —C(O)Ar, —C(O)(CH2)nOR6, —C(O)(CH2)nNR4R5, —C(O)alkoxy, —C(O)NR4R5, —(CH2)nC(O)alkoxy, —(CH2)nOC(O)R6, —(CH2)nOR6, —(CH2)nR4R5, —(CH2)nC(O)NR4R5, —(CH2)nN(R4)C(O)R6, —(CH2)nS(O)2NR4R5, —(CH2)nN(R4)S(O)2R6, —(CH2)nS(O)2R6, —(CH2)nN(R4)S(O)2R6, —(CH2)nN(R4)C(O)R6 or —(CH2)nC(O)alkyl; or where X is NR8 and Y is C(R9)2, R8 may combine with R1 to form a benzoquinuclidine group; R9 is —H or R1; Ar is aryl or heteroaryl, each of which may be optionally substituted by R2; Z is a bond, O, S, NR7 or CH2; m is 0, 1 or 2; n is an integer value from 1 to 6; q and r are independently selected from 0, 1, 2 or 3; s is 0, 1, 2 or 3; and X and Y are selected from the following combinations: X Y N CR9 NR8 C(R9)2 CR9 N C(R9)2 NR8 with the proviso that said compound of formula (I) is not a compound selected from: N-{3-[(N,N-Dimethylamino)methyl]-1,2,3,4-tetrahydro-7-quinolinyl}-4-biphenylcarboxamide; N-{3-[(N,N-Dimethylamino)methyl]-1-formyl-1,2,3,4-tetrahydro-7-quinolinyl}-4-biphenylcarboxamide; N-{1-Acetyl-3-[(N,N-dimethylamino)methyl]-1,2,3,4-tetrahydro-7-quinolinyl}-4-biphenylcarboxamide; N-{3-[(N,N-Dimethylamino)methyl]-1-methylsulfonyl-1,2,3,4-tetrahydro-7-quinolinyl}-4-biphenylcarboxamide; 5-amino-N-isoquinolin-5-yl-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide; 5-methyl-N-quinolin-8-yl-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide, 5-methyl-N-quinolin-7-yl-1-[3-trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide, 5-methyl-N-quinolin-3-yl-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide, 5-isoquinolin-5-yl-5-methyl-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide, 5-methyl-N-quinolin-5-yl-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide, 1-(3-chlorophenyl)-N-isoquinolin-5-yl-5-methyl-1H-pyrazole-3-carboxamide, N-isoquinolin-5-yl-1-(3-methoxyphenyl)-5-methyl-1H-pyrazole-3-carboxamide, 1-(3-fuorophenyl)-N-isoquinolin-5-yl-5-methyl-1H-pyrazole-3-carboxamide, 1-(2-chloro-5-trifluoromethylphenyl)-N-isoquinolin-5-yl-5-methyl-1H-pyrazole-3-carboxamide, 5-methyl-N-(3-methylisoquinolin-5-yl)-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide, 5-methyl-N-(1,2,3,4-tetrahydroisoquinolin-5-yl)-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide; and N-[3-[2-(diethylamino)ethyl]-1,2-dihydro-4-methyl-2-oxo-7-quinolinyl]-4-phenyl-1-piperazinecarboxamide. Suitably, P is phenyl, pyridyl, furanyl, thienyl, piperazinyl, piperidinyl or fluorenyl. Suitably, P is phenyl or pyridyl. Suitably, P is furanyl, thienyl, piperazinyl, piperidinyl or fluorenyl. More suitably, P is phenyl. More suitably, P is pyridyl. Suitably, R1 is ═O or alkyl. More suitably, R1 is ═O or methyl. Suitably, R2 is halo. More suitably, R2 is bromo or chloro. Suitably, R3 is alkyl, alkoxy, halo, —CF3, —O(CH2)nOR6, —O(CH2)nNR4R5, phenyl, thienyl, imidazolyl, pyridyl, pyrazinyl, indanyl, piperazinyl, pyrazolyl, benzo[1,3]dioxolyl, morpholinyl, piperidinyl, cyclohexyl or thiazolyl; wherein said alkyl, phenyl, thienyl, imidazolyl, pyridyl, pyrazinyl, indanyl, piperazinyl, pyrazolyl, benzo[1,3]dioxolyl, morpholinyl, piperidinyl, cyclohexyl and thiazolyl groups may be optionally substituted by one or more groups, which may be the same or different, selected from R2. Suitably, R3 is phenyl, alkyl, alkoxy, halo, —CF3, —O(CH2)nOR6, —O(CH2)nNR4R5, phenyl, thienyl, imidazolyl, pyridyl, pyrazinyl, indanyl, piperazinyl, pyrazolyl, benzo[1,3]dioxolyl, morpholinyl, piperidinyl, cyclohexyl or thiazolyl; wherein said alkyl, phenyl, thienyl, imidazolyl, pyridyl, pyrazinyl, indanyl, piperazinyl, pyrazolyl, benzo[1,3]dioxolyl, morpholinyl, piperidinyl, cyclohexyl and thiazolyl groups may be optionally substituted by one or more groups, which may be the same or different, selected from —H, halo, —CF3, alkyl, alkoxy, ═O, —CONR4R5, —N(R4)C(O)R6, —C(O)alkyl, —S(O)2NR4R5, —C(O)alkoxy, —O(CH2)nOR6 and —O(CH2)nR4R5. Suitably, R3 is phenyl or pyridyl; each of which may be optionally substituted by one or more groups, which may be the same or different, selected from R2. Suitably, R3 is phenyl or pyridyl; each of which may be optionally substituted by one or more groups, which may be the same or different, selected from —H, halo, —CF3, alkyl, alkoxy, ═O, —CONR4R5, —N(R4)C(O)R6, —C(O)alkyl, —S(O)2NR4R5, —C(O)alkoxy, —O(CH2)nOR6 and —O(CH2)nR4R5. Suitably, R4 is —H or alkyl. Suitably, R5 is —H or alkyl. Suitably, R6 is alkyl. Suitably, R8 is —H, alkyl, hydroxyalkyl, alkoxyalkyl, heterocyclylalkyl, —C(O)CF3, —C(O)alkyl, —C(O)(CH2)nOR6, —(CH2)nOC(O)R6, —(CH2)nC(O)alkoxy or —(CH2)nR4R5. More suitably, R8 is —H, methyl, —C(O)CF3, —C(O)Me, —C(O)CH2OMe, —(CH2)2OC(O)Me, —(CH2)2CO2Me, —(CH2)2OH, —(CH2)2O(CH2)2CH3, —(CH2)2OMe, —(CH2)2NMe2, —(CH2)2N(Pri)2 or —(CH2)2-morpholinyl. Suitably, R9 is H. Suitably R9 is R1. Suitably, q and r are independently selected from 0, 1 or 2. Suitably, q and r are independently selected from 0 or 1. Suitably, s is 0, 1 or 2. Suitably, X is N and Y is CR9. Suitably, X is NR8 and Y is C(R9)2. Suitably, X is CR9 and Y is N. Suitably, X is C(R9)2 and Y is NR8. In a further aspect of the present invention there is provided a subset of compounds of formula (I), of formula (IA), or a pharmaceutically acceptable salt or solvate thereof, wherein, P is selected from phenyl, heteroaryl or heterocyclyl; R1 and R2 are independently selected from halo, alkyl, alkoxy, cycloalkyl, aralkyl, aralkoxy, cycloalkylalkyl, cycloalkylalkoxy, —CN, —NO2, —OH, ═O, —OCF3, —CF3, —NR4R5, —S(O)mR6, —S(O)2NR4R5, —OS(O)2R6, —OS(O)2CF3, —O(CH2)nNR4R5, —C(O)CF3, —C(O)alkyl, —C(O)cycloalkyl, —C(O)aralkyl, —C(O)Ar, —C(O)(CH2)nOR6, —C(O)(CH2)nNR4R5, —C(O)alkoxy, —C(O)NR4R5, —(CH2)nC(O)alkoxy, —(CH2)nOC(O)R6, —O(CH2)nOR6, —(CH2)nOR6, —(CH2)nR4R5—(CH2)nC(O)NR4R5, —(CH2)nN(R4)C(O)R6, —(CH2)nS(O)2NR4R5, —(CH2)nN(R4)S(O)2R6, -ZAr, —(CH2)nS(O)2R6, —(OCH2)nS(O)2R6, —N(R4)S(O)2R6, —N(R4)C(O)R6, —(CH2)nN(R4)S(O)2R6, —(CH2)nN(R4)C(O)R6 or —(CH2)nC(O)alkyl; R3 is selected from alkyl, —CF3, halo, phenyl, cyclohexyl, benzo[1,3]dioxolyl morpholinyl, pyridyl, pyrimidinyl, pyrazinyl, piperazinyl piperidinyl, pyridizinyl, thienyl, furyl, pyrazolyl, pyrrolyl, triazolyl, indanyl, imidazolyl, oxazolyl, thiazolyl, oxadiazolyl, isothiazolyl, isoxazolyl or thiadiazolyl; wherein said alkyl, alkoxy, phenyl, cyclohexyl, benzo[1,3]dioxolyl, morpholinyl, pyridyl, pyrimidinyl, pyrazinyl, piperazinyl, piperidinyl, pyridizinyl, thienyl, furyl, pyrazolyl, pyrrolyl, triazolyl, indanyl, imidazolyl, oxazolyl, thiazolyl, oxadiazolyl, isothiazolyl, isoxazolyl and thiadiazolyl groups may be optionally substituted by one or more groups, which may be the same or different, selected from R2; R4 and R5 may be the same or different and represent —H or alkyl or R4 and R5 together with the nitrogen atom to which they are attached form a heterocyclic ring; R6 is —H, alkyl or aryl; R7 is —H, alkyl or aryl; R8 is selected from —H, alkyl, hydroxyalkyl, cycloalkyl, aralkyl, alkoxyalkyl, cycloalkylalkyl, heterocyclylalkyl, —S(O)mR6, —C(O)CF3, —C(O)alkyl, —C(O)cycloalkyl, —C(O)aralkyl, —C(O)Ar, —C(O)(CH2)nOR6, —C(O)(CH2)nNR4R5, —C(O)alkoxy, —C(O)NR4R5, —(CH2)nC(O)alkoxy, —(CH2)nOC(O)R6, —(CH2)nOR6, —(CH2)nR4R5, —(CH2)nC(O)NR4R5, —(CH2)nN(R4)C(O)R6, —(CH2)nS(O)2NR4R5, —(CH2)nN(R4)S(O)2R6, —(CH2)nS(O)2R6, —(CH2)nN(R4)S(O)2R6, —(CH2)nN(R4)C(O)R6 or —(CH2)nC(O)alkyl; or where X is NR8 and Y is C(R9)2, R8 may combine with R1 to form a benzoquinuclidine group; R9 is —H or R1. Ar is aryl or heteroaryl, each of which may be optionally substituted by R2; Z is a bond, O, S, NR7 or CH2; m is 0, 1 or 2; n is an integer value from 1 to 6; q and r are independently selected from 0, 1, 2 or 3; s is 0, 1, 2 or 3; and X is C(R9)2 and Y is NR8 or X is NR8 and Y is C(R9)2; with the proviso that said compound of formula (I) is not a compound selected from: N-{3-[(N,N-Dimethylamino)methyl]-1,2,3,4-tetrahydro-7-quinolinyl}-4-biphenylcarboxamide; N-{3-[(N,N-dimethylamino)methyl]-1-formyl-1,2,3,4-tetrahydro-7-quinolinyl}-4-biphenylcarboxamide; N-{1-Acetyl-3-[(N,N-dimethylamino)methyl]-1,2,3,4-tetrahydro-7-quinolinyl}-4-biphenylcarboxamide; N-{3-[(N,N-Dimethylamino)methyl]-1-methylsulfonyl-1,2,3,4-tetrahydro-7-quinolinyl}-4-biphenylcarboxamide; and 5-methyl-N-(1,2,3,4-tetrahydroisoquinolin-5-yl)-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide. Suitably, P is phenyl, pyridyl, furyl, thienyl or piperazinyl. Suitably, P is phenyl. Suitably, P is pyridyl. Suitably, R1 is alkyl. More suitably, R1 is methyl. Suitably, R2 is halo or alkyl. Suitably, R3 is alkyl, phenyl, indanyl, pyridyl, pyrazinyl, pyrazolyl or thienyl; each of which may be optionally substituted by one or more groups, which may be the same or different, selected from R2. More suitably, R3 is alkyl, phenyl or pyridyl; which phenyl and pyridyl groups may be optionally substituted by alkyl, halo, —CF3, —CONHMe, —NHCOMe, —CONMe2, —C(O)Me, —SO2NHMe, —CONH2. Suitably, R8 is —H, alkyl, hydroxyalkyl, alkoxyalkyl, heterocyclylalkyl, —C(O)CF3, —C(O)alkyl, —C(O)(CH2)nOR6, —(CH2)nOC(O)R6, —(CH2)nC(O)alkoxy or —(CH2)nR4R5. More suitably, R8 is —H, methyl, —C(O)CF3, —C(O)Me, —C(O)CH2OMe, —(CH2)2OC(O)Me, —(CH2)2CO2Me, —(CH2)2OH, —(CH2)2O(CH2)2CH3, —(CH2)2OMe, —(CH2)2NMe2, —(CH2)2N(Pri)2 or —(CH2)2-morpholinyl. Suitably, R9 is H. Suitably, R9 is R1. Suitably, m is 2. Suitably, n is 1 or 2. Suitably, q and r are independently selected from 0, 1 or 2. Suitably, s is 0, 1 or 2. Suitably, X is C(R9)2 and Y is NR8. Suitably, or X is NR8 and Y is C(R9)2. In a further aspect of the present invention there is provided a subset of compounds of formula (I), of formula (IB), or a pharmaceutically acceptable salt or solvate thereof, wherein, P is selected from phenyl, heteroaryl or heterocyclyl; R1 and R2 are independently selected from halo, alkyl, alkoxy, cycloalkyl, aralkyl, aralkoxy, cycloalkylalkyl, cycloalkylalkoxy, —CN, —NO2, —OH, —OCF3, —CF3, —NR4R5, —S(O)mR6, —S(O)2NR4R5, —OS(O)2R6, —OS(O)2CF3, —O(CH2)nNR4R5, —C(O)CF3, —C(O)alkyl, —C(O)cycloalkyl, —C(O)aralkyl, —C(O)Ar, —C(O)(CH2)nOR6, —C(O)(CH2)nNR4R5, —C(O)alkoxy, —C(O)NR4R5, —(CH2)nC(O)alkoxy, —(CH2)nOC(O)R6, —(CH2)nOR6, —(CH2)nR4R5, —(CH2)nC(O)NR4R5, —(CH2)nN(R4)C(O)R6, —(CH2)nS(O)2NR4R5, —(CH2)nN(R4)S(O)2R6, -ZAr, —(CH2)nS(O)2R6, —(OCH2)nS(O)2R6, —N(R4)S(O)2R6, —N(R4)C(O)R6, —(CH2)nN(R4)S(O)2R6, —(CH2)nN(R4)C(O)R6 or —(CH2)nC(O)alkyl; R3 is selected from halo, —CF3, alkyl, alkoxy, —O(CH2)nOR6, —O(CH2)nNR4R5, phenyl, cyclohexyl, benzo[1,3]dioxolyl, morpholinyl, pyridyl, pyrimidinyl, pyrazinyl, piperazinyl, piperidinyl, pyridizinyl, thienyl, furyl, pyrazolyl, pyrrolyl, triazolyl, imidazolyl, oxazolyl, thiazolyl, oxadiazolyl, isothiazolyl, isoxazolyl or thiadiazolyl; which alkyl, alkoxy, phenyl, cyclohexyl, benzo[1,3]dioxolyl, morpholinyl, pyridyl, pyrimidinyl, pyrazinyl, piperazinyl, piperidinyl, pyridizinyl, thienyl, furyl, pyrazolyl, pyrrolyl, triazolyl, imidazolyl, oxazolyl, thiazolyl, oxadiazolyl, isothiazolyl, isoxazolyl and thiadiazolyl groups may be optionally substituted by one or more groups, which may be the same or different, selected from R2; R4 and R5 may be the same or different and represent —H or alkyl or R4 and R5 together with the nitrogen atom to which they are attached form a heterocyclic ring; R6 is —H, alkyl or aryl; R7 is —H, alkyl or aryl; Ar is aryl or heteroaryl; each of which may be optionally substituted by R2; X and Y are selected from CR9 and N with the proviso that X and Y may not be the same; Z is a bond, O, S, NR7 or CH2; m is 0, 1 or 2; n is an integer value from 1 to 6; q and r are independently selected from 0, 1, 2 or 3; and s is 0, 1, 2 or 3; with the proviso that said compound of formula (IB) is not a compound selected from: 5-amino-N-isoquinolin-5-yl-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide; 5-methyl-N-quinolin-8-yl-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide, 5-methyl-N-quinolin-7-yl-1-[3-trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide, 5-methyl-N-quinolin-3-yl-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide, N-isoquinolin-5-yl-5-methyl-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide, 5-methyl-N-quinolin-5-yl-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide, 1-(3-chlorophenyl)-N-isoquinolin-5-yl-5-methyl-1H-pyrazole-3-carboxamide, N-isoquinolin-5-yl-1-(3-methoxyphenyl)-5-methyl-1H-pyrazole-3-carboxamide, 1-(3-fuorophenyl)-N-isoquinolin-5-yl-5-methyl-1H-pyrazole-3-carboxamide, 1-(2-chloro-5-trifluoromethylphenyl)-N-isoquinolin-5-yl-5-methyl-1H-pyrazole-3-carboxamide, 5-methyl-N-(3-methylisoquinolin-5-yl)-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide; and N-[3-[2-(diethylamino)ethyl]-1,2-dihydro-4-methyl-2-oxo-7-quinolinyl]-4-phenyl-1-piperazinecarboxamide. Suitably, P is phenyl, pyridine, piperazine, piperidine or fluorene. Suitably, P is phenyl. Suitably, P is pyridine. Suitably, R1 is alkyl. More suitably, R1 is methyl. Suitably, R2 is halo. More suitably, R2 is chloro. Suitably, R3 is halo, —CF3, alkyl, alkoxy, —O(CH2)nOR6, —O(CH2)nNR4R5, phenyl, cyclohexyl, benzo[1,3]dioxolyl, morpholinyl, pyridyl, piperazinyl, piperidinyl, pyrazolyl, thienyl, isothiazolyl; which alkyl, phenyl, cyclohexyl, benzo[1,3]dioxolyl, morpholinyl, pyridyl, piperazinyl, piperidinyl, pyrazolyl, thienyl, and isothiazolyl groups may be optionally substituted by one or more groups, which may be the same or different, selected from R2. More suitably, R3 is halo, —CF3, alkyl, alkoxy, —O(CH2)nOR6, —O(CH2)nNR4R5, phenyl, cyclohexyl, benzo[1,3]dioxolyl, morpholinyl, pyridyl, piperazinyl, piperidinyl, pyrazolyl, thienyl, isothiazolyl; which alkyl, phenyl, cyclohexyl, benzo[1,3]dioxolyl, morpholinyl, pyridyl, piperazinyl, piperidinyl, pyrazolyl, thienyl, and isothiazolyl groups may be optionally substituted by one or more groups, which may be the same or different, selected from halo, —CF3, alkyl, alkoxy, —C(O)alkyl, —C(O)alkoxy and —S(O)2NR4R5. Suitably, q is 0 or 1. Suitably, r is 0 or 1. Suitably, s is 0, 1 or 2. Suitably, X is CR9 and Y is N. Suitably, X is N and Y is CR9. Preferred compounds according to this invention include Examples 1-133 (as shown below) or pharmaceutically acceptable salts or solvates thereof. Certain of the carbon atoms of formula (I) are chiral carbon atoms, and therefore compounds of formula (I) may exist as stereoisomers. The invention extends to all optical isomers such as stereoisomeric forms of the compounds of formula (I) including enantiomers and mixtures thereof, such as racemates. The different stereoisomeric forms may be separated or resolved one from the other by conventional methods or any given isomer may be obtained by conventional stereospecific or asymmetric syntheses. As indicated above, the compounds of formula (I) can form salts, especially pharmaceutically acceptable salts. Suitable pharmaceutically acceptable salts are those used conventionally in the art and include those described in J. Pharm. Sci., 1977, 66, 1-19, such as acid addition salts. Suitable pharmaceutically acceptable salts include acid addition salts. Suitable pharmaceutically acceptable acid addition salts include salts with inorganic acids such, for example, as hydrochloric acid, hydrobromic acid, orthophosphoric acid or sulphuric acid, or with organic acids such, for example as methanesulphonic acid, toluenesulphonic acid, acetic acid, propionic acid, lactic acid, citric acid, fumaric acid, malic acid, succinic acid, salicylic acid, maleic acid, glycerophosphoric acid or acetylsalicylic acid. The salts and/or solvates of the compounds of the formula (I) which are not pharmaceutically acceptable may be useful as intermediates in the preparation of pharmaceutically acceptable salts and/or solvates of compounds of formula (I) or the compounds of the formula (I) themselves, and as such form another aspect of the present invention. The compounds of formula (I) may be prepared in crystalline or non-crystalline form, and if crystalline, may be optionally hydrated or solvated. This invention includes in its scope stoichiometric hydrates as well as compounds containing variable amounts of water. Suitable solvates include pharmaceutically acceptable solvates, such as hydrates. Solvates include stoichiometric solvates and non-stoichiometric solvates. As used herein the term “alkyl” as a group or part of a group refers to a straight or branched chain saturated aliphatic hydrocarbon radical containing 1 to 12 carbon atoms, suitably 1 to 6 carbon atoms. Such alkyl groups in particular include methyl (“Me”), ethyl (“Et”), n-propyl (“Prn”), iso-propyl (“Pri”), n-butyl (“Bun”), sec-butyl (“Bus”), tert-butyl (“But”), pentyl and hexyl. Where appropriate, such alkyl groups may be substituted by one or more groups selected from halo (such as fluoro, chloro, bromo), —CN, —CF3, —OH, —OCF3, C2-6 alkenyl, C3-6 alkynyl, C1-6 alkoxy, aryl and di-C1-6 alkylamino. As used herein, the term “alkoxy” as a group or part of a group refers to an alkyl ether radical, wherein the term “alkyl” is defined above. Such alkoxy groups in particular include methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, iso-butoxy, sec-butoxy and tert-butoxy. Where appropriate, such alkoxy groups may be substituted by one or more groups selected from halo (such as fluoro, chloro, bromo), —CN, —CF3, —OH, —OCF3, C1-6 alkyl, C2-6 alkenyl, C3-6 alkynyl, aryl and di-C1-6 alkylamino. As used herein, the term “aryl” as a group or part of a group refers to a carbocyclic aromatic radical (“Ar”). Suitably such aryl groups are 5-6 membered monocyclic groups or 8-10 membered fused bicyclic groups, especially phenyl (“Ph”), biphenyl and naphthyl, particularly phenyl. The term “naphthyl” is used herein to denote, unless otherwise stated, both naphth-1-yl and naphth-2-yl groups. As used herein, the term “heteroaryl” as a group or part of a group refers to a stable 5-7-membered monocyclic or 7- to 10-membered bicyclic heterocyclic aromatic ring which consists of carbon atoms and from 1 to 4 heteroatoms independently selected from the group consisting of N, O and S. It is preferred that the total number of S and O atoms in the aromatic heterocycle is not more than 1. Examples of suitable heteroaryl groups include, but are not limited to, acridinyl, azocinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazolyl, carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl, 2H, 6H-1,5,2-dithiazinyl, dihydrobenzofuranyl, furanyl, furazanyl, imidazolyl, 1H-indazolyl, indolinyl, indolyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, naphthyridinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolyl, pyrimidinyl, phthalazinyl, pteridinyl, purinyl, pyrazinyl, pyrazolyl, pyridooxazolyl, pyridoimidazolyl, pyridothiazolyl, pyridyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thiazolyl, thienyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, triazinyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl and xanthenyl. As used herein, the terms “heterocyclyl” and “heterocyclic” as a group or part of a group refer to stable heterocyclic non-aromatic single and fused rings containing one or more heteroatoms independently selected from nitrogen, oxygen and sulfur. A fused heterocyclyl ring system may include carbocyclic rings and need include only one heterocyclic ring. Examples of suitable heterocyclyl groups include, but are not limited to, piperazinyl, homopiperazinyl, piperidinyl, pyrrolidinyl and morpholinyl. The term “halo” is used herein to describe, unless otherwise stated, a group selected from fluorine (“fluoro”), chlorine (“chloro”), bromine (“bromo”) or iodine (“iodo”). The present invention also provides a process for the preparation of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, which process comprises: (a) reacting a compound of formula (II): wherein, R1, R2, q, r, X and Y are as defined in relation to formula (I), with a compound of formula (III): wherein, P, R3 and s are as defined in relation to formula (I) and thereafter, as necessary, carrying out one or more of the following reactions: (i) converting one compound of formula (I) into another compound of formula (I); (ii) removing any protecting group; (iii) preparing a salt or a solvate of the compound so formed. The reaction between a compound of formula (II) and a compound of formula (III) may be effected using conventional methods for the formation of an amide bond, such as those described in J March, Advanced Organic Chemistry, 4th edition, J Wiley & Sons, 1992, p. 419-421. Typically, the reaction may be carried out in a solvent such as dichloromethane, in the presence of a suitable diimide, such as 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. According to a further aspect of the present invention there is provided an alternative process for the preparation of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof where P is phenyl or heteroaryl, which process comprises reacting a compound of formula (II) with a compound of formula (IV), wherein, R3 and s are as defined in relation to formula (I), P is phenyl or heteroaryl and L′ is selected from iodo, bromo or —OSO2CF3, in the presence of carbon monoxide and a suitable catalyst; and thereafter, as necessary, carrying out one or more of the following reactions: (i) converting one compound of formula (I) into another compound of formula (I); (ii) removing any protecting group; (iii) preparing a salt or a solvate of the compound so formed. A suitable catalyst is trans-bis-triphenylphosphinepalladium(II)bromide. According to still a further aspect of the present invention there is provided an alternative process for the preparation of a compound of formula (I) where P is heterocyclyl, or a pharmaceutically acceptable salt or solvate thereof, which process comprises reacting a compound of formula (II) with a compound of formula (V): wherein, P is heterocyclyl and R3 and s are as defined in relation to formula (I); and thereafter, as necessary, carrying out one or more of the following reactions: (i) converting one compound of formula (I) into another compound of formula (I); (ii) removing any protecting group; (iii) preparing a salt or a solvate of the compound so formed. The reaction between a compound of formula (II) and a compound of formula (V) may be effected using conventional methods for the formation of a urea derivative, for example, by treatment of a compound of formula (II) with a suitable activating reagent, such as phosgene, di-tertbutyl tricarbonate, or phenylchloroformate and a suitable base, followed by treatment with a compound of formula (V). The reaction may be carried out in a suitable solvent such as dichloromethane. A suitable base is triethylamine. According to still a further aspect of the present invention, there is provided an alternative process for the preparation of compounds of formula (I), which process comprises reacting a compound of formula (VI), wherein R1, R2, q, r, X and Y are as defined in relation to formula (I), and one R3a represents a group W wherein W is a halogen atom or a trifluoromethylsulfonyloxy group, or W is a group M selected from a boron derivative, for example, a boronic acid function B(OH)2 or a metal function such as trialkyl stannyl, for example SnBu3, zinc halide or magnesium halide; and when s is 2 the other R3a is R3; with a compound of formula (VII), R3—W1 (VII) wherein, R3 is as defined in relation to formula (I) and W1 is a halogen atom or a trifluoromethylsulfonyloxy group when W is a group M or W1 is a group M when W is a halogen atom or a trifluoromethylsulfonyloxy group; and thereafter, as necessary, carrying out one or more of the following reactions: (i) converting one compound of formula (I) into another compound of formula (I); (ii) removing any protecting group; (iii) preparing a salt or a solvate of the compound so formed. The reaction of a compound of formula (VI) with a compound of formula (VII) may be effected in the presence of a transition metal catalyst such as tetrakis-triphenylphosphinepalladium (0). When M represents a boronic acid function such as B(OH)2, the reaction may be carried out under basic conditions, for example using aqueous sodium carbonate in a suitable solvent such as dioxane. When M is trialkylstannyl, the reaction may be carried out in an inert solvent, such as xylene or dioxane optionally in the presence of LiCl. When M is a zinc or magnesium halide, the reaction may be effected in an aprotic solvent such as tetrahydrofuran. The substituent W is preferably a halogen atom such as bromine, or a sulfonyloxy group such as trifluoromethylsulfonyloxy; and W1 is preferably a group M, such as trialkylstannyl or B(OH)2. Compounds of formula (II) may be prepared by the reaction of a compound of formula (VIII), wherein, R1, R2, q and r are as defined in relation to formula (I), with a suitable reducing agent. The reaction of a compound of formula (VIII) with a reducing agent may be effected by methods well known in the art, such as those described in J March, Advanced Organic Chemistry, 4th edition, J Wiley & Sons, 1992, p. 1216-1218. Suitable reducing agents include (a) iron or zinc metal in hydrochloric acid, or (b) hydrogen in the presence of a suitable catalyst, such as, 5% palladium on charcoal. Reduction using hydrogen may conveniently be performed in a solvent such as methanol or ethanol. Compounds of formula (VIII) where X is NR8 where R8 is H and Y is C(R9)2, may be prepared by reaction of a compound of formula (IX), wherein, R1, R2, q and r are as defined in relation to formula (I), X is NR8 where R8 is H and Y is C(R9)2, with concentrated sulfuric acid and concentrated nitric acid. The reaction of a compound of formula (IX) with concentrated sulfuric acid and concentrated nitric acid may be effected by methods well known in the art, such as those described in J March, Advanced Organic Chemistry, 4th edition, J Wiley & Sons, 1992, p. 522-525. Compounds of formula (VIII) where X is N and Y is CR9 may be prepared by reaction of a compound of formula (VIII) where X is NR8 where R8 is H and Y is C(R9)2 with (a) a suitable aromatisation reagent, such as a suitable quinone, for example, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone; or (b) a suitable hydrogenation catalyst, for example, 10% Pd on charcoal, in the presence of a suitable solvent such as xylene. The reaction of a compound of formula (VIII) where X is NR8 where R8 is H and Y is CH2 with a suitable aromatisation reagent or a suitable hydrogenation catalyst may be effected by methods well known in the art, such as those described in J March, Advanced Organic Chemistry, 4th edition, J Wiley & Sons, 1992, p. 1162-1164. Compounds of formula (VIII) wherein X is NR8 where R8 is alkyl, hydroxyalkyl, cycloalkyl, aralkyl, alkoxyalkyl, cycloalkylalkyl, heterocyclylalkyl, —S(O)mR6, —C(O)CF3, —C(O)alkyl, —C(O)cycloalkyl, —C(O)aralkyl, —C(O)Ar, —C(O)(CH2)nOR6, —C(O)(CH2)nNR4R5, —C(O)alkoxy, —C(O)NR4R5, —(CH2)nC(O)alkoxy, —(CH2)nOC(O)R6, —(CH2)nOR6, —(CH2)nR4R5, —(CH2)nC(O)NR4R5, —(CH2)nN(R4)C(O)R6, —(CH2)nS(O)2NR4R5, —(CH2)nN(R4)S(O)2R6, —(CH2)nS(O)2R6, —(CH2)nN(R4)S(O)2R6, —(CH2)nN(R4)C(O)R6 or —(CH2)nC(O)alkyl and Y is C(R9)2 where R9 is as defined in relation to formula (I) may be prepared by reaction of a compound of formula (VIII) wherein X is NR8 where R8 is H and Y is C(R9)2 where R9 is as defined in relation to formula (I), with (a) a suitable acylating agent; or (b) a suitable acylating reagent and thereafter, reacting the product so formed with a suitable reducing agent; or (c) a suitable alkylating agent. The reaction between a compound of formula (VIII) with a suitable acylating agent may be effected by methods well known in the art, such as those described in J March, Advanced Organic Chemistry, 4th edition, J Wiley & Sons, 1992, p417. A suitable acylating agent is an acyl chloride. Typically, the acylation is performed in the presence of a suitable base, such as triethylamine, in a suitable solvent, such as, dichloromethane. The reduction of an acylated product so formed may be effected by methods well known in the art such as those descibed in J March, Advanced Organic Chemistry, 4th edition, J Wiley & Sons, 1992, p. 1212. A suitable reducing agent is borane-THF complex. Typically, the reduction is performed in a suitable solvent, such as, tetrahydrofuran. The reaction between a compound of formula (VIII) with a suitable alkylating agent may be effected by methods well known in the art, such as those described in J March, Advanced Organic Chemistry, 4th edition, J Wiley & Sons, 1992, p411. A suitable alkylating reagent is an alkyl halide. Typically the reaction is performed in the presence of a suitable base, such as, potassium carbonate or cesium carbonate, in a suitable solvent, such as, dimethylformamide. Compounds of formula (VIII) where Y is NR8 where R8 is H, and X is C(R9)2 may be prepared by methods described in International Patent Application, Publication Number WO 00/09486. Compounds of formula (IX) are commercially available. Compounds of formula (III) may be prepared according to a variety of known methods in accordance with the nature of the moiety, P. For example, compounds of formula (III) or their corresponding esters, where P is phenyl or heteroaryl may be prepared in accordance with methods described in J. Hassan et al., Chem. Rev., 2002, 102, 1359. Hydrolysis of the corresponding ester compounds to compounds of formula (III) may be carried out in accordance with methods disclosed in J March, Advanced Organic Chemistry, 4th edition, J Wiley & Sons, 1992, p. 378-383. Compounds of formula (III) where P is heteroaryl or heterocyclyl may be prepared in accordance with, for example, methods disclosed in the following references: H. Vorbruggen, Adv. Het. Chem., 1990, 49, 117 and E. Graf et al, Synthesis, 1999, 7, 1216. Compounds of formula (IV) may be prepared in accordance with methods disclosed in J. Hassan et al., Chem. Rev., 2002, 102, 1359. Compounds of formula (V) may be prepared by reaction of a compound of formula (X), (R3)s-L″ (X) wherein R3 is as defined in relation to compound of formula (I), s is 1, 2 or 3 and L″ is halo, such as chloro or bromo, with a compound of formula (XI), wherein P is heterocyclyl. Compounds of formula (V) where R3 is heteroaryl may be prepared in accordance with the methods disclosed in H. Vorbruggen et al., Adv. Het. Chem., 1990, 49, 117. Compounds of formula (X) where R3 is heteroaryl and compounds of formula (XI) are commercially available. Compounds of formula (V) where R3 is phenyl are commercially available. Compounds of formula (VI) may be prepared by analogous methods to those described herein for the preparation of compounds of formula (I). Compounds of formula (VII) are commercially available. The above-mentioned conversions of a compound of formula (I) into another compound of formula (I) include any conversion, which may be effected using conventional procedures, but in particular the said conversions include any combination of: (i) converting one group R1 into another group R1; (ii) converting one group R2 into another group R2; (iii) converting one group R3 into another group R3; and (iv) converting one group R8 into another group R8. The above-mentioned conversions (i), (ii), (iii) and (iv) may be performed using any appropriate method under conditions determined by the particular groups chosen. Suitable conversions of one group R8 into another group R8, as in conversion (iv) above, include, (a) converting a group R8 which represents —H, into another group R8 which represents alkyl, such as methyl. Such a conversion may be performed using an appropriate alkylation procedure, for example, by treating a compound of formula (I) wherein R8 is —H with an agent, R8-Z, where R8 is alkyl and Z is halo, such as bromo, chloro or iodo, or —OSO2CF3. Typically, such an interconversion is performed in the presence of a suitable base, such as, potassium carbonate or cesium carbonate. A suitable solvent is dimethylformamide; (b) converting a group R8 which represents —H, into another group R8 which represents acyl, such as acetyl. Such a conversion may be performed using an appropriate acylation procedure, for example, by treating a compound of formula (I) wherein R8 is —H with an agent, R8-Z, where R8 is acyl and Z is halo, such as chloro. Typically, such an interconversion is performed in the presence of a suitable base, such as, triethylamine. A suitable solvent is dichloromethane. It will be appreciated by those skilled in the art that it may be necessary to protect certain reactive substituents during some of the above procedures. Standard protection and deprotection techniques, such as those described in Greene T. W. ‘Protective groups in organic synthesis’, New York, Wiley (1981), can be used. For example, primary amines can be protected as phthalimide, benzyl, benzyloxycarbonyl or trityl derivatives. Carboxylic acid groups can be protected as esters. Aldehyde or ketone groups can be protected as acetals, ketals, thioacetals or thioketals. Deprotection of such groups is achieved using conventional procedures known in the art. Pharmaceutically acceptable salts may be prepared conventionally by reaction with the appropriate acid or acid derivative. Compounds of formula (I) and their pharmaceutically acceptable salts and solvates thereof have Vanilloid receptor antagonist (VR1) activity and are believed to be of potential use for the treatment or prophylaxis of certain disorders, or treatment of the pain associated with them, such as: pain, chronic pain, neuropathic pain, postoperative pain, postrheumatoid arthritic pain, osteoarthritic pain, back pain, visceral pain, cancer pain, algesia, neuralgia, dental pain, headache, migraine, neuropathies, carpal tunnel syndrome, diabetic neuropathy, HIV-related neuropathy, post-herpetic neuralgia, fibromyalgia, neuritis, sciatica, nerve injury, ischaemia, neurodegeneration, stroke, post stroke pain, multiple sclerosis, respiratory diseases, asthma, cough, COPD, broncho constriction, inflammatory disorders, oesophagitis, heart burn, Barrett's metaplasia, dysphagia, gastroeosophageal relux disorder (GERD), stomach and duodenal ulcers, functional dyspepsia, irritable bowel syndrome, inflammatory bowel disease, colitis, Crohn's disease, pelvic hypersensitivity, pelvic pain, menstrual pain, renal colic, urinary incontinence, cystitis, burns, itch, psoriasis, pruritis, emesis (hereinafter referred to as the “Disorders of the Invention”). Accordingly, the invention also provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, for use as an active therapeutic substance, in particular, in the treatment and/or prophylaxis of the Disorders of the Invention. In particular, the invention provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof for use in the treatment or prophylaxis of pain. The invention further provides a method for the treatment or prophylaxis of disorders in which antagonism of the Vanilloid (VR1) receptor is beneficial, in particular the Disorders of the Invention, in mammals including humans, which method comprises administering to a mammal in need thereof a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof. The invention provides for the use of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof in the manufacture of a medicament for the treatment or prophylaxis of disorders in which antagonism of the Vanilloid (VR1) receptor is beneficial, particularly the Disorders of the Invention. In order to use the compounds of the invention in therapy, they will normally be formulated into a pharmaceutical composition in accordance with standard pharmaceutical practice. Thus, the present invention also provides a pharmaceutical composition, which comprises a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof and a pharmaceutically acceptable carrier or excipient therefor. A pharmaceutical composition of the invention, which may be prepared by admixture, suitably at ambient temperature and atmospheric pressure, is usually adapted for oral, parenteral, rectal administration or intravesical adminstration to the bladder and, as such, may be in the form of tablets, capsules, oral liquid preparations, powders, granules, lozenges, reconstitutable powders, injectable or infusable solutions, suspensions or suppositories. Orally administrable compositions are generally preferred. Tablets and capsules for oral administration may be in unit dose form, and may contain conventional excipients, such as binding agents, fillers, tabletting lubricants, disintegrants and acceptable wetting agents. The tablets may be coated according to methods well known in normal pharmaceutical practice. Oral liquid preparations may be in the form of, for example, aqueous or oily suspension, solutions, emulsions, syrups or elixirs, or may be in the form of a dry product for reconstitution with water or other suitable vehicle before use. Such liquid preparations may contain conventional additives such as suspending agents, emulsifying agents, non-aqueous vehicles (which may include edible oils), preservatives, and, if desired, conventional flavourings or colourants. For parenteral administration, fluid unit dosage forms are prepared utilising a compound of the invention or pharmaceutically acceptable salt thereof and a sterile vehicle. The compound, depending on the vehicle and concentration used, can be either suspended or dissolved in the vehicle. In preparing solutions, the compound can be dissolved for injection and filter sterilised before filling into a suitable vial or ampoule and sealing. Advantageously, adjuvants such as a local anaesthetic, preservatives and buffering agents are dissolved in the vehicle. To enhance the stability, the composition can be frozen after filling into the vial and the water removed under vacuum. Parenteral suspensions are prepared in substantially the same manner, except that the compound is suspended in the vehicle instead of being dissolved, and sterilization cannot be accomplished by filtration. The compound can be sterilised by exposure to ethylene oxide before suspension in a sterile vehicle. Advantageously, a surfactant or wetting agent is included in the composition to facilitate uniform distribution of the compound. The composition may contain from 0.1% to 99% by weight, preferably from 10 to 60% by weight, of the active material, depending on the method of administration. The dose of the compound used in the treatment of the aforementioned disorders will vary in the usual way with the seriousness of the disorders, the weight of the sufferer, and other similar factors. For systemic administration, dosage levels from 0.01 mg to 100 mg per kilogramme of body weight are useful in the treatment of pain. However, as a general guide suitable unit doses may be 0.05 to 1000 mg, more suitably 0.05 to 20, 20 to 250, or 0.1 to 500.0 mg, for example 0.2 to 5 and 0.1 to 250 mg; and such unit doses may be administered more than once a day, for example two or three a day, so that the total daily dosage is in the range of about 0.5 to 1000 mg; and such therapy may extend for a number of weeks or months. No unacceptable toxicological effects are indicated with compounds of the invention when administered in accordance with the invention. All publications, including but not limited to patents and patent applications, cited in this specification are herein incorporated by reference as if each individual publication were specifically and individually indicated to be incorporated by reference herein as though fully set forth. The following Descriptions and Examples illustrate the preparation of the compounds of the invention. Abbreviations AIBN=2,2′-azobisisobutyronitrile BINAP=2,2′-bis(diphenylphosphino)-1,1′-binaphthyl CDCl3=chloroform-d DCM=Dichloromethane DME=1,2-Dimethoxyethane DMF=DimethylformamideDMSO=dimethylsulfoxide EtOAc=Ethyl acetate MeOH=Methanol MgSO4=Magnesium sulfate Na2SO4=Sodium Sulfate NCS=N-chlorosuccinimide Pd2(dba)3-tris(dibenzylideneacetone)dipalladium(0) SPE=solid phase extraction THF=Tetrahydrofuran tlc=Thin Layer Chromatography Xantphos—9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene Description 1 (D1) 7-Nitro-1,2,3,4-tetrahydroquinoline To a solution of 1,2,3,4-tetrahydroquinoline (6.5 g, 0.049 mol) in concentrated sulfuric acid (118 ml) cooled to 0° C. was added a solution of concentrated nitric acid (4.9 ml) in concentrated sulfuric acid (12 ml) dropwise over 0.3 h so as to maintain the temperature at 0-5° C. On completion of addition, the reaction mixture was poured onto crushed ice then neutralised with solid potassium carbonate. EtOAc (500 ml) was added and the mixture was filtered to remove undissolved solids then extracted with further EtOAc (4×500 ml). The combined extracts were dried over MgSO4 and concentrated in vacuo to give the crude product which was purified by flash column chromatography. Elution with 5% EtOAc/60-80° C. petroleum ether gave the title compound as an orange solid (5.46 g). 1H NMR (250 MHz, CDCl3) δ(ppm): 7.40 (dd, 1H), 7.26 (d, 1H), 7.02 (d, 1H), 4.16 (br, 1H), 3.35 (m, 2H), 2.81 (t, 2H), 1.95 (m, 2H). Description 2 (D2) 1-Methyl-7-nitro-1,2,3,4-tetrahydroquinoline To a solution of 7-nitro-1,2,3,4-tetrahydroquinoline (D1) (7.03 g, 39.4 mmol) in dimethylformamide (50 ml) was added potassium carbonate (16.3 g, 118 mmol) and iodomethane (3.7 ml, 59.1 mmol) and the reaction stirred at ambient temperature overnight. The solvent was removed under reduced pressure and the residue was taken up in water (400 ml) and extracted into ether (3×200 ml). The combined ether extracts were washed with brine (100 ml), dried over MgSO4 and concentrated in vacuo to give the crude product which was purified by flash column chromatography. Elution with 20-40% EtOAc/40-60° C. petroleum ether gave the title compound as an orange solid (5.35 g). 1H NMR (250 MHz, CDCl3) δ (ppm): 7.42 (dd, 1H), 7.33 (d, 1H), 7.01 (d, 1H), 3.31 (m, 2H), 2.96 (s, 3H), 2.80 (t, 2H), 1.99 (m, 2H). Description 3 (D3) 7-Amino-1-methyl-1,2,3,4-tetrahydroquinoline A mixture of 1-methyl-7-nitro-1,2,3,4-tetrahydroquinoline (D2) (5.35 g, 27.9 mmol) and 10% palladium on charcoal (2 g, 54% water) in methanol (150 ml) was hydrogenated at atmospheric pressure and ambient temperature temperature for 3 d. The catalyst was filtered off and washed with further methanol. The combined filtrated and washings were concentrated in vacuo to give the crude product, which was purified by flash column chromatography. Elution with 5-10% EtOAc/DCM gave the title compound as a brown oil (2.58 g). 1H NMR (250 MHz, CDCl3) δ(ppm): 6.73 (dd, 1H), 5.99 (m, 2H), 3.49 (br, 1H), 3.18 (m, 2H), 2.84 (s, 3H), 2.66 (t, 2H), 1.93 (m, 2H). Description 4 (D4) 7-Nitro-1-trifluoroacetyl-1,2,3,4-tetrahydroquinoline To solution of 7-nitro-1,2,3,4-tetrahydroquinoline (D1) (1 g, 5.6 mmol) and triethylamine (1.2 ml, 8.6 mmol) in DCM (30 ml) at 0° C. was added trifluoroacetic anhydride (0.8 ml, 5.7 mmol) and the reaction was then stirred at ambient temperature overnight. The reaction mixture was diluted with DCM (30 ml), washed with water (100 ml), dried over MgSO4 and concentrated in vacuo to give the title compound as a yellow solid (1.52 g). 1H NMR (250 MHz, CDCl3) δ(ppm): 8.64 (br, 1H), 8.04 (dd, 1H), 7.36 (d, 1H), 3.90 (m, 2H), 2.99 (t, 2H), 1.98 (m, 2H). Description 5 (D5) 7-Amino-1-trifluoroacetyl-1,2,3,4-tetrahydroquinoline A mixture of 7-nitro-1-trifluoroacetyl-1,2,3,4-tetrahydroquinoline (D4) (1.51 g, 5.5 mmol) and 10% palladium on charcoal (150 mg, 54% water) in methanol (80 ml) was hydrogenated at atmospheric pressure and ambient temperature for 24 h. The catalyst was removed by filtration and was washed with further methanol. The combined filtrated and washings were concentrated in vacuo to give the title compound as a pale orange solid (1.29 g). 1H NMR (250 MHz, CDCl3) δ (ppm): 7.05 (br, 1H), 6.95 (d, 1H), 6.54 (dd, 1H), 3.78 (m, 2H), 3.65 (br, 2H), 2.74 (br, 2H), 2.03 (m, 2H). Description 6 (D6) 1-(2-Methoxyacetyl)-7-nitro-1,2,3,4-tetrahydroquinoline Using the procedure outlined in Description 4, the title compound was prepared from 7-nitro-1,2,3,4-tetrahydroquinoline (D1) (178 mg, 1 mmol) and methoxyacetyl chloride (101 ul, 1.1 mmol) as a yellow gum (212 mg). 1H NMR (250 MHz, CDCl3) δ (ppm): 8.54 (br, 1H), 7.96 (dd, 1H), 7.30 (d, 1H), 4.25 (s, 2H), 3.81 (m, 2H), 3.48 (s, 3H), 2.88 (t, 2H), 2.04 (qn, 2H). Description 7 (D7) 1-(2-Dimethylaminoacetyl)-7-nitro-1,2,3,4-tetrahydroquinoline Using the procedure outlined in Description 4 followed by silica SPE chromatography eluting with 20% EtOAc/MeOH the title compound was prepared from 7-nitro-1,2,3,4-tetrahydroquinoline (D1) (178 mg, 1 mmol) and dimethylaminoacetyl chloride hydrochloride (174 mg, 1.1 mmol) as a yellow solid (103 mg). 1H NMR (250 MHz, CDCl3) δ (ppm): 8.74 (d, 1H), 7.92 (dd, 1H), 7.28 (d, 1H), 3.87 (m, 2H), 3.25 (s, 2H), 2.87 (t, 2H), 2.35 (s, 6H), 1.95 (m, 2H). Description 8 (D8) 1-(2-Chloroacetyl)-7-nitro-1,2,3,4-tetrahydroquinoline Using the procedure outlined in Description 4, the title compound was prepared from 7-nitro-1,2,3,4-tetrahydroquinoline (D1) (4.41 g, 25 mmol) and chloroacetyl chloride (2.2 ml, 27.6 mmol) as a dark brown solid (5.853 g). 1H NMR (250 MHz, CDCl3) δ (ppm): 8.49 (br, 1H), 8.00 (dd, 1H), 7.33 (d, 1H), 4.27 (s, 2H), 3.86 (m, 2H), 2.90 (t, 2H), 2.09 (m, 2H). Description 9 (D9) 1-(2-Diisopropylaminoacetyl)-7-nitro-1,2,3,4-tetrahydroquinoline A mixture of 1-(2-chloroacetyl)-7-nitro-1,2,3,4-tetrahydroquinoline (D8) (6.7 g, 26 mmol) and diisopropylamine (50 ml) in THF (50 ml) was heated at reflux for 5d then cooled to room temperature. Aqueous work-up yielded a crude oil which was purified by flash column chromatography. Elution with 0-5% methanol/DCM gave the title compound as a dark oil (6.56 g). 1H NMR (250 MHz, CDCl3) δ (ppm): 8.62 (br, 1H), 7.91 (dd, 1H), 7.27 (d, 1H), 3.95 (m, 2H), 3.54 (s, 2H), 3.02 (sp, 2H), 2.87 (t, 2H), 2.02 (m, 2H), 1.02 (d, 12H). Description 10 (D10) 1-(2-Methoxyethyl)-7-nitro-1,2,3,4-tetrahydroquinoline To a solution of 1-(2-methoxyacetyl)-7-nitro-1,2,3,4-tetrahydroquinoline (D6) (212 mg, 0.85 mmol) in dry THF (9 ml) at 0° C. under an argon atmosphere, was added borane/THF complex (4.5 ml, 4.5 mmol). The reaction was stirred at 0° C. for 0.5 h then ambient temperature for 3 h. 2M Hydrochloric acid (3 ml) was added cautiously followed by water (10 ml). The mixture was extracted with EtOAc (2×10 ml) which was dried over MgSO4 and concentrated in vacuo to give the desired product as an orange solid in quantitative yield. 1H NMR (250 MHz, CDCl3) δ (ppm): 7.39 (m, 2H), 7.00 (m, 1H), 3.61 (dd, 2H), 3.52 (dd. 2H), 3.41 (m, 2H), 3.37 (s, 3H), 2.80 (t, 2H), 1.95 (m, 2H). Description 11 (D11) 1-(2-Dimethylaminoethyl)-7-nitro-1,2,3,4-tetrahydroquinoline Using the procedure outlined in Description 10, the title compound was prepared from 1-(2-dimethylaminoacetyl)-7-nitro-1,2,3,4-tetrahydroquinoline (D7) (103 mg, 0.39 mmol) as an orange solid (80 mg). 1H NMR (250 MHz, CDCl3) δ (ppm): 7.43 (dd, 1H), 7.35 (d, 1H), 7.04 (d, 1H), 3.83 (m, 2H), 3.39 (m, 2H), 2.91 (m, 2H), 2.81 (t, 2H), 2.72 (s, 6H), 1.98 (m, 2H). Description 12 (D12) 1-(2-Diisopropylaminoethyl)-7-nitro-1,2,3,4-tetrahydroquinoline Using the procedure outlined in Description 10, the title compound was prepared from 1-(2-diisopropylaminoacetyl)-7-nitro-1,2,3,4-tetrahydroquinoline (D9) (6.56 g, 21 mmol) as an orange oil (4.85 g). 1H NMR (250 MHz, CDCl3) δ (ppm): 7.42 (d, 1H), 7.33 (dd, 1H), 6.98 (d, 1H), 3.41 (m, 2H), 3.31 (m, 2H), 3.05 (sp, 2H), 2.78 (t, 2H), 2.62 (m, 2H), 1.92 (m, 2H), 1.04 (d, 12H). Description 13 (D13) 7-Amino-1-(2-methoxyethyl)-1,2,3,4-tetrahydroquinoline Using the procedure outlined in Description 5, the title compound was prepared from 1-(2-methoxyethyl)-7-nitro-1,2,3,4-tetrahydroquinoline (D10) (215 mg, 0.91 mmol) as a colourless gum, (152 mg). 1H NMR (250 MHz, CDCl3) δ (ppm): 6.71 (m, 1H), 5.96 (m, 2H), 3.55 (t, 2H), 3.41 (t, 2H), 3.35 (s, 3H), 3.31 (m, 2H), 2.95 (br), 2.64 (t, 2H), 1.89 (m, 2H). Description 14 (D14) 7-Amino-1-(2-dimethylaminoethyl)-1,2,3,4-tetrahydroquinoline Using the procedure outlined in Description 5, the title compound was prepared from 1-(2-dimethylaminoethyl)-7-nitro-1,2,3,4-tetrahydroquinoline (D10) (75 mg, 0.3 mmol) as a crude yellow solid, (79 mg). 1H NMR (250 MHz, CDCl3) δ (ppm): 6.75 (d, 1H), 6.35 (d, 1H), 6.05 (dd, 1H), 3.81 (m, 2H), 3.27 (m, 2H), 3.16 (t, 2H), 2.85 (s, 6H), 2.64 (t, 2H), 1.90 (m, 2H). Description 15 (D15) 7-Amino-1-(2-diisopropylaminoethyl)-1,2,3,4-tetrahydroquinoline Using the procedure outlined in Description 5, the title compound was prepared from 1-(2-diisopropylaminoethyl)-7-nitro-1,2,3,4-tetrahydroquinoline (D12) (4.70 g, 17 mmol) as a brown oil (2.85 g). 1H NMR (400 MHz, CDCl3) δ (ppm): 6.71 (d, 1H), 5.95 (m, 2H), 3.43 (br, 2H), 3.29 (m, 2H), 3.20 (m, 2H), 3.02 (sp, 2H), 2.62 (m, 4H), 1.89 (m, 2H), 1.04 (d, 12H). Description 16 (D16) 1-(2-Morpholin-4-ylethyl)-7-nitro-1,2,3,4-tetrahydroquinoline To a solution of 7-nitro-1,2,3,4-tetrahydroquinoline (D1) (246 mg, 1.38 mmol) in DMF (2.7 ml) was added potassium carbonate (574 mg, 4.15 mmol) followed by a solution of 4-(2-iodoethyl)morpholine (500 mg, 2.07 mmol) in DMF (2 ml) and the reaction heated to 70° C. After cooling to ambient temperature the reaction mixture was diluted with water and extracted with EtOAc which was washed with water, dried over MgSO4 and concentrated in vacuo to give the crude product which was purified by silica SPE chromatography. Elution with 80% EtOAc/petroleum ether gave the title compound as an orange gum (29 mg). 1H NMR (250 MHz, CDCl3) δ (ppm): 7.39 (m, 2H), 7.00 (d, 1H), 3.73 (m, 4H), 3.47 (m, 2H), 3.38 (m, 2H), 2.79 (t, 2H), 2.49-2.59 (m, 6H), 1.96 (m, 2H). Description 17 (D17) 7-Amino-1-(2-morpholin-4-ylethyl)-1,2,3,4-tetrahydroquinoline Using the procedure outlined in Description 5, the title compound was prepared from 1-(2-morpholin-4-ylethyl)-7-nitro-1,2,3,4-tetrahydroquinoline (D16) (29 mg, 0.1 mmol) as a pink gum, which was used directly in the next step. Description 18 (D18) Ethyl 2-methyl-6-phenylnicotinate The title compound was prepared according to E. Graf & R. Troschutz, Synthesis, 1999, 7, 1216. Description 19 (D19) Ethyl 6-(4-fluorophenyl)-2-methylnicotinate The title compound was prepared from dimethylamino-(4-fluorophenyl)propan-1-one and ethyl 3-aminocrotonate using the general procedure outlined in D18. MS (ES): MH+ 260. Description 20 (D20) Ethyl 6-(3-fluorophenyl)-2-methylnicotinate The title compound was prepared from dimethylamino-(3-fluorophenyl)propan-1-one and ethyl 3-aminocrotonate using the general procedure outlined in D18. 1H NMR (250 MHz, CDCl3) δ (ppm): 8.27 (d, 1H), 7.83 (m, 2H), 7.61 (d, 1H), 7.44 (m, 1H), 7.13 (m, 1H), 4.41 (q, 2H), 2.91 (s, 3H), 1.42 (t, 3H). Description 21 (D21) Ethyl 6-(2,3-difluorophenyl)-2-methylnicotinate The title compound was prepared from dimethylamino-(2,3-difluorophenyl)-propan-1-one and ethyl 3-aminocrotonate using the general procedure outlined in D18. 1H NMR (250 MHz, CDCl3) δ (ppm): 8.28 (d, 1H), 7.83 (m, 1H), 7.70 (dd, 1H), 7.22 (m, 2H), 4.41 (q, 2H), 2.91 (s, 3H), 1.42 (t, 3H). Description 22 (D22) (R)-2-Methyl-4-(3-trifluoromethyl-2-pyridyl)piperazine The title compound was prepared according to R. Bakthavalatcham, International Patent Application, Publication Number, WO 02/08221). Description 23 (D23) 2-Methyl-6-phenylnicotinic acid Ethyl 2-methyl-6-phenylnicotinate (D18) (284 mg, 1.2 mmol) was treated with aq. 2M NaOH in ethanol at reflux giving the title compound as an off white solid (108 mg). MS (AP): MH+ 214, M-H+ 212. Description 24 (D24) 6-(4-Fluorophenyl)-2-methylnicotinic acid Using the procedure outlined in Description 23, the title compound was prepared from ethyl 6-(4-fluorophenyl)-2-methylnicotinate (D19) (500 mg, 1.9 mmol) as an off white solid (250 mg). 1H NMR (400 MHz, DMSO) δ (ppm): 8.25 (d, 1H), 8.21 (dd, 2H), 7.92 (d, 1H), 7.35(t, 2H), 2.80(s, 3H). Description 25 (D25) 6-(3-Fluorophenyl)-2-methylnicotinic acid Using the procedure outlined in Description 23, the title compound was prepared from ethyl 6-(3-fluorophenyl)-2-methylnicotinate (D20) (500 mg, 1.9 mmol) as an off white solid (254 mg). 1H NMR (250 MHz, MeOH-d4) δ (ppm): 8.13 (d, 1H), 7.80 (m, 2H), 7.69 (d, 1H), 7.47 (m, 1H), 7.16 (m, 1H), 2.81 (s, 3H). Description 26 (D26) 6-(2,3-Difluorophenyl)-2-methylnicotinic acid Using the procedure outlined in Description 23, the title compound was prepared from ethyl 6-(2,3-difluorophenyl)-2-methylnicotinate (D21) (500 mg, 1.8 mmol) as an off white solid (344 mg). 1H NMR (250 MHz, CDCl3) δ (ppm): 8.42(d, 1H), 7.87 (m, 1H), 7.76 (m, 1H), 7.24 (m, 2H), 2.97 (s, 3H). Description 27 (D27) 4,4-Dimethyl-7-nitro-1-trifluoroacetyl-1,2,3,4-tetrahydroquinoline To a suspension of 4,4-dimethyl-1,2,3,4-tetrahydroquinoline (W. W. Hoffman, A. R. Kraska, European Patent Application No. EP 0 130 795) (470 mg, 2.92 mmol) in concentrated sulfuric acid (5 ml) at 0° C. was added dropwise a mixture of concentrated nitric acid (0.3 ml) in concentrated sulfuric acid (2.8 ml) such that the temperature of the mixture remained below 5C. The reaction was allowed to warm to ambient temperature then poured onto ice, basified with 12M NaOH solution and extracted with EtOAc. The extracts were dried and concentrated in vacuo to give the crude 4,4-dimethyl-7-nitro-1,2,3,4-tetrahydroquinoline (514 mg) which was then dissolved in DCM (12 ml) and triethylamine (533 ul, 3.82 mmol) and trifluoroacetic anhydride (357 ul, 2.51 mmol) were added. The mixture was stirred at ambient temperature for 18 h then diluted with further DCM, washed with water, dried over MgSO4 and concentrated in vacuo to give the crude product. Purification by column chromatography eluting with 0-30% EtOAc/40-60° C. petroleum ether gave the title compound as an orange solid (341 mg). 1H NMR (250 MHz, CDCl3) δ (ppm): 8.62 (br, 1H), 8.06 (dd, 1H), 7.55 (d, 1H), 3.91 (m, 2H), 1.96 (m, 2H), 1.39 (s, 6H). Description 28 (D28) 7-Amino-4,4-dimethyl-1-trifluoroacetyl-1,2,3,4-tetrahydroquinoline Using the procedure outlined in Description 5, the title compound was prepared from 4,4-dimethyl-7-nitro-1-trifluoroacetyl-1,2,3,4-tetrahydroquinoline (D27) (282 mg, 0.93 mmol) as a green oil (237 mg). 1H NMR (400 MHz, DMSO) δ (ppm): 7.09 (d, 1H), 6.70-6.80 (br, 1H), 6.48 (dd, 1H), 5.08 (br, 2H), 3.70-3.80 (m, 2H), 1.70-1.80 (m, 2H), 1.20 (s, 6H). MS (ES): MH+ 273. Description 29 (D29) 4-(6-Methyl-2-pyridyl)benzoic acid To a stirred, degassed mixture of 2-bromo-6-methylpyridine (3 g, 17 mmol), sodium carbonate (10.8 g, 100 mmol) and 4-carboxybenzeneboronic acid (2.3 g, 14 mmol) in DME (150 ml) and water (150 ml) under an argon atmosphere was added tetrakis(triphenylphosphine) palladium (0) (350 mg) and the mixture heated to reflux for 18 h. On cooling, ˜50% of the solvent was removed in vacuo and the residual aqueous solution was washed with EtOAc, then acidified to pH1 with concentrated HCl and washed with further EtOAc. The aqueous was then adjusted to pH 5 by addition of potassium carbonate causing formation of a white precipitate which was collected by filtration, washed with water and dried to give the title compound as a white solid (2.3 g). MS (ES): MH+ 212. Description 30 (D30) 7-Amino-3,4-dihydro-2H-1,4-ethanoquinoline Using the procedure outlined in Description 5, the title compound was prepared from 3,4-dihydro-2H-1,4-ethano-7-nitroquinoline (R. P. Duke et al, Tetrahedron Lett., 1970, 21, 1809) (239 mg, 0.113 mmol) as a white solid (199 mg). 1H NMR (400 MHz, CDCl3) δ (ppm): 6.96 (d, 1H), 6.59 (d, 1H), 6.55 (dd, 1H), 3.28 (br, 2H), 3.18 (ddd, 2H), 3.02 (m, 1H), 2.70 (m, 2H), 1.81 (m, 2H), 1.52 (m, 2H). Description 31 (D31) N-Methyl-4′-carboxamido-1,1′-biphenyl-4-carboxylic acid Using the procedure outlined in Description 29, the title compound was prepared from N-methyl-4-bromobenzamide (0.76 g, 3.6 mmol) and 4-carboxybenzeneboronic acid (0.56 g, 3.4 mmol) as a white solid (0.63 g). MS (API): MH+ 254. Description 32 (D32) N,N-Dimethyl-4′-carboxamido-1,1′-biphenyl-4-carboxylic acid Using the procedure outlined in Description 29, the title compound was prepared from N,N-dimethyl-4-bromobenzamide (2.0 g, 8.7 mmol) and 4-carboxybenzeneboronic acid (1.38 g, 8.3 mmol) as a white solid (1.46 g). MS (API): MH+ 268. Description 33 (D33) N-Methyl-3′-sulfonamido-1,1′-biphenyl-4-carboxylic acid Using the procedure outlined in Description 29, the title compound was prepared from N-methyl-3-bromobenzenesulfonamide (1 g, 4 mmol) and 4-carboxybenzeneboronic acid (0.56 g, 3.3 mmol) as a cream solid (0.93 g). MS (API): MH+ 290. Description 34 (D34) 2-(4-Pyridyl)furan-4-carboxylic acid Using the procedure outlined in Description 29, the title compound was prepared from 2-bromo-furan-4-carboxylic acid (S. W. En, M. C. Yuen, H. N. C. Wong, Tetrahedron, 1996, 52(37), 12137) and 4-pyridylboronic acid. The following acids may be prepared according to literature precedent: Description 35 (D35) 4′-Acetylamino-2′-methyl-1,1′-biphenyl-4-carboxylic acid L. M. Gaster, P. Ham, D. F. King and P. A. Wyman, International Patent Application, Publication Number WO 97/34901. Description 36 (D36) 2′-Methyl-1,1′-biphenyl-4-carboxylic acid S. I. Klein et al, J. Med. Chem., 1998, 41, 437. Description 37 (D37) 3′-Acetyl-1,1′-biphenyl-4-carboxylic acid G. Stemp and A. Johns, International Patent Application, Publication Number WO 97/43262. Description 38 (D38) 3′-Carboxamido-1,1′-biphenyl-4-carboxylic acid G. Stemp and A. Johns, International Patent Application, Publication Number WO 97/43262. Description 39 (D39) 3-Methyl-1,1′-biphenyl-4-carboxylic acid L. M. Gaster, International Patent Application, Publication Number WO 96/06079. Description 40 (D40) 2-Chloro-1,1′-biphenyl-4-carboxylic acid H. Ogawa et al, International Patent Application, Publication Number WO 9534540. Description 41 (D41) 3-(4-Carboxyphenyl)thiophene G. Stemp and A. Johns, International Patent Application, Publication Number WO 97/43262. Description 42 (D42) 2-(4-Carboxyphenyl)thiophene C. A. Axton et al, J. Chem. Soc., Perkin Trans. I, 1992, 2203. Description 43 (D43) 4-(4-Carboxyphenyl)-1-methylpyrazole G. Stemp and A. Johns, International Patent Application, Publication Number WO 97/43262. Description 44 (D44) 2-(4-Carboxyphenyl)pyrazine L. M. Gaster, H. K. Rami and P. A. Wyman, International Patent Application, Publication Number WO 98/50358. Description 45 (D45) 1-(3-Carboxyphenyl)pyrazole M. S. Hadley, C. N. Johnson, G. J. Macdonald, G. Stemp and A. K. K. Vong, International Patent Application, Publication Number WO 00/21951. Description 46 (D46) 5-Phenylthiophene-2-carboxylic acid J. K. Myers et al, International Patent Application, Publication Number WO 02/17358. Description 47 (D47) 3-(3-Pyridyl)benzoic acid U. Hacksell et al, J. Med. Chem., 1981, 24(12), 1475. Description 48 (D48) 6-Phenylnicotinic acid L. M. Gaster, H. K. Rami and P. A. Wyman, International Patent Application, Publication Number WO 98/50358. Description 49 (D49) 6-(4-Fluorophenyl)nicotinic acid S. A. Baumeister et al, International Patent Application, Publication Number WO 02/24636. Description 50 (D50) 4-(1-oxo-indan-5-yl)-benzoic acid G. Stemp and A. Johns, International Patent Application, Publication Number WO 97/43262. Description 51 (D51) 4′-Carboxamido-4-biphenylcarboxylic acid The title compound may be prepared from 4-carboxybenzeneboronic acid and 4-bromobenzamide using the procedure outlined in International Patent Application, Publication number WO 97/4326, for the synthesis of 3′-carboxamido-1,1′-biphenyl-4-carboxylic acid. Description 52 (D52) 4′-Acetyl-4-biphenylcarboxylic acid The title compound may be prepared from 4-carboxybenzeneboronic acid and 4-bromoacetophenone using the procedure outlined in International Patent Application, Publication number WO 97/4326, for the synthesis of 3′-carboxamido-1,1′-biphenyl-4-carboxylic acid. Description 53 (D53) 3-Methyl-4-(3-pyridyl)benzoic acid The title compound may be prepared from 4-carboxy-2-methylbenzeneboronic acid (International Patent Application, Publication number WO 97/34901) and 3-bromopyridine using the general procedure outlined in International Patent Application, Publication number WO 00/06085, for the synthesis of 4-(3-pyridyl)benzoic acid. Description 54 (D54) 7-Nitroquinoline To a solution of 7-nitro-1,2,3,4-tetrahydroquinoline (D1) (2.20 g, 12.3 mmol) in toluene (300 ml) was added 2,3-dichloro-5,6-dicyanobenzoquinone (5.88 g, 25.9 mmol) and the reaction was heated to 90° C. for 1.5 h. After cooling to room temperature, the suspension was filtered and the filtrate concentrated in vacuo to give the crude product which was purified by flash column chromatography. Elution with 30% EtOAc in 40-60° C. petroleum ether gave the title compound as a cream solid (1.74 g). 1H NMR (250 MHz, CDCl3) δ (ppm): 9.08 (dd, 1H), 8.98 (d, 1H), 8.30 (dd, 2H), 7.99 (d, 1H), 7.62 (dd, 1H). Description 55 (D55) 7-Aminoquinoline A mixture of 7-nitroquinoline (D54) (0.65 g, 3.71 mmol) and 10% palladium on charcoal (65 mg, 54% water) in methanol (20 ml) was hydrogenated at 1 atm. and ambient temperature for until complete by tlc. The catalyst was filtered off and washed with further methanol. The combined filtrated and washings were concentrated in vacuo to give the title compound as a brown solid (0.53 g). 1H NMR (400 MHz, CDCl3) δ (ppm): 8.75 (dd, 1H), 7.98 (dd, 1H), 7.62 (d, 1H), 7.21 (d, 1H), 7.14 (dd, 1H), 6.99 (dd, 1H), 4.07 (br, 2H). Description 56 (D56) 4-(2,6-Dimethyl-3-pyridyl)-benzoic acid The title compound was prepared according to L. M. Gaster, H. K. Rami and P. A. Wyman, International Patent Application, Publication Number WO 98/50358. Description 57 (D57) 3-Methyl-4-(4-pyridyl)-benzoic acid The title compound was prepared according to L. M. Gaster and P. A. Wyman, International Patent Application, Publication Number WO 98/50346. Description 58 (D58) 3-Methyl-1,1′-biphenyl-4-carboxylic acid The title compound may be prepared from 4-bromo-2-methylbenzoic acid and benzeneboronic acid using the procedure outlined in International Patent Application, Publication number WO 96/06079, for the synthesis of 2-methyl-1,1′-biphenyl-4-carboxylic acid. Description (D59) (D59) 3-Methoxy-1,1′-biphenyl-4-carboxylic acid The title compound may be prepared from 4-bromo-2-methoxybenzoic acid and benzeneboronic acid using the procedure outlined in International Patent Application, Publication number WO 96/06079, for the synthesis of 2-methyl-1,1′-biphenyl-4-carboxylic acid. Description 60 (D60) 2-Methyl-1,1′-biphenyl-4-carboxylic acid The title compound was prepared according to L. M. Gaster, International Patent Application, Publication Number WO 96/06079. Description 61 (D61) 4-(4-Carboxyphenyl)-piperazine-1-carboxylic acid tert-butyl ester The title compound was prepared according to M. E. Duggan et al, U.S. Pat. No. 5,854,245. Description 62 (D62) 3,5-Dimethyl-4-(4-methyl-benzo[1,3]dioxol-5-yl)-benzoic acid The title compound may be prepared using the procedure outlined in U.S. Pat. No. 6,323,227, for the synthesis of 4-(benzo[1,3]dioxol-5-yl)benzoic acid. Description 63 (D63) 2-Methyl-1,2,3,4-tetrahydroquinoline A mixture of 2-methylquinoline (584 mg, 4.1 mmol), indium powder (4.21 g, 36.7 mmol), saturated aqueous ammonium chloride solution (6.3 ml) and ethanol (21 ml) were heated at reflux for 3 days. On cooling to room temperature, water was added and the mixture was filtered through Keiselguhr. The filtrate was adjusted to pH 9 with 2M sodium hydroxide solution and extracted with DCM (×2). The extracts were dried over MgSO4 and concentrated in vacuo to give the crude product which was purified by flash column chromatography. Elution with 10% EtOAc in 60-80C petroleum ether gave the title compound as a pale yellow oil (383 mg). 1H NMR (400 MHz, CDCl3) δ (ppm): 6.96 (m, 2H), 6.60 (t, 1H), 6.47 (d, 1H), 3.68 (br, 1H), 3.40 (m, 1H), 2.84 (ddd, 1H), 2.72 (ddd, 1H), 1.92 (m, 1H), 1.60 (m, 1H), 1.21 (d, 3H). Description 64 (D64) 2-Methyl-7-nitro-1,2,3,4-tetrahydroquinoline To a solution of 2-methyl-1,2,3,4-tetrahydroquinoline (D63) (383 mg, 2.6 mmol) in concentrated sulfuric acid (7.2 ml) at 0-5° C. was added concentrated nitric acid (0.26 ml) dropwise so as to maintain the temperature at 0-5° C. On completion of addition, the mixture was warmed to room temperature, stirred for 45 mins. then poured onto crushed ice and neutralised with 2M sodium hydroxide solution. The mixture was extracted with DCM which was washed with brine, dried over MgSO4 and concentrated in vacuo to give the crude product which was purified by flash column chromatography. Elution with 10% EtOAc in 60-80° C. petroleum ether gave the title compound as an orange solid (297 mg). 1H NMR (400 MHz, CDCl3) δ (ppm): 7.40 (dd, 1H), 7.27 (d, 1H), 7.03 (d, 1H), 4.01 (br, 1H), 3.46 (m, 1H), 2.87 (m, 2H), 1.92 (m, 1H), 1.59 (m, 1H), 1.24 (d, 3H). Description 65 (D65) 7-Amino-2-methyl-1,2,3,4-tetrahydroquinoline Using the procedure outlined in Description 55, the title compound was prepared from 2-methyl-7-nitro-1,2,3,4-tetrahydroquinoline (D64) (100 mg, 0.52 mmol) as a crude oil, (86 mg) which was used directly in the next step without further purification. 1H NMR (400 MHz, CDCl3) δ (ppm): 6.74 (d, 1H), 6.01 (dd, 1H), 5.84 (d, 1H), 3.57 (br, 1H), 3.36 (m, 1H), 2.72 (ddd, 1H), 2.62 (ddd, 1H), 1.87 (m, 1H), 1.56 (m, 1H), 1.24 (d, 3H). Description 66 (D66) 7-Amino-2-methylquinoline A mixture of 7-amino-2-methyl-1,2,3,4-tetrahydroquinoline (D65) (86 mg) and wet 10% palladium/charcoal (25 mg) in xylene (20 ml) was heated at reflux for 3.5 h. After cooling to room temperature the catalyst was removed via filtration and washed with further xylene. Evaporation of the combined filtrate and washings gave the title compound as a crude off-white solid (87 mg) which was used in the next step without further purification. 1H NMR (400 MHz, CDCl3) δ (ppm): 7.87 (d, 1H), 7.56 (d, 1H), 7.14 (d, 1H), 7.03 (d, 1H), 6.91 (dd, 1H), 4.02 (br, 2H), 2.67 (s, 3H). Description 67 (D67) 4-(2-Pyridyl)-benzoic acid The title compound was prepared according to N. J. Anthony et al, International Patent Application, Publication Number WO 97/36896. Description 68 (D68) 3′-Dimethylsulfamoyl-1,1′-biphenyl-4-carboxylic acid The title compound may be prepared from 4-carboxybenzeneboronic acid and 3-bromo-1-(dimethylsulfamoyl)benzene using the procedure outlined in International Patent Application, Publication number WO 97/4326, for the synthesis of 3′-carboxamido-1,1′-biphenyl-4-carboxylic acid. Description 69 (D69) 4-Bromo-3-methoxy-N-quinolin-7-yl-benzamide Using the procedure outlined in Example 56, the title compound was prepared from 7-aminoquinoline (D55) (36 mg, 0.25 mmol) and 4-bromo-3-methoxybenzoic acid (69 mg, 0.3 mmol) as a white solid (84 mg). MS(ES): MH+ 357/359, M-H+ 355/357. Description 70 (D70) 6-Chloro-N-quinolin-7-yl-nicotinamide Using the procedure outlined in Example 45, the title compound was prepared from 7-aminoquinoline (D55) (213 mg, 1.48 mmol) and 6-chloronicotinic acid (279 mg, 1.77 mmol) as a cream solid (405 mg). 1H NMR (250 MHz, CDCl3) δ (ppm): 8.94 (m, 2H), 8.24 (m, 2H), 8.16 (d, 1H), 8.14 (br.s, 1H), 8.01 (dd, 1H), 7.87 (d, 1H), 7.51 (d, 1H), 7.39 (dd, 1H). Description 71 (D71) 9H-Fluorene-2-carboxylic acid The title compound was prepared according to A. Newman et al., Journal of Medicinal Chemistry, 2001, 44, 3175. Description 72 (D72F) 4-(2-Methyl-4-pyridyl)-benzoic acid The title compound was prepared according to L. M. Gaster, H. K. Rami and P. A. Wyman, International Patent Application, Publication Number WO 98/50358. Description 73G (D73G) 6-(3-Fluorophenyl)nicotinic acid The title compound may be prepared from 3-fluorophenylboronic acid using the procedure outlined in International Patent Application, Publication Number WO 02/24636, for the synthesis of 6-(4-fluorophenyl)nicotinic acid. Description 74 (D74) 6-(2-Fluorophenyl)nicotinic acid The title compound may be prepared from 2-fluorophenylboronic acid using the procedure outlined in International Patent Application, Publication Number WO 02/24636, for the synthesis of 6-(4-fluorophenyl)nicotinic acid. Description 75 (D75) Methyl 4′-fluoro-2-hydroxy-1,1′-biphenyl-4-carboxylate Methyl 4-bromo-3-hydroxybenzoate (2.1 g, 9.0 mmol), 4-fluorophenyl-boronic acid (2.52 g, 18 mmol), tetrakis(triphenylphosphine)palladium (0.52 g, 0.45 mmol), and 2M aqueous sodium carbonate solution (11 ml) in ethanol/toluene (1:5, 30 ml) were heated at reflux overnight. After cooling the solvent was removed in vacuo and the residue dissolved in EtOAc then washed with sat. aq. sodium bicarbonate and dried over MgSO4. The crude product was purified by column chromatography eluting with 1% MeOH/DCM giving the title compound as a solid (1.9 g). MS(ES): MH+ 247, M-H+ 245. Description 76 (D76) Methyl 4′-fluoro-2-(2-methoxyethoxy)-1,1′-biphenyl-4-carboxylate To a suspension of methyl 4′-fluoro-2-hydroxy-1,1′-biphenyl-4-carboxylate (D75) (400 mg, 1.6 mmol) in DMF (10 ml) was added cesium carbonate (1.27 g, 3.9 mmol) and 2-methoxyethylbromide (400 mg, 1.6 mmol) and the reaction was heated at 80° C. overnight. The solvent was evaporated and the residue was dissolved in EtOAc, washed with water and brine, then dried over MgSO4 to give the title compound (494 mg) which was used without further purification in the next step. MS(ES): (M-MeOH)H+ 273. Description 77 (D77) 4′-Fluoro-2-(2-methoxyethoxy)-1,1′-biphenyl-4-carboxylic acid Methyl 4′-fluoro-2-(2-methoxyethoxy)-1,1′-biphenyl-4-carboxylate (D76) (494 mg) was treated with aq. 2M sodium hydroxide solution (2 ml) in ethanol (3 ml) at 90° C. overnight. After cooling, the ethanol was evaporated off and the residue dissolved in EtOAc and extracted with sat. aq. sodium bicarbonate solution. This was acidified to pH3 with 2M HCl and extracted with EtOAc which was dried over MgSO4 and concentrated in vacuo to give the title compound as a solid (55 mg). MS(ES): M-H+ 289. Description 78 (D78) Methyl 2-(2-dimethylaminoethoxy)-4′-fluoro-1,1′-biphenyl-4-carboxylate Using the procedure outlined in Description 76, the title compound was prepared from 4′-fluoro-2-hydroxy-1,1′-biphenyl-4-carboxylate (D75) (150 mg, 0.61 mmol)) and 2-(dimethylamino)ethylchloride hydrochloride (114 mg, 0.79 mmol) as a crude gum (200 mg) which was used without further purification in the next step. MS(ES): MH+ 318. Description 79 (D79) 2-(2-Dimethylaminoethoxy)-4′-fluoro-1,1′-biphenyl-4-carboxylic acid Using the procedure outlined in Description 77, the title compound was prepared from methyl 2-(2-dimethylaminoethoxy)-4′-fluoro-1,1′-biphenyl-4-carboxylate (D78) (200 mg, 0.61 mmol)) and 2-(dimethylamino)ethylchloride hydrochloride (114 mg, 0.79 mmol) as a solid (122 mg). MS(ES): MH+ 304, M-H+ 302. Description 80 (D80) 5-Iodo-7-nitro-1-trifluoroacetyl-1,2,3,4-tetrahydroquinoline A solution of 7-nitro-1-trifluoroacteyl-1,2,3,4-tetrahydroquinoline (D4) (2 g, 7.3 mmol) in conc. sulfuric acid (10 ml) was cooled to 0° C. and treated with iodine (1.11 μg, 4.4 mmol) and potassium iodate (0.625 g, 2.9 mmol). The reaction was stirred at 0° C. for 3 h then room temperature for 2 h. The reaction mixture was slowly poured into water (150 ml) at 0° C. and extracted with DCM. This was washed with aq. sodium metabisulfite and water then dried over MgSO4 and concentrated in vacuo to give the crude product. Purification by column chromatography gave the title compound (420 mg). 1H NMR (250 MHz, CDCl3) δ (ppm): 8.59 (m, 2H), 3.86 (m, 2H), 2.90 (t, 2H), 2.17 (m, 2H). Description 81 (D81) 5-Chloro-7-nitro-1,2,3,4-tetrahydroquinoline A solution of 5-iodo-7-nitro-1-trifluoroacetyl-1,2,3,4-tetrahydroquinoline (D53P) (1.69 g, 6.73 mmol) in DMF (25 ml) was treated with copper (I) chloride (1.66 g, 16.8 mmol) at 130C. for 7 h. On cooling the solution was filtered and the filtrate concentrated in vacuo. The residue was dissolved in EtOAc and washed with 5M HCl, then dried over MgSO4 and concentrated in vacuo. The crude product was purified by column chromatography to give a (1:1) mixture of the title compound and 5-chloro-7-nitro-1-trifluoroacetyl-1,2,3,4-tetrahydroquinoline (591 mg). This mixture was treated with potassium carbonate in methanol to yield the title compound (450 mg) as a brown solid. 1H NMR (400 MHz, CDCl3) δ (ppm): 7.49 (d, 1H), 7.19 (d, 1H), 4.31 (br.s, 1H), 3.33 (m, 2H), 2.82 (t, 2H), 1.98 (m, 2H). Description 82 (D82) 5-Chloro-7-nitroquinoline Using the procedure outlined in Description 54, the title compound was prepared from 5-chloro-7-nitro-1,2,3,4-tetrahydroquinoline (D81) (60 mg, 0.28 mmol) as an off white solid (54 mg). 1H NMR (400 MHz, CDCl3) δ (ppm): 9.14 (d, 1H), 8.96 (d, 1H), 8.67 (d, 1H), 8.45 (d, 1H), 7.72 (dd, 1H). Description 83 (D83) 7-Amino-5-chloroquinoline 5-Chloro-7-nitroquinoline (D82) (50 mg, 0.24 mmol) was treated with tin dichloride dihydrate (216 mg, 0.96 mmol) and conc. hydrochloric acid (2 ml) in ethanol (5 ml) at 70° C. for 4 h. After cooling to room temperature and the ethanol removed in vacuo then the residue was dissolved in water and neutralised with potassium carbonate. This was then extracted with EtOAc which was dried over MgSO4 and concentrated in vacuo to give the title compound as a brown solid (18 mg). 1H NMR (400 MHz, CDCl3) δ (ppm): 8.78 (d, 1H), 8.39 (d, 1H), 7.25 (dd, 1H), 7.18 (d, 1H), 7.11 (d, 1H). Description 84 (D84) 4-(3-Chloro-2-pyridyl)-benzoic acid The title compound may be prepared from 4-carboxybenzeneboronic acid and 2,3-dichloropyridine using the procedure outlined in Description 29 (D29), for the synthesis of 4-(6-methyl-2-pyridyl)-benzoic acid. Description 85 (D85) Ethyl 6-(4-fluorophenyl)-2-(bromomethyl)nicotinate Ethyl 6-(4-fluorophenyl)-2-methylnicotinate (82 mg, 0.32 mmol), N-bromosuccinimide (67 mg, 0.38 mmol) and AIBN (5 mg, 0.032 mmol) in carbon tetrachloride (7 ml) were irradiated (150W lamp) for 6 h then cooled to room temperature. The solid was filtered off and the filtrate concentated and purified by SPE chromatography to give the title compound (38 mg) as a 5:1 mixture with the dibrominated product. 1H NMR (250 MHz, CDCl3) δ (ppm): 8.32 (d, 1H), 8.11 (dd, 2H), 7.68 (d, 1H), 7.15 (t, 2H), 5.09 (s, 2H), 4.45 (q, 2H), 1.45 (t, 3H). Description 86 (D86) 6-(4-Fluorophenyl)-2-(methoxymethyl)nicotinic acid Ethyl 6-(4-fluorophenyl)-2-(bromomethyl)nicotinate (D85) (38 mg, 0.11 mmol) was treated with sodium methoxide (18 mg, 0.34 mmol) in methanol (1 ml) at room temperature for 1 h. 2M Sodium hydroxide solution was then added and the solution stirred for 1 h. The mixture was diluted with water and extracted with EtOAc which was dried over MgSO4 and concentrated in vacuo to give the title compound as a white solid (19 mg). MS(ES): MH+ 262, M-H+ 260. Description 87 (D87) 4-(2-Methylthiazol-4-yl)-benzoic acid The title compound was prepared according to P. J. Sanfilippo et al, U.S. Pat. No. 5,342,851. Description 88 (D88) 7-Amino-1,4-dimethyl-1H-quinolin-2-one To a solution of 7-amino-4-methyl-1H-quinolin-2-one (87 mg, 0.5 mmol) in dry DMF (2 ml) was added sodium hydride (24 mg, 60% disp. in oil, 0.6 mmol) followed by methyl iodide (38 μl, 0.6 mmol) and the reaction stirred at room temperature for 1.5 h. After quenching with water the mixture was extracted with EtOAc and the combined extracts were dried over MgSO4 and concentrated in vacuo to give the crude product. Purification by SPE column chromatography, eluting with 0-10% MeOH/EtOAc gradient gave title compound (64 mg) which was used in the next step without further purification. 1H NMR (250 MHz, CDCl3) δ (ppm): 7.47 (d, 1H), 6.59 (m, 2H), 6.55 (d, 1H), 4.45 (br, 2H), 3.61 (s, 3H), 2.38 (s, 3H). Description 89 (D89) 7-Amino-1H-quinolin-2-one The title compound may be prepared from 7-nitro-1H-quinolin-2-one (M. Nasr et al, J. Med. Chem., 1988, 31(7), 1347) using the procedure outlined in Description 55 for the synthesis of 7-aminoquinoline. Description 90 (D90) N-(2,2-Dimethoxyethyl)-(1-phenyl)ethylamine A solution of α-methylbenzylamine (8.37 g, 0.069 mol) and bromoacetaldehyde dimethylacetal (11.67 g, 0.069 mol) in acetonitrile (150 ml) containing potassium carbonate (12.39 g, 0.09 mol) was heated at reflux for 2 days then cooled. The resulting precipitate was filtered off and the filtrate was concentrated in vacuo to give the crude product as an oil. Chromatography on silica gel eluting with ethyl acetate afforded the title compound as an oil (10.1 g). 1H NMR (400 MHz, CDCl3) δ(ppm): 7.31 (m, 3H), 7.23 (m, 2H), 4.43 (t, 1H), 3.75 (q, 1H), 3.35 (s, 3H), 3.31 (s, 3H), 2.63 (dd, 1H), 2.55 (dd, 1H), 1.36 (d, 3H). Description 91 (D91) 1-Methylisoquinoline To cooled chlorosulfonic acid (−10° C.) (16 ml) was cautiously added N-(2,2-dimethoxyethyl)-(1-phenyl)ethylamine (D90) (5 g, 0.024 mol) over a period of 2 h. The reaction was allowed to warm to ambient temperature and stirring continued for 3 d. The reaction was then poured into ice-water slurry (500 ml), basified using solid potassium carbonate followed by extraction with DCM. The organic phase was separated, dried over MgSO4, filtered and concentrated in vacuo to give the crude product as an oil. Chromatography on silica gel eluting with ethyl acetate afforded the title compound as a yellow oil (1.04 g). 1H NMR (400 MHz, CDCl3) δ (ppm): 8.40 (d, 1H), 8.13 (d, 1H), 7.81 (d, 1H), 7.68 (t, 1H), 7.60 (t, 1H), 7.51 (d, 1H), 2.97 (s, 3H). Description 92 (D92) 1-Methyl-5-nitroisoquinoline A solution 1-methylisoquinoline (D91) (1 g, 7 mmol) in sulfuric acid (2.5 ml) was cooled (<4° C.) and concentrated nitric acid (1 ml) was added over 10 mins. The reaction was stirred for 30 mins and then heated at 60° C. for 2 h. After cooling, the reaction mixture was poured into ice water slurry (100 ml) and basified using solid potassium carbonate followed by extraction with DCM. The organic phase was separated, dried over MgSO4, filtered and concentrated in vacuo to afford the product as a white solid (1.05 g). 1H NMR (400 MHz, DMSO) δ (ppm): 8.69 (d, 1H), 8.59 (m, 2H), 8.11 (d, 1H), 7.88 (t, 1H), 2.99 (s, 3H). Description 93 (D93) 1-Methyl-5-aminoisoquinoline A solution of 1-methyl-5-nitroquinoline (D92) (1.0 g, 5.32 mmol) in methanol (40 ml) with 10% palladium on charcoal (0.15 g), was hydrogenated at atmospheric pressure for 5 h. The catalyst was removed by filtration and the filtrate concentrated in vacuo affording a solid which was resuspended in ether and filtered off to give the title compound (0.82 g). 1H NMR (400 MHz, CDCl3) δ (ppm): 8.36 (d, 1H), 7.55 (d, 1H), 7.45 (d, 1H), 7.39 (t, 1H), 6.94 (d, 1H), 4.20 (br, 2H), 2.93 (s, 3H). Description 94 (D94) 4-Bromo-N-isoquinolin-5-ylbenzamide A solution of 5-aminoisoquinoline (800 mg, 5.54 mmol), 4-bromobenzoic acid (1.68 g, 8.3 mmol), (3-dimethylaminopropyl)-ethyl-carbodiimide hydrochloride (1.64 g, 8.3 mmol) and 4-dimethylaminopyridine (70 mg, 0.6 mmol) was stirred at room temperature overnight. The mixture was diluted with DCM, washed with saturated aqueous sodium bicarbonate solution and water, then dried over MgSO4 and concentrated in vacuo to give the crude product. Purification by flash column chromatography eluting with an EtOAc/40-60° C. pet. ether gradient gave the title compound as a white solid (1.48 g). 1H NMR (400 MHz, CDCl3) δ (ppm): 9.29 (br, 2H), 8.57 (d, 1H), 8.11 (d, 1H), 7.97, (d, 2H), 7.90 (d, 2H), 7.66 (m, 3H). Description 95 8-Aminoisoquinoline The title compound was prepared according to W. A. Denny et al, J. Med. Chem., 2002, 45(3), 740. Description 96 7-Aminoisoquinoline The title compound was prepared according to J. E. Macdonald et al., International Patent Application, Publication Number WO 97/06158. Description 97 6-Aminoisoquinoline The title compound was prepared according to J. G. Durant et al, European Patent Application, Publication Number EP266949. Description 98 7-Amino-8-chloro-4,4-dimethyl-1-trifluoroacetyl-1,2,3,4-tetrahydroquinoline To a stirred solution of 7-amino-4,4-dimethyl-7-1-trifluoroacetyl-1,2,3,4-tetrahydroquinoline (D28) (200 mg, 0.735 mmol) in DCM was added NCS (118 mg, 0.882 mmol), portion-wise over 15 mins. The reaction was stirred at room temperaure for 18 h. After this period, solvents were evaporated in vacuo and the residue purified by column chromatography (0-10% EtOAc/40-60° C. pet. ether) to give the product as a an oil (76 mg). 1H NMR (400 MHz, CDCl3) δ (ppm): 7.08 (d, 1H), 6.72 (d, 1H), 4.15-4.25 (m, 1H), 4.05-4.15 (m, 2H), 3.40-3.50 (m, 1H), 1.75-2.00 (m, 2H), 1.30 (d, 6H). Description 99 (R)-2-Methyl-4-(6-methyl-2-pyridyl)piperazine The title compound may be prepared from 2-bromo-6-methylpyridine using the procedure outlined in R. Bakthavalatcham, International Patent Application, Publication number WO 02/0822 for the synthesis of (R)-2-methyl-4-(3-trifluoromethyl-2-pyridyl)piperazine. Description 100 (D100) (R)-2-Methyl-4-(3-methyl-2-pyridyl)piperazine The title compound may be prepared from 2-bromo-3-methylpyridine using the procedure outlined in R. Bakthavalatcham, International Patent Application, Publication number WO 02/0822 for the synthesis of (R)-2-methyl-4-(3-trifluoromethyl-2-pyridyl)piperazine. Description 101 (D101) 1-(5-Trifluoromethlpyrid-2-yl)-piperidine-4-carboxylic acid The title compound may be prepared from 2-chloro-5-trifluoromethyl-pyridine and piperidine-4-carboxylic acid using the procedure outlined in German Patent Application, Publication number DE4234295 for the synthesis of 1-(5-cyanopyrid-2-yl)-piperidine-4-carboxylic acid. Description 102 (D102) 1-(6-Trifluoromethlpyrid-2-yl)-piperidine-4-carboxylic acid The title compound may be prepared from 2-chloro-6-trifluoromethyl-pyridine and piperidine-4-carboxylic acid using the procedure outlined in German Patent Application, Publication number DE4234295 for the synthesis of 1-(5-cyanopyrid-2-yl)-piperidine-4-carboxylic acid. Description 103 (D103) 5-Chloro-7-nitro-1-trifluoroacetyl-1,2,3,4-tetrahydroquinoline Using the procedure outlined in Description 4, the title compound was prepared from 5-chloro-7-nitro-1,2,3,4-tetrahydroquinoline (D81) (200 mg, 0.94 mmol) as an orange solid (285 mg). 1H NMR (400 MHz, CDCl3) δ (ppm): 8.58 (br.s, 1H), 8.15 (d, 1H), 3.88 (m, 2H), 3.00 (t, 2H), 2.19 (m, 2H). Description 104 (D104) 7-Amino-5-chloro-1-trifluoroacetyl-1,2,3,4-tetrahydroquinoline Using the procedure outlined in Description 83, the title compound was prepared from 5-chloro-7-nitro-1-trifluoroacetyl-1,2,3,4-tetrahydroquinoline (D103) (280 mg, 0.91 mmol) as a white solid (237 mg). 1H NMR (400 MHz, CDCl3) δ (ppm): 7.00 (br.s, 1H), 6.65 (d, 1H), 3.77 (m, 2H), 3.70 (br, 2H), 2.78 (t, 2H), 2.06 (m, 2H). Description 105 (D105) Ethyl 6-(2,4-difluorophenyl)-2-methylnicotinate The title compound was prepared from dimethylamino-(2,4-difluorophenyl)-propan-1-one and ethyl 3-aminocrotonate using the general procedure outlined in D18. 1H NMR (250 MHz, CDCl3) δ (ppm): 8.25 (d, 1H), 8.13 (dt, 1H), 7.67 (dd, 1H), 6.86-7.05 (m, 2H), 4.40 (q, 2H), 2.90 (s, 3H), 1.41 (t, 3H). Description 106 (D106) 6-(2,4-Difluorophenyl)-2-methylnicotinic acid Using the procedure outlined in Description 23, the title compound was prepared from ethyl 6-(2,4-difluorophenyl)-2-methylnicotinate (D105) (2.1 g, 7.6 mmol) as a yellow solid (1.4 g). 1H NMR (250 MHz, CDCl3) δ (ppm): 8.30 (d, 1H), 8.12 (dt, 1H), 7.66 (dd, 1H), 6.86-7.05 (m, 2H), 2.91 (s, 3H). Description 107 (D107) Ethyl 6-(3,4-difluorophenyl)-2-methylnicotinate The title compound was prepared from dimethylamino-(3,4-difluorophenyl)-propan-1-one and ethyl 3-aminocrotonate using the general procedure outlined in D18. 1H NMR (250 MHz, CDCl3) δ (ppm): 8.26 (d, 1H), 7.96 (ddd, 1H), 7.79 (m, 1H), 7.57 (d, 1H), 7.20-7.31 (m, 1H), 4.40 (q, 2H), 2.90 (s, 3H), 1.42 (t, 3H). Description 108 (D108) 6-(2,4-Difluorophenyl)-2-methylnicotinic acid Using the procedure outlined in Description 23, the title compound was prepared from ethyl 6-(2,4-difluorophenyl)-2-methylnicotinate (D105) (5.3 g, 19.1 mmol) as a yellow solid (1.8 g). 1H NMR (250 MHz, CDCl3) δ (ppm): 8.32 (d, 1H), 7.96 (ddd, 1H), 7.79 (m, 1H), 7.57 (d, 1H), 7.20-7.31 (m, 1H), 2.92 (s, 3H). EXAMPLES Example 1 N-(1-Methyl-1,2,3,4-tetrahydroquinolin-7-yl)-1,1′-biphenyl-4-carboxamide To a solution of 7-amino-1-methyl-1,2,3,4-tetrahydroquinoline (D3) (325 mg, 2 mmol) in DCM (10 ml) was added 4-biphenylcarboxylic acid (476 mg, 2.4 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (444 mg, 2.4 mmol) and the reaction stirred at ambient temperature. After 1 h the reaction mixture was filtered to give the title compound as a white solid. The filtrate was diluted with DCM, washed with sat. aq. sodium bicarbonate solution, dried over MgSO4 and concentrated in vacuo to give further crude product which was purified by silica SPE chromatography. Elution with an EtOAc/60-80° C. petroleum ether gradient gave a mixture of the title compound and the starting acid. These fractions were washed with further sat. aq. sodium bicarbonate solution, dried over MgSO4 and concentrated in vacuo to give further title compound as a white solid. 1H NMR (400 MHz, CDCl3) δ (ppm): 7.94 (d, 2H), 7.70 (m, 3H), 7.63 (d, 2H), 7.48 (t, 2H), 7.40 (t, 1H), 7.07 (d, 1H), 6.93 (d, 1H), 6.75 (dd, 1H), 3.25 (m, 2H), 2.94 (s, 3H), 2.76 (t, 2H), 1.98 (m, 2H). Example 2 N-(1-Methyl-1,2,3,4-tetrahydroquinolin-7-yl)-6-phenylnicotinamide To a solution of 6-phenylnicotinic acid (D48) (500 mg, 2.51 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (963 mg, 5.03 mmol) and 1-hydroxybenzotriazole hydrate (340 mg, 2.51 mmol) in DCM (20 ml) was added a solution of 7-amino-1-methyl-1,2,3,4-tetrahydroquinoline (D3) (407 mg, 2.51 mmol) in DCM (5 ml). The reaction mixture was stirred overnight then washed with sat. aq. sodium hydrogen carbonate solution (2×20 ml) and brine (20 ml). The organics were dried over MgSO4 and concentrated in vacuo to give the crude product which was purified by flash column chromatography. Elution with 10-20% EtOAc/DCM gave the title compound as a yellow solid. 1H NMR (250 MHz, CDCl3) δ (ppm): 9.14 (d, 1H), 8.25 (dd, 1H), 8.07 (m, 2H), 7.85 (d, 1H), 7.71 (br, 1H), 7.48 (m, 3H), 7.03 (br, 1H), 6.93 (d, 1H), 6.75 (dd, 1H), 3.25 (m, 2H), 2.93 (s, 3H), 2.75 (t, 2H), 1.98 (m, 2H). Examples 3-23 7-amino-1-methyl-1,2,3,4-tetrahydroquinoline (D3) (0.03 mmol) in DCM (0.5 ml) was reacted with the appropriate acid (D31-47, D50 & D51-53) (0.03 mmol) in DMF (0.25 ml) in the presence of hydroxybenzotriazole hydrate (0.06 mmol) and excess polymer supported 1,3-dicyclohexylcarbodiimide in 1:1 DCM/THF (0.5 ml). On completion, the resin was removed by filtration and the impurities removed by ion-exchange yielding the products given in Table 1. TABLE 1 Example Name MH+ 3 N′-Methyl-N-(1-methyl-1,2,3,4-tetrahydroquinolin-7-yl)-1,1′- 400 biphenyl-4,4′-dicarboxamide 4 4′-Acetamido-2′-methyl-N-(1-methyl-1,2,3,4-tetrahydroquinolin-7-yl)- 414 1,1′-biphenyl-4-carboxamide 5 N′,N′-Dimethyl-N-(1-methyl-1,2,3,4-tetrahydroquinolin-7- 414 yl)-1,1′-biphenyl-4,4′-dicarboxamide 6 2′-Methyl-N-(1-methyl-1,2,3,4-tetrahydroquinolin-7-yl)-1,1′- 357 biphenyl-4-carboxamide 7 3′-Acetyl-N-(1-methyl-1,2,3,4-tetrahydroquinolin-7-yl)-1,1′- 385 biphenyl-4-carboxamide 8 3′-(Methylsulfamoyl)-N-(1-methyl-1,2,3,4- 436 tetrahydroquinolin-7-yl)-1,1′-biphenyl-4-carboxamide 9 N-(1-Methyl-1,2,3,4-tetrahydroquinolin-7-yl)-1,1′-biphenyl- 386 4,4′-dicarboxamide 10 N-(1-Methyl-1,2,3,4-tetrahydroquinolin-7-yl)-1,1′-biphenyl- 386 3′,4-dicarboxamide 11 4′-Acetyl-N-(1-methyl-1,2,3,4-tetrahydroquinolin-7-yl)-1,1′- 385 biphenyl-4-carboxamide 12 2-Methyl-N-(1-methyl-1,2,3,4-tetrahydroquinolin-7-yl)-1,1′- 357 biphenyl-4-carboxamide 13 3-Chloro-N-(1-methyl-1,2,3,4-tetrahydroquinolin-7-yl)-1,1′- 377/379 biphenyl-4-carboxamide 14 N-(1-Methyl-1,2,3,4-tetrahydroquinolin-7-yl)-4-(3- 349 thienyl)benzamide 15 N-(1-Methyl-1,2,3,4-tetrahydroquinolin-7-yl)-4-(2- 349 thienyl)benzamide 16 4-(1-Methyl-4-pyrazolyl)-N-(1-methyl-1,2,3,4- 347 tetrahydroquinolin-7-yl)benzamide 17 3-Methyl-N-(1-methyl-1,2,3,4-tetrahydroquinolin-7-yl)-4-(3- 358 pyridyl)benzamide 18 N-(1-Methyl-1,2,3,4-tetrahydroquinolin-7-yl)-4-(2- 345 pyrazinyl)benzamide 19 N-(1-Methyl-1,2,3,4-tetrahydroquinolin-7-yl)-3-(1- 333 pyrazolyl)benzamide 20 N-(1-Methyl-1,2,3,4-tetrahydroquinolin-7-yl)-2-(4- 334 pyridyl)furan-4-carboxamide 21 N-(1-Methyl-1,2,3,4-tetrahydroquinolin-7-yl)-5- 349 phenylthiophene-2-carboxamide 22 N-(1-Methyl-1,2,3,4-tetrahydroquinolin-7-yl)-3-(3- 344 pyridyl)benzamide 23 N-(1-Methyl-1,2,3,4-tetrahydroquinolin-7-yl)-4-(1-oxo- 397 indan-5-yl)-benzamide Example 24 N-(1,2,3,4-Tetrahydroquinolin-7-yl)-1,1′-biphenyl-4-carboxamide To a solution of 7-amino-1-trifluoroacetyl-1,2,3,4-tetrahydroquinoline (D5) (1.17 g, 4.78 mmol) in DCM (20 ml) was added 4-biphenylcarboxylic acid (1.14 g, 5.73 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.06 g, 5.73 mmol) and 4-dimethylaminopyridine (70 mg, 0.57 mmol) and the reaction stirred at room temperature. After 3.75 h the reaction mixture was treated with 2M sodium hydroxide solution overnight. An acid/base work-up followed by flash column chromatography with an EtOAc/60-80° C. petroleum ether gradient gave the title compound as a beige solid. 1H NMR (250 MHz, CDCl3) δ (ppm): 7.91 (d, 2H), 7.63 (m, 5H), 7.47 (t, 2H), 7.41 (t, 1H), 7.11 (d, 1H), 6.91 (d, 1H), 6.61 (dd, 1H), 3.94 (br, 1H), 3.31 (m, 2H), 2.74 (t, 2H), 1.93 (m, 2H), 1.57 (br, 2H). Example 25 6-Phenyl-N-(1-trifluoroacetyl-1,2,3,4-tetrahydroquinolin-7-yl)nicotinamide To a solution of 7-amino-1-trifluoroacetyl-1,2,3,4-tetrahydroquinoline (D5) (122 mg, 0.5 mmol) in DCM (2 ml) was added 6-phenylnicotinic acid (D48) (119 mg, 0.6 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (111 mg, 0.6 mmol) and 4-dimethylaminopyridine (7 mg, 0.06 mmol) and the reaction stirred at ambient temperature for until complete by tlc. The mixture was then washed with 2M sodium hydroxide solution (1 ml), dried over magnesium sufate and concentrated in vacuo to give the crude product which was purified by silica SPE chromatography. Elution with 20% EtOAc/60-80° C. petroleum ether gave an off-white solid which was recrystallised from EtOAc/60-80° C. petroleum ether giving the title compound as a white solid. 1H NMR (250 MHz, CDCl3) δ (ppm): 9.10 (d, 1H), 8.20 (m, 2H), 8.04 (m, 2H), 7.86 (br, 1H), 7.82 (dd, 1H), 7.72 (br, 1H), 7.50 (m, 3H), 7.19 (1H, d), 3.84 (m, 2H), 2.84 (m, 2H), 2.06 (m, 2H). Example 26 N-(1,2,3,4-Tetrahydroquinolin-7-yl)-6-phenylnicotinamide 6-Phenyl-N-(1-trifluoroacetyl-1,2,3,4-tetrahydroquinolin-7-yl)nicotinamide (Example 25) (155 mg, 0.364 mmol) and potassium carbonate (252 mg, 1.82 mmol) in water (2 ml) and methanol (8 ml) was stirred at ambient temperature for 40 mins. The resulting suspension was filtered and the solid was washed with water then dried in vacuo to give the title compound as a white solid. 1H NMR (250 MHz, CDCl3) δ (ppm): 9.11 (m, 1H), 8.22 (dd, 1H), 8.03 (m, 2H), 7.82 (d, 1H), 7.75 (br, 1H), 7.48 (m, 3H), 7.06 (d, 1H), 6.91 (d, 1H), 6.62 (dd, 1H), 3.95 (br, 1H), 3.30 (m, 2H), 2.73 (t, 2H), 1.93 (m, 2H). Example 27 N-(1-Acetyl-1,2,3,4-tetrahydroquinolin-7-yl)-1,1′-biphenyl-4-carboxamide To a solution of N-(1,2,3,4-tetrahydroquinolin-7-yl)-1,1′-biphenyl-4-carboxamide (Example 24) (66 mg, 0.2 mmol) in DCM (1 ml) was added triethylamine (42 ul, 0.3 mmol) followed by acetyl chloride (20.5 ul, 0.3 mmol). The reaction was stirred at ambient temperature for 15 mins then treated with polymer supported trisamine resin (31 mg, 0.1 mmol) and polymer supported isocyanate resin (20 mg, 0.04 mmol). After 5 mins the resins were removed by filtration and the filtrate was washed with 2M hydrochloric acid, dried over MgSO4 and concentrated in vacuo to give the title compound as an off-white solid. 1H NMR (250 MHz, CDCl3) δ (ppm): 7.94 (d, 2H), 7.84 (d, 1H), 7.78 (br, 1H), 7.72 (d, 2H), 7.64 (d, 2H), 7.45 (m, 4H), 7.15 (d, 1H), 3.80 (t, 2H), 2.74 (t, 2H), 2.33 (s, 3H), 1.98 (qn, 2H). Example 28 N-(1-Methoxyacetyl-1,2,3,4-tetrahydroquinolin-7-yl)-1,1′-biphenyl-4-carboxamide Using the procedure outlined in Example 27, the title compound was prepared from N-(1,2,3,4-tetrahydroquinolin-7-yl)-1,1′-biphenyl-4-carboxamide (Example 24) (66 mg, 0.2 mmol) and methoxyacetyl chloride (27.5 ul, 0.3 mmol) as a pale pink solid. 1H NMR (250 MHz, CDCl3) δ (ppm): 8.09 (br, 1H), 7.97 (d, 2H), 7.80 (s, 1H), 7.71 (d, 2H), 7.64 (d, 2H), 7.45 (m, 4H), 7.16 (d, 1H), 4.31 (s, 2H), 3.79 (t, 2H), 3.46 (s, 3H), 2.74 (t, 2H), 1.98 (t, 2H). Examples 29 & 30 N-[1-(2-Acetoxyethyl)-1,2,3,4-tetrahydroquinolin-7-yl]-1,1′-biphenyl-4-carboxamide & N-[1-(2-Acetoxyethyl)-6-bromo-1,2,3,4-tetrahydroquinolin-7-yl]-1,1′-biphenyl-4-carboxamide N-(1,2,3,4-Tetrahydroquinolin-7-yl)-1,1′-biphenyl-4-carboxamide (Example 24) (66 mg, 0.2 mmol), potassium carbonate (164 mg, 1.2 mmol) and 2-bromoethyl acetate (132 ul, 1.2 mmol) in dimethylformamide (1 ml) were heated at 800C for 20 h then 1200C for 24 h. Further 2-bromoethyl acetate (132 ul, 1.2 mmol) was added and heating was continued at 1200C for 20 h. After cooling to ambient temperature the reaction mixture was diluted with EtOAc (10 ml), filtered and concentrated in vacuo to give the crude product which was purified by silica SPE chromatography. Elution with 10% EtOAc/60-80° C. petroleum ether gave the 6-bromo-title compound (Example 30) as a yellow gum. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.38 (br, 1H), 8.01 (s, 1H), 8.00 (d, 2H), 7.73 (d, 2H), 7.64 (d, 2H), 7.48 (t, 2H), 7.40 (t, 1H), 7.10 (s, 1H), 4.34 (t, 2H), 3.62 (t, 2H), 3.36 (m, 2H), 2.72 (m, 2H), 2.06 (s, 3H), 1.93 (m, 2H). MS(ES): MH+ 493/495. Elution with 15% EtOAc/60-80° C. petroleum ether gave the non-brominated title compound (Example 29) as a white solid. 1H NMR (400 MHz, CDCl3) δ (ppm): 7.94 (d, 2H), 7.75 (br, 1H), 7.70 (d, 2H), 7.63 (d, 2H), 7.48 (t, 2H), 7.40 (t, 1H), 7.15 (d, 1H), 6.92 (d, 1H), 6.74 (dd, 1H), 4.30 (t, 2H), 3.57 (t, 2H), 3.36 (m, 2H), 2.74 (t, 2H), 2.06 (s, 3H), 1.94 (m, 2H). Example 31 N-[1-(2-Methoxycarbonylethyl)-1,2,3,4-tetrahydroquinolin-7-yl]-1,1′-biphenyl-4-carboxamide Using the procedure outlined in Example 29, the title compound was prepared from N-(1,2,3,4-tetrahydroquinolin-7-yl)-1,1′-biphenyl-4-carboxamide (Example 24) (66 mg, 0.2 mmol) and methyl 3-bromopropionate (264 ul, 2.4 mmol) as a yellow gum. 1H NMR (400 MHz, CDCl3) δ (ppm): 7.94 (d, 2H), 7.76 (br, 1H), 7.70 (d, 2H), 7.63 (d, 2H), 7.48 (t, 2H), 7.40 (t, 1H), 7.04 (d, 1H), 6.93 (d, 1H), 6.79 (dd, 1H), 3.69 (s, 3H), 3.65 (t, 2H), 3.31 (m, 2H), 2.72 (t, 2H), 2.67 (t, 2H), 1.93 (m, 2H). Example 32 N-[1-(2-Hydroxyethyl)-1,2,3,4-tetrahydroquinolin-7-yl]-1,1′-biphenyl-4-carboxamide N-(1,2,3,4-Tetrahydroquinolin-7-yl)-1,1′-biphenyl-4-carboxamide (Example 24) (100 mg, 0.304 mmol), potassium carbonate (126 mg, 0.913 mmol), sodium iodide (9 mg, 0.06 mmol) and 2-bromoethanol (216 ul, 3.04 mmol) in dioxane (1 ml) were heated at 60° C. for 8 d. After cooling to ambient temperature the reaction mixture was diluted with EtOAc (10 ml), filtered and concentrated in vacuo to give the crude product which was purified on a silica SPE column. Elution with an EtOAc/60-80° C. petroleum ether gradient gave the title compound as a beige solid. 1H NMR (400 MHz, CDCl3) δ (ppm): 7.93 (d, 2H), 7.78 (s, 1H), 7.70 (d, 2H), 7.63 (d, 2H), 7.48 (t, 2H), 7.40 (t, 1H), 7.19 (d, 1H), 6.93 (d, 1H), 6.74 (dd, 1H), 3.87 (m, 2H), 3.49 (t, 2H), 3.35 (m, 2H), 2.75 (t, 2H), 1.97 (m, 3H). Example 33 N-[1-(2-n-Propyloxyethyl)-1,2,3,4-tetrahydroquinolin-7-yl]-1,1′-biphenyl-4-carboxamide N-(1,2,3,4-Tetrahydroquinolin-7-yl)-1,1′-biphenyl-4-carboxamide (Example 24) (66 mg, 0.2 mmol), potassium carbonate (41 mg, 0.3 mmol), potassium iodide (100 mg, 0.6 mmol) and 2-chloroethyl-n-propyl ether (38 ul, 0.3 mmol) in DMF (1 ml) were heated at 60° C. for 17 h then 100° C. for 48 h. After cooling to ambient temperature the reaction mixture was purified on a silica SPE column. Elution with 8% EtOAc/60-80° C. petroleum ether gave the title compound as a yellow solid. 1H NMR (250 MHz, CDCl3) δ (ppm): 7.93 (d, 2H), 7.72 (br, 1H), 7.70 (d, 2H), 7.63 (d, 2H), 7.48 (t, 2H), 7.40 (t, 1H), 7.03 (d, 1H), 6.92 (d, 1H), 6.74 (dd, 1H), 3.66 (t, 2H), 3.50 (t, 2H), 3.40 (m, 4H), 2.73 (t, 2H), 1.93 (qn, 2H), 1.58 (sx, 2H), 0.91 (t, 3H). Example 34 N-[1-(2-Methoxyethyl)-1,2,3,4-tetrahydroquinolin-7-yl]-1,1′-biphenyl-4-carboxamide To a solution of 7-amino-1-(2-methoxyethyl)-1,2,3,4-tetrahydroquinoline (D13) (72 mg, 0.35 mmol) in DCM (2.5 ml) was added 4-biphenylcarboxylic acid (104 mg, 0.53 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (97 mg, 0.53 mmol) and 4-dimethylaminopyridine (6 mg, 0.05 mmol) and the reaction stirred at ambient temperature overnight. The mixture was diluted with DCM, washed with 2M sodium hydroxide solution, dried over MgSO4 and concentrated in vacuo to give the crude product which was purified by silica SPE chromatography. Elution with 20% EtOAc/60-80° C. petroleum ether gave the title compound as a pale yellow solid. 1H NMR (250 MHz, CDCl3) δ (ppm): 7.93 (d, 2H), 7.77 (br, 1H), 7.69 (d, 2H), 7.62 (d, 2H), 7.47 (t, 2H), 7.39 (t, 1H), 7.06 (d, 1H), 6.91 (d, 1H), 6.73 (dd, 1H), 3.63 (t, 2H), 3.49 (t, 2H), 3.37 (s, 3H), 3.36 (t, 2H), 2.73 (t, 2H), 1.91 (m, 2H). Example 35 N-[1-(2-Dimethylaminoethyl)-1,2,3,4-tetrahydroquinolin-7-yl]-4-biphenyl-carboxamide To a solution of 7-amino-1-(2-dimethylaminoethyl)-1,2,3,4-tetrahydroquinoline (D14) (38 mg, 0.152 mmol) in DCM (1 ml) was added 4-biphenylcarboxylic acid (45 mg, 0.22 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (42 mg, 0.22 mmol) and 4-dimethylaminopyridine (2.8 mg, 0.022 mmol) and the reaction stirred at ambient temperature overnight. The crude reaction mixture was loaded directly onto a silica SPE column and elution with EtOAc followed by 1% triethylamine/EtOAc gave the title compound as a red gum. 1H NMR (250 MHz, CDCl3) δ (ppm): 7.94 (d, 2H), 7.75 (br, 1H), 7.70 (d, 2H), 7.64 (d, 2H), 7.47 (t, 2H), 7.39 (t, 1H), 7.01 (d, 1H), 6.92 (d, 1H), 6.82 (dd, 1H), 3.43 (m, 2H), 3.33 (m, 2H), 2.73 (t, 2H), 2.55 (m, 2H), 2.33 (s, 6H), 1.95 (m, 2H). Example 36 N-[1-(2-Diisopropylaminoethyl)-1,2,3,4-tetrahydroquinolin-7-yl]-1,1′-biphenyl-4-carboxamide 7-Amino-1-(2-diisopropylaminoethyl)-1,2,3,4-tetrahydroquinoline (D15) (100 mg, 0.36 mmol), 4-biphenylcarbonyl chloride (258 mg, 1.11 mmol) and pyridine (0.5 ml, 6.2 mmol) in DCM (5 ml) were stirred at room temperatue for 4 hours. 10% Potassium carbonate solution was then added and the mixture extracted with DCM which was dried over MgSO4 and concentrated in vacuo to give the crude product. Purification by flash column chromatography eluting with 0-5% methanol/DCM gave the title compound as an off-white solid. 1H NMR (400 MHz, CDCl3) δ (ppm): 7.92 (d, 2H), 7.71 (d, 2H), 7.63 (m, 3H), 7.47 (t, 2H), 7.41 (t, 1H), 6.99 (br, 1H), 6.90 (d, 1H), 6.74 (d, 1H), 3.37 (m, 2H), 3.30 (m, 2H), 3.05 (sp, 2H), 2.72 (t, 2H), 2.66 (m, 2H), 1.93 (m, 2H), 1.05 (d, 12H). Example 37 N-[1-(2-Morpholin-4-ylethyl)-1,2,3,4-tetrahydroquinolin-7-yl]-1,1′-biphenyl-4-carboxamide Using the procedure outlined in Example 35, the title compound was prepared from 7-amino-1-(2-morpholin-4-ylethyl)-1,2,3,4-tetrahydroquinoline (D17) (0.1 mmol) and 4-biphenylcarboxylic acid (24 mg, 0.12 mmol) as a red gum. 1H NMR (250 MHz, CDCl3) δ (ppm): 7.94 (d, 2H), 7.86 (br, 1H), 7.69 (d, 2H), 7.62 (d, 2H), 7.50 (t, 2H), 7.39 (t, 1H), 7.13 (d, 1H), 6.91 (d, 1H), 6.78 (dd, 1H), 3.75 (m, 4H), 3.46 (m, 2H), 3.33 (m, 2H), 2.80-2.40 (m, 8H), 1.92 (qn, 2H). Example 38 6-(4-Fluorophenyl)-N-(1,2,3,4-tetrahydroquinolin-7-yl)nicotinamide To a solution of 7-amino-1-trifluoroacetyl-1,2,3,4-tetrahydroquinoline (D5) (46 mg, 0.19 mmol) in DCM (1 ml) was added 6-(4-fluorophenyl)nicotinic acid (D49) (41 mg, 0.19 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (44 mg, 0.23 mmol) and 4-dimethylaminopyridine (11 mg, 0.09 mmol) and the reaction stirred at ambient temperature overnight. The crude reaction mixture was purified on a silica SPE column eluting with 0-2% methanol/DCM to give the 1-trifluoroacetyl-intermediate. This was treated with potasium carbonate (52 mg, 0.38 mmol) in methanol (2 ml) until tlc showed complete deprotection. The reaction mixture was diluted with water and extracted with DCM which was dried over MgSO4, concentrated in vacuo and purified on a silica SPE column to give the title compound as a solid. 1H NMR (250 MHz, CDCl3) δ (ppm): 9.09 (d, 1H), 8.23 (dd, 1H), 8.06 (dd, 2H), 7.81 (d, 1H), 7.64 (br, 1H), 7.19 (t, 2H), 7.07 (br, 1H), 6.92 (d, 1H), 6.62 (dd, 1H), 3.95 (br, 1H), 3.32 (m, 2H), 2.74 (t, 2H), 1.94 (m, 2H). Example 39 6-(4-Fluorophenyl)-2-methyl-N-(1,2,3,4-tetrahydroquinolin-7-yl)nicotinamide Using the procedure outlined in Example 38 the title compound was prepared from 7-amino-1-trifluoroacetyl-1,2,3,4-tetrahydroquinoline (D5) (46 mg, 0.19 mmol) and 2-methyl-6-(4-fluorophenyl)-nicotinic acid (D24) (44 mg, 0.19 mmol) as a solid. 1H NMR (250 MHz, CDCl3) δ (ppm): 8.01 (dd, 1H), 7.81 (d, 1H), 7.56 (d, 1H), 7.29 (br, 1H), 7.16 (t, 2H), 7.08 (br, 1H), 6.91 (d, 1H), 6.57 (br, 1H), 3.96 (br, 1H), 3.31 (m, 2H), 2.74 (t, 2H), 1.94 (m, 2H). Example 40 N-(4,4-Dimethyl-1,2,3,4-tetrahydroquinolin-7-yl)-4-(3-chloro-2-pyridyl)-piperazine-1-carboxamide To a stirred solution of 7-amino-4,4-dimethyl-1-trifluoroacetyl-1,2,3,4-tetra-hydroquinoline (D28) (75 mg, 0.373 mmol) and pyridine (33 ul, 0.410 mmol) in DCM (5 ml) was added phenylchloroformate (51 ul, 0.410 mmol). The reaction mixture was stirred for 1 h at ambient temperature before triethylamine (57 ul, 0.410 mmol) was added and then left to stir for a further 30 min. After this period, 4-(3-chloro-2-pyridyl)-piperazine (U.S. Pat. No. 4,456,604) (74 mg, 0.373 mmol) in DCM (5 ml) was added and the reaction stirred at ambient temperature for 18 h. On completion, the solvents were evaporated in vacuo and the residue purified directly by chromatography, eluting with 10-100% EtOAc/40-60° C. petroleum ether, to give N-(4,4-dimethyl-1-trifluoroacetyl-1,2,3,4-tetrahydroquinol-7-yl)-4-(3-chloro-2-pyridiyl)-piperazine-1-carboxamide as a colourless oil. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.20 (dd 1H), 7.62 (dd, 1H), 7.50-7.55 (br, 1H), 7.40-7.45 (Br, 1H), 7.30 (d, 1H), 6.89 (dd, 1H), 6.42 (br, 1H), 3.80-3.85 (m, 2H), 3.60-3.65 (m, 4H), 3.40-3.45 (m, 4H), 1.33 (s, 6H). MS (ES): MH+ 496/498. A suspension of N-(4,4-dimethyl-1-trifluoroacetyl-1,2,3,4-tetrahydroquinol-7-yl)-4-(3-chloro-2-pyridyl)-piperazine-1-carboxamide (125 mg, 0.253 mmol) and potassium carbonate (105 mg, 0.758 mmol) in methanol (5 ml) and water (5 ml) was heated at 50° C. for 3 h. After this period, the solvents were evaporated in vacuo and the residue partitioned between DCM (50 ml) and water (50 ml). The aqueous layer was re-extracted with DCM (2×50 ml) and then the combined organic layers dried (Na2SO4) and the solvents evaporated in vacuo to give the title compound as a white solid. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.19 (dd, 1H), 7.61 (dd, 1H), 7.07 (d, 1H), 6.87 (dd, 1H), 6.75 (d, 1H), 6.41 (dd, 1H), 6.19 (br, 1H), 3.85-3.95 (br, 1H), 3.60-3.70 (m, 4H), 3.30-3.40 (m, 4H), 3.25-3.35 (m, 2H), 1.65-1.75 (m, 2H), 1.26 (s, 6H). MS (ES): MH+ 400/402. Example 41 N-(4,4-Dimethyl-1,2,3,4-tetrahydroquinolin-7-yl)-4-(3-trifluoromethyl-2-pyridyl)-piperazine-1-carboxamide To a stirred solution of 7-amino-4,4-dimethyl-1-trifluoroacetyl-1,2,3,4-tetrahydroquinoline (D28) (50 mg, 0.233 mmol) and triethylamine (65 ul, 0.465 mmol) in DCM (2 ml) at 0° C. was added triphosgene (23 mg, 0.077 mmol). The reaction mixture was stirred for 2 min at 0° C. and then at ambient temperature for 20 min. After this period, 4-(3-trifluoromethyl-2-pyridyl)-piperazine (54 mg, 0.233 mmol) in DCM (1 ml) was added and the reaction stirred at ambient temperature for 18 h. On completion, the solvents were evaporated in vacuo and the residue purified directly by chromatography, eluting with 10-100% EtOAc/40-60° C. petroleum ether, to give N-(4,4-dimethyl-1-trifluoroacetyl-1,2,3,4-tetrahydroquinol-7-yl)-4-(3-trifluoromethyl-2-pyridiyl)-piperazine-1-carboxamide as a colourless oil. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.46 (dd 1H), 7.89 (dd, 1H), 7.50-7.455 (br-s, 1H), 7.40-7.45 (m, 1H), 7.27 (d, 1H), 7.05 (dd, 1H), 6.57 (s, 1H), 3.80-3.85 (m, 2H), 3.60-3.65 (m, 4H), 3.25-3.35 (m, 4H), 1.85-1.90 (m, 2H), 1.33 (s, 6H). MS (ES): MH+ 530. A suspension of N-(4,4-dimethyl-1-trifluoroacetyl-1,2,3,4-tetrahydroquinol-7-yl)-4-(3-trifluoromethyl-2-pyridyl)-piperazine-1-carboxamide (50 mg, 0.0955 mmol) and potassium carbonate (40 mg, 0.287 mmol) in methanol (5 ml) and water (5 ml) was heated at 60° C. for 4 h. After this period, the solvents were evaporated in vacuo and the residue partitioned between DCM (50 ml) and water (30 ml). The aqueous layer was re-extracted with DCM (3×50 ml) and then the combined organic layers dried (Na2SO4) and the solvents evaporated in vacuo to give the title compound as a white solid. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.45 (dd, 1H), 7.90 (dd, 1H), 7.00-7.05 (m, 2H), 6.70 (d, 1H), 6.70 (d, 1H), 6.43 (dd, 1H), 6.32 (br-s, 1H), 3.60-3.65 (br, 4H), 3.20-3.30 (m, 6H), 1.65-1.70 (m, 2H), 1.26 (s, 6H). MS (ES): MH+ 434. Example 42 N-(4,4-Dimethyl-1,2,3,4-tetrahydroquinolin-7-yl)-4-(3-methyl-2-pyridyl)-piperazine-1-carboxamide To a stirred solution of 7-amino-4,4-dimethyl-1-trifluoroacetyl-1,2,3,4-tetrahydroquinoline (D28) (75 mg, 0.276 mmol) and triethylamine (56 ul, 0.551 mmol) in DCM (3 ml) at 0° C. was added triphosgene (27 ul, 0.092 mmol). The reaction mixture was stirred for 2 min at 0° C. and then at ambient temperature for 20 min. After this period, 4-(3-methyl-2-pyridyl)-piperazine (D100) (49 mg, 0.276 mmol) in DCM (2 ml) was added and the reaction stirred at ambient temperature for 18 h. On completion, the solvents were evaporated in vacuo and the residue purified directly by chromatography, eluting with 10-100% EtOAc/40-60° C. petroleum ether, to give N-(4,4-dimethyl-1-trifluoroacetyl-1,2,3,4-tetrahydroquinol-7-yl)-4-(3-methyl-2-pyridiyl)-piperazine-1-carboxamide as a colourless oil. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.16 (dd 1H), 7.50-7.55 (br, 1H), 7.40-7.45 (m, 2H), 7.26 (d, 1H), 6.89 (dd, 1H), 6.60 (br, 1H), 3.80-3.85 (m, 2H), 3.60-3.65 (m, 4H), 3.15-3.20 (m, 4H), 1.85-1.90 (m, 2H), 1.33 (s, 6H). MS (ES): MH+ 476. A suspension of N-(4,4-dimethyl-1-trifluoroacetyl-1,2,3,4-tetrahydroquinol-7-yl)-4-(3-methyl-2-pyridyl)-piperazine-1-carboxamide (100 mg, 0.210 mmol) and potassium carbonate (87 mg, 0.631 mmol) in methanol (5 ml) and water (5 ml) was heated at 60° C. for 3 h. After this period, the solvents were evaporated in vacuo and the residue partitioned between DCM (15 ml) and water (10 ml). The aqueous layer was re-extracted with DCM (2×15 ml) and then the combined organic layers dried (Na2SO4) and the solvents evaporated in vacuo to give the title compound as a white solid. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.16 (dd, 1H), 7.43 (dd, 1H), 7.05 (d, 1H), 6.88 (dd, 1H), 6.75 (d, 1H), 6.44 (dd, 1H), 6.29 (br, 1H), 3.85-3.95 (br, 1H), 3.55-3.65 (m, 4H), 3.25-3.30 (m, 2H), 3.15-3.25 (m, 4H), 2.29 (s, 3H), 1.65-1.70 (m, 2H), 1.26 (s, 6H). MS (ES): MH+ 380. Example 43 N-(8-Chloro-4,4-dimethyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-(3-chloro-2-pyridyl)-piperazine-1-carboxamide Using the procedure outlined in Example 42, the title compound was prepared from 7-amino-8-chloro-4,4-dimethyl-1-trifluoroacetyl-1,2,3,4-tetrahydroquinoline (D98) and 4-(3-chloro-2-pyridyl)-piperazine (U.S. Pat. No. 4,456,604), as a pale yellow oil. MH+ 434/436 Example 44 4-(6-Methyl-2-pyridyl)-N-(1,2,3,4-tetrahydroquinolin-7-yl)benzamide Using the procedure outlined in Example 38 the title compound was prepared from 7-amino-1-trifluoroacetyl-1,2,3,4-tetrahydroquinoline (D5) (46 mg, 0.19 mmol) and 4-(6-methyl-2-pyridyl)benzoic acid (D29) (41 mg, 0.19 mmol) as a solid. 1H NMR (250 MHz, CDCl3) δ (ppm): 8.10 (d, 2H), 7.93 (d, 2H), 7.67 (t, 2H), 7.57 (d, 1H), 7.15 (d, 1H), 7.11 (d, 1H), 6.92 (d, 1H), 6.62 (dd, 1H), 3.31 (m, 2H), 2.74 (t, 2H), 1.93 (m, 2H) Example 45 6-(4-Fluorophenyl)-N-(1-methyl-1,2,3,4-tetrahydroquinolin-7-yl)-2-methyl-nicotinamide To a solution of 7-amino-1-methyl-1,2,3,4-tetrahydroquinoline (D3) (31 mg, 0.19 mmol) in DCM (1 ml) was added 6-(4-fluorophenyl)-2-methylnicotinic acid (D24) (44 mg, 0.19 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (44 mg, 0.23 mmol) and 4-dimethylaminopyridine (11 mg, 0.09 mmol) and the reaction stirred at ambient temperature overnight. The crude reaction mixture was loaded directly onto a silica SPE column and eluted with 0-2% methanol/DCM to give the title compound as a solid. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.02 (dd, 2H), 7.84 (d, 1H), 7.57 (d, 1H), 7.35 (br, 1H), 7.17 (t, 2H), 7.00 (s, 1H), 6.93 (d, 1H), 6.74 (d, 1H), 3.25 (m, 2H), 2.93 (s, 3H), 2.80 (s, 3H), 2.74 (m, 2H), 1.96 (m, 2H) Example 46 N-(3,4-Dihydro-2H-1,4-ethanoquinolin-7-yl)-6-(4-fluorophenyl)-2-methyl-nicotinamide Using the procedure outlined in Example 45 the title compound was prepared from 3,4-dihydro-2H-1,4-ethanoquinolin-7-ylamine (D30) (35 mg, 0.2 mmol) and 6-(4-fluorophenyl)-2-methylnicotinic acid (D24) (46 mg, 0.2 mmol) as a solid. MS (ES): MH+ 388, MH− 386. Example 47 (R)-2-Methyl-4-(3-trifluoromethyl-2-pyridyl)-N-(1-methyl-1,2,3,4-tetrahydro-quinolin-7-yl) piperazine-1-carboxamide To a solution of 7-amino-1-methyl-1,2,3,4-tetrahydroquinoline (D3) (300 mg, 1.85 mmol) in DCM (5 ml) was added pyridine (164 ul, 2 mmol) followed by phenyl chloroformate (255 ul, 2 mmol) and the solution stirred at ambient temperature for 50 mins. Triethylamine (516 μl 3.7 mmol) was then added followed by a solution of (R)-2-methyl-4-(3-trifluoromethyl-2-pyridyl)piperazine (D22) (454 mg, 1.85 mmol) in DCM (5 ml) and the reaction stirred at ambient temperature until complete by tlc. The reaction mixture was washed (1M HCl, brine), dried over MgSO4 and concentrated in vacuo to give the crude product which was purified by flash chromatography, eluting with an EtOAc/40-60° C. petroleum ether gradient, to give the title compound as a white solid. 1H NMR (250 MHz, CDCl3) δ (ppm): 8.47 (dd, 1H), 7.90 (dd, 1H), 7.05 (dd, 1H), 6.84 (d, 1H), 6.78 (d, 1H), 6.49 (dd, 1H), 6.25 (br, 1H), 4.34 (m, 1H), 3.86 (m, 1H), 3.17-3.62 (m, 6H), 3.05 (m, 1H), 2.89 (s, 3H), 2.70.(t, 2H), 1.96 (m, 2H), 1.36 (d, 3H). MS (ES): MH+ 434. Example 48 N-(1-Methyl-1,2,3,4-tetrahydroquinolin-6-yl)-1,1′-biphenyl-4-carboxamide Using the procedure outlined in Example 25, the title compound was prepared from N-methyl-6-amino-1,2,3,4-tetrahydroquinoline (International Patent Application, Publication number WO 94/14801) (75 mg, 0.46 mmol) and 4-biphenylcarboxylic acid (140 mg, 0.71 mmol) as a yellow gum. 1H NMR (250 MHz, CDCl3) δ (ppm): 8.03 (d, 2H), 7.6-7.8 (m, 5H), 7.4-7.55 (m, 3H), 7.2-7.35 (m, 2H), 6.59 (d, 1H), 3.21 (m, 2H), 2.89 (s, 3H), 2.79 (m, 2H), 1.99 (m, 2H). Example 49 N-(4,4-Dimethyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-(3-trifluoromethyl-2-pyridyl)-piperazine-1-carboxamide To a stirred solution of 7-amino-4,4-dimethyl-1-trifluoroacetyl-1,2,3,4-tetrahydroisoquinoline (International Patent Application, Publication number WO 00/09486) (100 mg, 0.368 mmol) and pyridine (33 ul, 0.404 mmol) in DCM (5 ml) was added phenylchloroformate (51 ul, 0.404 mmol). The reaction mixture was stirred for 1 h at ambient temperature before triethylamine (56 ul, 0.404 mmol) was added and then left to stir for a further 30 min. After this period, 4-(3-trifluoromethyl-2-pyridyl)-piperazine (85 mg, 0.367 mmol) in DCM (5 ml) was added and the reaction stirred at ambient temperature for 18 h. On completion, the solvents were evaporated in vacuo and the residue purified directly by chromatography, eluting with 10-100% EtOAc/40-60° C. petroleum ether, to give N-(4,4-dimethyl-1-trifluoroacetyl-1,2,3,4-tetrahydroisoquinol-7-yl)-4-(3-trifluoromethyl-2-pyridiyl)-piperazine-1-carboxamide as a colourless oil. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.46 (dd 1H), 7.91 (dd, 1H), 7.05-7.35 (m, 4H), 6.39 (br-s, 1H), 4.77 (s, 2H), 3.60-3.65 (m, 5H), 3.53 (s, 1H), 3.30-3.35 (m, 4H), 1.20-1.25 (m, 6H). MS (ES): MH+ 530. A suspension of N-(4,4-dimethyl-1-trifluoroacetyl-1,2,3,4-tetrahydroisoquinol-7-yl)-4-(3-trifluoromethyl-2-pyridyl)-piperazine-1-carboxamide (30 mg, 0.057 mmol) and potassium carbonate (48 mg, 0.348 mmol) in methanol (4 ml) and water (4 ml) was heated at 50° C. for 6 h. After this period, the solvents were evaporated in vacuo and the residue partitioned between DCM (30 ml) and water (30 ml). The aqueous layer was re-extracted with DCM (2×30 ml) and then the combined organic layers dried (Na2SO4) and the solvents evaporated in vacuo to give the title compound as a white solid. 1H NMR (400 MHz, DMSO) δ (ppm): 8.45 (dd, 1H), 7.89 (dd, 1H), 7.22 (d, 1H), 7.10 (dd, 1H), 7.00-7.05 (m, 2H), 6.55 (s, 1H), 3.95 (s, 2H), 3.60-3.65 (m, 4H), 3.30-3.32 (m, 4H), 2.82 (s, 2H), 2.00 (br-s, 1H), 1.23 (s, 6H). MS (ES): MH+ 434. The following compounds shown in Table 3 were prepared as outlined above: TABLE 3 Example Name MH+ 50 N-(4,4-Dimethyl-1,2,3,4-tetrahydroisoquinolin- 400/402 7-yl)-4-(3-chloro-2-pyridyl)-piperazine-1- carboxamide 51 N-(4,4-Dimethyl-1,2,3,4-tetrahydroisoquinolin- 468/470 7-yl)-4-(3-chloro-5-trifluoromethyl-2-pyridyl)- piperazine-1-carboxamide Example 52 N-[4,4-Dimethyl-1,2,3,4-tetrahydroquinolin-7-yl-(3-chloro-pyridin-2-yl)-benzamide 7-Amino-4,4-dimethyl-1-trifluoroacetyl-1,2,3,4-tetrahydroquinoline (D28) (50 mg, 0.18 mmol) was combined with 4-(3-chloro-pyridin-2-yl)-benzoic acid (D84) (39.3 mg, 0.17 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (38.5 mg, 0.2 mmol) and dimethylaminopyridine (10.2 mg, 0.08 mmol) in DCM (2 ml). The reaction was stirred for 16 h and then diluted with DCM (18 ml). The solution was washed with 10% citric acid (20 ml), saturated NaHCO3 (20 ml) and brine (20 ml) then dried with Na2SO4 and concentrated. The resulting residue was purified by flash chromatography (EtOAc/40-60° C. pet.ether) to yield product as a white solid (19.3 mg). 1H NMR(400 MHz, CDCl3) δ (ppm): 8.61-8.63(dd, 1H), 8.11 (s, 1H), 7.94-7.97(d, 2H), 7.74-7.86(m, 5H), 7.37-7.39(1H, d), 7.26-7.33(1H, m), 4.08-4.16(2H, m), 1.88-1.93(2H, m), 1.33 (6H, s). MH+ 488/490. N-[4,4-Dimethyl-1-trifluoroacetyl-1,2,3,4-tetrahydroquinolin-7-yl-(3-chloro-pyridin-2-yl)-phenylcarboxamide (19.3 mg, 0.04 mmol) and potassium carbonate (16 mg, 0.12 mmol) in water (2 ml) and methanol (2 ml) were heated at 50° C. for 3 h. The methanol was then evaporated in vacuo and the residue diluted with water (10 ml). The mixture was extracted with DCM (4×10 ml) and the combined organics were dried with Na2SO4 and the solvents evaporated in vacuo to give an off-white solid. This product was then taken up in methanol and 1M HCl in ether (41 μl) was added. Evaporation of the solvent gave the final product as an off-white solid. 1H NMR(400 MHz, DMSO) δ (ppm): 10.32(1H, s), 8.67-8.68(1H, m), 8.04-8.11(4H, m), 7.82-7.85(3H, d), 7.33(2H, bs), 3.31(2H, bs), 1.77(2H, bs), 1.27(6H, s). MS (ES): MH+ 392/394. Example 53 6-(3-Fluorophenyl)-2-methyl-N-(1,2,3,4-tetrahydroquinolin-7-yl)nicotinamide Using the procedure outlined in Example 38, the title compound was prepared from 7-amino-1-trifluoroacetyl-1,2,3,4-tetrahydroquinoline (D5) (48 mg, 0.20 mmol) and 2-methyl-6-(3-fluorophenyl)-nicotinic acid (D25) (50 mg, 0.22 mmol) as an off-white solid. MS(ES): MH+ 362, M-H+ 360. Example 54 6-(2,3-Difluorophenyl)-2-methyl-N-(1,2,3,4-tetrahydroquinolin-7-yl)nicotinamide Using the procedure outlined in Example 38, the title compound was prepared from 7-amino-1-trifluoroacetyl-1,2,3,4-tetrahydroquinoline (D5) (48 mg, 0.20 mmol) and 2-methyl-6-(2,3-difluorophenyl)-nicotinic acid (D26) (54 mg, 0.22 mmol) as an off-white solid. MS(ES): MH+ 380, M-H+ 378. Example 55 N-(5-Chloro-1,2,3,4-tetrahydro-quinolin-7-yl)-6-phenyl-nicotinamide Using the procedure outlined in Example 38, the title compound was prepared from 7-amino-5-chloro-1-trifluoroacetyl-1,2,3,4-tetrahydroquinoline (D104) (50 mg, 0.251 mmol) and 6-phenyl nicotinic acid (60 mg, 0.302 mmol) as a white solid (55 mg). 1H NMR (400 MHz, CDCl3) δ (ppm): 9.11 (s, 1H), 8.22 (dd, 1H), 8.05 (dd, 1H), 7.85 (d, 1H), 7.65 (br-s, 1H), 7.45-7.55 (m, 3H), 7.00 (br.s, 1H), 6.79 (d, 1H), 4.10 (br-s, 1H), 3.25-3.30 (m, 2H), 2.75-2.80 (m, 2H), 1.95-2.00 (m, 1H), 1.57 (s, 6H). MS(ES): MH+ 364. Example 56 N-Quinolin-7-yl-1,1′-biphenyl-4-carboxamide To a solution of 7-aminoquinoline (D55) (100 mg, 0.69 mmol) in DCM (3 ml) was added 4-biphenylcarboxylic acid (206 mg, 1.04 mmol), 1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride (197 mg, 1.04 mmol) and 4-dimethylaminopyridine (10 mg, 0.08 mmol) and the reaction stirred at room temperature overnight. The mixture was diluted with DCM, washed with sat. aqueous sodium bicarbonate solution, dried over MgSO4 and concentrated in vacuo to give the crude product which was purified by SPE column chromatography. Elution with 50% EtOAc in 40-60° C. petroleum ether gave the title compound as an off-white solid. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.91 (dd, 1H), 8.19 (d, 1H), 8.12 (m, 2H), 8.02, (d, 2H), 7.86 (d, 1H), 7.75 (d, 2H), 7.65 (d, 2H), 7.49 (t, 2H), 7.42 (t, 1H), 7.36 (dd, 1H). Example 57 6-Phenyl-N-quinolin-7-ylnicotinamide Using the procedure outlined in Example 56, the title compound was prepared from 7-aminoquinoline (D55) (100 mg, 0.69 mmol) and 6-phenylnicotinic acid (D48) (198 mg, 1 mmol) as a solid. 1H NMR (400 MHz, CDCl3) δ (ppm): 9.23 (d, 1H), 8.92 (dd, 1H), 8.33 (dd, 1H), 8.23 (s, 1H), 8.15, (d, 1H), 8.14 (s, 1H), 8.08 (m, 3H), 7.90 (d, 1H), 7.87 (d, 1H), 7.50 (m, 3H), 7.38 (dd, 1H). Example 58 3′-Methyl-N-quinolin-7-yl-1,1′-biphenyl-4-carboxamide To a solution of 4-bromo-N-quinolin-7-ylbenzamide (Example 82) (50 mg, 0.153 mmol) in toluene (2 ml) and ethanol (0.4 ml) under an argon atmosphere was added 3-methyl-phenylboronic acid (21 mg, 0.153 mmol), 2M sodium carbonate solution (0.15 ml) and tetrakis(triphenylphosphine)palladium (0) (5 mg, 0.05 mmol). The reaction was heated at reflux for 18 h, then cooled to room temperature and diluted with EtOAc. The mixture was washed with sat. aq. sodium bicarbonate solution and water, dried over MgSO4 and concentrated to give the crude product which was purified by SPE column chromatography. Elution with 50% EtOAc in 40-60° C. petroleum ether gave the title compound as an off-white solid. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.92 (dd, 1H), 8.19 (d, 1H), 8.13 (m, 3H), 8.01, (d, 2H), 7.86 (d, 1H), 7.75 (d, 2H), 7.46 (m, 2H), 7.36 (m, 2H), 7.25 (m, 1H), 2.46 (s, 3H). Example 59 2′-Methyl-N-quinolin-7-yl-1,1′-biphenyl-4-carboxamide Using the procedure outlined in Example 58, the title compound was prepared from 4-bromo-N-quinolin-7-ylbenzamide (Example 82) (50 mg, 0.153 mmol) and 2-methyl-phenylboronic acid (23 mg, 0.168 mmol) as a white solid. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.92 (dd, 1H), 8.19 (d, 1H), 8.13 (m, 3H), 8.00, (d, 2H), 7.86 (d, 1H), 7.49 (d, 2H), 7.36 (dd, 1H), 7.29 (m, 4H), 2.30 (s, 3H). Example 60 2′-Methoxy-N-quinolin-7-yl-1,1′-biphenyl-4-carboxamide Using the procedure outlined in Example 58, the title compound was prepared from 4-bromo-N-quinolin-7-ylbenzamide (Example 82) (50 mg, 0.153 mmol) and 2-methoxy-phenylboronic acid (25 mg, 0.168 mmol) as a colourless gum. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.91 (dd, 1H), 8.17 (d, 1H), 8.14 (m, 3H), 7.98, (d, 2H), 7.86 (d, 1H), 7.70 (d, 2H), 7.36 (m, 3H), 7.30 (d, 1H), 7.07 (t, 1H), 3.85 (s, 3H). Example 61 2′,6′-Dimethyl-N-quinolin-7-yl-1,1′-biphenyl-4-carboxamide Using the procedure outlined in Example 58, the title compound was prepared from 4-bromo-N-quinolin-7-ylbenzamide (Example 82) (50 mg, 0.153 mmol) and 2,6-dimethyl-phenylboronic acid (25 mg, 0.17 mmol) as a white solid. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.92 (dd, 1H), 8.20 (d, 1H), 8.14 (m, 3H), 8.02, (d, 2H), 7.87 (d, 1H), 7.37 (dd, 1H), 7.34 (d, 2H), 7.21 (t, 1H), 7.14 (d, 2H), 2.05 (s, 6H). Example 62 2′-Acetyl-N-quinolin-7-yl-1,1′-biphenyl-4-carboxamide Using the procedure outlined in Example 58, the title compound was prepared from from 4-bromo-N-quinolin-7-ylbenzamide (Example 82) (50 mg, 0.153 mmol) and 2-acetyl-phenylboronic acid (28 mg, 0.17 mmol) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.92 (dd, 1H), 8.21 (d, 1H), 8.20 (s, 1H), 8.14 (d, 1H), 8.10 (dd, 1H), 7.86 (d, 1H), 7.63 (dd, 1H), 7.57 (td, 1H), 7.48 (m, 3H), 7.40 (dd, 1H), 7.35 (dd, 1H), 3.85 (s, 3H). Example 63 5′-Chloro-2′-methoxy-N-quinolin-7-yl-1,1′-biphenyl-4-carboxamide Using the procedure outlined in Example 58, the title compound was prepared from from 4-bromo-N-quinolin-7-ylbenzamide (Example 82) (65 mg, 0.199 mmol) and 5-chloro-2-methoxyphenylboronic acid (42 mg, 0.22 mmol) as a colourless gum. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.91 (dd, 1H), 8.18 (d, 1H), 8.13 (m, 3H), 7.98, (d, 2H), 7.86 (d, 1H), 7.66 (d, 2H), 7.36 (dd, 2H), 7.32 (m, 2H), 6.94 (d, 1H), 3.82 (s, 3H). Example 64 4-(2,6-Dimethyl-3-pyridyl)-N-quinolin-7-ylbenzamide Using the procedure outlined in Example 56, the title compound was prepared as the corresponding hydrochloride salt from 7-aminoquinoline (D55) (25 mg, 0.17 mmol) and 4-(2,6-dimethyl-3-pyridyl)benzoic acid (D56) (21 mg, 0.09 mmol) as a brown solid. 1H NMR (250 MHz, DMSO) δ (ppm): 9.15 (d, 1H), 9.01 (s, 1H), 8.94 (d, 1H), 8.28 (m, 5H), 7.84 (m, 2H), 7.72 (d, 2H), 2.79 (s, 3H), 2.70 (s, 3H). Example 65 3-Methyl-4-(4-pyridyl)-N-quinolin-7-ylbenzamide Using the procedure outlined in Example 56, the title compound was prepared from 7-aminoquinoline (D55) (25 mg, 0.17 mmol) and 3-methyl-4-(4-pyridyl)benzoic acid (D57) (44 mg, 0.21 mmol) as an orange solid. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.91(dd, 1H), 8.70 (d, 2H), 8.22 (m, 2H), 8.14 (dd, 1H), 8.11 (dd, 1H), 7.84 (m, 3H), 7.36 (m, 2H), 7.28 (m, 2H), 2.37 (s, 3H). Example 66 3-Methyl-N-quinolin-7-yl-1,1′biphenyl-4-carboxamide Using the procedure outlined in Example 56, the title compound was prepared from 7-aminoquinoline (D55) (31, 0.22 mmol) and 3-methyl-1,1′-biphenyl-4-carboxylic acid (D58) (55 mg, 0.26 mmol) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.91(dd, 1H), 8.14 (m, 3H), 7.86 (d, 1H), 7.78 (br, 1H), 7.66 (d, 1H), 7.62 (d, 2H), 7.53 (m, 2H), 7.48 (t, 2H), 7.40 (t, 1H), 7.36 (dd, 1H), 2.63 (s, 3H). Example 67 3-Methoxy-N-quinolin-7-yl-1,1′biphenyl-4-carboxamide Using the procedure outlined in Example 56, the title compound was prepared from 7-aminoquinoline (D55) (26 mg, 0.18 mmol) and 3-methoxy-1,1′-biphenyl-4-carboxylic acid (D59) (50 mg, 0.22 mmol) as an off-white solid. MS (ES): MH+ 355. Example 68 2-Methyl-N-quinolin-7-yl-1,1′biphenyl-4-carboxamide Using the procedure outlined in Example 56, the title compound was prepared from 7-aminoquinoline (D55) (30 mg, 0.21 mmol) and 2-methyl-1,1′-biphenyl-4-carboxylic acid (D60) (53 mg, 0.25 mmol) as a white solid. MS(ES): MH+ 339 Example 69 4-[(4-tert-Butoxycarbonyl)piperazin-1-yl]-2-methyl-N-quinolin-7-ylbenzamide Using the procedure outlined in Example 56, the title compound was prepared from 7-aminoquinoline (D55) (17 mg, 0.12 mmol) and 4-[(4-tert-butoxycarbonyl)piperazin-1-yl]-2-methylbenzoic acid (D61) (47 mg, 0.14 mmol) as a yellow oil. MS(ES): MH+ 447, M-H+ 445. Example 70 3,5-Dimethyl-4-(4-methyl-benzo[1,3]dioxol-5-yl)-N-quinolin-7-ylbenzamide Using the procedure outlined in Example 56, the title compound was prepared from 7-aminoquinoline (D55) (17 mg, 0.12 mmol) and 3,5-dimethyl-4-(4-methyl-benzo[1,3]-dioxol-5-yl)-benzoic acid (D62) (41 mg, 0.15 mmol) as a yellow oil. MS(ES): MH+ 411, M-H+ 409. Example 71 N-(2-Methylquinolin-7-yl)-1,1′-biphenyl-4-carboxamide Using the procedure outlined in Example 56, the title compound was prepared from from 7-amino-2-methylquinoline (D66) (80 mg, 0.51 mmol) and 4-biphenylcarboxylic acid (149 mg, 0.75 mmol) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.07 (m, 3H), 8.01 (m, 3H), 7.81 (d, 1H), 7.75 (d, 2H), 7.66 (d, 2H), 7.50 (t, 2H), 7.42 (t, 1H), 7.24 (d, 1H), 2.75 (s, 3H). Example 72 N-(2-Methylquinolin-7-yl)-6-phenylnicotinamide Using the procedure outlined in Example 56, the title compound was prepared from 7-amino-2-methylquinoline (D66) (100 mg, 0.63 mmol) and 6-phenylnicotinic acid (D48) (151 mg, 0.76 mmol) as a cream solid. 1H NMR (400 MHz, DMSO) δ (ppm): 10.75 (s, 1H), 9.25 (d, 1H), 8.50 (s, 1H), 8.45 (dd, 1H), 8.20 (m, 4H), 7.90 (m, 2H), 7.55 (m, 3H), 7.34 (d, 1H), 2.65 (s, 3H). Example 73 3-Methyl-4-(4-pyridyl)-N-(2-methylquinolin-7-yl)-benzamide Using the procedure outlined in Example 56, the title compound was prepared from 7-amino-2-methylquinoline (D66) (30 mg, 0.19 mmol) and 3-methyl-4-(4-pyridyl)benzoic acid (D57) (49 mg, 0.23 mmol) as an orange gum, (59 mg, 88%). 1H NMR (250 MHz, CDCl3) δ (ppm): 8.70 (dd, 2H), 8.10 (s, 2H), 8.03 (m, 2H), 7.87 (s, 1H), 7.80 (d, 2H), 7.35 (d, 1H), 7.27 (m, 3H), 2.74 (s, 3H), 2.37 (s, 3H). Example 74 N-(2-Methylquinolin-7-yl)-4-(2-pyridyl)benzamide Using the procedure outlined in Example 56, the title compound was prepared from 7-amino-2-methylquinoline (D66) (33 mg, 0.21 mmol) and 4-(2-pyridyl)benzoic acid (D67) (50 mg, 0.25 mmol) as a white solid. MS (ES): MH+ 340, M-H+ 338. Example 75 N-(2-Methylquinolin-7-yl)-4-(1-pyrazolyl)benzamide Using the procedure outlined in Example 56, the title compound was prepared from 7-amino-2-methylquinoline (D66) (33 mg, 0.21 mmol) and 4-(1-pyrazolyl)benzoic acid (47 mg, 0.25 mmol) as an off-white solid. MS (ES): MH+ 329, M-H+ 327. Example 76 N-(2-Methylquinolin-7-yl)-4-(6-methyl-2-pyridyl)benzamide Using the procedure outlined in Example 56, the title compound was prepared from 7-amino-2-methylquinoline (D66) (33 mg, 0.21 mmol) and 4-(6-methyl-2-pyridyl)benzoic acid (D29) (47 mg, 0.25 mmol) as an off-white solid. MS (ES): MH+ 354, M-H+ 352. Example 77 N-(2-Methylquinolin-7-yl)-4-(N-morpholino)benzamide A mixture of palladium (II) acetate (14 mg, 0.06 mmol), cesium carbonate (299 mg, 0.92 mmol) and BINAP (57 mg, 0.09 mmol) in dioxan (10 ml) was sonicated for 0.75 h under an argon atmosphere. To the resulting blood red solution was added a mixture of 4-bromo-N-quinolin-7-ylbenzamide (Example 82) (200 mg, 0.61 mmol) and morpholine (133 mg) in dioxane (10 ml) and the reaction was heated at 100° C. overnight. The resulting solution was concentrated in vacuo and the residue partitioned between DCM and water. The aqueous was further extracted with DCM and the combined organics were washed with sat. aq. sodium bicarbonate solution and brine, then dried over MgSO4 and concentrated in vacuo to give the crude product. Purification by flash chromatography eluting with 5% MeOH/EtOAc gave the title compound as a yellow solid. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.89 (dd, 1H), 8.22 (dd, 1H), 8.16 (m, 2H), 8.09 (s, 1H), 7.88 (d, 2H), 7.85 (d, 1H), 7.37 (dd, 1H), 6.96 (d, 2H), 3.89 (m, 4H), 3.31 (m, 4H). Example 78 N-(2-Methylquinolin-7-yl)-4-(N-piperidino)benzamide A mixture of 4-bromo-N-quinolin-7-ylbenzamide (Example 82) (200 mg, 0.61 mmol), Pd2(dba)3 (8.4 mg, 1.5 mol %), Xantphos (21 mg, 6 mol %), cesium carbonate (298 mg, 0.92 mmol) and piperidine (78 mg, 0.92 mmol) in dioxan (10 ml) was heated at reflux under an argon atmosphere overnight. The mixture was concentrated in vacuo and the residue was partitioned between 9:1 DCM/MeOH and water. The aqueous was further extracted with 9:1 DCM/MeOH and the combined organics were washed with saturated aqueous sodium bicarbonate solution and brine, then dried over MgSO4 and concentrated in vacuo to give the crude product. Purification by flash chromatography eluting with 50% EtOAc/DCM gave the title compound as a yellow solid. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.87 (dd, 1H), 8.13 (m, 4H), 7.83 (d, 2H), 7.80 (d, 1H), 7.32 (dd, 1H), 6.92 (d, 2H), 3.32 (m, 4H), 1.66 (m, 6H). Example 79 4-Phenyl-N-quinolin-7-ylpiperazine-1-carboxamide To a solution of di-tert-butyl tricarbonate (60 mg, 0.23 mmol) in DCM (1 ml) was added in one portion, a solution of 7-aminoquinoline (D55) (30 mg, 0.21 mmol) in DCM (1 ml). After 5 mins, when gas evolution was complete, tris-amine resin (12 mg 0.04 mmol) was added, then after 1 h a solution of 4-phenylpiperazine (32 ul, 0.21 mmol) was added and the reaction stirred at room temperature overnight. The reaction mixture was then purified directly by SPE column chromatography, eluting with an EtOAc/60-80° C.-petroleum ether gradient, followed by treatment with excess methyl isocyanate resin to remove unreacted 7-aminoquinoline starting material from the product. On completion the resin was removed by filtration and filtrate concentrated in vacuo to give the title compound as an orange gum. 1H NMR (250 MHz, CDCl3) δ (ppm): 8.85 (dd, 1H), 8.09 (dd, 1H), 7.93 (dd, 1H), 7.82 (s, 1H), 7.76 (d, 1H), 7.30 (m, 3H), 6.94 (m, 3H), 6.83 (br, 1H), 3.72 (m, 4H), 3.28 (m, 4H). Example 80 N-(2-Methylquinolin-7-yl)-4-phenylpiperazine-1-carboxamide Using the procedure outlined in Example 79, the title compound was prepared from 7-amino-2-methylquinoline (D66) (100 mg, 0.63 mmol) and 4-phenylpiperazine (123 μl, 0.76 mmol) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ (ppm): 7.97 (d, 1H), 7.84 (dd, 1H), 7.72 (s, 1H), 7.69 (dd, 1H), 7.30 (t, 2H), 7.18 (d, 1H), 6.95 (d, 2H), 6.92 (t, 1H), 6.70 (br, 1H), 3.72 (m, 4H), 3.27 (m, 4H), 2.71 (s, 3H). Example 81 4-Phenyl-N-quinolin-7-yl-piperidine-1-carboxamide Using the procedure outlined in Example 79, the title compound was prepared from 7-aminoquinoline (D55) (30 mg, 0.21 mmol) and 4-phenylpiperidine (40 mg, 0.25 mmol) as an orange gum. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.84 (dd, 1H), 8.08 (dd, 1H), 7.93 (dd, 1H), 7.78 (s, 1H), 7.27 (m, 6H), 6.78 (br, 1H), 4.29 (m, 2H), 3.06 (td, 2H), 2.76 (tt, 1H), 1.96 (m, 2H), 1.80 (td, 2H). Example 82 4-Bromo-N-quinolin-7-yl-benzamide Using the procedure outlined in Example 56, the title compound was prepared from 7-aminoquinoline (D55) (720 mg, 5 mmol) and 4-bromobenzoic acid (1.51 g, 7.5 mmol) as a white solid. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.91 (dd, 1H), 8.18 (d, 1H), 8.14 (dd, 1H), 8.06, (m, 2H), 7.85 (d, 1H), 7.81 (d, 2H), 7.67 (d, 2H), 7.37 (dd, 1H). Example 83 3′-Dimethylsulfamoyl-N-quinolin-7-yl-1,1′-biphenyl-4-carboxamide Using the procedure outlined in Example 56, the title compound was prepared from 7-aminoquinoline (D55) (18 mg, 0.13 mmol) and 3′-dimethylsulfamoyl-1,1′-biphenyl-4-carboxylic acid (D68) (45 mg, 0.15 mmol) as a yellow oil. MS(ES): MH+ 432, M-H+ 430 Example 84 4-Cyclohexyl-N-quinolin-7-yl-benzamide Using the procedure outlined in Example 45, the title compound was prepared from 7-aminoquinoline (D55) (30 mg, 21 mmol) and 4-cyclohexylbenzoic acid (51 mg, 0.25 mmol) as a yellow solid. MS(ES): MH+ 331, M-H+ 329 Example 85 4-tert-Butyl-N-quinolin-7-yl-benzamide Using the procedure outlined in Example 45, the title compound was prepared from 7-aminoquinoline (D55) (30 mg, 21 mmol) and 4-tert-butylbenzoic acid (45 mg, 0.25 mmol) as a yellow solid. MS(ES): MH+ 305, M-H+ 303 Example 86 4-iso-Propyl-N-quinolinyl-benzamide Using the procedure outlined in Example 45, the title compound was prepared from 7-aminoquinoline (D55) (30 mg, 21 mmol) and 4-isopropylbenzoic acid (41 mg, 0.25 mmol) as a yellow solid. MS(ES): MH+ 291, M-H+ 289 Example 87 N-Quinolinyl-4-trifluoromethyl-benzamide Using the procedure outlined in Example 45, the title compound was prepared from 7-aminoquinoline (D55) (30 mg, 21 mmol) and 4-trifluoromethyl-benzoic acid (48 mg, 0.25 mmol) as a yellow solid. MS(ES): MH+ 317, M-H+ 315 Example 88 9-Oxo-9H-fluorene-2-carboxylic acid quinolin-7-yl amide To a solution of 7-aminoquinoline (D55) (35 mg, 0.24 mmol) in DCM (3 ml) was added 9-oxo-9H-fluorene-2-carboxylic acid (60 mg, 0.27 mmol), (3-dimethylamino-propyl)-ethyl-carbodiimide hydrochloride (68 mg, 0.36 mmol) and 4-dimethylaminopyridine (5 mg, 0.04 mmol) and the reaction stirred at room temperature then at reflux until complete by tlc. After cooling to room temperature the resultant precipitate was filtered off to give the title compound as an off-white solid. MS(ES): MH+ 351, M-H+ 349 Example 89 2-Methyl-N-quinolin-7-yl-6-trifluoromethyl-nicotinamide Using the procedure outlined in Example 45, the title compound was prepared from 7-aminoquinoline (D55) (30 mg, 21 mmol) and 2-methyl-6-trifluoromethylnicotinic acid (51 mg, 0.25 mmol) as a yellow solid. MS(ES): MH+ 332, M-H+ 330 Example 90 4-(3-Pyridyl)-N-quinolin-7-yl-benzamide Using the procedure outlined in Example 58, the title compound was prepared from 4-bromo-N-quinolin-7-ylbenzamide (Example 82) (50 mg, 0.15 mmol) and 3-pyridylboronic acid (20 mg, 0.16 mmol) as a white solid. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.89 (d, 1H), 8.87 (dd, 1H), 8.65 (m, 1H), 8.26 (dd, 1H), 8.17 (dd, 1H), 8.14 (d, 1H), 8.09 (d, 2H), 7.96 (m, 1H), 7.88 (d, 1H), 7.74 (d, 2H), 7.45 (dd, 1H), 7.38 (dd, 1H). Example 91 4-(4-Pyridyl)-N-quinolin-7-yl-benzamide Using the procedure outlined in Example 58, the title compound was prepared from 4-bromo-N-quinolin-7-ylbenzamide (Example 82) (50 mg, 0.15 mmol) and 4-pyridylboronic acid (20 mg, 0.16 mmol) as a white solid. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.86 (d, 1H), 8.70 (d, 2H), 8.33 (dd, 1H), 8.18 (d, 1H), 8.12 (d, 2H), 8.07 (s, 1H), 7.88 (d, 1H), 7.79 (d, 2H), 7.58(d, 2H), 7.38 (dd, 1H). Example 92 (R)-2-Methyl-4-(3-trifluoromethyl-2-pyridyl)-N-quinolin-7-yl) piperazine-1-carboxamide Using the procedure outlined in Example 79, the title compound was prepared from 7-aminoquinoline (D55) (60 mg, 0.417 mmol) and (R)-2-methyl-4-(3-trifluoromethyl-2-pyridyl)piperazine (D22) (123 mg, 0.50 mmol) as a colourless oil. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.92 (1H, d), 8.66-8.69 (2H, m), 8.50 (2H, d), 8.27 (1H, bs), 7.99 (1H, d), 7.94 (1H, dd), 7.65-7.68 (1H, m), 7.09-7.12 (1H, m), 4.55 (1H, m), 4.06 (1H, d), 3.50-3.56 (2H, m), 3.41 (1H, d, J=), 3.26 (1H, dd), 3.01-3.08 (1H, m), 1.40 (3H, d). MS(ES): MH+ 416. Example 93 2-Methoxy-N-quinolin-7-yl-1,1′-biphenyl-4-carboxamide Using the procedure outlined in Example 58, the title compound was prepared from 4-bromo-3-methoxy-N-quinolin-7-ylbenzamide (D69) (76 mg, 0.21 mmol) and phenylboronic acid (28 mg, 0.23 mmol) as a white solid. MS(ES): MH+ 355, M-H+ 353. Example 94 6-(4-Methylpiperidin-1-yl)-N-quinolin-7-yl-nicotinamide 6-Chloro-N-quinolinylnicotinamide (D70) (50 mg, 0.18 mmol), 4-methylpiperidine (25 ul, 0.21 mmol) and potassium carbonate (73 mg, 0.53 mmol) in DMF (2 ml) were heated at 120° C. overnight. Further 4-methylpiperidine (11 ul, 0.09 mmol) was added and heating continued overnight. On cooling the reaction mixture was diluted with EtOAc and washed with water, then dried over MgSO4 and concentrated to give the crude product. Purification by SPE column chromatography gave the title compound as a yellow solid. MS(ES): MH+ 347, M-H+ 345. Example 95 2-Methyl-N-quinolin-7-yl-6-(2-thienyl)-nicotinamide Using the procedure outlined in Example 45, the title compound was prepared from 7-aminoquinoline (D55) (7 mg, 0.05 mmol) and 2-methyl-6-(2-thienyl)-nicotinic acid (10 mg, 0.05 mmol) as a yellow solid. 1H NMR (400 MHz, MeOH-d4) δ (ppm): 8.82 (dd, 1H), 8.58 (s, 1H), 8.34 (dd, 1H), 7.85-8.0 (m, 3H), 7.76 (m, 2H), 7.55 (dd, 1H), 7.48 (dd, 1H), 7.16 (dd, 1H), 2.70 (s, 3H). Example 96 6-Piperidin-1-yl-N-quinolin-7-yl-nicotinamide Using the procedure outlined in Example 94, the title compound was prepared from 6-chloro-N-quinolinylnicotinamide (D70) (50 mg, 0.18 mmol) and piperidine (30 ul, 0.30 mmol) to give the title compound as a yellow solid. MS(ES): MH+ 333, M-H+ 331. Example 97 4-(4-Fluorophenyl)-N-quinolin-7-yl piperazine-1-carboxamide Using the procedure outlined in Example 47, the title compound was prepared from 7-aminoquinoline (D55) (30 mg, 0.21 mmol) and 4-(4-fluorophenyl)-piperazine (37 mg, 0.21 mmol) as an off-white solid. MS(ES): MH+ 351, M-H+ 349 Example 98 (R)-2-Methyl-4-(6-methyl-2-pyridyl)-N-quinolin-7-yl)-piperazine-1-carboxamide Using the procedure outlined in Example 47, the title compound was prepared from 7-aminoquinoline (D55) (30 mg, 0.21 mmol) and (R)-2-methyl-4-(6-methyl-2-pyridyl)piperazine (D99) (40 mg, 0.21 mmol) as an off-white solid. 1H NMR (400 MHz, CDCl3) (ppm): 8.85 (dd, 1H), 8.09 (dd, 1H), 7.94 (dd, 1H), 7.80 (d, 1H), 7.77 (d, 1H), 7.40 (dd, 1H), 7.30 (dd, 1H), 6.69 (s, 1H), 6.52 (d, 1H), 6.44 (d, 1H), 4.41 (m, 1H), 4.25 (m, 1H), 4.06 (m, 1H), 4.00 (m, 1H), 3.49 (ddd, 1H), 3.38 (dd, 1H), 3.11 (ddd, 1H), 2.42 (s, 3H), 1.37 (d, 3H). Example 99 6-(4-Fluorophenyl)-N-quinolin-7-yl-nicotinamide Using the procedure outlined in Example 56, the title compound was prepared from 7-aminoquinoline (D55) (50 mg, 0.35 mmol) and 6-(4-fluoro-phenylnicotinic acid (D24) (83 mg, 0.38 mmol) as a cream solid. 1H NMR (250 MHz, CDCl3) δ (ppm): 9.23 (dd, 1H), 8.86 (dd, 1H), 8.37 (dd, 1H), 8.26 (dd, 1H), 8.18 (m, 2H), 8.08 (d, 1H), 8.06 (d, 1H), 7.85 (dd, 2H), 7.38 (dd, 1H), 7.20 (t, 2H). Example 100 N-Quinolin-7-yl-6-(4-trifluoromethylphenyl)-nicotinamide To a solution of 6-chloro-N-quinolin-7-yl-nicotinamide (D70) (40 mg, 0.14 mmol) in DME (0.9 ml) under an argon atmosphere was added 4-trifluoromethylphenylboronic acid (33 mg, 0.17 mmol), 2M sodium carbonate solution (0.17 ml) and tetrakis(triphenylphosphine)palladium (0) (8 mg, 0.007 mmol). The reaction was heated at reflux until complete by tlc, then cooled to room temperature and diluted with EtOAc and dried over MgSO4. The solvent was removed in vacuo and the resultant crude product was purified by SPE column chromatography. Elution with 75% EtOAc in 40-60° C. petroleum ether gave the title compound as an off-white solid. 1H NMR (250 MHz, CDCl3) δ (ppm): 9.31 (dd, 1H), 8.83 (dd, 1H), 8.46 (dd, 1H), 8.39 (dd, 1H), 8.20 (m, 3H), 8.07 (d, 1H), 7.94 (dd, 1H), 7.89 (d, 1H), 7.79 (d, 2H), 7.40 (dd, 1H). Example 101 9H-Fluorene-2-carboxylic acid quinolin-7-yl amide Using the procedure outlined in Example 56, the title compound was prepared from 7-aminoquinoline (D55) (50 mg, 0.35 mmol) and 9H-fluorene-2-carboxylic acid (D71) (83 mg, 0.38 mmol) as an off-white solid. MS(ES): MH+ 337, M-H+ 335. Example 102 6-(4-Chlorophenyl)-N-quinolin-7-yl-nicotinamide Using the procedure outlined in Example 100, the title compound was prepared from 6-chloro-N-quinolin-7-yl-nicotinamide (D70) (40 mg, 0.14 mmol) and 4-chlorophenylboronic acid (27 mg, 0.17 mmol) as a pale yellow solid. 1H NMR (250 MHz, CDCl3) δ (ppm): 9.25 (dd, 1H), 8.82 (dd, 1H), 8.43 (dd, 1H), 8.33 (dd, 1H), 8.22 (br.d, 1H), 8.11 (d, 1H), 8.00 (d, 2H), 7.89 (d, 1H), 7.87 (d, 1H), 7.51 (d, 2H), 7.40 (dd, 1H). Example 103 6-(3,4-Difluorophenyl)-N-quinolin-7-yl-nicotinamide Using the procedure outlined in Example 100, the title compound was prepared from 6-chloro-N-quinolin-7-yl-nicotinamide (D70) (40 mg, 0.14 mmol) and 3,4-difluorophenylboronic acid (27 mg, 0.17 mmol) as a cream solid. 1H NMR (250 MHz, CDCl3) δ (ppm): 9.24 (dd, 1H), 8.86 (dd, 1H), 8.39 (dd, 1H), 8.28 (dd, 1H), 8.14 (br.d, 1H), 8.13 (d, 1H), 7.97 (ddd, 1H), 7.85 (m, 3H), 7.39 (dd, 1H), 7.28 (m, 1H). Example 104 4-(2-Methylpyrid-4-yl)-N-quinolin-7-yl-benzamide To a solution of 7-aminoquinoline (D55) (338 mg, 0.26 mmol) in DCM (3 ml) was added 4-(2-methylpyrid-4-yl)-benzoic acid (D72) (62 mg, 0.29 mmol), 1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride (74 mg, 0.39 mmol) and 4-dimethylaminopyridine (6 mg, 0.05 mmol) and the reaction stirred at room temperature until complete by tlc. The resultant precipitate was filtered off to give the title compound as an off-white solid. MS(ES): MH+ 340, M-H+ 338 Example 105 6-(3-Fluorophenyl)-N-quinolin-7-yl-nicotinamide Using the procedure outlined in Example 104, the title compound was prepared from 7-aminoquinoline (D55) (28 mg, 0.19 mmol) and 6-(3-fluorophenyl)-nicotinic acid (D73) (50 mg, 0.23 mmol) as a yellow solid. MS(ES): MH+ 344, M-H+ 342 Example 106 6-(2-Fluorophenyl)-N-quinolin-7-yl-nicotinamide Using the procedure outlined in Example 104, the title compound was prepared from 7-aminoquinoline (D55) (28 mg, 0.19 mmol) and 6-(2-fluorophenyl)-nicotinic acid (D74) (50 mg, 0.23 mmol) as a yellow solid. MS(ES): MH+ 344, M-H+ 342 Example 107 N-Quinolin-7-yl-1-(5-trifluoromethylpyrid-2-yl)-piperidine-4-carboxamide 1-(5-Trifluoromethylpyrid-2-yl)-piperidine-4-carboxylic acid (D101) (100 mg, 0.36 mmol) was treated with oxalyl chloride (63 ul, 0.72 mmol) and catalytic DMF in 1,2-dichloroethane (3.5 ml) at 60° C. for 0.75 h. On cooling to room temperature the solvent was removed in vacuo and the residue was dissolved in DCM (2 ml). Triethylamine (30 ul, 0.2 mmol) and 7-aminoquinoline (D55) (27 mg, 0.19 mmol) were added and the reaction stirred at room temperature until complete by tlc. The resultant precipitate was collected by filtration to give the title compound as an off-white solid. MS(ES): MH+ 401, M-H+ 399. Example 108 2-Methyl-6-phenyl-N-quinolin-7-yl-nicotinamide Using the procedure outlined in Example 56, the title compound was prepared from 7-aminoquinoline (D55) (28 mg, 0.9 mmol) and 2-methyl-6-phenylnicotinic acid (D23) (50 mg, 0.24 mmol) as a yellow solid. MS(ES): MH+ 340, M-H+ 338 Example 109 6-(4-Fluorophenyl)-2-methyl-N-quinolin-7-yl-nicotinamide Using the procedure outlined in Example 45, the title compound was prepared from 7-aminoquinoline (D55) (26 mg, 0.8 mmol) and 6-(4-fluorophenyl)-2-methylnicotinic acid (D24) (50 mg, 0.22 mmol) as a white solid. MS(ES): MH+ 358, M-H+ 356. Example 110 N-Quinolin-7-yl-1-(6-trifluoromethylpyrid-2-yl)-piperidine-4-carboxamide Using the procedure outlined in Example 107, the title compound was prepared from 1-(6-trifluoromethylpyrid-2-yl)-piperidine-4-carboxylic acid (D102) (100 mg, 0.36 mmol) and 7-aminoquinoline (D55) (27 mg, 0.19 mmol) as an off white solid. MS(ES): MH+ 401, M-H+ 399. Example 111 4′-Fluoro-2-(2-methoxyethoxy)-N-quinolin-7-yl-1,1′-biphenyl-4-carboxamide Using the procedure outlined in Example 56, the title compound was prepared from 7-aminoquinoline (D55) (21 mg, 0.14 mmol) and 4′-fluoro-2-(2-methoxyethoxy)-1,1′-biphenyl-4-carboxylic acid (D77) (50 mg, 0.17 mmol) as an orange solid. MS(ES): MH+ 417, M-H+ 415 Example 112 2-(2-Dimethylaminoethoxy)-4′-fluoro-N-quinolin-7-yl-1,1′-biphenyl-4-carboxamide Using the procedure outlined in Example 56, the title compound was prepared from 7-aminoquinoline (D55) (20 mg, 0.14 mmol) and 2-(2-dimethylaminoethoxy)-4′-fluoro-1,1′-biphenyl-4-carboxylic acid (D79) (50 mg, 0.17 mmol) as a yellow solid. MS(ES): MH+ 430, M-H+ 428 Example 113 N-(5-Chloroquinolin-7-yl)-6-(4-Fluorophenyl)-2-methyl-nicotinamide To a solution of 7-amino-5-chloroquinoline (D83) (50 mg, 0.28 mmol) in DCM (3 ml) was added 6-(4-fluorophenyl)-2-methyl-nicotinic acid (D24) (30 mg, 0.13 mmol), 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (59 mg, 0.31 mmol) and 4-dimethylaminopyridine (17 mg, 0.14 mmol) and the reaction stirred at room temperature then at reflux until complete by tlc. The mixture was washed with sat. aq. sodium bicarbonate solution then dried over MgSO4 and concentrated to give the crude product. Purification by SPE column chromatography gave the title compound as an off white solid. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.94 (dd, 1H), 8.54 (d, 1H), 8.29 (s, 1H), 8.05 (m, 3H), 7.92 (d, 1H), 7.78 (br.s, 1H), 7.62 (d, 1H), 7.47 (dd, 1H), 7.18 (t, 2H), 2.84 (s, 3H). Example 114 4-(3-Chloro-2-pyridinyl)-N-quinolin-7-yl-benzamide Using the procedure outlined in Example 56, the title compound was prepared from 7-aminoquinoline (D55) (25 mg, 0.14 mmol) and 4-(3-Chloro-2-pyridyl)-benzoic acid (D84) (50 mg, 0.17 mmol) as a brown solid. MS(ES): MH+ 362/360, M-H+ 360/358. Example 115 6-(4-Fluorophenyl)-2-(methoxymethyl)-N-quinolin-7-yl-nicotinamide Using the procedure outlined in Example 56, the title compound was prepared from 7-aminoquinoline (D55) (11 mg, 0.076 mmol) and 6-(4-fluorophenyl)-2-(methoxymethyl)-nicotinic acid (D86) (19 mg, 0.073 mmol) as an orange solid. 1H NMR (250 MHz, CDCl3) δ (ppm): 10.40 (br.s, 1H), 8.92 (dd, 1H), 8.41 (d, 1H), 8.29 (d, 1H), 8.05-8.20 (m, 4H), 7.85 (m, 2H), 7.36 (dd, 1H), 7.20 (t, 2H), 4.91 (s, 2H), 3.68 (s, 3H). Example 116 6-(4-Fluorophenyl)-2-methyl-N-(2-methylquinolin-7-yl)-nicotinamide Using the procedure outlined in Example 56, the title compound was prepared from 7-amino-2-methylquinoline (D66) (20 mg, 0.13 mmol) and 6-(4-fluorophenyl)-2-methylnicotinic acid (D24) (30 mg, 0.13 mmol) then converted to the HCl salt as a beige solid by treatment with ethereal HCl. 1H NMR (400 MHz, DMSO) (HCl salt) δ (ppm): 11.39 (br.s, 1H), 9.04 (s, 1H), 8.96 (d, 1H), 8.30 (d, 1H), 8.23 (dd, 2H), 8.12 (d, 1H), 8.00 (m, 2H), 7.84 (d, 1H), 7.37 (t, 2H), 2.94 (s, 3H), 2.71 (s, 3H) Example 117 6-(3-Fluorophenyl)-2-methyl-N-quinolin-7-yl-nicotinamide Using the procedure outlined in Example 56, the title compound was prepared from 7-aminoquinoline (D55) (28 mg, 0.20 mmol) and 6-(3-fluorophenyl)-2-methyl-nicotinic acid (D25) (50 mg, 0.33 mmol), as an off-white solid. MS(ES): MH+ 358, M-H+ 356. Example 118 6-(2,3-Difluorophenyl)-2-methyl-N-quinolin-7-yl-nicotinamide Using the procedure outlined in Example 56, the title compound was prepared from 7-aminoquinoline (D55) (28 mg, 0.20 mmol) and 6-(2,3-difluorophenyl)-2-methyl-nicotinic acid (D26) (54 mg, 0.33 mmol), as a brown solid. MS(ES): MH+ 376, M-H+ 374. Example 119 4-(2-Methylthiazol-4yl)-N-quinolin-7-yl-benzamide Using the procedure outlined in Example 56, the title compound was prepared from 7-aminoquinoline (D55) (27 mg, 0.19 mmol) and 4-(2-methylthiazol-4-yl)-benzoic acid (D87) (50 mg, 0.23 mmol) as a solid. MS(ES): MH+ 346, M-H+ 344 Example 120 N-(4-Methyl-2-oxo-1,2-dihydro-quinolin-7-yl)-1,1′-biphenyl-4-carboxamide Using the procedure outlined in Example 56, the title compound was prepared from 7-amino-4-methyl-1-H-quinolin-2-one (50 mg, 0.29 mmol) and 4-biphenylcarboxylic acid (68 mg, 0.34 mmol) as a cream solid. 1H NMR (250 MHz, DMSO) δ (ppm): 11.60 (br, 1H), 10.55 (br, 1H), 8.09 (d, 2H), 8.02 (s, 1H), 7.86 (d, 2H), 7.77 (d, 2H), 7.69 (d, 1H), 7.55 (dd, 1H), 7.52 (t, 2H), 7.43 (t, 1H), 6.29 (s, 1H), 2.41 (s, 3H). Example 121 N-(1,4-Dimethyl-2-oxo-1,2-dihydro-quinolin-7-yl)-1,1′-biphenyl-4-carboxamide Using the procedure outlined in Example 56, the title compound was prepared from 7-amino-1,4-methyl-1H-quinolin-2-one (D89) (64 mg, 0.34 mmol) and 4-biphenylcarboxylic acid (82 mg, 0.41 mmol) as a pale pink solid. 1H NMR (250 MHz, DMSO) δ (ppm): 10.58 (br, 1H), 8.14 (s, 1H), 8.12 (d, 2H), 7.88 (d, 2H), 7.80 (m, 4H), 7.53 (t, 2H), 7.42 (t, 1H), 6.44 (d, 1H), 3.60 (s, 3H), 2.43 (d, 3H). Example 122 N-(2-Oxo-1,2-dihydro-quinolin-7-yl)-1,1′-biphenyl-4-carboxamide Using the procedure outlined in Example 56, the title compound was prepared from 7-amino-1H-quinolin-2-one (D89) (30 mg, 0.19 mmol) and 4-biphenylcarboxylic acid (44 mg, 0.22 mmol) as an off-white solid. 1H NMR (400 MHz, DMSO) δ (ppm): 11.80 (br, 1H), 10.58 (br, 1H), 8.09 (d, 2H), 8.04 (d, 1H), 7.85 (m, 3H), 7.77 (d, 2H), 7.62 (d, 1H), 7.52 (m, 3H), 7.44 (t, 1H), 6.39 (d, 1H). Example 123 N-(2-Oxo-1,2-dihydro-quinolin-7-yl)-6-phenylnicotinamide Using the procedure outlined in Example 56, the title compound was prepared from 7-amino-1H-quinolin-2-one (D89) (30 mg, 0.19 mmol) and 6-phenylnicotinic acid (D48) (45 mg, 0.22 mmol) as an off-white solid. 1H NMR (400 MHz, DMSO) δ (ppm): 11.80 (br, 1H), 10.73 (br, 1H), 9.21 (d, 1H), 8.42 (dd, 1H), 8.18 (m, 3H), 8.01 (d, 1H), 7.84 (d, 1H), 7.64 (d, 1H), 7.53 (m, 4H), 6.40 (dd, 1H). Example 124 N-(Isoquinolin-5-yl)-1,1′-biphenyl-4-carboxamide To a solution of 5-aminoisoquinoline (72 mg, 0.5 mmol) in DCM (3 ml) was added 4-biphenylcarboxylic acid (149 mg, 0.75 mmol), 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (143 mg, 0.75 mmol) and 4-dimethylaminopyridine (9 mg, 0.08 mmol) and the reaction stirred at room temperature overnight. The mixture was diluted with DCM, washed with 2M sodium hydroxide solution and 2M hydrochloric acid causing precipitation of a white solid which was filtered off and dried in vacuo to give the HCl salt of the title compound. 1H NMR (400 MHz, DMSO) δ (ppm): 10.94 (s, 1H), 9.88 (s, 1H), 8.67 (d, 1H), 8.41 (d, 1H), 8.38 (d, 1H), 8.24 (m, 3H), 8.04 (t, 1H), 7.91 (d, 2H), 7.80 (d, 2H), 7.54 (t, 2H), 7.45 (t, 1H), 4.00 (br). Example 125 N-(1-Methylisoquinolin-5-yl)-1,1′-biphenyl-4-carboxamide To a solution of 1-methyl-5-aminoisoquinoline (94 (75 mg, 0.47 mmol) in DCM (4 ml) was added 4-biphenylcarboxylic acid (141 mg, 0.71 mmol), 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (135 mg, 0.71 mmol) and 4-dimethylaminopyridine (10 mg, 0.08 mmol) and the reaction stirred at 38° C. for 3 days. The mixture was diluted with DCM, washed with sat. aqueous sodium bicarbonate solution and water, dried over MgSO4 and concentrated in vacuo to give the crude product which was triturated with methanol. The resulting precipitate was collected by filtration, washed with ether and dried in vacuo giving the title compound as an off-white solid. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.48 (d, 1H), 8.33 (d, 1H), 8.21 (br, 1H), 8.06 (m, 3H), 7.78 (d, 2H), 7.68 (m, 3H), 7.58 (d, 1H), 7.51 (t, 2H), 7.41 (t, 1H), 3.02 (s, 3H). Example 126 N-(Isoquinolin-5-yl)-3′-methyl-1,1′-biphenyl-4-carboxamide To a solution of 4-bromo-N-isoquinolin-5-ylbenzamide (D94) (50 mg, 0.153 mmol) in toluene (2 ml) and ethanol (0.4 ml) under an argon atmosphere was added 3-methyl-phenylboronic acid (21 mg, 0.153 mmol), 2M sodium carbonate solution (0.15 ml) and tetrakis(triphenylphosphine)palladium (0) (5 mg, 0.05 mmol). The reaction was heated at reflux for 18 h, then cooled to room temperature and diluted with EtOAc. The mixture was washed with sat. aq. sodium bicarbonate solution and water, dried over MgSO4 and concentrated to give the crude product which was purified by SPE column chromatography. Elution with 50% EtOAc/40-60° C. petroleum ether gave the title compound as an off-white solid. 1H NMR (400 MHz, CDCl3) δ (ppm): 9.32 (s, 1H), 8.62 (d, 1H), 8.34 (d, 1H), 8.22 (br, 1H), 8.07 (d, 2H), 7.90, (d, 1H), 7.78 (d, 2H), 7.70 (m, 3H), 7.47 (m, 2H), 7.40 (t, 1H), 2.47 (s, 3H). Example 127 N-(Isoquinolin-8-yl)-1,1′-biphenyl-4-carboxamide Using the procedure outlined in Example 56, the title compound was prepared from 8-aminoisoquinoline (D95) (85 mg, 0.59 mmol) and 4-biphenylcarboxylic acid (177 mg, 0.89 mmol) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ (ppm): 9.48 (s, 1H), 8.61 (d, 1H), 8.42 (br.s, 1H), 8.22 (d, 1H), 8.10 (d, 2H), 7.79 (d, 2H), 7.68-7.76 (m, 5H), 7.51 (t, 2H), 7.43 (t, 1H). Example 128 N-(Isoquinolin-7-yl)-1,1′-biphenyl-4-carboxamide To a solution of 7-aminoisoquinoline (D96) (88 mg, 0.61 mmol) in DCM (4 ml) was added 4-biphenylcarboxylic acid (145 mg, 0.73 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (140 mg, 0.73 mmol) and the reaction stirred at ambient temperature overnight. The reaction mixture was filtered to give the title compound as a white solid. The filtrate was diluted with DCM, washed with 2M sodium hydroxide solution, dried over MgSO4 and concentrated in vacuo to give further crude product which was purified by silica SPE chromatography. Elution with an EtOAc/60-80° C. petroleum ether gradient gave a further title compound which was combined with the sample obtained from the filtration. This was dissolved in ethanol and treated with ethereal HCl and the resultant precipitate was collected to give the HCl salt of the title compound as a white solid. 1H NMR (250 MHz, DMSO) δ (ppm): 9.80 (s, 1H), 9.09 (d, 1H), 8.58 (d, 1H), 8.40 (dd, 1H), 8.33 (d, 1H), 8.28 (d, 1H), 8.16 (d, 2H), 7.90 (d, 2H), 7.79 (d, 2H), 7.54 (t, 2H), 7.45 (t, 1H) Example 129 N-(Isoquinolin-6-yl)-1,1′-biphenyl-4-carboxamide Using the procedure outlined in Example 56, the title compound was prepared from 6-aminoisoquinoline (D97) (37 mg, 0.25 mmol) and 4-biphenylcarboxylic acid (75 mg, 0.38 mmol) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ (ppm): 9.20 (s, 1H), 8.52 (d, 1H), 8.46 (d, 1H), 8.09 (br.s, 1H), 8.00 (m, 3H), 7.77 (d, 2H), 7.65-7.70 (m, 4H), 7.50 (t, 2H), 7.43 (t, 1H). Example 130 N-Isoquinolin-5-yl-1-(5-trifluoromethylpyrid-2-yl)-piperidine-4-carboxamide Using the procedure outlined in Example 107, the title compound was prepared from 1-(5-trifluoromethylpyrid-2-yl)-piperidine-4-carboxylic acid (D101) (100 mg, 0.36 mmol) and 5-aminoisoquinoline (27 mg, 0.19 mmol) as an off white solid. MS(ES): MH+ 401, M-H+ 399. Example 131 6-(2,4-Difluorophenyl)-2-methyl-N-(1,2,3,4-tetrahydroquinolin-7-yl)nicotinamide Using the procedure outlined in Example 38, the title compound was prepared from 7-amino-1-trifluoroacetyl-1,2,3,4-tetrahydroquinoline (D5) (73 mg, 0.30 mmol) and 2-methyl-6-(2,4-difluorophenyl)nicotinic acid (D106) (82 mg, 0.33 mmol) then converted to the HCl salt as an off-white solid. 1H NMR (400 MHz, MeOH-d4) δ (ppm): 8.46 (d, 1H), 8.11 (d, 1H), 7.93-8.01 (m, 2H), 7.81 (d, 1H), 7.40 (d, 1H), 7.25 (m, 2H), 3.55 (m, 2H), 2.96 (t, 2H), 2.88 (s, 3H), 2.18 (m, 2H). Example 132 6-(3,4-Difluorophenyl)-2-methyl-N-(1,2,3,4-tetrahydroquinolin-7-yl)nicotinamide Using the procedure outlined in Example 38, the title compound was prepared from 7-amino-1-trifluoroacetyl-1,2,3,4-tetrahydroquinoline (D5) (73 mg, 0.30 mmol) and 2-methyl-6-(3,4-difluorophenyl)nicotinic acid (D108) (82 mg, 0.33 mmol) then converted to the HCl salt as a buff solid. 1H NMR (400 MHz, DMSO) δ (ppm): 8.23 (dd, 1H), 8.04 (m, 3H), 7.87 (d, 1H), 7.63 (d, 1H), 7.57 (m, 1H), 7.29 (d, 1H), 3.34 (m, 2H), 2.80 (m, 2H), 2.67 (s, 3H), 2.02 (m, 2H). Example 133 N-Quinolin-6-yl-1,1′-biphenyl-4-carboxamide Using the procedure outlined in Example 56, the title compoudn was prepared from 6-aminoquinoline (72 mg, 0.75 mmol) and 4-biphenylcarboxylic acid (149 mg, 0.75 mmol) as a white solid. 1H NMR (400 MHz, CDCl3) δ (ppm): 9.22 (d, 1H), 8.88 (dd, 1H), 8.52 (d, 1H), 8.33 (dd, 1H), 8.19 (d, 1H), 8.13 (d, 1H), 8.09 (d, 1H), 8.08 (m, 3H), 7.91 (d, 1H), 7.72 (dd, 1H), 7.52 (m, 3H), 7.43 (dd, 1H). Pharmacological Data (a) In Vitro Assay As referenced above, the compounds of the invention are vanilloid receptor (VR1) antagonists and hence have useful pharmaceutical properties. Vanilloid receptor (VR1) antagonist activity can be confirmed and demonstrated for any particular compound by use of conventional methods, for example those disclosed in standard reference texts such as D. Le Bars, M. Gozarin and S. W. Cadden, Pharmacological Reviews, 2001, 53(4), 597-652] or such other texts mentioned herein. The screen used for the compounds of this invention was based upon a FLIPR based calcium assay, similar to that described by Smart et al. (British Journal of Pharmacology, 2000, 129, 227-230). Transfected astrocytoma 1321N1 cells, stably expressing human VR1, were seeded into FLIPR plates at 25,000 cells/well (96-well plate) and cultured overnight. The cells were subsequently loaded in medium containing 4 μM Fluo-3 AM (Molecular Probes) for 2 hours, at room temperature, in the dark. The plates were then washed 4 times with Tyrode containing 1.5 mM calcium, without probenecid. The cells were pre-incubated with compound or buffer control at room temperature for 30 minutes. Capsaicin (Sigma) was then added to the cells. Compounds having antagonist activity against the human VR1 were identified by detecting differences in fluorescence when measured after capsaicin addition, compared with no compound buffer controls. Thus, for example, in the buffer control capsaicin addition results in an increase in intracellular calcium concentration resulting in fluorescence. A compound having antagonist activity blocks the capsaicin binding to the receptor, there is no signalling and therefore no increase in intracellular calcium levels and consequently lower fluorescence. pKb values are generated from the IC50 values using the Cheng-Prusoff equation. All compounds tested by the above methodology had pKb>6, preferred compounds having a pKb>7.0. (b) FCA-Induced Hyperalgesia in the Guinea Pig 100 μl of 1 mg/ml FCA was injected intraplantar into the left paw of 4 groups of 8 male Dunkin Hartley guinea-pigs (batch: 6282434, average weight 340 g). 24 hours later compounds were administered orally at 0 (vehicle), 3, 10 30 mg/kg with vehicle as 1% methylcellulose and dosing volume being 2 ml/kg and dosing straight into the stomach. The methylcellulose was added gradually to the compound into the pestle and mortar and ground together. Behavioural readouts of mechanical hyperalgesia were obtained before FCA administration (naïve reading), after FCA but before drug administration (predose reading) and 1 hour after drug administration. The readout used was paw pressure (Randall-Sellito) and the end point was paw withdrawal. The paw pressure equipment also had one silver disc placed on the point to increase the markings by a factor of 2. Compounds having a pKb>7.0 in vitro, according to model (a) above, were tested in this model and shown to be active.

20050926

20090526

20060629

59270.0

A61K314709

NORTHINGTON DAVI, ZINNA

VANILLOID RECEPTOR MODULATORS

UNDISCOUNTED

ACCEPTED

A61K

ACCEPTED

Compact printer

A printer comprises a printing unit that includes a printhead. A cartridge (22) containing a supply of print media (70) and a supply of ink (54) is received in the unit. The supply of print media and the supply of ink are arranged in stacked relationship relative to one another to reduce a footprint of the cartridge and, hence, the printing unit.

1. A printer, comprising: a printing unit, including a printhead; a replaceable cartridge containing a stack of print media sheets and an ink reservoir for supply to the printing unit, wherein the supply of print media and the ink reservoir are arranged in stacked relationship relative to one another within the cartridge; and an interface for receiving the replaceable cartridge. 2. The printer of claim 1, wherein the stack of sheets are received in a receptacle within the cartridge. 3. The printer of claim 2, wherein the receptacle is displaceably arranged relative to a floor of the cartridge. 4. The printer of claim 3, wherein the ink reservoir has at least one ink storage zone, the ink reservoir being arranged between the floor of the cartridge and the receptacle. 5. The printer of claim 4, wherein said at least one ink storage zone comprises a channel defining portion and a flexible membrane closing off said channel, said flexible membrane collapsing into the channel, in use, for inhibiting ingress of air into said channel as ink is withdrawn from the channel. 6. The printer of claim 2, wherein the supply of ink is arranged between the receptacle and a cover of the unit. 7. The printer of claim 1, being a full color printer. 8. The printer of claim 7, being a photo quality color printer. 9. The printer of claim 1 in which the printhead is a pagewidth inkjet printhead. 10. The printer of claim 9 in which the printhead comprises an inkjet nozzle array, the array being fabricated by microelectromechanical techniques. 11. The printer of claim 1, the printer including: a chassis adapted to receive the cartridge in use, the chassis including: (i) Ink hoses for coupling the printhead to the ink reservoir, and, (ii) A feed system for feeding sheets of paper from the stack to the printhead for printing thereon. 12. A printer according to claim 11, the feed system including (a) A pick-up roller for engaging sheets of paper in the stack; (b) A first motor; and, (c) A first gear train or coupling the motor to the pick-up roller. 13. A printer according to claim 12, the drive system further including: (a) A drive roller positioned between the pick-up roller and the printhead to feed sheets to the printhead; (b) A second motor; and, (c) A second gear train for coupling the second motor to the drive roller. 14. A printer according to claim 13, the cartridge including a sprung roller, wherein in use the sprung roller is urged toward the drive roller, the sheets of paper being fed between the drive roller and the sprung roller. 15. A printer according to claim 12, the cartridge including two first racks for engaging corresponding cogs mounted to an axle on the chassis to thereby prevent skewing of cartridge as it is inserted into and removed from the chassis. 16. A printer according to claim 15, the cartridge including a second rack for engaging the first gear train such that operation of the gear train can be used to feed the cartridge into the chassis. 17. A printer according to claim 16, the printer including a reversing mechanism adapted to selectively coupled the first gear train to the second rack or the pick-up roller. 18. A printer according to claim 1, the cartridge including: (i) A floor, (ii) A platen for receiving the stack of sheets in use; (iii) A plurality of leaf springs for urging the platen away from the floor, to thereby urge the stack of paper toward the pick-up roller. 19. A printer according to claim 1, the ink reservoir including: (a) an ink supply molding defining a plurality of ink supply channels for containing respective colours of ink; (b) a flexible membrane for sealing the molding; (c) an ink outlet coupled to each channel for coupling the ink channel to a respective ink hose. 20. A printer according to claim 9, the ink outlet including a rupterable seal, the chassis including an ink supply manifold having respective pins, each pin being in fluid communication with a respective the ink supply hose and being adapted to rupture the seal on the respective ink outlet. 21. A replaceable cartridge configured for use in the printer of claim 1.

FIELD OF INVENTION This invention relates to a printer for a conveyance and to a conveyance including such printer. In this specification, unless the context clearly indicates otherwise, the term “conveyance” is to be understood in a broad sense as any form of device which conveys persons and/or goods and includes, but is not necessarily limited to, road vehicles, rail vehicles, aircraft, spacecraft and waterborne craft. BACKGROUND OF THE INVENTION These days, more and more information is provided to people. The information is made available in various forms, including audible forms and visual forms. Often, the information is made available to persons in a conveyance. There are situations where it is desirable to have a record of such information. To date, making a record of such information means that the person needs some means to record the information, for example, on a magnetic recording medium by way of a dictation machine or by making written notes on paper. Often such recording devices are not readily to hand and vital information can be lost. It would be desirable if a relatively economical and robust printed could be provided in a conveyance for recording printable information in hard copy. CO-PENDING APPLICATIONS Various methods, systems and apparatus relating to the present invention are disclosed in the following co-pending applications filed by the applicant or assignee of the present invention on 12 Feb. 2003: PCT/AU03/00154 PCT/AU03/00151 PCT/AU03/00150 PCT/AU03/ 00145 PCT/AU03/00153 PCT/AU03/00152 PCT/AU03/00168 PCT/AU03/ 00169 PCT/AU03/00170 PCT/AU03/00162 PCT/AU03/00146 PCT/AU03/ 00159 PCT/AU03/00171 PCT/AU03/00149 PCT/AU03/00167 PCT/AU03/ 00158 PCT/AU03/00147 PCT/AU03/00166 PCT/AU03/00164 PCT/AU03/ 00163 PCT/AU03/00165 PCT/AU03/00160 PCT/AU03/00157 PCT/AU03/ PCT/AU03/00156 PCT/AU03/00155 00148 The disclosures of these co-pending applications are incorporated herein by cross-reference. 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No. 09/693,735 PCT/AU98/00550 PCT/AU00/00516 PCT/AU00/00517 PCT/AU00/00511 PCT/AU00/00754 PCT/AU00/00755 PCT/AU00/00756 PCT/AU00/00757 PCT/AU00/00095 PCT/AU00/00172 PCT/AU00/00338 PCT/AU00/00339 PCT/AU00/00340 PCT/AU00/00341 PCT/AU00/00581 PCT/AU00/00580 PCT/AU00/00582 PCT/AU00/00587 PCT/AU00/00588 PCT/AU00/00589 PCT/AU00/00583 PCT/AU00/00593 PCT/AU00/00590 PCT/AU00/00591 PCT/AU00/00592 PCT/AU00/00584 PCT/AU00/00585 PCT/AU00/00586 PCT/AU00/00749 PCT/AU00/00750 PCT/AU00/00751 PCT/AU00/00752 PCT/AU01/01332 PCT/AU01/01318 PCT/AU00/01513 PCT/AU00/01514 PCT/AU00/01515 PCT/AU00/01516 PCT/AU00/01517 PCT/AU00/01512 PCT/AU01/00502 PCT/AU02/01120 PCT/AU00/00333 PCT/AU01/00141 PCT/AU01/00139 PCT/AU01/00140 PCT/AU00/00753 PCT/AU01/01321 PCT/AU01/01322 PCT/AU01/01323 PCT/AU00/00594 PCT/AU00/00595 PCT/AU00/00596 PCT/AU00/00597 PCT/AU00/00598 PCT/AU00/00741 PCT/AU00/00742 SUMMARY OF THE INVENTION According to the invention there is provided a printer, comprising: a printing unit, including a printhead; a replaceable cartridge containing a supply of print media and a supply of ink for supply to the printing unit, wherein the supply of print media and the supply of ink are arranged in stacked relationship relative to one another within the cartridge; and an interface for receiving the replaceable cartridge. The supply of print media may be in the form of a stack of sheets of print media, such as paper, the stack of sheets being received in a receptacle. The receptacle may be in the form of a platen. The platen may be displaceably arranged relative to a floor of the cartridge so that one sheet of print media at a time may be fed to the printhead of the printing unit. The supply of ink may be in the form of an ink reservoir having at least one ink storage zone, the ink reservoir being arranged between the floor of the cartridge and the receptacle. The at least one ink storage zone may comprise a channel defining portion and a flexible membrane closing off the channel, the flexible membrane collapsing into the channel, in use, for inhibiting ingress of air into said channel as ink is withdrawn from the channel. In another embodiment of the invention, the supply of ink may be arranged between the receptacle and a cover of the unit. The printer may be a full color printer. More particularly, the printer may be a photo quality color printer. Accordingly, the ink storage zone may comprise a plurality of channels, one for each color of ink. The printhead may be a pagewidth inkjet printhead. The printhead may comprise an inkjet nozzle array, the array being fabricated by microelectromechanical techniques. BRIEF DESCRIPTION OF DRAWINGS A preferred and exemplary embodiment of the invention will now be described with reference to the accompanying drawings, in which:— FIG. 1 shows a three dimensional, front view of a printer, in accordance with the invention, for a conveyance; FIG. 2 shows a three dimensional, rear view of the printer; FIG. 3 shows a three dimensional, front view of the printer illustrating cartridge insertion or removal; FIG. 4 shows a three dimensional view of the printer with a top cover removed; FIG. 5 shows a three dimensional, exploded view of the printer; FIG. 6 shows a plan view of the printer; FIG. 7 shows a sectional, side view of the printer taken along line VII-VII in FIG. 6; FIG. 8 shows a sectional, end view of the printer taken along line VIII-VIII in FIG. 6; FIG. 9 shows a first drive arrangement of the printer, FIG. 10 shows a second drive arrangement of the printer, FIG. 11 shows a three dimensional, top view of an ink cartridge for the printer, FIG. 12 shows a three dimensional, bottom view of the cartridge; FIG. 13 shows a three dimensional, exploded view of the cartridge; FIG. 14 shows a plan view of the cartridge; FIG. 15 shows a sectional, end view taken along line XV-XV in FIG. 14; FIG. 16 shows a sectional, side view of the cartridge taken along line XVI-XVI in FIG. 14; FIG. 17 shows a schematic, plan view of one embodiment of the cartridge; FIG. 18 shows a schematic, plan view of another embodiment of the cartridge; FIG. 19 shows a schematic, plan view of a further embodiment of the cartridge; FIG. 20 shows a schematic, plan view of yet a further embodiment of the cartridge; FIG. 21 shows a schematic representation of an interior compartment of a vehicle indicating various locations for the printer of FIGS. 1 to 10; FIG. 22 shows a three dimensional view of a vehicle audio unit incorporating a printer, in accordance with the invention; FIG. 23 shows a three dimensional view of a further vehicle audio unit incorporating a printer and other devices; FIG. 24 shows a three dimensional view of yet a further vehicle audio unit incorporating the printer; and FIG. 25 shows a three-dimensional view of still a further vehicle audio unit incorporating a printer and other devices. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT Referring to the drawings, reference numeral 10 generally designates a printer, in accordance with the invention, for a conveyance as defined herein. The printer 10 is intended for use in any suitable type of conveyance of the type described. However, for ease of reference, the printer 10 will be described with reference to its application in a motor vehicle. The printer 10 includes a chassis 12 (FIG. 4) which is covered by a top cover 16 that has an access opening 18 closed off by a flap 20. The flap 20 is spring biased so that, when a cartridge 22 has been removed from the printer 10, the flap is urged to the position shown in FIG. 1 of the drawings. In the particularly preferred embodiment, the printer 10 does not have any of its own controls and, effectively, is a dumb unit. The unit is therefore actuated from a device from which it is desired to print material. The device that sends commands to the printer 10 can either be hard wired to the printer 10, for example, via a wiring loom of the motor vehicle or, instead, the device may send commands to the printer 10 in a wireless manner. For this purpose, the printer 10 includes a port 24 able to detect wireless communications of some form. Various forms of wireless communications can be employed such as an infrared communication system, a personal area network (PAN) system referred to as Bluetooth, a radio local area network (LAN) or a digital cordless telephone system. Further, the device which communicates with the printer 10 can be of various forms such as, for example, a palm computer, a laptop computer, a mobile telephone, a digital camera, a scanner, a diagnostics system for the motor vehicle, a navigation system, a vehicle entertainment system, or the like. This is not intended to be an exhaustive list and those skilled in the art will readily conceive of other devices that can communicate with the printer 10. The port 24 is mounted on a front face 26 of the printer 10. As shown in greater detail in FIG. 2 of the drawings, a rear face 28 of the printer 10 accommodates a data socket 30 and a power socket 32. It will be appreciated that, when the printer 10 communicates exclusively in a wireless manner, the data socket 30 may be omitted. The printer 10 incorporates a printhead 34 (FIG. 4). The printhead 34 is a pagewidth ink jet printhead. More particularly, the printhead 34 is a four color printhead, or three color plus infrared ink, printhead that prints photo quality prints on print media stored in the cartridge 22. The printhead 34 comprises an array of nozzles to provide printing at 1600 dpi. The nozzles of the printhead 34 are manufactured using the applicant's Memjet technology. The printhead 34 receives commands from a printed circuit board (PCB) 36 secured to the chassis 12. A pair of drive motors 38 and 40 is mounted on a sidewall 42 of the chassis 12. The drive motor 38, which is in the form of a stepper motor, drives a first drive arrangement in the form of a first gear train 44. The first gear train 44 is mounted on a side molding 46 of the chassis 12. The drive motor 40, which is also in the form of a stepper motor, drives a drive roller 48 via a second drive arrangement. The second drive arrangement comprises a second gear train 50. The printhead 34 receives ink from ink hoses 52 that communicate with an ink supply reservoir 54 (FIGS. 13 and 15) of the cartridge 22 via an ink supply manifold 56, as will be described in greater detail below. Referring to FIG. 5 of the drawings, an exploded view of the printer 10 is illustrated. It is to be noted that the printhead 34 communicates with the PCB 36 via a TAB film 54. A slot 58 is defined in the side molding 46. The slot 58 receives a corresponding formation of the cartridge 22 in it. Further, a roller set 60 is mounted on a base 62 of the printer 10. The roller set 60 comprises a rotatable axle 62. A cog 64 is mounted proximate each end of the axle 62. Each cog 64 engages a rack 100, 102 (FIG. 12) on the cartridge 22 for inhibiting skewing of the cartridge 22 as it is inserted into, or withdrawn from, the interior of the printer 10. The first gear train 44 engages a pick up roller 68 of the printer 10. The pick up roller 68 picks up print media in the form of a sheet of paper from a stack 70 of paper (FIG. 13) in the cartridge 22 for feeding to the printhead 34 of the printer 10 when printing is to be effected. As shown in greater detail in FIG. 9 of the drawings, the first gear train 44 is powered by the stepper motor 38 via an axle 72 extending across the printer 10 to convey power from the stepper motor 38 to the first gear train 44. A gear 74 is mounted against the molding 46 at one end of the axle 72. The gear 74 drives a reduction gear set 76. Further, the reduction gear set 76 communicates with a reversing mechanism 78. Accordingly, the gear train 44 performs two functions. When the reversing mechanism 78 is not selected, the gear train 44 engages an upper rack 80 on the cartridge 22 for feeding the cartridge 22 into the printer 10 or ejecting the cartridge 22 from the printer 10. Instead, when the reversing mechanism is in the position shown in FIG. 9 of the drawings, it engages the pick up roller 68 or, more particularly, a gear 82 mounted at an end of the pick up roller 68. The gear train 44 then serves to feed the paper to the drive roller 48 for conveying to the printhead 34. Referring now to FIGS. 11 to 20 of the drawings, the cartridge 22 is described in greater detail. The cartridge 22 comprises a base molding 90 closed off by a metal cover 92. The cover 92 has a pair of transversely spaced openings 94 defined in its front edge. These openings 94 permit the pick up roller 68 of the printer 10 to engage a topmost sheet of the stack 70 of paper within the cartridge 22. A toothed rack 96 is provided on one side of the cartridge 22. The toothed rack 96 defines the upper rack 80 that is engaged by a gear of the first gear train 44 for insertion of the cartridge 22 into, or its ejection from, the printer 10. A rib 98 extends longitudinally along the side of the toothed rack 96. The rib 98 is received in the slot 58 in the side molding 46 of the printer 10. A lower surface of the toothed rack 96 also has the rack 100 (FIG. 12) for engagement with one of the cogs 64. An opposed side of the base molding 90 of the cartridge 22 carries the other rack 102, which engages the other, cog 64 for inhibiting skewing of the cartridge 22 when it is inserted into, or ejected from, the printer 10. A feed slot 104 is defined at a front edge of the metal cover through which a sheet of paper to be printed is passed in use. The feed slot 104 is partially defined by a plastics strip 106 that inhibits more than one sheet of paper being fed to the printhead 34 at any one time. A transversely extending trough 108 is defined outwardly of the strip 106. The trough 108 accommodates a sprung roller 110 therein. The roller 110 is supported in the trough 108 via a plurality of clips 112. The roller 110 is biased upwardly relative to a base of the trough 108 via a plurality of leaf springs 114. The leaf springs 114 are formed integrally with an L-shaped metal bracket 116 that partially forms the trough 108. The roller 110 is a snap-fit in the clips 112. A platen 118 is accommodated in the base molding 90. The platen 118 is spring biased via a plurality of leaf springs 120 which engage a floor 122 of the base molding 90 for urging the stack 70 of paper against the cover 92. The ink supply reservoir 54 includes an ink supply molding 124 formed integrally with the base molding 90. The ink supply molding 124 defines a plurality of ink supply channels 126. Each ink supply channel 126 contains a particular color of ink. In this context, the term “color” is to be understood as including inks that are substantially invisible to humans, such as infrared inks. The channels 126 are closed off by a flexible bladder-like membrane 128, which is heat-sealed to the molding 124. It will be appreciated that, as ink is withdrawn from each channel 126, the associated membrane 128 collapses into the channel 126 thereby inhibiting the ingress of air into that channel 126. Each channel 126 communicates with an ink outlet 130. Each ink outlet 130 is in the form of a rupturable seal. As shown in greater detail in FIG. 5 of the drawings, the ink supply manifold 56 of the printer 10 includes pins 132. These pins 132 communicate with the ink supply hoses 52. When the cartridge 22 is inserted into the printer 10, and the cartridge 22 is driven home by the gear train 44, the pins 132 pierce the seals 130 to place the hoses 52 in communication with their associated ink supply channels 126. The cartridge 22 includes a quality assurance chip 134. This chip 134 ensures correct communications between the cartridge 22 and the printer 10 and that the cartridge 22 is of the required quality. The chip 134 communicates with the printer 10 via chip contacts 136 mounted on the ink supply manifold 56 of the printer 10. Thus, when the cartridge 22 is driven home by the gear train 44, the chip 134 engages the contacts 136 for enabling communications to be established between the chip 134 and the circuit board 36 of the printer 10. FIG. 17 shows a first embodiment of the cartridge 22 with the ink supply reservoir 54 arranged on a left side of the cartridge 22 and the stack 70 arranged on the right side of the cartridge 22. FIG. 18 shows another embodiment of the cartridge 22 with the stack 70 arranged on the left side of the cartridge 22 and the ink supply reservoir 54 being arranged on the right side of the cartridge 22. FIG. 19 shows yet a further embodiment with the stack 70 arranged at a front of the cartridge 22 with the ink supply reservoir 54 being arranged at a rear of the cartridge 22. FIG. 20 shows yet a further embodiment with the stack 70 arranged on the platen 118 with the ink supply reservoir 54 being arranged below the platen 118. It will be appreciated also, with reference to this embodiment that the ink supply reservoir 54 could be arranged above the stack of paper 70 although this will increase the height of the cartridge 22 and, accordingly, the height of the printer 10. The cartridge 22 is a disposable unit so that, once its ink supply and paper supply have been depleted, the cartridge is disposed of. Instead, the cartridge 22 may be re-useable. In the latter case, once the supply of ink and paper in the cartridge 22 have been depleted and the cartridge 22 is ejected from the printer 10, the used, empty cartridge 22 can be taken by a user to a supplier for a refund, credit or exchange. It is to be noted that the cartridge 22 is automatically ejected from the printer 10 once its supply of paper and/or ink has been depleted. As described above, the printer 10 is intended particularly for use in a motor vehicle. The printer 10 is dimensioned to fit in numerous positions in a passenger compartment 130 (FIG. 21) of a motor vehicle 132. The printer 10 is, desirably, mounted where it is readily accessible within the passenger compartment 130 of the vehicle 132. Various desirable locations within the passenger compartment 130 are now described. Firstly, a printer, designated by the reference numeral 10.1, can be mounted in a dashboard 134 of the vehicle 132. This provides a good location at least for front occupants of the passenger compartment 130 and, usually, this part of the dashboard 134 of the vehicle 132 is unoccupied by other equipment. A second desirable location is in an overhead fitting 136 arranged above a rear view mirror 138 of the passenger compartment 130. Thus, a printer 10.2 can be mounted in this fitting 136. Once again, this provides good access, at least for front occupants of the passenger compartment. Another location in the passenger compartment for a printer 10.3 is a glovebox 140. This is a convenient location in that the printer 10.3 can be built into the lid 140 of the glovebox. This renders the printer 10.3 readily accessible for servicing purposes. Yet a further location is in an upper region of a console 142 as illustrated by printer 10.4. Another suitable location for a printer 10.5 is in a lower region of the console 142 where, for example, coin trays or the like are sometimes mounted. A further suitable location is in a central armrest 144 of the passenger compartment 130 in which a printer 10.6 could be installed. Still further, if there is sufficient space, printers 10.7 could be built into door arm rests 146 of the passenger compartment Only the person adjacent such a door armrest will have easy access to the printer 10.7 but this need not necessarily be a major inconvenience. It will also be appreciated that more than one printer can be provided in the passenger compartment. Although not shown, printers can also be provided in back rests of the front seats of the passenger compartment 130. Those skilled in the art will appreciate that the exemplified locations as described above are not the only locations in which printers 10 could be installed and it is conceivable that printers could be stored in less convenient location such as in footwells of the passenger compartment 130, under the front seats, in an arm rest of a rear seat of the passenger compartment 130, or the like. Also, it is envisaged that receiving sockets for printers can be molded into relevant fittings in the passenger compartment 130 during manufacture of the vehicle 132. The receiving sockets could include wiring for the printer 10. The receiving sockets can then be closed off by blanking plates, the relevant blanking plate being removed to facilitate installation of the printer 10. In another embodiment of the invention, the printers 10 are built into and form part of car audio devices, which are also referred to as in car entertainment (ICE) units. Accordingly, as shown in FIG. 22 of the drawings, an ICE unit 150 is illustrated. The ICE unit 150 incorporates a radio having an LCD display 152, a CD player having a slot 154 in a front panel of the unit 150 and various controls 158. The ICE unit 150 includes a printer 10 as described above including the cartridge 22. The ICE unit 150 includes controls 160 for controlling printing from the printer 10. The controls 160 are used for instructing the printer 10 to print required information. Depending on the material to be printed, the LCD 152 can be used for previewing material to be printed. It is envisaged that this embodiment of the invention will be used for printing information from radio broadcasts, CD's played in the CD player 150, or the like. Referring now FIG. 23 of the drawings a variation of the ICE unit 150 illustrated in FIG. 22 is illustrated. With reference to FIG. 22, like reference numerals refer to like parts, unless otherwise specified. In this embodiment of the invention, the ICE unit 150 includes a slot 162 in which a digital camera 164 is received. The digital camera 164 and the slot 162 have corresponding electrical contacts so that information can be downloaded from the camera 164 to be printed via the printer 10. Accordingly, it is an advantage of this embodiment of the invention that information from a digital camera can be downloaded as soon as a user of the camera has used the camera and/or has returned to the vehicle 132. Thus, the user need not, unlike at present, await the user's return to a venue where the camera can communicate with a computer for downloading information captured by the camera 164. It is also contemplated that a suitable slot 162 could be incorporated in, for example, the dashboard 134 of the vehicle 132 as illustrated at 166 so that a camera can be incorporated in the vehicle 132 for printing on any one of the printers 10.1 to 10.7. In other words, the slot 166 need not form part of an ICE unit but may be provided as a separate feature in the vehicle 132 in association with one of the printers 10.1 to 10.7. Referring now to FIGS. 24 and 25 of the drawings, a further ICE unit 170 is provided. In this embodiment, the ICE unit 170, in addition to a CD player 172 and a radio having controls 174, includes a full color LCD 176. The ICE unit 170 further functions as a satellite navigation unit and may also be used for receiving television signals. The unit 170 incorporates a printer 10 of the type described above. The unit 170 includes controls 178. These controls 178 are GPS controls and are used for satellite navigation purposes. In addition, a further bank of controls 180 is provided for controlling the printer 10. With this unit 170, a map, or the like, can be downloaded and printed via the printer 10 or images from the LCD 176 when it is used as a television receiver can be printed via the printer 10. The unit 170 shown in FIG. 25 of the drawings, once again, incorporates a slot 182 for receiving a digital camera 184. The slot 182 and the digital camera 184 therefore have corresponding electrical contacts for enabling data to be downloaded from the digital camera 184 to be printed on the printer 10. Accordingly, it is an advantage of the invention that an in-vehicle printer 10 is provided for enabling suitable materials to be downloaded and printed rapidly. Further, the fact that the printhead 34 of the printer 10 uses a pagewidth, full color printhead means that high quality images can be printed using the printer 10. It will also be appreciated that, due to the fact that the printhead 34 is a pagewidth printhead and does not traverse the media on which an image is being printed, it is less susceptible to jolting, bumping or other such disturbances. In other words, it is less likely to produce a poor quality image even if printing is taking place while the vehicle is moving. Although the invention has been described with reference to a number of specific embodiments, it will be appreciated by those skilled in the art that the invention can be embodied in many other forms without departing from the spirit and intended scope of the invention.

<SOH> BACKGROUND OF THE INVENTION <EOH>These days, more and more information is provided to people. The information is made available in various forms, including audible forms and visual forms. Often, the information is made available to persons in a conveyance. There are situations where it is desirable to have a record of such information. To date, making a record of such information means that the person needs some means to record the information, for example, on a magnetic recording medium by way of a dictation machine or by making written notes on paper. Often such recording devices are not readily to hand and vital information can be lost. It would be desirable if a relatively economical and robust printed could be provided in a conveyance for recording printable information in hard copy.

<SOH> SUMMARY OF THE INVENTION <EOH>According to the invention there is provided a printer, comprising: a printing unit, including a printhead; a replaceable cartridge containing a supply of print media and a supply of ink for supply to the printing unit, wherein the supply of print media and the supply of ink are arranged in stacked relationship relative to one another within the cartridge; and an interface for receiving the replaceable cartridge. The supply of print media may be in the form of a stack of sheets of print media, such as paper, the stack of sheets being received in a receptacle. The receptacle may be in the form of a platen. The platen may be displaceably arranged relative to a floor of the cartridge so that one sheet of print media at a time may be fed to the printhead of the printing unit. The supply of ink may be in the form of an ink reservoir having at least one ink storage zone, the ink reservoir being arranged between the floor of the cartridge and the receptacle. The at least one ink storage zone may comprise a channel defining portion and a flexible membrane closing off the channel, the flexible membrane collapsing into the channel, in use, for inhibiting ingress of air into said channel as ink is withdrawn from the channel. In another embodiment of the invention, the supply of ink may be arranged between the receptacle and a cover of the unit. The printer may be a full color printer. More particularly, the printer may be a photo quality color printer. Accordingly, the ink storage zone may comprise a plurality of channels, one for each color of ink. The printhead may be a pagewidth inkjet printhead. The printhead may comprise an inkjet nozzle array, the array being fabricated by microelectromechanical techniques.

20040809

20061219

20050721

72244.0

VO, ANH T N

COMPACT PRINTER

UNDISCOUNTED

ACCEPTED

ACCEPTED

Methods for casein determination in milk

The content of casein in milk is determined by two measurements of infrared absorbance in a milk sample by infrared spectrometry before and after a separation of the casein. The casein content is calculated by use of absorbance data recorded during the two absorbance measurements. The new method is considerable faster than the known wet-chemical methods, such as the normal wet chemical reference method for casein determination in milk using a Kjeldahl nitrogen determination of the milk sample, then a coagulation of the milk, and finally a Kjeldahl nitrogen determination of the filtrate. Further the new method provides a more reliable accuracy than the know determination using a single infrared analysis of a milk sample.

1. A method for the determination of the content of casein in milk, wherein a milk sample is measured before and after a separation into casein and a liquid phase, called a supernatant promoted by adding to the milk sample at least one chemical solution adequate for precipitation of casein, and comprising the steps of measuring by infrared spectrometry the infrared absorbance in the milk sample before separation, measuring by infrared spectrometry the infrared absorbance in the supernatant (liquid phase of the milk sample after separation of casein), and calculating the casein content by use of absorbance data recorded during the two infrared spectrometry measurements of absorbance, characterised in that a dilution factor (Df) indicating the dilution of the supernatant compared to the original milk sample is calculated using absorbance data recorded during the infrared spectrometry measurement of absorbance in the supernatant, said dilution factor being applied for the calculation of the concentration of casein. 2. A method according to claim 1, wherein the concentration of protein, (P(Milk)) in the milk sample before separation is determined from the infrared absorbance in the milk sample before separation, and wherein the concentration of protein, (P(SN)) in the supernatant is determined from the infrared absorbance in supernatant, and wherein the concentration of casein is calculated as the difference between the concentration of protein (P(Milk)) in the milk sample and the dilution factor (Df) multiplied by the concentration of protein (P(SN)) in the supernatant as defined by the equation: P(casein)=P(Milk)−(Df*P(SN)). 3. A method according to claim 1, characterised by comprising the following steps 1) a fraction of a milk sample is analysed by mid-infrared spectroscopy to determine the content of protein, P(Milk), 2) an acid, initiating a precipitation of casein, is added to a remaining fraction of the milk sample and mixed with the sample, 3) a salt of the acid is added to obtain a pH about 4.6 and the sample is mixed again, 4) the fluid mixture is subjected to a separation process separating the fluid mixture into a liquid phase, called the supernatant, and a precipitate of casein, 5) the supernatant is transferred into a container, and a sample of the supernatant is analysed by mid-infrared spectroscopy to determine the content of protein in the supernatant, P(SN) 6) the content of whey-protein, P(Whey) in the original milk sample is calculated from the content of protein in the supernatant (liquid phase) by incorporating the dilution of the supernatant, caused by the addition of acid and salt, 7) the casein content in the original milk sample is calculated as Content of casein=P(Milk)−P(Whey) 4. A method according to claim 1, wherein the separation comprises a filtration. 5. A method according to claim 1, wherein the separation comprises a centrifugation. 6. A method according to claim 3, wherein the acid is acetic acid. 7. A method according to claim 3, wherein the salt is sodium acetate. 8. A method according to claim 1, characterised in that the method is carried out by use of spectroscopic infrared analysis instrument having a plurality of infrared filters enabling a determination of the protein content in a milk sample. 9. A method according to claim 1, characterised in that the method is carried out by use of a full spectrum instrument arranged for recording a spectrum substantially comprising the spectral range from about 1000- 3000 cm−1, such as a MilkoScan FT120. 10. A method according to claim 1, characterised in method is carried out by use of a full spectrum instrument, having a first protein calibration enabling a calculation of the protein content from the spectrum of the milk. 11. A method according to claim 1, characterised in that the method is carried out by use of a full spectrum instrument having a dilution calibration enabling a calculation of the dilution factor from the spectrum of the supernatant-sample. 12. A method according to claim 10, characterised in that the method is carried out by use of a full spectrum instrument having a second protein calibration enabling calculation of the protein content from the spectrum of the supernatant-sample (also called the filtrate). 13. A method according to claim 12 characterised in that the second protein calibration is robust to variations in the concentrations (different additions) of acetic add/sodium acetate. 14. A mid IR spectrometric analysis instrument characterized in that the instrument comprises a software program enabling an execution of the calculations involved in a method for the determination of the content of casein according to claim 1 by use of data recorded by the mid IR spectrometric analysis instrument. 15. A mid IR spectrometric analysis instrument according to claim 14 characterized in that the instrument comprises a software program enabling an execution of the calculations of the content of casein by use of data enabling a calculation of a dilution factor indicating the dilution of the whey compared to the original milk sample. 16. The mid IR spectrometric analysis instrument according to claim 14 further comprising a software program enabling an execution of a method a method that is carried out by use of a full spectrum instrument having a first protein calibration enabling a calculation of the protein content from the spectrum of milk and a second protein calibration enabling a calculation of the protein content from the spectrum of the supernatant-sample (also called the filtrate). 17. A mid IR spectrometric analysis instrument according to claim 14 further comprising a software program enabling an execution of a method method for the determination of the content of casein in milk, wherein a milk sample is measured before and after a separation into casein and a liquid phase, called a supernatant promoted by adding to the milk sample at least one chemical solution adequate for precipitation of casein, and comprising the steps of measuring by infrared spectrometry the infrared absorbance in the milk sample before separation, measuring by infrared spectrometry the infrared absorbance in the supernatant, and calculating the casein content by use of absorbance data recorded during the two infrared spectrometry measurements of absorbance, wherein a dilution factor (Df) indicating the dilution of the supernatant compared to the original milk sample is calculated using absorbance data recorded during the infrared spectrometry measurement of absorbance in the supernatant, said dilution factor being applied for the calculation of the concentration of casein and wherein the spectrometric instrument comprises a plurality of interchangeable optical IR filters able to be inserted into the light path of the spectrometric instrument. 18. A mid IR spectrometric analysis instrument according to claim 14 further comprising a software program enabling an execution of a method method for the determination of the content of casein in milk, wherein a milk sample is measured before and after a separation into casein and a liquid phase, called a supernatant promoted by adding to the milk sample at least one chemical solution adequate for precipitation of casein, and comprising the steps of measuring by infrared spectrometry the infrared absorbance in the milk sample before separation, measuring by infrared spectrometry the infrared absorbance in the supernatant, and calculating the casein content by use of absorbance data recorded during the two infrared spectrometry measurements of absorbance, wherein a dilution factor (Df) indicating the dilution of the supernatant compared to the original milk sample is calculated using absorbance data recorded during the infrared spectrometry measurement of absorbance in the supernatant, said dilution factor being applied for the calculation of the concentration of casein and wherein the spectrometric instrument is a Full spectrum instrument providing data representing a substantial portion of the MID-IR spectrum. 19. A mid IR spectrometric analysis Instrument according to claim 14 further comprising a software program enabling an execution of a method method for the determination of the content of casein in milk, wherein a milk sample is measured before and after a separation into casein and a liquid phase, called a supernatant promoted by adding to the milk sample at least one chemical solution adequate for precipitation of casein, and comprising the steps of measuring by infrared spectrometry the infrared absorbance in the milk sample before separation, measuring by infrared spectrometry the infrared absorbance in the supernatant, and calculating the casein content by use of absorbance data recorded during the two infrared spectrometry measurements of absorbance, wherein a dilution factor (Df) indicating the dilution of the supernatant compared to the original milk sample is calculated using absorbance data recorded during the infrared spectrometry measurement of absorbance in the supernatant, said dilution factor being applied for the calculation of the concentration of casein and wherein the spectrometric instrument provides data representing substantial portions of the MID-IR wavebands wherein proteins absorb. 20. A mid IR spectrometric analysis instrument according to claim 19 characterized in that the spectrometric instrument provides data representing substantial portions of the MID-IR wavebands wherein the added acid and/or salt absorb.

The present invention concerns a method for casein determination in milk and instruments enabled to carry out the method. BACKGROUND Milk contains proteins such as caseins. The caseins are specifically useful for cheese-making, due to their ability to coagulate. Accordingly chemical methods for determining the content of casein in milk are known. They are however time consuming. Further, It is known to determine the casein content in milk directly by fast infrared analysis methods. However, the accuracy of these methods depends on the match between the calibration samples applied for the calibration of the infrared analysis instrument and the routine samples for which the content of casein is to be determined. The purpose of the present invention is to propose a method, which is more universal, such as independent of the origin of calibration samples, than the known infrared analysis. In the present description the word “milk” relates to the milk sample to be analysed. The words “liquid phase” and supernatant are used for the remaining portion of the milk sample after a separation of the casein. The supernatant contains whey-protein. Supernatant is in this description intended also to address the case when the liquid phase in fact is a filtrate. THE INVENTION The present invention concerns a method for determination of the content of casein in milk, wherein a milk sample is measured before and after a separation into casein and a liquid phase, called a supernatant. According to the invention the protein content is determined by measuring the infrared absorbance in the milk sample before separation by infrared spectrometry and, measuring the infrared absorbance in the supernatant (liquid phase of the milk sample after separation of casein) by infrared spectrometry, and calculating the casein content by use of absorbance data recorded during the two infrared spectrometry measurements of absorbance. Preferably and according to the invention the separation of casein is promoted by adding at least one chemical solution, adequate for precipitation of casein, to the milk sample, and a dilution factor (Df) indicating the dilution of the supernatant compared to the original milk sample is calculated and applied for the calculation of the concentration of casein. Preferably and according to the invention the concentration of protein, (P(Milk)) in the milk sample before separation is determined from the infrared absorbance in the milk sample before separation, and the concentration of protein, (P(SN)) in the supernatant is determined from the infrared absorbance in supernatant, and the concentration of casein is calculated as the difference between the concentration of protein (P(Milk)) in the milk sample and the dilution factor (Df) multiplied by the concentration of protein (P(SN)) in the supernatant as defined by the equation: P(Casein)=P(Milk)−(Df*P(SN)) In the present description P(Milk) means the concentration of total proteins measured in a milk sample. The total protein is a combination of caseins and whey-proteins. The whey-protein does not precipitate; it remains fluent in the supernatant. P(W hey) means the concentration of whey-protein in a milk sample, and P(SN) means the concentration of whey-protein measured in the supernatant. The dilution factor is important because the addition of chemicals to obtain the precipitation of casein causes a dilution of the sample. Accordingly the measured P(SN) is lower than the P(Whey) due to the dilution. Preferably and according to the invention the method is characterised by comprising the steps 1) a fraction of a milk sample is analysed by mid-infrared spectroscopy to determine the content of protein, P(Milk), 2) an acid, initiating a precipitation of casein, is added to a remaining fraction of the milk sample and mixed with the sample, 3) a salt of the acid is added to obtain a pH about 4.6 and the sample is mixed again 4) the fluid mixture is subjected to a separation process separating the fluid mixture into a liquid phase, called the supernatant, and a precipitate of casein, 5) the supernatant is transferred into a container, and a sample of the supernatant is analysed by mid-infrared spectroscopy to determine the content of protein in the supernatant, P(SN) 6) the content of whey-protein, P(Whey) in the original milk sample is calculated from the content of protein in the supernatant (liquid phase) by incorporating the dilution of the supernatant, caused by the addition of acid and salt, 7) the casein content in the original milk sample is calculated as: Content of casein=P(Milk)−P(Whey). The separation may be carried out by adding an acid initiating a precipitation of casein, preferably adding a salt of the acid maintaining a pH supporting the precipitation of casein, mixing or stirring the mixture, centrifuging the mixture, and collecting the liquid phase, also called the supernatant in a receptacle. Preferably the separation comprises a filtration. A filtration is advantageous, as the infrared spectrometric instruments generally require samples without particles bigger than about 20 μm. Preferably the separation comprises a centrifugation. Preferably the acid is acetic acid. Preferably the salt is sodium acetate. These chemicals promote effectively a precipitation of the casein. The method may be carried out by use of spectroscopic infrared analysis instrument having a plurality of infrared filters enabling an accurate determination of the protein content in a milk sample. Preferably the instrument further includes one or more filters enabling a correction or compensation taking account of the added chemicals, such as acid and salt, in order to ensure that the accuracy of the protein determination is not considerably deteriorated by the presence of the added chemicals. More preferably the method is carried out by use of a full spectrum instrument arranged for recording a spectrum substantially comprising the spectral range from about 1000-3000 cm−1 , such as a MilkoScan FT120. Preferably the method is carried out by use of a full spectrum instrument, having a first protein calibration enabling a calculation of the protein content from the spectrum of the milk. The full spectrum instrument with adequate calibrations is preferred in order to ensure enabling of an accurate determination of the protein content in a milk sample, the accuracy not being substantially deteriorated by the presence of the added chemicals. This specification does not include an example disclosing a calibration as such calibrations are highly dependent on the type of instrument and further may depend on local environmental conditions. However, it is a well-known fact that such calibrations may be provided in many ways by people skilled in the art of multivariate calibration of spectrometric instruments. Preferably the method is carried out by use of a full spectrum instrument having a “dilution” calibration enabling a calculation of the dilution factor from the spectrum of the supernatant-sample. Preferably the method is carried out by use of a full spectrum instrument having a second protein calibration enabling a calculation of the protein content from the spectrum of the supernatant-sample (also called the filtrate). Preferably the protein calibration for the supernatant sample is robust to variations in the concentrations (different additions) of acetic acid/sodium acetate. According to the present invention a preferred method for determination of casein in milk is proposed, comprising the following steps: 1) a fraction of a milk sample is analysed by mid-infrared spectroscopy to determine the content of protein, P(Milk), 2) acetic acid is added to a remaining fraction of the milk sample and mixed with the sample so that a precipitation of casein is initiated, 3) sodium acetate is added to obtain a pH about 4.6 and the sample is mixed again 4) the fluid mixture is centrifuged, 5) the supernatant is transferred into a receptacle, such as a new bottle or flask, and the resulting supernatant sample is analysed by MID-infrared spectroscopy to determine the content of protein, P(SN), 6) a dilution factor is calculated, 7) the whey-protein is calculated as P(Whey)=P(SN) * dilution factor, 8) the casein content in the milk is calculated as Content of casein=P(Milk)−P(Whey). The new method is considerable faster than the known chemical methods, such as the normal wet chemical reference method for casein determination in milk using a Kjeldahl nitrogen determination of the milk sample, then a coagulation of the milk, and finally a Kjeldahl nitrogen determination of the filtrate. Further the new method provides a more reliable accuracy than the know determination using a single infrared analysis of a milk sample. Preferably, the mid-infrared spectroscopy is carried out by use of a full spectrum instrument, such as a MilkoScan FT120 in order to obtain recorded spectral data comprising sufficient information. Preferably the recorded spectrum includes the spectral range from about 1000- 3000 cm−1 or at least substantial wavebands thereof. Preferably, the full spectrum instrument includes data processing means for analysing the spectral data. Preferably, the full spectrum instrument comprises a protein calibration enabling a calculation of the protein content from the spectral data representing the spectrum of the milk. Advantageously, the full spectrum instrument may be arranged to calculate the protein content almost immediately to provide a rapid result. Alternatively the spectral data might be transferred to remote data processing means arranged to perform a calculation of the protein content from the spectrum of the milk. Preferably, the full spectrum instrument also comprises a further protein calibration, also called a whey-protein calibration, enabling a calculation of the whey-protein content from the spectrum of the supernatant-sample (also called the filtrate or the whey). Advantageously, the full spectrum instrument may be arranged to calculate the protein content all most immediately to provide a rapid result. Alternatively the spectral data might be transferred to remote data processing means arranged to perform a calculation of the protein content from the spectrum of the supernatant. The dilution factor may be calculated from weight results measured by a scale or from volumetric determinations. Accordingly, the casein content may be determined from the two recorded spectra and the calculated dilution factor: P(Milk)−P(SN)*dilution factor. Alternatively and preferably, the full spectrum instrument comprises a “dilution factor”calibration enabling a calculation of the dilution factor from the spectral data representing the spectrum of the supernatant-sample. Experience has proved that calculation of a dilution factor from the spectrum of the supernatant sample may improve the accuracy of the measurement. Also this feature supports rapid provision of a result. Accordingly, the casein content may be determined from the two recorded spectra and the dilution factor calculated from the spectrum: P(Milk)−P(SN)*dilution factor. Preferably, the whey-protein calibration for the supernatant sample is robust to variations in the concentrations (different additions) of acetic acid/sodium acetate. This feature is advantageous in that it will compensate for variation in the amount of added acetic acid/sodium acetate. Such variations are unavoidable in the practical life. According to a further alternative method, the whey-protein may be determined directly from the spectroscopy using a single calibration, enabling the calculation of whey-protein in milk from the spectral data representing the spectrum of the supernatant (also called the whey sample). Accordingly, this single calibration may replace the above “whey-protein in supernatant”-calibration and the “dilution”-calibration for calculation of the “dilution factor”. Such single calibration is preferably a calibration incorporating the dilution factor, i.e. a calibration providing the same result for P(whey) as the result obtained from the calculation P(SN)*dilution factor, when using the two separate calibrations for the supernatant (also called the whey). Among the advantages of the methods according to the present invention is that the methods may be carried out on a great number of instruments already located in laboratories all over the world. A further advantage is that a method according to the invention is more accurate than the known methods. Further the present invention relates to a mid IR spectrometric analysis instrument characterized in that the instrument comprises a software program enabling an execution of the calculations involved in a method for the determination of the content of casein according to any of the preceding claims by use of data recorded by the mid IR spectrometric analysis instrument. In a preferred embodiment the mid IR spectrometric analysis instrument is characterized in that the instrument comprises a software program enabling an execution of the calculations of the content of casein by use of data enabling a calculation of a dilution factor indicating the dilution of the whey compared to the original milk sample. In a preferred embodiment the mid IR spectrometric analysis instrument is characterized in that the instrument comprises a software program enabling an execution of a method, the instrument having a second protein calibration enabling a calculation of the protein content from the spectrum of the supernatant-sample (also called the filtrate). In a preferred embodiment the mid IR spectrometric analysis instrument is characterized in that the instrument comprises a software program enabling an execution of the method according to any of the method claims, and wherein the spectrometric instrument comprises a plurality of interchangeable optical IR filters able to be inserted into the light path of the spectrometric instrument as known per se. In a preferred embodiment the mid IR spectrometric analysis instrument is characterized in that the instrument comprises a software program enabling an execution of a method according to the invention and wherein the spectrometric instrument is a Full spectrum instrument providing data representing a substantial portion of the MID-IR spectrum. In a preferred embodiment the mid IR spectrometric analysis instrument is characterized in that the instrument comprises a software program enabling an execution of a method according to any of the method claims and wherein the spectrometric instrument provides data representing substantial portions of the MID-IR wavebands wherein proteins absorb and/or wherein the added acid and/or salt absorb. The use of a full spectrum instrument, such as a FTIR instrument is specifically advantageous as the data of the full spectrum allow for a good compensation of the influence from the added acetic acid. However, a mid IR instrument having a plurality of filters may also be applied for executing the method according to the invention. BRIEF DESCRIPTION OF DRAWINGS FIG. 1 shows a flow diagram illustrating the broadest aspect of the method according to the invention. FIG. 2 shows a flow diagram illustrating a preferred method according to the invention. FIG. 3 shows a flow diagram illustrating an alternative method according to the invention. FIG. 4 shows a prediction plot for whey-protein in milk corresponding to the predicted protein in the filtrate times the dilution factor calculated by weight results (approximately 1.4). FIG. 5 shows a resulting prediction plot for the differential casein determination using the weight results to calculate the dilution factor. FIG. 6 shows a prediction plot for casein predicted by a known multiplication method. FIG. 7 shows the resulting prediction plot for the differential casein determination using the prediction of the dilution factor. DETAILED DESCRIPTION OF INVENTION FIG. 1 illustrates the broadest aspect of the invention. A fraction of a milk sample is analysed by mid-infrared spectrometry in step 101. The content of protein, P(milk ), is determined from the spectral data by use of well-known chemometric methods for quantitative determinations. An acid of known concentration/strength able to precipitate casein is added to a remaining fraction of the milk sample, and mixed with the sample in step 102. A salt of the acid of known concentration is added to obtain a stable pH, such as about 4.6, and the sample is mixed again to complete the precipitation of casein in step 103. The fluid mixture is separated into a liquid phase called the supernatant and a precipitate of casein, preferably by centrifugation and/or by filtration in step 104. The supernatant is then transferred to a container, such as a receptacle and a sample of the supernatant (or filtrate) is analysed by mid-infrared spectrometry in step 105. A dilution factor accounting for the dilution in the supernatant compared to the milk sample is calculated. The dilution is due to the addition of acid and salt in order obtain the precipitation. The content of protein P(whey) is determined from the spectral data and the dilution factor in step 106. The casein content in the original milk sample may then be calculated as P(milk)−P(whey) as indicated in step 107. Example of a Preferred Method FIG. 2 illustrates a preferred method using acetic acid and sodium acetate for the precipitation of the casein. In step 201 a fraction of a milk sample is analysed by mid-infrared spectroscopy to determine the content of protein, P(Milk), P(Milk) is determined from the spectrum of milk by chemometry using a calibration for protein in milk. In step 202 Acetic acid is added to a remaining fraction of the milk sample and mixed with the sample. In step 203 Sodium acetate is added to obtain a pH about 4.6 and the sample is mixed again. In step 204 The fluid mixture is centrifuged. In step 205 the supernatant is transferred into a new container, such as a bottle or flask and the resulting “supernatant”sample is analysed by mid-infrared spectroscopy to determine the content of protein, P(SN). In step 206 P(SN) is determined from the spectrum of supernatant by chemometry using a calibration for protein in supernatant. The next steps 207 and 208 are alternative. The dilution factor has to be found. The dilution factor may e.g. be calculated from measured weights or volumes (step 207) or from the whey spectrum using a chemometric method (step 208). In step 209 the casein content is calculated as Content of casein=P(Milk)−P(SN)*dilution FIG. 3 shows a procedure very similar to FIG. 2. In fact the steps 301-305 are identical to steps 201-205. The next step 306 will be explained in further details later in this description. According to the invention the following fast differential infrared method for casein determination is recommended. Instrumentation. The method may be carried out by use of a mid-IR spectrometer, preferably a MilkoScan FT120 from FOSS Electric A/S. In the following text the abbreviation MScFT120 is used. The preferred instrument is a full spectrum instrument, such as MScFT120, able to record at least essential portions of a mid IR spectrum. However, as an alternative a spectrometric instrument, such as the Milkoscan 4000, using a plurality of filters enabling a good determination (prediction) of the content protein in milk, may also be used. Chemicals. 1. 10% Acetic acid 2. 1.0M (mol/litre) sodium acetate Procedure. The milk sample should have a temperature about 20-38 degree (Celsius). The milk may be preserved. Measure the undiluted milk sample by MScFT120 Determination of the protein content of the milk Sample 100 ml (or 100 g) of the milk Add 20 ml (or 20 g) of the 10% acetiOc acid. Mix the sample. Add 20 ml (or 20 g) of the 1.0M sodium acetate. Mix the sample. Centrifuge the sample using minimum 10500 rpm in 5 min. or until separation between supernatant and precipitate looks fine. The supernatant do not have to look clear. The supernatant is carefully poured into a test tube through a filter. Some of the precipitate may break up. The filter will prevent that it pollutes the filtrate. Therefore it may be a fast filter (e.g. a mechanical filter). Measure the supernatant (the filtrate) by MScFT120. Determination of the Protein content in the filtrate and the dilution factor. The added amount of acetic acid may vary. Preferably an amount of no less than 10 ml 10% acetic acid for 100 ml milk sample is applied in order to obtain the desired precipitation. It is not recommended to add more than about 30 ml, as the dilution increases and deteriorate the spectrum. The concentration of the acetic acid and the sodium acetate must be very accurate when using the dilution calibration to determine the dilution factor. Alternatively a buffer solution is added directly to the milk in one step to obtain the precipitation. IR calibrations. The casein content in the sample is determined by 3 different IR calibrations stored in the MScFT120. 1) Protein calibration for milk 2) Whey-protein calibration for the supernatant (filtrate) 3) Dilution factor calibration Although addition of acetic acid results in high absorbancies in the same region as protein, this makes no problems for the protein determination using a full-spectrum IR instrument. Therefore the combination of the recommended procedure with this kind of instrument is recomended. The protein calibration for the filtrate may be made robust for various concentrations (different additions) of acetic acid/sodium acetate. The calibration for the dilution factor is also a new feature in the system allowing an inaccurate addition of the acetic acid and the sodium acetate. This, however, assumes that the concentrations of the chemicals are accurate. The prediction of the dilution factor from the spectrum (mentioned in FIG. 2 step 208) replaces the weight results from a scale or replaces a volume determination. Advantageously, and as indicated in step 306 in FIG. 3, the last two calibrations may be combined into a single calibration. However, where a more flexible system is wanted it may be preferred to have the two separate calibrations, as shown in FIG. 2 step 207, 208, thereby providing a possibility to choose between the weight results or the dilution factor calibration. FIG. 4 shows prediction of the whey protein in a plurality of milk samples. Number of samples: 106 samples in 1×1, 105×2 replicates The obtained absolute accuracy is: RMSEP=0.051; SEP=0.029; SEPCorr=0.028; SDrep=0.011; Mean=0.82. The accuracy relative to the mean is: RMSEP=6.18% CV; SEP=3.50% CV; SEPCorr=3.46% CV; SDrep=1.35% CV. Slope: 0.9711; Intercept: 0.0643; correlation coefficient r: 0.9856; Bias: 0.0418. In this context RMSEP is the “root mean square” of Error of Prediction. SEP is the Standard Error of Prediction. SEPCorr is the slope- and intercept-corrected SEP. SDrep is the standard deviation of the repeatability. Mean is the mean value of the constituent (content of proteins, whey or casein). Correlation coefficient: r The content of whey-protein is determined as predicted protein in the supernatant multiplied by a dilution factor. This dilution factor can be calculated from the weight results or it can be determined by prediction too. In FIG. 4 the weight results are used to calculate the dilution factor. The predicted casein content is calculated as: Casein=Pm−Pf*Df where Pm=Predicted protein in milk Pf=Predicted protein in the supernatant of the corresponding milk Df=Dilution factor The reference casein versus predicted casein by the method according to the invention is presented in a prediction plot in FIG. 5 (using the weight results for calculation of the Df). The FIG. 5 plot relates to the same samples as FIG. 4: Number of samples: 106 samples in 1×1, 105×2 replicates The obtained absolute accuracy is: RMSEP=0.071; SEP=0.038; SEPCorr=0.036; SDrep=0.011; Mean=2.57. The accuracy relative to the mean is: RMSEP=2.76% CV; SEP=1.47% CV; SEPCorr=1.39% CV; SDrep=0.43% CV. Slope: 0.9502; lntcpt: 0.0710; r: 0.9856; Bias: 0.0599 According to a known method, a so-called “multiplication method” the casein content may be determined as approximately equal to the protein content multiplied by 0.76. A prediction plot resulting from the use of this multiplication method is presented in FIG. 6 for comparison with the new method as presented in FIG. 5. In FIG. 6: Number of samples: 53 samples in 2 replicates The obtained absolute accuracy is: RMSEP=0.112; SDrep=0.007; Mean=2.57. The accuracy relative to the mean is: RMSEP=4.35% CV; SDrep=0.29% CV Slope: 0.7705; Intcpt: 0.5721; r: 0.9280; Bias: 0.0217. By comparison the prediction plots FIGS. 5 and 6 show that the new method determines casein with a relative accuracy (SEPCorr) of 1.39% cv, which is three times as good as the multiplication method (relative accuracy (RMSEP) of 4.35% cv). The multiplication method has special troubles in the high casein concentrations, which makes it more problematic for practical use. In FIG. 7 the casein prediction plot is presented for the new method using a predicted dilution factor, i.e. a dilution factor predicted from the absorbance data recorded by the spectrometric analysis instrument. In FIG. 7: Number of samples: 106 samples in 1×1, 105×2 replicates The obtained absolute accuracy is: RMSEP=0.073; SEP=0.038; SEPCorr=0.035; SDREP=0.011; Mean=2.57 The accuracy relative to the mean is RMSEP=2.85% CV; SEP=1.48% CV; SEPCorr=1.36% CV; SDrep=0.43% CV Slope: 0.9404; intercept: 0.0940; r: 0.9891; Bias:−0.0626 The relative accuracy, SEPCorr, of 1.36%cv is slightly better than the relative accuracy found in the example shown in FIG. 5 for the casein prediction using the weight results, but the slope is slightly lower. This shows that the method incorporating a prediction of the dilution factor will function well in practise. It is obvious to people skilled in the art that the preferred method according to the invention and as described above may be varied in several ways within the scope of protection as defined in the following patent claims. Other spectrometric instruments than the presently preferred Milkoscan FT120 may be used for carrying out the invention. Other acids able to precipitate the casein might be used, as well as other separation methods.

<SOH> BACKGROUND <EOH>Milk contains proteins such as caseins. The caseins are specifically useful for cheese-making, due to their ability to coagulate. Accordingly chemical methods for determining the content of casein in milk are known. They are however time consuming. Further, It is known to determine the casein content in milk directly by fast infrared analysis methods. However, the accuracy of these methods depends on the match between the calibration samples applied for the calibration of the infrared analysis instrument and the routine samples for which the content of casein is to be determined. The purpose of the present invention is to propose a method, which is more universal, such as independent of the origin of calibration samples, than the known infrared analysis. In the present description the word “milk” relates to the milk sample to be analysed. The words “liquid phase” and supernatant are used for the remaining portion of the milk sample after a separation of the casein. The supernatant contains whey-protein. Supernatant is in this description intended also to address the case when the liquid phase in fact is a filtrate.

<SOH> BRIEF DESCRIPTION OF DRAWINGS <EOH>FIG. 1 shows a flow diagram illustrating the broadest aspect of the method according to the invention. FIG. 2 shows a flow diagram illustrating a preferred method according to the invention. FIG. 3 shows a flow diagram illustrating an alternative method according to the invention. FIG. 4 shows a prediction plot for whey-protein in milk corresponding to the predicted protein in the filtrate times the dilution factor calculated by weight results (approximately 1.4). FIG. 5 shows a resulting prediction plot for the differential casein determination using the weight results to calculate the dilution factor. FIG. 6 shows a prediction plot for casein predicted by a known multiplication method. FIG. 7 shows the resulting prediction plot for the differential casein determination using the prediction of the dilution factor. detailed-description description="Detailed Description" end="lead"?

20050502

20100427

20051020

59941.0

GERIDO, DWAN A

METHOD FOR CASEIN DETERMINATION IN MILK

UNDISCOUNTED

ACCEPTED

ACCEPTED

Integrated vi probe

Integrated voltage and current (VI) probe (18) for integration inside a transmission line (17) having inner (3) and an outer (4) conductors. Current probes, often implemented as loop antennas, can be coupled to the outer conductor. The probes can either be built onto the same panel or on different panels.

1. An integrated voltage probe, for integration inside a transmission line between a capacitively coupled plasma processing electrode and a power source, the probe comprising: a voltage probe electrode integrated into the transmission line; first and second electrical leads connected to the voltage probe electrode; and a first window for passing the first and second electrical leads inside the transmission line to the voltage probe electrode. 2. The integrated voltage probe according to claim 1, wherein the first electrical lead of the voltage probe is coupled to the capacitively coupled plasma processing electrode, and the second electrical lead of the voltage probe is coupled to an outer conductor of the transmission line. 3. The integrated voltage probe according to claim 2, wherein the first electrical lead of the voltage probe is coupled to the capacitively coupled plasma processing electrode, and the second electrical lead of the voltage probe is coupled to the inner conductor of the transmission line. 4. The integrated voltage probe according to claim 2, wherein the outer conductor of the transmission line comprises a grounding housing for the capacitively coupled plasma processing electrode. 5. The integrated voltage probe according to claim 1, wherein the capacitively coupled plasma processing electrode comprises an upper electrode. 6. The integrated voltage probe according to claim 1, wherein the capacitively coupled plasma processing electrode comprises a lower electrode. 7. The integrated voltage probe according to claim 1, further comprising a match network coupled to the transmission line between the capacitively coupled plasma processing electrode and the power supply. 8. An integrated current probe, for integration inside a transmission line between a capacitively coupled plasma processing electrode and a power source, the probe comprising: a current probe integrated into the transmission line; first and second electrical leads connected to the current probe; and a first window for passing the first and second electrical leads inside the transmission line to the current probe. 9. The integrated current probe according to claim 7, wherein the current probe comprises a loop antenna. 10. The integrated current probe according to claim 8, wherein the first electrical lead of the current probe is coupled to the loop antenna, and the second electrical lead of the current probe is coupled to an outer conductor of the transmission line. 11. The integrated current probe according to claim 7, further comprising a match network coupled to the transmission line between the capacitively coupled plasma processing electrode and the power supply. 12. The integrated current probe according to claim 8, wherein the capacitively coupled plasma processing electrode comprises an upper electrode. 13. The integrated current probe according to claim 8, wherein the capacitively coupled plasma processing electrode comprises an lower electrode. 14. An integrated voltage and current (VI) probe, for integration inside a transmission line between a capacitively coupled plasma processing electrode and a power source, the probe comprising: a voltage probe including (1) a voltage probe electrode integrated into the transmission line and (2) first and second electrical leads connected to the voltage probe electrode; a current probe including (1) a current probe integrated into the transmission line and (2) third and fourth electrical leads connected to the current probe; and a first window for passing (1) the first and second electrical leads inside the transmission line to the voltage probe electrode and (2) the third and fourth electrical leads inside the transmission line to the current probe. 15. The integrated VI probe according to claim 14, wherein the voltage and current probes are mounted on a single VI probe panel. 16. The integrated VI probe according to claim 14, further comprising a detector for detecting at least one of a voltage and a current transmitted through the transmission line. 17. An integrated voltage and current (VI) probe, for integration inside a transmission line between a capacitively coupled plasma processing electrode and a power source, the probe comprising: a voltage probe including (1) a voltage probe electrode integrated into the transmission line and (2) first and second electrical leads connected to the voltage probe electrode; a current probe including (1) a current probe integrated into the transmission line and (2) third and fourth electrical leads connected to the current probe; a first window for passing the first and second electrical leads inside the transmission line to the voltage probe electrode; and a second window for passing the third and fourth electrical leads inside the transmission line to the current probe. 18. The integrated VI probe according to claim 17, wherein the voltage and current probes are mounted to separate panels which are oriented on different sides of the transmission line. 19. The integrated VI probe according to claim 14, further comprising a detector for detecting at least one of a voltage and a current transmitted through the transmission line.

CROSS REFERENCES TO RELATED APPLICATIONS The present application claims priority and is related to U.S. provisional Ser. No. 60/360,016, filed on Feb. 28, 2002. The present application is related to U.S. provisional application Ser. No. 60/259,862, entitled “Capacitively coupled RF voltage probe”, filed on Jan. 8, 2001; and co-pending application 60/359,986, entitled “Portable VI probe,” filed on Feb. 28, 2002. The contents of all of those applications are incorporated herein by reference in their entirety. BACKGROUND OF THE INVENTION 1. Field of the Invention This invention is directed to a method and a system for measuring voltage and current levels using an Integrated (i.e. in-line) Voltage and Current (VI) Probe. 2. Discussion of the Background In the fabrication and processing of semi-conductor wafers, such as silicon wafers, a variety of different semiconductor equipment and processes can be utilized. For example, wafer processing techniques are known in the art and may include, for example, photolithography, ion beam deposition, vapor deposition, etching, as well as a variety of other processes. In one method of wafer processing, plasma generators are used to process a wafer, for example by etching a layer formed on the surface of the wafer. In employing this technique, electrical power is coupled to the plasma generator from an electrical source. Typically, the electrical energy has a frequency in the radio frequency (RF) range. Control of the process is performed in part by measuring and monitoring the RF signal. The power input into the system can be determined by measuring the RF voltage (V) and the current (I) components of the RF power source coupled to the plasma generator. Thus, a common practice for measuring RF power is to install a sensor for monitoring current and voltage in series with the transmission medium coupling the RF power to the plasma generator. Sometimes, however, the presence of the RF probes can itself disrupt the propagating electro-magnetic fields the probes are intended to measure. This may occur through reflections of the RF signal, for example, that are imposed by the implementation of the RF probe(s). Consequently, there exists a need for an integrated voltage and current probe to monitor a source of RF electrical power which minimally intrudes in the RF transmission line in which the probes are placed. Moreover, the presence of RF probes can affect proven processes, which is entirely unacceptable to device manufacturers. As the probes are installed in the RF transmission structure outside the chamber and sometimes beyond the output of the match network, the above-identified problem can be further exacerbated when commercially available probes are utilized. Therefore, there exists a need for an integrated voltage and current probe to monitor a source of RF electrical power, which minimally affects a proven process. SUMMARY OF THE INVENTION A need exists for a voltage and or current probe which can be installed along a transmission line in a plasma generator and which will minimally perturb or impact the propagating electro-magnetic fields or the plasma process. Therefore, an exemplary embodiment of this invention provides for an apparatus and a system for integrating the apparatus into a transmission line of a plasma generator. The apparatus can detect voltage and/or current within a transmission line while minimally impacting or perturbing the propagating electro-magnetic fields. This minimal impact arises from the voltage and current probes being placed within the existing chamber structure proximate the power coupling (or plasma) electrode. Other objects, features and advantages of the present invention will become apparent from the following detailed description, the accompanying drawings, and the appended claims. BRIEF DESCRIPTION OF THE DRAWINGS A more complete appreciation of the invention and many of the attendant advantages thereof will become readily apparent with reference to the following detailed description particularly when considered in conjunction with the accompanied drawings, in which: FIG. 1A is a perspective view of a voltage probe integrated into a transmission line; FIG. 1B is a perspective view of a voltage probe integrated into an inner conductor of a transmission line; FIG. 2 is a side view of the various sections of the invention showing the integration of the voltage probe and the current probe; FIG. 3 is a schematic view of the voltage and current probe constructed within an upper electrode structure; and FIG. 4 is a schematic view of the voltage and current probe constructed within a lower electrode structure. DETAILED DESCRIPTION OF THE INVENTION Referring to FIG. 1A, a transmission line 17 includes an inner conductor 3 and an outer conductor 4. Each runs along the transmission line in an axial direction such that the inner conductor has a diameter substantially smaller than that of the outer conductor. A non-limiting embodiment of an integrated VI probe 18 is shown broken away from the outer conductor of the transmission line. For example, the integrated VI probe can be attached, for example, as a panel, to the outer conductor 4 as shown by arrows 30A, 30B, 30C and 30D. Arrows 30A, 30B, 30C and 30D can, for example, represent fasteners (e.g., bolts, solder, adhesive) utilized to affix the VI probe panel 18 to a windowed section of the outer conductor 4 of RF transmission line 17, wherein the VI probe panel 18 serves as the outer conductor. When attached, the VI probe panel 18 should be within the transmission line, as shown in FIGS. 1A through 4, proximate to the plasma processing electrode in a space sufficiently large to accommodate the size of the probe. Typically, the latitudinal and longitudinal dimensions of the probe are on the order of one centimeter and the thickness is on the order of a millimeter. Once installed, the probe should not alter the geometric configuration of the transmission line or the material properties of the conductors. Thus, the intrinsic impedance of the transmission line is to remain substantially constant or constant. Voltage and current probes 19 and 20, respectively, with electrical leads 19A, 19B, 20A and 20B can mounted upon the VI probe panel 18 using techniques conventional in the art. For example, in a plasma processing environment, lead 19A can be directly coupled to the capacitively coupled electrode and lead 19B can be coupled to the outer conductor 4 of RF transmission line 17. Alternatively, the pair of leads 19A, 19B can be replaced with a standard electrical connector such as, for example, a SMA connector or a BNC connector. For example, lead 20A can be coupled to the loop antenna and lead 20B can be coupled to the outer conductor 4 of RF transmission line 17. Alternatively, the pair of leads 20A, 20B can be replaced with a standard electrical connector such as, for example, a SMA connector or a BNC connector. The construction and calibration of VI probes are well known to those skilled in the art of voltage-current diagnostics. For example, VI probe construction and calibration is described in detail in pending U.S. application Ser. No. 60/259,862 filed on Jan. 8, 2001, and U.S. Pat. No. 5,467,013 issued to Sematech, Inc. on Nov. 14, 1995; each of which is incorporated herein by reference in its entirety. In FIG. 1A, voltage and current probes, 19 and 20, respectively are shown mounted to a single VI probe panel 18. Alternatively, each probe can be mounted to separate panels, for example, a pair of VI probe panels can be oriented on diametrically opposing sides of RF transmission line 17, to which a voltage probe is fabricated on a first panel and a current probe is fabricated on a second, opposing panel. Desirably, transmission line 17 is mounted within a process chamber (not shown). FIG. 1B shows the same voltage probe discussed above integrated onto an inner conductor 3 of a transmission line. Voltage probe 119 comprises electrical leads 119A and 119B, wherein lead 119A is coupled to voltage probe electrode 108 or an electrode ring and exits the transmission line through outer conductor 4. Voltage probe electrode 108 can be a ring electrode as shown in FIG. 1B, or alternately, can comprises a plate electrode in close proximity to the inner conductor. FIG. 2 represents an alternate embodiment of an implementation of a VI probe in a RF transmission line 17. The RF transmission line 17 includes various sections including sections 17A, 17B and 17C as shown. Section 17A can represent the output transmission line of an impedance match network, section 17C can represent the input transmission line to a plasma reactor, and section 17B can represent a transmission line section within which a voltage and current probe are mounted. Section 17B can be, for example, mounted between sections 17A and 17C using standard flanges (e.g., CF flanges, KF flanges) and the characteristic impedance of the overall transmission line (sections 17A, 17B and 17C) can be preserved. Desirably, sections 17B and 17C are mounted within the chamber. Outer conductor 4B is the area on the transmission line 17 in which the probes have been installed. The outer conductor 4B contains access areas 27, 28 through which the probes attach to and exit from the outer conductor. The outer conductor 4B surrounds its corresponding part of the inner conductor 3B. In the illustrated embodiment, the various elements of the voltage and current probe are attached to the inner surface of the outer conductor. The voltage and current probes comprise similar elements as described with reference to FIG. 1. The voltage probe comprises a voltage probe electrode 19 that is connected to first and second leads 19A and 19B. At least one of the leads 19A and 19B is connected to one of the conductors (e.g., the outer conductor 4B) and acts as a ground reference. The pair of leads 19A, 19B, however, can be replaced with a standard electrical connector such as, for example, a SMA connector or a BNC connector. The current probe comprises a loop antenna 20 to which a lead 20A is coupled. A second lead 20B is coupled to the outer conductor 4B. The pair of leads 20A, 20B can be replaced with a standard electrical connector such as, for example, a SMA connector or a BNC connector. The VI probe construction and calibration is performed in a manner equivalent to the VI probe of FIG. 1A and described in detail in pending U.S. application Ser. No. 60/259,862 filed on Jan. 8, 2001, and U.S. Pat. No. 5,467,013 issued to Sematech, Inc. on Nov. 14, 1995. An Integrated VI probe can be built onto a transmission line within a plasma reactor. In a first embodiment, as shown in FIG. 3, a plasma generator 100 includes a plasma processing electrode 2, a match network 1, and a “transmission line” formed of (1) a conductor (acting as an inner conductor 3) between the electrode 2 and the match network 1 and (2) an electrode housing (acting as an outer conductor 4). An exemplary plasma reactor comprising a plasma processing electrode, to which RF power is applied, is described in U.S. Pat. No. 5,900,103 issued to Tokyo Electron Ltd. on May 4, 1999, which is incorporated herein by reference in its entirety. A match network 1 is employed to optimize the transfer of power from a RF source to plasma through a plasma processing electrode 2 by matching the output impedance of the RF source to the load impedance which includes the plasma. In general, an impedance match is obtained when the output impedance of the match network 1 is the complex conjugate of the load impedance. The interesting feature is that the characteristic impedance of the structure following the output of the match network 1 and including the plasma is not generally 50 Ohms. In fact, this impedance is usually very small. Therefore, when a VI probe is arranged within the electrode structure as shown in FIG. 3, it maximally complies with the designed characteristic impedance of the system and, hence, it minimally perturbs the propagating electro-magnetic fields. Such a system design can minimize any impact on the proven process in the plasma processing system while providing reliable measurement of the RF voltage and current. FIG. 3 also shows a schematic view of the connection between the probes and the outer conductor that are analogous the structures shown in FIGS. 1A, 1B and 2. In FIG. 3, the voltage probe 19 and the current probe 20 are attached to the outer conductor in such a way as to be substantially close to one another. Alternately, they can be mounted on opposite sides of the outer conductor. In general, a voltage probe measures a voltage between a capacitively couple plasma electrode and a grounded housing. Similarly, the current probe 20 can be implemented as a loop antenna that captures at least a fraction of the azimuthal magnetic flux from the “transmission line”. The voltage probe 5 and the current probe 6 are installed onto the inner surface of the outer conductor. As described above, the construction and calibration of the voltage and current probes are described in detail in pending U.S. application Ser. No. 60/259,862 filed on Jan. 8, 2001, and U.S. Pat. No. 5,467,013 issued to Sematech, Inc. on Nov. 14, 1995. As shown in FIG. 4, a similarly effective result can be accomplished by having the voltage probe 19 and the current probe 20 installed onto the lower electrode structure. Here, FIG. 4 presents a second embodiment of an Integrated VI probe built into a “transmission line” for a lower electrode 2 of a plasma generator using structures analogous to those shown in FIGS. 1 and 2. In FIG. 4, the voltage probe 19 and the current probe 20 are built into the RF path between the lower electrode 2 and the match network 1. The probes can be mounted on opposite sides of the outer conductor as shown, on the same side, or on adjacent sides. As discussed above, the implementation of voltage and current probes using the structures described in FIGS. 1 and 2, and shown in FIG. 4, can be expected to minimally perturb the propagating electro-magnetic fields by not introducing (1) substantive changes in the characteristic impedance of the RF transmission line and, hence, (2) additional reflections. Therefore, such probes will reduce any impact on proven process in the plasma processing system. At least one detector can be coupled to each probe in order to detect a voltage and/or current being transmitted on the transmission line to which the probes are connected. Such a detector can be an oscilloscope or an A/D device coupled to a computer to provide the voltage and/or current to the computer in periodic samples. As would be understood by one of ordinary skill in the art, the voltage and current probes may be integrated into a transmission line separately. Thus, a current probe may be used without a voltage probe and vice versa. Numerous modifications and variations of the present invention are possible in light of the above teachings. It is therefore to be understood that, within the scope of the appended claims, the invention may be practiced otherwise than as specifically described herein.

<SOH> BACKGROUND OF THE INVENTION <EOH>1. Field of the Invention This invention is directed to a method and a system for measuring voltage and current levels using an Integrated (i.e. in-line) Voltage and Current (VI) Probe. 2. Discussion of the Background In the fabrication and processing of semi-conductor wafers, such as silicon wafers, a variety of different semiconductor equipment and processes can be utilized. For example, wafer processing techniques are known in the art and may include, for example, photolithography, ion beam deposition, vapor deposition, etching, as well as a variety of other processes. In one method of wafer processing, plasma generators are used to process a wafer, for example by etching a layer formed on the surface of the wafer. In employing this technique, electrical power is coupled to the plasma generator from an electrical source. Typically, the electrical energy has a frequency in the radio frequency (RF) range. Control of the process is performed in part by measuring and monitoring the RF signal. The power input into the system can be determined by measuring the RF voltage (V) and the current (I) components of the RF power source coupled to the plasma generator. Thus, a common practice for measuring RF power is to install a sensor for monitoring current and voltage in series with the transmission medium coupling the RF power to the plasma generator. Sometimes, however, the presence of the RF probes can itself disrupt the propagating electro-magnetic fields the probes are intended to measure. This may occur through reflections of the RF signal, for example, that are imposed by the implementation of the RF probe(s). Consequently, there exists a need for an integrated voltage and current probe to monitor a source of RF electrical power which minimally intrudes in the RF transmission line in which the probes are placed. Moreover, the presence of RF probes can affect proven processes, which is entirely unacceptable to device manufacturers. As the probes are installed in the RF transmission structure outside the chamber and sometimes beyond the output of the match network, the above-identified problem can be further exacerbated when commercially available probes are utilized. Therefore, there exists a need for an integrated voltage and current probe to monitor a source of RF electrical power, which minimally affects a proven process.

<SOH> SUMMARY OF THE INVENTION <EOH>A need exists for a voltage and or current probe which can be installed along a transmission line in a plasma generator and which will minimally perturb or impact the propagating electro-magnetic fields or the plasma process. Therefore, an exemplary embodiment of this invention provides for an apparatus and a system for integrating the apparatus into a transmission line of a plasma generator. The apparatus can detect voltage and/or current within a transmission line while minimally impacting or perturbing the propagating electro-magnetic fields. This minimal impact arises from the voltage and current probes being placed within the existing chamber structure proximate the power coupling (or plasma) electrode. Other objects, features and advantages of the present invention will become apparent from the following detailed description, the accompanying drawings, and the appended claims.

20050318

20061226

20050825

73146.0

VU, DAVID HUNG

INTEGRATED VI PROBE

UNDISCOUNTED

ACCEPTED

ACCEPTED

Turbocharger actuator

A turbocharger actuator and a method of calibrating the actuator is particularly applicable to a variable nozzle turbocharger (VNT). The actuator comprises an actuator housing having a diaphragm connected across it, a piston, a compression spring arranged to be generally centred in the actuator housing and to bias the piston and keep the diaphragm for calibrating a turbocharger. The actuator housing may be connected to a bracket using three rivets and the diaphragm may crimped to connect it to the actuator housing coated with elastomer bead to improve and control the crimping process. The shape of the piston is modified to reduce the overall length of the actuator. The bracket for attaching the actuator assembly to the variable nozzle turbocharger housing comprises a first planar portion having a plurality of rivet holes formed therein for connection to the actuator assembly, and at least one, preferably two, second portion(s) extending generally perpendicular to the first portion and having an elongate hole formed therein to receive a bolt to attach the bracket to the turbocharger housing, the elongate hole allowing a sliding movement of the actuator assembly relative to the turbocharger housing. The calibration method comprises applying a predetermined vacuum to the actuator to allow the actuator to take a calibrated position determined by gravity whilst keeping the pin crank in contact with the flow screw of the turbocharger and tightening the or each bolt, at a predetermined torque, to tighten the attachment of the actuator assembly to turbine housing. The actuator calibration is controlled as normal and if it is not correct hen the process is repeated using a different predetermined vacuum value.

1. An actuator for a variable nozzle turbocharger, comprising: an actuator housing; a piston; a diaphragm, connected across the actuator housing; at least one compression spring arranged to be generally centred in the actuator housing and to bias the piston; a spaded rod, connected to the piston, for calibrating a turbocharger, and a bracket comprising a first planar portion for fixedly connecting to the actuator assembly, and at least one second portion extending generally perpendicular to the first portion and having an elongate hole formed therein to receive means for attaching the bracket to the turbocharger housing, the elongate hole allowing a sliding movement of the actuator assembly relative to the turbocharger housing. 2. An actuator according to claim 1 wherein the bracket further comprises a third portion extending perpendicular to the first portion and being generally parallel to the second portion and the third portion having an elongate hole formed therein to receive a bolt to attach the bracket to the turbocharger housing, the elongate hole allowing a sliding movement of the actuator assembly relative to the turbocharger housing. 3. An actuator according to claim 1 or claim 2 wherein the or each elongate hole allow(s) approximately 4 mm of sliding movement. 4. An actuator according to any one of the preceding claims wherein the actuator housing is connected to the bracket using at least one rivet. 5. An actuator according to claim 4 wherein the actuator housing is connected to the bracket using three rivets. 6. An actuator according to any one of the preceding claims wherein the diaphragm is crimped to connect it to the actuator housing. 7. An actuator according to any one of the preceding claims wherein the diaphragm is coated with elastomer bead. 8. A turbocharger comprising a turbine, a compressor and an actuator, for controlling movement of the piston to control the air inlet to the turbine or the compressor, wherein the actuator is made accordingly to any one of the preceding claims. 9. A method of calibrating a variable nozzle turbocharger comprising the steps of: a) using an actuator assembly which has a spaded rod; b) using at least one bolt to attach the actuator assembly to an end housing of a turbocharger which has a pin crank so that the spaded rod is adjacent to the pin crank; c) applying a predetermined vacuum to the actuator, through an actuator port to allow the actuator to take a calibrated position determined by gravity; d) keeping the pin crank in contact with the flow screw of the turbocharger; e) tightening the or each bolt, at a predetermined torque, to tighten the attachment of the actuator assembly to an end housing; f) controlling the actuator calibration in accordance with predetermined process instructions; g) determining whether the calibration process is correct and if it is not correct then repeating the process from step c)using a different predetermined vacuum value. 10. A method according to claim 9 when conducted using the actuator of any one of the preceding claims. 11. An actuator according to any one of claims 1 to 7 when used in the method of claim 9 or claim 10.

The present invention relates to a turbocharger actuator and a method of calibrating the actuator. It is particularly applicable to a variable nozzle turbocharger (VNT). Turbochargers are used extensively in modem diesel engines to improve fuel economy and minimize noxious emissions. Traditionally a turbocharger comprises a turbine wheel in a chamber within a turbine housing, a compressor wheel and housing, and a central cast bearing housing for journaling a shaft which connects the compressor and turbine wheels. The turbine wheel rotates when driven by exhaust gasses from an internal combustion engine and causes the compressor wheel to rotate and compress air for delivery to the engine at a rate that is greater than the rate the engine can naturally aspirate. The turbocharger pressure output is a function of component efficiencies, mass flow through the turbine and compressor and the pressure drop across the turbine. A VNT typically comprises a substantially cylindrical piston received within the turbine housing concentrically aligned with the rotational axis of the turbine. The piston is longitudinally movable to set the area of the inlet nozzle to the turbine from the volute so as to modulate the performance of the turbocharger for different operating conditions. The piston is moved by an actuator which is usually pneumatically operated and which is attached to the turbine housing by a bracket. It is necessary to calibrate the actuator when it is fitted. Traditionally a VNT is calibrated using two fixed end points with a manually adjustable connecting rod and end. The rod and end is held in place by a locknut and the actuator assembly is held by two bolts and nuts. Conventional parts of a VNT are difficult to fit and adjust in confined spaces, and the manual calibration process reduces assembly line productivity, increases costs and tends to be relatively unreliable. There is a need for a more robust actuator design and calibration process to enable automatic calibration and compact turbocharger installations, as well as to increase assembly line productivity and reduce the cost of an actuator. It is also desirable to make the calibration process calibration process to enable automatic calibration and compact turbocharger installations, as well as to increase assembly line productivity and reduce the cost of an actuator. It is also desirable to make the calibration process more reliable and reduce the warranty returns, for example for loss of calibration. According to one aspect of the present invention there is provided an actuator for a variable nozzle turbocharger, comprising: an actuator housing; a piston; a diaphragm, connected across the actuator housing; at least one compression spring arranged to be generally centred in the actuator housing and to bias the piston; a spaded rod, connected to the piston, for calibrating a turbocharger, and a bracket comprising a first planar portion for fixedly connecting to the actuator assembly, and at least one second portion extending generally perpendicular to the first portion and having an elongate hole formed therein to receive means for attaching the bracket to the turbocharger housing, the elongate hole allowing a sliding movement of the actuator assembly relative to the turbocharger housing. Preferably the actuator housing is connected to the bracket using at least one, and preferably three, rivets. The diaphragm may be crimped to connect it to the actuator housing and it may be coated with elastomer bead to improve and control the crimping process. Advantageously the shape of the piston in the actuator is modified to reduce the overall length of the actuator. According to a preferred embodiment the bracket comprises a third portion extending perpendicular to the first portion and being generally parallel to the second portion and the third portion having an elongate hole formed therein to receive a bolt to attach the bracket to the turbocharger housing, the elongate hole allowing a sliding movement of the actuator assembly relative to the turbocharger housing. Preferably the elongate holes allow around 4 mm of sliding movement (+/−2 mm). According to a second aspect of the present invention there is provided a method of calibrating a variable nozzle turbocharger comprising the steps of: a) using an actuator assembly which has a spaded rod; b) using at least one bolt to attach the actuator assembly to an end housing (of either a compressor or a turbine) which has a pin crank so that the spaded rod is adjacent to the pin crank; c) applying a predetermined vacuum to the actuator, through an actuator port to allow the actuator to take a calibrated position determined by gravity; d) keeping the pin crank in contact with the flow screw of the turbocharger; e) tightening the or each bolt, at a predetermined torque, to tighten the attachment of the actuator assembly to the end housing; f) controlling the actuator calibration in accordance with predetermined process instructions; g) determining whether the calibration process is correct and if it is not correct then repeating the process from step c) using a different predetermined vacuum value. According to a preferred embodiment of the second aspect of the invention the method is conducted using the actuator assembly of the first aspect. The compact design of the new actuator and the novel calibration procedure enable application of a VNT in confined spaces where conventional parts would be difficult or impossible to fit and adjust. In addition, automation of the calibration process is enabled, providing increased production line capacity. For a better understanding of the present invention, and to show how the same may be carried into effect, reference will now be made to the accompanying drawings, in which: FIG. 1 is a cross-section of an actuator for a variable nozzle turbocharger according to one embodiment of the invention; FIG. 1A is a cross section of an actuator for a variable nozzle turbocharger showing a design according to the prior art; FIG. 2 is a perspective view of part of the known actuator of FIG. 1A. FIG. 3 is a perspective view of part of the actuator of FIG. 1, according to one embodiment of the invention; FIG. 4 is a side view of a known bracket for fixing the known actuator of FIG. 2 to a variable nozzle turbocharger; FIG. 5 is a perspective view of one embodiment of a new bracket for fixing the new actuator of FIG. 3 to a variable nozzle turbocharger. FIG. 6 is a side elevation view of the known actuator of FIG. 2 attached by the known bracket of FIG. 4 to a variable nozzle turbocharger. FIG. 7 is a side elevation view of the new actuator of FIG. 3 attached by the new bracket of FIG. 5 to a variable nozzle turbocharger. FIG. 8 is a cross-sectional view of the new actuator of FIG. 3 illustrating the new calibration method. FIG. 9 is a perspective view of the new actuator and another embodiment of a new bracket. In FIG. 1A the known actuator assembly comprises a diaphragm 1A crimped at 2A into the side wall of an actuator assembly 3A. A spring 4A holds the diaphragm 1A taut and controls the position of actuator piston 8A. Two sets of bolts and nuts, of which one is shown at 9A, are used to hold the bottom wall of the actuator assembly 3A to a bracket assembly 18A which in turn will be connected to a turbine housing (not shown). A calibration rod 5A extends through a gimball 11A and is held in place by a locknut 6A and is fixed at one end to the actuator piston 8A. A heat shield 12A protects the actuator. A stud 13A passes through the bottom wall of the actuator assembly 3A and a double plate 17A. The rod 5A has an adjustable rod end 15A and a bolt hole 21A for fixing to either the compressor or the turbine housing of the turbocharger. By contrast, in FIG. 1, a modified actuator assembly is shown according to the invention. The two bolts and nuts 9A are replaced by three rivets, of which two are shown at 7, and the actuator assembly 3 combines the functions of actuator assembly and bracket assembly. The rod end 5A and the locknut 6A are replaced by a rod 5 with spaded (flattened) end portion 15 shown in profile in FIG. 1. This new shape for the rod end assists the calibration process as will be described later. A spaded rod is a design known for use in wastegated turbochargers but has not hitherto been used in variable nozzle technology because the calibration process is not the same. Specifically the spaded rod 5 has a flat portion at one end formed by cold forging with a hole to be connected to the pin crank of the turbocharger. A compression spring 4, in the inventive modification, is centered in the actuator assembly 3 and this reduces the hysteresis, ie the inaccuracies, particularly in calibration, due to the imperfections in the spring 4 itself. The diaphragm 1 is crimped into the side wall 3 of the actuator assembly at 2 and this is improved in the invention by a crimping control achieved by the addition of elastomer bead 46 on the diaphragm 1. Elastomer bead can accept more variation in compression during the crimping process used to close the actuator than a flat shape which is traditionally used by the applicant, or a metal to metal contact as traditionally used by other people in the field. The elastomer bead 46 also improves the seal capability. The convolution of the diaphragm 1 has a reduced width to reduce the diaphragm stress and the overall diameter of the actuator. In addition, the piston 8 has a shape modification which reduces the overall length of the actuator assembly, as can be seen by comparing FIG. 1 with FIG. 1A. The new bracket is shown at 18 and the gimble is shown unchanged at 11. The piston 8 must withstand 1.7NM torque, with respect to the rod end 5, without relative motion. The engineering requirements are 0.15 SCCM max under 1.5 bars and a pull test of 100 Kg. FIG. 2 is a perspective view from below of a traditional design of a turbocharger actuator assembly, ie a view from below of the assembly in the left hand side of FIG. 1. The heat shield 12A is shown part cut-away and the side wall of the actuator assembly 3A is attached to the bracket assembly 18A by two nuts 9A. The rod end 15A is held in place by a locknut 6A and is adjustable. Thus, traditionally, calibration is effected by two fixed end points with a manually adjustable connecting rod and end. By contrast, the inventive actuator assembly of FIG. 3 has a side wall of actuator 3 held to the bracket assembly 18 by the three rivets 7 and no locknut is needed because the rod 5 is spaded at the end 15 and of fixed length. Thus, the actuator end-point is allowed to move, and the rod and the second end point are fixed. When a calibrated vacuum is applied to the actuator, the actuator body is moved towards the fixed end point until forces are equalized. The actuator 3 is then in the calibrated position and is fixed to the compressor or the turbine housing by accessible bolts and bracket. The traditional shape of the bracket 18A is shown in detail in the plan drawing of FIG. 4 which also shows the positions of two bolts 10A which hold the bracket 18A to a traditional turbocharger body. Such an arrangement is shown in the side view of FIG. 6 where a traditional turbocharger 20 is attached to a traditional actuator 30A by the traditional bracket 18A which is attached to the actuator by two bolts and nuts 19A. The traditional adjustable rod end 15A is shown. In FIG. 5 the shape of the new bracket 18 is shown with a generally triangular plate section 31 having three rivet holes 32, and two bent sections 33 and 34 having elongate bolt holes 35 and 36 respectively. A central hole 37 accommodates the fixed length new shaped rod 5 with end 15. As shown in the side view of FIG. 7, the new bracket 18 is used to connect the new actuator body 30 to a turbocharger 20. The plate section 31 is riveted to the actuator housing by three rivets 7 and the bent portions 33 and 34 are connected to the turbocharger 20 either to the turbine housing or the compressor housing by two bolts 38 through the slot shaped holes 35 and 36. The elongate shape of the holes 35, 36 allows adjustment during calibration and obviates the need for the rod end 15 on the actuator 30 to be adjustable. FIG. 6 shows a traditional actuator assembly 30A, such as that shown in FIG. 2 and of FIG. 1A, attached to a turbine housing 20 by means of the bracket of FIG. 4 by means of bolts and nuts 19A. The rod end 15A is shown. FIG. 7 shows a new actuator assembly 30, such as that shown in FIG. 3 and FIG. 1, attached to a turbine housing 20 by means of the bracket of FIG. 5. The attachment is by rivets 7 through the first portion of the bracket 31 and bolts 38 through at least the second portion of the bracket allowing a sliding movement of the actuator 30 relative to the turbine housing 20 as shown by the arrow 39. FIG. 8 illustrates the new calibration method and comprises a cross sectional view of the inventive actuator. The new calibration process comprises attaching the actuator 30 and bracket assembly 18 onto the turbocharger 20 in a vertical position with the actuator head down and the spaded rod 5 adjacent to the pin crank 40. Vacuum is applied to the actuator port 42. The actuator will naturally take its calibrated position under the influence of gravity. The pin crank 40 is put in contact with the VNT flow screw as shown by the arrow 41. The attachment bolts 38 (FIG. 7) are then tightened at the required torque and the actuator calibration is controlled according to normal process instructions. If the actuator calibration is not correct, then the bolts 38 are unscrewed and the process is repeated from step 2 with a modified vacuum value. FIG. 9 shows the new actuator 3 assembled to the bracket 18 and shows the rod 5 and spaded rod end 15 together with the rivet holes 32 and the slot holes 35, 36 in the bent portions 33, 34 respectively. The slot-type holes 35, 36 accept a sliding movement The heat shield 12 is also shown.

20050429

20080311

20051006

96084.0

TRIEU, THAI BA

TURBOCHARGER ACTUATOR

UNDISCOUNTED

ACCEPTED

ACCEPTED

Method and device for supplying of a data set stored in a database

To supply of a data set, e.g. the content of a copy protected audio CD, which is stored in a database (6), e.g. to a user PC (2) on which said content of a copy protected audio CD cannot be accessed, the following steps are performed: receiving a serial code of a set of serial codes assigned to said data set (S3); verifying of said received serial code (S4); in case of a positive verification, accessing said data set corresponding to said received and positively verified serial code from said database (S5, S6); and outputting of at least parts of said accessed data (S7).

1. Method for supplying of a data set stored in a database (6), characterized by the following steps: receiving a serial code of a set of serial codes assigned to said data set (S3), verifying of said received serial code (S4), in case of a positive verification, accessing said data set corresponding to said received and positively verified serial code from said database (S5, S6), and outputting of at least parts of said accessed data set (S7). 2. Method according to claim 1, characterized by an encryption of said data set with a digital right management encryption (S8) after said data set is accessed (S5, S6) and before it is output (S7). 3. Method according to claim 2, characterized in that said digital right management encryption (S8) is based on the serial code assigned to said data set. 4. Method according to claim 1, characterized in that a user who wants to receive said data set stored in said database (6) obtains said serial code after a contract about the rights to use said data set is made with the supplier of said data set. 5. Method according to claim 1, characterized in that a user who wants to receive said data set stored in said database (6) obtains said serial code when purchasing said data set on a data carrier (1). 6. Method according to claim 5, characterized in that said serial code is an unique serial code which is assigned to only one data carrier (1) storing said data set and said set of serial codes are all serial codes assigned to all or a predetermined part of all data carriers storing the same data set. 7. Method according to claim 5, characterized in that said serial code is stored as data on said data carrier (1). 8. Method according to claim 5, characterized in that said serial code is associated to said data carrier (1) by being supplied on a case of said data carrier (1) and/or on a written description delivered with said data carrier (1). 9. Method according to claim 5, characterized in that said data carrier (1) is protected against copying said data set from said data carrier (1). 10. Method according to claim 1, characterized in that said step of verifying of said received serial code (S4) comprises the step of: determining a positive verification in case said serial code is valid in terms of general rules for the structure of a serial code. 11. Method according to claim 1, characterized in that said step of verifying of said received serial code (S4) comprises the step of: determining a positive verification in case said data set should be downloaded and said serial code is not disabled for the data retrieval. 12. Method according to claim 1, characterized in that a serial code gets disabled for the data retrieval in case the associated data set was output a first predetermined amount of times as download. 13. Method according to claim 1, characterized in that a serial code gets disabled for the data retrieval in case the associated data set was output a second predetermined amount of times as streaming. 14. Method according to claim 1, characterized in that said database (6) is remotely accessible. 15. Method according to claim 1, characterized in that said database (6) is accessible via the internet or any other network. 16. Method according to claim 1, characterized in that said serial code comprises an alphanumeric code with a predetermined number of digits. 17. Method according to claim 1, characterized in that said serial code comprises a computer readable code, e.g. a barcode. 18. Method according to claim 1, characterized in that said data set comprises video and/or audio data. 19. Computer program product, comprising computer program means adapted to perform the method steps as defined in claim 1 when being executed on a computer, digital signal processor, or the like. 20. Storage medium, characterized by storing a computer program product according to claim 19. 21. Data set supplying device (9), comprising a database (6) for storing data sets, characterized by a serial code receiving means (3) for receiving a serial code of a set of serial codes assigned to said data set, a verification means (4) for verifying of said received serial code, an accessing means (5) for, in case of a positive verification, accessing said data set corresponding to said received and positively verified serial code from said database (6), and an output means (7) for outputting of at least parts of said accessed data set. 22. Data set supplying device (9) according to claim 21, characterized by an encryption means (8) for encryption of said data set with a digital right management encryption after said data set is accessed and before it is output. 23. Data set supplying device (9) according to claim 22, characterized in that said digital right management encryption is based on the serial code assigned to said data. 24. Data set supplying device (9) according to claim 21, characterized in that said serial code is an unique serial code which is assigned to only one data carrier (1) storing said data set and said set of serial codes are all serial codes assigned to all or a predetermined part of all data carriers storing the same data. 25. Data set supplying device (9) according claim 21, characterized in that said verification means (4) determines a positive verification in case said serial code is valid in terms of general rules for the structure of a serial code. 26. Data set supplying device (9) according to claim 21, characterized in that said verification means (4) determines a positive verification in case said data set should be downloaded and said serial code is not disabled for the data retrieval. 27. Data set supplying device (9) according to claim 21, characterized in that said verification means (4) disables a serial code for the data retrieval in case the associated data set was output a predetermined amount of times as download. 28. Data set supplying device (9) according to claim 21, characterized in that said verification means (4) does not disable a serial code for the data retrieval in case the associated data set was output as streaming. 29. Data set supplying device (9) according to claim 21, characterized by being remotely accessible. 30. Data set supplying device (9) according to claim 21, characterized by being accessible via the internet or any other network. 31. Data set supplying device (9) according to claim 21, characterized in that said serial code comprises an alphanumeric code with a predetermined number of digits. 32. Data set supplying device (9) according to claim 21, characterized in that said serial code comprises a computer readable code, e.g. a barcode. 33. Data set supplying device (9) according to claim 21, characterized in that said data set comprises video and/or audio data. 34. Data carrier (1), comprising a copy protection for a data set stored on said data carrier, characterized by a serialization associated to said data set stored on said data carrier (1). 35. Data carrier (1) according to claim 34, characterized in that the data carrier (1) is not readable by a computer. 36. Data carrier (1) according to claim 34, characterized in that the data carrier (1) is a CD or a DVD.

The present invention relates to a method for supplying of a data set stored in a database and a corresponding data set supplying device as well as a data carrier relating to said method and device. In particular, the present invention relates to a method for supplying of a data set via a database, which data set is normally stored and distributed to users on a copy protected data carrier, e.g. the audio data stored on a copy protected audio compact disc (CD) or the audio/video data stored on a copy protected digital versatile disc (DVD). Most modern personal computers are already well-equipped with recording hard- and software which makes it easy to record music and/or video on compact disc recordables (CD-R) or digital versatile disc recordables (DVD-R). Within the last couple of years the number of copies made from a single sound carrier tremendously increased. Therefore, the music and video industry found different solutions to protect their audio and video CDs and DVDs from illegal duplication and copy right infringement. These copy protection solutions normally allow to play copy protected record carriers on CD-audio players, car hi-fi systems, game consoles, like Play Station™ and PS2™, DVD-players and SACD players. However, the special signatures used prevent playback and a copying on personal computers and thus offer high robustness on copy protection. The special signature might be designed to not change a single bit in the audio and/or video data stream to protect the quality of the original recording by the artist and to comply with the respective standards, e.g. the Red-Book for CDs, which do not allow built-in uncorrectable errors. However, due to the fact that such copy protected CDs or DVDs cannot be played back on a PC, customers who purchased such record carriers feel restricted in their playback possibilities due to not being able to use these record media on their personal computers or laptops. Therefore, it is the object underlying the present invention to provide such a content, i.e. data set, so that a user is able to install it on a personal computer or laptop which is not able to read the copy protected record media. This object is solved by a method for supplying of a data set stored in a database according to the present invention as defined in independent claim 1, a data set supplying device according to the present invention as defined in independent claim 21, and a data carrier according to the present invention as defined in independent claim 34. Preferred embodiments thereof are respectively defined in the respective following sub claims. A computer program product according to the present invention is defined in claim 19 and a storage medium storing a computer program product according to the present invention is defined in claim 20. The key feature of the present invention is that every data set, e.g. content of an audio CD or a DVD, gets at least one serial code assigned with which after verification said data set might be supplied from a database to a customer. Therewith, according to the present invention an individual copy protected audio CD might be supplied with an individual serial code, normally a unique alphanumeric number on the record carrier, inside or on back of the booklet supplied together with the CD, with which serial code the content of the particular audio CD might be downloaded to the personal computer of a user, since the serial code comprises a pointer functionality to said particular data set by the assignment thereto. The database might additionally be secured with an access restriction, such as a password, etc. The key might also be stored as data on the record carrier in which case an automatic access, e.g. streaming or download, of the corresponding data after insertion of the respective CD into a correspondingly designed CD player or a computer, such as a PC or laptop, will be possible. A data set in the sense of the present invention might be the complete audio content of a CD or the complete audio/video content of a DVD, i.e. a fixed amount of data representing a predetermined content of a storage medium. The method for supplying of a data set stored in a database according to the present invention comprises the following steps: receiving a serial code of a set of serial codes assigned to said data set, verifying of said received serial code, in case of a positive verification, accessing said data set corresponding to said received and positively verified serial code from said database, and outputting of at least parts of said accessed data set. Corresponding thereto, a data set supplying device, comprising a database for storing data sets, according to the present invention comprises the following additional means: a serial code receiving means for receiving a serial code of a set of serial codes assigned to said data set, a verification means for verifying of said received serial code, an accessing means for, in case of a positive verification, accessing said data set corresponding to said received and positively verified serial code from said database, and an output means for outputting of at least parts of said accessed data set. Finally, a data carrier, comprising a copy protection for a data set stored on said data carrier, according to the present invention comprises a serialization associated to said data set stored on said data carrier. Therewith, according to the present invention, a unique serial code might be associated to only one individual record carrier, i.e. assigned to a data set stored on said individual record carrier. All other record carriers of the same type, i.e. storing the same data set, might have a respective other serial code of the set of serial codes assigned, which set of serial codes might be assigned to all or a predetermined part of all record carriers of the same type. In other words, a customer buying a copy protected audio CD might receive a unique serial code with the audio CD, which serial code is assigned to the audio data recorded on the CD. Another customer, buying another copy protected audio CD with the same content might receive another serial code associated to the same audio data. Having a serial code, the customer might download the associated data set, e.g. the whole audio content of the CD, or selected parts thereof, e.g. only selected tracks. It is also possible that additional data, e.g. bonus tracks which are not included on the record carrier, e.g. the audio CD, are additionally accessible for the user. This additional access might have an extra limitation, e.g. to the first access or to a predetermined access type (e.g. streaming or download). Further, after a data set supplying device according to the present invention, e.g. an internet server, received such a serial code, e.g. through a user interface, a verification is performed and in case the serial code is positively verified, the corresponding data set, i.e. the audio data to which the serial code is assigned, is output to the user. It is possible to log the procedure and to supply the corresponding data set only a predetermined amount of times, e.g. once. Also, a distinction between download, i.e. storing of the supplied data set on the user side, and streaming, i.e. only output, but no storing of the supplied data set on the user side, could be made so that streaming might be always allowed whereas download might only be allowed a predetermined amount of times, e.g. once. In such a case a data set supplying device according to the present invention would additionally comprise a logging means for monitoring the use of a serial code and restricting the access to the corresponding data set, e.g. by affecting the verification. In a preferred embodiment of the method according to the present invention, an encryption of said data set with a digital right management encryption is performed, e.g. after said data set is accessed and before it is output. Correspondingly, a data set supplying device according to this preferred embodiment of the present invention additionally comprises an encryption means for encryption of said data set with a digital right management encryption after said data set is accessed and before it is output. In this case, said digital right management encryption might be based on the serial code assigned to said data set. As will be further elucidated below, the digital right management encryption is a system according to which it is secured that data which is installed or copied on a PC can only be properly accessed with an decryption key which is only supplied a predetermined amount of times, e.g. once. In other words, the content of an audio CD downloaded on a user PC also which received the proper decryption key can only be played back on said particular user PC, if the decryption key is not supplied to another user PC which also received the downloaded audio data. In the method and/or for the data set supplying device according to the present invention a user who wants to receive said data set stored in said database might obtain said serial code after a contract about the rights to use said data set is made with the supplier of said data set. Alternatively or additionally, in the method and/or for the data set supplying device according to the present invention a user who wants to receive said data set stored in said database might obtain said serial code when purchasing said data set on a data carrier. In the latter case, said serial code might be an unique serial code which is assigned to only one data carrier storing said data set and said set of serial codes are all serial codes assigned to all or a predetermined part of all data carriers storing the same data set. In the latter case, alternatively or additionally, said serial code might be stored as data on said data carrier. In the latter case, further alternatively or additionally, said serial code might be associated to said data carrier by being supplied on a case of said data carrier and/or on a written description delivered with said data carrier. In the latter case, still further alternatively or additionally, said data carrier might be protected against copying said data set from said data carrier. In the method according to the present invention said step of verifying of said received serial code might comprise the step of: determining a positive verification in case said serial code is valid in terms of general rules for the structure of a serial code. In the method according to the present invention said step of verifying of said received serial code might alternatively or additionally comprise the step of: determining a positive verification in case said data set should be downloaded and said serial code is not disabled for the data retrieval. In the method according to the present invention a serial code might get disabled for the data retrieval in case the associated data set was output a first predetermined amount of times as download. Alternatively or additionally, in the method according to the present invention a serial code might get disabled for the data retrieval in case the associated data set was output a second predetermined amount of times as streaming. Correspondingly, in a data set supplying device according to the present invention these verifying and/or disabling steps might be performed by said verification means. In the method according to the present invention said database might be remotely accessible. In the method according to the present invention said database might be accessible via the internet or any other network. Correspondingly, a data set supplying device according to the present invention might be remotely accessible, e.g. via the internet or any other network. As set out above, the data set supplying device according to the present invention might be realized as internet server. In the method and/or for the data set supplying device according to the present invention said serial code might comprise an alphanumeric code with a predetermined number of digits. Alternatively or additionally, in the method and/or for the data set supplying device according to the present invention said serial code might comprise a computer readable code, e.g. a barcode. In the method and/or for the data set supplying device according to the present invention said data set might comprise video and/or audio data. A computer program product according to the present invention comprises computer program means adapted to perform the method steps as elucidated above when being executed on a computer, digital signal processor, or the like. A storage medium according to the present invention stores a computer program product according to the present invention. A data carrier according to the present invention might be not readable by a computer. Alternatively or additionally, a data carrier according to the present invention might be a CD or a DVD. Further objects, features and advantages of the method, the device and the data carrier according to the present invention are elucidated in the following on basis of an exemplary embodiment according to the present invention in connection with the accompanying FIG. 1 which shows a sequence diagram elucidating the method, device and record carrier according to an illustrative embodiment of the present invention to offer a customer the possibility to transfer the content of a purchased copy protected record carrier to a personal computer. The illustrative preferred embodiment described in the following is an audio copy control system which is designed to fight domestic piracy by preventing CD to CD-R copying. The main benefits of the here applied copy protection scheme which is disclosed in the Applicant's PCT-Patent Application PCT/EP01/02633 which is herewith incorporated by reference into this Application is highest copy protection efficiency together with full compatibility with the existing audio CD players, car hi-fi-systems, DVD video players, SuperAudio CD players, and game consoles such as PlayStation™ and PlayStation 2™ consoles. Extensive testing regarding the efficiency of the system provided that 90% of the CD-ROM/DVD drives judge the protected CD as not readable and therefore the audio CD can neither be copied nor ripped. On the other hand, the audio part fully complies with the Red Book standard, i.e. not a single bit is changed in the audio data stream which means that no uncorrectable errors are used to protect the audio data. This gives the highest audio quality for the protected music. Further, the method, device and record carrier according to the present invention provide a full playability of the data recorded on the copy protected record carrier on a computer via an internet download or streaming solution which is—in a preferred embodiment—again secured against unauthorized copying by way of a digital rights management, as described in the following in connection with FIG. 1. A data carrier according to the present invention, such as an audio CD 1 which comprises a copy protection for the audio data which is stored thereon, comprises a serialization associated to said audio data stored thereon. In the shown example the serialization is a unique serial code, i.e. a serial code which is only once associated to said particular audio data on said particular audio CD. In other words, also another audio CD comprising the same audio data does not have the same serial code. The serial code in FIG. 1 is a 9 digit code which is divided in three packets of three digits and which reads KK2-PK4-LMS. In case a user wants to transfer the audio data comprised on the audio CD 1 to a user PC 2, the serial code KK2-PK4-LMS associated to the particular audio data on the particular audio CD 1 has to be entered in a step S1 to the user PC 2, e.g. within an internet browser. Thereafter, the serial code is transferred from the user PC 2 to a data set supplying device 9 according to the present invention, e.g. an internet server, in a step S2. The data set supplying device 9 receives said serial code in a step S3 with a serial code receiving means 3. The serial code might be one of a set of serial codes assigned to said particular audio data, wherein each particular audio CD storing said particular audio data has a different unique serial code and all serial codes or a particular part of all serial codes associated to the same audio data, but to different audio CDs, built the set of serial codes. The serial code received in step S3 gets verified in a step S4 by a verification means 4. In case the verification is negative, i.e. the serial code is invalid, the process proceeds to a step S9 and stops. This means, the audio data is not transferred to the user, since the serial code entered in step S1 and transferred to the data set supplying device 9 in step S2 was invalid. Invalidity of a serial code might be given in case of a wrong serial code structure, e.g. a different number of digits, a not assigned serial code, a already disabled serial code, an infringement of serial code design rules, etc. In case the verification result is positive, the process proceeds with a step S5 in which an accessing means 5 accesses a database 6 which supplies the requested audio data in a step S6 to the accessing means 5. The accessed data is passed on to an output means 7 which outputs the audio data corresponding to the input serial code in a step S7. In the preferred embodiment an encryption of the accessed data is performed in a step S8 by an encryption means 8 after said data is accessed and before it is output. The output data is transferred to the user PC 2 as a download in step S10. Alternatively, the output data could be supplied to the user PC 2 as a streaming in which case an encryption of the accessed data might be not necessary depending on the music player installed on the user PC 2 which is used for reproducing the streamed audio data. In case the user wants to reproduce the downloaded audio data with the user PC 2, the digital right management system which is explained in the following ensures that no unauthorized copying and distribution of the transferred audio data is performed. When a request for playing the music corresponding to the downloaded audio data is issued from the user to the playback program installed within the user PC 2 this program looks for a decryption key to decrypt the encrypted and downloaded audio data in a step S11. This decryption key corresponds to the license to play the corresponding audio data on the particular user PC 2. In case the encryption key exists on the user PC 2 the audio data is played in step S12. In case no encryption key for the particular audio data exists on the user PC 2 a request is issued to a digital rights management server to provide the encryption key. This request might be issued via the internet. The digital rights management server checks in a step S13 whether a license number for this particular audio data might be issued or not. For example, for an audio CD only one license number might be issued. In case it is still possible to issue the license number, e.g. no license number was issued before, it is transferred to the user PC 2, installed thereon and the audio data are played back in step S15. In case the limit of license numbers to be issued for the particular audio data is reached, the process stops in step S14 and no license number is installed on the user PC 2. In this case no playback of the audio data would be possible with the user PC 2. The digital rights management server might be included within the data set supplying device 9, e.g. within the same internet portal or on the same internet server. The described Online Solution according to the present invention enables CD-owners to download or stream the music tracks which are on the copy protected audio CD. The system can also be integrated in artists' web sites seamlessly—so it does not have to be seen as a special music portal. In order to prevent file sharing with online music exchange portals or the like, the music files are in general supplied with the described copy protection system. Each copy protected CD according to the present invention is supplied with a serial code, e.g. an unique alphanumeric number inside or on the back of the booklets. The serial code might consist of 9-digit combination of numbers and characters which is different for every CD. The buyer of a copy protected CD can download or stream the respective music tracks from artist's web site or a special music portal after entering this code. The serial code is checked for its validity and the procedure might be logged. Thus the origin of this copy protected CD is theoretically retraceable down to the production process. The described Online Solution offers the tracks for tethered download or streaming. When downloading, the music file is transmitted once to the customer's hard disk and can be played back from there after the download is completed. The digital rights management system, e.g. the described online copy protection system, ensures that music files are unusable for third parties or illegitimate users. When streaming the music files are (in contrast to the download) not stored on the customers hard disk. The data stream is not recorded but directly played back by the computer. The advantage of this method is that music can be played back from the very first second of the transmission. Streaming does not currently play a major role in the internet compared to download, but it is becoming more and more important with the increasing use of flat rates and broad band internet. Another advantage of streaming is its ability to adapt itself to the speed of the customers internet connection (sure stream). Thus, even users with a very slow internet connection are able to stream music files without any interruption although with a lower audio quality). In general, any available file formats for streaming or downloading can be used with this system, e.g. Windows Media™ and Real Audio™. Windows Media™ is similar to MP3, but comes with a higher compression rate and above all with an integrated digital rights standard. Real Media™ is the most common streaming solution at the present time. Both formats offer good audio quality with low bandwidth requirements and can be used with Apple MAC and PC MS-Windows systems. The Microsoft Windows Media Player™ can be used for streaming and download. It can be used with MAC or Microsoft operating systems. The Real Player™ is used for streaming the music files. It can be used with MAC or Microsoft operating systems. The described Online Solution shall be understood as a supplement of the above referenced audio copy protection system. Therefore, security and copy protection of the offered music files have highest priority. In addition to the validation of the serial codes, the preferred embodiment including the Digital Rights Management of the music files plays a central role. The function of these two mechanisms in context with the music is explained below: Layer 1: The Serial Code In a central security database each audio disc is associated with a serial code. This code might be a 9-digit alpha numerical combination which does not contain the numbers [0] and [1] and the characters numbers [O] and [I] in order to ensure good legibility. Accordingly more than 35 Trillions of combinations are available. Example for Serial Code: KK2-PK4-LMS When the user has entered his serial code into the music portal, the code is verified and if it is valid the tracks of the corresponding CD are offered for tethered download or streaming. Layer 2: Digital Rights Management Whenever a download is requested by a user, the music file is encrypted with individual parameters and supplied with digital rights. Such an encrypted file cannot be played back until a proper key is installed on the user's computer. Such a key is an encrypted file with few kB memory space, which is integrated into the operating system of the consumer's PC. When the music file is played back for the very first time, usually immediately after the download, the installed player contacts the key server, which determines the rights to be issued from the security database. The publisher can define different rights in the Digital Rights Management—such as access rights per title, per individual music track—or even expiration date on usage. Based on the information contained by the encrypted music file and the rights set in the security database, a key is generated and sent to the installed player of the user. This key is implemented into the operating system of the user. The complete Rights Management procedure happens fairly imperceptible for the user and is finished within a couple of seconds. Once there is a key installed for the respective music file, there is no connection to the key server required any more. Thus, after a music file has been installed with its proper key, it can be played back offline any time. As the key is associated with the computer's internal data, it cannot be copied. Therefore, the music file will not play on another computer if passed on. A further key will only be issued if this is permitted by the publisher—for example to three PCs (Home PC, Office PC and Laptop). With the described music portal i.e. data set supplying device 9, the issued keys are in general valid for all tracks of a CD. Thus, if a key has been installed on a computer, each online track of this CD can be played back immediate offline without requiring a separate key. The most important specification of this copy protection system is that the music file cannot be passed on. There are a number of further features which allow to specify the rights of a music file more precisely. The following list outlines some of the most important digital rights possibilities without going to much into detail: Date limitation of the possibility to play back: works offline, file is locked when the system clock is set to a previous date. Limitation of the number of play backs: works offline The right to copy the file to a portable player. Limitation of the number of copies to portable players. A further application area are pre-releases for radio stations. Such pre-releases can be protected with the Digital Rights Management system. The protected pre-releases can either be published on CD-R or provided for download in combination with the serial code, e.g. the unique 9-digit code. The publisher is able to specify a start-date and an expiration date or a maximum number of uses, for example. Therefore, music releases can be distributed simultaneously to different radio stations, thus giving them the possibility to have different release dates. With the described mechanism the publisher is able to control the date of release by the minute for each radio station separately. As mentioned above, because of the serial code serial code supplied with the CD or DVD, only customers who have purchased the CD or DVD have access to the online files. As a future opinion, a combination with an online shop for purchasing a serial code can be established. This will enable customers to buy music download without having bought the CD or DVD. Of course, also all other storage media are applicable to the present invention. An illegal user might be able to download the music files with a illegally obtained serial code. But when he tries to play back one of the downloaded songs, the system recognizes that the key for these files has already been issued to another user and refuses to play back the files. Even streaming of music files can be furnished with a digital rights management in order to refuse streaming with shared serial codes.

20040812

20100706

20050421

60892.0

LEMMA, SAMSON B

METHOD AND DEVICE FOR SUPPLYING OF A DATA SET STORED IN A DATABASE

UNDISCOUNTED

ACCEPTED

ACCEPTED

Broadcast receiver and recording method

A broadcast receiver is provided which can prevent recording of uncopyable contents without failing to record copyable contents. A copy information detecting unit (4) detects copy control information attached to contents. A discriminating unit (5) discriminates the copyability or uncopyability. The contents recorded in a user-unreadable recording unit (6) is transferred to a user-readable recording unit (7) only if copyable.

1. A broadcast receiver having a recording unit for recording contents characterized by: an input unit for receiving a command for recording the contents from a user; a contents receiving unit for receiving the contents; a copy information detecting unit for detecting copy control information including at least information relating to copyability or uncopyability of the contents from the contents; a discriminating unit for discriminating the copyability or uncopyability of the contents based on the copy control information; a user-unreadable first recording unit for recording the contents in accordance with the record command; and a user-readable second recording unit for receiving the contents from the first recording unit only when the contents is copyable. 2. A broadcast receiver according to claim 1 further characterized by a signal output control unit for inputting multiple input contents, selecting the input contents to be output in accordance with a selection by the user, and selecting the contents to be recorded in the first recording unit from the input contents. 3. A broadcast receiver according to claim 1 further characterized by: the multiple copy information detecting unit corresponding to the multiple copy control information and a stop unit for, when the copy control information from one of the copy information detecting unit is determined as uncopyable by the discriminating unit, stopping an operation of the other copy information detecting unit. 4. A broadcast receiver according to claim 1, further characterized by a display unit for displaying information relating to the copyability or uncopyability, which is determined by the discriminating unit. 5. A method for recording contents having copy control information including at least information relating to copyability or uncopyability, the method characterized by the steps of: storing the contents in a user-unreadable first recording medium; discriminating the copy control information of the contents; transferring the contents to a user-readable second recording medium by the first recording medium if copyable; and not transferring the contents to the second recording medium by the first recording medium if uncopyable.

TECHNICAL FIELD The present invention relates to a broadcast receiver for receiving broadcast contents and, in particular, to a broadcast receiver including a recording unit for recording broadcast contents. BACKGROUND ART With the development of recent digital technologies, fraud copies of video and/or audio contents in digital broadcasting have been increased. Therefore, the copyright protection has become important. Conventionally, in order to prevent the fraud, Macrovision (where Macrovision is a trademark of MacroVision in the U.S.), CGMS (Copy Generation Management System)-A and so on exist as copy control systems for analog interfaces. Macrovision is a copy guard system broadly used for commercially available video sources, satellite broadcasts and so on. Macrovision adopts a copy control method for preventing an output source from being normally recorded by causing AGC (Automatic Gain Control) of a video deck to malfunction. CGMS-A adopts a copy control method for outputting contents having copy control information such as “copyable”, “only one generation copyable” and “uncopyable”. On the other hand, for digital outputs to a digital video, for example, DTCP (Digital Transmission Copy Protection) is used, for example. DTCP is a standard for encoding and exchanging data between digital devices connected by using IEEE-1394 (Institute of Electrical and Electronics Engineers 1394) and has a function for exchanging copy control information. Thus, controls for inhibiting copies and/or permitting the copy of one generation only are allowed. Contents include copy control information thereof. The copy control information is detected by a copy control information detecting circuit of the broadcast receiver. Copyability and uncopyability thereof can be judged by a microcontroller. Signals output from a player such as a VTR (Video Tape Recorder) may also include copy control information. However, a certain amount of time is required from the detection of copy control information to the judgement of copyability/uncopyability in order to prevent false detection due to noise, for example. When contents during the period is recorded in a storage device such as an HDD (Hard Disk Drive), uncopyable contents may be also recorded before a result from the judgement regarding copy control information is confirmed, which is a problem. On the other hand, once the recording starts after the judgement result is confirmed, video scenes and/or audio and data contents that a user needs to record may be missed, which is another problem. Multiple copy control systems such as the CGMS-A and Macrovision may exist. In this case, the uncopyability is detected by one of copy control information detecting circuits and is judged by the microcontroller. Thus, the other copy control information detecting circuits are not required. However, due to the communication of detected data between the copy control information detecting circuits and the microcontroller, the processing performance of the microcontroller is reduced. In addition, in order to continue the detection, extra power is consumed in the copy control information detecting circuits, which is another problem. When multiple copy control systems exist, priority may not be given to copy information detection. In this case, all of detection and judgement are always performed, and the processing becomes redundant thereby, which is another problem. The present invention was made in view of these points. It is an object of the present invention to provide a broadcast receiver, which cannot play broadcast contents until the permission for copying thereof is determined. DISCLOSURE OF THE INVENTION In order to overcome these problems, according to the invention, there is provided a broadcast receiver having a recording unit for recording contents characterized by an input unit for receiving a command for recording the contents from a user, a contents receiving unit for receiving the contents, a copy information detecting unit for detecting copy control information including at least information relating to copyability or uncopyability of the contents from the contents, a discriminating unit for discriminating the copyability or uncopyability of the contents based on the copy control information, a user-unreadable first recording unit for recording the contents in accordance with the record command, and a user-readable second recording unit for receiving the contents from the first recording unit only when the contents is copyable. Under this construction, contents recorded in the first recording unit in accordance with the record command is not transferred to the user readable second recording unit until the copyability is determined. There is further provided a method for recording contents having copy control information including at least information relating to copyability or uncopyability, the method characterized by the steps of storing the contents in a user-unreadable first recording medium, discriminating the copy control information of the contents, transferring the contents to a user-readable second recording medium by the first recording medium if copyable, and not transferring the contents to the second recording medium by the first recording medium if uncopyable. Under this method, contents recorded in the first recording unit in accordance with the record command is not transferred to the user readable second recording unit until the copyability is determined. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a configuration diagram of a broadcast receiver according to an embodiment of the present invention. FIG. 2 is a flowchart illustrating a recording method. FIG. 3 is a hardware configuration diagram of a digital broadcast receiver. FIG. 4 is a diagram showing a state of control of a copy information detecting portion. FIG. 5 is a flowchart illustrating a recording method. BEST MODE FOR CARRYING OUT THE INVENTION An embodiment of the present invention will be described below with reference to drawings. FIG. 1 is a configuration diagram of a broadcast receiver according to an embodiment of the invention. A broadcast receiver 1 includes an input unit 2 receiving a command for recording or playing contents in response to an input by a user via a remote control 2a, a contents receiving unit 3 for receiving contents, a copy information detecting unit 4 for detecting, from contents, copy control information including information relating to at least copyability/uncopyability of the contents, a judging unit 5 for judging the copyability/uncopyability of broadcast contents based on copy control information, a user-unreadable recording unit 6 for recording broadcast contents in accordance with a record command, a user-readable recording unit 7 for receiving contents from the recording unit 6 only when the contents is copyable, and a signal output controlling unit 8 for selecting one of the copy information detecting unit 4 and the recording unit 7 and causing a display apparatus 8a to output broadcast contents. An operation of the broadcast receiver 1 will be described below. When the contents receiving unit 3 receives broadcast contents provided from a broadcast station or contents input from an external apparatus such as a VTR (Video Tape Recorder) the signal output control unit 8 outputs and plays the received contents to the display apparatus 8a through the copy information detecting unit 4. Here, when a command for recording contents is input by a user's manipulation on the remote control 2a, the signal is received by the input unit 2. The signal output control unit 8 receives contents and transfers the contents to the recording unit 6. The recording unit 6 is user-unreadable, and the information of contents stored therein cannot be referred. Here, the signal output control unit 8 may output the contents to the display apparatus 8a. Contents received by the contents receiving unit 3 include copy control information including information relating to the copyability/uncopyability for preventing fraud copies. This is detected by the copy information detecting unit 4 and is transferred to the judging unit 5. The judging unit 5 judges whether the received contents is copyable or uncopyable with reference to the received copy control information. Here, if the copyability is judged, a command for transferring contents to the recording unit 7 is sent to the recording unit 6. The recording unit 6 transfers the contents to the recording unit 7. If the uncopyability is judged, the contents are not transferred from the recording unit 6 to the recording unit 7. Then, for example, the data recorded in the recording unit 6 is deleted. The recording unit 7 can output contents to the signal output control unit 8. When a command for playing recorded contents is input by a user via the remote control 2a, the command is received by the input unit 2. The signal output control unit 8 displays on the display apparatus 8a the contents stored in the recording unit 7. FIG. 2 is a flowchart illustrating processing for recording contents. When a command for recording contents is input by a user, the signal output control unit 8 records the contents into the user-unreadable recording unit 6 (S1). Next, copy control information attached to the contents detected by the copy information detecting unit 4 is judged with respect to the copyability/uncopyability by the judging unit 5. If copyable, the processing advances to a step S3. If uncopyable, the processing ends (S2). If the copyability is judged, the contents recorded in the user-unreadable recording unit 6 is transferred to the user-readable recording unit 7. Then, the processing ends (S3). As described above, copy control information attached to contents is detected by the copy information detecting unit 4, and the copyability or uncopyability of the contents is judged by the judging unit 5. The contents recorded in the user-unreadable recording unit 6 is transferred to the user-readable recording unit 7 only when the contents is copyable. Thus, copyable contents can be recorded without delay. Furthermore, uncopyable contents can be prevented from recording in the user-readable recording unit 7. Details of this embodiment will be described below. FIG. 3 is a hardware configuration diagram of a digital broadcast receiver according to this embodiment of the invention. A digital broadcast receiver 10 according to this embodiment of the invention includes a remote control receiving portion 11 for receiving a command input by a user through a manipulation of a remote control 20, an external signal input portion 12 for receiving analog external input signal from a VTR, for example, a digital broadcast receiving portion 13 for receiving a digital broadcast, a CPU (Central Processing Unit) 14 for receiving signals from the external signal input portion 12, the digital broadcast receiving portion 13 and the remote control receiving portion 11, a user-unreadable recording device 15 operating under the control of the CPU 14, a user-readable recording device 16, which is connected to the recording device 15, and a signal output control portion 17 operating in response to a command from the CPU 14 and outputting transferred contents to the recording device 15, a monitor (not shown) or the like. Furthermore, the external signal input portion 12 includes a low-pass filter (LPF) 12a receiving externally input signals and an A/D (Analog/Digital) converter 12b, which are connected in series, and copy information detecting portions 12c and 12d connected to the A/D converter 12b in parallel. The A/D converter 12b is connected to the signal output control portion 17, to which a processed signal is output from the A/D converter 12b. The copy information detecting portions 12c and 12d are connected to the CPU 14 to which detected copy control information is output. The digital broadcast receiving portion 13 includes a front-end portion 13a having a tuner (not shown), a demultiplexer portion 13b for demultiplexing TS (Transport Stream) signals, a decoder portion 13c for decoding encoded data, which are connected in series. The demultiplexer portion 13b is connected to the CPU 14 to which the copy control information separated and detected here is output. Functions of the components will be described below. The remote control receiving portion 11 receives a command input by a user via the remote control 20 through infrared rays and converts the command to the data in a format processable by the CPU 14. The external signal input portion 12 will be described below. The LPF 12a receives analog signals of contents from an external apparatus such as a VTR, not shown, and removes high frequency noise. The analog signals processed by the LPF 12a are transmitted to the A/D converter 12b and the copy information detecting portions 12c and 12d. The A/D converter 12b converts the analog signals to digital signals and transmits the digital signals to the signal output control portion 17. Copy control information attached to the contents is detected by the copy information detecting portions 12c and 12d. The detected copy control information is transmitted to the CPU 14. CGMS-A and Macrovision are known as analog copy control systems. The copy information detecting portions 12c and 12d correspond to different copy control systems, respectively. The digital broadcast receiving portion 13 will be described. The front-end portion 13a receives and demodulates RF (Radio Frequency) signals. The demultiplexer portion 13b has a function demultiplexing multiplexed TS signals. Here, copy control information is also retrieved from the multiplexed TS signals. Demultiplexed audio and/or video signals are decoded by the decoder portion 13c and are output to the signal output control portion 17. The retrieved copy control information is transmitted to the CPU 14. The CPU 14 reads the copy control information transmitted from the external signal input portion 12 or the digital broadcast receiving portion 13 and judges whether the received contents is copyable or uncopyable. Furthermore, in response to an input from a user, the CPU 14 controls the output selection of the signal output control portion 17. The recording device 15 is a user-unreadable recording device and may be a semiconductor memory. Alternatively, a hard disk may be used, and an unreadable area may be provided therein. Furthermore, the recording device 15 has a function temporarily recording contents transferred from the signal output control portion 17 as record data when a command for recording the contents is given from a user. Here, the recorded contents is transferred to the recording device 16 only when the CPU 14 gives a transfer command to the recording device 16. The recording device 16 is a user-readable recording device and may be a hard disk. The recording device 16 is connected to the user-unreadable recording device 15. If the contents is copyable, the recording device 16 receives the contents from the recording device 15 having received the command from the CPU 14. When a user gives a command for playing recorded broadcast contents, the recorded contents is output to the signal output control portion 17 in accordance with the output selection by the signal output control portion 17. The signal output control portion 17 receives the contents from the external signal input portion 12 and the digital broadcast receiving portion 13 and selects signals to be output to a monitor (not shown) for example, in accordance with a command of the CPU 14. When a user gives a command for recording the contents, the signal-output control portion 17 transfers signals of received contents as record data to the recording device 15 under the control of the CPU 14. The signal output control portion 17 has a function for reading signals of contents recorded in the recording device 16 as play data and outputting the play data to a monitor (not shown), for example, under the control of the CPU 14 when a user gives the command for playing the contents. An operation of the digital broadcast receiver 10 will be described below. While digital broadcasting is being viewed, a digital broadcast received by the front-end portion 13a is demultiplexed by the demultiplexer portion 13b. The demultiplexed audio and video signals are decoded by the decoder portion 13c and are transferred to the signal output control portion 17. Then, the resulting signals are output to a display apparatus such as a monitor (not shown). When analog signals of contents are received by the digital broadcast receiver 10 from a VTR, for example, connected thereto through a video terminal, high frequency noise is removed by the low-pass filter 12a. The processed data is converted to digital signals by the A/D converter 12b and are transferred to the signal output control portion 17. Then, the resulting signals are output to a display apparatus such as a monitor (not shown). When a command for recording contents is given by a user through a manipulation on the remote control 20, the remote control receiving portion 11 sends a signal indicating the command to the CPU 14. The CPU 14 controls the signal output control portion 17 and transfers the signals of the contents transferred to the signal output control portion 17 to the recording device 15 as record data. With this, the CPU 14 having received copy control information of the contents retrieved by the demultiplexer portion 13b while digital broadcasting is being viewed or copy control information detected by the copy information detecting portions 12c and 12d for analog contents input from the external signal input portion 12 discriminates copy control information. Thus, the CPU 14 discriminates whether the received contents is copyable or uncopyable. Here, if determined as copyable, the CPU 14 gives a command for recording contents in the recording device 15 and transfers the temporarily recorded contents to the user-readable recording device 16. If determined as uncopyable, the contents is not transferred. In this way, the contents transferred to and recorded in the recording device 16 can be played. When a play command is input by a user through a manipulation on the remote control 20, the remote control receiving portion 11 receives and transfers the signal indicating the command to the CPU 14. Under the control of the CPU 14, the signal output control portion 17 outputs, as a signal output, the signals of the contents recorded in the recording device 16 based on an output selection. In this way, when a command for recording contents is given, the contents is temporarily recorded in a user-unreadable recording device. Then, copy control information attached to the contents is detected, and the copyability or uncopyability thereof is discriminated. Only if copyable, the contents is transferred to a user-readable recording device so that the copyable contents can be recorded without delay. Control over the copy information detecting portions. 12c and 12d of the external signal input portion 12 will be described below. FIG. 4 is a diagram showing a state of control over the copy information detecting portions. As shown in the figure, a structure is provided in which the CPU 14 is connected to the copy information detecting portions 12c and 12d through a control line for control or a shared bus such as I2C-bus (where I2C-bus is a trademark of PHILIPS ELECTRONICS N. V.). Thus, the CPU 14 controls the starting and stopping of operations by the copy information detecting portions 12c and 12d. A method for recording contents input to the external signal input portion 12 will be described below which includes control over the copy information detecting portions 12c and 12d by the CPU 14. FIG. 5 is a flowchart illustrating processing of the recording method. S10: Determine Whether Recording is Started or is Being Performed The CPU 14 determines whether a command for recording contents having been input to the external signal input portion 12 is given by a user through a manipulation on the remote control 20 or the contents is being recorded or not. Here, if the recording is started or is being performed, the processing advances to a step S1. If no record commands are given by a user, the processing ends. S11: Record in the User-Unreadable Recording Device Under the control of the CPU 14, the signal output control portion 17 records contents having been input to the external signal input portion 12 to the user-unreadable recording device 15. S12: Wait Until Copy Control is Determined The CPU 14 discriminates whether the contents is copyable or uncopyable based on copy control information detected by the copy information detecting portion 12c. Since the determination regarding the copyability or uncopyability requires a certain period of time, the processing waits until the determination is confirmed. Upon confirmed, the processing advances to a step S13. S13: Determine If the Copy is Ok or not by a First Copy Information Detecting Portion For example, the CGMS-A copy control system finishes determining copy control information earlier than that of the Macrovision copy control system. Therefore, the CGMS-A copy control system is handled as the first copy information detecting portion 12c. Here, if the result from the determination of the copy control information detected by the copy information detecting portion 12c under the control of the CPU 14 at the step S12 is “copyable”, the processing advances to a step S14. If “uncopyable”, the processing advances to a step S19. S14: Determine Whether a Second Copy Information Detecting Portion is ON or Not. The CPU 14 determines whether the copy information detecting portion 12d corresponding to a different copy control system from the one for the copy information detecting portion 12c is operating or not. Here, if operating, the processing advances to a step S16. If not, the processing advances to a step S15. S15: Turn On the Second Copy Information Detecting Portion. Since it is determined at the step S14 that the copy information detecting portion 12d is not operating, the CPU 14 starts the operation of the copy information detecting portion 12d. For example, when the copy information detecting portion 12d corresponds to Macrovision, the detection of Macrovision signals is started. Then, the processing advances to the step S16. S16: Determine If the Copy is Ok or not by the Second Copy Information Detecting Portion. Here, the CPU 14 determines whether the contents input to the external signal input portion 12 is copyable contents or not based on the copy control information detected by the copy information detecting portion 12d. If copyable, the processing advances to a step S17. If uncopyable, the processing advances to a step S20. S17: Copy to a User-Readable Recording Device In the processing up to the step S16, it is determined that the signals of the contents having been input to the external signal input portion 12 are copyable. Thus, under the control of the CPU 14, the signals of the contents recorded in the user-unreadable recording device 15 are transferred to and recorded in the user-readable recording device 16. Then, the processing advances to a step S18. S18: Display a Message Indicating the Copyability. In the processing up to the step S16, it is determined that the signals of the contents input to the external signal input portion 12 is copyable. Thus, a message indicating the copyability is displayed on a display apparatus such as a monitor (not shown) under the control of the CPU 14. Then, the processing ends. S19: Stop the Second Copy Information Detecting Portion. As a result of the analysis of the copy control information detected by the copy information detecting portion 12c by the CPU 14 at the step S13, it is determined that the contents input to the external signal input portion 12 is uncopyable. Thus, the copy information detecting portion 12d does not have to operate. Therefore, the CPU 14 sends a stop signal to the copy information detecting portion 12d and stops the operation thereof. S20: Display a Message Indicating the Uncopyability. Since it is determined the contents is uncopyable from the step S13 or the step S16, a message indicating the uncopyability is displayed on a display device such as a monitor (not shown) under the control of the CPU 14. Then, the processing ends. As described above, in accordance with a determination result regarding detected copy control information, the CPU 14 controls operations of the copy information detecting portions 12c and 12d. Thus, when multiple copy control systems exist, an operation of the copy information detecting portion, which does not have to detect copy control information, can be terminated. Therefore, the processing power of the microcontroller can be improved through communication of detected data with the microcontroller, and the power consumption in the copy information detecting portions can be reduced. Furthermore, when multiple copy control systems exist, priority is given to copy information detection. Thus, processing for detection and discrimination can be simplified. In the description above, priority is given to the determination on copy control information of the copy information detecting portion 12c but is not limited thereto. The priority of control of the copy information detecting portions with respect to the contents input to the external signal input portion 12 was described above. However, priority may be determined for a case with the digital broadcast receiving portion 13, and a recording operation may be performed then. In the description above, the two copy information detecting portions 12c and 12d are provided. However, two or more copy information detecting portions may be provided in accordance with three or more kinds of copy control system. In the description above, the user-readable recording device 16 is provided in the digital broadcast receiver 10. However, an external apparatus may be provided which is connected to a user-unreadable recording device 15 through i. Link (where i. Link is a trademark of Sony). In the description above, a stream of contents to be received by the digital broadcast receiver 10 is a TS but is not limited thereto. The same copy control can be achieved by inputting non-TS streams to the demultiplexer 13b. As described above, according to the present invention, the copyability or uncopyability of contents is detected by a copy information detecting unit and is discriminated by a discriminating unit based on copy control information attached to the contents. The contents recorded in a user-unreadable recording unit is transferred to a user-readable recording unit only when the contents is copyable. Thus, the copyable contents can be recorded without delay. Furthermore, uncopyable contents can be prevented from being recorded in a user-readable recording unit.

<SOH> BACKGROUND ART <EOH>With the development of recent digital technologies, fraud copies of video and/or audio contents in digital broadcasting have been increased. Therefore, the copyright protection has become important. Conventionally, in order to prevent the fraud, Macrovision (where Macrovision is a trademark of MacroVision in the U.S.), CGMS (Copy Generation Management System)-A and so on exist as copy control systems for analog interfaces. Macrovision is a copy guard system broadly used for commercially available video sources, satellite broadcasts and so on. Macrovision adopts a copy control method for preventing an output source from being normally recorded by causing AGC (Automatic Gain Control) of a video deck to malfunction. CGMS-A adopts a copy control method for outputting contents having copy control information such as “copyable”, “only one generation copyable” and “uncopyable”. On the other hand, for digital outputs to a digital video, for example, DTCP (Digital Transmission Copy Protection) is used, for example. DTCP is a standard for encoding and exchanging data between digital devices connected by using IEEE-1394 (Institute of Electrical and Electronics Engineers 1394) and has a function for exchanging copy control information. Thus, controls for inhibiting copies and/or permitting the copy of one generation only are allowed. Contents include copy control information thereof. The copy control information is detected by a copy control information detecting circuit of the broadcast receiver. Copyability and uncopyability thereof can be judged by a microcontroller. Signals output from a player such as a VTR (Video Tape Recorder) may also include copy control information. However, a certain amount of time is required from the detection of copy control information to the judgement of copyability/uncopyability in order to prevent false detection due to noise, for example. When contents during the period is recorded in a storage device such as an HDD (Hard Disk Drive), uncopyable contents may be also recorded before a result from the judgement regarding copy control information is confirmed, which is a problem. On the other hand, once the recording starts after the judgement result is confirmed, video scenes and/or audio and data contents that a user needs to record may be missed, which is another problem. Multiple copy control systems such as the CGMS-A and Macrovision may exist. In this case, the uncopyability is detected by one of copy control information detecting circuits and is judged by the microcontroller. Thus, the other copy control information detecting circuits are not required. However, due to the communication of detected data between the copy control information detecting circuits and the microcontroller, the processing performance of the microcontroller is reduced. In addition, in order to continue the detection, extra power is consumed in the copy control information detecting circuits, which is another problem. When multiple copy control systems exist, priority may not be given to copy information detection. In this case, all of detection and judgement are always performed, and the processing becomes redundant thereby, which is another problem. The present invention was made in view of these points. It is an object of the present invention to provide a broadcast receiver, which cannot play broadcast contents until the permission for copying thereof is determined.

<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>FIG. 1 is a configuration diagram of a broadcast receiver according to an embodiment of the present invention. FIG. 2 is a flowchart illustrating a recording method. FIG. 3 is a hardware configuration diagram of a digital broadcast receiver. FIG. 4 is a diagram showing a state of control of a copy information detecting portion. FIG. 5 is a flowchart illustrating a recording method. detailed-description description="Detailed Description" end="lead"?

20050201

20100511

20050609

97212.0

HUNTER, MISHAWN N

BROADCAST RECEIVER AND RECORDING METHOD

UNDISCOUNTED

ACCEPTED

ACCEPTED

Support for appliances to be worn on the head

The invention relates to a support (1) for appliances (40) to be worn on the head, which comprises a bow-shaped base (2) and support elements (10) in the area of its front end (3), said support elements resting on the front of a user, support elements (10) in a further section, for example its center section (4), said support elements resting on the head of the user in the area of the top, and support elements (10) disposed on the bow (2) in the area of its rear end (5), said support elements resting on the back of the user's head. All support elements (10) can be adapted to be adjustable relative to the bow (2). On one end (3) of the bow (2), especially the front end, an appliance (40) can be fastened. Such an appliance (40) can be a visual aid or the like. On the other end (5) of the bow (2), especially the rear end, electronic components and/or a counterweight are provided for the purpose of balance and are preferably disposed in a housing (30) linked with a slide (22) for adjusting the support elements (10) that rest on the back of the head.

1-34. (canceled) 35. Support (1) for devices (40) which are to be worn on the head, such as for example optical vision aids or the like or protective devices, with a bow-shaped base body (2) which bears several support elements (10) which can be placed against the head of the user, there being support elements (10) in the area of the two ends (3, 5) and in the area of the middle sections (4) of the bow (2), and support elements (10) being supported to be able to swivel freely to all sides on the bow (2) via levers (12, 14), characterized in that there are support elements (10) in the area of the front end (3) of the bow (2), which end is located in the position of use in the area of the forehead of the user, further in the area of the middle section (4) of the bow (2) which is located in the position of use in the area of the crown of the head of the user, and in the area of the back end (5) of the bow (2) which is located in the position of use in the area of the back of the head of the user, and that the support elements (10) in the area of the back end (5) of the bow (2) are located on a carrier, for example, a carriage (22), which can be moved along the back end (5) of the bow (2). 36. Support as claimed in claim 35, wherein support elements (10) are combined into several groups (6, 7, 8) of two or more support elements (10). 37. Support as claimed in claim 35, wherein the swivelling capacity of the support elements (10) is limited or can be limited. 38. Support as claimed in claim 35, wherein the support elements (10) are supported to be able to swivel on the levers (12). 39. Support as claimed in claim 38, wherein the levers (12) for their part are supported to be able to swivel on the bow (2) via base levers (14). 40. Support as claimed in claim 35, wherein the support elements (10) have cushions which can be placed against the head of the user. 41. Support as claimed in claim 40, wherein the cushions can be supplied with negative pressure. 42. Support as claimed in claim 35, wherein the support elements (10) in the area of the back end (5) of the bow (2) can be moved in the lengthwise direction of the bow (2). 43. Support as claimed in claim 35, wherein there is an actuating device such as a set screw (24) for moving the carriage (22). 44. Support as claimed in claim 35, wherein on the carriage (22) there is a housing (30) with a holding space for electronic components and the like and/or counterweights. 45. Support as claimed in claim 35, wherein on the carriage (22) and/or on the bow (2) there is at least one connecting point for transmission elements, for example sockets or infrared ports, jacks for connection of lines such as power supply lines, data lines, control lines and the like. 46. Support as claimed in claim 35, wherein the back end (5) of the bow (2) is made straight. 47. Support as claimed in claim 35, wherein the back end (5) of the bow (2) is made bent. 48. Support as claimed in claim 35, wherein the middle section (4) of the bow (2) is made straight. 49. Support as claimed in claim 35, wherein the middle section (4) of the bow (2) is made bent. 50. Support as claimed in claim 35, wherein the support elements (10) which are located in the middle section (4) of the bow (2) are arranged in at least two rows which run preferably parallel to the bow (2). 51. Support as claimed in claim 35, wherein the support elements (10) are carried by a carriage (20) which is movably arranged in the middle section (4) of the bow (2). 52. Support as claimed in claim 35, wherein the support elements (10) are located on the front end of the bow (3) in a row which is aligned transversely to the bow (2). 53. Support as claimed in claim 35, wherein the support elements (10) are located on the back end (5) of the bow (2) in a row which is aligned transversely to the bow (2). 54. Support as claimed in claim 35, wherein on one end, preferably on the front end (3), of the bow (2) there is a connecting point (50) for at least one device (40) or contrivance which is to be attached to the support (1). 55. Support as claimed in claim 54, wherein a swivelling drive is assigned to the connection (50) for the device (40) which is to be attached to the support (1). 56. Support as claimed in claim 55, wherein a device (40) which is attached to the connecting point (50) can be moved by the swivelling drive, proceeding from a given, optionally adjustable base position. 57. Support as claimed in claim 35, wherein the bow (2) is made hollow. 58. Support as claimed in claim 35, wherein on the bow (2) there is a groove (26). 59. Support as claimed in claim 58, wherein there is a groove (26) in the area of the middle section (4) of the bow (2). 60. Support as claimed in claim 35, wherein it is equipped with at least one sensor which adjoins the head of the wearer and which accepts measured physiological values and current pulses of the wearer. 61. Support as claimed in claim 60, wherein at least one of the support elements (10) is made as a sensor. 62. Support as claimed in claim 35, wherein on the bow (2) there is at least one housing (30) with a holding space for electronic components and the like.

The invention relates to a support for devices which are to be worn on the head. These supports are known in the prior art, in which connection for example reference can be made to WO 01/003819. The known supports can be used for example by surgeons in surgery for holding vision aids. The known supports are not only constructed in a relatively complex manner, they also cannot be easily matched to the shape and size of the head of the user. It is also difficult to put on the known support. The known supports for devices which are to be worn on the head generally have a ring which encompasses the head and which in use on the head of the user is arranged similarly to a hatband, and a crown band which runs from the forehead to the back of the head of the user. WO 01/003819 A discloses equalizing as much as possible, in these supports, the weight of the device which is attached to the support, for example a vision aid for surgeons, by counterweights which are mounted in the area of the back of the head in order to increase the comfort of wearing. The object of the invention is to make available a support of the initially mentioned type which is simple in structure and is very comfortable to wear. This object is achieved as claimed in the invention with a support which has the features of claim 1. Preferred and advantageous embodiments of the support as claimed in the invention are the subject matter of the dependent claims. The support as claimed in the invention consists in its basic structure of a bow which extends from the front of the head (forehead) to the back of the head of a user and which is supported via several support elements on the head. Due to the support elements which are located on the bow the support as claimed in the invention can be easily matched to the shape of the head of the user by the support elements being changed with respect to their location and/or alignment. The matching of the support as claimed in the invention to different head shapes and/or sizes in the support as claimed in the invention is made especially easy when support elements combined into groups are arranged on the bow of the support. In one embodiment of the support of the invention at least one group of support elements is adjustably mounted on the bow. Thus the support can be quickly matched to the size of the head and it becomes easier to put on/take off the support. Within the framework of the invention it is preferable if the support elements are made in the manner of cushions. The support elements can be supported to be able to swivel on the bow in several directions so that their alignment can be automatically matched to the alignment of the head of the user in the areas in which support elements adjoin. In order to still guarantee a secure fit of the support, it can be provided that the support elements can be freely swivelled only to a limited degree, therefore within a limited area. In one practical embodiment it can be provided that support elements, optionally combined into groups of several support elements, are located on the end of the bow which lies in the area of the forehead of the user, on the end of the bow which lies in the area of the back of the head, and in the middle section of the bow. It can be provided that the support elements are located on the front end of the bow and on the back end of the bow, each in a row which extends preferably transversely to the bow, conversely the support elements located in the middle section of the bow, therefore the support elements which fit tightly in the area of the crown of the head of the user, lie in at least two rows which are located on the two sides of the bow and which are aligned preferably essentially parallel to the bow. A movement capacity of the support elements can be achieved by their being supported to be able to swivel on the bow, preferably on levers. Here it can be provided that the levers on which the support elements are located for their part are supported to be able to swivel by base levers which are pivotally supported on the bow of the support. On the front end of the bow, therefore the end which lies in the area of the forehead of the user, there can be a connecting point for a device which is to be attached to the support. These devices can be vision aids which are used by surgeons or precision mechanics, for example with zoom and autofocus, for example vision aids of the construction described in WO 96/09566 A and/or WO 01/03819 A. On the support as claimed in the invention however also other devices which are to be worn on the head, such as displays, in which data, installation diagrams, and the like are displayed, night vision devices, spotlights, lights, protective devices (welding shields), protective shields and the like are attached. In the support as claimed in the invention the support elements can be made differently and/or can consist of different materials, in order to match them to the respective location on the head of the user. Thus the type and configuration of the support elements can take into account whether they adjoin the skin or the hair of the user. In one embodiment of the invention it can be provided that the support elements have cushions which are supplied with negative pressure in order to improve the fit of the support as claimed in the invention on the head of the user. In order to achieve at least partial weight equalization between a device which is mounted on the front end of the bow of the support as claimed in the invention, which ends lies in the area of the forehead of the user, with the remaining part of the support as claimed in the invention, it can be provided that heavy components such as electronic components and the like, as well as connection points for transmission elements, such as for example sockets or infrared ports, for the connection of supply and/or data and/or control lines, are provided in the area of the back end of the bow. These heavy-weight components can be provided for example also in the area of the middle section of the bow. In order to be able to easily match the support as claimed in the invention to the head size, it can be provided that the support elements which fit tightly in the area of the back end on the back of the head of the user are attached optionally via levers/base levers to a carrier which can be moved on the back end of the bow, for example a carriage. To adjust this carriage, for example there can be a set screw which is equipped with a control knob. The support elements which are located in the middle section of the bow can be mounted to be able to move along the bow on a carrier, for example, a carriage, in order to be able to move it into a location which is favorable for contact with the crown of the head of the user of the support. Swivelling means can be assigned to the connection point for the device which is to be attached to the support as claimed in the invention and which lies preferably in the area of the front end of the bow. With such a swivelling means the device can be swivelled out of the position of use into a position of nonuse. This is important for example in optical vision aids for surgeons when they want to obtain an overview of the surgical field for example without using the vision aid and must swivel the vision aid away for this purpose. Here it is provided that when the device is swivelled back into its position of use the base position is reached again in any case automatically and without further help. The swivelling, specifically swivelling in and/or out, can take place by hand or using a drive which is assigned to the swivelling means. The bow of the support can be made hollow in order to accommodate in it lines for the power supply, control and/or data transmission from or to the device which is mounted on the bow. In addition, in the bow of the support, especially in the crown area, there can be a trough which is open to the top for holding lines, for example cold light lines. Other details, features and advantages of the support as claimed in the invention follow from the description of one embodiment below using the drawings. FIG. 1 shows a support as claimed in the invention without a device attached to it in a side view; FIG. 2 shows the support from FIG. 1 viewed from obliquely forward and overhead, FIG. 3 shows the support from FIG. 1 viewed from overhead, FIG. 4 shows a section along line C-C in FIG. 1, FIG. 5 shows a section along line E-E in FIG. 1, FIG. 6 shows in a side view a support placed on the head of the user with a device attached to it in the form of an optical vision aid, and FIG. 7 shows in an oblique view from obliquely forward a support as claimed in the invention with the optical vision aid attached to it. As shown in FIGS. 1 and 2, the support 1 as claimed in the invention has a bow 2 with a front end 3 which can be located in the area of the forehead of the user, with a middle section 4 which is located in the area of the crown of the user, and with a back end 5 which, when the support 1 as claimed in the invention is located on the head of the user, is located in the area of the back of his head. In the area of the front end 3, in the area of the middle section 4 and in the area of the back end 5 of the bow 2 of the support 1 as claimed in the invention, there are groups 6, 7, and 8 respectively of several support elements 10. The group 6 which is provided in the area of the front end 3 of the bow 2 in the embodiment has four support elements 10 which are made in the manner of round cushions. In the area of the middle section 4 of the bow 2 the group 7 has support elements 10 which are located on either side of the bow 2 (FIGS. 2 and 3) in the form of round cushions. The group 8 which is located in the area of the back end 5 of the bow 2 has four support elements 10 in the form of round cushions. The support elements 10 of the group 6 in the area of the front end 3 and those of the group 8 in the area of the back end 5 of the bow 2 are each arranged essentially in a row which is aligned transversely to the lengthwise extension (plane of symmetry) of the bow 2. The support elements 10 of the group 7 which is located in the middle section of the bow 2 are arranged in two rows which are aligned on either side of the bow 2 and essentially parallel to its middle section 4 (FIG. 3). So that the support elements 10 which are made in the embodiment as round cushions can be easily matched to the shape and/or position of the area of the head of the user on which they fit tightly, the support elements 10 are pivotally attached to the bow 2. In the embodiment the support elements 10 are attached for example to be able to swivel on the levers 12 via pivot ball bearings. Each of these levers 12 which on its ends bears one cushion-shaped support element 10 at a time, in the area of its middle is articulated to another lever, the base lever 14. The base levers 14 for their part are pivotally supported on the bow 2 of the support 1. The levers 12 can be pivotable on the base levers 14 around an axle or around a pivot (ball joint). The base levers 14 on the bow 2 can be swivelled around an axle or around a swivelling point in the manner of a ball joint. A combination of these two swivelling possibilities (swivelling around an axle on the one hand and swivelling around a pivot (ball joint) on the other) are possible. For example, the support elements 10 on the levers 12 and the base levers 14 can be swivelled to all sides on the bow 2 and the levers 12 can be supported on the base levers 14 to be able to swivel around the axles which are preferably aligned perpendicular to the plane of symmetry of the bow 2. The group 7 of support elements 10 in the middle section 4 of the bow 2 is mounted on a carriage 20 which can be moved in the lengthwise direction of the middle section 4 and which can be fixed in the desired position. The group 8 of support elements 10 in the area of the back end 5 of the bow 2 is mounted on a carriage 22 which using a set screw which is equipped with an control knob 24 can be moved along the back end 5 of the bow 2, which end is straight in the embodiment shown. The adjustability of the support elements 10 in the middle section 4 of the bow 2, which section is made bent flat in the embodiment shown, is used mainly to match the support 1 as claimed in the invention to the shape of the head of the user. The adjustability of the support elements 10 in the area of the back end 5 of the bow 2, therefore of the support elements 10 which adjoin the back of the head of the user, when the support 1 is being used, is used mainly for putting on the support 1. For example, the support 1 with the group 8 of support elements 10 which has been pushed to the rear is put on—the support elements 10 of the groups 6 and 7 fit tightly on the head of the user—and then the support elements 10 are brought into contact with the back of the head by moving the carriage 22. Thus a secure fit of the support 1 on the head of the user is achieved by the support elements 10 of the group 6 fitting tightly in the area of the forehead, the group 8 in the area of the back of the head and the group 7 in the area of the crown. The carriage 22 on the back, straight end 5 of the bow 2 on which the back support elements 10 are located, can have a housing 30 for holding electronic components and/or weights so that equalization of the weight between a device 40 (FIGS. 6 and 7) which is attached to the front end 3 of the bow 2 can be achieved, therefore the support 1 is essentially in equilibrium with support in the area of the group 7 of support elements 10. In the wall of the housing 30 on the carriage 22 and/or on the bow 2 there can be at least one connecting point for transmission elements, for example a socket 32 or infrared ports for connection of power supply, data and/or control lines. The bow 2 is preferably made hollow so that lines can be accommodated in its interior from and to the device 40 which has been attached to its front end. In addition, especially in the crown area, on the outside of the bow there can be a groove 26 for holding at least one line (FIGS. 2 and 4). Here it can be for example a line to a cold light source which is attached to the bow 2 and which is located especially on the front end of the groove 26. This cold light source in the manner of a head-mounted spotlight illuminates the field of vision and thus follows the movements of the head of the user of the support 1 as claimed in the invention. On the end 3 of the bow 2, which end is the front end in the embodiment and which is located roughly in the area of the forehead of the user of the support 1 as claimed in the invention (FIG. 6), there is a connecting point 50 for a device 40 which is to be worn on the head of the user via the support 1 as claimed in the invention. In the illustrated embodiment, it is shown in FIGS. 6 and 7 that an optical vision aid 40, as is used for example by surgeons in surgery, can be mounted on the support 1 as claimed in the invention. To do this, on the optical vision aid 40 there is a lever system 42, 43 which is made in the manner of a knee joint, and with its free end 44 is attached to the front end 3 of the bow 2 of the support 1. Here it is provided that at the connecting point 50 for the device 40 which is to be attached to the support 1 there is a swivelling drive which makes it possible to swivel the device 40 for example out of the position of use shown in FIG. 6 up into the readiness position. The swivelling drive of the connecting point 50 in the area of the front end 3 of the bow 2 is aligned such that when the device 40 is swivelled back into the position of use shown in FIGS. 6 and 7 the same (optionally preset) initial position is always reached. The swivelling can take place by hand or using the (motorized) swivelling drive. This embodiment of the connecting point 50 makes it possible for example for a surgeon, during surgery, by swivelling up the vision aid 40 using the swivelling drive of the connecting point 50 (initiated for example by a foot-operated switch) to survey the entire surgical field and after swivelling the vision aid 40 back into the position of use (FIGS. 6 and 7), to continue the surgery. It is advantageous if the optical vision aid 40 after swivelling back again assumes exactly the position of use which it had before. The position of use can take place by adjusting the lever system 42, 43, therefore the angle which is assumed by the two parts of the lever system 42, 43 with the vision aid 40 on the one hand and the front end 3 of the bow 2 on the other, and to one another. In summary, one preferred embodiment of the invention can be described as follows: A support 1 for devices 40 which are to be worn on the head has an essentially bow-shaped base body 2 and in the area of its front end 3 has support elements 10 which adjoin the forehead of the user, in another, for example in its middle section 4, support elements 10 which in the area of the crown adjoin the head of the user, and support elements 10 which are located in the area of its back end 5 on the bow 2 and which adjoin the back of the head of the user. All support elements 10 can be adjustable to the bow 2. A device 40 can be attached to one end 3 of the bow 2, especially the front end. Such a device 40 can be a vision aid or the like. On the other, especially the back end 5 of the bow 2, as weight equalization there are electronic components and/or a counterweight, preferably in a housing 30 which is connected to a carriage 22 for adjusting the support elements 10 which adjoins the back of the head.

20050110

20100921

20050804

99361.0

RAJAN, KAI

SUPPORT FOR APPLIANCES TO BE WORN ON THE HEAD

UNDISCOUNTED

ACCEPTED

ACCEPTED

Novel dewaxing aid

The present invention relates to dewaxing aids comprising the mixture of two or more polyalkyl(meth)acrylates having an exothermic heat initiation temperature within the specific range when chilled at 30° C./minute rate, to be added together with the wax-containing hydrocarbon oil to the dewaxing solvent. The dewaxing aid according to the present invention can be used in the solvent dewaxing method containing the stage in which the chilling rate during the chilling is 30° C./minute or higher, is effective for heavy type wax-containing hydrocarbon oils, and is chlorine-free.

1. A dewaxing aid for use in the dewaxing method to produce a dewaxed oil by dissolving the dewaxing aid together with a wax-containing hydrocarbon oil into a dewaxing solvent, separating-out wax by chilling, and removing the separated-out wax with the liquid/solid separation method, characterized in that said dewaxing aid comprises a mixture of (A) at least one polyalkyl(meth)acrylate having alkyl groups of 10 to 30 carbon atoms, and (B) at least one polyalkyl(meth)acrylate having alkyl groups of 10 to 30 carbon atoms which is different from component (A), the mass ratio of component (A)/component (B) being 3/97 to 97/3, and that said dewaxing aid satisfies the conditions of formulas (1) and (2) below at the exothermic heat initiation temperature as measured by a differential scanning calorimeter at the chilling rate of 30° C./minute: −4.0° C.≦Ta≦ta≦−1.0° C.+Ta (1) Ta≦tb≦4.0° C.+Ta (2) wherein (Ta) is the exothermic heat initiation temperature of the wax-containing hydrocarbon oil without the addition of said dewaxing aid, (ta) is the exothermic heat initiation temperature of the wax-containing hydrocarbon oil with the addition of 0.25% by mass of the component (A) to the wax-containing hydrocarbon oil, and (tb) is the exothermic heat initiation temperature of the wax-containing hydrocarbon oil with the addition of 0.25% by mass of the component (B) to the wax-containing hydrocarbon oil. 2. The dewaxing aid according to claim 1, characterized in that said dewaxing aid is used in the dewaxing method comprising dissolving the wax-containing hydrocarbon oil and the dewaxing aid into the dewaxing solvent, separating-out wax by chilling, and removing the separated-out wax by the liquid/solid separation method to produce a dewaxed oil, wherein the chilling rate during the chilling is 30° C./minute or higher.

TECHNICAL FIELD The present invention relates to a dewaxing aid used in the dewaxing stage of lubricant production processes. The present invention also relates to a dewaxing aid used in the production of dewaxed oil in the so-called solvent dewaxing method, especially in the dewaxing stage, by dissolving a wax-containing hydrocarbon oil and a dewaxing aid into a dewaxing solvent and chilling, separating-out wax existing in the wax-containing hydrocarbon oil, and separating the separated-out wax by the liquid/solid separation method. BACKGROUND ART In general, in order to prepare a hydrocarbon oil from the crude oil, the crude oil is at first subjected to the atmospheric distillation, and then the resulting residual oil is further subjected to the vacuum distillation to be separated into wax-containing hydrocarbon oils with from low to high various viscosities and vacuum distillation residual oils. In addition, the vacuum distillation residual oil is further treated to remove the asphalt component by the solvent deasphalting process so that Brightstock that is wax-containing hydrocarbon oil with the highest degree of viscosity can be produced. The wax-containing hydrocarbon oils with various viscosities thus obtained become hydrocarbon oils upon a series of treatment stages such as a combination of solvent extraction, hydrogenation refining and dewaxing, or a combination of hydrogenolysis, solvent extraction, hydrogenation refining and dewaxing among other combinations. The dewaxing process among these production processes described above is the process wherein wax components in a wax-containing hydrocarbon oil are removed and a hydrocarbon oil with low pour point is produced. Press filtration may be utilized in the process when the dewaxing process is industrially carried out. In this instance, the wax-containing hydrocarbon oil is chilled in the absence of a solvent to separate out wax, and then the wax is subjected to the press filtration. Generally, the dewaxing method with the press filtration process can only treat light type wax-containing hydrocarbon oils because the filtration is limited with viscosity. Thus, a solvent dewaxing method which is capable of treating wax-containing hydrocarbon oils of the light type, the heavy type and the like is universally employed. In the solvent dewaxing method, wax is separated-out and forms a slurry while a wax-containing hydrocarbon oil, a dewaxing solvent and a dewaxing aid are dissolved and chilled. Said slurry is fed to a solid/liquid separator (a filtration apparatus, a centrifugal separator or the like), and a dewaxed oil is obtained by removing the dewaxing solvent upon separation. Examples of the dewaxing solvent used for the solvent dewaxing method include hydrocarbons (propane, propylene, butane, pentane, and the like), ketones (acetone, methyl ethyl ketone (MEK), methyl isobutyl ketone (MIBK) and the mixtures thereof, and the like), aromatic hydrocarbons (benzene, toluene, xylene, and the like), and mixtures of ketones and aromatic hydrocarbons (MEK/toluene, acetone/benzene, and the like). A factor limiting the treatment capacity in the solvent dewaxing process is the filtration rate during the filtration removal of the wax from the slurry, and said rate may be influenced by the crystal structure of the wax separated-out. The crystal structure of the wax separated-out is influenced by the operating conditions in the dewaxing process. Particularly, the condition of the wax separated-out such as the size and the crystal structure of the wax, oil in the crystal, and the like dramatically varies for the same wax-containing hydrocarbon oil depending on the change in the conditions such as the chilling rate, the stirring speed, the chilling temperature, and the like, and thus the filtration rate and the yield of the dewaxed oil are affected. Especially, when the wax-containing hydrocarbon oil is Brightstock, the separation by the filtration has often been running into the problems such as a decrease in the filtration rate, a decrease in the yield of the dewaxed oil, an increase in the pour point of the dewaxed oil due to passing of the fine crystals, clogging of the filter, and the like, because the wax crystals are fine. Various improvements have been achieved in the processes in order to improve the filtration rate and the yield of the dewaxed oil, but the method of adding a dewaxing aid has been carried out as a method for easy control as well as great efficiency. In particular, it has been essential to add a dewaxing aid in a autochilling type dewaxing method such as propane dewaxing. The prior art technologies such as described below heretofore exist for dewaxing aids. The effect of the mixed use of ethylene vinyl acetate copolymers and polyalkylacrylates or polyalkylmethacrylates is disclosed in JP Patent Publication No. Sho 45-15379, JP Patent Publication No. Sho 49-26922, and JP Patent Laid-open No. Sho 54-11104. The effect of alkylnaphthalene condensation products, or the mixed use thereof with polyalkylmethacrylates is described in JP Patent Laid-open No. Sho 45-15379, JP Patent Publication No. Sho 4946361 and JP Patent Laid-open No. Sho 53-129202. The effect of the use of α-olefin polymers, or copolymers of a-olefin and vinyl acetate is described in JP Patent Laid-open No. Sho 53-121804 and JP Patent Laid-open No. Sho 53-121803. The effect of the use of polyalkylacrylates is described in JP Patent Laid-open No. Sho 404210, JP Patent Laid-open No. Sho 54-123102, JP Patent Laid-open No. Sho 57-30792 and JP Patent Laid-open No. Hei 7-316567. The effect of the use of polyvinylpyrrolidone is described in JP Patent Laid-open No. Sho 55-89392. The effect of the use of copolymers of dialkyl fumarate and vinyl acetate is described in JP Patent Laid-open No. Sho 60-217218 and JP Patent Laid-open No. Sho 61-247793. Among these prior art technologies, the use as dewaxing aid of a copolymer of a compound having reactive double bonds (a reactive monomer) and vinyl acetate is disclosed in JP Patent Publication No. Sho 49-26922, JP Patent Laid-open No. Sho 54-11104, JP Patent Laid-open No. Sho 53-121804, JP Patent Laid-open No. Sho 53-121803, JP Patent Laid-open No. Sho 60-217218 and JP Patent Laid-open No. Sho 61-247793. Compounds with vinyl acetate groups are decomposed by heat and the like, and acetic acid may be generated. Acetic acid in this case displays corrosiveness against metals such as SUS and the like, to say nothing of iron, and thus their presence is not desirable for the apparatus. In addition, the use of an alkylnathphthalene condensation product as dewaxing aid is disclosed in JP Patent Laid-open No. Sho 45-15379 and JP Patent Publication No. Sho 49-46361. As such alkylnaphthalene condensation products can be generally obtained through Friedel-Crafts reaction using chlorinated paraffin as the raw material, the complete removal of the chlorine content therein is not easy. Recently, however, there has been a strong demand for chlorine-free products in every field. Furthermore, the use of polyalkylacrylates as dewaxing aids described in the prior art references shows a good performance under the investigation in the laboratory, but a more effective aid is required since they do not show a good effect, especially, against heavy type wax-containing hydrocarbon oil in the evaluation with the actual apparatus in which the chilling rate during the chilling is 30° C./minute or higher. The problems to be solved by present invention are that the dewaxing method using the dewaxing aid described in the prior art can not be used for the general purposes depending on the kind of wax-containing hydrocarbon oils used and that the shortcomings (containing of chlorine, corrosion of the apparatus by the product at the time of decomposition, and the like) which can not be avoided due to the structure of these compounds and the production method have to be compensated for. That is to say, in the case of the dewaxing method using a dewaxing aids known heretofore, for instance, a polyalkylmethacrylate, the dewaxing aid alone does not show the effect on both the light type and the heavy type wax-containing hydrocarbon oils, and it is required to further add further compounds, such as alkylnaphthalene condensation products which inevitably contain chlorinated compounds due to their production process and copolymers of reactive monomer/vinyl acetate which may liberate monomeric acids during their decomposition due to their structures, as described above. The present inventors earnestly investigated in order to solve these problems. As the result, the dewaxing aids whose evaluation under the laboratory scale correlating to the evaluation with the actual apparatus in which the chilling rate during the chilling is 30° C./minute or higher have been found under condition of adding prechilling process (rapid chilling process) just like the actual apparatus to the solvent dewaxing method. They further exhibited the effect against any kinds, from the light type to the heavy type, of the wax-containing hydrocarbon oils, and were found to improve the filtration rate and the yield of the dewaxed oils, as compared with the conventional dewaxing aids. DISCLOSURE OF THE INVENTION Namely, the present invention relates to a dewaxing aid for use in the dewaxing method to produce a dewaxed oil by dissolving the dewaxing aid together with a wax-containing hydrocarbon oil into a dewaxing solvent, separating-out wax by chilling, and removing the separated-out wax with the liquid/solid separation method, characterized in that said dewaxed aid comprises a mixture of (A) at least one polyalkyl(meth)acrylate having alkyl groups of 10 to 30 carbon atoms, and (B) at least one polyalkyl(meth)acrylate having alkyl groups of 10 to 30 carbon atoms, which is different from component (A), the mass ratio of component (A)/component (B) being 3/97 to 97/3, and that said dewaxing aid satisfies the conditions of formulas (1) and (2) below at the exothermic heat initiation temperature as measured by a differential scanning calorimeter at the chilling rate of 30° C./minute: −4.0C.+Ta≦ta≦−1.0° C.+Ta (1) Ta≦tb≦4.0° C.+Ta (2) wherein (Ta) is the exothermic heat initiation temperature of the wax-containing hydrocarbon oil without the addition of said dewaxing aid, (ta) is the exothermic heat initiation temperature of the wax-containing hydrocarbon oil with the addition of 0.25% by mass of the component (A) to the wax-containing hydrocarbon oil, and (tb) is the exothermic heat initiation temperature of the wax-containing hydrocarbon oil with the addition of 0.25% by mass of the component (B) to the wax-containing hydrocarbon oil. Dewaxing methods in which the dewaxing aid of the present invention is effective is solvent dewaxing methods wherein the chilling rate during the chilling is 30° C./minute or higher. Examples of such methods are the dewaxing method using hydrocarbons which are gaseous at the normal temperature (propane, propylene, butane, butene, and the like), the dewaxing method using ketones (acetone, methyl ethyl ketone (MEK), methyl isobutyl ketone (MIBK), and the like, and the mixture thereof), the dewaxing method using aromatic hydrocarbons (benzene, toluene, xylene, and the like), and the dewaxing method using mixtures of ketones and aromatic hydrocarbons (MEK/toluene, acetone/benzene, and the like) among other methods. Heavy type wax-containing hydrocarbon oils in the present specification mean wax-containing oils which, after dewaxed, have a kinematic viscosity at 40° C. in the range of 60 to 150 mm2/s, and light type wax-containing oils mean wax-containing oils which, after dewaxed, have a kinematic viscosity at 40° C. in the range of 10 to 60 mm2/s. The component (A) and the component (B) that are polyalkyl (meth)acrylates having alkyl groups of 10 to 30 carbon atoms may each be one or a mixture of more than one. In addition, these polymers may consist of one type of monomer or a combination of different monomers. General examples of alkyl(meth)acrylates having alkyl groups of 10 to 30 carbon atoms which are the monomers constituting the component (A) and the component (B) are decyl(meth)acrylate, undecyl(meth)acrylate, dodecyl(meth)acrylate, tridecyl(meth)acrylate, tetradecyl(meth)acrylate, pentadecyl(meth)acrylate, hexadecyl(meth)acrylate, heptadecyl(meth)acrylate, octadecyl(meth)acrylate, nonadecyl(meth)acrylate, eicosyl(meth)acrylate, docosylacrylate and the like and the mixture thereof. Here, the existing mass ratio (A):(B) of the component (A) to the component (B) is 3:97 to 97:3, and a good dewaxing effect can not be obtained against the heavy type wax-containing hydrocarbon oils unless the ratio is within this range. The ratio is especially preferable in the range between 10:90 to 90:10 for performance. Further, the component (A) is preferably the one with a weight-average molecular weight of 10,000 to 800,000 having alkyl chain length of 10 to 20 carbon atoms. In addition, the component (B) is preferably the one with a weight-average molecular weight of 10,000-800,000 having alkyl chain length of 16 to 30 carbon atoms. When said weight-average molecular weight is less than 10,000, the performance as a dewaxing aid may not sometimes be manifested, and when said weight-average molecular weight is greater than 800,000, it is undesirable because the solubility characteristics into wax-containing hydrocarbon oils or dewaxing solvents grow worsen. The component (A) and the component (B) can be synthesized according to any prior art method. For example, they may be obtained through the radical polymerization using peroxides or azo-bis type compounds as initiators, or the heat polymerization, after the esterification reaction of alcohol having 10 to 30 carbon atoms with methacrylic acid or acrylic acid. Moreover, the dewaxing aid according to the present invention may contain further additives within the range that does not impair the effect of the present invention. Examples of additives which is thought to be combinable upon the consideration of dewaxing performance (with respect to the improvement in the dewaxing rate, the dewaxed oil yield) are polyalkylacrylates or polyalkylmethacrylates other than the component (A) and the component (B), or copolymers of alkylacrylates with alkylmethacrylates, alkylnaphthalene condensation products, or copolymers of ethylene with vinyl acetate, and the like,. The dewaxing aid according to the present invention can be used in, for instance, the following dewaxing method. At first, a wax-containing hydrocarbon oil is dissolved into a dewaxing solvent and the dewaxing aid according to the present invention is added, homogenized and heated. Next, the mixture is chilled to the predetermined temperature. The slurry comprising the wax separated-out, the dewaxed oil, the dewaxing solvent and the dewaxing aid is formed in this chilling process, and then said slurry is subjected to the wax separation by a liquid/solid separation method such as filtration or centrifugal filtration to obtain the dewaxed oil upon removal of the dewaxing solvent. The performance of the dewaxing aid can be evaluated by measuring the filtration rate and the dewaxed oil yield in the aforementioned process. In addition, the exothermic heat initiation temperature for the dewaxing aid according to the present invention may be measured with a differential scanning calorimeter such as a thermal analyzer DSC-6200 by Seiko Instruments Inc. and the temperature, at which the exothermic heat initiated by extrapolation when chilling is conducted, for example, at the chilling rate of 30° C./minute from 140° C. to −30° C., is taken as the exothermic heat initiation temperature. For the measurement, a poly(meth)acrylate which becomes the dewaxing aid is added to the wax-containing hydrocarbon oil so as to be the concentration of 0.25% by mass to said wax-containing hydrocarbon oil, and solution-mixed, and 5 mg of this mixture is used. BEST MODE FOR CARRYING OUT THE INVENTION The present invention is explained by showing Synthetic Examples of the component (A) and the component (B), Working Examples, and Test method in the followings, but the present invention is not be limited by such Synthetic Examples of the component (A) and the component (B), Working Examples and Test methods. SYNTHETIC EXAMPLE 1 A flask equipped with a stirrer, a nitrogen blowing tube, a thermometer and a condenser is charged with 40 parts of an alkylmethacrylate having 12 to 18 carbon atoms (C12=15%, C14=18%, C16=25%, C18=42%) and 60 parts of a mineral oil, and the nitrogen displacement was completely done for 3 hours. Upon addition of the initiator, heating to 100° C. and ageing for 8 hours at that temperature, a polyalkylmethacrylate with weight-average molecular weight of 400,000 was obtained. The compound obtained by this process was named as aid (1). SYNTHETIC EXAMPLE 2 A flask equipped with a stirrer, a nitrogen blowing tube, a thermometer and a condenser is charged with 40 parts of an alkylacrylate having 18 to 22 carbon atoms (Cl8=43%, C20=11%, C22=44%) and 60 parts of a mineral oil, and the nitrogen displacement was completely done for 3 hours. Upon addition of the initiator, heating to 100° C. and ageing for 8 hours at that temperature, a polyalkylacrylate with weight-average molecular weight of 400,000 was obtained. The compound obtained by this process was named as aid (2). SYNTHETIC EXAMPLE 3 A flask equipped with a stirrer, a nitrogen blowing tube, a thermometer and a condenser is charged with 40 parts of an alkylmethacrylate having 6 to 10 carbon atoms (C6=5%, C8=75%, C10=20%) and 60 parts of a mineral oil, and the nitrogen displacement was completely done for 3 hours. Upon addition of the initiator, heating to 100C and ageing for 8 hours at that temperature, a polyalkylmethacrylate with weight-average molecular weight of 400,000 was obtained. The compound obtained by this process was named as aid (3). SYNTHETIC EXAMPLE 4 A flask equipped with a stirrer, a nitrogen blowing tube, a thermometer and a condenser is charged with 40 parts of an alkylacrylate having 12 to 15 carbon atoms (C12=20%, C13=31%, C14=33%, C15=16%) and 60 parts of a mineral oil, and the nitrogen displacement was completely done for 3 hours. Upon addition of the initiator, heating to 100° C. and ageing for 8 hours at that temperature, a polyalkylacrylate with weight-average molecular weight of 400,000 was obtained. The compound obtained by this process was named as aid (4). The dewaxing aid according to the present invention which is the mixture combining said aids (1) to (4) was used in the solvent dewaxing method outlined below. That is to say, a wax-containing hydrocarbon oil was dissolved into a dewaxing solvent, and the dewaxing aid according to the present invention was added, homogenized and heated. Next, the mixture was chilled to the predetermined temperature. The slurry comprising the wax separated-out, the dewaxed oil, the dewaxing solvent and the dewaxing aid is formed in this chilling process, and then said slurry is subjected to the wax separation by filtration to obtain the dewaxed oil upon removal of the dewaxing solvent. The performance of the dewaxing aid was evaluated by measuring the filtration rate and the dewaxed oil yield in the aforementioned process. The Measuring Method for the Exothermic Heat Initiating Temperature of Each Aid: The thermal analyzer DSC-6200 by Seiko Instruments Inc. was used as the differential scanning calorimeter. Poly(meth)acrylates which comprise the dewaxing aid were added to the wax-containing hydrocarbon oil (heavy type, an exothermic heat initiation temperature of 46.7° C.) so as to be the concentration of 0.25% by mass to said wax-containing hydrocarbon oil and solution-mixed, 5 mg of this mixture was harvested, and the temperature, at which the exothermic heat initiated by extrapolation when chilling is conducted at the chilling rate of 30° C./minute from 140° C. to −30° C., was taken as the exothermic heat initiation temperature. Test Method: The wax-containing hydrocarbon oil (heavy type, an exothermic heat initiation temperature of 46.7° C.) was heated at 50° C. to dissolve it into normal hexane (quadruple against the wax-containing hydrocarbon oil), and the dewaxing aid synthesized above was added and chilled with stirring to 30°0 C. at the chilling rate of 30° C./minute, and then chilled to −40° C. at the chilling rate of 2° C./minute. The resultant slurry comprising the wax, normal hexane, the dewaxed oil and the dewaxing aid was then filtered under a reduced pressure at 600 mmHg at −40° C. through a Buchner funnel with a cooling jacket circulated with −40° C. refrigeration medium. The amount of filtrate filtered in 2 minutes was measured, and filtration rate was calculated according to the formula below. In addition, normal hexane contained in each of the filtrate and in the wax after filtration was removed by the vacuum topping, each mass was measured and the dewaxed oil yield was calculated according to the formula below. The Calculation Formula for the Filtration Rate (mL/s·cm2): The ⁢ ⁢ amount ⁢ ⁢ of ⁢ ⁢ the ⁢ ⁢ filtrate ⁢ ⁢ filtered in ⁢ ⁢ 120 ⁢ ⁢ seconds ⁢ ⁢ ( mL ) 120 ⁢ ⁢ ( s ) × effective ⁢ ⁢ filtration ⁢ ⁢ area ⁢ ⁢ ( cm 2 ) = Filtration ⁢ ⁢ rate The Calculation Formula for the Dewaxed Oil Yield (mass %): [ The ⁢ ⁢ filtrate ⁢ ⁢ mass after ⁢ ⁢ the ⁢ ⁢ removal ⁢ of ⁢ ⁢ normal ⁢ ⁢ hexane ] × 100 [ The ⁢ ⁢ filtrate ⁢ ⁢ mass after ⁢ ⁢ the ⁢ ⁢ removal ⁢ of ⁢ ⁢ normal ⁢ ⁢ hexane ] + [ The ⁢ ⁢ wax ⁢ ⁢ mass after ⁢ ⁢ the ⁢ ⁢ removal ⁢ of ⁢ ⁢ normal ⁢ ⁢ hexane ] = The ⁢ ⁢ dewaxed ⁢ ⁢ oil ⁢ ⁢ yield WORKING EXAMPLE 1 0.50 g of the aid (1) according to the present invention obtained in SYNTHETIC EXAMPLE 1 and 0.50 g of the aid (2) according to the present invention obtained in SYNTHETIC EXAMPLE 2 were each added and dissolved into 200 g of the heavy type wax-containing hydrocarbon oil while heating, and further dissolved with the addition of 700 mL normal hexane, and the test was conducted according to Test method. That is to say, the amount to be added of the mixture consisting of the aid (1) and the aid (2) according to the present invention was set at 0.5% by mass (0.20% by mass when converted to the pure substance of the aids) to the heavy type wax-containing hydrocarbon oil, and the test was conducted. WORKING EXAMPLE 2 0.90 g of the aid (1) according to the present invention obtained in SYNTHETIC EXAMPLE 1 and 0.10 g of the aid (2) according to the present invention obtained in SYNTHETIC EXAMPLE 2 were each added and dissolved into 200 g of the heavy type wax-containing hydrocarbon oil while heating, and further dissolved with the addition of 700 mL normal hexane, and the test was conducted according to Test method. That is to say, the amount to be added of the mixture consisting of the aid (1) and the aid (2) according to the present invention was set at 0.5% by mass (0.20% by mass when converted to the pure substance of the aids) to the heavy type wax-containing hydrocarbon oil, and the test was conducted. WORKING EXAMPLE 3 0.10 g of the aid (1) according to the present invention obtained in SYNTHETIC EXAMPLE 1 and 0.90 g of the aid (2) according to the present invention obtained in SYNTHETIC EXAMPLE 2 were each added and dissolved into 200 g of the heavy type wax-containing hydrocarbon oil while heating, and further dissolved with the addition of 700 mL normal hexane, and the test was conducted according to Test method. That is to say, the amount to be added of the mixture consisting of the aid (1) and the aid (2) according to the present invention was set at 0.5% by mass (0.20% by mass when converted to the pure substance of the aids) to the heavy type wax-containing hydrocarbon oil, and the test was conducted. COMPARATIVE EXAMPLE 1 0.50 g of the aid (3) according to the present invention obtained in SYNTHETIC EXAMPLE 3 and 0.50 g of the aid (4) obtained according to the present invention in SYNTHETIC EXAMPLE 4 were each added and dissolved into 200 g of the heavy type wax-containing hydrocarbon oil while heating, and further dissolved with the addition of 700 mL normal hexane, and the test was conducted according to Test method. That is to say, the amount to be added of the mixture consisting of the aid (3) and the aid (4) according to the present invention was set at 0.5% by mass (0.20% by mass when converted to the pure substance of the aids) to the heavy type wax-containing hydrocarbon oil, and the test was conducted. COMPARATIVE EXAMPLE 2 0.50 g of the aid (1) according to the present invention obtained in SYNTHETIC EXAMPLE 1 and 0.50 g of the aid (3) according to the present invention obtained in SYNTHETIC EXAMPLE 3 were each added and dissolved into 200 g of the heavy type wax-containing hydrocarbon oil while heating, and further dissolved with the addition of 700 mL normal hexane, and the test was conducted according to Test method. That is to say, the amount to be added of the mixture consisting of the aid (1) and the aid (3) according to the present invention was set at 0.5% by mass (0.20% by mass when converted to the pure substance of the aids) to the heavy type wax-containing hydrocarbon oil, and the test was conducted. COMPARATIVE EXAMPLE 3 0.50 g each of the aid (2) according to the present invention obtained in SYNTHETIC EXAMPLE 2 and the aid (3) according to the present invention obtained in SYNTHETIC EXAMPLE 3 was added and dissolved into 200 g of the heavy type wax-containing hydrocarbon oil while heating, and further dissolved with the addition of 700 mL normal hexane, and the test was conducted according to Test method. That is to say, the amount to be added of the mixture consisting of the aid (2) and the aid (3) according to the present invention was set at 0.5% by mass (0.20% by mass when converted to the pure substance of the aids) to the heavy type wax-containing hydrocarbon oil, and the test was conducted. COMPARATIVE EXAMPLE 4 The test was conducted for a heavy type wax containing hydrocarbon oil without the use of any aid. The exothermic heat initiation temperatures for the mixtures of each aid and the wax-containing hydrocarbon oil described above are shown in Table 1, and the dewaxing performance for the heavy type wax-containing hydrocarbon oil obtained in Working Examples 1 to 3 and Comparative Examples 1 to 4 is shown in Table 2. TABLE 1 Aid Exothermic heat initiation temperature (° C.) No addition 46.7 (1) 48.5 (2) 44.0 (3) 46.2 (4) 47.0 TABLE 2 Dewaxing performance for heavy type wax- containing hydrocarbon oil Amount to be added De- (converted to the Filtration Dewaxed waxing effective com- rate oil yield aid ponent) (%) (mL/s · cm2) (%) Working (1)/(2) (1)/(2) = 0.10:0.10 2.0 68.0 Example 1 Working (1)/(2) (1)/(2) = 0.18:0.02 2.2 65.2 Example 2 Working (1)/(2) (1)/((2) = 0.02:0.18 2.5 63.6 Example 3 Comparative (3)/(4) (3)/(4) = 0.10:0.10 1.2 52.6 Example 1 Comparative (1)/(3) (1)/(3) = 0.10:0.10 1.5 54.5 Example 2 Comparative (2)/(3) (2)/(3) = 0.10:0.10 1.5 55.1 Example 3 Comparative No — 0.7 49.5 Example 4 addition It is apparent from Table 2 that the use of the dewaxing aids according to the present invention in the dewaxing process with the rapid chilling greatly improves both the filtration rate and the dewaxed oil yield. This is a remarkable effect attained by the product according to the present invention.

<SOH> BACKGROUND ART <EOH>In general, in order to prepare a hydrocarbon oil from the crude oil, the crude oil is at first subjected to the atmospheric distillation, and then the resulting residual oil is further subjected to the vacuum distillation to be separated into wax-containing hydrocarbon oils with from low to high various viscosities and vacuum distillation residual oils. In addition, the vacuum distillation residual oil is further treated to remove the asphalt component by the solvent deasphalting process so that Brightstock that is wax-containing hydrocarbon oil with the highest degree of viscosity can be produced. The wax-containing hydrocarbon oils with various viscosities thus obtained become hydrocarbon oils upon a series of treatment stages such as a combination of solvent extraction, hydrogenation refining and dewaxing, or a combination of hydrogenolysis, solvent extraction, hydrogenation refining and dewaxing among other combinations. The dewaxing process among these production processes described above is the process wherein wax components in a wax-containing hydrocarbon oil are removed and a hydrocarbon oil with low pour point is produced. Press filtration may be utilized in the process when the dewaxing process is industrially carried out. In this instance, the wax-containing hydrocarbon oil is chilled in the absence of a solvent to separate out wax, and then the wax is subjected to the press filtration. Generally, the dewaxing method with the press filtration process can only treat light type wax-containing hydrocarbon oils because the filtration is limited with viscosity. Thus, a solvent dewaxing method which is capable of treating wax-containing hydrocarbon oils of the light type, the heavy type and the like is universally employed. In the solvent dewaxing method, wax is separated-out and forms a slurry while a wax-containing hydrocarbon oil, a dewaxing solvent and a dewaxing aid are dissolved and chilled. Said slurry is fed to a solid/liquid separator (a filtration apparatus, a centrifugal separator or the like), and a dewaxed oil is obtained by removing the dewaxing solvent upon separation. Examples of the dewaxing solvent used for the solvent dewaxing method include hydrocarbons (propane, propylene, butane, pentane, and the like), ketones (acetone, methyl ethyl ketone (MEK), methyl isobutyl ketone (MIBK) and the mixtures thereof, and the like), aromatic hydrocarbons (benzene, toluene, xylene, and the like), and mixtures of ketones and aromatic hydrocarbons (MEK/toluene, acetone/benzene, and the like). A factor limiting the treatment capacity in the solvent dewaxing process is the filtration rate during the filtration removal of the wax from the slurry, and said rate may be influenced by the crystal structure of the wax separated-out. The crystal structure of the wax separated-out is influenced by the operating conditions in the dewaxing process. Particularly, the condition of the wax separated-out such as the size and the crystal structure of the wax, oil in the crystal, and the like dramatically varies for the same wax-containing hydrocarbon oil depending on the change in the conditions such as the chilling rate, the stirring speed, the chilling temperature, and the like, and thus the filtration rate and the yield of the dewaxed oil are affected. Especially, when the wax-containing hydrocarbon oil is Brightstock, the separation by the filtration has often been running into the problems such as a decrease in the filtration rate, a decrease in the yield of the dewaxed oil, an increase in the pour point of the dewaxed oil due to passing of the fine crystals, clogging of the filter, and the like, because the wax crystals are fine. Various improvements have been achieved in the processes in order to improve the filtration rate and the yield of the dewaxed oil, but the method of adding a dewaxing aid has been carried out as a method for easy control as well as great efficiency. In particular, it has been essential to add a dewaxing aid in a autochilling type dewaxing method such as propane dewaxing. The prior art technologies such as described below heretofore exist for dewaxing aids. The effect of the mixed use of ethylene vinyl acetate copolymers and polyalkylacrylates or polyalkylmethacrylates is disclosed in JP Patent Publication No. Sho 45-15379, JP Patent Publication No. Sho 49-26922, and JP Patent Laid-open No. Sho 54-11104. The effect of alkylnaphthalene condensation products, or the mixed use thereof with polyalkylmethacrylates is described in JP Patent Laid-open No. Sho 45-15379, JP Patent Publication No. Sho 4946361 and JP Patent Laid-open No. Sho 53-129202. The effect of the use of α-olefin polymers, or copolymers of a-olefin and vinyl acetate is described in JP Patent Laid-open No. Sho 53-121804 and JP Patent Laid-open No. Sho 53-121803. The effect of the use of polyalkylacrylates is described in JP Patent Laid-open No. Sho 404210, JP Patent Laid-open No. Sho 54-123102, JP Patent Laid-open No. Sho 57-30792 and JP Patent Laid-open No. Hei 7-316567. The effect of the use of polyvinylpyrrolidone is described in JP Patent Laid-open No. Sho 55-89392. The effect of the use of copolymers of dialkyl fumarate and vinyl acetate is described in JP Patent Laid-open No. Sho 60-217218 and JP Patent Laid-open No. Sho 61-247793. Among these prior art technologies, the use as dewaxing aid of a copolymer of a compound having reactive double bonds (a reactive monomer) and vinyl acetate is disclosed in JP Patent Publication No. Sho 49-26922, JP Patent Laid-open No. Sho 54-11104, JP Patent Laid-open No. Sho 53-121804, JP Patent Laid-open No. Sho 53-121803, JP Patent Laid-open No. Sho 60-217218 and JP Patent Laid-open No. Sho 61-247793. Compounds with vinyl acetate groups are decomposed by heat and the like, and acetic acid may be generated. Acetic acid in this case displays corrosiveness against metals such as SUS and the like, to say nothing of iron, and thus their presence is not desirable for the apparatus. In addition, the use of an alkylnathphthalene condensation product as dewaxing aid is disclosed in JP Patent Laid-open No. Sho 45-15379 and JP Patent Publication No. Sho 49-46361. As such alkylnaphthalene condensation products can be generally obtained through Friedel-Crafts reaction using chlorinated paraffin as the raw material, the complete removal of the chlorine content therein is not easy. Recently, however, there has been a strong demand for chlorine-free products in every field. Furthermore, the use of polyalkylacrylates as dewaxing aids described in the prior art references shows a good performance under the investigation in the laboratory, but a more effective aid is required since they do not show a good effect, especially, against heavy type wax-containing hydrocarbon oil in the evaluation with the actual apparatus in which the chilling rate during the chilling is 30° C./minute or higher. The problems to be solved by present invention are that the dewaxing method using the dewaxing aid described in the prior art can not be used for the general purposes depending on the kind of wax-containing hydrocarbon oils used and that the shortcomings (containing of chlorine, corrosion of the apparatus by the product at the time of decomposition, and the like) which can not be avoided due to the structure of these compounds and the production method have to be compensated for. That is to say, in the case of the dewaxing method using a dewaxing aids known heretofore, for instance, a polyalkylmethacrylate, the dewaxing aid alone does not show the effect on both the light type and the heavy type wax-containing hydrocarbon oils, and it is required to further add further compounds, such as alkylnaphthalene condensation products which inevitably contain chlorinated compounds due to their production process and copolymers of reactive monomer/vinyl acetate which may liberate monomeric acids during their decomposition due to their structures, as described above. The present inventors earnestly investigated in order to solve these problems. As the result, the dewaxing aids whose evaluation under the laboratory scale correlating to the evaluation with the actual apparatus in which the chilling rate during the chilling is 30° C./minute or higher have been found under condition of adding prechilling process (rapid chilling process) just like the actual apparatus to the solvent dewaxing method. They further exhibited the effect against any kinds, from the light type to the heavy type, of the wax-containing hydrocarbon oils, and were found to improve the filtration rate and the yield of the dewaxed oils, as compared with the conventional dewaxing aids.

20040816

20080617

20050310

75225.0

HARLAN, ROBERT D

NOVEL DEWAXING AID

UNDISCOUNTED

ACCEPTED

ACCEPTED

Pattern recognition system

A star pattern recognition system (1) comprises an optical filter arrangement (10) in the form of an array (12) of independently tiltable mirrors (M1), (M2). Light from a distant starfield (2) is incident upon the mirror array (12). Each mirror (M1), (M2) reflects a respective image of the starfield, and these images are brought to a common overlapping focus at a detector (18) by a parabolic mirror (14). The mirrors M1, M2 are tilted relative to each other such that when a given star pattern to be recognised is present in the field of view of the filter, each mirror reflects the image of a different star in the pattern onto a common point on a detector (18), thereby providing a detectable output intensity peak that indicates the presence of the star pattern in the field of view of the filter arrangement.

1-57. (canceled) 58. An optical pattern recognition system, comprising: an optical filter arrangement for receiving an optical input comprising an input scene and for providing an optical output in response to the optical input; and a detector for detecting the output of the filter arrangement; wherein: the optical filter arrangement comprises a plurality of reflective surfaces that are or can be arranged to be tilted relative to one another for producing a plurality of images of the input scene that can be brought to a common focus at the detector; and wherein the optical filter arrangement is arrangeable to provide an identifiable optical output when an input scene containing a predetermined pattern that the filter arrangement is set up to recognise is input appropriately to the filter arrangement. 59. The system of claim 58, wherein the reflective surfaces are arranged in an array. 60. The system of claim 59, wherein each reflective surface is independently tiltable about two axes of rotation. 61. The system of claim 58, wherein the reflective surfaces comprise mirror elements. 62. The system of claim 58, wherein said optical filter arrangement comprises a holographic element comprising plural sets of series of similarly orientated Bragg planes arranged through its depth, with each set of Bragg planes having, or being capable of being arranged to have, a different orientation with respect to other sets of Bragg planes, for producing a plurality of images of the input scene that can be brought to a common focus at the detector. 63. The system of claim 62, wherein each set of Bragg planes has a gradient in the relative spacing of the Bragg planes in the set through the depth of the holographic element. 64. The system of claim 58, wherein the optical filter arrangement is arrangeable to recognise a plurality of different predetermined patterns. 65. The system of claim 64, wherein the filter arrangement is adjustable in use to allow recognition of different patterns. 66. The system of claim 64, wherein the filter arrangement is programmable in use to allow recognition of a plurality of different predetermined patterns. 67. The system of claim 64, wherein said reflective elements are movable relative to one another in use to allow recognition of a plurality of different predetermined patterns. 68. The system of claim 64, wherein the filter arrangement comprises a single filter construction capable of recognising a plurality of different patterns. 69. The system of claim 62, wherein said optical filter arrangement comprises a holographic element comprising a plurality of sets of series of similarly orientated Bragg planes recorded at different angular or spatial locations in the element to allow a plurality of different predetermined patterns to be recognised. 70. The system of claim 58, wherein the input scene has a frequency plane and the optical filter arrangement is a phase modulator in the frequency plane of the input scene. 71. The system of claim 58, wherein the optical filter arrangement is arrangeable to produce a plurality of mutually displaced images of the input scene, such that different parts of each respective image overlap or can be arranged to overlap at the common focus at the detector. 72. The system of claim 71, wherein the input scene is a starfield and the pattern to be recognised is a star pattern in the starfield, wherein the optical filter arrangement is arranged such that when a star pattern in the input starfield matches the predetermined pattern to be recognised by the optical filter arrangement; parts of each of the respective images of the starfield corresponding to images of different stars in the star pattern to be recognised overlap at the common focus of the detector. 73. The system of claim 58, wherein each of said plurality of reflective surfaces is arrangeable to provide one image of the input scene. 74. The system of claim 58, wherein the filter arrangement has an optical axis and a rotational orientation about the optical axis relative to the input scene, and wherein the filter arrangement provides the identifiable output in response to the presence of the predetermined pattern to be recognised in the input scene regardless of the rotational orientation of the filter arrangement about the optical axis of the filter arrangement relative to the input scene. 75. The system of claim 58, wherein the filter arrangement has an optical axis and a rotational orientation about the optical axis relative to the input scene, and wherein the filter arrangement provides the identifiable output in response to the presence of the predetermined pattern to be recognised in the input scene only when the input scene is at a particular rotational orientation with respect to the optical filter arrangement about the optical axis of the filter arrangement. 76. The system of claim 75, wherein the optical filter arrangement is rotatable about its optical axis relative to the input scene. 77. The system of claim 76, wherein the optical filter arrangement is mounted in a spacecraft or satellite having a major rotational axis and wherein the filter arrangement is mounted such that its optical axis coincides with the major rotational axis of the spacecraft or satellite. 78. The system of claim 58, further comprising a processor for measuring the position on the detector relative to a reference position on the detector of a detected output intensity peak. 79. The system of claim 58, wherein the identifiable output of the filter arrangement comprises a light intensity peak. 80. The system of claim 58, further comprising a processor for assessing the intensity of the detected output peak and a processor for determining whether the predetermined pattern is present in the input scene on the basis of the assessed intensity. 81. The system of claim 58, wherein the optical filter arrangement is achromatic. 82. The system of claim 58, further comprising a plurality of detectors. 83. The system of claim 82, comprising a first detector with a relatively large field of view and a second detector with a narrower field of view. 84. The system of claim 58, wherein the filter arrangement has a field of view and the system further comprises an aperture arranged in front of the filter arrangement to restrict the field of view of the filter arrangement. 85. The system of claim 58, wherein said input scene is a starfield and said predetermined pattern is a star pattern. 86. An optical pattern recognition method, comprising inputting a scene to be analysed onto an optical filter arrangement arranged to provide an identifiable optical output when an input scene containing a predetermined pattern that the filter arrangement is set up to recognise is input appropriately to the filter arrangement; wherein the optical filter arrangement comprises a plurality of reflective surfaces, said reflective surfaces being tilted relative to one another for producing a plurality of images of the input scene that can be brought to a common focus at a detector, and focussing the images produced by the reflective surfaces onto a detector. 87. The method of claim 86, wherein the reflective surfaces comprise mirror elements. 88. The method of claim 86, wherein said optical filter arrangement comprises a holographic element having plural sets of series of similarly orientated Bragg planes arranged through its depth with each set of Bragg planes having a different orientation with respect to other sets of Bragg planes for producing said plurality of images of the input scene. 89. The method of claim 86, wherein said identifiable optical output comprises a light intensity peak. 90. The method of claim 86, further comprising assessing the intensity of the detected output to determine whether the predetermined pattern is present in said input scene. 91. The method of claim 86, wherein the input scene has a frequency plane and further comprising the step of arranging the optical filter arrangement to act as a phase modulator in the frequency plane of the input scene. 92. The method of claim 86, wherein the optical filter arrangement has a field of view and further comprising arranging the optical filter arrangement such that it forms a plurality of images of the input scene lying within its field of view that can brought to a common focus at the detector. 93. The method of claim 92, wherein the input scene is a starfield and the pattern to be recognised is a star pattern, further comprising arranging the optical filter arrangement such that when a pattern in the input starfield matches the predetermined pattern to be recognised by the filter arrangement, parts of each of the respective images of the starfield corresponding to images of different stars in the star pattern to be recognised overlap at the common focus of the detector. 94. The method of claim 86, further comprising arranging the filter arrangement such that it produces a plurality of mutually displaced images of the input scene. 95. The method of claim 86, further comprising rotating the optical filter arrangement relative to the input scene. 96. The method of claim 86, wherein the optical filter has an optical axis and further comprising mounting the optical filter arrangement in a spacecraft or satellite having a major rotational axis, and positioning the optical filter arrangement such that its optical axis coincides with the major rotational axis of the spacecraft or satellite. 97. The method of claim 86, comprising detecting the output of the filter arrangement on a detector, and determining the position of a detected output light intensity peak on the detector relative to a reference position on the detector. 98. The method of claim 97, wherein the filter arrangement has an optical axis, and further comprising using the position of the detected peak to determine the pointing direction of the optical axis of the optical filter arrangement relative to the pattern being recognised. 99. The method of claim 86, further comprising using the optical filter arrangement to recognise a plurality of different predetermined patterns. 100. The method of claim 99, wherein the optical filter arrangement is able to recognise only one pattern at any one time, and further comprising adjusting the filter arrangement in use to recognise different patterns. 101. The method of claim 99, further comprising programming the optical filter to allow recognition of a plurality of different predetermined patterns. 102. The method of claim 99, further comprising arranging the relative tilt of said reflective surfaces to allow recognition of a first predetermined pattern in the input scene, and adjusting the relative tilt of said surfaces to allow recognition of a second different predetermined pattern. 103. The method of claim 99, wherein the optical filter arrangement comprises a single filter construction capable of recognising a plurality of different patterns. 104. The method of claim 86, wherein the filter arrangement has a field of view and further comprising providing an aperture in front of the filter arrangement to restrict the field of view of the input scene available to the filter arrangement. 105. The method of claim 86, wherein said input scene is a starfield and said predetermined pattern is a star pattern. 106. One or more processor readable storage devices having processor readable code embodied on said process readable storage devices, said process readable code for programming said one or more processors to perform an optical pattern recognition method comprising: inputting a scene to be analysed onto an optical filter arrangement arranged to provide an identifiable optical output when an input scene containing a predetermined pattern that the filter arrangement is set up to recognise is input appropriately to the filter arrangement; wherein the optical filter arrangement comprises a plurality of reflective surfaces, said reflective surfaces being tilted relative to one another for producing a plurality of images of the input scene that can be brought to a common focus at a detector, and focussing the images produced by the reflective surfaces onto a detector.

The present invention relates to a pattern recognition system and method, and more particularly to an optical pattern recognition system and method that is particularly suitable for star pattern recognition. Satellites and spacecraft commonly use so-called “star-tracking” systems to assist in their positioning and navigation. These systems use predetermined reference or guide star field patterns to allow the satellite or space craft to determine its position and orientation. In such a system, images of the surrounding star field are collected and compared with one or more reference star patterns to allow the position and attitude of the satellite or spacecraft to be determined. Such star pattern recognition is typically carried out electronically in a computer. The imaged star field is compared to stored reference star patterns using iterative pattern identification algorithms. However, due to the iterative nature of the process, these methods are computationally intensive and so require relatively large processing times. Furthermore, the computational requirement increases rapidly with the number of stars in the reference star pattern to be matched. Thus, although high levels of accuracy and resolution can be achieved with a sufficiently high level of processing power and complexity in the hardware and software systems used, as such higher processing power is typically not always available onboard a spacecraft or satellite due to the power, space, weight, etc., restrictions that inevitably exist, the accuracy and processing speed available in practice with such electronic star pattern recognition systems is restricted. Furthermore, electronic systems tend to be relatively fragile, and so pattern recognition systems that rely on electronic processing can be more susceptible to failure in the relatively extreme conditions encountered in space. It is also known to carry out pattern recognition optically, and optical pattern recognition systems can avoid some of the problems of electronic pattern recognition systems discussed above, such as the need for extensive computer processing of data. In an optical pattern recognition system, the input scene to be analysed is Fourier transformed from an imaged input plane onto a so-called “matched” filter arrangement, which filter arrangement records the conjugate Fourier spectrum of the pattern to be recognised (and so is representative of the pattern to be recognised). The output of the filter arrangement is then detected optically using e.g. a charge coupled device (CCD) camera. The filter arrangement is such that a bright spot (light intensity peak) can be imaged onto the detector when part of the input scene matches the scene the filter is set-up to recognise. The presence or otherwise of the bright spot gives an indication of the correlation (match) between the input scene and the image the filter is set to recognise. In practice so-called 4-f coherent correlators are used for optical pattern recognition systems. In such arrangements, incoherent illumination from an input scene to be analysed is imaged to a device such as a spatial light modulator (SLM) to form an intermediate image of the original scene to be analysed in the form of a temporary recording of an image of the original input scene. This intermediate image is then illuminated with illumination from a coherent source (such as a laser). The intermediate image of the input scene (SLM) produces a corresponding modulation of the coherent wavefront with which it is being illuminated. The coherent light wavefront (now modulated with the input scene) then passes through a Fourier transforming element (lens) that transforms the imaged input scene into its spatial frequencies onto the optical filter arrangement. The optical output of the filter arrangement is focussed by a second Fourier transforming element (lens) onto the detector. As discussed above, a correlation (light intensity) peak is detected when (part of) the image of the input scene “matches” the predetermined image which the filter is intended to recognise. In effect, in such a system the filter arrangement is set up such that its impulse response matches the component of the input signal it would receive when the image it is intended to recognise is part of the input image. The field distribution incident on the filter arrangement is the Fourier transform of the input signal and the field distribution transmitted by the filter contains a plane wave that can be brought to a bright focus by a Fourier transforming element when a match exists. One drawback with such a coherent correlator arrangement is that the correlator needs coherent input illumination. As the input scene will normally be illuminated incoherently, it is therefore necessary to somehow provide from that scene coherent input illumination for the correlator. As described above, this is typically done by forming an intermediate image (typically an (up-dateable) recording) of the original input scene which can then be illuminated using a coherent light source such as a laser so as to provide the required coherent input illumination for the correlator. The intermediate image for illumination by the laser may be formed e.g. by recording the original input scene on photographic film or by recreating it using a spatial light modulator (SLM) such as a Liquid Crystal Light Valve (LCLV). It is also known to carry out incoherent optical correlation in which the incoherent original input image is passed directly to a correlator without conversion to a coherent image. However, incoherent correlators have worse signal to noise ratios than coherent correlators and so are less sensitive and less able to reliably distinguish objects from a background than coherent correlators. According to a first aspect of the present invention, there is provided a method of recognising a pattern of stars, comprising: inputting light from a star field to an optical filter arrangement, the filter-arrangement being arranged to provide an identifiable optical output in response to an input comprising light from a predetermined star pattern to be recognised; and detecting the output of the filter arrangement. From a second aspect, the present invention provides a system for recognising a pattern of stars, the system comprising: an optical filter arrangement which is arranged to provide an identifiable optical output in response to input light from a predetermined star pattern intended to be recognised; and a detector for detecting the output of the filter arrangement; the system being arrangable such that light from a star field can be input to the filter arrangement. The star pattern recognition system of the present invention uses an optical filtering arrangement to recognise particular star patterns in a distant star field. Star pattern recognition is therefore carried out optically, and so the present invention can avoid, for example, the need for extensive computer processing of data for pattern recognition. However, in the present invention, in contrast to conventional optical correlation systems, the light emanating from the distant star field is used as the input to the optical filter arrangement. In other words, the available original starlight is used directly by the system to determine whether a predetermined star pattern is present in the starfield (i.e. the light which is incident upon the filter arrangement originates from the stars themselves). The present invention does not therefore involve the formation of an intermediate image of the distant star field, (e.g. on an SLM) which is then illuminated by a laser to provide a source of coherent illumination for the pattern recognition filter arrangement. The present invention therefore avoids the need to generate some form of intermediate image of the distant star field (e.g. on an SLM), and the-need to provide a laser to then illuminate such an intermediate image. The Applicants have recognised that in practice the stars in a distant star field effectively comprise a set of isolated point sources against a dark background, and that that means that optical identification of a star pattern in the star field can be carried out to a sufficiently high level of accuracy using the available light from the star field directly. The Applicants have found that even with the star light directly incident on the filter arrangement, a sufficiently distinguishable output can be obtained in response to illumination from a predetermined star pattern to allow that star pattern to be recognised. The present invention thus provides a method and system in which star pattern recognition is carried out optically, but without the need to form an intermediate image of the starfield which has to be illuminated by a coherent light source to provide an input on which the system may operate. The present invention therefore provides a relatively fast, accurate, robust, lightweight, compact star pattern recognition system which may operate at a relatively low level of power consumption, as compared to existing star tracking systems (whether electronic or optical). The optical filter arrangement that is used to recognise a particular star pattern can be any suitable such arrangement that can give an indication of whether there is a match between the distant star field and the predetermined star pattern that the filter is intended to recognise. In particular, it should give an identifiable output that can be detected by the detector when illumination from a distant star field which matches the predetermined pattern that the filter is intended to recognise appropriately illuminates the filter arrangement. The output of the filter arrangement could be and preferably is such that when it is appropriately focussed onto the detector, a light intensity peak is formed on the detector when a star pattern match exists, as in existing optical correlation arrangements. The presence of the light intensity peak would thus indicate a suitable pattern match (i.e. pattern recognition). A lower intensity peak may be output when there is no match, or there could be no light output at all. Generally speaking the filter arrangement can be any suitable such arrangement. It is effectively in the frequency plane of the distant star pattern and should effectively act as a phase modulator in the frequency plane (i.e. provide an output which is phase modulated with respect to the input light, such that the phase of the individual frequency terms is manipulated by the filter). Thus, for example, appropriate phase filtering optical filters known for use in existing optical correlators, such as a holographic element, can be used for the filter arrangement. As discussed above, each star in the star field may be treated as a point source of light, and, furthermore, the Applicants have recognised that at the relatively great distances involved, the light originating from the stars will approximate to plane waves across the field of view of the filter arrangement. The Applicants have further recognised that by redirecting these plane waves in an appropriate manner, it is possible to provide multiple mutually displaced overlapping images of the star field that can be brought to a common focus, such that by, for example, arranging the overlapping images such that different stars in each of the images of the star field formed overlap (coincide) at the same point on the detector when the correct star field is incident on the filter arrangement, then a light intensity peak will be detected by the detector when a match exists. (It will be appreciated that as the images can be brought to a common focus, they may be moved relative to one another in the plane of the common focus so that different parts of the images overlap.) Thus, in a particularly preferred embodiment, the filter arrangement is arranged to form a plurality of images of the star field lying within its field of view that can be brought to a common focus at the detector. The arrangement should further be such that different parts of each respective image can be arranged to overlap (coincide) at the common focus at the detector. In this arrangement, the different images of the starfield formed by the filter arrangement are preferably arranged such that when a pattern in the input starfield matches the predetermined pattern to be recognised by the filter arrangement, parts of each of the respective images of the starfield corresponding to images of different stars in the star pattern to be recognised will overlap (coincide) at a common point on the detector to provide an output peak of higher intensity (which can be detected to indicate a pattern match). On the other hand, if no pattern in the input distant star field matches the pattern the filter is set up to recognise, the respective images of the starfield formed by the filter arrangement will not be aligned correctly for images of component stars of the input starfield to overlap exactly at a common point on the detector. In this case there should be no (or a smaller) light intensity peak at the detector. In this arrangement, each image of the starfield formed by the filter arrangement can effectively be used to redirect the image of one particular star in the star pattern to be recognised appropriately onto the detector. Thus the filter arrangement should produce at least as many differently oriented (star pattern) images as there are stars in the pattern to be recognised. It should be noted in this regard that while the filter arrangement itself may be more complex the greater the number of stars in the pattern to be recognised, in use the recognition process is effectively independent of the number of stars in the pattern to be recognised. Thus the present embodiment can be used to recognise patterns containing many stars (for example up to 100, although 16 has been found to be a suitable number) and hence be correspondingly more accurate without performance degradation, or increasing the processing time, as compared to, for example, electronic pattern recognition systems. It will be appreciated that when a pattern is recognised in this arrangement, the intensity of the output peak obtained will depend upon the number of stars whose images are combined at the common point on the detector. The measured intensity of an output peak obtained at the detector may thus be used to assess whether the star pattern has been correctly “matched”. In its simplest case, the detector could simply assess whether a peak above a given threshold is obtained. In a more sophisticated arrangement, the output peak detected could be compared to an expected peak intensity value (based e.g. on the known intensities of the stars whose images will overlap when the pattern is matched) to see if a match has been obtained. This can enhance the chances of successful pattern identification without a large increase in the complexity of the system. It is believed that the above optical pattern recognition arrangement is advantageous in its own right, and not just in the star pattern recognition context. Thus, according to a third aspect of the present invention, there is provided an optical pattern recognition system, comprising an optical filter arrangement that will provide an identifiable optical output when an input scene containing a predetermined pattern that the filter arrangement is set up to recognise is input appropriately to the filter arrangement, the filter arrangement being such that it can produce a plurality of images of the input scene that can be brought to a common focus at a detector; and a detector for detecting the output of the filter arrangement. According to a fourth aspect of the present invention, there is provided an optical pattern recognition method, comprising inputting a scene to be analysed to an optical filter arrangement that will provide an identifiable optical output when an input scene containing a predetermined pattern that the filter arrangement is set up to recognise is input appropriately onto the filter arrangement, the filter arrangement being such that it can produce a plurality of images of the input scene that can be brought to a common focus at a detector; focussing the images produced by the filter arrangement onto a detector; and detecting the output of the filter arrangement with the detector. In these aspects of the invention, since the filter arrangement should, as discussed above, be in a frequency plane, rather than an image plane, it may be necessary depending on the nature of the illumination from the scene to be analysed, to image the scene to be analysed to an image plane (e.g. to an input aperture, e.g. using a lens), and then optically Fourier transform (preferably achromatically) the light distribution onto the filter arrangement to provide the appropriate input illumination for the filter arrangement. This could be done, for example, by using an imaging lens to form an image at a plane (e.g. at an input aperture) of the scene to be analysed, which image is then Fourier transformed to the filter plane. Such imaging of the scene to be analysed may in particular be necessary where, for example, the input scene to be analysed is not in the far field (unlike a distant starfield which is in the far field). As discussed above, in these aspects and embodiments of the present invention the multiple images formed by the filter arrangement will normally be displaced relative to one another, such that different parts of each respective image will or can be arranged to overlap (coincide) at the common focus at the detector. Thus preferably the filter arrangement produces a plurality of mutually displaced images of the input scene. The filter arrangement could produce the multiple images by transmission or reflection. In a particularly preferred embodiment the multiple images are produced by appropriate reflection of the input scene. Thus preferably the filter arrangement comprises a plurality of reflective surfaces, each arranged to provide one appropriate image of the star field. The reflective surfaces should each be oriented and tilted appropriately relative to each other. They can be provided by mirror elements or a holographic element arranged to reflect light. Particularly where they comprise mirrors, the reflective surfaces are preferably arranged in an array, and are preferably tiltable relative to each other. In such an arrangement each reflective surface is preferably independently tiltable about two axes of rotation. In such an arrangement each reflective surface (e.g. mirror) will reflect an image of the input star field. By tilting the reflective surfaces relative to one another, different parts of each reflected image can be arranged to overlap when the reflected images are combined at the detector. Each reflective surface can thus be arranged to reflect one particular star from the star pattern to be recognised onto a common point on the detector when the correct input starfield is in the field of view of the system. In other words, although each reflective surface will reflect the whole star pattern in the field of view of the system, by differentially aligning each individual reflective surface, a different individual star from the pattern will be imaged onto a common point on the detector by each reflective surface when the correct input star field is in the field of view of the system. As discussed above, the number of reflective surfaces should match or exceed the number of stars in the pattern to be matched. Thus, for example, there may be up to 100 reflective surfaces, although 16 has been found to be a suitable number. A transmission filter arrangement for providing the multiple (overlapping) images would operate in a corresponding manner, and could use, for example, a transmission volume phase hologram for the filter arrangement. The optical filter arrangement may be arranged to be rotationally invariant, i.e. such that it will provide an identifiable output, e.g. light intensity peak, in response to light input from a predetermined star pattern to be recognised regardless of the in-plane (i.e. about the optical axis of the filter arrangement) rotational orientation of the filter arrangement relative to the distant star field being assessed. This can be achieved with, for example, a holographic filter element by recording the element with an appropriate pattern of concentric circles each arranged a distance away from the common centre of the circles corresponding to the relevant star's distance from a central point of the star pattern to be recognised. An output peak will be obtained when the spacing of the circles from their common centre matches the spacing of a group of stars from a given centre point. However, in a particularly preferred embodiment, the filter arrangement only gives the identifiable output “recognising” the star pattern in the input distant starfield when the star field is correctly rotationally oriented with respect to the filter about the optical axis of the filter arrangement. It can be important for satellites and spacecraft to know their rotational orientation and so having a filter arrangement that is rotationally sensitive allows this to be determined. A rotationally sensitive filter arrangement could, e.g., comprise an array of relatively tilted mirrors or other reflective surfaces of the type discussed above. In such an arrangement, rotation of the filter array relative to the distant star field will give rise to a corresponding rotation in the star field images reflected by the filter. The parts of the reflected images which overlap at the detector will therefore differ, depending on the rotational orientation of the filter to the distant star field and so only when the correct rotational orientation is achieved will the images of the appropriate stars in the star field overlap at the detector. Where the filter arrangement is rotationally sensitive, it is preferably arranged to be rotatable relative to the distant star field so that the star field can be tested at different rotational orientations. In this way the filter can be rotated until an identifiable output is obtained, thereby indicating the correct rotational orientation relative to the predetermined star pattern in the input star field. In a particularly preferred such arrangement, the optical axis of the optical filter arrangement is arranged to coincide with a rotational axis of the spacecraft or satellite in which it is mounted, and preferably with the major rotational axis of the spacecraft or satellite in which it is mounted. In this way the filter can be fixed to rotate as the e.g. satellite rotates about its major axis, without the need for a power supply. The output of the filter arrangement could simply be used as an indication of the presence or otherwise of the star pattern to be recognised in the field of view of the pattern recognition system. However, in a particularly preferred embodiment, the arrangement is such that the output can also be used to give an indication of the angle at which the optical axis of the filter arrangement is pointing. This can be important particularly in the satellite and spacecraft context, as it is often desirable to know the pointing angle of a spacecraft or satellite. Preferably the arrangement is such that if the optical axis is pointing straight at the star pattern to be recognised then the filter output peak is in one position on the detector (e.g. at its centre), but the output peak is moved relative to that “on-axis” position if the optical axis is pointing away from the star pattern (but the star pattern is still within the field of view of the system). In this way, the position of the output “recognition” peak on the detector can give an indication of the pointing direction of the optical axis of the pattern recognition system relative to the position of the star pattern being recognised. The above discussed reflective surface array filter arrangement can operate in this manner, since tilting that filter arrangement relative to the input starfield will result in a uniform translation of the position of each of the images formed, such that any parts of the images which previously overlapped will still do so, but at a different common point on the detector. The position of the output peak corresponding to the common overlap point will simply be translated across the output focal plane at the detector. The magnitude of this shift of the output peak may be used to determine the pointing angle of the spacecraft or satellite on which the system is mounted. In a particularly preferred arrangement of this embodiment, the filter arrangement is arranged with its optical axis parallel to the major rotational axis of the satellite or spacecraft and is arranged to rotate freely about the major axis of the spacecraft or satellite, such that the filter arrangement will then rotate at the same rate, but in the opposite direction, to the rotation of the spacecraft or satellite. This will then provide continual observation of the pointing angle of the spacecraft or satellite without requiring a power supply. In a particularly preferred embodiment, the optical filter arrangement can be used to recognise a plurality of different predetermined star patterns, i.e. is or can be arranged to provide an identifiable output in response to input light from a plurality of predetermined star patterns. In one such arrangement a single filter construction could, for example, be set to recognise a plurality of different star patterns. For example, the filter could be arranged to recognise different star patterns depending upon the angle at which the input light is incident upon the filter or the part of the filter upon which it is incident. In such an arrangement the input light would then be directed so as to be incident on different parts of the filter and/or to be incident upon the filter at different angles, depending upon which star pattern it is desired to recognise. This type of arrangement is particularly suitable where a holographic filter element is used, as a plurality of different star patterns to be recognised may be recorded in the volume of the hologram, e.g. at different angular or spatial locations. Additionally or alternatively, the filter arrangement may be able to recognise only one star pattern at any one time, but can be adjusted in use to recognise different star patterns. For example, where the filter arrangement comprises an array of reflective (mirror) surfaces, those surfaces could be movable relative to each other in use so that the array can be changed to recognise different star patterns. Preferably the filter arrangement is programmable in use to detect different star patterns. In such an arrangement, a plurality of sets of relative positions for each reflective surface corresponding to each of the star patterns to be recognised could be stored and then used as desired. Thus preferably, where the filter arrangement comprises a mirror-array, the array is preferably programmable such that the individual mirrors can be adjusted to adopt different relative positions in use. With a programmable filter arrangement, many star patterns could be recognised by a single system and that could allow full 4n steradian coverage by the system, thereby facilitating more autonomous operation. The optical output from the filter arrangement should be brought appropriately to the detector, e.g. focussed by a Fourier transforming element (to transform the filter's output from a frequency plane distribution into an image plane distribution) onto the detector for detection. This could be done using, for example, a separate focussing (and Fourier transforming) element, such as a lens or mirror, provided after the filter. However, in a particularly preferred embodiment the filter arrangement itself focuses, etc., its output onto the detector as this reduces the number of components in the system. For example, if the filter is a holographic element, the element may be recorded with a converging reference wave so that the filter will act to focus the output light. Where the filter comprises a plurality of reflective (e.g. mirror) surfaces, the same effect may be achieved by using focussing, such as parabolic or spherical, shapes for the reflective surfaces. The optical system is preferably achromatic, so that plural (and preferably all) frequencies in the multispectral star light can be brought to a common focus at the detector. This helps to maximise the available star light used at the detector for the pattern recognition. Thus the filter arrangement is preferably achromatic, as are any lenses, etc. used. With regard to the filter arrangement, a mirror array arrangement is achromatic by its very nature. In the case of a holographic filter element, the holographic element can, e.g., be recorded with a gradient in the spatial periods (spacing) of its (reflecting or transmitting) Bragg planes through its depth (i.e. be “chirped”), to allow it to reflect (or transmit) multiple wavelengths. It is also preferred that, where necessary, the system is adapted to compensate for any dispersion (e.g. chromatic dispersion) that may take place in the system. Such compensation can be carried out in any suitable manner known in the art. It will be appreciated from the above that the use of a mirror array as an optical filter arrangement in a pattern recognition system is particularly advantageous, since, for example, mirrors are achromatic, and a mirror array can readily be used as a programmable filter arrangement. Thus, according to a fifth aspect of the present invention, there is provided an optical pattern recognition system, comprising an optical filter arrangement comprising a plurality of mirrors that have or can be arranged to have different orientations with respect to one another for producing a plurality of images of the input scene that can be brought to a common focus at a detector; and a detector for detecting the output of the filter arrangement. According to a sixth aspect of the present invention, there is provided an optical pattern recognition method, comprising inputting a scene to be analysed onto an optical filter arrangement comprising a plurality of mirrors having different orientations with respect to one another; and focussing the images produced by the mirrors onto a detector. It is also believed that using a “chirped” holographic filter element is new and advantageous in its own right (since it is again, e.g. more achromatic). Thus, according to a seventh aspect of the present invention, there is provided an optical pattern recognition system, comprising: an optical filter arrangement comprising a holographic element having a plurality of similarly orientated Bragg planes arranged through its depth, the Bragg planes further having a gradient in their relative spacing through the depth of the holographic element; and a detector for detecting the output of the filter arrangement. According to an eighth aspect of the present invention, there is provided an optical pattern recognition method, comprising: inputting a scene to be analyzed to a optical filter arrangement comprising a holographic element having a plurality of similarly orientated Bragg planes arranged through its depth, the Bragg planes further having a gradient in their relative spacing 5 through the depth of the holographic element; and focussing the image produced by the holographic element onto a detector. In these aspects of the invention, the holographic element preferably comprises plural sets of series of similarly orientated Bragg planes, with each set of Bragg planes having, or capable of being arranged to have, a different orientation with respect to other sets of Bragg planes, for producing, as discussed above, a plurality of images of the input scene that can be brought to a common focus at the detector. As has already been discussed above, in the above fifth to eighth aspects of the invention, it may again be necessary to appropriately image and Fourier transform the scene to be analysed to provide an appropriate input to the (frequency plane) filter arrangement, for example, where the scene to be analysed is not in the far field. It will be appreciated that in these aspects and embodiments of the present invention, the multiple images formed by the filter arrangement will normally be displaced with respect to one another, such that different parts of each respective image will or can be arranged to overlap (coincide) at the detector. Thus the images produced by the filter arrangement are preferably mutually displaced with respect to each other. The detector used in any of the aspects and embodiments of the present invention may be selected as appropriate depending upon the nature of the response to be identified. For example the detector may be a camera or charge-coupled device (CCD). The detector may detect only visible light or only radiation not lying in the visible part of the electromagnetic spectrum, or both visible light and other electromagnetic radiation. It should be noted in particular that the present invention extends to the case in which the star light detected for the pattern recognition is not or may not be visible. The range from visible light to microwave radiation frequencies has been found to be particularly suitable for the present invention. As discussed above, the detector can preferably assess the intensity of any detected light intensity peak. It can more preferably determine whether a peak is above a particular, preferably predetermined, threshold, so as to, for example, facilitate more reliable identification of a true correlation peak. It can also preferably determine whether the peak is within a particular, preferably predetermined, margin of a given intensity value. If desired, more than one detector for the output of the filter arrangement may be provided. For example, the output from the filter arrangement may be provided to a plurality of detectors which are, e.g., provided for different purposes, such as to provide progressively more accurate identification of the star pattern. In such an arrangement, preferably two detectors are used. For example, a first detector with a relatively large field of view may be used to provide a relatively coarse estimate of the pointing angle of a satellite, with a second detector with a narrower field of view then being used to provide finer determination. It would also be possible to use two (or more) filter arrangements (and corresponding detector(s)) if desired. For example, a rotationally invariant filter could be used for coarse identification with a rotationally sensitive filter then used to determine rotational orientation. Steps may be taken to reduce unwanted noise and/or stray light interference in the light incident upon the detector. For example, an aperture may be arranged in front of the detector. Further, e.g. electronic, processing of the detected response may also be carried out, for example to reduce background noise, or to enhance the correlation peak obtained. The system of the present invention preferably further includes an aperture arranged in front of the optical filter arrangement to restrict the field of view of the system. This can help to, for example, reduce stray light interference at the filter. It can also help to ensure that the light incident on the filter is in the form of plane waves (as a restricted aperture can ensure that the wavefronts are planar at least over the area of the aperture). A suitable aperture size has been found to be around 10 cm diameter. A suitable field of view for the system has been found to be up to 5° or 6°. (This should be contrasted with conventional systems which typically can only have a 1° field of view). Other optical components, such as a lens to focus the star light onto the filtering arrangement can be placed in front of the optical filter arrangement if desired. However, unlike in conventional optical correlators, it is not necessary in the system of the present invention to provide a component, such as a Fourier transforming element (e.g. lens), to transform the light to be input to the filter arrangement. This is because the input star light will already be achromatically Fourier transformed (i.e. transformed into spatial frequency components) by free space propagation of the light fields as a result of the astronomical distances over which it travels to reach the pattern recognition system. The filter arrangement is therefore effectively in the frequency plane of the distant starfield. Although the present invention has been described with particular reference to star pattern recognition systems, as will be appreciated by those skilled in the art, it is also applicable to pattern recognition in other contexts, particularly where the pattern to be recognised consists of relatively isolated point-like sources in a relatively uncluttered, uniform background (i.e. is like a star pattern). For example, it could be used to identify planetary arrangements in a similar fashion to a star pattern. In this case, although the planets may be more extended than stellar point sources, the consequence would simply be that any correlation peak would be less precise and there may be greater probability of erroneous image overlaps giving rise to secondary peaks. This could reduce the accuracy of the system but would not prevent it from working. It would also be possible to perform computational operations such as sub-pixel interpolation techniques to try to enhance the accuracy if broader correlation peaks are being obtained if desired. This problem would be exacerbated, the larger the individual image sources to be recognised become. The invention could also be used, for example, in spacecraft docking applications where a target in the form of a number of point sources against a uniform background could be arranged on the docking target and then tracked using a pattern recognition system in accordance with the present invention. In this case, as the two craft approach, some refocussing of the system may be necessary as the distance to the target pattern reduces to ensure appropriate imaging of the target (i.e. the output of the filter) onto the detector array when the target is within the field of view of the system. The amount of de-focus could also be used to determine distance, and the rate of de-focus could be used to determine rate of approach. As the size of the target would also change as the craft approach, a scale-invariant system, or some form of scale compensation or adjustment may also be necessary. Thus, according to a ninth aspect of the present invention, there is provided an optical pattern recognition method, comprising: inputting light from a scene to be analysed to an optical filter arrangement, the filter arrangement being arranged to provide an identifiable optical output in response to an input comprising light from a predetermined pattern to be recognised; and detecting the output of the filter arrangement. From a tenth aspect, the present invention provides an optical pattern recognition system, the system comprising: an optical filter arrangement which is arranged to provide an identifiable optical output in response to input light from a predetermined pattern intended to be recognised; and a detector for detecting the output of the filter arrangement; the system being arranged such that light from a scene to be analysed can be input to the filter arrangement. These aspects of the present invention can include any or all of the above preferred features of the present invention. A number of preferred embodiments of the present invention will now be described, by way of example only, and with reference to the accompanying drawings, in which: FIG. 1 is a schematic diagram of a star pattern recognition system according to a first embodiment of the present invention; FIG. 2 is a schematic diagram of a star pattern recognition system in accordance with a second embodiment of the present invention; FIG. 3 is a schematic diagram of a star pattern recognition system in accordance with a third embodiment of the present invention; FIG. 4 is a cross-sectional view of the holographic element used for the filter arrangement used in the embodiment of FIG. 3; FIG. 5 shows a mask which may be used to record a rotationally invariant holographic filter in accordance with a further embodiment of the present invention; and FIGS. 6, 7, and 8 show exemplary detected filter arrangement outputs when using a pattern recognition system in accordance with preferred embodiments of the present invention. FIG. 1 shows a first embodiment of a pattern recognition system for star tracking in accordance with the present invention. The system 1 includes an optical filter arrangement 10 having an optical axis 4, which axis is arranged to coincide with the major axis of rotation of the satellite on which the pattern recognition system is mounted. The filter arrangement 10 consists of an array 12 of two mirrors M1, M2, each of which is independently tiltable about two axes of rotation. The system further includes an aperture 6 arranged in front of the filter arrangement 10 to restrict the field of view 8 of the filter arrangement. A parabolic mirror 14 (which acts as an achromatic Fourier transforming element to allow the beams reflected by the mirror array to come to a common focus) is located at a distance equal to its focal length beyond the filter arrangement 10. The mirror 14 focuses light output from the filter arrangement 10 to a common focus 7 at which a detector 18 in the form of a CCD camera is located. An aperture 16 is arranged in front of the detector 18 to restrict the field of light incident upon the detector 18. The detector 18 detects the output (correlation) signal from the filter arrangement 10. In use of this star pattern recognition system, light 3 from a distant star field 2 will enter the system 1 through the aperture 6 and be incident upon the mirror array 12 of the filter arrangement 10. The light 5 output from the filter arrangement 10 is then incident on the parabolic mirror 14 which acts to redirect and focus it onto the detector 18. Each mirror, M1, M2, of the mirror array 12, reflects an image of the distant star field and those images are brought to a common overlapping focus at the detector 18 by the parabolic mirror 14. The mirrors M1, M2 are tilted relative to each other so that the images they produce are displaced relative to each other at the detector 18 (i.e. such that they do not overlap exactly, but rather different parts of the two images overlap and are coincident on the detector 18). This feature is used as discussed above to recognise a given star pattern by arranging the mirrors M1, M2 such that they reflect different stars in the star pattern to be recognised to the same point on the detector 18 when the correct pattern is in the filter arrangement's field of view, thereby providing an intensity peak at the detector 18 when the pattern is recognised. The case where the star pattern recognition system 1 of FIG. 1 is arranged to recognise a predetermined pattern in the input star field 2 consisting of two stars S1 and S2 will now be considered by way of example. The mirrors M1 and M2 of the mirror array 12 each reflect an image of the whole of the starfield 2 lying within the field of view 8 of the filter arrangement 10. Mirror M1 is arranged such that the whole of the Fourier plane of the starfield which it reflects will be redirected onto the detector 18 and furthermore, such that the part of that image containing star S1 will be located at a given point on the detector 18 when the correctly oriented star pattern is in the field of view of the system. Mirror M2 is correspondingly aligned such that it will reflect the part of its reflected image of the whole star field containing star S2 onto the same point on the detector 18 when the correctly oriented star pattern is in its field of view. The two parts of the reflected images of the whole starfield produced by mirrors M1 and M2 containing stars S1 and S2 will thus coincide and overlap at the common point on the detector when the correct star pattern is in the system's field of view, giving rise to an output intensity peak at the detector 18 which can be detected. This is illustrated by FIG. 6 which shows an exemplary detector image with an output peak at its centre indicating pattern recognition. The star pattern recognition system of FIG. 1 is sensitive to in-plane rotation between the filter arrangement and distant star field (i.e. relative rotation in the plane perpendicular to the optical axis 4 of the filter arrangement). This is because if the filter arrangement 10 is rotated relative to the star field 2, that will give rise to a corresponding rotation in the star field pattern far field distribution as reflected by the mirrors M1 and M2 of the array 12. However, as the images are rotated, the portions of each image which overlap at the detector 18 will no longer necessarily correspond to the positions of stars S1 and S2 and so no output peak of higher intensity will be detected at the detector 18. The effect of such in-plane rotation relative to the star field is illustrated by FIGS. 6 and 7. FIG. 6 shows the detected image for no in-plane rotation (θ=0° in-plane field rotation, where θ is the relative in-plane angle between the filter and the star pattern it is set up to recognise and can be anywhere between +180° and −180°) and FIG. 7 shows the detected image where there is some relative in-plane rotation (θ=4.5° in-plane field rotation). As can be seen, the bright detected spot in FIG. 6 indicating pattern recognition is not present in FIG. 7, as the relevant stars in the different images produced by the mirrors M1, M2 no longer overlap. To take account of this rotational sensitivity, the star pattern recognition system 1 is rotatable in use, so that its in-plane rotation can be changed. This could be achieved, e.g., by mounting it on an appropriately driven stage or platform. In one preferred arrangement, the system 1 is arranged such that its optical axis 4 coincides with the major axis of rotation of the satellite on which it is mounted. It could then be fixed so that as the satellite rotates, the filter arrangement 10 will also rotate about its optical axis 4. A correlation peak would then be detected by the detector 18 when the mirror array 12 of the filter 10 faces the star field 2 at the correct in-plane angle. This arrangement would allow the pattern recognition system to rotate in use without the need for additional power to drive its rotation. Rotation of the system about the major axis of the satellite may also allow information regarding the spin rate, precession angle and precession rate of the satellite to be obtained. As well as being rotationally sensitive, in the FIG. 1 arrangement if the pointing direction of the optical axis 4 of the filter arrangement changes (because, e.g., the pointing direction of the satellite changes), then the detected filter output will again change. This is because as the optical axis 4 tilts, so does the mirror array 12. This will cause a translation in the light output 5 from the filter arrangement 10 across the parabolic mirror 14, and hence of each of the reflected images across the output plane at the detector 18. However, the same parts of the reflected images will still overlap. Thus once a correlation peak has been obtained, a change in the pointing direction of the filter arrangement (satellite) will simply result in a translation of the light intensity peak across the plane of the detector 18. The magnitude of the translation of the peak may be measured and used to determine the change in pointing angle of the satellite. This translation of the correlation peak as a result of a change in pointing direction is illustrated by FIGS. 6 and 8. FIG. 6 shows the case where the star pattern is in the centre of the field of view of the filter arrangement 10 (i.e. the optical axis 4 is pointing directly at the star pattern being recognised) and FIG. 8 shows the case where the star pattern is “off-centre” (i.e. the optical axis is pointing away from (at an angle to) the star pattern. (In both cases there is no relative rotational misorientation (i.e. relative in-plane rotation θ=0°).) It can be seen from FIG. 8 that the light intensity peak indicating pattern recognition has been translated from its central position in FIG. 6 due to azimuthal and altitude shifts caused by the pointing direction angular displacement. This feature can be exploited to provide continuous observation of the satellite's pointing direction with minimal power consumption by aligning the optical axis 4 with the major rotational axis of the satellite but allowing the filter array to rotate freely about that axis (e.g. by placing it on a suitably mounted platform) rather than fixing it to rotate with the satellite. Conservation of angular momentum means that the filter arrangement will then rotate in the opposite direction but at the same angular frequency as the satellite. The operation of the above star pattern recognition system can be considered as follows. Since the light from the star field reaching the filter arrangement 10 has been achromatically Fourier transformed due to the astronomical distances that separate the star field and the filter arrangement, each star effectively provides a planar wave front across the filter aperture that can be characterised with its own unique directional unit vector (perpendicular to the planar wave front) when viewed from the fixed position of the filter arrangement. The mirror array of the filter arrangement then acts as a multiplexing device that effectively transforms and redirects these unit vectors. For example, considering a star field of three stars, S1, S2, S3, with unit vectors K1, K2, K3 incident on a mirror array comprising three mirrors M1, M2, M3, then the resulting vectors due to the action of the mirrors will be K1n, K2j, K3m, with n, j, and m able to take any value between 1 and 3. The set (n, j, m) indicates the reorientation of a certain vector due to any of the three mirrors (e.g. K12 means reorientation of vector K1 due to the action of mirror M2). Matching of a star pattern (i.e. a correlation peak at the detector) occurs when each incident vector is redirected in the same manner by a different mirror, i.e.: K1n=K2j=K3m, n≠j≠m (1) When this requirement is met, a plane wave that can be brought to a bright focus by a Fourier transforming element placed after the filter array is obtained. If the system rotates relative to the star field, this provides a corresponding rotation of what is the far field of the star pattern at the input aperture of the system (i.e. where the mirror array is located). Although the relative in-plane rotation each star is subjected to is the same, rotation of the stellar field relative to the mirror array causes the directional unit vectors to re-direct in a non-uniform fashion and the condition above then ceases to be satisfied. The output plane at the detector is then composed of appropriate individual (non-overlapping) star images. On the other hand, a change in pointing direction is equivalent to simple translations across the input plane of the Fourier transforming element and since these have the same value for all the star vectors, the result is simply translation of the correlation peak at the detector (which translation indicates the pointing direction). Thus the system effectively uses the mirrors to align different stars in the images of the star field at the detector. If the system is tilted, the aligned stars remain aligned but their common position shifts on the detector. If the system is rotated about its optical axis, the stars' images no longer line up. It can be seen that with this arrangement, a target star pattern is successfully identified when it appears with the field of view of the optical system and its in-plane orientation is matched with the latent orientation of the filter arrangement. The pointing direction of the star pattern recognition system can be determined by the lateral and longitudinal shifts of the recognition signal across the output plane at the detector. Because the system is entirely optical, it provides high speed processing and can be made compact and lightweight. In a particularly preferred embodiment, each mirror in the array is independently adjustable in use to allow different array set-ups (and hence different star patterns to be recognised). Preferably, a programmable mirror array is used, with each mirror of the array 12 preferably being pre-programmed with a number of positions corresponding to those required to produce an appropriate image of particular stars in a number of different star patterns to be recognised. Using such a programmable array, the system could be programmed to achieve star pattern recognition for many star fields so that full 4Π steradian sky coverage could be achieved. This could allow a fully autonomous system, which is highly desirable for a star tracking arrangement. FIG. 2 shows a modification of the star pattern recognition system. In this arrangement a beam splitter 20 and a mirror 22 are placed in the path of the light 5 output from the filter arrangement 10, and the parabolic mirror 14 is replaced by two Fourier transforming lenses 24 and 26. Detectors 30 and 34 with entrance apertures 28 and 32 are placed in the focal planes of the respective lenses 24 and 26. In this embodiment of the present invention, the filter arrangement 10 acts in the same way as in the first embodiment, but its output is provided to two detectors 30 and 34 by means of the beam splitter 20 and mirror 22 arrangement. The beam splitter 20 directs part of the output light 5 from the filter arrangement 10 towards lens 24, while the second part of the output light passes through the beam splitter 20 and is incident upon mirror 22 which redirects it to lens 26. Detector 30 has a wider field of view than detector 34. Detector 30 may therefore be used to provide a rough estimate of, for example, the general pointing direction of the satellite. Once this has been established, the second narrower field of view provided to the detector 34 may be used to give a more accurate determination of the pointing angle within the estimated range provided by the first detector 30. This arrangement, although more complex in construction, can allow faster scanning and establishment of the general pointing direction without sacrificing accuracy in use. The use of two detectors can also allow false readings caused by e.g. random radiation effects scintillating individual pixels in the detectors to be eliminated. Each detector can also provide a back-up in case of the other's failure. FIG. 3 shows a third embodiment of the present invention which is similar to the arrangement shown in FIG. 1, except that the filter arrangement 10 comprises a reflective holographic optical element 40 supported on a substrate 42 rather than a mirror array. The parabolic mirror 14 has been replaced by a mirror 44 and a Fourier transforming focusing lens 46 which act together to bring the light 5 output from the filter arrangement 10 to a focus in the plane of the detector 18. The holographic element 40 is a reflection volume phase holographic element and is recorded (using known holographic techniques) with a series of Bragg planes allowing it to act as a reflecting mirror-like surface for light whose wavelength matches that of the grating. One series of Bragg planes is recorded at an appropriate orientation and geometry for each star in the target star pattern. FIG. 4 shows a cross-section of the holographic element 40, illustrating the Bragg planes recorded across the depth of the holographic film. The filter 40 is recorded with two series of Bragg planes denoted respectively by the continuous and dotted lines of FIG. 4. As described above, this will allow the filter to act as a reflective element for two stars in a pattern to be recognised. Achromatisation is achieved by creating a gradient in the spacing of the Bragg planes for each series across the depth of the element (i.e. the holographic element 40 is chirped). This ensures that the element will reflect and allow to be brought to a common focus the multiple wavelengths present in the starlight (rather than just a single wavelength), thereby providing a stronger and more localised output signal at the detector. The holographic element 40 reflects incident light which satisfies the Bragg condition: 2di(z).sin θi=λk Where di(z) is the spatial period of the grating at depth z of the ith plane wave grating (there being, as discussed above, one such grating for each star in the pattern to be recognised), θi is the incident angle of the ith plane wave (i.e. particular star wavefront) illuminating the hologram, and λk are the multiple illumination wavelengths incident on the filter originating from the stellar sources. As can be seen from this equation, by creating a gradient in the spatial periods, the Bragg condition will be satisfied for multiple wavelengths, allowing the holographic element 40 to function as a mirror-like element. Recording many such differently oriented Bragg plane gradients on the hologram, creates appropriate “mirrors” for each star in the pattern to be recognised. The gradient of the spacing of the Bragg planes can be achieved, e.g., by appropriate chemical processing and temperature control (e.g. in relation to the temperature of the dehydrating agent in the final processing) of the holographic film. A plurality of sets of series of Bragg planes, each matching a different star pattern may be spatially or angularly multiplexed on the same holographic element 40 at different spatial or angular positions, to allow the same element to be used to recognise multiple different star patterns (e.g. by directing the incident light onto different parts of the element and/or at different angles to the element). The holographic element 40 could also be arranged to focus its output onto the detector 18, thereby eliminating the need for the lens 46 (and, if desired, the mirror 44) and allowing the focussed output signal to be produced by a single optical element. This could be achieved by recording the hologram with a spherical or converging, rather than a plane, reference wave. As well as a reflection volume phase hologram of the reference star pattern as discussed above, it would also be possible to use a transmission volume phase hologram that similarly produces multiple overlapping images at the detector. In such an arrangement, as is known in the art, the Bragg planes within the volume transmission hologram would be at an angle to the plane of the hologram and the incident light would come in at an angle and diffract from the grating planes so as to propagate through the hologram and emerge on the other side of the hologram in a direction governed by Bragg's law of diffraction. Using a holographic element as the matched filter has the advantage that the filter arrangement can be very compact and light-weight. It is also possible when using a holographic optical element for the filter to construct the element so that it is rotationally invariant, i.e. such that the target star pattern may be recognised regardless of the relative rotational orientation of the filter arrangement, for any given or for each star pattern the element can recognise. In this case, a rotationally invariant mask, such as the one illustrated in FIG. 5, is used to record the hologram. In the mask of FIG. 5, the series of concentric circles 52, 54, 56 and 58 represent the position of each star S1, S2, S3, S4 of a star pattern to be recognised at any possible rotation about the common centre point 0 of the circles. An identifiable output will be obtained when the spacing of the circles 52, 54, 56, 58 from their common centre 0 matches the displacement of a group of stars from a given centre point in the region of the sky which is being scanned. In this way, the holographic filter element is rotationally invariant. In this arrangement recognition results from matching the relative spacing of the circles from their common centre to the corresponding displacements of stars from the chosen centre point (defined in the template used to make the hologram) in the star field being analysed. This type of filter arrangement is inherently shift-invariant and thus allows both recognition of a given star pattern and determination of its location, albeit in a less reliable manner than a system based on individual star positions and relative rotation (since there would be, for example, more scope for different star patterns matching the rotationally invariant filter). However, a rotationally invariant filter arrangement would allow rapid scans of large sky areas to be carried out to at least identify candidate sky regions independent of the relative in-plane rotation of the filter arrangement and star field. Once candidate sky regions have been located using the rotationally invariant filter, those regions could then be confirmed (or negated) with higher certainty, and the relative in-plane rotation, etc., determined, by using a rotationally sensitive filter arrangement as described with reference to FIGS. 1 to 3 above. Combining the two filter arrangements in this way would allow large regions of the sky to be rapidly scanned and candidate regions identified for subsequent checking with a more accurate filter arrangement. Thus, in a preferred arrangement, a rotationally invariant holographic filter of this type is used to provide a rough estimation of the location of a star pattern, with a second filter of the type described with reference to the embodiments of FIGS. 1 to 3 then being used to provide more accurate determination. The field of view of the pattern recognition system can be selected as desired. It has been found that a range up to 6° field of view is most suitable. For example, a field of view of approximately 6 degrees by 6 degrees can be obtained by using a CCD camera of size 512×512 pixels as the detector and a lens of f-number=2 (e.g. diameter D=25 mm and focal length F=50 mm). A suitable aperture size in front of the filter arrangement is 10 cm diameter. It should be appreciated that in any of the embodiments described, the focusing and/or transforming lenses positioned after the filter arrangement may be combined with the filter in a single optical element. For example, in the embodiment of FIGS. 1 and 2, the mirror array 12 may comprise parabolic or spherical mirrors which will focus as well as redirect light incident upon them. As discussed above, where a holographic filter element is used, the element may be recorded using a converging reference wave so as to produce an element which also has a focusing effect. Although the present invention has been described with particular reference to star tracking applications and indeed is particularly suited to star tracking applications, it can be used for other optical pattern recognition, particularly where the pattern to be recognised is similar to a star field, i.e. comprises relatively isolated point light sources against a relatively uncluttered background. Thus, for example, the system could be used to recognise as well as a star field, a close juxtaposition of planets that a satellite or spacecraft could point towards. In such an arrangement, the planets may not be perfect point sources but may be extended and so could be imaged at the detector as extended regions. The overlap of the common point on the detector may not therefore be as precise as for a star field, and there may therefore be a corresponding loss of accuracy in both locating the peak and determining when the in-plane rotation was matched. It may also be the case that the probability of multiple overlaps off-axis would also increase. However, the system would still be able to provide some form of pattern recognition, albeit possibly at lower accuracy. It would also be possible to use, for example, sub-pixel interpolation techniques to improve the accuracy, although that would involve some numerical post-processing which may be undesirable. Another application to which the present invention could be applied could be, for example, spacecraft docking. Such docking usually requires the accurate tracking of fiducial points on the spacecraft on which docking is desired. The fiducial points could be provided in the form of a pattern of point sources produced, for example, by multiple laser or light emitting diode (LED) sources. The pattern of point sources could be recognised and located by a pattern recognition system in accordance with the present invention mounted on the docking spacecraft. The correlation peak location on the detector could, for example, provide a directional signal to an automatic guidance system. Alternatively, the pattern recognition system could be mounted on the spacecraft being docked to (i.e. on which the docking manoeuvre is being made), in which case a control signal may be generated in response to the output of the pattern recognition system and transmitted to the docking spacecraft. One difficulty with this system would be that as the docking craft approaches, the scale of the pattern being tracked will change. This could be compensated for either by using a scale-invariant filter or by applying a compensating multiple tilt to each mirror of the multiple mirror array acting as the filter as the distance to the target changes. Furthermore, on close approach, some degree of re-focussing to maintain the correlation peak's sharpness at the detector may be required, since the light emanating from the individual point sources may no longer be adequately approximated as plane waves at shorter distances (i.e. the point sources will no longer give rise to angled plane waves at the sensor aperture) and the image plane would move away from the lens as the object distance moves in from infinity. The amount of de-focus could be measured and used to determine distance, and/or, the rate de-focus could be used to determine rate of approach. It can be seen from the above that the present invention, particularly its preferred embodiments, provides an optical pattern recognition system, and in particular an optical star pattern recognition system that can have a relatively low mass and volume, can operate autonomously, can have enhanced reliability and survivability in a space environment, can have greater ease of manufacture and hence a lower cost, can have greater versatility and multifunctionality, and faster update rates and lower computer processing requirements than existing conventional pattern recognition systems. In particular, a pattern recognition system in accordance with the present invention can be inherently simple and therefore designed to relatively low volume, mass and cost. Particularly with a programmable mirror array, it can be arranged to have full 4Π steradian coverage without burdening computer processing requirements and therefore can provide greater autonomy. As the pattern matching is performed optically, it can be performed rapidly and without the need for extensive digital electronic computing power and electronic sub-components (which means that overall power consumption can be low and complexity can be reduced). The use of passive optical components means that the system can have greater tolerance in the harsh radiation environments encountered in space applications. Furthermore, the pattern recognition technique can be realised in real time and other than in relation to the construction of the filter arrangement, there is no in use penalty when using a large number of guide stars for identification (which can provide greater accuracy).

20050523

20080506

20050929

99351.0

WYATT, KEVIN

PATTERN RECOGNITION SYSTEM

SMALL

ACCEPTED

ACCEPTED

Reagents for asymmetric allylation, aldol, and tandem aldol and allylation reactions

A new class of reagents and method of use of the reagents in the reaction of the reagents with electrophilic compounds. The invention in one embodiment is directed to a method for the formation of an alcohol of the formula (I). The method includes reacting reagent of the formula (II) with an aldehyde of the formula R10CHO to form the alcohol. X3 is one of O and C(R4)(R5). Each of X1 and X2 is independently O or N—R. Each of Ca and Cb is independently an achiral center, an (S) chiral center or an (R) chiral center. Ra and Rb are (i) each independently C1-10 alkyl, C6-10 aryl or C3-9 heteroaryl, or (ii) taken together to form a C3-C4 alkylene chain which together with Ca and Cb forms a 5-membered or 6-membered aliphatic ring. Rc and Rd are each independently hydrogen, C1-10 alkyl, C6-10 aryl or C3-9 heteroaryl. R is C1-10 alkyl, C6-10 aryl or C3-9 heteroaryl. Each of R1, R2, R3, R4, R5 is independently hydrogen, C1-C10 alkyl, C6-10 aryl, C3-9 heteroaryl, C1-10 alkoxy, C6-10 aryloxy, C1-10 dialkylamino, C1-10 alkyl-C6-10 arylamino, C1-10 diarylamino, or halogen. R6 is halogen, hydrogen, C1-10 alkyl, C6-10 aryl, C3-9 heteroaryl, C1-10 alkoxy, C6-10 aryloxy, C1-10 alkyl-C6-10 arylamino, C1-10 diarylamino, OSO2CF3 or SR. R10 may be C1-10 alkyl, C6-10 aryl, or C3-9 heteroaryl.

1. A method for forming of an allylation reagent of formula comprising reacting a silane of formula with a compound of formula A to form the allylation reagent, wherein: each of X1 and X2 is independently selected from a group consisting of O and N—R; each of Ca and Cb is independently selected from a group consisting of an achiral center, an (S) chiral center, and an (R) chiral center; Ra and Rb are (i) each independently selected from a group consisting of C1-10 alkyl, C6-10 aryl, and C3-9 heteroaryl, or (ii) taken together to form a C3-C4 alkylene chain which together with Ca and Cb forms one of a 5-membered aliphatic ring and a 6-membered aliphatic ring; Rc and Rd are each independently selected from a group consisting of hydrogen, C1-10 alkyl, C6-10 aryl, and C3-9 heteroaryl; R6 is selected from a group consisting of halogen, hydrogen, C1-10 alkyl, C6-10 aryl, C3-9 heteroaryl, C1-10 alkoxy, C6-10 aryloxy, C1-10 dialkylamino, C1-10 alkyl-C6-10 arylamino, C1-10 diarylamino, and SR; R is selected from a group consisting of C1-10 alkyl, C6-10 aryl, and C3-9 heteroaryl; and each of R1, R2, R3, R4, R5, is independently selected from a group consisting of hydrogen, C1-C10 alkyl, C6-10 aryl, C3-9 heteroaryl, C1-10 alkoxy, C6-10 aryloxy, C1-10 dialkylamino, C1-10 alkyl-C6-10 arylamino, C1-10 diarylamino, and a halogen. 2. The method of claim 1, wherein each of R1, R2, R3, R4, and R5 is hydrogen, and R6 is chlorine. 3. The method of claim 1, wherein X1═X2═O. 4. The method of claim 3, wherein the compound of formula A is 5. The method of claim 1, wherein X1═NR and X2═O. 6. The method of claim 5, wherein each of Ca and Cb is an (S) chiral center. 7. The method of claim 5, wherein each of Ca and Cb is an (R) chiral center. 8. The method of claim 5, wherein R is selected from a group consisting of methyl, benzyl and phenyl. 9. The method of claim 8, wherein each of Ra and Rb is independently selected from a group consisting of methyl and phenyl, and each of Rc and Rd is independently selected from a group consisting of methyl and hydrogen. 10. The method of claim 5, wherein the compound of formula A is selected from a group consisting of 11. The method of claim 1, wherein X1═X2═NR. 12. The method of claim 11, wherein each of Ca and Cb is an (S) chiral center. 13. The method of claim 11, wherein each of Ca and Cb is an (R) chiral center. 14. The method of claim 11, wherein R is selected from a group consisting of methyl, benzyl and phenyl. 15. The method of claim 14, wherein each of Ra and Rb is independently selected from a group consisting of methyl and phenyl, and each of Rc and Rd is hydrogen. 16. The method of claim 11, wherein Ra and Rb are taken together to form a C4 alkylene chain which together with Ca and Cb forms a 6-membered aliphatic ring. 17. The method of claim 16, wherein the compound of formula A is selected from a group consisting of (1R,2R)-N,N-Dibenzyl-cyclohexane-1,2-diamine, (1R,2R)-N,N-Dip-bromobenzyl)-cyclohexane-1,2-diamine, and (1R,2R)-N,N-Di(p-methoxybenzyl)-cyclohexane-1,2-diamine. 18. A method for forming a first reagent of formula comprising reacting a second reagent of formula with one equivalent of a lithium enolate of formula Li—O—C(R3)═C(R1)(R2) to form the first reagent, wherein each of X1 and X2 is independently selected from a group consisting of O and N—R; each of Ca and Cb is independently selected from a group consisting of an achiral center, an (S) chiral center and an (R) chiral center; Ra and Rb are (i) each independently selected from a group consisting of C1-10 alkyl, C6-10 aryl, and C3-9 heteroaryl, or (ii) taken together to form a C3-C4 alkylene chain which together with Ca and Cb forms one of a 5-membered aliphatic ring and a 6-membered aliphatic ring; Rc and Rd are each independently selected from a group consisting of hydrogen, C1-10 alkyl, C6-10 aryl, and C3-9 heteroaryl; R6 is selected from a group consisting of halogen, hydrogen, C1-10 alkyl, C6-10 aryl, C3-9 heteroaryl, C1-10 alkoxy, C6-10 aryloxy, C1-10 dialkylamino, C1-10 alkyl-C6-10 arylamino, C1-10 diarylamino, O—C(R3)═C(R2)(R1), and SR; R is selected from a group consisting of C1-10 alkyl, C6-10 aryl, C3-9 heteroaryl; and each of R1, R2, and R3, is independently selected from a group consisting of hydrogen, C1-C10 alkyl, C6-10 aryl, C3-9 heteroaryl, C1-10 alkoxy, C6-10 aryloxy, C1-10 dialkylamino, C1-10 alkyl-C6-10 arylamino, C1-10 diarylamino, and a halogen. 19. The method of claim 18, wherein each of R1, R2, and R3 is hydrogen, and R6 is chlorine. 20. The method of claim 18, wherein X1═X2═O. 21. The method of claim 20, wherein Rc═Rd═H, and Ra═Rb=2-methoxy-2-propyl. 22. The method of claim 18, wherein X1═NR and X2═O. 23. The method of claim 22, wherein each of Ca and Cb is an (S) chiral center. 24. The method of claim 22, wherein each of Ca and Cb is an (R) chiral center. 25. The method of claim 22, wherein R is selected from a group consisting of methyl, benzyl and phenyl. 26. The method of claim 25, wherein each of Ra and Rb is independently selected from a group consisting of methyl and phenyl, and each of Rc and Rd is one of methyl and hydrogen. 27. The method of claim 26, wherein each of Rc and Rd is hydrogen. 28. The method of claim 18, wherein X1═X2═NR. 29. The method of claim 28, wherein each of Ca and Cb is an (S) chiral center. 30. The method of claim 28, wherein each of Ca and Cb is an (R) chiral center. 31. The method of claim 28, wherein R is selected from a group consisting of methyl, benzyl and phenyl. 32. The method of claim 31, wherein each of Ra and Rb is independently selected from a group consisting of methyl and phenyl, and each of Rc and Rd is hydrogen. 33. The method of claim 28, wherein Ra and Rb are taken together to form a C4 alkylene chain which together with Ca and Cb forms a 6-membered aliphatic ring. 34. The method of claim 33, wherein R is selected from a group consisting of benzy, p-bromobenzyl, and p-methoxybenzyl. 35. A reagent of the formula wherein X3 is selected from a group consisting of O and C(R4)(R5); each of X1 and X2 is independently selected from a group consisting of O and N—R; each of Ca and Cb is independently selected from a group consisting of an achiral center, an (S) chiral center and an (R) chiral center; Ra and Rb are (i) each independently selected from a group consisting of C1-10 alkyl, C6-10 aryl, C3-9 heteroaryl, or (ii) taken together to form a C3-C4 alkylene chain which together with Ca and Cb forms one of a 5-membered aliphatic ring and a 6-membered aliphatic ring; Rc and Rd are each independently selected from a group consisting of hydrogen, C1-10 alkyl, C6-10 aryl, and C3-9 heteroaryl; R6 is selected from a group consisting of halogen, hydrogen, C1-10 alkyl, C6-10 aryl, C3-9 heteroaryl, C1-10 alkoxy, C6-10 aryloxy, C1-10 dialkylamino, C1-10 alkyl-C6-10 arylamino, C1-10 diarylamino, —O—C(R9)═C(R7)(R8), OSO2CF3 and SR; R is selected from a group consisting of C1-10 alkyl, C6-10 aryl, and C3-9 heteroaryl; and each of R1, R2, R3, R4, R5, R7, R8, and R9 is independently selected from a group consisting of hydrogen, C1-C1-10 alkyl, C6-10 aryl, C3-9 heteroaryl, C1-10 alkoxy, C6-10 aryloxy, C1-10 dialkylamino, C1-10 alkyl-C6-10 arylamino, C1-10 diarylamino, and a halogen. 36. The reagent of claim 35, wherein X3═O. 37. The reagent of claim 35, wherein X3═C(R4)(R5). 38. The reagent of claim 35, wherein each of R1, R2, R3, R4, and R5 is hydrogen, and R6 is chlorine. 39. The reagent of claim 35, wherein X1═X2═O. 40. The reagent of claim 39, wherein the each of Rc and Rd is hydrogen, each of Ra and Rb is 2-methoxy-2-propyl, and each of Ca and Cb is an (R) chiral center. 41. The reagent of claim 35, wherein X1═NR and X2═O. 42. The reagent of claim 41, wherein each of Ca and Cb is an (S) chiral center. 43. The reagent of claim 41, wherein each of Ca and Cb is an (R) chiral center. 44. The reagent of claim 41, wherein R is selected from a group consisting of methyl, benzyl and phenyl. 45. The reagent of claim 44, wherein each of Ra and Rb is independently selected from a group consisting of methyl and phenyl, and each of Rc and Rd is independently selected from a group consisting of methyl and hydrogen. 46. The reagent of claim 41, wherein the reagent is selected from a group consisting of 47. The reagent of claim 35, wherein X1═X2═NR. 48. The reagent of claim 47, wherein each of Ca and Cb is an (S) chiral center. 49. The reagent of claim 47, wherein each of Ca and Cb is an (R) chiral center. 50. The reagent of claim 47, wherein R is selected from a group consisting of methyl, benzyl and phenyl. 51. The reagent of claim 50, wherein each of Ra and Rb is independently selected from a group consisting of methyl and phenyl, and each of Rc and Rd is hydrogen. 52. The reagent of claim 47, wherein Ra and Rb are taken together to form a C4 alkylene chain which together with Ca and Cb forms a 6-membered aliphatic ring. 53. The reagent of claim 52, wherein the reagent is selected from a group consisting of 54. A method for forming a homoallylic alcohol of formula comprising reacting a reagent of formula with an aldehyde of formula R10CHO to form the homoallylic alcohol, wherein: X3 is selected from a group consisting of O and C(R4)(R5); each of X1 and X2 is independently selected from a group consisting of O and N—R; each of Ca and Cb is independently selected from a group consisting of an achiral center, an (S) chiral center and an (R) chiral center; Ra and Rb are (i) each independently selected from a group consisting of C1-10 alkyl, C6-10 aryl, and C3-9 heteroaryl, or (ii) taken together to form a C3-C4 alkylene chain which together with Ca and Cb forms one of a 5-membered aliphatic ring and a 6-membered aliphatic ring; Rc and Rd are each independently selected from a group consisting of hydrogen, C1-10 alkyl, C-10 aryl, and C3-9 heteroaryl; R6 is selected from a group consisting of a halogen, hydrogen, C1-10 alkyl, C6-10 aryl, C3-9 heteroaryl, C1-10 alkoxy, C6-10 aryloxy, C1-10 dialkylamino, C1-10 alkyl-C6-10 arylamino, C1-10 diarylamino, OSO2CF3 and SR; R is selected from a group consisting of C1-10 alkyl, C6-10 aryl, and C3-9 heteroaryl; each of R1, R2, R3, R4, R5 is independently selected from a group consisting of hydrogen, C1-C10 alkyl, C6-10 aryl, C3-9 heteroaryl, C1-10 alkoxy, C6-10 aryloxy, C1-10 dialkylamino, C1-10 alkyl-C6-10 arylamino, C1-10 diarylamino, and halogen; and R10 is selected from a group consisting of C1-10 alkyl, C6-10 aryl, and C3-9 heteroaryl. 55. The method of claim 54, wherein X3═O. 56. The method of claim 54, wherein X3═C(R4)(R5). 57. The method of claim 54, wherein each of R1, R2, R3, R4, and R5 is hydrogen, and R6 is chlorine. 58. The method of claim 54, wherein X1═X2═O. 59. The method of claim 58, wherein the each of Rc and Rd is hydrogen, each of Ra and Rb is 2-methoxy-2-propyl, and each of Ca and Cb is an (R) chiral center. 60. The method of claim 54, wherein X1═NR and X2═O. 61. The method of claim 60, wherein each of Ca and Cb is an (S) chiral center. 62. The method of claim 60, wherein each of Ca and Cb is an (R) chiral center. 63. The method of claim 60, wherein R is selected from a group consisting of methyl, benzyl and phenyl. 64. The method of claim 63, wherein each of Ra and Rb is independently selected from a group consisting of methyl and phenyl, and each of Rc and Rd is independently selected from a group consisting of methyl and hydrogen. 65. The method of claim 60, wherein the reagent is selected from a group consisting of 66. The method of claim 54, wherein X1═X2═NR. 67. The method of claim 66, wherein each of Ca and Cb is an (S) chiral center. 68. The method of claim 66, wherein each of Ca and Cb is an (R) chiral center. 69. The method of claim 66, wherein R is selected from a group consisting of methyl, benzyl and phenyl. 70. The method of claim 66, wherein each of Ra and Rb is independently selected from a group consisting of methyl and phenyl, and each of Rc and Rd is hydrogen. 71. The method of claim 66, wherein Ra and Rb are taken together to form a C4 alkylene chain which together with Ca and Cb forms a 6-membered aliphatic ring. 72. The method of claim 71, wherein the reagent is selected from a group consisting of 73. The method of claim 54, wherein R10 is selected from a group consisting of methyl, t-butyl, phenyl, 2-phenylethyl, (E)-2-phenylethenyl, benzyloxymethyl, cyclohexyl, iso-butyl, and tributylsilyloxymethyl. 74. The method of claim 54, wherein the reagent is reacted with the aldehyde R10CHO in a solvent selected from a group consisting of toluene, tetrahydrofuran, N,N-dimethylformamide, ethyl acetate, dichloromethane, hexane, t-butyl methyl ether, diethylether, acrylonitrile, and benzene. 75. The method of claim 74, wherein the concentration of the aldehyde in the solvent is about 0.2 M. 76. The method of claim 54, wherein the reagent is reacted with the aldehyde in the absence of solvent. 77. A method for forming a compound of the formula comprising reacting a reagent of formula with a compound of formula R12C(R14)═N—X4—CO—R11, wherein: X3 is selected from a group consisting of O and (R4)(R5); X4 is selected from a group consisting of O and NH; each of X1 and X2 is independently selected from a group consisting of O and N—R; each of Ca and Cb is independently selected from a group consisting of an achiral center, an (S) chiral center and an (R) chiral center; Ra and Rb are (i) each independently selected from a group consisting of C1-10 alkyl, C6-10 aryl and C3-9 heteroaryl, or (ii) taken together to form a C3-C4 alkylene chain which together with Ca and Cb forms one of a 5-membered aliphatic ring and a 6-membered aliphatic ring; Rc and Rd are each independently selected from a group consisting of hydrogen, C1-10 alkyl, C6-10 aryl and C3-9 heteroaryl; R6 is selected from a group consisting of halogen, hydrogen, C1-10 alkyl, C6-10 aryl, C3-9 heteroaryl, C1-10 alkoxy, C6-10 aryloxy, C1-10 dialkylamino, C1-10 alkyl-C6-10 arylamino, C1-10 diarylamino, OSO2CF3 and SR; R is selected from a group consisting of C1-10 alkyl, C6-C10 aryl and C3-9 heteroaryl; each of R1, R2, R3, R4, R5 is independently selected from a group consisting of hydrogen, C1-C10 alkyl, C6-10 aryl, C3-9 heteroaryl, C1-10 alkoxy, C6-10 aryloxy, C1-10 dialkylamino, C1-10 alkyl-C6-10 arylamino, C1-10 diarylamino, and halogen; R10 is selected from a group consisting of C1-10 alkyl, C6-10 aryl and C3-9 heteroaryl; R11 is one of hydrogen, C1-10 alkyl, C6-10 aryl and C3-9 heteroaryl; R12 is selected from a group consisting of C1-10 alkyl, C6-10 aryl and C3-9 heteroaryl; and R14 is selected from a group consisting of hydrogen, C1-10 alkyl, C6-10 aryl and C3-9 heteroaryl. 78. The method of claim 77, wherein X3═O. 79. The method of claim 77, wherein X3═C(R4)(R5). 80. The method of claim 77, wherein each of R1, R2, R3, R4, and R5 is hydrogen, and R6 is chlorine. 81. The method of claim 77, wherein X1═X2═O. 82. The method of claim 81, wherein each of Rc and Rd is hydrogen; each of R3 and Rb is 2-methoxy-2-propyl; and each of Ca and Cb is an (R) chiral center. 83. The method of claim 81, wherein X1═NR and X2═O. 84. The method of claim 83, wherein each of Ca and Cb is an (S) chiral center. 85. The method of claim 83, wherein each of Ca and Cb is an (R) chiral center. 86. The method of claim 83, wherein R is selected from a group consisting of methyl, benzyl and phenyl. 87. The method of claim 86, wherein each of Ra and Rb is independently selected from a group consisting of methyl and phenyl, and each of Rc and Rd is independently selected from a group consisting of methyl and hydrogen. 88. The method of claim 83, wherein the reagent is selected from a group consisting of 89. The method of claim 77, wherein X1═X2═NR. 90. The method of claim 89, wherein each of Ca and Cb is an (S) chiral center. 91. The method of claim 89, wherein each of Ca and Cb is an (R) chiral center. 92. The method of claim 89, wherein R is selected from a group consisting of methyl, benzyl and phenyl. 93. The method of claim 92, wherein each of Ra and Rb is independently selected from a group consisting of methyl and phenyl, and each of Rc and Rd is hydrogen. 94. The method of claim 89, wherein Ra and Rb are taken together to form a C4 alkylene chain which together with Ca and Cb forms a 6-membered aliphatic ring. 95. The method of claim 94, wherein the reagent is selected from a group consisting of 96. The method of claim 77, wherein each of R11 and R12 is independently selected from a group consisting of methyl, t-butyl, phenyl, 2-phenylethyl, (E)-2-phenylethenyl, benzyloxymethyl, cyclohexyl, iso-butyl, and tributylsilyloxymethyl. 97. The method of claim 77, wherein the reagent is reacted with the compound of the formula R12C(R14)═N—X4—CO—R11 in a solvent selected from a group consisting of toluene, tetrahydrofuran, N,N-dimethylformamide, ethyl acetate, dichloromethane, hexane, t-butyl methyl ether, diethyl ether, acrylonitrile, and benzene. 98. The method of claim 77, wherein the reagent is reacted with the compound of the formula R12C(R14)═N—X4—CO—R11 in the absence of solvent. 99. A method for forming a first allylation reagent of formula comprising reacting a second allylation reagent of formula with an alcohol HOR13 in the presence of a base to form the first allylation reagent, wherein: each of X1 and X2 is independently selected from a group consisting of O and N—R; each of Ca and Cb is independently selected from a group consisting of an achiral center, an (S) chiral center and an (R) chiral center; Ra and Rb are (i) each independently selected from a group consisting of C1-10 alkyl, C6-10 aryl, and C3-9 heteroaryl, or (ii) taken together to form a C3-C4 alkylene chain which together with Ca and Cb forms one of a 5-membered aliphatic ring and a 6-membered aliphatic ring; Rc and Rd are each independently selected from a group consisting of hydrogen, C1-10 alkyl, C6-10 aryl, and C3-9 heteroaryl; R6 is one of a halogen and OSO2CF3; R is selected from a group consisting of C1-10 alkyl, C6-10 aryl, and C3-9 heteroaryl; each of R1, R2, R3, R4, R5 is independently selected from a group consisting of hydrogen, C1-C10 alkyl, C6-10 aryl, C3-9 heteroaryl, C1-10 alkoxy, C6-10 aryloxy, C1-10 dialkylamino, C1-10 alkyl-C6-10 arylamino, C1-10 diarylamino, and halogen; and R13 is selected from a group consisting of C1-C10 alkyl, C6-10 aryl, and C3-9 heteroaryl. 100. A method for forming a first allylation reagent of formula comprising reacting a second allylation reagent of formula with a lithium enolate of formula Li—O—C(R9)═C(R7)(R8) to form the first allylation reagent, wherein each of X1 and X2 is independently selected from a group consisting of O and N—R; each of Ca and Cb is independently selected from a group consisting of an achiral center, an (S) chiral center and an (R) chiral center; Ra and Rb are (i) each independently selected from a group consisting of C1-10 alkyl, C6-10 aryl, and C3-9 heteroaryl, or (ii) taken together to form a C3-C4 alkylene chain which together with Ca and Cb forms one of a 5-membered aliphatic ring and a 6-membered aliphatic ring; Rc and Rd are each independently selected from a group consisting of hydrogen, C1-10 alkyl, C6-10 aryl, and C3-9 heteroaryl; R6 is one of halogen and OSO2CF3; R is selected from a group consisting of C1-10 alkyl, C6-10 aryl, and C3-9 heteroaryl; and each of R1, R2, R3, R4, R5, R7, R8, and R9 is independently selected from a group consisting of hydrogen, C1-C10 alkyl, C6-10 aryl, C3-9 heteroaryl, C1-10 alkoxy, C6-10 aryloxy, C1-10 dialkylamino, C1-10 alkyl-C6-10 arylamino, C1-10 diarylamino, and a halogen. 101. A method for forming a first reagent of the formula comprising reacting a second reagent of formula with two equivalents of a lithium enolate of formula Li—O—C(R3)═C(R1)(R2) to form the first reagent, wherein each of X1 and X2 is independently selected from a group consisting of O and N—R; each of Ca and Cb is independently selected from a group consisting of an achiral center, an (S) chiral center and an (R) chiral center; Ra and Rb are (i) each independently selected from a group consisting of C1-10 alkyl, C6-10 aryl and C3-9 heteroaryl, or (ii) taken together to form a C3-C4 alkylene chain which together with Ca and Cb forms one of a 5-membered aliphatic ring and a 6-membered aliphatic ring; Rc and Rd are each independently selected from a group consisting of hydrogen, C1-10 alkyl, C6-10 aryl and C3-9 heteroaryl; R is selected from a group consisting of C1-10 alkyl, C6-C10 aryl and C3-9 heteroaryl; and each of R1, R2, R3, is independently selected from a group consisting of hydrogen, C1-C10 alkyl, C6-10 aryl, C3-9 heteroaryl, C1-10 alkoxy, C6-10 aryloxy, C1-10 dialkylamino, C1-10 alkyl-C6-10 arylamino, C1-10 diarylamino, and halogen. 102. A method for forming a diol of formula comprising reacting a reagent of formula with an aldehyde of formula R10CHO to form the diol, wherein: X3 is selected from a group consisting of O and (R4)(R5); each of X1 and X2 is independently selected,from a group consisting of O and N—R; each of Ca and Cb is independently selected from a group consisting of an achiral center, an (S) chiral center and an (R) chiral center; Ra and Rb are (i) each independently selected from a group consisting of C1-10 alkyl, C6-10 aryl, and C3-9 heteroaryl, or (ii) taken together to form a C3-C4 alkylene chain which together with Ca and Cb forms one of a 5-membered aliphatic ring and a 6-membered aliphatic ring; Rc and Rd are each independently selected from a group consisting of hydrogen, C1-10 alkyl C6-10 aryl and C3-9 heteroaryl; R is selected from a group consisting of C1-10 alkyl, C6-C10 aryl and C3-9 heteroaryl; each of R1, R2, R3, R4, R5, R7, R8, and R9 is independently selected from a group consisting of hydrogen, C1-C10 alkyl, C6-10 aryl, C3-9 heteroaryl, C1-10 alkoxy, C6-10 aryloxy,. C1-10 dialkylamino, C1-10 alkyl-C6-10 arylamino, C1-10 diarylamino, and halogen; and R10 is selected from a group consisting of C1-10 alkyl, C6-10 aryl, and C3-9 heteroaryl. 103. A method for forming a compound of the formula comprising reacting a reagent of formula with a compound of formula R12C(R14)═N—X4—CO—R11, wherein: X3 is selected from a group consisting of O and (R4)(5); X4 is selected from a group consisting of O and NH; each of X1 and X2 is independently selected from a group consisting of O and N—R; each of Ca and Cb is independently selected from a group Consisting of an achiral center, an (S) chiral center and an (R) chiral center; Ra and Rb are (i) each independently selected from a group consisting of C1-10 alkyl, C6-10 aryl, and C3-9 heteroaryl, or (ii) taken together to form a C3-C4 alkylene chain which together with Ca and Cb forms one of a 5-membered aliphatic ring and a 6-membered aliphatic ring; Rc and Rd are each independently selected from a group consisting of hydrogen, C1-10 alkyl, C6-10 aryl and C3-9 heteroaryl; R is independently selected from a group consisting of C1-10 alkyl, C6-C10 aryl and C3-9 heteroaryl; each of R1, R2, R3, R4, R5, R7, R8, and R9 is independently selected from a group consisting of hydrogen, C1-C10 alkyl, C6-10 aryl, C3-9 heteroaryl, C1-10 alkoxy, C6-10 aryloxy, C1-10 dialkylamino, C1-10 alkyl-C6-10 arylamino, C1-10 diarylamino, and halogen; R11 is selected from a group consisting of hydrogen, C1-10 alkyl, C6-10 aryl, and C3-9 heteroaryl; R12 is one selected from a group consisting of of C1-10 alkyl, C6-10 aryl and C3-9 heteroaryl; and R14 is selected from a group consisting of hydrogen, C1-10 alkyl, C6-10 aryl, and C3-9 heteroaryl;

This work was supported by Grant No. GM58133 from the National Institutes of Health (NIH). FIELD OF THE INVENTION The present invention relates to reagents which are useful for asymmetric allylations, aldols, and tandem aldol and allylation reactions. In particular, the presente invention relates to cyclic reagents containing a silicon atom which are useful for the preparation by asymmetric allylations, aldols, and tandem aldol and allylation reactions of chiral alcohols and hydrazines. BACKGROUND OF THE INVENTION Asymmetric additions of allyl groups and enolates to the carbonyl (C═O) group of aldehydes and to the C═N group of related electrophilic compounds remains one of the most important and fundamental carbonyl addition reactions for the synthesis of optically active chiral compounds containing a chiral carbon center bonded to an oxygen or nitrogen atom. Such compounds may have utility, for example, as pharmaceutically active compounds, or may be used to prepare other pharmaceutically active compounds. Many highly enantioselective allylation reagents and catalysts have been developed, as described, for example, in Brown, H. C. and Jadhav, P. K., J. Am. Chem. Soc., Vol. 105 (1983), p. 2092; Jadhav, P. K., Bhat, K. S., Perumal P. T. and Brown, H. C., J. Org. Chem., Vol. 51 (1986), p. 432; Racherla, U. S. and Brown, H. C., J. Org. Chem., Vol. 56 (1991), p. 401; Roush, W. R., Walts, A. E. and Hoong, L. K., J. Am. Chem. Soc., Vol. 107 (1985), p. 8186; Roush, W. R. and Banfi, W. L., J. Am. Chem. Soc., Vol. 110 (1988), p. 3979; Hafner, A., Duthaler R. O., Marti, R., Ribs, G., Rothe-Streit, P. and Schwarzenbach, F., J. Am. Chem. Soc., Vol. 114 (1992), p. 2321; Wang, Z., Wang, D. and Sui, X., Chem. Commun. (1996), p. 2261; Wang, D., Wang, Z. G., Wang, M. W., Chen, Y. J., Liu, L. and Zhu, Y., Tetrahedron: Asymmetry, Vol. 10 (1999), p. 327; Zhang, L. C., Sakurai, H. and Kira, M., Chem. Lett. (1997), p. 129. Similarly, highly enantioselective enolate reagents have been developed, as described, for example, in Paterson, I., Lister, M. A. and McClure, C. K., Tetrahedron Lett., vol. 27, (1986), p. 4787; Paterson, I. and Goodman, J. M., Tetrahedron Lett., vol. 30, (1989), p. 997; Paterson, I.,Goodman, J. M., Lister, M. A., Schumann, R. C., McClure, C. K. and Norcross, R. D., Tetrahedron, Vol. 46, (1990), p. 4663; and Cowden, C. J. and Paterson, I., Org. React. Vol. 51, (1997), p. 1. However, several problems have been found to be associated with the allylation and enolate reagents and catalysts of the prior art, including the expense of preparation, the instability of the reagents or the catalysts, the need for using the reagents or the catalysts in situ or shortly after their preparation, the toxicity of the reagents and the byproducts of the reactions of the reagents and the catalysts with aldehydes, and the ease of separation and purification of the reaction products. A generally applicable method for the allylation and the addition of enolates to aldehydes and related electrophilic compounds requires easily and inexpensively formed, stable, and storable reagents and catalysts, reagents and byproducts having little or no toxicity, and easy separation and purification of the products formed. A method combining all these characteristics has until now proven elusive. SUMMARY OF THE INVENTION In accordance with the present invention, there is provided a new class of reagents and method of use of the reagents that solves the above-described problems of the prior art, and there is further provided excellent enantioselectivities in the reaction of the reagents with electrophilic compounds. The invention in a first embodiment is a method for the formation of an allylation reagent of formula The method includes reacting a silane of formula with a compound of formula to form the allylation reagent of formula (1). Each of X1 and X2 is independently O or N—R. Each of Ca and Cb is independently an achiral center, an (S) chiral center or an (R) chiral center. Ra and Rb are (i) each independently C1-10 alkyl, C6-10 aryl or C3-9 heteroaryl, or (ii) taken together to form a C3-C4 alkylene chain which together with Ca and Cb forms a 5-membered or 6-membered aliphatic ring. Rc and Rd are each independently hydrogen, C1-10 alkyl, C6-10 aryl or C3-9 heteroaryl. R6 of formulas (1) and (2) is a halogen, hydrogen, C1-10 alkyl, C6-10 aryl, C3-9 heteroaryl, C1-10 dialkylamino, C1-10 alkyl-C6-10 arylamino, C1-10 diarylamino, or SR. R is C1-10 alkyl, C6-10 aryl or C3-9 heteroaryl. Each of R1, R2, R3, R4, R5 of formulas (1) and (2) is independently hydrogen, C1-C10 alkyl, C6-10 aryl, C3-9 heteroaryl, C1-10 alkoxy, C6-10 aryloxy, C1-10 dialkylamino, C1-10 alkyl-C6-10 arylamino, C1-10 diarylamino, or halogen. The invention in another embodiment is a reagent of formula where X3 is one of O and C(R4)(R5) and X1, X2, Ca, Cb, R, Ra, Rb, Rc, Rd, R1, R2, R3, R4, R5 are as defined above in connection with formulas (1) and (2). R6 in formula (4) is halogen, hydrogen, C1-10 alkyl, C6-10 aryl, C3-9 heteroaryl, C1-10 alkoxy, C6-10 aryloxy, C1-10 dialkylamino, C1-10 alkyl-C6-10 arylamino, C1-10 diarylamino, —O—C(R9)═C(R7)(R8), OSO2CF3 or SR. Each of R7, R8 and R9 are defined in the same way as R1, R2, R3, R4, and R5 in connection with formulas (1) and (2). The invention in another embodiment is a method for the formation of a first reagent of formula The method includes reacting a second reagent of formula with one equivalent of a lithium enolate of the formula Li—O—C(R3)═C(R1)(R2) to form the first reagent. Each of X1 and X2 is independently O or N—R. Each of Ca and Cb is independently an achiral center, an (S) chiral center or an (R) chiral center. Ra and Rb are (i) each independently C1-10 alkyl, C6-10 aryl or C3-9 heteroaryl, or (ii) taken together to form a C3-C4 alkylene chain which together with Ca and Cb forms a 5-membered or 6-membered aliphatic ring. Rc and Rd are each independently hydrogen, C1-10 alkyl, C6-10 aryl or C3-9 heteroaryl. R6 is a halogen, hydrogen, C1-10 alkyl, C6-10 aryl, C3-9 heteroaryl, C1-10 dialkylamino, C1-10 alkyl-C6-10 arylamino, C1-10 diarylamino, O—C(R3)═C(R1)(R2), or SR. R is C1-10 alkyl, C6-10 aryl or C3-9 heteroaryl. Each of R1, R2, and R3, is independently hydrogen, C1-C10 alkyl, C6-10 aryl, C3-9 heteroaryl, C1-10 alkoxy, C6-10 aryloxy, C1-10 dialkylamino, C1-10 alkyl-C6-10 arylamino, C1-10 diarylamino, or halogen. The invention in another embodiment is a method for the formation of an alcohol of formula The method includes reacting a reagent of formula with an aldehyde of formula R10CHO to form the alcohol of formula (7), where X3 is one of O and C(R4)(R5) and X1, X2, Ca, Cb, R, Ra, Rb, Rc. Rd, R1, R2, R3, R4, and R5 are as defined above in connection with formulas (1), (2) and (3). R6 is a halogen, hydrogen, C1-10 alkyl, C6-10 aryl, C3-9 heteroaryl, C1-10 alkoxy, C6-10 aryloxy, C1-10 dialkylamino, C1-10 alkyl-C6-10 arylamino, C1-10 diarylamino, OSO2CF3 or SR. R10 is C1-10 alkyl, C6-10 aryl, or C3-9 heteroaryl. The invention in another embodiment is a method for the formation of a compound of formula The method includes reacting a reagent of formula with a compound of the formula R12C(R14)═N—X4—CO—R11. X3 is one of O and C(R4)(R5). X4 is O or NH. X1, X2, Ca, Cb, R, Ra, Rb, Rc. Rd, R1, R2, R3, R4, and R5 are as defined above in connection with formulas (1), (2) and (3). R6 is a halogen, hydrogen, C1-10 alkyl, C6-10 aryl, C3-9 heteroaryl, C1-10 alkoxy, C6-10 aryloxy, C1-10 dialkylamino, C1-10 alkyl-C6-10 arylamino, C1-10 diarylamino, OSO2CF3 or SR. R11 is hydrogen, C1-10 alkyl, C6-10 aryl, or C3-9 heteroaryl, R12 is C1-10 alkyl, C6-10 aryl or C3-9 heteroaryl. R14 is hydrogen, C1-10 alkyl, C6-10 aryl, or C3-9 heteroaryl. The invention in another embodiment is a method for the formation of a first allylation reagent of formula The method includes reacting a second allylation reagent of formula with an alcohol of the formula H—O—R13 in the presence of a base to form the first allylation reagent of formula (11). X1, X2, Ca, Cb, R, Ra, Rb, Rc , Rd, R1, R2, R3, R4, and R5, are as defined above in connection with formulas (1), (2) and (3). R6 is a halogen or OSO2CF3. R13 is C1-C10 alkyl, C6-10 aryl, or C3-9 heteroaryl. The invention in another embodiment is a method for the formation of a first allylation reagent of formula The method includes reacting a second allylation reagent of formula with a lithium enolate of the formula Li—O—C(R9)═C(R7)(R8) to form the first allylation reagent. X1, X2, Ca, Cb, R, Ra, Rb, Rc, Rd, R1, R2, R3, R4, R5, R7, R8 and R9 are as defined above in connection with formulas (1), (2) and (3). R6 is a halogen or OSO2CF3. The invention in another embodiment is a method for the formation of a first reagent of formula The method includes reacting a second reagent of formula with two equivalents of a lithium enolate of the formula Li—O—C(R3)═C(R1)(R2) to form the first reagent of formula (15). X1, X2 and R are as defined above in connection with formulas (1), (2) and (3). Each of Ca and Cb is independently an achiral center, an (S) chiral center or an (R) chiral center. Ra and Rb are (i) each independently C1-10 alkyl, C6-10 aryl or C3-9 heteroaryl, or (ii) taken together to form a C3-C4 alkylene chain which together with Ca and Cb forms a 5-membered or 6-membered aliphatic ring. Rc and Rd are each independently hydrogen, C1-10 alkyl, C6-10 aryl or C3-9 heteroaryl. Each of R1, R2, and R3, is independently hydrogen, C1-C10 alkyl, C6-10 aryl, C3-9 heteroaryl, C1-10 alkoxy, C6-10 aryloxy, C1-10 dialkylamino, C1-10 alkyl-C6-10 arylamino, C1-10 diarylamino, or halogen. The invention in another embodiment is a method for the formation of a diol of formula The method includes reacting a reagent of formula with an aldehyde of formula R10CHO to form the diol of formula (17). X3 is one of O and C(R4)(R5). X1, X2, Ca, Cb, R, Ra, Rb, Rc, Rd, R1, R2, R3, R4, R5, R7, R8 and R9 are as defined above in connection with formulas (1), (2), (3) and (4). R10 is C1-10 alkyl, C6-10 aryl, or C3-9 heteroaryl. The invention in another embodiment is a method for the formation of a compound of formula The method includes reacting a reagent of formula with a compound of the formula R12C(R14)═N—X4—CO—R11 to obtain the compound of formula (19). X3 is one of O and C(R4)(R5). X4 is one of NH and O. X1, X2, Ca, Cb, R, Ra, Rb, Rc. Rd, R1, R2, R3, R4, R5, R7, R8 and R9 are as defined above in connection with formulas (1), (2), (3) and (4). R11 is hydrogen, C1-10 alkyl, C6-10 aryl, or C3-9 heteroaryl. R12 is C1-10 alkyl, C6-10 aryl or C3-9 heteroaryl. R14 is hydrogen, C1-10 alkyl, C6-10 aryl, or C3-9 heteroaryl. In the foregoing formulas (1)-(20), the double bond between C(R3) and C(R1)(R2), the double bond between X and C(R3), and the double bond between C(R9) and C(R8)(R7) may each be an (E) double bond, a (Z) double bond, or a double bond that does not exhibit (E)/(Z) isomerism. In the compound of the formula R12C(R14)═N—X4—CO—R11, the double bond between C and N may be an (E) double bond or a (Z) double bond. BRIEF DESCRIPTION OF THE FIGURES FIG. 1 shows the 1H NMR spectrum of allylation reagent 3. FIG. 2 shows the 1H NMR spectrum of allylation reagent 10. FIG. 3 shows a chiral HPLC analysis of the alcohol obtained by allylation of benzaldehyde with allylation reagent 3 and of the corresponding racemic alcohol. FIG. 4 shows a chiral HPLC analysis of the alcohol obtained by allylation of cinnamaldehyde with allylation reagent 3 and of the corresponding racemic alcohol. FIG. 5 shows a chiral HPLC analysis of the alcohol obtained by allylation of dihydrocinnamaldehyde with allylation reagent 3 and of the corresponding racemic alcohol. FIG. 6 shows a 19F NMR (C6D6, 282 MHz) spectrum of the Mosher ester of the alcohol obtained by allylation of isovaleraldehyde with allylation reagent 3 and of the corresponding racemic alcohol. FIG. 7 shows a 19F NMR (C6D6, 282 MHz) spectrum of the Mosher ester of the alcohol obtained by allylation of cyclohexanecarboxaldehyde with allylation reagent 3 and of the corresponding racemic alcohol. FIG. 8 shows a 19F NMR (C6D6, 282 MHz) spectrum of the Mosher ester of the alcohol obtained by allylation of pivaldehyde with allylation reagent 3 and of the corresponding racemic alcohol. FIG. 9 shows a 19F NMR (C6D6, 282 MHz) spectrum of the Mosher ester of the alcohol obtained by allylation of benzyloxyacetaldehyde with allylation reagent 3 and of the corresponding racemic alcohol. FIG. 10 shows a 19F NMR (C6D6, 282 MHz) spectrum of the Mosher ester of the alcohol obtained by allylation of tert-Butyldimethylsilyloxyacetaldehyde with allylation reagent 3 and of the corresponding racemic alcohol. FIG. 11 shows the 1H NMR spectrum of allylation reagent (R,R)-21. FIG. 12 shows a chiral HPLC analysis of the alcohol obtained by allylation of 3-(Benzyloxy)propionaldehyde with allylation reagent (R,R)-21 and of the corresponding racemic alcohol. FIG. 13 shows a chiral HPLC analysis of the alcohol obtained by allylation of 3-p-anisaldehyde with allylation reagent (R,R)-21 and of the corresponding racemic alcohol. FIG. 14 shows a chiral HPLC analysis of the alcohol obtained by allylation of 3-p-CF3-benzaldehyde with allylation reagent (R,R)-21 and of the corresponding racemic alcohol. FIG. 15 shows a chiral HPLC analysis of the alcohol obtained by allylation of 3-trans-2-hexenal with allylation reagent (R,R)-21 and of the corresponding racemic alcohol. DETAILED DESCRIPTION OF THE INVENTION The term “alkyl”, as used herein, unless otherwise indicated, refers to a monovalent aliphatic hydrocarbon radical having a straight chain, branched chain, monocyclic moiety, or polycyclic moiety or combinations thereof, wherein the radical is optionally substituted at one or more carbons of the straight chain, branched chain, monocyclic moiety, or polycyclic moiety or combinations thereof with one or more substituents at each carbon, where the one or more substituents are independently C1-C10 alkyl, C1-C10 alkoxy, C6-10 aryl, C3-9 heteroaryl, C6-10 aryloxy, C1-C10 dialkylamino, or silyloxy in which the silicon has three substituents, where each substituent is independently hydrogen, C1-10 alkyl, C6-10 aryl or C3-9 heteroaryl, or halogen. The alkyl group may contain one or more carbon-carbon double bonds, one or more carbon-carbon triple bonds, or a combination thereof Examples of “alkyl” groups include methyl, ethyl, propyl, isopropyl, butyl, iso-butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, norbomyl, methoxymethyl, phenylmethyl, 4-bromophenylmethyl, 4-methoxyphenylmethyl, phenoxymethyl, dimethylaminomethyl, chloromethyl, 2-phenylethyl, (E)- and (Z)-2-phenylethenyl (Ph-CH═CH—), benzyloxymethyl, and the like. The term “halogen”, as used herein, means chlorine (Cl), fluorine (F), iodine (I) or bromine (Br). The term “alkoxy”, as used herein, means “alkyl-O—”, wherein “alkyl” is defined as above and O represents oxygen. Examples of “alkoxy” groups include methoxy, ethoxy, n-butoxy, tert-butoxy, and alkoxy groups in which the alkyl group is halogenated, such as alkoxy groups in which the alkyl group is fluorinated, including, for example, trifluoroethoxy and 1-trifluoromethyl-2-trifluoroethoxy. The term “alkylthio”, as used herein, means “alkyl-S—”, wherein “alkyl” is defined as above and S represents sulfur. Examples of “alkylthio” groups include methylthio, ethylthio, n-butylthio, and tert-butylthio. The term “aryl”, as used herein, unless otherwise indicated, includes an organic radical obtained from an aromatic hydrocarbon by removal of one hydrogen from a carbon of the aromatic hydrocarbon, wherein the radical is optionally substituted at between one and three carbons with a substituent at each carbon, where the substituent at each carbon is independently C1-C10 alkyl, C1-C10 alkoxy, C6-10 aryl, C6-10 aryloxy, C1-C10 dialkylamino, or halogen. Examples of “aryl” groups include phenyl, 1-naphthyl, 2-naphthyl, o-, m-, and p-methylphenyl, o-, m-, and p-methoxyphenyl, o-, m-, and p-diphenyl, o-, m-, and p-phenoxyphenyl, and o-, m-, and p-chlorophenyl. The term “heteroaryl”, as used herein, unless otherwise indicated, includes an organic radical obtained from a heteroaromatic hydrocarbon having a heteroaromatic ring and one or two heteroatoms in the heteroaromatic ring by removal of one hydrogen from a carbon of the heteroaromatic hydrocarbon, wherein one or two heteroatoms are selected from the group consisting of O, N and S the radical is optionally substituted at between one and three carbons, at the one or two heteroatoms, or at a combination thereof with a substituent at each carbon, heteroatom or combination thereof, where the substituent is independently C1-C10 alkyl, C1-C10 alkoxy, C6-10 aryl, C6-10 aryloxy, C1-C10 dialkylamino, C10 alkoxycarbonyl, or halogen. Examples of “heteroaryl” groups include 2-furyl, 3-furyl, 2-thiophenyl, 3-indolyl, 3-(N-t-butoxycarbonyl)-indolyl, 2-pyridyl, 3-pyridyl, 2-chloro-5-pyridyl, 2-pyrrolyl and 2-(N-t-butoxycarbonyl)-pyrrolyl. The term “aryloxy”, as used herein, means “aryl-O—”, wherein “aryl” is defined as above and O represents oxygen. Examples of “aryloxy” groups include phenoxy, 1-naphthoxy, and 2-naphthoxy. The term “dialkylamino”, as used herein, means “alkyl-N-alkyl”, wherein “alkyl” is defined as above and N represents nitrogen. The two alkyl groups in the dialkylamino group may be the same or different. The term “C1-10 dialkylamino” as used herein is intended to denote a dialkylamino group in which each of the two alkyl groups is a C1-10 alkyl group. Examples of “dialkylamino” groups include dimethylamino, diethylamino, and ethylmethylamino. The term “alkylarylamino”, as used herein, means “alkyl-N-aryl”, wherein “alkyl” and “aryl” are defined above and N represents nitrogen. The term “C1-10 alkyl-C6-10 arylamino” as used herein is intended to denote an alkylarylamino group in which the alkyl group is a C1-10 alkyl group and the aryl group is a C6-10 aryl group. An example of “alkylarylamino” group is methylphenylamino. The term “diarylamino”, as used herein, means “aryl-N-aryl”, wherein “aryl” is defined as above and N represents nitrogen. The two aryl groups may be the same or different. The term “C6-10 diarylamino” as used herein is intended to denote a diarylamino group in which each of the two aryl groups is a C6-10 aryl group. An example of a “diarylamino” group is diphenylamino. The term “alkylene chain” as used herein, unless otherwise indicated, refers to a monovalent aliphatic hydrocarbon diradical having a straight chain, branched chain, monocyclic, or polycyclic moiety or combinations thereof, wherein the diradical is optionally substituted at one or more carbons with one or more substituents at each carbon, where the one or more substituents are independently C1-C10 alkyl, C1-C10 alkoxy, C6-10 aryl, C6-10 aryloxy, C1-C10 dialkylamino, or halogen. The alkylene chain may contain one or more carbon-carbon double bonds. Examples of alkylene chains include —CH2—CH2—CH2—, —CH2—CH2—CH2—CH2—, and —CH2—CH═CH—CH2—. The term “base” as used herein, unless otherwise indicated, refers to a compound capable of removing a proton from an acidic group such as an —OH group. Exemplary bases include mono-, di-, and trialkylamines, such as, for example, diazabicycloundecene (DBU), diazabicyclononene (DBN) and triethylamine. Exemplary silanes which may react with compounds of formula (3) according to the method of the invention include allyltrichlorosilane, allylmethyldichlorosilane, allylphenyldichlorosilane, and silanes having the formula CH2═CH—CH2SiCl2Y, where Y═I, Br, F, OSO2CF3, C1-10 alkoxy, C6-10 aryloxy, C1-10 dialkylamino, or C1-10 alkylthio. In an exemplary embodiment of the invention, Ca and Cb are achiral centers in the compound of the formula (3) and the reagents of the invention are achiral compounds. In this embodiment, the diols formed from the reagents of the invention according to the method of the invention are formed diastereoselectively. In another exemplary embodiment of the invention, Ca and Cb are chiral centers in the compound of the formula (3) and the reagents of the invention are chiral compounds. In this embodiment, the homoallylic alcohols and the diols formed from the reagents of the invention according to the method of the invention are formed enantioselectively, and the diols are also formed diastereoselectively. As used herein, the term “enantioselectively” refers to forming a first of two enantiomers in an amount in excess of the second enantiomer. As used herein, the term “diastereoselectively” refers to forming a first of two or more diastereomers an amount in excess of the remaining diastereomer or diastereomers. The term “enantiomeric excess” denotes the amount by which the first enantiomer is in excess of the second enantiomer. The term “diastereomeric excess” denotes the amount by which the first diastereomer is in excess of the remaining diastereomer or diastereomers. The compounds of formula (3) may include, for example, compounds in which Ra and Rb are independently methyl or phenyl, and in which Rc and Rd are independently methyl or hydrogen. For example, the compounds of formula (3) include aminoalcohols (1S,2S)-pseudoephedrine, (1R,2R)-pseudoephedrine. The compounds of formula I also include the aminoalcohols shown in Chart 1, which may react with, for example, allyltrichlorosilane to give the corresponding reagents. Exemplary aminoalcohols further include compounds of the formula (3) in which each of Ra and Rb is independently methyl or phenyl, X2═O and X1═NR, where R is methyl, benzyl, or phenyl. Exemplary compounds of formula (3) also include diols, including pinacol ((CH3)2COH)2 and chiral diols such as, for example, diol 28, having the following formula: Reaction of 28 with allyltrichlorosilane leads to the formation of chiral reagent 29, as shown in the following equation. The compounds of formula (3) also include, for example, compounds in which Ra and Rb taken together form a C4 alkylene chain which together with Ca and Cb forms a 6-membered aliphatic ring. For example, compounds of formula (3) include the diamine (1R,2R)-N,N-Dibenzyl-cyclohexane-1,2-diamine. In one embodiment, the reaction between the silane and the compound of formula (3) takes place in the absence of a catalyst. The reaction may also take place in the absence of an additional reagent. In another embodiment, the reaction between the silane and the compound of formula I takes place in the presence of a catalyst. In an exemplary embodiment of the invention, in the reagent having the formula (10) X3═C(R4)(R5) and the reagent is an allylation reagent. The allylation reagent may be a stable compound which does not decompose when stored at a temperature lower or equal to 25° C. for a period of time of up to several weeks, such as, for example, a period of time of two months. As an example, when allyltrichlorosilane was treated with the diol pinacol and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in CH2Cl2, allylation reagent 1 was formed in accordance with Scheme 1. Compound 1 was purified by distillation and obtained with 70% yield. As another example, the reaction of the aminoalcohol (1S,2S)-pseudoephedrine with allyltrichlorosilane and Et3N in CH2Cl2 allowed the isolation of chiral allylation reagent 3 as an approximately 2:1 mixture of diastereomers with 88% yield, as shown in Scheme 1. 3 may be purified by distillation. Reagent 3 is stable and may be stored for several weeks without appreciable decomposition. The 1H NMR spectrum of reagent 3, which is shown in FIG. 1, is in agreement with the structure of reagent 3. Reagent 3 is available in both enantiomeric form, which may be obtained by reaction with allyltrichlorosilane of (1S,2S)-pseudoephedrine and of (1R,2R)-pseudoephedrine, respectively, both of which are inexpensive starting materials. The reaction between the reagent having formula (8) and the aldehyde R10CHO may be performed using a solvent which may be, for example, toluene, tetrahydrofuran (THF), N,N-dimethylformamide (DMF), ethyl acetate (EtOAc), dichloromethane (CH2Cl2), hexane, t-butyl methyl ether (t-BuOMe), diethyl ether (Et2O), acetonitrile (CH3CN), and benzene. In a preferred embodiment, the solvent is toluene. In an exemplary embodiment, the concentration of the aldehyde in the solvent may range from 0.05 M to 0.5 M. For example, a concentration of about 0.2 M aldehyde may be used. In another exemplary embodiment, the reaction may be performed in the absence of solvent. The reaction may be performed at a temperature ranging from about −78° C. to about 25° C. In a preferred embodiment, the temperature is about −10° C. The reaction is preferably performed in the absence of a catalyst. The group R10 in the aldehyde, which is a C1-10 alkyl or C6-10 aryl group, may be, for example, a methyl group, a t-butyl group, or a phenyl group. When the reagent is an allylation reagent (X═C(R4)(R5)), the product of the reaction is a homoallylic alcohol. As an example, the reaction of reagent 1 with benzaldehyde (R10=phenyl) gave alcohol 2, as shown in Scheme 2, in racemic form. The reaction of reagent 3 with benzaldehyde in benzene at room temperature gave the S enantiomer of alcohol 2 (2(S)) with 81% enantiomeric excess (ee), in accordance with Scheme 2. Reagent 3 may be reacted with several other exemplary aldehydes, as shown in Scheme 3. Thus, for example, dihydrocinnamaldehyde was allylated to give alcohol 4(R) with 88% ee, cinnamaldehyde to give alcohol 5(S) with 78% ee, benzyloxyacetaldehyde to give alcohol 6(S) with 88% ee and cyclohexanecarboxaldehyde to give alcohol 7(S) with 86% ee. In each case, the chiral alcohol is readily isolated upon completion of the allylation reaction, which typically requires about 12-16 hours, by adding 1 M HCl and ethyl acetate to the reaction mixture. The resulting mixture is stirred for 15 minutes. An aqueous phase and an organic phase are formed. The aqueous phase and the organic phase are separated. The organic phase is then concentrated to give the chiral alcohol. The pseudoephedrine originally used to form reagent 3 according to Scheme 2 is regenerated upon addition of the 1 M HCl, and remains in the aqueous phase after the aqueous phase and the organic phase are separated. The pseudoephedrine may be recovered from the aqueous phase and used to prepare additional amounts of reagent 3. FIGS. 3-5 illustrate chiral high performance liquid chromatography (HPLC) analyses of the alcohols obtained by allylation with allylation reagent 3 of benzaldehyde, cinnamaldehyde and dihydrocinnamaldehyde, respectively. In each of FIGS. 3-5, the chiral HPLC analysis of the corresponding racemic alcohol is also shown. FIGS. 6-10 show the 19F NMR (C6D6, 282 MHz) spectra of the Mosher esters of the alcohols obtained by allylation with allylation reagent 3 of isovaleraldehyde, cyclohexanecarboxaldehyde, pivaldehyde, benzyloxyacetaldehyde and tert-butyldimethylsilyloxyacetaldehyde, respectively. As shown in each of FIGS. 3-10, one optical isomer of the alcohol product is formed in excess of the other optical isomer, thereby showing that each reaction is enantioselective. The aldehyde:reagent ratio may vary from about 1.5:1 to about 5:1, which is an exemplary range of ratios for the reaction of inexpensive aldehydes, or the aldehyde:reagent ratio may be about 1:1.5, which is an exemplary ratio for expensive aldehydes. In an exemplary embodiment of the invention, the asymmetric allylations shown in Schemes 2 and 3 may be performed using 1.5 equivalents of reagent 3 for every equivalent of the aldehyde. Additional exemplary chiral allylation reagents include reagents 8 and 9, which may be formed in accordance with Scheme 4, and which react with benzaldehyde to give 1-phenyl-3-buten-1-ol with an enantioselectivity of 42% and 58%, respectively. The allylation reagents of the invention may also be formed from diamines, including chiral 1,2-diamines. Exemplary chiral diamines include diamines having the formula (3) in which X2 and X1 are the same group NR, where R is methyl, benzyl, or phenyl; alternatively, X2 and X1 may be two different groups NR′ and NR″, where each of R′ and R″ is independently C1-10 alkyl, C6-10 aryl, or C3-9 heteroaryl. For example, the reaction of (1R,2R)-N,N-Dibenzyl-cyclohexane-1,2-diamine with allyltrichlorosilane and DBU (diazabicycloundecene) in CH2Cl2 gave chiral allylation reagent 10, as shown in Scheme 5, with 99% crude yield and in sufficient purity for use in the allylation reaction. The 1H NMR spectrum of reagent 10, shown in FIG. 2, is in agreement with the structure of reagent 10. Reaction of reagent 10 with benzaldehyde in benzene for 72 hours led to the production of alcohol 2(S) in 51% yield and 90% ee. Accordingly, the reaction of reagent 10 with aromatic and conjugated aldehydes provides high enantioselectivity. In the allylation reagents formed from chiral 1,2-diamines, each nitrogen atom of the 1,2-diamine fragment may be substituted with an arylmethyl (Ar—CH2—) group in which the aryl group may be, for example, a phenyl group having a substituent para to the CH2 group. For example, as shown in Table 1, the arylmethyl group may be p-bromophenylmethyl or p-methoxyphenylmethyl. The 1H NMR spectrum of allylation reagent (R,R)-21, in which the arylmethylgroup is p-bromophenylmethyl, is shown in FIG. 11. FIGS. 12-15 show chiral HPLC analyses of the alcohols obtained by allylation with allylation reagent (R,R)-21 of 3-(Benzyloxy)propionaldehyde, p-anisaldehyde, p-CF3-benzaldehyde and trans-2-bexenal, respectively. In each of FIGS. 12-15, the chiral HPLC analysis of the corresponding racemic alcohol is also shown. Each of FIGS. 12-15 shows that one optical isomer of the alcohol product is formed in excess of the other optical isomer, thereby showing that each reaction is enantioselective. The reaction of allylation reagent (R,R)-21 with the aldehydes shown in Tables 2 and 3, proceeds with high yield and enantioselectivity. Moreover, as shown in Scheme 6, Aldehyde 22 reacts with reagents (R,R)-21 and (S,S)-21 to give, respectively, syn β-benzyloxy alcohol 23 and anti β-benzyloxy alcohol 24. TABLE 1 Optimization of the Diamine Auxiliary. entry[a] X R yield(%)[b] ee(%)[c] H PhCH2CH2 79 96 H Ph 61 94 OMe PhCH2CH2 77 98 Br PhCH2CH2 90 98 Br Ph 69 98 [a]Reactions run with silane (1.0 equiv) and aldehyde (1.0 equiv) in CH2Cl2 at −10° C. for 20 h. [b]Isolated yield. [b]Determined by chiral HPLC analysis or by the Mosher ester method. See the supporting information. TABLE 2 Enantioselective Allylation of Aliphatic Aldehydes. entry[a] aldehyde product yield(%)[b] ee(%)[c] 90 98 80[d] 96 93 96 67 97 87 98 61 98 [a]Reactions run with silane 3 (1.0 equiv) and aldehyde (1.0 equiv) in CH2Cl2 at −10° C. for 20 h. [b]Isolated yield. [c]Determined by chiral HPLC analysis or by the Mosher ester method. See the supporting information. [d]Due to product volatility, an altermative workup and purification was employed. See the supporting information. TABLE 3 entry[a] aldehyde product yield(%)[b] ee(%)[c] 69 98 [d] 62 96 66 96 [e] 66 96 [e] 71[f] 95 [a]Reactions: run with silane 3 (1.0 equiv) and aldehyde (1.0 equiv) in CH2Cl2 at −10° C. for 20 h. [b]Isolated yield. [c]Determined by chiral HPLC analysis or by the Mosher ester method. See the supporting information. [d]Reaction run for 60 h. [e]Reaction run at 8° C. for 72 h. [f]Due to product volatility, an alternative workup and purification was employed. See the supporting information. In another embodiment of the invention, the reagent is an allylation reagent and has formula (11) where OR13 is an alkoxy group, and R13 is C1-C10 alkyl, C6-10 aryl, or C3-9 heteroaryl. The reagent may be formed, for example, by the reaction of an alcohol HOR13 with allylation reagent 3 in the presence of a base. The base may be an amine, such as, for example, triethylamine. Exemplary allylation reagents containing an alkoxy group include reagents where the alkoxy group OR13 is methoxy, isopropoxy, or butoxy. For example, the reaction of allylation reagent 25, in which OR13 is isopropoxy, with 3-phenylpropanal gives the homoallylic alcohol with 94% ee, as shown in Scheme 7: In another embodiment of the invention, a compound of formula is formed by reacting a reagent of formula (4) with a compound of formula R12C(R14)═N—X4—CO—R11. In the compound of formula R12C(R14)═N—X4—CO—R11, R12 may be, for example, methyl, t-butyl, phenyl, 2-phenylethyl, (E)-2-phenylethenyl, benzyloxymethyl, cyclohexyl, iso-butyl, or tributylsilyloxymethyl. In the same compound, R11 and R14 may be, for example, hydrogen methyl, t-butyl, phenyl, 2-phenylethyl, (E)-2-phenylethenyl, benzyloxymethyl, cyclohexyl, iso-butyl, or tributylsilyloxymethyl. The reagent may be an allylation reagent (X3═C(R4)(R5)). For example, the reaction of the (S,S)-allylation reagent 26 with Ph-CH═N—NH—CO—CH3 gives compound 27 in 98% ee and 80% yield, as shown in Scheme 8: may be a reagent in which X3═O. This reagent may be prepared by reacting a second reagent having formula with one equivalent of a lithium enolate of the formula Li—O—C(R3)═C(R1)(R2). The second reagent may in turn be prepared by a compound having formula (3) with a silane having the formula SiCl3R6, which may be, for example, tetrachlorosilane. The reagent having formula (5) may react with an aldehyde R10—CHO to form a compound having formula The reaction may be performed under similar conditions to those used for the reaction of R10—CHO with an allylation reagent. Similarly, the reagent having formula (5) may react with a compound of the formula R12C(R14)═N—X4—CO—R11 to form a compound having formula The reaction may be performed under similar conditions to those used for the reaction of a compound of the formula R12C(R14)═N—X4—CO—R11 with an allylation reagent. In another embodiment of the invention, a reagent having formula (18) is reacted with an aldehyde to give a diol. Without wishing to be bound by any theory or mechanism, it is believed that the formation of the diol takes place according to Scheme 9, in which the enol terminal carbon attacks the aldehyde to form aldol addition intermediate A, which further undergoes a diastereoselective intramolecular allylation to give a diol having two chiral centers. The reagent may be, for example, an allylation reagent containing an enol group and having formula which may be formed by reacting (R7)(R8)C═C(R9)OLi with an allylation reagent of formula (12) where R6 is halogen or —OSO2CF3. As an example, the substituents R7, R8 and R9 may each be independently hydrogen, methyl, or phenyl. The allylation reagent containing an enol group may be formed by treating allylation reagent 1 with a lithium enolate, which may be generated, for example, by treatment of a vinyltrimethoxysilane of the formula R7R8C═CR9OSiMe3 with methyllithium in ether. For example, treatment of H2C═CHOSiMe3 with methyllithium in ether gives acetaldehyde lithium enolate, which reacts with reagent 1 to give allylenolsilane reagent 11 with 72% yield, as shown in Scheme 10. Reagent 11 may be distilled to purity, and has a shelf-life of at least several weeks without noticeable decomposition. When treated with benzaldehyde in benzene at 50° C. for 8 hours, reagent 11 reacted to form diol 12 with 66% yield as an 8:1 syn:anti mixture of diastereomers. The direct allylation product 2 was also obtained with 13% yield. The reaction of 11 with cyclohexanecarboxaldehyde for 13 hours gave diol 13 with 56% yield as a 10:1 syn:anti mixture of diastereomers. The allylation product 7 was also obtained with 15% yield, as shown in Scheme 10. The allylation reagent may be reacted with the aldehyde R10CHO to give a diol in a solvent, which may be, for example, toluene, tetrahydrofuran, N,N-dimethylformamide, ethyl acetate, dichloromethane, hexane, t-butyl methyl ether, diethyl ether, acrylonitrile, or benzene. In an exemplary embodiment, the concentration of the aldehyde in the solvent may range from 0.05 M to 0.5 M. For example, a concentration of about 0.2 M aldehyde may be used. In another exemplary embodiment, the reaction may be performed in the absence of solvent. Exemplary aldehydes include aldehydes where Rio is methyl, t-butyl, phenyl, 2-phenylethyl, (E)-2-phenylethenyl, benzyloxymethyl, cyclohexyl, iso-butyl, or tributylsilyloxymethyl. As another example, trans-crotylenolsilane 14 reacted with cyclohexanecarboxaldehyde according to the equation shown in Scheme 11 to form diol 15, in which 3 new chiral centers are created, in 45% yield and >10:1 diastereoselectivity. No crotylation product analogous to 7 was obtained (see Scheme 10). Without wishing to be bound by any mechanism or theory, it is believed that the trans-disposed methyl group of 14 slows the rate of transfer of the crotyl group, and that therefore no crotyl group transfer occurs until after the formation of an aldol addition intermediate, in accordance with Scheme 9. As another example, shown in Scheme 11, allyl-cis-enolsilane 16 reacted with cyclohexanecarboxaldehyde to give a 10:3:1 mixture of diastereomers with 60% yield. Diol 17 was shown to be the major diastereomer. An allylation reagent containing an enol group may also be formed, for example, by treating allylation reagent 29, formed from the reaction of chiral diol 28 with allyltrichlorosilane as previously discussed, in connection with equation (I), with a lithium enolate. For example, allylation reagent 30 may be formed as shown in Scheme 12. When allylation reagent 30 is reacted with benzaldehyde, the corresponding diol is formed in 70% yield and 68% ee. The reagent which reacts with an aldehyde to give a diol may be a reagent containing two enol groups and having formula (15) In one embodiment of the invention, the group C(R9)═C(R8)(R7) is identical to the group C(R3)═C(R1)(R2). In this embodiment, the reagent may be formed by reacting a second reagent of the formula (6) with two equivalents of a lithium enolate of the formula Li—)—C(R3)═C(R1)(R2), or by reacting a third reagent of formula (5) where R6 is a halogen or —OSO2CF3, with one equivalent of a lithium enolate of formula Li—O—C(R3)═C(R1)(R2). The reagent containing two enol groups may react with an aldehyde R10—CHO to form a diol under similar conditions to those used for the reaction of R10—CHO with an allylation reagent containing an enol group. In another embodiment, a compound of formula (19) is formed by reacting a reagent of formula (20) with a compound of the formula R12C(R14)═N—X4—CO—R11 to form the compound of formula (19). The reagent of formula (20) may be an allylation reagent containing an enol group (X3═C(R4)(R5)) or a reagent containing two enol groups (X3═O). In an exemplary embodiment where X3═O, the two enol groups O—C(R9)═C(R8)(R7) and O—C(R3)═C(R1)(R2) are identical. The reagent may be reacted with the compound of the formula R12C(R14)═N—X4—CO—R11 in a solvent such as toluene, tetrahydrofuran, N,N-dimethylformamide, ethyl acetate, dichloromethane, hexane, t-butyl methyl ether, diethyl ether, acrylonitrile, or benzene. In an exemplary embodiment, the concentration of the compound of the formula R12C(R4)═N—X4—CO—R11 in the solvent may range from 0.05 M to 0.5 M. For example, a concentration of about 0.2 M of compound of the formula R12C(R14)═N—X4—CO—R11 may be used. In another exemplary embodiment, the reaction may be performed in the absence of solvent. Examples of the compound of the formula R12C(R14)═N—X4—CO—R11 include compounds where R12 is methyl, t-butyl, phenyl, 2-phenylethyl, (E)-2-phenylethenyl, benzyloxymethyl, cyclohexyl, iso-butyl, or tributylsilyloxymethyl, and each of R11 and R14 is independently hydrogen, methyl, t-butyl, phenyl, 2-phenylethyl, (E)-2-phenylethenyl, benzyloxymethyl, cyclohexyl, iso-butyl, or tributylsilyloxymethyl. The invention may be further described by the following examples, which are illustrative of the invention but which are not intended to define the scope of the invention in any way. EXAMPLES Preparation of (4S,5S)-2-Allyl-2-chloro-3,4-dimethyl-5-phenyl-[1,3,2]oxazasilolidine: To a cooled (0° C.) solution of allyltrichlorosilane (101 mL, 0.696 mol) in methylene chloride (1.8 L) under argon was added triethylamine (170 mL, 1.21 mol). (1S,2S)-pseudoephedrine (100 g, 0.605 mol) was then added portionwise over 30 min, to maintain internal temperature below 15° C. After the addition was complete the mixture was stirred for 12 hours at ambient temperature. The methylene chloride was removed by distillation and the residue was diluted with pentane (1.5 L). The mixture was vigorously stirred for 12 hours to ensure complete precipitation of the triethylamine salts. Filtration of the resulting suspension through a pad of celite and concentration of the filtrate by distillation afforded the crude product as a pale yellow oil. Purification by distillation under reduced pressure (bp˜120 C, 5 mm Hg) provided 149 g (92%) of (4S, 5S)-2-Allyl-2-chloro-3,4-dimethyl-5-phenyl-[1,3,2]oxazasilolidine as a ˜2:1 mixture of diastereomers. Preparation of (4R,5R)-2-(cis)-but-2-enyl-2-chloro-3,4-dimethyl-5-phenyl-[1,3,2]oxazasilolidine: To a cooled (0° C.) solution of cis-but-2-enyl-trichlorosilane (7.0 g, 37 mmol) in methylene chloride (80 mL) was added triethylamine (8.75 mL, 63 mmol). (1R,2R)-psuedoephedrine (5.20 g, 31 mmol) was added portionwise and the mixture was allowed to stir for 12 hours. The methylene chloride was removed by distillation and pentane (50 mL) was added to the residue. The mixture was allowed to stir for 1 hour to ensure complete precipitation of the triethylamine salts. The suspension was filtered through a pad of celite. The filtrate was concentrated to give a pale yellow oil which was distilled under reduced pressure to give 5.85 g (68%) of (4R,5R)-2-(cis)-but-2-enyl-2-chloro-3,4-dimethyl-5-phenyl-[1,3,2]oxazasilolidine as a ˜2.4:1 mixture of diastereomers. Preparation of (4S,5S)-2-Allyl-2-isopropoxy-3,4-dimethyl-5-phenyl-[1,3,2]oxazasilolidine: To a solution of (4S,5S)-2-Allyl-2-chloro-3,4-dimethyl-5-phenyl-[1,3,2]oxazasilolidine (2.08 g, 7.8 mmol) in methylene chloride (25 mL) was added triethylamine (1.2 mL, 8.6 mmol). 2-Propanol (0.6 mL, 7.8 mmol) was added slowly by syringe and the mixture was allowed to stir for 12 hours. The methylene chloride was removed by distillation and pentane (20 ml) was added to the residue. The mixture was stirred for 3 hours. The mixture was then filtered through a pad of celite. The filtrate was concentrated to afford an oil which was distilled under reduced pressure (b.p. ˜72° C., ˜0.2 mm Hg) to yield 1.08 g (48%) of (4S,5S)-2-Allyl-2-isopropoxy-3,4-dimethyl-5-phenyl-[1,3,2]oxazasilolidine as a ˜2:1 mixture of diastereomers. Preparation of (4R,5R)-2-Allyl-1,3-bis-(4-bromo-benzyl)-2-chloro-octahydro-benzo[1,3,2]diazasilole: To a cooled (0° C.) solution of allyltrichlorosilane (2.05 ml, 14.1 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (4.24 ml, 28.4 mmol) in dichloromethane (50 ml) was added (R,R)-N,N′-bis-(4-bromo-benzyl)-cyclohexane-1,2-diamine (5.37 g, 11.9 mmol) in dichloromethane (20 ml) over 50 min. After 2 h, the mixture was warmed to room temperature, and was stirred for 13 h. The reaction mixture was concentrated. Diethylether (60 ml) was added, and the mixture was stirred for 1 h. The mixture was filtrated through a pad of celite with ether washes (2×10 ml). The filtrate was concentrated. Benzene (10 ml) was added, and the solution was concentrated. This procedure was repeated and upon standing in a freezer, the resulting oil solidified to give 5.37 g (88%) of (4R ,5R)-2-Allyl-1,3-bis-(4-bromo-benzyl)-2-chloro-octahydro-benzo[1,3,2]diazasilole as a white solid. Enantioselective allylation of dihydrocinnamaldehyde to give (3R)-1-phenyl-hex-5-en-3-ol: To a cooled (−10° C.) solution of (4S,5S)-2-Allyl-2-chloro-3,4-dimethyl-5-phenyl-[1,3,2]oxazasilolidine (380 mg, 1.5 mmol) in toluene (5 mL) was added dihydrocinnamaldehyde (1.0 mmol). The reaction mixture was maintained at −10° C. for 2 h. To this cooled solution was added 1N HCl (4 mL) and EtOAc (4 mL) and the mixture was vigorously stirred for 15 min. The layers were separated and the aqueous layer was extracted with EtOAc (2×5 mL). The combined organics were dried (MgSO4), filtered, and concentrated. The residue was purified by flash chromatography on silica gel to give (3R)-1-phenyl-hex-5-en-3-ol in 84% yield and 88% enantiomeric excess (ee). Enantioselective crotylation of dihydrocinnamaldehyde to give (3S,4S)-4-Methyl-1-phenyl-hex-5-en-3-ol: To a cooled (−10° C.) solution of (4R,5R)-2-((cis)-but-2-enyl)-2-chloro-3,4-dimethyl-5-phenyl-[1,3,2]oxazasilolidine (0.431 g, 1.5 mmol) in toluene (2.5 mL) was added dihydrocinnamaldehyde (0.132 mL, 1.0 mmol). The reaction mixture was allowed to stir for 12 hours at −10° C. To this solution was added 1N HCl (4 mL) and EtOAc (4 mL) and the mixture was stirred for 10 min. The layers were separated and the aqueous layer was extracted with EtOAc (3×5 mL). The combined organics were dried over MgSO4, filtered, and concentrated. HPLC analysis of the residue at this stage revealed a syn:anti diastereoselectivity of 10:1, and an enantiomeric excess for the major syn product of 81%. The residue was purified by chromatography on silica gel to afford 0.116 g (61%) of (3S,4S)-4-Methyl-1-phenyl-hex-5-en-3-ol (81% ee). Enantioselective allylation of dihydrocinnamaldehyde to give (3R)-1-phenyl-hex-5-en-3-ol: To a solution of (4S,5S)-2-Allyl-2-isopropoxy-3,4-dimethyl-5-phenyl-[1,3,2]oxazasilolidine (0.437 g, 1.5 mmol) in toluene (2.5 mL) was added dihydrocinnamaldehyde (0.132 mL, 1.0 mmol). The mixture was allowed to stir at ambient temperature (˜21° C.) for 18 hours. To this solution was added 1N HCl (4 mL) and EtOAc (4 mL) and the mixture was stirred for 10 min. The layers were separated and the aqueous layer was extracted with EtOAc (3×5 mL). The combined organics were dried over MgSO4, filtered, and concentrated. The residue was purified by chromatography on silica gel (5% EtOAc/hexanes) to afford 0.119 g (69%) of (3R)-1-phenyl-hex-5-en-3-ol in 94% enantiomeric excess (ee). Enantioselective allylation of 3-benzyloxypropionaldehyde to give (3S)-1-benzyloxy-hex-5-en-3-ol: To a cooled (−10° C.) solution of(4R,5R)-2-Allyl-1,3-bis-(4-bromo-benzyl)-2-chloro-octahydro-benzo[1,3,2]diazasilole (1.0 mmol) in CH2Cl2 (5 mL) was added 3-benzyloxypropionaldehyde (1.0 mmol). The reaction mixture was transferred to a freezer (−10° C.) and maintained at that temperature for 20 h. To this cooled solution was added 1N HCl and EtOAc, and the mixture was vigorously stirred at room temperature for 15 min. The layers were separated and the aqueous layer was extracted with EtOAc 3 times. The combined organic layers were diluted with hexane, dried (MgSO4), filtered, and concentrated. Purification of the residue by chromatography on silica gel gave (3S)-1-benzyloxy-hex-5-en-3-ol in 87% yield and 98% ee. Enantioselective allylation of acetic acid benzylidene-hydrazide (8) to give (1R)-acetic acid N′-(1-phenyl-but-3-enyl)-hydrazide: To a cooled (10° C.) solution of (4S,5S)-2-Allyl-2-chloro-3,4-dimethyl-5-phenyl-[1,3,2]oxazasilolidine (9.90 g, 37.0 mmol) in CH2Cl2 (300 mL) was added acetic acid benzylidene-hydrazide (5.00 g, 30.8 mol) as a solid. The resulting solution was stirred for 16 hours and methanol (40 mL) was then added. After 15 min all volatiles were removed by distillation and the residue was diluted with EtOAc (150 mL) and H2O (500 mL). The phases were separated and the aqueous layer was extracted with EtOAc (2×150 mL). The combined organic layers were washed with H20 and brine, dried (MgSO4), filtered and concentrated. Analysis of the residue by HPLC revealed an ee of 87%. The residue was dissolved in boiling toluene (80 mL) and the solution was then cooled to ambient temperature. Pentane (380 mL) was layered on top of the toluene solution and the resulting biphasic solution was allowed to stand for 16 hours. The resulting crystalline solid precipitate was filtered, washed (pentane:toluene (5:1)) and then dried in vacuo to give 5.04 g (80%) of (1R)-acetic acid N′-(1-phenyl-but-3-enyl)-hydrazide in 98% ee. Preparation of 2-allyl-2-chloro-4,4,5 5-tetramethyl-[1,3,2]dioxasilolane: To a cooled (0° C.) solution of allyltrichlorosilane (4.9 mL; 34 mmol) in CH2Cl2 (50 mL) was added 1,8-Diazabicyclo[5.4.0]undec-7-ene (13 mL; 84 mmol). A solution of pinacol (4.0 g; 34 mmol) in CH2Cl2 (50 mL) was then added slowly and the resultant solution was warmed to room temperature and stirred for 12 hours. The solution was concentrated and the residue was treated with diethylether (100 mL). The mixture was stirred for 1 hour during which time the formation of a precipitate was observed. The mixture was then filtered and the filtrate was concentrated. The residue was distilled under reduced pressure to give 5.2 g (72%) of 2-allyl-2-chloro-4,4,5,5-tetramethyl-[1,3,2]dioxasilolane as a clear, colorless liquid. Preparation of 2-allyl-4,4,5,5-tetramethyl-2-vinyloxy-[1,3,2]dioxasilolane: To a cooled (0° C.) solution of MeLi (16.2 mL; 23 mmol; 1.4 M in Et20) was added trimethylvinyloxysilane (2.7 g; 23 mmol). The solution was warmed to room temperature and was stirred for 1 hour. The solution was cooled to −78° C., and 2-allyl-2-chloro-4,4,5,5-tetramethyl-[1,3,2]dioxasilolane (5.5 g; 25 mmol) was added. The solution was warmed to room temperature and stirred for 2 hours. The solution was diluted with pentane (20 mL), and the mixture was then filtered through a pad of celite. The filtrate was concentrated, and the residue was distilled under reduced pressure to give 3.8 g (70%) of 2-allyl-4,4,5,5-tetramethyl-2-vinyloxy-[1,3,2]dioxasilolane as a clear, colorless liquid. Tandem aldol-allylation reaction of cyclohexanecarboxaldehyde to give (syn)-1-cyclohexyl-hex-5-ene-1,3-diol: To a solution of 2-allyl-4,4,5,5-tetramethyl-2-vinyloxy-[1,3,2]dioxasilolane (0.63 mmol) in toluene (0.4 mL) was added cyclohexanecarboxaldehyde (48 mg; 0.42 mmol). The solution was heated to 40° C. and stirred at that temperature for 24 h. The solution was cooled and 1 M HCl (5 mL) was added followed by ethyl acetate (5 mL). The mixture was stirred for 20 min and the layers were separated. The organic layer was washed with saturated aqueous NaHCO3 (5 mL), washed with brine (5 mL), dried (Na2SO4), filtered, and concentrated. The residue was purified by chromatography on silica gel to give racemic (syn)-1-cycloliexyl-hex-5-ene-1,3-diol in 59% yield. Tandem aldol-allylation reaction of cyclohexanecarboxaldehyde to give (syn,anti,syn)-1-cyclohexyl-2,4-dimethyl-hex-5-ene-1,3-diol: To a solution of (trans,trans)-2-but-2-enyl-4,4,5,5-tetramethyl-2-propenyloxy-[1,3,2]dioxasilolane (prepared by an exactly analogous procedure to that used for the preparation of 2-allyl-4,4,5,5-tetramethyl-2-vinyloxy-[1,3,2]dioxasilolane) (0.63 mmol) in benzene (0.4 mL) was added cyclohexanecarboxaldehyde (48 mg; 0.42 mmol). The solution was heated to 40° C. and stirred at that temperature for 132 h. The solution was cooled and 1 M HCl (5 mL) was added followed by ethyl acetate (5 mL). The mixture was stirred for 20 min and the layers were separated. The organic layer was washed with saturated aqueous NaHCO3 (5 mL), washed with brine (5 mL), dried (Na2SO4), filtered, and concentrated. 1H NMR analysis at this stage revealed the presence of 4 diastereomeric products in a 86:11:3:1 ratio. The major product was isolated by chromatography on silica gel to give racemic (syn,anti,syn)-1-cyclohexyl-2,4-dimethyl-hex-5-ene-1,3-diol in 60% yield. Preparation of (4R,5R)-2-allyl-2-chloro-4,5-bis-(1-methoxy-1-methyl-[1,3,2]dioxasilolane: To a cooled (0° C.) solution of allyltrichlorosilane (7.0 mL; 48 mmol) in CH2Cl2 (80 mL) was added 1,8-diazabicyclo[5.4.0]undec-7-ene (15 mL; 102 mmol). A solution of (3R,4R)-2,5-dimethoxy-2,5-dimethyl-hexane-3,4-diol (10.0 g; 48 mmol) in CH2Cl2 (80 mL) was then added and the mixture was allowed to warm to ambient temperature and stirred for 12 hours. The solution was concentrated and the residue was treated with diethylether (100 mL). The mixture was stirred for 1 hour. The mixture was then filtered and the filtrate was concentrated. The residue was distilled under reduced pressure to give 6.6 g (44%) of (4R,5R)-2-allyl-2-chloro-4,5-bis-(1-methoxy-1-methyl-ethyl)-[1,3,2]dioxasilolane as a clear, colorless liquid. Preparation of (4R,5R)-2-allyl-2-isopropenyloxy-4,5-bis-(1-methoxy-1-methyl-ethyl)-[1,3,2]dioxasilolane: To a cooled (0° C.) solution of MeLi (13.0 mL; 21 mmol; 1.6 M in Et2O) was added 2-(trimethylsilyloxy)propene (2.8 g; 21 mmol). The solution was stirred 30 minutes at 0° C., and then warmed to room temperature and was stirred for 1 hour. The mixture was recooled to 0° C., and (4R,5R)-2-allyl-2-chloro-4,5-bis-(1-methoxy-1-methyl-ethyl)-[1,3,2]dioxasilolane (6.6 g; 21 mmol) was added. The mixture was warmed to room temperature and stirred for 2 hours. The solution was diluted with pentane (20 mL), and the mixture was then filtered through a pad of celite. The filtrate was concentrated, and the residue was distilled under reduced pressure to give 3.0 g (43%) of (4R,5R)-2-allyl-2-isopropenyloxy-4,5-bis-(1-methoxy-1-methyl-ethyl)-[1,3,2]dioxasilolane as a clear, colorless liquid. Asymmetric tandem aldol-allylation reaction of benzaldehyde to give (1S,3S)-3-methyl-1-phenyl-hex-5-ene-1,3-diol: To a solution of (4R,5R)-2-allyl-2-isopropenyloxy-4,5-bis-(1-methoxy-1-methyl-ethyl)-[1,3,2]dioxasilolane (0.75 mmol) in benzene (0.3 mL) was added benzaldehyde (0.50 mmol). The mixture was heated to 40° C. (oil bath) and stirred at that temperature for 48 hours. The solution was cooled and 1 M HCl (10 mL) was added followed by ethyl acetate (10 mL). The mixture was stirred for 20 min. The layers were separated and the aqueous layer was extracted with ethyl acetate (10 mL). The combined organic layers were washed with saturated aqueous NaHC03 (10 mL) and brine (10 mL), dried (Na2SO4), filtered, and concentrated. Analysis of the residue by HPLC and 1H NMR revealed a 5.5:1 mixture of diastereomers and an enantiomeric excess for the major product of 68%. The residue was purified by chromatography on silica gel to give (1S,3S)-3-methyl-1-phenyl-hex-5-ene-1,3-diol in 70% yield and in 68% ee. Determination of Enantioselectivity and Absolute Configuration of Homoallylic Alcohol Products: Allylation of Benzaldehyde with allylation reagent 3: The ee was determined by chiral HPLC analysis using a chiralcel OD column, as shown in FIG. 3. The (R) enantiomer elutes first. Allylation of Cinnamaldehyde with allylation reagent 3: The ee was determined by chiral HPLC analysis using a chiralcel OD column, as shown in FIG. 4. The (R) enantiomer elutes first. Allylation of Dihydrocinnamaldehyde with allylation reagent 3: The ee was determined by chiral HPLC analysis using a chiralcel OD column, as shown in FIG. 5. The (S) enantiomer elutes first. Allylation of Isovaleraldehyde with allylation reagent 3: The ee was determined by 19F NMR (C6D6, 282 MHz) analysis of the Mosher ester of the product, as shown in FIG. 6. The absolute configuration (R) of the alcohol product was determined by optical rotation and comparison to the literature value: [α]D20+18.2° (CH2Cl2, c 0.74); literature: [α]D20−2.5° (CH2Cl2, c 9.26) for the (S) enantiomer of 16% ee. Allylation of Cyclohexanecarboxaldehyde with allylation reagent 3: The ee was determined by 19F NMR (C6D6, 282 MHz) analysis of the Mosher ester of the product, as shown in FIG. 7. The absolute configuration (S) of the alcohol product was determined by optical rotation and comparison to the literature value: [α]D20−6.67° (EtOH, c 0.775); lit: [α]D24+9.7° (EtOH, c 1.00) for the (R) enantiomer of 98% ee. Allylation of Pivaldehyde with allylation reagent 3: The ee was determined by 19F NMR (C6D6, 282 MHz) analysis of the Mosher ester of the product, as shown in FIG. 8. The absolute configuration (S) of the alcohol product was determined by optical rotation and comparison to the literature value: [α]D20−13.2° (PhH, c 0.28); lit: [α]D+10.3° (PhH, c 10.5) for the (R) enantiomer of 88% ee. Allylation of Benzyloxyacetaldehyde with allylation reagent 3: The ee was determined by 19F NMR (C6D6, 282 MHz) analysis of the Mosher ester of the product, as shown in FIG. 9. The absolute configuration (S) of the alcohol product was determined by optical rotation and comparison to the literature value: [α]D18+5.77° (CHCl3, c 1.06); lit: [α]D25−6.6° (CHCl3, c 2.1) for the (R) enantiomer of >99% ee. Allylation of tert-Butyldimethylsilyloxyacetaldehyde with allylation reagent 3: The ee was determined by 19F NMR (C6D6, 282 MHz) analysis of the Mosher ester of the product, as shown in FIG. 10. The absolute configuration (S) of the alcohol product was determined by optical rotation and comparison to the literature value: [α]D20+1.4° (CHCl3, c 1.00); lit: [α]D20+1.7° (CHCl3, c 0.24) for the (S) enantiomer of 59% ee. Allylation of 3-(Benzyloxy)pronionaldehyde with allylation reagent (R,R)-21: The ee was determined by chiral HPLC analysis using a chiralcel OD column, as shown in FIG. 12. Allylation of p-Anisaldehyde with allylation reagent (R,R)-21: The ee was determined by chiral HPLC analysis using a chiralcel OD column, as shown in FIG. 13. The (R) enantiomer elutes first. Allylation of p-CF3-Benzaldehyde with allylation reagent (R,R)-21: The ee was determined by chiral HPLC analysis using a chiralcel OJ-H column, as shown in FIG. 14. The (S) enantiomer elutes first. Allylation of trans-2-Hexenal with allylation reagent (R,R)-21: The ee was determined by chiral HPLC analysis of the derived benzoate using a chiralcel AD-H column, as shown in FIG. 15. Determination of Enantioselectivity and Absolute Configuration of Products of Tandem Aldol Allylation Reactions of Cyclohexanecarboxaldehyde: The diol having the formula was treated with 2,2-dimethoxypropane and a catalytic amount of (+)-camphorsulfonic acid (CSA) in CH2Cl2 to give acetonide A (equation XVIII). The 13C NMR spectrum of acetonide A was analyzed to reveal that the acetonide possessed the syn relative configuration, establishing the syn stereochemistry of the diol. Spectroscopic data for acetonide A: 1H NMR (400 MHz, CDCl3) δ 5.85-5.72 (m, 1H, CH═CH2), 5.10-4.99 (m, 2H, CH═CH2), 3.85-3.77 (m, 1H, CH), 3.52-3.45 (m, 1H, CH), 2.33-2.24 (m, 1H, one of CH2), 2.17-2.08 (m, 1H, one of CH2), 1.92-1.83 (m, 1H, one of CH2), 1.74-1.58 (m, 4H, one of CH2 and three of C6H11), 1.51-0.81 (m, 8H, eight of C6H11), 1.38 (s, 3H, CH3) 1.36 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3) δ 134.4, 116.9, 98.3, 73.2, 68.8, 42.8, 41.0, 33.4, 30.2, 28.9, 27.9, 26.6, 26.1, 25.9, 19.8; IR (thin film) 3077, 2992, 2925, 2853, 1643, 1451, 1379, 1262, 1200, 1171 cm−1. The diol having the formula was treated with 2,2-dimethoxypropane and a catalytic amount of (+)-camphorsulfonic acid in CH2Cl2 to give acetonide B (equation XIX). The 13C NMR spectrum of this acetonide was analyzed to reveal that the acetonide possessed the syn relative configuration, establishing the syn stereochemistry of the diol. The relative configuration of the allylic methyl group was deduced from the sterochemistry of acetonide D, which was assigned as described below. Spectroscopic data for acetonide B: 1H NMR (300 MHz, CDCl3) δ 5.73-5.60 (m, 1H, CH═CH2), 5.00-4.91 (m, 2H, CH═CH2), 3.50-3.37 (m, 2H, two CHOC(CH3)2, 2.17-2.05 (m, 1H, CH(CH3)CH═CH2), 1.85-1.00 (br m, 13H, CH2 and C6H11), 1.31 (s, 3H, one of CH3), 1.30 (s, 3H, one of CH3), 0.95 (d, J=6.7 Hz, 3H, CH(CH3)CH═CH2); 13C NMR (75 MHz, CDCl3) δ 140.4, 114.7, 98.2, 73.3, 72.5, 43.5, 42.9, 31.5, 30.2, 28.9, 28.0, 26.6, 26.1, 26.0, 19.7, 15.7; IR (thin film) 3078, 2921, 2852, 1636, 1450, 1376, 1259, 1200, 1106 cm−1. The diol having the formula was treated with 2,2-dimethoxypropane and a catalytic amount of (+)-camphorsulfonic acid in CH2Cl2 to give acetonide C (equation XX). The 13C NMR spectrum of this acetonide was analyzed to reveal that the acetonide possessed the syn relative configuration, establishing the syn stereochemistry of the diol. The relative configuration of the allylic methyl group was assigned as described below. Spectroscopic data for acetonide C: 1H NMR (300 MHz, CDCl3) δ 5.90-5.78 (m, 1H, CH═CH2), 5.04-4.98 (m, 2H, CH═CH2), 3.70-3.64 (m, 1H, one of CHOC(CH3)2), 3.52-3.45 (m, 1H, one of CHOC(CH3)2), 2.24-2.20 (m, 1H, CH(CH3)CH═CH2), 1.93-0.88 (m, 13H, C6H11 and CH2), 1.38 (s, 3H, one of CH3), 1.36 (s, 3H, one of CH3), 1.00 (d, J=6.9 Hz, 3H, CH(CH3)CH═CH2); 13C NMR (75 MHz, CDCl3); δ 140.6, 114.2, 98.0, 73.1, 72.4, 42.8, 42.4, 30.4, 30.0, 28.8, 28.0, 26.6, 26.0, 25.9, 19.6, 14.8; IR (thin film) 3078, 2921, 2852, 1636, 1450, 1376, 1259, 1200, 1106cm−1. Acetonide C was subjected to ozonolysis with a reductive workup with NaBH4, and the resulting alcohol was treated with PPTS in CH2Cl2 to give acetonide D (equation XXI). Analysis of the coupling constants of D in the 1H NMR spectrum established the anti relative configuration of the allylic methyl group. Since acetonides B and D were both shown to have the syn diol stereochemistry and since they are different compounds, the syn relative configuration of the allylic methyl group in B and in the diol starting material is also thereby proven. Spectroscopic data for acetonide D: 1H NMR (300 MHz, acetone-d6) δ 3.75-3.67 (m, 1H, CHOC(CH3)2 or CHOH), 3.57 (dd, J=5.4, 11.6 Hz, 1H, one of CH2OC(CH3)2), 3.48 (dd, J=11.0, 11.0 Hz, 1H, one of CH2OC(CH3)2), 3.50-3.45 (m, 1H, CHOC(CH3)2 or CHOH), 3.36 (br s, 1H, OH), 1.83-0.98 (m, 14H, C6H11, CH2, and CHCH3), 1.41 (s, 3H, one of CH3), 1.25 (s, 3H, one of CH3), 0.72 (d, J=6.7 Hz, 3H, CH(CH3)); 13C NMR (100 MHz, CDCl3) δ 98.2, 77.6, 76.4, 65.8, 43.9, 36.4, 34.5, 29.7, 28.9, 27.8, 26.6, 26.3, 26.2, 19.2, 12.6; IR (thin film) 3522, 2925, 1450, 1377, 1264, 1200, 1111 cm−1. The diol having the formula was treated with 2,2-dimethoxypropane and a catalytic amount of (+)-camphorsulfonic acid in CH2Cl2 to give acetonide E (equation XXII). The 13C NMR spectrum of this acetonide was analyzed to reveal that the acetonide possessed the syn relative configuration, establishing the syn stereochemistry of the diol. Analysis of the coupling constants of E, obtained from decoupling experiments, in the 1H NMR spectrum established the anti relative configuration of the methyl group. Spectroscopic data for acetonide E: 1H NMR (400 MHz, CDCl3) δ 5.86-5.96 (m, 1H, CH═CHZ), 5.01-5.08 (m, 2H, CH═CH2), 3.50 (m, 1H, OCHCH2), 3.28 (d, 1H, J=10.3 Hz, c-C6H11CHO), 2.34-2.41 (m, 1H, one of CH2CH═CH2), 2.13-2.21 (m, 1H, one of CH2CH═CH2), 1.71-1.77 (m, 2H, two of c-C6H11), 1.37 (s, 3H, three of C(CH3)2), 1.34 (s, 3H, three of C(CH3)2), 1.11-1.65 (m, 10H, CHCH3 and nine of c-C6H11), 0.74 (d, 3H, J=6.6 Hz, CHCH3); 13C NMR (100 MHz, CDCl3) δ 135.3, 116.1, 97.7, 77.7, 74.2, 38.4, 37.6, 34.2, 30.4, 30.1, 26.9, 26.6, 26.5, 24.8, 19.5, 11.8; IR (film) 3075, 2991, 2931, 2853, 1641, 1451, 1379, 1264, 1203, 1176, 1131, 1051, 1015, 987, 935, 910 cm−1. The diol having the formula was treated with 2,2-dimethoxypropane and a catalytic amount of (+)-camphorsulfonic acid in CH2Cl2 to give acetonide F (equation XXIII). The 13C NMR spectrum of this acetonide was analyzed to reveal that the acetonide possessed the syn relative configuration, establishing the syn stereochemistry of the diol. Analysis of the coupling constants in the 1H NMR spectrum established the anti relative configuration of the methyl group between the two OH groups. Spectroscopic data for acetonide F: 1H NMR (400 MHz, CDCl3) δ 5.96-5.82 (m, 1H, CH═CH2), 5.07-4.94 (m, 2H, CH═CH2), 3.35 (dd, J=10.1, 1.7 Hz, 1H, CHO), 3.28 (d, J=10.8 Hz, 1H, CHO), 2.51-2.39 (m, 1H, CH), 1.84-1.12 (m, 12H, CH and C6H11), 1.37 (s, 3H, CH3), 1.34 (s, 3H, CH3), 1.07 (d, J=6.9 Hz, 3H, CHCH3), 0.72 (d, J=6.6 Hz, 3H, CHCH3); 13C NMR (100 MHz, CDCl3) δ 140.1, 114.5, 97.5, 77.8, 77.6, 39.6, 38.5, 32.4, 30.5, 30.1, 26.9, 26.6, 24.9, 19.3, 18.1 11.2; IR (thin film) 3072, 2990, 2930, 2853, 1642, 1451, 1378, 1256, 1202, 1176 cm−1. To establish the relative configuration of the allylic methyl group of the diol, the diol was first converted to a mixture of benzyl ethers which was treated with Hg(OAc)Cl in acetone to give terahydropyran G (equation XXIV) along with other products. Analysis of the coupling constants and NOE studies established the stereochemistry of the allylic methyl group of the diol. Spectroscopic data for tetrahydropyran G: 1H NMR (400 MHz, CDCl3) δ 7.42-7.28 (m, 5H, C6H5), 4.69-4.61 (m, 2H, PhCH2), 3.80 (ddd, J=9.8, 7.6, 4.7 Hz, 1H, CH), 3.52-3.44 (m, 2H, two CH), 2.35 (dd, J=11.7, 4.7 Hz, 1H, one of CH2HgCl), 2.08 (dd, J=11.7, 7.6 Hz, 1H, one of CH2HgCl), 1.85-1.13 (m, 13H, two CH and C6H11), 1.00 (d, J=6.9 Hz, 3H, CHCH3), 0.95 (d, J=7.0 Hz, CHCH3); 13C NMR (100 MHz, CDCl3) δ 139.0, 128.2, 127.4, 127.2, 83.4, 80.4, 75.8, 75.7, 46.1, 38.2, 38.0, 37.9, 30.9, 26.9, 26.6, 24.6, 14.5, 13.8; IR (KBr) 3025, 2930, 2855, 1654, 1607, 1450, 1376, 1337, 1193, 1095, 1067 cm−1. The diol having the formula was treated with 2,2-dimethoxypropane and a catalytic amount of (+)-camphorsulfonic acid in CH2Cl2 to give acetonide H (equation XXV). The 13C NMR spectrum of this acetonide was analyzed to reveal that the acetonide possessed the syn relative configuration, establishing the syn stereochemistry of the diol. Analysis of the coupling constants in the 1H NMR spectrum established the anti relative configuration of the methyl group between the two OH groups. Since the anti allylic methyl group stereocenter of acetonide F has been established, and since the diol starting materials corresponding to acetonides F and H differ only in the allylic methyl group stereochemistry, the syn orientation of the allylic methyl group in acetonide H and in the corresponding diol starting material is therefore established. Spectroscopic data for acetonide H: 1H NMR (400 MHz, CDCl3) δ 6.00-5.89 (m, 1H, CH═CH2), 5.06-4.95 (m, 2H, CH═CH2), 3.47 (dd, J=10.1, 2.4 Hz, 1H, CH), 3.30 (dd, J=10.1, 1.2 Hz, 1H, CH), 2.46-2.37 (m, 1H, CH), 1.83-1.11 (m, 12H, CH and C6H11), 1.36 (s, 3H, CH3), 1.33 (s, 3H, CH3), 1.00 (d, J=6.9 Hz, 3H, CHCH3), 0.76 (d, J=6.7 Hz, 3H, CHCH3); 13C NMR (100 MHz, CDCl3) δ 143.3, 112.8, 97.6, 77.9, 77.3, 38.6, 31.8, 30.5, 30.1, 26.9, 26.6, 24.9, 19.5, 12.5, 11.5; IR (thin film) 3073, 2968, 2931, 2853, 1640, 1451, 1379, 1256, 1202, 1138, 1031cm−1. The diol having the formula was treated with HgClOAc in CH2Cl2/THF to give tetrahydropyran 1 (equation XXVI). As illustrated, analysis of the coupling constants and selective 1D NOESY experiments unambiguously confirmed the relative stereochemistry of the diol. Spectroscopic data for tetrahydropyran I: 1H NMR (400 MHz, CDCl3) δ 3.40 (d, J=9.9 Hz, 1 H, CH), 3.27 (ddd, J=9.4, 8.2, 4.3 Hz, 1 H, CH), ), 3.03 (dd, J=9.7, 1.8 Hz, 1H, CH), 2.39 (dd, J=11.9, 4.3 Hz, 1 H, one of CH2HgCl), 2.14 (dd, J=11.9, 8.2 Hz, 1H, one of CH2HgCl), 2.16-2.07 (m, 2H, two H of C6H11), 2.07-2.98 (m, 1H, CH) 1.82-1.05 (m, 8H, CH, OH, and six H of C6H11), 0.99 (d, J=6.5 Hz, 3H, CHCH3), 0.89 (d, J=6.9 Hz, 3H, CHCH3), 0.94-0.75 (m, 3H, three H of C6H11); 13C NMR (100 MHz, CDCl3) δ 83.53, 80.4, 42.2, 38.2, 37.3, 35.9, 30.4, 28.0, 26.5, 25.9, 25.7, 13.8, 5.7; IR (KBr) 3434, 2924, 2851, 1720, 1450, 1386, 1334, 1262, 1100, 1027 cm−1.

<SOH> BACKGROUND OF THE INVENTION <EOH>Asymmetric additions of allyl groups and enolates to the carbonyl (C═O) group of aldehydes and to the C═N group of related electrophilic compounds remains one of the most important and fundamental carbonyl addition reactions for the synthesis of optically active chiral compounds containing a chiral carbon center bonded to an oxygen or nitrogen atom. Such compounds may have utility, for example, as pharmaceutically active compounds, or may be used to prepare other pharmaceutically active compounds. Many highly enantioselective allylation reagents and catalysts have been developed, as described, for example, in Brown, H. C. and Jadhav, P. K., J. Am. Chem. Soc., Vol. 105 (1983), p. 2092; Jadhav, P. K., Bhat, K. S., Perumal P. T. and Brown, H. C., J. Org. Chem., Vol. 51 (1986), p. 432; Racherla, U. S. and Brown, H. C., J. Org. Chem., Vol. 56 (1991), p. 401; Roush, W. R., Walts, A. E. and Hoong, L. K., J. Am. Chem. Soc., Vol. 107 (1985), p. 8186; Roush, W. R. and Banfi, W. L., J. Am. Chem. Soc., Vol. 110 (1988), p. 3979; Hafner, A., Duthaler R. O., Marti, R., Ribs, G., Rothe-Streit, P. and Schwarzenbach, F., J. Am. Chem. Soc., Vol. 114 (1992), p. 2321; Wang, Z., Wang, D. and Sui, X., Chem. Commun. (1996), p. 2261; Wang, D., Wang, Z. G., Wang, M. W., Chen, Y. J., Liu, L. and Zhu, Y., Tetrahedron: Asymmetry, Vol. 10 (1999), p. 327; Zhang, L. C., Sakurai, H. and Kira, M., Chem. Lett. (1997), p. 129. Similarly, highly enantioselective enolate reagents have been developed, as described, for example, in Paterson, I., Lister, M. A. and McClure, C. K., Tetrahedron Lett., vol. 27, (1986), p. 4787; Paterson, I. and Goodman, J. M., Tetrahedron Lett., vol. 30, (1989), p. 997; Paterson, I.,Goodman, J. M., Lister, M. A., Schumann, R. C., McClure, C. K. and Norcross, R. D., Tetrahedron, Vol. 46, (1990), p. 4663; and Cowden, C. J. and Paterson, I., Org. React. Vol. 51, (1997), p. 1. However, several problems have been found to be associated with the allylation and enolate reagents and catalysts of the prior art, including the expense of preparation, the instability of the reagents or the catalysts, the need for using the reagents or the catalysts in situ or shortly after their preparation, the toxicity of the reagents and the byproducts of the reactions of the reagents and the catalysts with aldehydes, and the ease of separation and purification of the reaction products. A generally applicable method for the allylation and the addition of enolates to aldehydes and related electrophilic compounds requires easily and inexpensively formed, stable, and storable reagents and catalysts, reagents and byproducts having little or no toxicity, and easy separation and purification of the products formed. A method combining all these characteristics has until now proven elusive.

<SOH> SUMMARY OF THE INVENTION <EOH>In accordance with the present invention, there is provided a new class of reagents and method of use of the reagents that solves the above-described problems of the prior art, and there is further provided excellent enantioselectivities in the reaction of the reagents with electrophilic compounds. The invention in a first embodiment is a method for the formation of an allylation reagent of formula The method includes reacting a silane of formula with a compound of formula to form the allylation reagent of formula (1). Each of X 1 and X 2 is independently O or N—R. Each of C a and C b is independently an achiral center, an (S) chiral center or an (R) chiral center. R a and R b are (i) each independently C 1-10 alkyl, C 6-10 aryl or C 3-9 heteroaryl, or (ii) taken together to form a C 3 -C 4 alkylene chain which together with C a and C b forms a 5-membered or 6-membered aliphatic ring. R c and R d are each independently hydrogen, C 1-10 alkyl, C 6-10 aryl or C 3-9 heteroaryl. R 6 of formulas (1) and (2) is a halogen, hydrogen, C 1-10 alkyl, C 6-10 aryl, C 3-9 heteroaryl, C 1-10 dialkylamino, C 1-10 alkyl-C 6-10 arylamino, C 1-10 diarylamino, or SR. R is C 1-10 alkyl, C 6-10 aryl or C 3-9 heteroaryl. Each of R 1 , R 2 , R 3 , R 4 , R 5 of formulas (1) and (2) is independently hydrogen, C 1 -C 10 alkyl, C 6-10 aryl, C 3-9 heteroaryl, C 1-10 alkoxy, C 6-10 aryloxy, C 1-10 dialkylamino, C 1-10 alkyl-C 6-10 arylamino, C 1-10 diarylamino, or halogen. The invention in another embodiment is a reagent of formula where X 3 is one of O and C(R 4 )(R 5 ) and X 1 , X 2 , C a , C b , R, R a , R b , R c , R d , R 1 , R 2 , R 3 , R 4 , R 5 are as defined above in connection with formulas (1) and (2). R 6 in formula (4) is halogen, hydrogen, C 1-10 alkyl, C 6-10 aryl, C 3-9 heteroaryl, C 1-10 alkoxy, C 6-10 aryloxy, C 1-10 dialkylamino, C 1-10 alkyl-C 6-10 arylamino, C 1-10 diarylamino, —O—C(R 9 )═C(R 7 )(R 8 ), OSO 2 CF 3 or SR. Each of R 7 , R 8 and R 9 are defined in the same way as R 1 , R 2 , R 3 , R 4 , and R 5 in connection with formulas (1) and (2). The invention in another embodiment is a method for the formation of a first reagent of formula The method includes reacting a second reagent of formula with one equivalent of a lithium enolate of the formula Li—O—C(R 3 )═C(R 1 )(R 2 ) to form the first reagent. Each of X 1 and X 2 is independently O or N—R. Each of C a and C b is independently an achiral center, an (S) chiral center or an (R) chiral center. R a and R b are (i) each independently C 1-10 alkyl, C 6-10 aryl or C 3-9 heteroaryl, or (ii) taken together to form a C 3 -C 4 alkylene chain which together with C a and C b forms a 5-membered or 6-membered aliphatic ring. R c and R d are each independently hydrogen, C 1-10 alkyl, C 6-10 aryl or C 3-9 heteroaryl. R 6 is a halogen, hydrogen, C 1-10 alkyl, C 6-10 aryl, C 3-9 heteroaryl, C 1-10 dialkylamino, C 1-10 alkyl-C 6-10 arylamino, C 1-10 diarylamino, O—C(R 3 )═C(R 1 )(R 2 ), or SR. R is C 1-10 alkyl, C 6-10 aryl or C 3-9 heteroaryl. Each of R 1 , R 2 , and R 3 , is independently hydrogen, C 1 -C 10 alkyl, C 6-10 aryl, C 3-9 heteroaryl, C 1-10 alkoxy, C 6-10 aryloxy, C 1-10 dialkylamino, C 1-10 alkyl-C 6-10 arylamino, C 1-10 diarylamino, or halogen. The invention in another embodiment is a method for the formation of an alcohol of formula The method includes reacting a reagent of formula with an aldehyde of formula R 10 CHO to form the alcohol of formula (7), where X 3 is one of O and C(R 4 )(R 5 ) and X 1 , X 2 , C a , C b , R, R a , R b , R c . R d , R 1 , R 2 , R 3 , R 4 , and R 5 are as defined above in connection with formulas (1), (2) and (3). R 6 is a halogen, hydrogen, C 1-10 alkyl, C 6-10 aryl, C 3-9 heteroaryl, C 1-10 alkoxy, C 6-10 aryloxy, C 1-10 dialkylamino, C 1-10 alkyl-C 6-10 arylamino, C 1-10 diarylamino, OSO 2 CF 3 or SR. R 10 is C 1-10 alkyl, C 6-10 aryl, or C 3-9 heteroaryl. The invention in another embodiment is a method for the formation of a compound of formula The method includes reacting a reagent of formula with a compound of the formula R 12 C(R 14 )═N—X 4 —CO—R 11 . X 3 is one of O and C(R 4 )(R 5 ). X 4 is O or NH. X 1 , X 2 , C a , C b , R, R a , R b , R c . R d , R 1 , R 2 , R 3 , R 4 , and R 5 are as defined above in connection with formulas (1), (2) and (3). R 6 is a halogen, hydrogen, C 1-10 alkyl, C 6-10 aryl, C 3-9 heteroaryl, C 1-10 alkoxy, C 6-10 aryloxy, C 1-10 dialkylamino, C 1-10 alkyl-C 6-10 arylamino, C 1-10 diarylamino, OSO 2 CF 3 or SR. R 11 is hydrogen, C 1-10 alkyl, C 6-10 aryl, or C 3-9 heteroaryl, R 12 is C 1-10 alkyl, C 6-10 aryl or C 3-9 heteroaryl. R 14 is hydrogen, C 1-10 alkyl, C 6-10 aryl, or C 3-9 heteroaryl. The invention in another embodiment is a method for the formation of a first allylation reagent of formula The method includes reacting a second allylation reagent of formula with an alcohol of the formula H—O—R 13 in the presence of a base to form the first allylation reagent of formula (11). X 1 , X 2 , C a , C b , R, R a , R b , R c , R d , R 1 , R 2 , R 3 , R 4 , and R 5 , are as defined above in connection with formulas (1), (2) and (3). R 6 is a halogen or OSO 2 CF 3 . R 13 is C 1 -C 10 alkyl, C 6-10 aryl, or C 3-9 heteroaryl. The invention in another embodiment is a method for the formation of a first allylation reagent of formula The method includes reacting a second allylation reagent of formula with a lithium enolate of the formula Li—O—C(R 9 )═C(R 7 )(R 8 ) to form the first allylation reagent. X 1 , X 2 , C a , C b , R, R a , R b , R c , R d , R 1 , R 2 , R 3 , R 4 , R 5 , R 7 , R 8 and R 9 are as defined above in connection with formulas (1), (2) and (3). R 6 is a halogen or OSO 2 CF 3 . The invention in another embodiment is a method for the formation of a first reagent of formula The method includes reacting a second reagent of formula with two equivalents of a lithium enolate of the formula Li—O—C(R 3 )═C(R 1 )(R 2 ) to form the first reagent of formula (15). X 1 , X 2 and R are as defined above in connection with formulas (1), (2) and (3). Each of C a and C b is independently an achiral center, an (S) chiral center or an (R) chiral center. R a and R b are (i) each independently C 1-10 alkyl, C 6-10 aryl or C 3-9 heteroaryl, or (ii) taken together to form a C 3 -C 4 alkylene chain which together with C a and C b forms a 5-membered or 6-membered aliphatic ring. R c and R d are each independently hydrogen, C 1-10 alkyl, C 6-10 aryl or C 3-9 heteroaryl. Each of R 1 , R 2 , and R 3 , is independently hydrogen, C 1 -C 10 alkyl, C 6-10 aryl, C 3-9 heteroaryl, C 1-10 alkoxy, C 6-10 aryloxy, C 1-10 dialkylamino, C 1-10 alkyl-C 6-10 arylamino, C 1-10 diarylamino, or halogen. The invention in another embodiment is a method for the formation of a diol of formula The method includes reacting a reagent of formula with an aldehyde of formula R 10 CHO to form the diol of formula (17). X 3 is one of O and C(R 4 )(R 5 ). X 1 , X 2 , C a , C b , R, R a , R b , R c , R d , R 1 , R 2 , R 3 , R 4 , R 5 , R 7 , R 8 and R 9 are as defined above in connection with formulas (1), (2), (3) and (4). R 10 is C 1-10 alkyl, C 6-10 aryl, or C 3-9 heteroaryl. The invention in another embodiment is a method for the formation of a compound of formula The method includes reacting a reagent of formula with a compound of the formula R 12 C(R 14 )═N—X 4 —CO—R 11 to obtain the compound of formula (19). X 3 is one of O and C(R 4 )(R 5 ). X 4 is one of NH and O. X 1 , X 2 , C a , C b , R, R a , R b , R c . R d , R 1 , R 2 , R 3 , R 4 , R 5 , R 7 , R 8 and R 9 are as defined above in connection with formulas (1), (2), (3) and (4). R 11 is hydrogen, C 1-10 alkyl, C 6-10 aryl, or C 3-9 heteroaryl. R 12 is C 1-10 alkyl, C 6-10 aryl or C 3-9 heteroaryl. R 14 is hydrogen, C 1-10 alkyl, C 6-10 aryl, or C 3-9 heteroaryl. In the foregoing formulas (1)-(20), the double bond between C(R 3 ) and C(R 1 )(R 2 ), the double bond between X and C(R 3 ), and the double bond between C(R 9 ) and C(R 8 )(R 7 ) may each be an (E) double bond, a (Z) double bond, or a double bond that does not exhibit (E)/(Z) isomerism. In the compound of the formula R 12 C(R 14 )═N—X 4 —CO—R 11 , the double bond between C and N may be an (E) double bond or a (Z) double bond.

20050726

20090519

20051229

68402.0

PRICE, ELVIS O

REAGENTS FOR ASYMMETRIC ALLYLATION, ALDOL, AND TANDEM ALDOL AND ALLYLATION REACTIONS

SMALL

ACCEPTED

ACCEPTED

Gas generating device

The present invention relates to a gas generator device used in automobile safety to inflate an airbag. This device is characterized in that it comprises at least one gas source for inflating the airbag and at least one gas outlet orifice, called the first orifice, for gas to flow into the airbag, characterized in that it includes means for making the gas pass through other gas outlet orifices, called second orifices, which are distributed over the device so that it is given a neutral-thrust configuration when it is initiated, although not in service, the device also including means for closing off these second orifices when the device is in service, so that when the device is initiated, the gas passes via the first outlet orifice.

1. A gas generator device used in automobile safety to inflate an airbag (3), comprising at least one gas source for inflating the airbag (3) and at least one gas outlet orifice (6, 106, 206), called the first orifice, for gas to flow out into the airbag (3), comprising flow guide for making the gas pass exclusively through other gas outlet orifices (7, 107, 207), called second orifices, when the device is initiated, although not in service, these second orifices (7, 107, 207) being separate from said first orifice (6, 106, 206) and distributed over the device so as to render it with a neutral thrust configuration when it is initiated, although not in service, the device further comprising a closing mechanism that closes off these second orifices when the device is in service, so that when the device is initiated the gas passes via the first outlet orifice. 2. The device as claimed in claim 1, further comprising a first portion comprising the gas source and a second portion having the shape of a cylindrical tube (1, 101, 201) that comprises a ferrule onto which the airbag (3) can be fitted, the tube (1, 101, 201) further comprising a central channel (10, 110, 210) having an internal profile that defines a gas outflow section, for outflow in a given flow direction (f1) between one end, called the upstream end, which is connected to the gas source and a closed end, called the downstream end, which constitutes a solid end section (8, 108, 208) of the tube (1, 101, 201), the first orifice being formed through this solid end section and the tube (1, 101, 201) also having a side wall (2, 102, 202) through which the second orifices are formed radially. 3. A gas generator device used in automobile safety to inflate an airbag (3), comprising a first portion comprising at least one gas source to inflate said airbag (3) and a second portion having the shape of a cylindrical tube (1, 101, 201) that includes a ferrule onto which the airbag (3) can be fitted, this tube (1, 101, 201) comprising a central channel (10, 110, 210) having an internal profile that defines a gas outflow section, for outflow in a given flow direction (f1) between one end, called the upstream end, which is connected to the gas source and a closed end, called the downstream end, which constitutes a solid end section (8, 108, 208) of the tube (1, 101, 201), at least one gas outlet orifice (6, 106, 206), called the first orifice, for outputting the gas to the airbag (3) being formed through this solid end section and the tube (1, 101, 201) also having a side wall (2, 102, 202) through which other gas outlet orifices (7, 107 207), called second orifices, are formed radially, and flow guide for making the gas pass through these second orifices (7, 107, 207) when the device is initiated, although not in service, these second orifices (7, 107, 207) being distributed over the device so as to give the device a neutral thrust configuration when the device is initiated, although not in service, the device further comprising closing mechanism that closes off these second orifices (7, 107, 207) when the device is in service, so that when the device is initiated the gas passes through the first outlet orifice (6, 106, 206). 4. The device as claimed in claim 2 or claim 3, wherein the flow guide for making the gas pass through the second orifices when the device is initiated, although not in service, comprises a particular internal profile for flow in the tube (1), which comprises, upstream of the second orifices, along the flow direction (f1), a flow section that decreases down to a minimum flow section of nonzero given diameter (D1) forming a restriction, extended approximately in the same radial plane by a flow section of diameter (D2) greater than the diameter (D1) of the minimum section, which is itself extended by an increasing flow section (13) so as to form, with this particular internal profile, a Venturi-effect system, the difference between the two diameters (D1, D2) being defined so as to leave an opening near an annular passage (5) connected to the first orifice formed by an axial nozzle (6) oriented in the direction of the airbag (3), said nozzle being formed longitudinally in the side wall (2) of the tube (1) and, at one of its ends, passing through the end section (8) of the tube (1). 5. The device as claimed in claim 4, wherein the decreasing section located upstream of the restriction is formed by a central channel (40) of a part (4), the part (4) having the shape of a truncated cone open at both its ends and having a variable defined thickness (e), which decreases from an upstream end, located on the same side as the upstream end of the tube (1), toward a downstream end, located on the same side as the downstream end of the tube (1), the part (4) having a side wall (41), on a portion of which is formed, near the upstream end, a projecting circular flat (42), the surface of which is parallel to the internal wall (20) of the tube (1) and is fastened to said internal wall. 6. The device as claimed in claim 2 or claim 3, wherein the flow guide for bringing the gas toward the second orifices further comprises a deflector (104, 204) placed so as to face the inlet (105, 205) of a duct (106, 206), the inlet (105, 205) constituting one end of the duct (106, 206) located inside the tube (101, 201), the duct (106, 206), at another end, called the outlet end, passing through the end section (108, 208) of the tube in order to emerge outside the tube (101, 201), the deflector (104, 204) having at least one solid portion placed facing the inlet of the duct (106, 206), the solid portion located at a defined distance from the inlet of the duct so as to leave a space between the solid portion and the inlet (105, 205) of the duct (106, 206), at least one passage being formed around the solid portion of the deflector (104, 204), the passage (140, 240) constituting a reduction in the flow section in the tube between the upstream end and the downstream end. 7. The device as claimed in claim 6, wherein the deflector (104) includes, on either side of its solid portion (115), at least two orifices (140) allowing the gas to pass between the upstream end and the downstream end of the deflector (104). 8. The device as claimed in claim 7, wherein the solid part (115) of the deflector is domed toward the upstream end, making it possible to form the space between the solid portion (115) and the inlet of the duct (106). 9. The device as claimed in claim 6, wherein the deflector (204) has a frustoconical shape, the axis of symmetry of which coincides with the axis (A) of the tube (201) and with the axis of the duct (206), the larger section (221) of the frustoconical shape facing the inlet (205) of the duct (206) and having a diameter (D8) greater than or equal to the diameter (D9) of the duct (206) at its inlet, and less than the internal diameter (D4) of the tube (201) at this point, so as to form the passage (240) between the upstream end and the downstream end. 10. The device as claimed in claim 9, wherein the inlet (205) of the duct (206) is flared and in that the deflector (204) comprises a connecter that fixes the deflector onto the edge of the flared inlet (205) of the duct (206). 11. The device as claimed in claim 2 or claim 3, wherein the inflatable airbag (3) has an open end with a perimeter fitted to the ferrule, applied to the second orifices and held against the orifices so as to form the flow guide for closing off the second orifices when the device is in service. 12. The device as claimed in claim 11, wherein the link for joining the airbag (3) onto the ferrule is formed by a clamping clip (9, 109, 209). 13. The device as claimed in claim 12, wherein the link for joining the airbag (3) onto the ferrule formed by a clamping clip (9, 109, 209) is meltable thereby permitting the release of the second orifices and providing the device a neutral thrust configuration when the device is fired. 14. The device as claimed in claim 1 or claim 3, wherein the gas source comprises a reservoir connected to or integrated with the tube (1, 101) and containing a pressurized gas. 15. The device as claimed in claim 1 or claim 3, wherein the gas source comprises a combustion chamber for burning at least one pyrotechnic charge.

The present invention relates to the field of automobile safety and relates more particularly to a gas generator comprising a neutral-thrust diffusion system. The gas generators used in automobile safety must not become dangerous projectiles when they are initiated, although not in service, that is to say when they are being handled, transported or stored. It is therefore imperative to guarantee the optimum safety level when these generators are outside their module. This safety level can be achieved using a neutral-thrust diffusion system. This consists, for example on gas generators of tubular shape, in producing balanced radial gas outlets distributed in such a way that the forces generated upon gas liberation cancel out. The generator will thus have a neutral-thrust configuration and will present no hazard when it is initiated outside its module. However, in certain modules, in order for the airbag to inflate rapidly, it is often preferable for the gas to penetrate along a single thrust axis. To obtain this single thrust axis directed toward the airbag, a diffuser is often added which makes it possible to channel, in a single direction, the streams of gas escaping from the radial outlets of the generator. The fitting of a diffuser allows a generator with a diffusion system to remain in a neutral-thrust configuration. However, this type of module is less effective than a module using an axial-outflow generator, that is to say one that releases the gas along a single axis in the direction of the airbag. Patent WO 93/18942 discloses a module comprising in particular a gas generator fixed to a specific structure and an airbag that can be inflated by the gas delivered by this generator. The generator described in that patent includes a pressurized-gas reservoir and a plurality of outlet orifices arranged and distributed so as to give the generator a neutral-thrust configuration when it is not fixed onto its structure. The module also includes obturators for closing off certain outlet orifices of the generator so as to give it an axial-thrust configuration when it is attached to its structure. If, for example, the generator has two diametrically opposed orifices, one being oriented so as to be able to take the gas directly into the airbag, the other orifice will be closed off so as to give the module an axial-thrust configuration. In that document, the orifice used for inflating the airbag is also used to give the device a neutral-thrust configuration when it is initiated, although not in service. Said patent WO 93/18942 also proposes to fix the generator using the obturators. In this way, whenever the generator has to be removed from its module, it will be necessary to remove the obturators and therefore open all the radial orifices. This generator will therefore always be in a neutral-thrust configuration when it is outside its module. The systems employed in the prior art use one or more specific parts so as to obtain axial gas outflow in generators normally in a neutral-thrust configuration when they are outside their modules. These parts are, for example, the diffuser or the obturators disclosed in patent WO 93/18942. The object of the invention is to propose a gas generator with direct axial outflow toward the airbag, not requiring for this the use of a specific structure, nor an obturator or diffuser, and nevertheless having a neutral-thrust diffusion system allowing it to represent no hazard when it is initiated outside its module. This object is achieved by a gas generator device used in automobile safety to inflate an airbag, comprising at least one gas source for inflating the airbag and at least one gas outlet orifice, called the first orifice, for gas to flow out into the airbag, this device being characterized in that it includes means for making the gas pass through other gas outlet orifices, called second orifices, when the device is initiated, although not in service, these second orifices being distributed over the device so as to render it with a neutral-trust configuration when it is initiated, although not in service, the device also including means for closing off these second orifices when the device is in service, so that when the device is initiated the gas passes via the first outlet orifice. In one embodiment, the device comprises a first portion comprising the gas source and a second portion having the shape of a cylindrical tube that includes a ferrule onto which the airbag can be fitted, this tube comprising a central channel having an internal profile that defines a gas outflow section, for outflow in a given flow direction between one end, called the upstream end, which is connected to the gas source and a closed end, called the downstream end, which constitutes a solid end section of the tube, the first orifice being formed through this solid section and the tube also having a side wall on which the second orifices are formed radially. According to a first embodiment, the means for making the gas pass through the second orifices when the device is initiated, although not in service, consist of a particular internal profile for flow in the tube, which comprises, upstream of the second orifices, along the flow direction, a flow section that decreases down to a minimum flow section of nonzero given diameter forming a restriction, extended approximately in the same radial plane by a flow section of diameter greater than the diameter of the minimum section, which is itself extended by an increasing flow section so as to form, with this particular internal profile, a Venturi-effect system, the difference between the two diameters being defined so as to leave an opening near an annular passage connected to the first orifice, this first orifice being formed by what is called an axial nozzle oriented in the direction of the airbag, said nozzle being formed in the side wall of the tube and, at one of its ends, passing through the end section of the tube. According to one feature of the first embodiment, the decreasing section located upstream of the restriction is formed by a central channel of a part, this part having the shape of a truncated cone open at both its ends and having a variable defined thickness, which decreases from its upstream end, located on the same side as the upstream end of the tube, toward its downstream end, located on the same side as the downstream end of the tube, this part having a side wall, on a portion of which is formed, near its upstream end, a projecting circular flat, the surface of which is parallel to the internal wall of the tube and is fastened to said internal wall. According to a second embodiment, the means for bringing the gas toward the second orifices comprise a deflector placed so as to face the inlet of a duct, this inlet constituting one end of the duct located inside the tube, the duct, at its other end, called the outlet end, passing through the end section of the tube in order to emerge outside the tube, the deflector having at least one solid portion placed facing the inlet of the duct, this solid portion being formed or located at a defined distance from the inlet of the duct so as to leave a space between the solid portion and the inlet of the duct, at least one passage being formed around the solid portion of the deflector, this passage constituting a reduction in the flow section in the tube between the upstream end and the downstream end. According to a first variant of this second embodiment, the deflector includes, on either side of its solid portion, at least two orifices allowing the gas to pass between the upstream end and the downstream end of the deflector. According to one feature of this first variant, the solid portion of the deflector is domed toward the upstream end, making it possible to form the space between the solid portion and the inlet of the duct. According to a second variant of this second embodiment, the deflector has a frustoconical shape, the axis of symmetry of which coincides with the axis of the tube and with the axis of the duct, the larger section of this frustoconical shape facing the inlet of the duct and having a diameter greater than or equal to the diameter of the duct at its inlet, and less than the internal diameter of the tube at this point, so as to form the passage between the upstream end and the downstream end. According to one feature of this second variant, the inlet of the duct is flared and the deflector has means for catching onto the edge of the flared inlet of the duct. According to one feature, the inflatable airbag has an open end with its perimeter fitted to the ferrule, applied to the second orifices and held against them so as to form the means for closing off the second orifices when the device is in service. According to another feature, the link, for joining the airbag onto the ferrule, formed by means of a clamping clip, can melt, which makes it possible in the event of firing the device, to release the second orifices and thus give the device a neutral-trust configuration. According to another feature, the gas source comprises a reservoir connected to or integrated with the tube and containing a pressurized gas. According to another feature, the gas source comprises a combustion chamber for burning at least one pyrotechnic charge. The invention, with its features and advantages, will become more clearly apparent on reading the description, which is given with reference to the appended drawings in which: FIG. 1A shows, in longitudinal sectional view, a first embodiment of a downstream portion of a tubular generator not in service; FIG. 1B shows, in longitudinal sectional view, the downstream portion of the gas generator shown in FIG. 1A, onto which the inflatable airbag has been fitted; FIG. 2A shows, in longitudinal sectional view, a second embodiment of the downstream portion of the generator not in service; FIG. 2B shows, in longitudinal sectional view, the downstream portion of the generator shown in FIG. 2A, onto which the inflatable airbag has been fitted; FIG. 3A shows, in longitudinal sectional view, the downstream portion of the generator not in service in a variant of the second embodiment; FIG. 3B shows, in longitudinal sectional view, the downstream portion of the generator shown in FIG. 3A, onto which the airbag has been fitted; and FIG. 4 shows, in longitudinal sectional view, an embodiment in which the ferrule onto which the airbag is fitted is oriented at 90° to the axis of the tube. The invention will now be described in conjunction with FIGS. 1A to 4. To inflate an airbag for protecting the occupants of a motor vehicle, a gas generator is used. Certain widely used generators are called axial outflow generators, which means that the gas is sent into the airbag along a single axis. The axis as defined here does not therefore correspond to the axis of the generator when the latter is of tubular shape, but corresponds to the axis of entry of the gas into the airbag. Other generators are called neutral-thrust generators. When these neutral-thrust generators are of tubular shape, they have a plurality of outlet orifices distributed over a portion of the side wall of the tube so that the forces generated by the gas outflow are cancelled out. Generators with axial outflow may become dangerous projectiles if they are initiated outside their module. However, they are very effective for inflating certain airbags. The invention therefore consists in using an axial-outflow generator when it is in its module, that is to say when it is fitted onto the airbag, which has a neutral-thrust diffusion system allowing it to be of no hazard when it is being handled, stored or transported. The invention may be applied in particular to tubular generators, having any gas source (not shown) whether or not integrated into the generator. This generator may therefore have a pressurized gas reservoir or may use the combustion of a pyrotechnic charge, or it may be of hybrid type, that is to say having a pressurized gas reservoir and a combustion chamber for burning a pyrotechnic charge. Let us take, for example, a hybrid generator comprising several gas sources. Since the invention relates to the discharging of the gas out of the generator, the appended figures show only that portion of a generator close to the end via which the gas is discharged. This end is called the downstream end. The generator has a tubular shape, closed at its downstream end by what is called end section (8, 108, 208) of the tube (1, 101, 201), the tube (1, 101, 201) having a central axis (A) and a side wall (2, 102, 202). The tube (1, 101, 201) has a central channel (10, 110, 210) with an internal profile defining a flow section perpendicular to the axis (A) of the tube (1, 101, 201). The gas flows through the tube in a flow direction defined by the arrow f1 in the appended figures, between what is called the upstream end, connected to the gas source, and the downstream end of the tube (1, 101, 201). That portion of the tube (1, 101, 201) shown in FIGS. 1A to 3B has, in a defined radial plane, over a defined length L as far as its end section (8, 108, 208), a different, reduced section, thus reducing the flow section of the tube (1, 101, 201) and constituting a ferrule for fitting the airbag. When the generator is in service, as shown in FIGS. 1B, 2B and 3B, an airbag (3) for protecting the occupants of a vehicle is fitted to the generator. This airbag (3) is in the form of a bag and therefore has an open end and a closed end. The open end of the airbag (3) has a perimeter designed to surround the tube (1, 101, 201) in a gastight manner on its reduced section. In a first embodiment shown in FIGS. 1A and 1B, an internal nozzle (4), inside the tube (1), is fixed to its internal wall (20), starting from a transition (12) in the section of the tube (1), over a portion of the length L of the reduced section of the tube. This internal nozzle (4) is, for example, fixed by crimping it onto the internal wall (20) of the tube (1). It consists of a part having a central channel (40), the axis of which roughly coincides with the axis (A) of the tube (1). This central channel (40) has a specified shape so that it defines, in the tube (1), along the flow direction given by the arrow f1, a flow section that decreases up to the end of the part where the flow cross section is a minimum with a nonzero diameter D1. The part forming this nozzle (4) has the shape of a truncated cone having the central channel (40), the axis of which coincides with the axis of symmetry of the truncated cone. This truncated cone is open at both its ends and its thickness e varies, decreasing from the upstream end toward the downstream end. This truncated cone has, over a portion of its side wall (41) located near its most upstream end, over its entire periphery, a projecting flat (42), the surface of which is parallel to the internal wall (20) of the tube (1) and is fixed to said internal wall. Lying approximately in the radial plane including the most downstream end of the nozzle (4), this end having the minimum section of diameter D1 of the central channel (40) of the nozzle (4), the internal wall (20) of the tube (1) has a particular profile consisting of a large increase (11) in the thickness of the side wall (2) in the tube (1), and therefore consisting of the reduction in the flow section in the tube (1) in this radial plane. The latter flow section has a diameter D2 greater than the sum of the diameter D1 of the minimum section and of twice the thickness e of the nozzle (4) in this radial plane. Continuing along the flow direction, the tube (1) then has a flow section (13) that increases over a certain length and then a flow section (14) that remains constant up to the closed end section (8) of the tube (1). This constant flow section has a smaller diameter D3 than the diameter D4 of the flow section in the tube taken in the reduced section of the tube (1). The difference between the diameter D2 of the flow section taken at the thickness increase (11) of the side wall (2) of the tube (1) and the sum of the diameter D1 of the minimum section and of twice the thickness e of the part (4) in the radial plane defined above forms an opening toward an annular passage (5). This annular passage (5) is formed between the surface of the side wall (41) of the frustoconical part (4) and that section of the tube (1) which is formed, in this radial plane, by the increase (11) in the thickness of the side wall (2) of the tube (1). At least one nozzle (6) is formed in the side wall (2) of the tube (1) longitudinally with respect to the axis (A) of the tube (1), said at least one nozzle (6), at one of its ends, passing through the downstream end section (8) of the tube (1) in order to emerge outside the tube (1), in the airbag when the latter is fitted, the other end of this nozzle (6) emerging in the annular passage (5). This nozzle (6) is called an axial nozzle as it constitutes a means for axial gas outflow in the direction of the airbag (3) when the latter is fitted. The axis as defined here therefore does not necessarily correspond to the axis (A) of the tube, but corresponds to the axis for gas entry into the airbag. This principle is illustrated in FIG. 4, in which the ferrule (308) used for fitting the airbag is, for example, oriented at 90° to the axis (A) of the tube (301) so that the axial gas outflow (306) into the airbag is also oriented at 90° to the axis (A) of the tube (301). In the sectional view shown in FIGS. 1A and 1B, only a single axial nozzle is visible. However, there are other axial nozzles (6) emerging in the annular passage (5). Radial nozzles (7) are formed through the side wall (2) of the tube (1) in the constant flow section (14) of diameter D3. These nozzles (7) are distributed over the side wall (2) of the tube (1) so that the forces resulting from the gas outflow through these nozzles are cancelled out. The decreasing flow section formed by the nozzle (4) extended by the increasing flow section (13) of the tube (1) thus forms a Venturi-effect system. The Venturi effect causes the gas to accelerate in the restriction formed by the minimum flow section of diameter D1. Referring to FIG. 1A, when the generator is initiated but is not in service, the gas accelerates at this restriction. This acceleration takes the gas directly into the radial tubes (7) as shown diagrammatically by the arrows f2 in FIG. 1A. In this configuration, since the opening toward the annular passage (5) leading to the axial nozzles (6) is not along the path of the gas, said gas is not discharged via the axial nozzles (6). Thus, no axial thrust is created when the generator is initiated, although not in service. The use of the Venturi-effect system therefore limits the hazards associated with the initiation of the generator while it is outside its module. Referring to FIG. 1B, when the generator is in service, the perimeter of the airbag (3) closes off the radial nozzles (7), thereby preventing gas outflow via the radial nozzles (7). In this configuration, the gas, being unable to escape via the closed-off radial nozzles (7), flows via the annular passage (5) before joining the axial nozzles (6) formed in the side wall (2) of the tube (1) and thus reaching the inflatable airbag (3), as shown by the arrows f3 in FIG. 1B. In order for the radial nozzles (7) to be properly closed off, the perimeter of the open end of the airbag (3) is held in place by means of a clamping clip (9) that surrounds the tube (1). In a second embodiment shown in FIGS. 2A to 3B, a duct (106, 206) passes through the closed end section (108, 208) of the tube (101, 201), approximately along its center, the axis of said duct being roughly coincident with the axis (A) of the tube (101, 201) and thus constituting axial gas outflow toward the airbag (103, 203) when the latter is fitted. This duct (106, 206) has a first end, called the outlet end, which emerges outside the tube (101, 201) into the airbag, when it is fitted, and a second end (105, 205), called the inlet end, which emerges inside the tube (101, 201). The inlet (105, 205) of the duct (106, 206) lies roughly level with the abovementioned transition (112, 212) in the section of the tube (1). In a first variant of this second embodiment, shown in FIGS. 2A and 2B, a deflector (104) is placed in front of the inlet (105) of the duct (106), said deflector having a solid circular domed central portion (115), the convexity of which is oriented toward the upstream end of the tube (101). Formed in the deflector (104) on either side of this central portion (115) are two orifices (140), the axes of which are roughly parallel to the axis (A) of the tube (101). This deflector (104) is fixed via its perimeter (142) to the internal wall (120) of the tube (1) just upstream of the section transition (112) of the tube (101). The solid central portion (115) of the deflector (104) is placed in front of the inlet (105) of the duct (106). The diameter D6 of this solid central portion, bounded by the orifices (140), is greater than the diameter of the duct (106) at its inlet (105), defined by D5 in FIGS. 2A and 2B. The radius of curvature of the doming of the central portion (115) of the deflector (104) is sufficient to leave a space between the inlet (105) of the duct (106) and the central portion (115) of the deflector (104). A cylindrical part (117) is placed just upstream of the deflector (104). This part (117) is fixed via its periphery to the internal wall (120) of the tube (101). This part (117) has a central channel (116) of frustoconical shape, the axis of symmetry of which is roughly coincident with the axis (A) of the tube (101), this frustoconical shape thus creating, in the tube (101), a change in the flow section. This frustoconical channel (116) is oriented in such a way that the smallest flow section is the most upstream. The largest flow section of this central channel (116) has a diameter D7 defined in such a way as to be equal to or greater than the sum of the diameter D6 of the central portion (115) of the deflector (104) and of the diameter of each orifice (140) of the deflector (104). In this variant, orifices or nozzles (107) are formed radially through the side wall (102) of the tube (101), downstream of the section transition (112) of the tube (101). These orifices or nozzles (107) are distributed so as to give the generator a neutral-thrust configuration when it is initiated outside its module. These orifices or nozzles (107) may be closed off as in the first variant described with reference to FIGS. 1A and 1B by the perimeter of the airbag (3). The central portion (115) of the deflector (104) and the frustoconical shape of the central channel (116) of the part (117) located upstream, deflect and guide the gas toward the orifices (140) of the deflector (104). At the orifices (140), the gas accelerates owing to the Venturi effect created by the restriction formed by these orifices. Upon accelerating, the gas expands around the duct (106), to be directed toward the radial nozzles (107), as indicated by the arrows f102 in FIG. 2A. If the generator is not in service, i.e. it is outside its module, the gas escapes via these radial nozzles (107) thus creating neutral thrust owing to the balanced distribution of the radial nozzles (107). If these radial nozzles (107) are closed off, for example by the perimeter of the open end of the airbag (3) as described above, the gas can then flow only via the space existing between the central portion of the deflector (104) and the inlet (105) of the duct (106), in order thus to reach the duct (106) and be discharged into the airbag (3) as indicated by the arrow f103 in FIG. 2B. In order for the radial nozzles (107) to be properly closed off, the perimeter of the airbag (3) is held in place by means of a clamping clip (109) that surrounds the tube (101). In a second variant of this second embodiment, shown in FIGS. 3A and 3B, the inlet (205) of the duct (206) is flared. A deflector (204) is fixed to the flared edge of the inlet (205) of the duct (206), over a portion of its perimeter, for example less than one half. In this variant, said deflector (204) is a frustoconical part placed in such a way that its axis of symmetry is roughly coincident with the axis (A) of the tube (201) and the axis of the duct (206). The end (220) of smallest section of this part is located furthermost upstream and the end (221) of largest section is located roughly level with the section transition (212) of the tube (201). The end (221) of largest section of this part has a diameter D8 equal to or greater than the diameter D9 of the duct (206) taken at its inlet at the end of the flared edge. The end (221) of largest section has a smaller diameter D8 than the inside diameter D4 of the tube (201) taken at the reduced section of the tube (201) so that a passage (240) is formed, around the deflector (204), between the upstream end and the downstream end of the deflector (204). Along a portion of the perimeter of its largest section (221), the deflector (204) has a projecting portion (218), allowing it to catch onto a corresponding portion of the flared edge of the inlet (205) of the duct (206). When the deflector (204) is secured to the inlet of the duct (206), a space (219) is left between the plane formed by the inlet (205) of the duct (206) and the plane containing the end (221) of largest section of the deflector (204). The duct (206) also has, near its outlet, a projecting ring (222), one of the lateral surfaces of which bears inside the tube (201) against the end section (208) of the tube (201). This ring (222) has a diameter D10 smaller than the inside diameter D4 of the tube (201) taken at its reduced section, so as not to close off the radial nozzles. A fillet (223) is formed all around the duct (206) between the lateral surface opposite the lateral surface for bearing against the end section (208) of the tube (201). The fillet is able, for example, to guide the gas toward the radial nozzles (207). Placed upstream of the deflector (204) is a part (217) with a central channel identical to that described in the first embodiment with reference to FIGS. 2A and 2B. In this second variant, the frustoconical shape of the deflector (204) makes it possible to deflect and guide the gas toward the passage (240) existing between the perimeter (240) of the deflector (204) and the internal wall (220) of the tube (201). The passage (240) constitutes a restriction in the flow section in the tube (201). As the gas flows into this restriction, a Venturi effect is created, that is to say the gas is accelerated. Owing to this acceleration, the gas is directed directly into the radial nozzles (207) of the tube (201) that are formed in the first variant of this second embodiment. If these radial nozzles (207) are not closed off, the gas escapes via the radial nozzles (207) as indicated by the arrows f202 in FIG. 3A. If these radial nozzles (207) are closed off, for example by the perimeter of the airbag (3) held in place by a clamping clip (209), the gas has no other option but to pass into the space (219) existing between the deflector (204) and the inlet (205) of the duct (206). This gas then escapes directly via the duct (206), constituting an axial gas outflow into the airbag, as indicated by the arrow f203 in FIG. 3B. Since the projecting portion (218) of the deflector (204), serving to fasten the deflector (204) to a portion of the perimeter of the flared edge of the duct (206), is solid, it also allows the gas to be guided into the duct (206). In both embodiments described above, the Venturi-effect makes it possible to direct and lead the gas into the radial nozzles (7, 107, 207) and thus to give the generator a neutral-thrust configuration when it is not in service. When these radial nozzles (7, 107, 207) are closed off, the gas has no other option but to escape axially in the direction of the airbag (3), that is to say via the axial nozzles (6) in the first embodiment or via the duct (106, 206) in the second embodiment. In a variant, the clamping clip (9, 109, 209) may for example be meltable, so as to release the radial outlets (7, 107, 707) of the generator when the module is fired, and thus gives the generator a neutral-thrust configuration. It should be obvious to those skilled in the art that the present invention allows embodiments in many other specific forms without departing from the field of application of the invention as claimed. Consequently, the embodiments presented must be regarded by way of illustration; however, they may be modified within the field defined by the scope of the appended claims and the invention must not be limited to the details given above.

20050325

20081021

20050818

68838.0

FLEMING, FAYE M

GAS GENERATING DEVICE

UNDISCOUNTED

ACCEPTED

ACCEPTED

Device for opening a locked door or drawer

A device for opcning a locked door or drawer, which device comprises; a) means for facilitating the insertion of a key into a lock; and b) means for rotating said key when inserted.

1-30. (canceled) 31. A device for opening a locked door or drawer, which device comprises; a) means for facilitating the insertion of a key into a lock, said means comprising a rotatable guide having a slot for accommodating the shank of a key and facilitating the entry of said key into a lock; b) means for rotating said key when inserted; and c) means which, in use, will either return said slot to a position in which it is aligned with said lock to facilitate insertion of a key therein or will indicate when said slot is in such a position. 32. A device as claimed in claim 31, wherein said rotatable guide comprises a concave cavity to facilitate the passage of a key to said slot. 33. A device as claimed in claim 31, wherein said means (c) includes means to bias said rotatable guide to a predetermined position. 34. A device as claimed in claim 33, wherein said means comprises a spring. 35. A device as claimed in claim 34, further comprising a backing plate having an opening through which can pass the body of a cylinder latch but not the head thereof so that said device can be secured to a door via said cylinder latch. 36. A device as claimed in claim 35, further comprising a cover removeably mounted on said backing plate, and said rotatable guide is rotatably mounted between said backing plate and said cover. 37. A device as claimed in claim 31, including a handle displaceable to rotate said rotatable guide. 38. A device as claimed in claim 37, wherein said handle has a recess to accommodate at least part of the head of a key when inserted in a lock. 39. A device as claimed in claim 37, wherein said handle comprises an elongate member which can be attached to said rotatable guide in two positions, one extending to one side of said rotatable guide and the other to the other side of said rotatable guide. 40. A device as claimed in claim 37, wherein said handle comprises a knob. 41. A device as claimed in claim 40, wherein said knob has a tortuous periphery to facilitate the gripping thereof. 42. A device as claimed in claim 37, wherein said handle is connected to said rotatable guide via a train of interacting wheels. 43. A device as claimed in claim 31, wherein said means (c) comprises a spring loaded detent which acts (or reacts) on said rotatable guide to index said rotatable guide when said slot is aligned with said lock. 44. A device as claimed in claim 31, wherein said means (c) comprises a frame pivotally mounted on said rotatable guide and pivotal, in use, between a hanging position and an operative, raised position in which it co-operates with a key so that when said frame is turned said rotatable guide and said key turn therewith. 45. A device as claimed in claim 31, which comprises a bush and a handle having a cylindrical section rotatably mountable in said bush. 46. A device as claimed in claim 45, wherein said cylindrical section and said handle are formed integrally. 47. A device as claimed in claim 45, wherein said cylindrical section is provided with a groove which extends circumferentially thereof and which, in use, accommodates an edge of a backing plate to inhibit removal of said handle. 48. A device as claimed in claim 47, wherein a lug is provided in said groove which lug, in use, cooperates with said backing plate to limit rotational movement of said handle. 49. A device as claimed in claim 31, wherein said means for rotating said key comprises a handle which is operably connected to said rotatable guide so that rotation of said handle will rotate said rotatable guide, and is movable towards and away from said rotatable guide. 50. A device as claimed in claim 49, wherein said rotatable guide is provided with a projection which extends outwardly from said rotatable guide, supports said handle, and defines a tapered cavity which, in use, facilitates the insertion of a key. 51. A device as claimed in claim 49, further comprising a backing plate. 52. A device as claimed in claim 51, wherein said backing plate is provided with an extension which extends rearwardly of the backing plate and is provided with a passageway of substantially constant key-hole cross section for allowing the passage therethrough of a key for a mortice lock. 53. A device as claimed in claim 52, further comprising a retaining cover, and wherein one of said handle and said retaining cover is provided with a tongue and the other with a groove, alignment of said tongue with said groove ensuring alignment of said tapered cavity with said passageway to facilitate the insertion of a key. 54. A device as claimed in claim 49, including a backing plate, and a spring which urges said handle away from said backing plate. 55. A device as claimed in claim 54, further comprising a retaining cover, wherein said handle has a hub which projects through said retaining cover and is slidable relative thereto, and said device comprises a spring plate which is mounted on said hub and inhibits separation of said hub and said retaining cover. 56. A device as claimed in claim 55, wherein one of said spring plate and said retaining cover has an upstand and the other a surface which, at least when said handle is urged into said retaining cover, engages said upstand, said surface having an indentation such that engagement of said upstand in said indent indexes said handle. 57. A device as claimed in claim 49, including means for inhibiting removal of a key from a lock. 58. A device as claimed in claim 57, wherein said means comprises an arm moveable from an inoperative position in which a key may be freely inserted into or withdrawn and an operative position in which removal of said key is inhibited, and means to move said arm between its operative and inoperative positions. 59. A door fitted with a lock having a device as claimed in claim 31 operatively associated therewith. 60. A drawer fitted with a lock having a device as claimed in claim 31 operatively associated therewith.

This invention relates to a device for opening a locked door or drawer, and to a door or drawer fitted with a lock having such a device operatively associated therewith. Most external doors are secured by a cylinder lock or a combination of a cylinder lock and a mortice lock. One of the difficulties some people face, particularly those who are aging or who suffer with arthritis in their hands, is locating the key in the lock and then rotating the key once it is inserted therein. Such people also have difficulty operating the locks conventionally fitted to office and domestic furniture. The present invention aims to mitigate these problems. According to the present invention there is provided a device for opening a locked door or drawer, which device comprises; a) means for facilitating the insertion of a key into a lock; and b) means for rotating said key when inserted. Preferably, said means for facilitating the insertion of a key into said lock comprises a rotatable guide. Advantageously, said rotatable guide comprises a slot for accommodating the shank of a key and facilitating the entry of said key into a lock. Preferably, said rotatable guide comprises a concave cavity to facilitate the passage of a key to said slot. Advantageously, said device includes means to bias said rotatable guide to a predetermined position. Preferably, said means comprises a spring. Advantageously, said device comprises a backing plate having an opening through which can pass the body of a cylinder latch but not the head thereof so that said device can be secured to a door via said cylinder latch. Preferably, said device further comprises a cover removably mounted on said backing plate, and said rotatable guide is rotatably mounted between said backing plate and said cover. Advantageously, said device includes a handle displaceable to rotate said rotatable guide. Preferably, said handle has a recess to accommodate at least part of the head of a key when inserted in a lock. In one embodiment, said handle comprises an elongate member which can be attached to said rotatable guide in two positions, one extending to one side of said rotatable guide and the other to the other side of said rotatable guide. In another embodiment, said handle comprises a knob. Preferably, said knob has a tortuous periphery to facilitate the gripping thereof. In another embodiment, said handle is connected to said rotatable guide via a train of interacting wheels. If desired, the device may include a spring loaded detent which acts (or reacts) on said rotatable guide to index said rotatable guide when said slot is in a predetermined position. In a further embodiment, the device comprises a rotatable guide, and a frame pivotally mounted on said rotatable guide and pivotal, in use, between a hanging position and an operative, raised position in which it co-operates with a key so that when said frame is turned said rotatable guide and said key turn therewith. In a further embodiment the device comprises a bush and a handle having a cylindrical section rotatably mountable in said bush. Preferably, said cylindrical section and said handle are formed integrally. Advantageously, said cylindrical section is provided with a groove which extends circumferentially thereof and which, in use, accommodates an edge of a backing plate to inhibit removal of said handle. Preferably, a lug is provided in said groove which lug, in use, cooperates with said backing plate to limit rotational movement of said handle. In a further embodiment, said means for rotating said key comprises a handle which is operably connected to said rotatable guide so that rotation of said handle will rotate said rotatable guide, and is movable towards and away from said rotatable guide. Preferably, said rotatable guide is provided with a projection which extends outwardly from said rotatable guide, supports said handle, and defines a tapered cavity which, in use, facilitates the insertion of a key. Advantageously, said device further comprising a backing plate. Preferably, said backing plate is provided with an extension which extends rearwardly of the backing plate and is provided with a passageway of substantially constant key-hole cross section for allowing the passage therethrough of a key for a mortice lock. Advantageously, said device further comprises a retaining cover, and one of said handle and said retaining cover is provided with a tongue and the other with a groove, alignment of said tongue with said groove ensuring alignment of said tapered cavity with said passageway to facilitate the insertion of a key. The present invention also provides, a device in accordance with the present invention including a backing plate, and a spring which urges said handle away from said backing plate. Preferable, said device further comprises a retaining cover, wherein said handle has a hub which projects through said retaining cover and is slidable relative thereto, and said device comprises a spring plate which is mounted on said hub and inhibits separation of said hub and said retaining cover. Advantageously, one of said spring plate and said retaining cover has an upstand and the other a surface which, at least when said handle is urged into said retaining cover, engages said upstand, said surface having an indentation such that engagement of said upstand in said indent indexes said handle. Preferable, said device includes means for inhibiting removal of a key from a lock. In one embodiment said means comprises an arm moveable from an inoperative position in which a key may be freely inserted into or withdrawn and an operative position in which removal of said key is inhibited, and means to move said arm between its operative and inoperative positions. The present invention also provides a door fitted with a lock having a device in accordance with the present invention operatively associated therewith. The present invention also provides a drawer fitted with a lock having a device in accordance with the present invention operatively associated therewith. For a better understanding of the present invention reference will now be made, by way of example, to the accompanying drawings, in which: FIG. 1 is a front view of a first embodiment of a device in accordance with the present invention ready to receive a key; FIG. 2 is a side view of a key; FIG. 3 is a side view, partly in section, of the device shown in FIG. 1 mounted on a conventional cylinder lock with the key inserted therein; FIG. 4 is an underneath plan view, partly in section, of the arrangement shown in FIG. 3; FIG. 5 is a front view of a backing plate which forms part of the device shown in FIG. 1; FIG. 6 is a section on line VI-VI of FIG. 5; FIG. 7 is a section on line VII-VII of FIG. 5; FIG. 8 is a front view of a rotatable guide which forms part of the device shown in FIG. 1; FIG. 9 is a section taken on line IX-IX of FIG. 8; FIG. 10 is a section taken on line X-X of FIG. 8; FIG. 11 is a rear view of a cover which forms part of the device shown in FIG. 1; FIG. 12 is a section taken on line XII-XII of FIG. 11; FIG. 13 is a section taken on line XIII-XIII of FIG. 11; FIG. 14 is a rear view of the cover and rotatable guide of the device shown in FIG. 1; FIG. 15 is a front view of a second embodiment of a device in accordance with the present invention; FIG. 16 is a side view, partly in section, of the device shown in FIG. 15 mounted on a conventional cylinder lock with the key inserted therein; FIG. 17 is an underneath plan view, partly in section, of the arrangement shown in FIG. 16; FIG. 18 is a front view of a third embodiment of a device in accordance with the present invention; FIG. 19 is an underneath plan view of the device shown in FIG. 18; FIG. 20 is a side view, partly in section, of the device shown in FIG. 18; FIG. 21 is a front view of a fourth embodiment of a device in accordance with the present invention; FIG. 22 is a side view of the device shown in FIG. 21; FIG. 23 is an exploded perspective view of a fifth embodiment of a device in accordance with the present invention; FIG. 24 is a simplified cross-section showing the device of FIG. 23 in use with a key inserted in the lock; FIG. 25 is view taken on line XXV-XXV of FIG. 24; FIG. 26 is a section taken on line XXVI-XXVI of FIG. 24; FIG. 27 is a front elevation of the device shown in FIG. 23; FIG. 28 is a front elevation of a sixth embodiment of a device in accordance with the present invention; FIG. 29 is a section taken on line XXIX-XXIX of FIG. 28; FIG. 30 is a bottom plan view of the device shown in FIG. 28; FIG. 31 is a plan view of part of a seventh embodiment of a device according to the present invention; FIG. 32 is a section taken on line XXXII-XXXII of FIG. 31; FIG. 33 is a section taken on line XXXIII-XXXIII of FIG. 31; FIG. 34 is an exploded view of an eighth embodiment of a device according to the present invention; FIG. 35 is a vertical section showing the device shown in FIG. 34 mounted on a door with a key grip in a first position and with a key inserted; FIG. 36 is a view looking in the direction of the arrows XXXVI-XXXVI of FIG. 35 but with the key removed; FIG. 37 is a view taken on line XXXVII-XXXVII of FIG. 36 with the key grip in a second position; FIG. 38 is an exploded perspective view of a ninth embodiment of a device in accordance with the present invention; and FIG. 39 is a view of part of the device shown in FIG. 38 provided with a modification to inhibit a key being dislodged. Referring to FIGS. 1 to 3 of the drawings there is shown a device which is generally identified by the reference numeral 1. The device 1 comprises a backing plate 2 on which is mounted a cover 3. The cover 3 is secured to the backing plate 2 by two screws 4 and 5 (FIG. 4). The space between the cover 3 and the backing plate 2 accommodates a rotatable guide 6. As can be better seen in FIGS. 8, 9 and 10, the rotatable guide 6 has a concave cavity 7 which is provided with a slot 8 which is intended to accommodate the shaft 9 of a key 10. The rotatable guide 6 is also provided with two threaded holes 11 and 12 which accommodate respective bolts 13 and 14 whereby a reversible handle 15 can be mounted on the rotatable guide 6. A coil spring 25 is provided to bias the rotatable guide 6 to a starting position in which the slot 8 is normally substantially vertical. Typically, a cylinder latch, such as the cylinder latch 16 shown in FIG. 3 comprises a body 17 having a face plate 18 and a tongue 19. The face plate 18 is supported by an annular ring which bears on the frame 20 of the door and the body is held in position by tightening two bolts 21 and 22 which act between a plate 23 and the body 17. In the arrangement shown in FIG. 3 the annular ring is replaced by the backing plate 2 which is rotated until the slot 8 is aligned with the key receiving slot in the cylinder latch 16. This is typically vertical. The backing plate is then held in position by sufficiently tightening the bolts 21 and 22. The device 1 is then ready for use. In particular, the key 10 is guided by the concave cavity 7 and the slot 8 of the rotatable guide 6 into the key receiving slot of the cylinder latch 16. When the key 10 is fully inserted the head 23 of the key 10 lies in a recess 24 in the reversible handle 15. When the reversible handle 15 is depressed the rotatable guide 6 rotates with respect to the cover 3 and the backing plate 2. The key 10 also rotates as a result of the side of the cavity in the reversible handle 15 engaging against the head 23 of the key 10. After the door has been opened the reversible handle 15 is returned to its initial (horizontal) position and the slot 8 to its initial (vertical) position by the coil spring 25 as will hereinafter be described. In this connection it should be understood that the key receiving slot of the cylinder latch will also have been returned to its initial (vertical) position by the action of the internal latch mechanism (not shown) acting on the tongue 19. As indicated previously, the rotatable guide 6 is biased to an initial position by the coil spring 25. In particular, as shown in FIG. 14, a band 26 of metal which subtends an angle of approximate 130°is secured to the cover 3 by a bolt 27 part of which extends inwardly of the cover 3 and forms a post to which one end of the coil spring 25 is attached. The other end of the coil spring 25 is secured to a bolt 28 which is screwed into the rotatable guide 6. In use the action of the coil spring 25 rotates the rotatable guide until the bolt 28 engages the free extremity 29 of the band 26. In this position the slot 8 is vertical and the reversible handle horizontal. When the reversible handle 15 is rotated the rotatable guide 6 rotates until the bolt 28 engages the other end of the band 26. If desired the reversible handle 15 could be removed and replaced so that the reversible handle 15 projects to the left (as viewed in FIG. 1). At the same time the band 26 would be removed and its position reversed so that it extended clockwise around the cover 3 rather than counter-clockwise as shown. The coil spring 25 would also be moved to the opposite side of the rotatable guide 6. Referring now to FIGS. 15 to 17, there is shown a second embodiment of a device in accordance with the present invention which is generally identified by the reference numeral 101. The device shown in FIGS. 15 to 17 is generally similar to the device shown in FIGS. 1 to 14 and parts having similar functions have been identified by the same reference numerals but in the ‘100’ series. The main difference is that the reversible handle 15 has been replace with a knob 115 having a tortuous perimeter to facilitate the gripping thereof. The diameter of the knob 115 is approximately the same as the diameter of the backing plate 102. Although this embodiment does not provide as much leverage as the reversible handle 15 it can be used in more confined situations and is less susceptible to being damaged by vandals. In addition the knob 15 can be rotated as many times as desired. This is particularly useful if the device 101 is to be used with certain types of deadbolt latches which require two full turns to advance the bolt and then move an abutment into position to inhibit the latch being urged back into the lock by, for example a crowbar or other housebreaking implement. It will be appreciated that with this arrangement there is no mechanism for automatically biasing the rotatable guide 106 to a position where the slot 108 is exactly aligned with the key receiving slot of the cylinder latch. However, a spring loaded detent 130 may be provided which is arranged to enter an appropriately positioned recess 131 in the back of the rotatable guide 106 to enable the desired alignment to be felt. It will be understood that the action of the spring loaded detent 130 does not prevent the knob 115 being rotated but merely enables the knob 115 to be conveniently indexed. Referring now to FIG. 18 to 20, there is shown a third embodiment of a device in accordance with the present invention. The device, which is generally identified by reference numeral 201, is similar to the device shown in FIG. 1 to 14 except that the reversible handle 15 has been replace by a gear train comprising a handle 215a which is connected to a friction wheel 215b, and an idler wheel 215c which engages the outer surface of the rotatable guide 206. In use, after the key has been inserted in the cylinder lock the knob 215a is rotated. The relative sizes of the friction wheel 215b and the idler wheel 215c can be varied to adjust the mechanical advantage desired. Other parts having similar functions to parts shown in FIGS. 1 to 14 have been identified by similar reference numerals in the ‘200’ series. As with the embodiment shown in FIGS. 15 to 17, there is no mechanism for automatically biasing the rotatable guide 206 to a position where the slot 208 is exactly aligned with the key receiving slot of the cylinder latch. However, a spring loaded detent 230 is provided which co-opereates with a recess in the rotatable guide 206 in a manner similar to that described with reference to the embodiment shown in FIGS. 15 to 17. Referring now to FIGS. 21 and 22 there is shown a fourth embodiment of a device in accordance with the present invention. The device, which is generally identified by reference numeral 301 is generally similar to the device shown in FIGS. 1 to 14 and parts having similar functions have been identified by similar reference numerals in the ‘300’ series. The device differs form that shown in FIGS. 1 to 14 in that the rotatable guide 306 is provided with a frame 315a which is pivotally mounted thereto and which can be pivoted from an inoperative, hanging position (FIG. 21) to an operative, horizontal position (shown in chain-dotted lines in FIG. 22). A handle 315b is attached to one end of a shaft 315c which is non-rotatably mounted in the frame 315a and has a bifurcated end 315d the sides of which, in the operative position of the frame 315a lie to either side of the head of the key 310 which has been placed in the cylinder latch. In use, after the key 310 has been inserted through the slot in the concave cavity of the rotatable guide the handle 315b is swung upwardly until the head 323 of the key 310 lies between the sides of the bifurcated end 315d of the shaft 315c. The handle 315b is then turned so that the rotatable guide 306 and the key 310 turn to open the lock. When the handle 315b is released it swings downward to the position shown in FIG. 21. The pendulum effect of the handle 315b helps ensure that the slot 308 returns to a vertical position in alignment with the key receiving slot on the cylinder latch. Referring to FIG. 23 there is shown a device which is generally identified by reference numeral 401. The device 401 is primarily intended for use with locks on office and domestic furniture, for example with locks on the doors of cupboards or the drawers of desks and filing cabinets. Such locks can be fitted in the doors or drawers or in the carcasses therefor. The device 401 comprises a backing plate 402, a bush 403 and a rotatable guide 406. The rotatable guide 406 comprises a cylindrical section 406a one end of which is provided with a handle 415 part of which has a concave cavity 407 which is provided with a slot 408 which is intended to accommodate the shaft 409 of a key 410. The other end of the cylindrical section 406a is provided with a circumferentially extending groove 432. A lug 433 extends across part of the circumferentially extending groove 432 as shown and serves to limit rotational movement of the handle 415 as will be explained hereinafter. By way of example it will be assumed that it is desired to provide the door of an office cabinet with a lock. Firstly, a hole is drilled through through door 434 (FIG. 24). The bush 403 is then pressed into the hole. The cylindrical portion 406a of the rotatable guide 406 is then slid into bush 403 until the circumferentially extending groove 432 projects beyond the end of the bush 403. The backing plate 402 is then slid along the rear surface of the door 434 until part of it enters the circumferentially extending groove 432. The lock 416 is then slidably inserted into the cylindrical section 406a of the rotatable guide 406 and secured in place by screws 421 and 422 which pass through a flange 435 on the lock 416 and through holes in the backing plate 402 before entering the door 434. The handle 415 can be rotated through 180° from a first position where the handle 415 extends horizontally to the left of the bush 403 with the slot 408 vertical to a second position (as shown) where the handle 415 extends horizontally to the right of the bush 403 and the slot 408 is again vertical (but rotated through 180°with respect to its orientation when the handle 415 was in its first position). Rotation of the handle 415 is limited by engagement of the lug 433 on the backing plate 402. The projection of the backing plate 402 into the circumferentially extending groove 432 also serves to prevent the handle 415 being removed. For the purposes of illustration it will be assumed that the door is locked and the handle is in the position shown in FIG. 23. The user first advances the key 410 toward the lock 416. The shank 409 of the key 410 enters the concave cavity 407 which facilitates the entry of the shank into the lock 416. Once the key 410 is fully inserted the user rotates the handle 415 through 180° anti-clockwise which rotates the key through 180° anti-clockwise and opens the lock 416. It should perhaps be mentioned that the lock 416 is of a conventional office furniture type where the slot moves through 180° when moving from the locked to the open position and vice-versa. Referring now to FIGS. 28 to 30 there is shown a device which is generally identified by the reference numeral 501. The device 501 is generally similar to the device shown in FIGS. 18 to 20 and parts having similar functions have been identified by the same reference numerals but in the ‘500’ series. The main difference is that the intermediate wheel 215c has been replace by a connecting rod 536 which transfers rotational movement of the handle 515a to the rotatable guide 506. A stop pin 537 is mounted on the connecting rod 536 and serves to limit the rotational movement of the rotatable guide 536 on engagement therewith. FIGS. 31 to 33 show a backing plate 606 which differs from the backing plates previously described in that it is provided with a tubular stub 638 which, in use, extends into the hole cut through the door. The tubular stub 638 helps prevent the device being broken off the door by vandals or burglars. This embodiment is also provided with a threaded security pin 639 which threadely engages in a threaded hole 640 in the backing plate 606 and, in use, extends into a bore drilled into the door. The backing plate 606 is provided with a shaped aperture 642 designed to support a standard ‘ERA’ cylinder lock. Various modifications to the embodiments described are envisaged. For example, the coil spring 25 could be replaced by a torsional spring. The recess may be provided with a slot which, in use, engages the side of a key inserted in the lock. In this way, rotational forces applied to the rotatable guide act on the side of the head of the key rather than the shank. Referring now to FIG. 34 to 36 there is shown an eighth embodiment of a device in accordance with the present invention. The device, which is generally identified by the reference numeral 701, comprises a backing plate 702 which is provided with an extension 702a which extends rearwardly of the backing plate 702 and is provided with a passage 702b of substantially constant key-hole cross section for allowing the passage therethrough of a key 710 for a mortice lock 716 (FIG. 35). A retaining cover 703 is secured to the backing plate 702 by two screws 704 and 705. The space between the retaining cover 703 and the backing plate 702 accommodates a rotatable guide 706. The rotatable guide 706 is provided with a projection 707a which extends forwardly from the rotatable guide 706 and defines a tapered cavity 707b which is intended to facilitate the insertion of a key 710 into the passage 702b and thence into the mortice lock 716. A handle 715 is mounted on the rotatable guide 706 and, although it cannot be rotated relative to the rotatable guide 706, can be moved axially relative thereto between a first (retracted) position (FIG. 35) and a second(extended) position (FIG. 37). In order to use the device 701 shown in FIGS. 35 to 37, the user first gently presses the handle 715 toward the door and rotates it until a tongue 715a on the handle 715 enters a slot 703a on the cover 703. In this position the tapered cavity 707b extends vertically and is aligned with the passage 702b and the key hole 716a in the mortice lock 716. As the key 710 is inserted the sides of the tapered cavity 707b facilitate the proper orientation of the key 710. When fully inserted, the head 723 of the key 710 lies outside the confines of the handle 715 (FIG. 35). The handle 715 is then pulled outwardly to its second (extended) position (FIG. 37). In this position the head 723 of the key 710 lies within the confines of the handle 715. Rotation of the handle 715 results in rotation of the projection 707a (which is not rotatable relative to the handle 715) and rotation of the key 710 (via the engagement of its head 723 to operate the mortice lock 716. In order to remove the key 710, the handle 715 is rotated until the tongue 715a is aligned with the slot 703a at which position the handle 715 can be pushed fully home towards the door and the key 710 can be withdrawn from the mortice lock 716. Referring now to FIG. 38 there is shown a device which is generally identified by the reference numeral 801. The device 801 comprises a backing plate 802 which, like the backing plate 702 shown in FIG. 34, is provided with an extension (not visible) which extends rearwardly of the backing plate 702 and is provided with a passage 802b of substantially constant key-hole cross section for allowing the passage therethrough of a key 810 for a mortice lock 816. A retainer cover 803 can be secured to the backing plate 802 by two screws (not shown). The space between the retainer cover 803 and the backing plate 802 accommodates a spacer 832, a compression spring 833 and a spring plate 834. The compression spring, which has a greater internal diameter than the external diameter of the spring plate 834, acts between the backing plate 802 and the handle 815 to bias the handle 815 away from the frame 820 of a door. The handle 815, which can move axially into and out of the retainer cover 830, is provided with a concave cavity 807 provided with a slot 808. In use, the user inserts the key into the concave cavity 807 which facilitates entry of the key 810 into the slot 808. As will be explained in greater detail hereinafter the slot 808 is aligned with the passage 802b. Accordingly, the key 810 can pass into the mortice lock 816. When fully home the majority of the head 823 of the key 810 lies inside the slot 808. Rotation of the handle 815 causes rotation of the key 810 which, in turn, throws the bolt of the mortice lock 816. Typically, the key 810 will be rotated through 360° in one sense to extend the bolt of the mortice lock 816 and 360° in the opposite sense to retract the bolt. In order to remove the key 810 the user simply presses the knob 815 toward the frame 820 which exposes the head 823 of the key 810 to facilitate withdraw thereof. The spring plate 834 interacts with the handle 815 and the backing plate 802 to facilitate alignment of the slot 808 and the passage 802b to insert and withdraw the key 810. In particular, the spring plate 834 is provided with two leaves 834a and 834b which project toward the backing plate 802 and define a generally rectangular opening through which the hub 815a extends. The spring plate 834 prevents the handle 815 being withdrawn from the retainer cover 803. However, in addition, the spring plate 834 is provided with a small upstand 834c and the side of the retainer cover 803 facing the frame 820 is provided with a circular hub having a single indentation therein facing the retainer cover 803. As the handle 815 is rotated the upstand 834b rides on the circular hub. When the upstand 834c enters the single indentation this can be felt and acts as an indexing mechanism signifying that the slot 808 and the passage 802b are in alignment. Depending on the height of the upstand 834b and the construction of the spring plate 834 this indexing feature might only be felt when the handle 815 is pushed inwardly towards the frame 820. Turning now to FIG. 39 a modification is shown for preventing the key 810 being pushed out of the mortice lock by a person who has access to the other side of the mortice lock. The modification comprises an arm 840 which, in its operative position, sits between the head 823 of the key 810 and the collar 841 provided on conventional mortice keys. The collar 841 is mounted on a plate 842 which can slide perpendicular to the longitudinal axis of the key 810 and is biased to an open position by a spring 843. A plunger 845 can be depressed a first time to displace and hold the arm 840 in its locking position. When pressed a second time the plunger allows the arm 840 to be moved to its inoperative position by the spring 843. In principle, the operation of the mechanism is similar to that use in a retractable ball point pen. It should be noted that this embodiment does not have the indexing feature of the embodiment shown in FIG. 38.

20040818

20061212

20050428

59891.0

BARRETT, SUZANNE LALE DINO

DEVICE FOR OPENING A LOCKED DOOR OR DRAWER

SMALL

ACCEPTED

ACCEPTED

Play apparatus

Play facility that lets play participants experience visual stimulation, and with which a decorative effect can be attained. The play facility includes a frame, partition members attached to the frame and forming a play space, a gas-filled transparent tubular member that is arranged within the play space at the bottom of the facility, an air-filled air mat that is enclosed by the tubular member, a pressurizing device for filling the inside of the tubular member and the air mat with air to increase their internal pressures, an air-flow generation device for causing air within the tubular member to flow in one direction, and balloons accommodated within the tubular member and caused to flow and circulate within the tubular member by the airflow generated by the airflow generation device. Play participants can step onto the tubular member or the air-mat and feel their elasticity, and by seeing the balloons flowing and circulating inside the tubular member, they can experience visual stimulation.

1. A play facility comprising: partition members for forming a play space partitioned from an external space, and configured to let play participants play within the play space; a tubular member shaped into a tubular loop form from a pliant transparent sheet material, and formed to be gastight, said tubular member being interiorly filled with gas; a pressurizing means for charging said tubular member internally with gas to elevate its internal pressure; a gas-flow generation means for unidirectionally flowing the gas inside the said tubular member; and a plurality of flowing members accommodated inside said tubular member, for being caused to flow inside said tubular member by the gas flow generated by said gas-flow generation means. 2. The play facility according to claim 1, wherein said tubular member accommodating said flowing members is arranged at least in one location among: a bottom region inside the play space, a top region inside the play space, above said partition members, and peripherally around said partition members. 3. The play facility according to claim 1, wherein: said tubular member is arranged in a bottom region inside the play space; a pouchlike member formed similarly to said tubular member of a pliant sheet material and to be gastight is arranged to the inside of the tubular member loop; the internal space of said pouch-like member is communicated with the internal space of said tubular member; and said pressurizing means charges said tubular member and said pouch-like member with gas to elevate their internal pressure. 4. The play facility according to claim 1, wherein said gas-flow generation means is disposed inside said tubular member. 5. The play facility according to claim 1, wherein: said gas-flow generation means includes a suction port for sucking in gas, and a discharge port for discharging gas that has been sucked in and pressurized, and said gas-flow generation means is disposed externally to and in the vicinity of said tubular member; said tubular member is provided with a gas outflow port and a gas inflow port, said gas outflow port being connected to said suction port of said gas-flow generation means, and said gas inflow port being connected to said discharge port of said gas-flow generation means; and the gas inside said tubular member is fed to said gas-flow generation means through said gas outflow port and pressurized, and the pressurized gas is fed into said tubular member through said gas inflow port, so as to flow in said one direction the gas inside said tubular member. 6. The play facility according to claim 5, wherein said gas outflow port and said gas inflow port are arranged close to one another, said gas outflow port being arranged upstream and said gas inflow port being arranged downstream within said tubular member. 7. The play facility according to claim 5, wherein said gas outflow port and said gas inflow port are ranged vertically in line, with the gas outflow port being disposed above and the gas inflow port being disposed below. 8. The play facility according to claim 5, wherein said gas outflow port is provided with an adsorption prevention member, being a component having numerous through-holes and lent a form bulging from said gas outflow port into the space inside said tubular member. 9. The play facility according to claim 1, further comprising a humidifying means for humidifying the interior of said tubular member. 10. The play facility according to claim 9, wherein said humidifying means comprises a water holding means provided inside said tubular member and a water supply means for supplying water to said water holding means.

TECHNICAL FIELD The present invention relates to play facilities intended mainly for little children and that can be set up in amusement parks, department stores, or supermarkets. BACKGROUND ART Various conventional play facilities of the above-noted kind are known, in which the play participants play within a predetermined play space that is partitioned by partition members. For example, one known play facility includes pillars erected at four corners, net-like partition members stretched out between the pillars, and an air-mat or the like arranged at the bottom within the play space enclosed by the partition members. In such play facilities, a play participant such as a child rides on the air-mat and can enjoy playing on the air-mat while experiencing its elasticity by moving or jumping around on the air-mat. The partitioning with the partition members prevents children playing on the mat from inadvertently jumping outside. However, with the above-described play facility, even though the play participants can enjoy the mat's elasticity by moving about or jumping and bouncing on the mat, their visual interest is not stimulated. Decorative devices to attract the attention of the play participants for the most part have been limited to static materials such as pictures or photos attached to the partition members, and thus have not left a strong impression on the viewers nor been very attention-getting. In view of the above circumstances, it is an object of the present invention to make available a play facility that allows play participants to be given a real sense of visual interest and enables ornamental effectiveness. DISCLOSURE OF INVENTION In order to attain the above-noted objects, a play facility according to the present invention comprises partition members forming a play space that is partitioned from an outside space and configured such that a play participant can play within the play space, an gastight tubular member filled with a gas, the tubular member being made of a pliant transparent sheet member shaped into a tubular loop form; a pressurizing means for filling the tubular member with a gas and increasing its internal pressure; a gas-flow generation means for letting the gas inside the tubular member flow in one direction; and a plurality of flowing members accommodated inside the tubular member and caused to flow inside the tubular member by the gas flow generated by the gas-flow generation means. With this invention, first the pressurizing means fills the tubular member with gas and increases its internal pressure, the tubular member expands, and assumes a state in which it exhibits elasticity. Thus, play participants or the like can step onto the tubular member and jump around or sit on the tubular member, experiencing its elasticity. When the tubular member is filled with a gas, then the gas-flow generation means causes the gas inside the tubular member flow in one direction, and the plurality of flowing members accommodated inside the tubular member are caused to flow and circulate inside the tubular member by the gas flow. The play participants can see the flowing members that flow and circulate inside the tubular member through the transparent sheet member, and experience this visual stimulation. The tubular member accommodating the flowing members inside may be arranged at least at one location selected from a bottom portion inside the play space, a top portion inside the play space, a location above the partition members and the circumferential periphery of the partition members. In this case, the pressurizing means and the gas-flow generation means may be provided separately for each of the tubular members, or one set of pressurizing means and gas-flow generation means may be provided for all tubular members. When a tubular member is arranged at the upper portion of the play space or around the partition members, then a decorative effect can be attained by the flowing members that flow and circulate inside the tubular member. The tubular member may be arranged at a bottom portion inside the play space, an gastight pouchlike member made of a sheet member similarly being pliant may be arranged to the inside of the tubular member loop, an internal space of this pouchlike member being in communication with an internal space of the tubular member, and the pressurizing means may fill the gas into the tubular member and the pouchlike member, and increase their internal pressure. Thus, the pressurizing means fills both the tubular member and the pouchlike member with the gas, they expand and assume a state in which they exhibit elasticity, and play participants can step onto the tubular member and the pouchlike members, and jump around on them, experiencing their elasticity. As long as the gas-flow generation means generates a gas flow inside the tubular member, it may have any configuration, for example it may be a fan or a blower, and it may be disposed inside the tubular member. Alternatively, the gas-flow generation means may be disposed outside the tubular member in a vicinity thereof. In this case, the gas-flow generation means includes a suction port for sucking in gas, and a discharge port for discharging gas that has been sucked in and pressurized, whereas the tubular member is provided with a gas outflow port and a gas inflow port, the gas outflow port being connected to the suction port of the gas-flow generation means, and the gas inflow port being connected to the discharge port of the gas-flow generation means, and the gas inside the tubular member is fed to the gas-flow generation means through the gas outflow port and pressurized, and the pressurized gas is fed into the tubular member through the gas inflow port, so that the gas inside the tubular member flows in said one direction. Furthermore, in the above-noted case, the gas outflow port and the gas inflow port may be arranged close to one another, the gas outflow port being arranged upstream and the gas inflow port being arranged downstream within the tubular member. Alternatively, the gas outflow port and the gas inflow port may be disposed above one another, with the gas outflow port being disposed at the top and the gas inflow port being disposed at the bottom. Also, in the above-noted case, it is preferable that the gas outflow port is provided with an adsorption prevention member, which is a member having a multitude of through holes and provided with a shape that bulges from the gas outflow port into the space inside the tubular member. Thus, the gas outflow port is covered by the inward-protruding adsorption prevention member, so that flowing members flowing and circulating through the tubular member do not easily stick to gas outflow port, and it can be prevented that some of the flowing members stick to the gas outflow port and impede the flow of the other flowing members, or that the volume of gas flowing through the gas inflow port is reduced. The flowing members that are caused to flow and circulate inside the tubular member tend to rub against one another and when they are charged with static electricity, the flowing members may attract each other and stick together, impeding their ability to flow, or in extreme cases even clogging the inside of the tubular member. In this case, a humidifying means for humidifying the inside of the tubular member should be provided. Thus, the inside of the tubular member is humidified, the static electricity on the flowing members is eliminated, and the flowing members can be caused to flow and circulate with verve over long periods of time. The humidifying means may be made of a water holding means provided inside the tubular member and a water supply means for supplying water to the water holding means. Thus, static electricity can be eliminated from the flowing members flowing and circulating through the tubular member as the flowing members come in contact with the water holding means or with the moisture evaporating from the water holding means. The water holding means may be a sponge, and the water supply means may be configured with a tank storing water, and a pump for supplying the water from the tank to the water holding means, for example. For the sheet member, a sheet made of a synthetic resin, such as nylon or vinyl may be used, and for the partition members, nets made of natural or synthetic fibers may be used. Also, examples of the flowing members are balloons, such as rubber balloons, flowing members made of foamed styrene or ping-pong balls, and they can be provided with various shapes and colors. BRIEF DESCRIPTION OF DRAWINGS FIG. 1 is an isometric view showing the overall configuration of a preferred play facility according to the present invention; FIG. 2 is a plan view showing this play facility, in a section taken along view-directing B-B in FIG. 3; FIG. 3 is a elevation view in a section taken along view-directing A-A in FIG. 2; FIG. 4 is a side view in a section taken along view-directing C-C in FIG. 3; FIG. 5 is a fragmentary section taken along view-directing D-D in FIG. 2; and FIG. 6 is a fragmentary section taken along view-directing E-E in FIG. 5. Furthermore, FIG. 7 is a sectional view showing the overall configuration of another preferred play facility according to the present invention; FIG. 8 is a sectional plan view fragmentarily showing yet another preferred play facility according to the present invention; FIG. 9 is a sectional elevation view showing the overall configuration of still another preferred play facility according to the present invention; and FIG. 10 is a sectional view showing the overall configuration of yet a further preferred play facility according to the present invention. BEST MODE FOR CARRYING OUT THE INVENTION The following is a more detailed explanation of the present invention, with reference to the accompanying drawings. As shown in FIGS. 1 to 4, a play facility 1 of this example includes a frame 10, partition members 14 attached to the frame 10 and forming a predetermined play space Y, a tubular member 20 filled with air that is arranged at the bottom within the play space Y, an air-mat 25 filled with air that is arranged at the center at the bottom within the play space Y and enclosed by the tubular member 20, a plurality of balloons 30 accommodated within the tubular member 20, a pressurizing means 31 for filling the inside of the tubular member 20 and the air-mat 25 with air and increasing their internal pressure, a gas-flow generation means 32 for letting air within the tubular member 20 flow in one direction, and a humidifying means 33 for humidifying the inside of the tubular member 20. Moreover, this play facility 1 is provided with an entrance 15 through which play participants can enter or leave the play space Y, and steps 16. The frame 10 is made of pole members 11, girder members 12 and bottom side members 13, as well as joints (not shown in the drawings) for linking these together in a deconstructable manner. The pole members 11, the girder members 12 and the bottom side members 13 are each made of a thin-walled pipe made of steel or aluminum, a shock-absorbing material such as a urethane sponge wound around the outer circumferential surface of the thin-walled pipe, and a vinyl sheet covering this shock-absorbing member. The partition members 14 are, for example, formed of nets made of natural or synthetic fibers, and are arranged at the portions corresponding to the four lateral sides (except for the entrance 15) of the play space Y and the upper side of the play space Y. It should be noted that the partition members 14 are attached at their periphery to the frame 10 in a removable manner by fastening means (not shown in the drawings) such as zippers or Velcro™. The tubular member 20 is shaped into a tubular loop form (rectangular in plan view) from a transparent sheet member made of a synthetic resin, such as nylon or vinyl, for example. The tubular member 20 is formed gastight, and attached at its outer periphery to the partition members 14 and the bottom side members 13 in a removable manner with fastening means (not shown in the drawings) such as zippers or Velcro™. The air-mat 25 is made by connecting three tubular members 26 such that their inner spaces are linked to one another. Each of the tube members 26 is made gastight from a transparent sheet member made of a synthetic resin, such as nylon or vinyl, for example, and linked to the tubular member 20 such that its inside is in communication with the inside of the tubular member 20. The pressurizing means 31 is constituted from a blower or the like, which is connected to the circumferential periphery of the tubular member 20, supplies air into the tubular member 20, and raises the air pressure inside the tubular member 20 to a predetermined pressure. It should be noted that, as pointed out above, the inside of the tubular member 20 is in communication with the inside of the air-mat 25, so that the air that is supplied from the pressurizing means 31 also flows from the tubular member 20 to the air-mat 25, pressurizing the inside of the air-mat 25 together with the tubular member 20. Moreover, the humidifying means 33 is constituted from a humidifier connected to the circumferential periphery of the tubular member and that supplies steam to the inside of the tubular member 20, thus humidifying the inside of the tubular member 20. The gas-flow generation means 32 is constituted from a blower or the like, and, as shown in FIGS. 5 and 6, is provided with a suction port 32a for sucking in air and a discharge port 32b for discharging air that has been sucked in and pressurized. The suction port 32a is connected to a gas outflow port 20a formed in the tubular member 20, whereas the discharge port 32b is similarly connected to a gas inflow port 20a formed in the tubular member 20. The air inside the tubular member 20 flows from the gas outflow port 20a into the gas-flow generation means 32, is pressurized, and the pressurized air is fed through the gas inflow port 20b into the tubular member 20. Through this operation, the air inside the tubular member 20 is caused to flow in the direction indicated by the arrows in FIG. 2. Moreover, the suction port 32a and the gas outflow port 20a on the one hand and the discharge port 32b and the gas inflow port 20b on the other hand are arranged above one another, with the suction port 32a and the gas outflow port 20a being arranged on top and the discharge port 32b and the gas inflow port 20b being arranged below that. Furthermore, the gas outflow port 20a (suction port 32a) is provided with an adsorption prevention member 34, which is a member provided with a multitude of through holes and having a (semispherical) shape that bulges from the gas outflow port 20a into the space inside the tubular member 20. Moreover, the suction port 32a, the gas outflow port 20a, the discharge port 32b and the gas inflow port 20b are arranged at a corner of the tubular member 20, when viewed from above, so that the direction of the air flow from the discharge port 32b (gas inflow port 20b) into tubular member 20 is aligned with one side of the tubular member 20. A space is provided inside the steps 16, and the pressurizing means 31, the gas-flow generation means 32 and the humidifying means 33 are accommodated inside this internal space. Moreover, the steps 16 are covered by a shock-absorbing material, such as urethane sponge, and the shock-absorbing member is furthermore covered by a vinyl sheet or the like. This shock-absorbing member has the function of absorbing shocks and preventing a play participant from getting bruised if he or she should fall down, and also functions to reduce noise, so that the operating noise of the pressurizing means 31, the gas-flow generation means 32 and the humidifying means 33 does not escape outside. With the play facility 1 of the example configured as described above, first, the pressurizing means 31 supplies air into the tubular member 20. Thus, air is filled into the tubular member 20 and the air-mat 25, whose internal pressure is raised to a predetermined pressure, and the tubular member 20 and the air-mat 25 expand, assuming an elastic state. Thus, a play participant can step onto the tubular member 20 and the air-mat 25 in this state, and can enjoy experiencing the mat's elasticity by jumping and bouncing on the mat. After the inside of the tubular member 20 and the air-mat 25 have been pressurized to a certain pressure, it is possible to either keep supplying air with the pressurizing means 31 or to seal the supply portion shut, in order to sustain the pressure. After this, the gas-flow generation means 32 is driven, the air inside the tubular member 20 flows into the gas-flow generation means 32 through the gas outflow port 20a (suction port 32) and is pressurized, and the pressurized air is ejected through the gas inflow port 20b (discharge port 32b) into the tubular member 20. This operation generates an air flow that lets the air inside the tubular member 20 flow and circulate in the direction of the arrows in FIG. 2. Thus, with this generated air flow, the plurality of balloons 30 accommodated inside the tubular member 20 are caused to flow and circulate inside the tubular member 20, and viewing the balloons 30 from the outside, the visual interest of the play participants is stimulated. It should be noted that when the gas inflow port 20b (discharge port 32b) and the gas outflow port 20a (suction port 32a) are arranged at a distance from one another, then the air flow inside the tubular member 20 will weaken between the gas inflow port 20b (discharge port 32b) and the gas outflow port 20a (suction port 32a), which may compromise the flow properties of the balloons 30 or make it impossible to let the balloons 30 flow with verve, thus diminishing the above-noted visually stimulating effect. In this example, the gas inflow port 20b (discharge port 32b) and the gas outflow port 20a (suction port 32a) are arranged close together, and moreover arranged on top of one another, so that the air flow in the tubular member 20 between the gas inflow port 20b (discharge port 32b) and the gas outflow port 20a (suction port 32a) is not weakened, and the balloons 30 are vigorously circulated. Also, gravity tends to pull the balloons 30 to the bottom inside the tubular member 20, but since the gas inflow port 20b (discharge port 32b) is arranged at the bottom, the air flow discharged from the gas inflow port 20b (discharge port 32b) directly hits the balloons 30 which tend to be located at the bottom, and also in this regard the balloons 30 can be vigorously circulated. Moreover, if nothing is provided at the gas outflow port 20a (suction port 32a), then it may occur that a balloon 30 is sucked against the gas outflow port 20a (suction port 32a), closing it and extinguishing the air flow within the tubular member 20, but in the present example, the adsorption prevention member 34 with the above-noted shape is provided at the gas outflow port 20a (suction port 32a), so that it does not occur that the gas outflow port 20a (suction port 32a) is closed shut by the balloons 30, and stable flow of the balloons 30 can be ensured. Furthermore, the balloons 30 that are caused to flow and circulate inside the tubular member 20 tend to rub against one another and be charged with static electricity, and when they are charged with static electricity, the balloons 30 may attract each other and stick together, impeding their ability to flow, or in extreme cases even clogging the inside of the tubular member. In the present example, the humidifying means 33 is arranged inside the tubular member 20, so that the inside of the tubular member 20 is humidifyied by this humidifying means 33, eliminating the static electricity that has formed on the balloons 30, so that long-term vigorous flow and circulation of the balloons 30 can be ensured. Moreover, shock-absorbing material is wound around the pillar members 11 and the girder members 12, so that if children playing inside the play space Y accidentally hit the pillar members 11 or girder members 12, then the shock of the collision is absorbed by the shock-absorbing members, effectively preventing the play participants from hurting themselves. The foregoing is an explanation of an embodiment of the present invention, but specific forms that can be adopted for the present invention are not limited to the above configuration. For example, as shown in FIG. 7, the tubular member 20 may be provided not only at the bottom inside the play space Y, but also on top of the play space Y Thus, the balloons 30, which flow and circulate inside the tubular member 20 provided on top of the play space Y, can be observed from the play space Y and from the outside, and their decorative effect can be enhanced. In this case, the pressurizing means 31 and the gas-flow generation means 32 may be provided separately for each of the tubular members 20, or one set of pressurizing means 31 and gas-flow generation means 32 may be provided for both tubular members 20. The location where the tubular member 20 is arranged in order to attain the above-noted decorative effect is not limited to the top of the play space Y, and the tubular member 20 may also be provided around the play space Y or at an upper portion within the play space Y. Also, there is no particular limitation regarding the shape of the tubular member 20, as long as the balloons 30 can flow and circulate within the tubular member 20. Moreover, the gas inflow port 20b (discharge port 32b) and the gas outflow port 20a (suction port 32a) were arranged above one another, but there is no limitation to this, and it is also possible to arrange the gas outflow port 20a (suction port 32a) at an upstream location and the gas inflow port 20b (discharge port 32b) at a downstream location within the tubular member 20, as shown in FIG. 8. However, for the above-noted reasons, it is preferable that they are arranged close to one another. Moreover, the gas-flow generation means 32 was arranged outside the tubular member 20, but there is no limitation to this, and it is also possible to arrange a gas-flow generation means 32′ within the tubular member 20, as shown in FIG. 9. In FIG. 9, reference numeral 32a′ denotes a suction port and reference numeral 32b′ denotes a discharge port. Moreover, as shown in FIG. 9, the humidifying means 33 may also be made of a water holding means 33a disposed inside the tubular member 20 and a water supply means supplying water to this water holding means 33a. Thus, static electricity on the balloons 30 circulating inside the tubular member 20 is eliminated as the balloons 30 come in contact with the water holding means 33a or with the moisture evaporating from the water holding means 33a. An example of the water holding means 33a is a sponge, and an example of the water supply means is a configuration made of a tank 33b storing water, and a pump for supplying the water from the tank 33b to the water holding means 33a. Furthermore, in this case, if the tank 33b is arranged at a high location, such as above the girder members 12, and water is supplied from the tank 33b via a water supply pipe 33c to the water holding means 33a, then the water is supplied to the water holding means 33a through the water pressure, so that there is no particular need to install a pump. Also, in the foregoing example, an air-mat 25 was placed in the center at the bottom of the play space Y, surrounded by the tubular member 20, but there is no limitation to this, and as shown in FIG. 10, it is also possible to place a mat 50 filled with a liquid and made of a sheet member formed into an gastight pouch, in the center at the bottom of the play space Y Thus, it becomes possible to experience different sensations than with the air-mat 25. Instead of the mat 50, it is also possible to provide a ball pool in the region enclosed by the tubular member 20 and accommodating a multitude of balls, or to provide smaller versions of the tubular 20 in a concentric arrangement. Thus, by arranging various members and contrivances in the region enclosed by the tubular member 20, it is possible to provide a variety of play options. Also, for the balloons 30, it is possible to use balloons of various shapes, patterns and colors. Moreover, there is no limitation to balloons 30, and it is possible to use anything that can be circulated by a gas flow, such as foamed styrene or ping-pong balls. INDUSTRIAL APPLICABILITY As explained in the foregoing, a play facility according to the present invention can be installed in amusement parks, department stores or supermarkets, and is mainly suitable as a play facility for children.

<SOH> BACKGROUND ART <EOH>Various conventional play facilities of the above-noted kind are known, in which the play participants play within a predetermined play space that is partitioned by partition members. For example, one known play facility includes pillars erected at four corners, net-like partition members stretched out between the pillars, and an air-mat or the like arranged at the bottom within the play space enclosed by the partition members. In such play facilities, a play participant such as a child rides on the air-mat and can enjoy playing on the air-mat while experiencing its elasticity by moving or jumping around on the air-mat. The partitioning with the partition members prevents children playing on the mat from inadvertently jumping outside. However, with the above-described play facility, even though the play participants can enjoy the mat's elasticity by moving about or jumping and bouncing on the mat, their visual interest is not stimulated. Decorative devices to attract the attention of the play participants for the most part have been limited to static materials such as pictures or photos attached to the partition members, and thus have not left a strong impression on the viewers nor been very attention-getting. In view of the above circumstances, it is an object of the present invention to make available a play facility that allows play participants to be given a real sense of visual interest and enables ornamental effectiveness.

<SOH> BRIEF DESCRIPTION OF DRAWINGS <EOH>FIG. 1 is an isometric view showing the overall configuration of a preferred play facility according to the present invention; FIG. 2 is a plan view showing this play facility, in a section taken along view-directing B-B in FIG. 3 ; FIG. 3 is a elevation view in a section taken along view-directing A-A in FIG. 2 ; FIG. 4 is a side view in a section taken along view-directing C-C in FIG. 3 ; FIG. 5 is a fragmentary section taken along view-directing D-D in FIG. 2 ; and FIG. 6 is a fragmentary section taken along view-directing E-E in FIG. 5 . Furthermore, FIG. 7 is a sectional view showing the overall configuration of another preferred play facility according to the present invention; FIG. 8 is a sectional plan view fragmentarily showing yet another preferred play facility according to the present invention; FIG. 9 is a sectional elevation view showing the overall configuration of still another preferred play facility according to the present invention; and FIG. 10 is a sectional view showing the overall configuration of yet a further preferred play facility according to the present invention. detailed-description description="Detailed Description" end="lead"?

20040819

20071225

20050804

74020.0

NGUYEN, KIEN T

Play facility

SMALL

ACCEPTED

ACCEPTED

Semiconductor nanoparticle and method for producing same

The invention provides a semiconductor nanoparticle comprising a semiconductor nanoparticle core on the surface of which electron-releasing groups are arranged, the semiconductor nanoparticle having a fluorescent property and water-solubility. The invention also provides a water-soluble semiconductor nanoparticle with an excellent fluorescent property that can be easily prepared by adding a surface-treating material for providing a semiconductor nanoparticle with one or more kinds of electron-releasing groups, and arranging the electron-releasing groups on the surface of the semiconductor nanoparticle core.

1. A semiconductor nanoparticle comprising a core on the surface of which electron-releasing groups are arranged, said semiconductor nanoparticle having a fluorescent property. 2. The semiconductor nanoparticle according to claim 1, wherein said electron-releasing groups are of at least one type selected from the group consisting of —OR, —OCH2R, —OCOCH2R, —NHR, —N(CH2R)2, —NHCOCH2R, —CH2R, and —C6H4R, where R is one selected from the group consisting of hydrogen and substituted or unsubstituted hydrocarbon groups. 3. The semiconductor nanoparticle according to claim 1, wherein the surface of the semiconductor nanoparticle on which the electron-releasing groups are arranged is stabilized by an ionic compound. 4. The semiconductor nanoparticle according to claim 1, wherein the ionic compound is of at least one type selected from the group consisting of ammonia, primary amines (R1NH2), secondary amines (R1R2NH), tertiary amines (R1R2R3N), quaternary ammonium compounds (R4R5R6R7N), where R1 to R7 are each selected from the group consisting of hydrogen and substituted or unsubstituted hydrocarbon groups. 5. The semiconductor nanoparticle according to claim 1, wherein a material of the core of the semiconductor nanoparticle is selected from the group consisting of ZnO, ZnS, ZnSe, ZnTe, CdO, CdS, CdMnS, CdSe, CdMnSe, CdTe, CdMnTe, HgS, HgSe, HgTe, InP, InAs, InSb, InN, GaN, GaP, GaAs, GaSb, TiO2, WO3, PbS, PbSe, MgTe, AlAs, AlP, AlSb, AlS, Ge, and Si. 6. The semiconductor nanoparticle according to claim 1, wherein said semiconductor nanoparticle is water-soluble. 7. A process of manufacturing a semiconductor nanoparticle having a fluorescent property, said process comprising adding a surface-treating material for providing the semiconductor nanoparticle with electron-releasing groups of one or more kinds, and arranging the electron-releasing groups on the surface of the core of the semiconductor nanoparticle. 8. The process of manufacturing a semiconductor nanoparticle according to claim 7, wherein the surface-treating material for providing the surface of the semiconductor nanoparticle with electron-releasing groups is of at least one kind of nitrogenated compounds selected from the group consisting of ammonia, amines, ammoniums, nitriles, and isocyanates, or oxygenated compounds selected from the group consisting of alcohols, phenols, ketones, aldehydes, carboxylic acids, esters of organic or inorganic acids, ethers, acid amides, and acid anhydrides. 9. The process of manufacturing a semiconductor nanoparticle according to claim 7, wherein the surface-treating material for providing the surface of the semiconductor nanoparticle with an electron-releasing groups is of at least one kind selected from the group consisting of ammonia, primary amines (R1NH2), secondary amines (R1R2NH), tertiary amines (R1R2R3N), quaternary ammonium compounds (R4R5R6R7N+), where R1 to R7 are each selected from the group consisting of hydrogen and substituted or unsubstituted hydrocarbon groups. 10. The process of manufacturing a semiconductor nanoparticle according to any one of claims 7, wherein, on the surface of a semiconductor nanoparticle modified with a thiol group, the thiol compound is ionized and isolated in an alkaline environment, and then a surface-treating material for providing electron-releasing groups is added in order to substitute a functional group. 11. The process of manufacturing a semiconductor nanoparticle according to claim 7, wherein said semiconductor nanoparticle is water-soluble. 12. A fluorescent reagent comprising a semiconductor nanoparticle having a core on the surface of which electron-releasing groups are arranged, said semiconductor nanoparticle having a fluorescent property. 13. An optical device comprising a semiconductor nanoparticle having a core on the surface of which electron-releasing groups are arranged, said semiconductor nanoparticle having a fluorescent property. 14. The fluorescent agent according to claim 12, wherein said electron-releasing groups are of at least one type selected from the group consisting of —OR, —OCH2R, —OCOCH2R, —NHR, —N(CH2R)2, —NHCOCH2R, —CH2R, and —C6H4R, where R is one selected from the group consisting of hydrogen and substituted or unsubstituted hydrocarbon groups. 15. The fluorescent agent according to claim 12, wherein the surface of said semiconductor nanoparticle on which the electron-releasing groups are arranged is stabilized by an ionic compound. 16. The fluorescent agent according to claim 12, wherein the ionic compound is of at least one type selected from the group consisting of ammonia, primary amines (R1NH2), secondary amines (R1R2NH), tertiary amines (R1R2R3N), quaternary ammonium compounds (R4R5R6R7N+), where R1 to R7 are each selected from the group consisting of hydrogen and substituted or unsubstituted hydrocarbon groups. 17. The fluorescent agent according to claim 12, wherein a material of the core of said semiconductor nanoparticle is selected from the group consisting of ZnO, ZnS, ZnSe, ZnTe, CdO, CdS, CdMnS, CdSe, CdMnSe, CdTe, CdMnTe, HgS, HgSe, HgTe, InP, InAs, InSb, InN, GaN, GaP, GaAs, GaSb, TiO2, WO3, PbS, PbSe, MgTe, AlAs, AlP, AlSb, AlS, Ge, and Si. 18. The fluorescent agent according to claim 12, wherein said semiconductor nanoparticle is water-soluble. 19. The optical device according to claim 13, wherein said electron-releasing groups are of at least one type selected from the group consisting of —OR, —OCH2R, —OCOCH2R, —NHR, —N(CH2R)2, —NHCOCH2R, —CH2R, and —C6H4R, where R is one selected from the group consisting of hydrogen and substituted or unsubstituted hydrocarbon groups. 20. The optical device according to claim 13, wherein the surface of said semiconductor nanoparticle on which the electron-releasing groups are arranged is stabilized by an ionic compound. 21. The optical device according to claim 13, wherein the ionic compound is of at least one type selected from the group consisting of ammonia, primary amines (R1NH2), secondary amines (R1R2NH), tertiary amines (R1R2R3N), quaternary ammonium compounds (R4R5R6R7N+), where R1 to R7 are each selected from the group consisting of hydrogen and substituted or unsubstituted hydrocarbon groups. 22. The optical device according to claim 13, wherein a material of the core of said semiconductor nanoparticle is selected from the group consisting of ZnO, ZnS, ZnSe, ZnTe, CdO, CdS, CdMnS, CdSe, CdMnSe, CdTe, CdMnTe, HgS, HgSe, HgTe, InP, InAs, InSb, InN, GaN, GaP, GaAs, GaSb, TiO2, WO3, PbS, PbSe, MgTe, AlAs, AlP, AlSb, AlS, Ge, and Si. 23. The optical device according to claim 13, wherein said semiconductor nanoparticle is water-soluble.

FIELD OF THE INVENTION The present invention relates to a semiconductor nanoparticle and a process of manufacturing the same. In particular, the invention relates to a stable and water-soluble semiconductor nanoparticle and a process of manufacturing the same. The invention also relates to a fluorescent reagent and an optical device comprising the semiconductor nanoparticle. BACKGROUND ART Semiconductor nanoparticles with a particle size of less than 10 nm lie in a transition region between bulk semiconductor crystals and molecules. They exhibit physicochemical properties that are different from those of both bulk semiconductor crystals and molecules. In this region, the energy gap of the semiconductor nanoparticles increases with decreasing particle size, due to the emergence of the quantum size effect. This is further accompanied by the removal of the energy band degeneracy that is observed in bulk semiconductors, so that the orbits become discrete, with the lower end of the conduction band shifted to the negative side and the upper end of the valence band shifted to the positive side. CdS semiconductor nanoparticles can be easily prepared by dissolving equimolar amounts of Cd and S precursors. The same is true for the manufacture involving CdSe, ZnS, ZnSe, HgS, HgSe, PbS, or PbSe, for example. Semiconductor nanoparticles are gaining much attention because they are capable of emitting strong fluorescence with a narrow full width at half maximum, which makes it possible to produce a variety of fluorescent colors, thereby opening up a great variety of future applications. However, the semiconductor nanoparticles obtained by simply mixing precursors as mentioned above exhibit a wide particle size distribution, and consequently the properties of the semiconductor nanoparticles cannot be fully utilized. Attempts have been made to accurately conduct particle size separation on semiconductor nanoparticles immediately after preparation that have a wide particle size distribution, using a chemical technique, and then separate and extract only those semiconductor nanoparticles with a specific particle size, with a view to achieving monodispersion. Such attempts include an electrophoretic separation process utilizing the fact that the surface charge possessed by nanoparticles varies depending on particle size, an exclusion chromatography process that takes advantage of the difference in retention time depending on particle size, and a size-selective precipitation process that utilizes the difference in dispersibility into an organic solvent depending on particle size. The foregoing are examples of techniques for classifying the nanoparticles prepared by mixing precursors according to particle size. Another technique for achieving monodispersion of particle size has also been reported; namely, a size-selective photoetching process that utilizes the oxidizing dissolution of a metal chalcogenide semiconductor upon light irradiation in the presence of dissolved oxygen. There is yet another method in which monodispersion of particle size is controlled at the stage of mixture of the precursors. One typical example is a reversed micelle method. In this method, amphipathic molecules, such as diisooctyl sodium sulfosuccinate, and water are mixed in an organic solvent, such as heptane, thereby forming a reverse micelle in the organic solvent, such that precursors are reacted with each other using only the aqueous phase in the reverse micelle. The size of the reverse micelle is determined by the quantitative ratio of the amphipathic molecules to the water, so that the size can be relatively uniformly controlled. The size of the thus prepared semiconductor nanoparticle is dependent on the size of the reverse micelle, so that it is possible to prepare semiconductor nanoparticles with relatively uniform particle sizes. While the semiconductor nanoparticles obtained by the aforementioned processes exhibit a relatively narrow particle size distribution, the fluorescent properties of the thus prepared semiconductor nanoparticles exhibit a gradual fluorescent spectrum without any significant peaks. Moreover, the fluorescent spectrum exhibits a peak at a wavelength that is different from the theoretical value of the fluorescence that is supposed to be emitted by the semiconductor nanoparticles. Specifically, in addition to the bandgap fluorescence exhibited from the inside of the semiconductor nanoparticles, the aforementioned semiconductor nanoparticles emit totally separate fluorescence that is believed to be emitted by energy levels existing in the forbidden band of energy levels of the semiconductor nanoparticles. The energy levels that emit this fluorescence are believed to exist mainly at a surface site of the semiconductor nanoparticles. This is a phenomenon that adversely affects the properties of the semiconductor nanoparticles with a narrow particle size distribution and has remained a problem to be solved, as the changes in fluorescent properties brought about by controlling the particle size of semiconductor nanoparticles originally appear in bandgap fluorescence. As a typical solution to the above problem, a method has been attempted that would coat a semiconductor material as a core with a semiconductor material that has a larger bandgap than that of the core's semiconductor material, an inorganic material, and an organic material, thereby forming a multilayer structure in order to suppress the aforementioned fluorescence. Typical examples of coating with an inorganic material include a coating of a CdSe nanoparticle with CdS (J. Phys. Chem. 100: 8927 (1996)), a coating of a CdS nanoparticle with ZnS (J. Phys. Chem. 92: 6320 (1988)), and a coating of a CdSe nanoparticle with ZnS (J. Am. Chem. Soc. 112: 1327 (1990)). With regard to the coating of a CdSe nanoparticle with ZnS, the Ostwald ripening phenomenon has been successfully utilized to obtain semiconductor nanoparticles with a sufficient fluorescent property by conducting the coating in a coordination solvent (J. Phys. Chem. B. 101: 9463 (1997)). In the aforementioned multilayered semiconductor nanoparticle, the particle is coated with a material having a larger bandgap than that of the semiconductor nanoparticle and having no bandgap in the forbidden band thereof. This is in order to suppress the defective sites on the surface of the semiconductor nanoparticle so that the inherent fluorescent property of the semiconductor nanoparticle can be obtained. In a method of surface processing in an aqueous solution, an improvement has been reported in the fluorescent property of the semiconductor nanoparticle in an alkali aqueous solution (J. Am. Chem. Soc. 109: 5655 (1987)). Although various experiments and reports have been made based on this report, none have successfully shed light on the mechanism (J. Phys. Chem. 100: 13226 (1996); J. Am. Chem. Soc. 122: 12142 (2000), for example). Moreover, none of the semiconductor nanoparticles in the alkali solution have sufficient reproducibility, and the reproduction conditions have not been identified. Furthermore, none of the experiments or reports has succeeded in isolating the final product. As an example of the method for coating with an organic material, a synthesization process can be cited that utilizes the Ostwald ripening phenomena in a coordination solvent. It employs a coating material such as TOPO (trioctylphosphine) or hexadecylamine (HDA) as the coating material, for example, to obtain semiconductor nanoparticles with high light-emission properties (J. Am. Chem. Soc. 122: 12142 (2000), J. Lumin. 98, 49 (2002), for example). It should be noted, however, that the finally obtained semiconductor nanoparticle is not water-soluble. The semiconductor nanoparticle obtained by the above-described methods is capable of suppressing a defect site to some extent and has the inherent properties of a semiconductor nanoparticle to some extent. However, in order to prepare such a semiconductor nanoparticle, a highly sophisticated technique is required, and in order to achieve high quality, a variety of equipment is required. Further, they are seriously deficient for the purpose of industrial production from the viewpoint of the cost of reagents and safety during high temperature reaction. DISCLOSURE OF THE INVENTION The properties of semiconductor nanoparticles are such that they are more durable than the currently employed reagents such as organic pigments, and they hardly fades. By varying the particle size, reagents that exhibit various spectra with narrow full widths at half maximum can be created from the same material. Thus, the semiconductor nanoparticle can be adapted not only for optical devices but also biopolymer detection and bioimaging purposes, for example, in a wide variety of applications. For these reasons, the semiconductor nanoparticles have been gaining attention in recent years, and the solving of the aforementioned problems has been an issue among researchers. As mentioned above, the surface condition of the semiconductor nanoparticle is thought to be involved in the defective fluorescence of a monolayer semiconductor nanoparticle. Based on this hypothesis, the inventors conducted an analysis of the influence of the surface condition of the semiconductor nanoparticle. As a solution for the relevant defects, the inventors conducted studies, focusing on the fact that the emission properties of semiconductor nanoparticles in the aforementioned alkaline aqueous solution are very good. As a result, they eventually succeeded in isolating and purifying only those semiconductor nanoparticles that have been subjected to an alkaline treatment, and successfully shed light on the mechanism of light emission. Nevertheless, the resultant semiconductor nanoparticles were obtained in the form of a cottony precipitation that did not completely dissolve in water, such that the semiconductor nanoparticles were very inconvenient to handle. The inventors proceeded with further research and studies and arrived at the present invention after realizing that the semiconductor nanoparticles could be rendered completely water-soluble by subjecting them to a treatment involving a group of specific compounds. In a first aspect, the invention provides a semiconductor nanoparticle comprising a core on the surface of which electron-releasing groups are arranged, said semiconductor nanoparticle having a fluorescent property. The semiconductor nanoparticle per se can be formed from a wide variety of known materials. Examples of the material of the core of the semiconductor nanoparticle include ZnO, ZnS, ZnSe, ZnTe, CdO, CdS, CdMnS, CdSe, CdMnSe, CdTe, CdMnTe, HgS, HgSe, HgTe, InP, InAs, InSb, InN, GaN, GaP, GaAs, GaSb, TiO2, WO3, PbS, PbSe, MgTe, AlAs, AlP, AlSb, AlS, Ge, and Si. The electron-releasing groups arranged on the surface of the core of the semiconductor nanoparticle should preferably be of at least one type selected from the group consisting of —OR, —OCH2R, —OCOCH2R, —NHR, —N(CH2R)2, —NHCOCH2R, —CH2R, and —C6H4R, where R is one selected from the group consisting of hydrogen and substituted or unsubstituted hydrocarbon groups. The surface of the semiconductor nanoparticle on which the electron-releasing groups are arranged should preferably be further stabilized by an ionic compound. As the ionic compound, at least one type should preferably be selected from the group consisting of ammonia, primary amines (R1NH2), secondary amines (R1R2NH), tertiary amines (R1R2R3N), quaternary ammonium compounds (R4R5R6R7N+), where R1 to R7 are each selected from the group consisting of hydrogen and substituted or unsubstituted hydrocarbon groups. The semiconductor nanoparticle in which the electron-releasing groups are arranged on the surface of the core of the semiconductor nanoparticle is normally water-soluble as well as it has a fluorescent property. In a second aspect, the invention provides a process of manufacturing a semiconductor nanoparticle having a fluorescent property, said process comprising adding a surface-treating material for providing the semiconductor nanoparticle with electron-releasing groups of one or more kinds, and arranging the electron-releasing groups on the surface of the semiconductor nanoparticle core. Examples of the surface-treating material for providing the one or more types of electron-releasing groups include those with an unshared electron pair, such as ammonia, a variety of amines, and ether. Specifically, the surface-treating material should preferably be of one or more kind of nitrogenated compounds selected from the group consisting of ammonia, amines, ammoniums, nitriles, and isocyanates, or oxygenated compounds selected from the group consisting of alcohols, phenols, ketones, aldehydes, carboxylic acids, esters of organic or inorganic acids, ethers, acid amides, and acid anhydrides. Of these nitrogenated compounds, preferable examples include one or more selected from the group consisting of ammonia, primary amines (R1NH2), secondary amines (R1R2NH), tertiary amines (R1R2R3N), quaternary ammonium compounds (R4R5R6R7N+), where R1 to R7 are each selected from the group consisting of hydrogen and substituted or unsubstituted hydrocarbon groups. Examples of the aforementioned nitrogenated compounds include amines such as methylamine, ethylamine, propylamine, butylamine, dimethylamine, diethylamine, dipropylamine, dibutylamine, trimethylamine, triethylamine, tripropylamine, tributylamine, piperidine, tribenzylamine, aniline, pyridine, picoline, and tetramethylethylenediamine; quaternary ammoniums such as ammonium hydroxide, ammonium halide, and trialkylammonium; nitriles such as acetonitrile, benzonitrile, and tolunitrile; and amino acids, amido amines, etheramines, amine hydroxides, and carboxylic amines that include various functional groups in the molecules thereof. Examples of the oxygenated compounds include alcohols with the number of carbon atoms 1 to 18, such as methanol, ethanol, propanol, pentanol, hexanol, octanol, dodecanol, octadecyl alcohol, oleyl alcohol, benzyl alcohol, phenylethyl alcohol, cumyl alcohol, isopropyl alcohol, isopropyl benzyl alcohol; phenols with the number of carbon atoms 6 to 20 that may include a lower alkyl group, such as phenol, cresol, xylenol, ethylphenol, propylphenol, nonyl phenol, cumyl phenol, and naphthol; ketones with the number of carbon atoms 3 to 15, such as acetone, methyl ethyl ketone, methyl isobutyl ketone, acetophenone, benzophenone, and benzoquinone; aldehydes with the number of carbon atoms 2 to 15, such as acetoaldehyde, propionaldehyde, octyl aldehyde, benzaldehyde, tolualdehyde, and naphthoaldehyde; organic acid esters with the number of carbon atoms 2 to 30, such as methyl formate, methyl acetate, ethyl acetate, vinyl acetate, propyl acetate, octyl acetate, cyclohexyl acetate, ethyl propylate, ethyl valerate, methyl chloroacetate, ethyl dichloroacetate, ethyl methacrylate, ethyl crotonate, ethyl cyclohexane carboxylate, methyl benzoate, ethyl benzoate, propyl benzoate, butyl benzoate, octyl benzoate, cyclohexyl benzoate, phenyl benzoate, benzyl benzoate, methyl toluate, ethyl toluate, amyl toluate, ethyl ethylbenzoate, methyl anisate, di-n-hexyl cyclohexenecarboxylate, γ-butyrolactone, δ-valerolactone, coumarin, phthalide, and ethylene carbonate; acid halides with the number of carbon atoms 2 to 15, such as acetyl chloride, benzoyl chloride, toluic acid chloride, and anisic acid chloride; ethers or diethers with the number of carbon atoms 2 to 20, such as methyl ether, ethyl ether, isopropyl ether, butyl ether, amyl ether, tetrahydrofuran, and anisole; acid amides such as acetic acid amide, amide benzoate, toluic acid amide; and acid anhydrides such as acetic anhydride, phthalic anhydride, and benzoic anhydride. A major feature of the semiconductor nanoparticle of the invention on which the aforementioned electron-releasing groups are arranged is that it is water-soluble, such that it can be handled with ease in various applications. In a third aspect, the invention provides a fluorescent reagent that takes advantage of the fluorescent property of the aforementioned semiconductor nanoparticle. In a fourth aspect, the invention provides an optical device that takes advantage of the fluorescent property of the aforementioned semiconductor nanoparticle. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 shows the absorption spectrum of a semiconductor nanoparticle prepared in Example 1. FIG. 2 shows the fluorescent spectrum of a semiconductor nanoparticle prepared in Example 1. FIG. 3 shows the absorption spectrum of a semiconductor nanoparticle prepared in Example 2. FIG. 4 shows the fluorescent spectrum of the semiconductor nanoparticle prepared in Example 2. FIG. 5 shows the absorption spectrum of a semiconductor nanoparticle prepared in Example 3. FIG. 6 shows the fluorescent spectrum of the semiconductor nanoparticle prepared in Example 3. FIG. 7 shows the absorption spectrum of a semiconductor nanoparticle prepared in Example 4. FIG. 8 shows the fluorescent spectrum of the semiconductor nanoparticle prepared in Example 4. FIG. 9 shows the absorption spectrum of a semiconductor nanoparticle prepared in Example 5. FIG. 10 shows the fluorescent spectrum of a semiconductor nanoparticle prepared in Example 5. FIG. 11 shows the absorption spectrum of a semiconductor nanoparticle prepared in Example 6. FIG. 12 shows the fluorescent spectrum of the semiconductor nanoparticle prepared in Example 6. FIG. 13 shows the absorption spectrum of a semiconductor nanoparticle prepared in Example 7. FIG. 14 shows the fluorescent spectrum of the semiconductor nanoparticle prepared in Example 7. FIG. 15 shows the absorption spectrum of a semiconductor nanoparticle prepared in Example 8. FIG. 16 shows the fluorescent spectrum of the semiconductor nanoparticle prepared in Example 8. FIG. 17 shows the absorption spectrum of the semiconductor nanoparticle prepared in Example 9. FIG. 18 shows the fluorescent spectrum of a semiconductor nanoparticle prepared in Example 9. FIG. 19 shows the absorption spectrum of the semiconductor nanoparticle prepared in Example 10. FIG. 20 shows the fluorescent spectrum of a semiconductor nanoparticle prepared in Example 10. DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereafter, processes for manufacturing the semiconductor nanoparticle according to the invention will be described by way of examples. While the following examples involve the size-selective optical etching process, any other process may be employed as long as it is capable of producing a stabilized or modified semiconductor nanoparticle as a final product. Process of Preparing a Semiconductor Nanoparticle Semiconductor nanoparticles have a surface area that is extremely large in comparison with its volume, and they are easily agglomerated. Therefore, in order to allow the semiconductor nanoparticles to exist stably, measures must be taken to prevent the collision or fusion of particles. A variety of methods have so far been devised for this purpose, which can be roughly divided into: the physical isolation of individual semiconductor nanoparticles by taking them into a solid and a polymer matrix; and the inactivation of the particle surface by chemically modifying a metal ion site on the particle surface with a low-molecular-weight organic material that has a high level of ability of forming a complex with the metal ion site. Based on the latter concept, hexametaphosphate is used as a stabilizing agent in the present method. One thousand ml of an aqueous solution of sodium hexametaphosphate (0.1 mmol) and cadmium perchlorate (0.2 mmol) is prepared, and the pH is adjusted to 10.3. Then, bubbling is performed in the solution using nitrogen gas, and hydrogen sulfide gas (0.2 mmol) is injected into the solution while stirring the same violently. The stirring is continued for a time during which the color of the solution changes from being optically transparent colorless to optically transparent yellow. At this time, although semiconductor nanoparticles that have been stabilized by hexametaphosphate already exist in the solution, they have a wide particle size distribution with their standard deviation extending more than 15 % of the average particle size. The overall fluorescent intensity of the semiconductor nanoparticles in this state is very weak. The size-selective photoetching method is described below. The physicochemical properties of semiconductor nanoparticles appear in dependence on particle size due to the quantum size effect. Thus, physical properties in this state are averaged, so that the properties of the semiconductor nanoparticles cannot be fully exploited. Accordingly, it is necessary to accurately conduct a particle-size separation on the semiconductor nanoparticles immediately after preparation, which have a wide particle-size distribution, using a chemical technique, so that only semiconductor nanoparticles of a specific particle size can be isolated and extracted to achieve monodispersion. As a method of performing this operation, the size-selective photoetching method can be employed. This method utilizes the fact that the energy gap increases with decreasing size of the particle size of the semiconductor nanoparticles due to the quantum size effect, and that a metal chalcogenide semiconductor undergoes oxidizing melting as it is irradiated with light in the presence of dissolved oxygen. Specifically, when semiconductor nanoparticles with a wide particle-size distribution are irradiated with monochromatic light of a wavelength shorter than the wavelength of the absorption edge of the particles, semiconductor nanoparticles with larger particle sizes are selectively optically excited and dissolved, thereby obtaining smaller semiconductor nanoparticles with uniform particle size. First, bubbling is performed using nitrogen gas in the above-described semiconductor nanoparticle solution that is stabilized by hexametaphosphate and that has a wide particle-size distribution. Bubbling is further conducted using oxygen for 10 min. Then, methylviologen is added to the solution to 50 μmol/L, and laser is irradiated while stirring. The irradiation of monochromatic light in the present invention is conducted to optically dissolve the semiconductor nanoparticles, and the wavelength of the monochromatic light is 450 nm. By changing the wavelength of the monochromatic light, the fluorescent wavelength at the peak of the fluorescent spectrum of the semiconductor nanoparticles can be controlled. When the thus obtained semiconductor nanoparticles are irradiated with light with wavelength 476.5 nm, the particles exhibit a very narrow particle-size distribution where an average particle size is 3.2 nm and the standard deviation is 0.19 nm, which means the standard deviation is about 6% of the average particle size. Thus, a solution of semiconductor nanoparticles that is extremely close to monodispersion can be obtained. In this process, the semiconductor nanoparticles in the solution are monodispersed and come to produce band gap fluorescence that exhibits a narrow full width at half maximum spectrum corresponding to the irradiating monochromatic light and the particle size of the semiconductor nanoparticles. The defective fluorescence, which is believed mainly due to the energy level on the surface of the semiconductor nanoparticles, is emitted with a stronger intensity than the band gap fluorescence intensity. Such defective fluorescence is originally considered a factor obstructive to the properties of the semiconductor nanoparticles and should therefore be suppressed. Method for Modification of the Surface of Semiconductor Nanoparticles and Purification In order to purify the monodispersed semiconductor nanoparticles obtained by the above-described method that were stabilized by hexametaphosphate, surface modification was provided by adding 300 μL of mercaptopropionic acid (MPA) and then stirring for several hours. The solution was then ultrafiltrated to remove the methylviologen, hexametaphosphate, unreacted thiol compounds, and ions that had dissolved during photoetching, for example, in the aqueous solution, thereby obtaining a solution of semiconductor nanoparticles stabilized by a pure thiol compound. Thereafter, 1 L of the resultant semiconductor nanoparticles the surface of which was modified by the thiol compound was condensed by ultrafiltration to 10 mL, and then washing with pure water was conducted. Methods of Treating the Surface of the Semiconductor Nanoparticles A surface treatment was conducted on the purified and thiol-modified nanoparticles obtained by the above method. Examples of surface treatment are described below. EXAMPLE 1 An aqueous solution of the purified and thiol-modified nanoparticles was diluted to an absorbance of 0.5 using an aqueous solution of 0.1 M NH3-HCl of pH 11. The solution was allowed to stand for several days to several weeks, thereby obtaining a semiconductor nanoparticle solution with high-emission properties. The resultant solution was optically transparent yellow and had superior emission properties. Temporal changes in the absorbance in accordance with this preparation process are shown in FIG. 1, and temporal changes in the fluorescent intensity are shown in FIG. 2. EXAMPLE 2 An aqueous solution of the purified and thiol-modified nanoparticles was diluted to an absorbance of 0.5 using an aqueous solution of 0.1 M dimethylamine-HCl of pH 11. The solution was allowed to stand for several days to several weeks, thereby obtaining a semiconductor nanoparticle solution with high-emission properties. The resultant solution was optically transparent yellow and had superior emission properties. Temporal changes in the absorbance in accordance with this preparation process are shown in FIG. 3, and temporal changes in the fluorescent intensity are shown in FIG. 4. EXAMPLE 3 An aqueous solution of the purified and thiol-modified nanoparticles was diluted to an absorbance of 0.5 using an aqueous solution of 0.1 M tetramehylamine-HCl of pH 11. The solution was allowed to stand for several days to several weeks, thereby obtaining a semiconductor nanoparticle solution with high-emission properties. The resultant solution was optically transparent yellow and had superior emission properties. Temporal changes in the absorbance in accordance with this preparation process are shown in FIG. 5, and temporal changes in the fluorescent intensity are shown in FIG. 6. EXAMPLE 4 Beta-alanine was added to an aqueous solution of the purified and thiol-modified nanoparticles, which was then allowed to stand for several days to several weeks in an environment of pH 9, thereby obtaining a semiconductor nanoparticle solution with high-emission properties. The resultant solution was optically transparent yellow and had superior emission properties. Temporal changes in the absorbance in accordance with this preparation process are shown in FIG. 7, and temporal changes in the fluorescent intensity are shown in FIG. 8. EXAMPLE 5 An aqueous solution of the purified and thiol-modified nanoparticles was diluted to an absorbance of 0.5 using an aqueous solution of 0.1 M methylamine-HCl of pH 11. The solution was allowed to stand for several days to several weeks, thereby obtaining a semiconductor nanoparticle solution with high-emission properties. The resultant solution was optically transparent yellow and had superior emission properties. Temporal changes in the absorbance in accordance with this preparation process are shown in FIG. 9, and temporal changes in the fluorescent intensity are shown in FIG. 10. EXAMPLE 6 An aqueous solution of the purified and thiol-modified nanoparticles was diluted to an absorbance of 0.5 using an aqueous solution of 0.1 M trimethylamine-HCl of pH 11. The solution was allowed to stand for several days to several weeks, thereby obtaining a semiconductor nanoparticle solution with high-emission properties. The resultant solution was optically transparent yellow and had superior emission properties. Temporal changes in the absorbance in accordance with this preparation process are shown in FIG. 11, and temporal changes in the fluorescent intensity are shown in FIG. 12. EXAMPLE 7 An aqueous solution of the purified and thiol-modified nanoparticles was diluted to an absorbance of 0.5 using an aqueous solution of 0.1 M propylamine-HCl of pH 11. The solution was allowed to stand for several days to several weeks, thereby obtaining a semiconductor nanoparticle solution with high-emission properties. The resultant solution was optically transparent yellow and had superior emission properties. Temporal changes in the absorbance in accordance with this preparation process are shown in FIG. 13, and temporal changes in the fluorescent intensity are shown in FIG. 14. EXAMPLE 8 An aqueous solution of the purified and thiol-modified nanoparticles was diluted to an absorbance of 0.5 using an aqueous solution of 0.1 M dipropylamine-HCl of pH 11. The solution was allowed to stand for several days to several weeks, thereby obtaining a semiconductor nanoparticle solution with high-emission properties. The resultant solution was optically transparent yellow and had superior emission properties. Temporal changes in the absorbance in accordance with this preparation process are shown in FIG. 15, and temporal changes in the fluorescent intensity are shown in FIG. 16. EXAMPLE 9 An aqueous solution of the purified and thiol-modified nanoparticles was diluted to an absorbance of 0.5 using an aqueous solution of 0.1 M tripropylamine-HCl of pH 11. The solution was allowed to stand for several days to several weeks, thereby obtaining a semiconductor nanoparticle solution with high-emission properties. The resultant solution was optically transparent yellow and had superior emission properties. Temporal changes in the absorbance in accordance with this preparation process are shown in FIG. 17, and temporal changes in the fluorescent intensity are shown in FIG. 18. EXAMPLE 10 An aqueous solution of the purified and thiol-modified nanoparticles was diluted to an absorbance of 0.5 using an aqueous solution of 0.1 M tetrapropylamine-HCl of pH 11. The solution was allowed to stand for several days to several weeks, thereby obtaining a semiconductor nanoparticle solution with high-emission properties. The resultant solution was optically transparent yellow and had superior emission properties. Temporal changes in the absorbance in accordance with this preparation process are shown in FIG. 19, and temporal changes in the fluorescent intensity are shown in FIG. 20. The stabilizing agent can be selected from a wide variety of substances that are available and is not therefore limited to the above-described examples. The material of the core portion of the semiconductor nanoparticle is not particularly limited either. Examples of the core material include ZnO, ZnS, ZnSe, ZnTe, CdO, CdS, CdMnS, CdSe, CdMnSe, CdTe, CdMnTe, HgS, HgSe, HgTe, InP, InAs, InSb, InN, GaN, GaP, GaAs, GaSb, TiO2, WO3, PbS, PbSe, MgTe, AlAs, AlP, AlSb, AlS, Ge, and Si. Industrial Applicability By arranging electron-releasing groups on the surface of the semiconductor nanoparticle core, a water-soluble semiconductor nanoparticle with superior fluorescent properties can be easily prepared.

<SOH> BACKGROUND ART <EOH>Semiconductor nanoparticles with a particle size of less than 10 nm lie in a transition region between bulk semiconductor crystals and molecules. They exhibit physicochemical properties that are different from those of both bulk semiconductor crystals and molecules. In this region, the energy gap of the semiconductor nanoparticles increases with decreasing particle size, due to the emergence of the quantum size effect. This is further accompanied by the removal of the energy band degeneracy that is observed in bulk semiconductors, so that the orbits become discrete, with the lower end of the conduction band shifted to the negative side and the upper end of the valence band shifted to the positive side. CdS semiconductor nanoparticles can be easily prepared by dissolving equimolar amounts of Cd and S precursors. The same is true for the manufacture involving CdSe, ZnS, ZnSe, HgS, HgSe, PbS, or PbSe, for example. Semiconductor nanoparticles are gaining much attention because they are capable of emitting strong fluorescence with a narrow full width at half maximum, which makes it possible to produce a variety of fluorescent colors, thereby opening up a great variety of future applications. However, the semiconductor nanoparticles obtained by simply mixing precursors as mentioned above exhibit a wide particle size distribution, and consequently the properties of the semiconductor nanoparticles cannot be fully utilized. Attempts have been made to accurately conduct particle size separation on semiconductor nanoparticles immediately after preparation that have a wide particle size distribution, using a chemical technique, and then separate and extract only those semiconductor nanoparticles with a specific particle size, with a view to achieving monodispersion. Such attempts include an electrophoretic separation process utilizing the fact that the surface charge possessed by nanoparticles varies depending on particle size, an exclusion chromatography process that takes advantage of the difference in retention time depending on particle size, and a size-selective precipitation process that utilizes the difference in dispersibility into an organic solvent depending on particle size. The foregoing are examples of techniques for classifying the nanoparticles prepared by mixing precursors according to particle size. Another technique for achieving monodispersion of particle size has also been reported; namely, a size-selective photoetching process that utilizes the oxidizing dissolution of a metal chalcogenide semiconductor upon light irradiation in the presence of dissolved oxygen. There is yet another method in which monodispersion of particle size is controlled at the stage of mixture of the precursors. One typical example is a reversed micelle method. In this method, amphipathic molecules, such as diisooctyl sodium sulfosuccinate, and water are mixed in an organic solvent, such as heptane, thereby forming a reverse micelle in the organic solvent, such that precursors are reacted with each other using only the aqueous phase in the reverse micelle. The size of the reverse micelle is determined by the quantitative ratio of the amphipathic molecules to the water, so that the size can be relatively uniformly controlled. The size of the thus prepared semiconductor nanoparticle is dependent on the size of the reverse micelle, so that it is possible to prepare semiconductor nanoparticles with relatively uniform particle sizes. While the semiconductor nanoparticles obtained by the aforementioned processes exhibit a relatively narrow particle size distribution, the fluorescent properties of the thus prepared semiconductor nanoparticles exhibit a gradual fluorescent spectrum without any significant peaks. Moreover, the fluorescent spectrum exhibits a peak at a wavelength that is different from the theoretical value of the fluorescence that is supposed to be emitted by the semiconductor nanoparticles. Specifically, in addition to the bandgap fluorescence exhibited from the inside of the semiconductor nanoparticles, the aforementioned semiconductor nanoparticles emit totally separate fluorescence that is believed to be emitted by energy levels existing in the forbidden band of energy levels of the semiconductor nanoparticles. The energy levels that emit this fluorescence are believed to exist mainly at a surface site of the semiconductor nanoparticles. This is a phenomenon that adversely affects the properties of the semiconductor nanoparticles with a narrow particle size distribution and has remained a problem to be solved, as the changes in fluorescent properties brought about by controlling the particle size of semiconductor nanoparticles originally appear in bandgap fluorescence. As a typical solution to the above problem, a method has been attempted that would coat a semiconductor material as a core with a semiconductor material that has a larger bandgap than that of the core's semiconductor material, an inorganic material, and an organic material, thereby forming a multilayer structure in order to suppress the aforementioned fluorescence. Typical examples of coating with an inorganic material include a coating of a CdSe nanoparticle with CdS (J. Phys. Chem. 100: 8927 (1996)), a coating of a CdS nanoparticle with ZnS (J. Phys. Chem. 92: 6320 (1988)), and a coating of a CdSe nanoparticle with ZnS (J. Am. Chem. Soc. 112: 1327 (1990)). With regard to the coating of a CdSe nanoparticle with ZnS, the Ostwald ripening phenomenon has been successfully utilized to obtain semiconductor nanoparticles with a sufficient fluorescent property by conducting the coating in a coordination solvent (J. Phys. Chem. B. 101: 9463 (1997)). In the aforementioned multilayered semiconductor nanoparticle, the particle is coated with a material having a larger bandgap than that of the semiconductor nanoparticle and having no bandgap in the forbidden band thereof. This is in order to suppress the defective sites on the surface of the semiconductor nanoparticle so that the inherent fluorescent property of the semiconductor nanoparticle can be obtained. In a method of surface processing in an aqueous solution, an improvement has been reported in the fluorescent property of the semiconductor nanoparticle in an alkali aqueous solution (J. Am. Chem. Soc. 109: 5655 (1987)). Although various experiments and reports have been made based on this report, none have successfully shed light on the mechanism (J. Phys. Chem. 100: 13226 (1996); J. Am. Chem. Soc. 122: 12142 (2000), for example). Moreover, none of the semiconductor nanoparticles in the alkali solution have sufficient reproducibility, and the reproduction conditions have not been identified. Furthermore, none of the experiments or reports has succeeded in isolating the final product. As an example of the method for coating with an organic material, a synthesization process can be cited that utilizes the Ostwald ripening phenomena in a coordination solvent. It employs a coating material such as TOPO (trioctylphosphine) or hexadecylamine (HDA) as the coating material, for example, to obtain semiconductor nanoparticles with high light-emission properties (J. Am. Chem. Soc. 122: 12142 (2000), J. Lumin. 98, 49 (2002), for example). It should be noted, however, that the finally obtained semiconductor nanoparticle is not water-soluble. The semiconductor nanoparticle obtained by the above-described methods is capable of suppressing a defect site to some extent and has the inherent properties of a semiconductor nanoparticle to some extent. However, in order to prepare such a semiconductor nanoparticle, a highly sophisticated technique is required, and in order to achieve high quality, a variety of equipment is required. Further, they are seriously deficient for the purpose of industrial production from the viewpoint of the cost of reagents and safety during high temperature reaction.

<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>FIG. 1 shows the absorption spectrum of a semiconductor nanoparticle prepared in Example 1. FIG. 2 shows the fluorescent spectrum of a semiconductor nanoparticle prepared in Example 1. FIG. 3 shows the absorption spectrum of a semiconductor nanoparticle prepared in Example 2. FIG. 4 shows the fluorescent spectrum of the semiconductor nanoparticle prepared in Example 2. FIG. 5 shows the absorption spectrum of a semiconductor nanoparticle prepared in Example 3. FIG. 6 shows the fluorescent spectrum of the semiconductor nanoparticle prepared in Example 3. FIG. 7 shows the absorption spectrum of a semiconductor nanoparticle prepared in Example 4. FIG. 8 shows the fluorescent spectrum of the semiconductor nanoparticle prepared in Example 4. FIG. 9 shows the absorption spectrum of a semiconductor nanoparticle prepared in Example 5. FIG. 10 shows the fluorescent spectrum of a semiconductor nanoparticle prepared in Example 5. FIG. 11 shows the absorption spectrum of a semiconductor nanoparticle prepared in Example 6. FIG. 12 shows the fluorescent spectrum of the semiconductor nanoparticle prepared in Example 6. FIG. 13 shows the absorption spectrum of a semiconductor nanoparticle prepared in Example 7. FIG. 14 shows the fluorescent spectrum of the semiconductor nanoparticle prepared in Example 7. FIG. 15 shows the absorption spectrum of a semiconductor nanoparticle prepared in Example 8. FIG. 16 shows the fluorescent spectrum of the semiconductor nanoparticle prepared in Example 8. FIG. 17 shows the absorption spectrum of the semiconductor nanoparticle prepared in Example 9. FIG. 18 shows the fluorescent spectrum of a semiconductor nanoparticle prepared in Example 9. FIG. 19 shows the absorption spectrum of the semiconductor nanoparticle prepared in Example 10. FIG. 20 shows the fluorescent spectrum of a semiconductor nanoparticle prepared in Example 10. detailed-description description="Detailed Description" end="lead"?

20040819

20080527

20050707

93937.0

HU, SHOUXIANG

SEMICONDUCTOR NANOPARTICLE, AND A PROCESS OF MANUFACTURING THE SAME

UNDISCOUNTED

ACCEPTED

ACCEPTED

Signal processing system, recording method, program, recording medium, reproduction device and information processing device

A recorder is composed of a drive 102 and a host 103 that mutually authenticate each other. A C2_G 141 of the drive 102 calculates a medium ID and a medium key and obtains a medium unique key. The medium unique key is encrypted using a session key Ks generated by the mutual authentication and transferred to the host 103. A title key generated by a random number generator 143 of the drive 102 is transferred to the host 103. A content key calculated by a C2_G 145 of the drive 102 using the title key and the CCI 232 is encrypted using the session key Ks and then transferred to the host 103. A content is encrypted using a content key decrypted by the host 103. The drive 102 records the encrypted content, the encrypted title key, and the CCI 232 to the medium 101.

1. A signal processing system having a reproducing apparatus for reading information from a recording medium having information unique thereto and an information processing apparatus for mutually authenticating and connecting the reproducing apparatus through a transferring portion, wherein the reproducing apparatus comprises: final encryption key generating means for generating a content information encryption key in accordance with intermediate key information; a first transmitting portion for transmitting the intermediate key information to the information processing/apparatus through the transferring portion; and a second transmitting portion for transmitting the content information encryption key to the information processing apparatus through the transferring portion, and wherein the information processing apparatus comprises: a content information encrypting portion for encrypting content information using the content information encryption key; an intermediate key information encrypting portion for encrypting the intermediate key information using key information unique to the recording medium, the key information being generated in accordance with information unique to the recording medium; and a recording portion for recording the encrypted content information and the encrypted intermediate key information to the recording medium. 2. The signal processing system as set forth in claim 1, wherein the reproducing apparatus further comprises a random number generating portion for generating a random number, and wherein the intermediate key information is a random number generated by the random number generating portion. 3. A recording method of a reproducing apparatus and an information processing apparatus for recording information to a recording medium, the reproducing apparatus being configured to read information from the recording medium having information unique thereto and the information processing apparatus being configured to mutually authenticate and connect the reproducing apparatus through a transferring portion, the recording method comprising the steps of: causing the reproducing apparatus to generate a content information encryption key in accordance with intermediate key information; causing the reproducing apparatus to transmit the intermediate key information to the information processing apparatus through the transferring portion; causing the reproducing apparatus to transmit the content information encryption key to the information processing apparatus through the transferring portion; causing the information processing apparatus to encrypt content information using the content information encryption key; causing the information processing apparatus to encrypt the intermediate key information using key information unique to the recording medium, the key information being generated in accordance with information unique to the recording medium; and causing the information processing apparatus to record the encrypted content information and the encrypted intermediate key information to the recording medium. 4. The recording method as set forth in claim 3, further comprising the step of: causing the reproducing apparatus to generate a random number, wherein the intermediate key information is a random number generated at the random number generating step. 5. A program of a reproducing apparatus and an information processing apparatus for recording information to a recording medium, the reproducing apparatus being configured to read information from the recording medium having information unique thereto and the information processing apparatus being configured to mutually authenticate and connect the reproducing apparatus through a transferring portion, the program comprising the steps of: causing the reproducing apparatus to generate a content information encryption key in accordance with intermediate key information; causing the reproducing apparatus to transmit the intermediate key information to the information processing apparatus through the transferring portion; causing the reproducing apparatus to transmit the content information encryption key to the information processing apparatus through the transferring portion; causing the information processing apparatus to encrypt content information using the content information encryption key; causing the information processing apparatus to encrypt the intermediate key information using key information unique to the recording medium, the key information being generated in accordance with information unique to the recording medium; and causing the information processing apparatus to record the encrypted content information and the encrypted intermediate key information to the recording medium. 6. The program as set forth in claim 5, further comprising the step of: causing the reproducing apparatus to generate a random number, wherein the intermediate key information is a random number generated at the random number generating step. 7. A recording medium for storing a program-of a reproducing apparatus and an information processing apparatus for recording information to a recording medium, the reproducing apparatus being configured to read information from the recording medium having information unique thereto and the information processing apparatus being configured to mutually authenticate and connect the reproducing apparatus through a transferring portion, the program comprising the steps of: causing the reproducing apparatus to generate a content information encryption key in accordance with intermediate key information; causing the reproducing apparatus to transmit the intermediate key information to the information processing apparatus through the transferring portion; causing the reproducing apparatus to transmit the content information encryption key to the information processing apparatus through the transferring portion; causing the information processing apparatus to encrypt content information using the content information encryption key; causing the information processing apparatus to encrypt the intermediate key information using key information unique to the recording medium, the key information being generated in accordance with information unique to the recording medium; and causing the information processing apparatus to record the encrypted content information and the encrypted intermediate key information to the recording medium. 8. The recording medium as set forth in claim 7, further comprising the step of: causing the reproducing apparatus to generate a random number, wherein the intermediate key information is a random number generated at the random number generating step. 9. A reproducing apparatus, connected to an information processing apparatus through a transferring portion, for reading information from a recording medium having information unique thereto, the reproducing apparatus comprising: final encryption key generating means for generating a content information encryption key in accordance with intermediate key information; a first transmitting portion for transmitting the intermediate key information to the information processing apparatus through the transferring portion; a second transmitting portion for transmitting the content information encryption key to the information processing apparatus through the transferring portion, wherein the reproducing apparatus is mutually authenticated with the information processing apparatus and connected thereto, the information processing apparatus comprising a content information encrypting portion for encrypting content information using the content information encryption key; an intermediate key information encrypting portion for encrypting the intermediate key information using key information unique to the recording medium, the key information being generated in accordance with information unique to the recording medium; and a recording portion for recording the encrypted content information and the encrypted intermediate key information to the recording medium. 10. The reproducing apparatus as set forth in claim 9, further comprising: a random number generating portion for generating a random number, and wherein the intermediate key information is a random number generated by the random number generating portion. 11. An information processing apparatus connected to a reproducing apparatus through a transferring portion, the reproducing apparatus being configured to read information from a recording medium having information unique thereto, the information processing apparatus being mutually authenticated with the reproducing apparatus and connected thereto through the transferring portion, the reproducing apparatus comprising final encryption key generating means for generating a content information encryption key in accordance with intermediate key information; a first transmitting portion for transmitting the intermediate key information to the information processing apparatus through the transferring portion; and a second transmitting portion for transmitting the content information encryption key to the information processing apparatus through the transferring portion, the information processing apparatus comprising: a content information encrypting portion for encrypting content information using the content information encryption key; an intermediate key information encrypting portion for encrypting the intermediate key information using key information unique to the recording medium, the key information being generated in accordance with information unique to the recording medium; and a recording portion for recording the encrypted content information and the encrypted intermediate key information to the recording medium. 12. The information processing apparatus as set forth in claim 11, wherein the reproducing apparatus further comprises a random number generating portion for generating a random number, and wherein the intermediate key information is a random number generated by the random number generating portion. 13. A reproducing apparatus, comprising: at least one of a recording portion for recording encrypted data to a recording medium on which first information for invalidating an illegal electronic device, second information that differs in each content, third information definable for each encrypted unit, and identification data that differs in each stamper are pre-recorded and a reproducing portion for reproducing encrypted data recorded on the recording medium; a storing portion for storing fourth information unique to a valid electronic device or application software; a revoking processing portion for determining whether or not the forth information is information unique to a valid electronic device or application software using the first information and the fourth information; a calculating portion for obtaining intermediate key information unique to each recording medium using the first information, the fourth information, the second information, and the identification data when the determined result of the revoking processing portion represents that the fourth information is information unique to a valid electronic device or application software; and a transmitting portion for transmitting the intermediate key information to the final encryption key generating portion of an information processing apparatus through a transferring portion. 14. The recording and reproducing apparatus as set forth in claim 13, further comprising: an authenticating portion for mutually authenticating a data processing apparatus for at least encrypting data or decrypting encrypted data using a key generated in accordance with the intermediate key information; and an intermediate key information encrypting portion for encrypting the intermediate key information using a session key generated when the authentication has been successfully performed and transmitting the encrypted intermediate key information to the data processing apparatus. 15. A data processing apparatus, comprising: an authenticating portion for authenticating a recording and reproducing apparatus, the recording and reproducing apparatus having fourth information unique to a valid electronic device or application software, for at least recording encrypted data to a recording medium on which first information for invalidating an illegal electronic device, second information that differs in each content, third information definable for each encrypted unit, and identification data that differs in each stamper are pre-recorded or reproducing encrypted data recorded on the recording medium; a key information decrypting portion for receiving the first information, the fourth information, and intermediate key information from the recording and reproducing apparatus and decrypting the intermediate key information, the first information and the forth information having been encrypted using a session key generated when the authentication has been successfully performed, the intermediate key information being unique to each recording medium and generated using the second information and the identification data; a final encryption key generating portion for generating a final encryption key using the third information received from the recording and reproducing apparatus and the decrypted intermediate key information; and an encrypting and decrypting portion for at least encrypting data using the final encryption key or decrypting data using the final encryption key.

TECHNICAL FIELD The present invention relates to a signal processing system, a recording method, a program, a recording medium, a reproducing apparatus, and an information processing apparatus that cause a drive connected to for example a personal computer to record an encrypted content to a disc medium and to reproduce an encrypted content from a disc medium. BACKGROUND ART On one recording medium such as a DVD (Digital Versatile Disc), which has been recently developed, a large capacity of data for one movie can be recorded as digital information. When video information and so forth can be recorded as digital information, it will become important to protect copyright of digital information against illegal copies. In DVD-Video, as a copy protection technology, CSS (Content Scrambling System) has been employed. The use of the CSS is permitted for only DVD-ROM media, not recordable DVDs such as a DVD−R, a DVD−RW, a DVD+R, a DVD+RW, and so forth due to CSS contract. Thus, the CSS contract does not permit the user to copy the contents of a DVD-Video disc that has been copyright-protected in accordance with the CSS system to a recordable DVD (so-called bit-by-bit copy). However, there was a serious situation of which the CSS encrypting system was broken. Illegal software called “DeCSS” that is capable of easily decrypting contents that has been encrypted in accordance with the CSS encryption system and copying the decrypted contents to a hard disk was published on the Internet. As a background of the advent of “DeCSS”, reproduction software was designed with a CSS decryption key that was not anti-tampered although it was supposed to be anti-tampered. The reproduction software was reverse-engineered and the encryption key was decrypted. As a result, all the CSS algorithm was decrypted. As a successor of the CSS, CPPM (Content Protection for Pre-Recorded Media) as a copyright protection technology for DVD-ROMs such as a DVD-Audio disc and CPRM (Content Protection for Recordable Media) as a copyright protection technology for recordable DVDs and memory cards have been proposed. In these systems, even if there is a problem about encryption for contents, storage of management information, and so forth, the systems can be updated. Even if data of a whole disc is copied, the reproduction can be restricted. A method for protecting copyright for DVDs is described in the following non-patent related art reference 1. The CPRM is described in the following document distributed by its licenser, 4C Entity, LLC, USA. “Spreading-out Copyright Protection Space Starting from DVD”, Yamada, Nikkei Electronics, pp. 143-153, 2001.8.13. “Content Protection for Recordable Media Specification DVD Book”, Internet <URL: http:// www.4Centrity.com/> In a personal computer (hereinafter, sometimes abbreviated as PC) environment, since a PC and a drive are connected with a standard interface, secret data may be leaked out or tampered at the standard interface. As a result, there is a risk of which application software may be reverse-engineered and secret information may be stolen or tampered. Such a risk hardly occurs in an electronic apparatus that has a recording and reproducing apparatus that is integrated thereinto. When a copyright protection technology is implemented to an application program that is executed on a PC, to prevent the copyright protection technology from being analyzed, the application program is generally anti-tampered. However, there is no index that represents the strength of tamper-resistance. As a result, countermeasures against reverse-engineering depend on the decision and capability of each implementer. Thus, the CSS was broken. The copyright protecting technologies CPPM and CPRM for recordable DVDs, which were proposed as a successor of the CSS are based on the known CSS and have new additional functions. In addition, most of algorithms of copyright protection technologies depend on implementation to a PC. Thus, it cannot be said that they have strong content protection functions. In other words, an encrypting system would be broken by analyzing secret information of a copyright protection technology for example reverse-engineering using application software. Encrypted content read as data from a disc by a PC would be decrypted by decrypting software such as “DeCSS”. The decrypted data would be repeatedly copied as a clear content in non-copy-protection state. Thus, there was a risk of which the copyright protection would not work. An object of the present invention is to provide a mutual authenticating method, a program, a recording medium, a signal processing system, a reproducing apparatus, and an information processing apparatus that allow safety of a copyright protection technology in a PC environment to be secured. DISCLOSURE OF THE INVENTION To solve the foregoing problem, a first aspect of the present invention is a signal processing system having a reproducing apparatus for reading information from a recording medium having information unique thereto and an information processing apparatus for mutually authenticating and connecting the reproducing apparatus through a transferring portion, wherein the reproducing apparatus comprises: final encryption key generating means for generating a content information encryption key in accordance with intermediate key information; a first transmitting portion for transmitting the intermediate key information to the information processing apparatus through the transferring portion; and a second transmitting portion for transmitting the content information encryption key to the information processing apparatus through the transferring portion, and wherein the information processing apparatus comprises: a content information encrypting portion for encrypting content information using the content information encryption key; an intermediate key information encrypting portion for encrypting the intermediate key information using key information unique to the recording medium, the key information being generated in accordance with information unique to the recording medium; and a recording portion for recording the encrypted content information and the encrypted intermediate key information to the recording medium. A second aspect of the present invention is a recording method of a reproducing apparatus and an information processing apparatus for recording information to a recording medium, the reproducing apparatus being configured to read information from the recording medium having information unique thereto and the information processing apparatus being configured to mutually authenticate and connect the reproducing apparatus through a transferring portion, the recording method comprising the steps of: causing the reproducing apparatus to generate a content information encryption key in accordance with intermediate key information; causing the reproducing apparatus to transmit the intermediate key information to the information processing apparatus through the transferring portion; causing the reproducing apparatus to transmit the content information encryption key to the information processing apparatus through the transferring portion; causing the information processing apparatus to encrypt content information using the content information encryption key; causing the information processing apparatus to encrypt the intermediate key information using key information unique to the recording medium, the key information being generated in accordance with information unique to the recording medium; and causing the information processing apparatus to record the encrypted content information and the encrypted intermediate key information to the recording medium. A third aspect of the present invention is a program of a reproducing apparatus and an information processing apparatus for recording information to a recording medium, the reproducing apparatus being configured to read information from the recording medium having information unique thereto and the information processing apparatus being configured to mutually authenticate and connect the reproducing apparatus through a transferring portion, the program comprising the steps of: causing the reproducing apparatus to generate a content information encryption key in accordance with intermediate key information; causing the reproducing apparatus to transmit the intermediate key information to the information processing apparatus through the transferring portion; causing the reproducing apparatus to transmit the content information encryption key to the information processing apparatus through the transferring portion; causing the information processing apparatus to encrypt content information using the content information encryption key; causing the information processing apparatus to encrypt the intermediate key information using key information unique to the recording medium, the key information being generated in accordance with information unique to the recording medium; and causing the information processing apparatus to record the encrypted content information and the encrypted intermediate key information to the recording medium. A fourth aspect of the present invention is a recording medium for storing a program of a reproducing apparatus and an information processing apparatus for recording information to a recording medium, the reproducing apparatus being configured to read information from the recording medium having information unique thereto and the information processing apparatus being configured to mutually authenticate and connect the reproducing apparatus through a transferring portion, the program comprising the steps of: causing the reproducing apparatus to generate a content information encryption key in accordance with intermediate key information; causing the reproducing apparatus to transmit the intermediate key information to the information processing apparatus through the transferring portion; causing the reproducing apparatus to transmit the content information encryption key to the information processing apparatus through the transferring portion; causing the information processing apparatus to encrypt content information using the content information encryption key; causing the information processing apparatus to encrypt the intermediate key information using key information unique to the recording medium, the key information being generated in accordance with information unique to the recording medium; and causing the information processing apparatus to record the encrypted content information and the encrypted intermediate key information to the recording medium. A fifth aspect of the present invention is a reproducing apparatus, connected to an information processing apparatus through a transferring portion, for reading information from a recording medium having information unique thereto, the reproducing apparatus comprising: final encryption key generating means for generating a content information encryption key in accordance with intermediate key information; a first transmitting portion for transmitting the intermediate key information to the information processing apparatus through the transferring portion; a second transmitting portion for transmitting the content information encryption key to the information processing apparatus through the transferring portion, wherein the reproducing apparatus is mutually authenticated with the information processing apparatus and connected thereto, the information processing apparatus comprising a content information encrypting portion for encrypting content information using the content information encryption key; an intermediate key information encrypting portion for encrypting the intermediate key information using key information unique to the recording medium, the key information being generated in accordance with information unique to the recording medium; and a recording portion for recording the encrypted content information and the encrypted intermediate key information to the recording medium. A sixth aspect of the present invention is an information processing apparatus connected to a reproducing apparatus through a transferring portion, the reproducing apparatus being configured to read information from a recording medium having information unique thereto, the information processing apparatus being mutually authenticated with the reproducing apparatus and connected thereto through the transferring portion, the reproducing apparatus comprising final encryption key generating means for generating a content information encryption key in accordance with intermediate key information; a first transmitting portion for transmitting the intermediate key information to the information processing apparatus through the transferring portion; and a second transmitting portion for transmitting the content information encryption key to the information processing apparatus through the transferring portion, the information processing apparatus comprising: a content information encrypting portion for encrypting content information using the content information encryption key; an intermediate key information encrypting portion for encrypting the intermediate key information using key information unique to the recording medium, the key information being generated in accordance with information unique to the recording medium; and a recording portion for recording the encrypted content information and the encrypted intermediate key information to the recording medium. A seventh aspect of the present invention is a reproducing apparatus, comprising: at least one of a recording portion for recording encrypted data to a recording medium on which first information for invalidating an illegal electronic device, second information that differs in each content, third information definable for each encrypted unit, and identification data that differs in each stamper are pre-recorded and a reproducing portion for reproducing encrypted data recorded on the recording medium; a storing portion for storing fourth information unique to a valid electronic device or application software; a revoking processing portion for determining whether or not the forth information is information unique to a valid electronic device or application software using the first information and the fourth information; a calculating portion for obtaining intermediate key information unique to each recording medium using the first information, the fourth information, the second information, and the identification data when the determined result of the revoking processing portion represents that the fourth information is information unique to a valid electronic device or application software; and a transmitting portion for transmitting the intermediate key information to the final encryption key generating portion of an information processing apparatus through a transferring portion. An eighth aspect of the present invention is a data processing apparatus, comprising: an authenticating portion for authenticating a recording and reproducing apparatus, the recording and reproducing apparatus having fourth information unique to a valid electronic device or application software, for at least recording encrypted data to a recording medium on which first information for invalidating an illegal electronic device, second information that differs in each content, third information definable for each encrypted unit, and identification data that differs in each stamper are pre-recorded or reproducing encrypted data recorded on the recording medium; a key information decrypting portion for receiving the first information, the fourth information, and intermediate key information from the recording and reproducing apparatus and decrypting the intermediate key information, the first information and the forth information having been encrypted using a session key generated when the authentication has been successfully performed, the intermediate key information being unique to each recording medium and generated using the second information and the identification data; a final encryption key generating portion for generating a final encryption key using the third information received from the recording and reproducing apparatus and the decrypted intermediate key information; and an encrypting and decrypting portion for at least encrypting data using the final encryption key or decrypting data using the final encryption key. According to the present invention, the reproducing apparatus side generates a content key. The information processing apparatus side encrypts a content using the content key. Since the reproducing apparatus generates key information with which copyright of a content is protected, the content key can be generated by hardware. As a result, tamper-resistance for secret information is improved. In addition, since the reproducing apparatus generates a random number as an intermediate key, a true random number or a random number close thereto can be generated by hardware for example an LSI in the reproducing apparatus. Thus, it becomes difficult to replace a generated random number with a fixed value. As a result, according to the present invention, it is not necessary for application software installed in the information processing apparatus to have all secret information of a copyright protection technology. Thus, the system according to the present invention is capable of having tamper-resistance for secret information against reverse-engineering for software and securing safety of a copyright protection technology. According to the present invention, since the recording and reproducing apparatus has a device key as information unique to an electronic device, the recording and reproducing apparatus itself can be revoked. According to the present invention, since random number information necessary for calculating a content key in the information processing apparatus can be generated by for example an LSI in the recording and reproducing apparatus, a true random number or a random number close thereto can be generated in comparison with the case that a random number is generated by software in a PC. Thus, the risk of which a random number is replaced with a fixed value can be suppressed. BRIEF DESCRIPTION OF DRAWINGS FIG. 1 is a block diagram describing a proposed system composed of a recorder, a player, and a DVD medium. FIG. 2 is a block diagram describing a PC based DVD medium recording and reproducing system. FIG. 3 is a schematic diagram describing steps of processes of a DVD drive 4 and a host 5 of the system shown in FIG. 2. FIG. 4 is a flow chart describing an authenticating operation of the system shown in FIG. 2. FIG. 5 is a block diagram showing a structure for performing mutual authentication according to an embodiment of the present invention. FIG. 6 is a flow chart describing steps of a process of an authenticating operation of the drive according to the embodiment of the present invention. FIG. 7 is a flow chart describing steps of a process of an authenticating operation of the host according to the embodiment of the present invention. FIG. 8 is a block diagram showing an example of a structure of a recorder that integrates the drive and the host according to the embodiment of the present invention. FIG. 9 is a schematic diagram describing an example of steps of a communicating procedure of the recorder. FIG. 10 is a block diagram showing an example of a structure of a player that integrates the drive and the host according to the embodiment of the present invention. FIG. 11 is a schematic diagram describing an example of steps of a communicating procedure of the player. FIG. 12 is a block diagram showing an example of a structure of a recorder that integrates a drive and a host according to another embodiment of the present invention. FIG. 13 is a block diagram showing an example of a structure of a player that integrates the drive and the host according to the other embodiment of the present invention. BEST MODES FOR CARRYING OUT THE INVENTION Next, before embodiments of the present invention is described, the relation between terminology used in the claims and terminology used in the embodiments will be described. Recording medium: medium, for example a disc, reproducing apparatus: drive, information processing apparatus: host, transferring means: drive-host interface, signal processing system: system of which the drive that reproduces data from a medium and the host are connected through the drive-host interface. First transmitting means: means for transmitting information from the drive side to the host side in accordance with a common key encrypting system using a session key as a common key, second transmitting means: means for reversely transmitting information from the host side to the drive side using a session key as a common key. Content information: information recorded on a medium or information to be recorded. Information unique to a recording medium: medium ID. Random number generating means for generating a random number; random number generator (RNG). Key information unique to a recording medium: medium unique key, intermediate key information: title key. Content information encryption key: content key (content key used to record data is referred to as content information encryption key, content key used to reproduce data is referred to as content information decryption key). For easy understanding of the present invention, first of all, with reference to FIG. 1, a copyright protection technology for example an architecture of the CPRM for DVDs will be described. In FIG. 1, reference numeral 1 represents for example a recordable DVD medium such as DVD−R/RW or DVD-RAM based on the CPRM standard. Reference numeral 2 represents for example a recorder based on the CPRM standard. Reference numeral 3 represents for example a player based on the CPRM standard. The recorder 2 and the player 3 are each an apparatus or application software. In a blank state of the DVD medium 1, in areas called BCA (Burst Cutting Area) or NBCA (Narrow Burst Cutting Area) of a lead-in area on the innermost periphery side of the DVD medium 1, a medium ID 11 is recorded. In an emboss or pre-recorded data zone of the lead-in area, a medium key block (hereinafter sometimes abbreviated as MKB) 12 is pre-recorded. The medium ID 11 is a number that is unique to each medium for example disc. The medium ID 11 is composed of a medium manufacturer code and a serial number. The medium ID 11 is required when a medium key is converted into a medium unique key that is unique to each medium. A medium key block MKB is a bundle of keys to obtain a medium key and revoke the apparatus. The medium ID and medium key block are first information unique to the recording medium. In a data rewritable or recordable region of the disc 1, an encrypted content 13 that is encrypted with a content key is recorded. As an encrypting system, C2 (Cryptomeria Ciphering) is used. On the DVD medium 1, an encrypted title key 14 and a CCI (Copy Control Information) 15 are recorded. The encrypted title key 14 is encrypted title key information. The title key information is key information that is added for each title. The CCI is copy control information such as copy no more, copy once, copy free, or the like. The recorder 2 comprises structural elements that are a device key 21, a process MKB 22, a C2_G 23, a random number generator 24, a C2_E 25, a C2_G 26, and a C2_ECBC 27. The player 3 comprises structural elements that are a device key 31, a process MKB 32, a C2_G 33, a C2_D 35, a C2_G 36, and a C2_DCBC 37. The C2_G 23 and 33 are blocks for calculating medium unique key from the medium ID and the medium key respectively. The C2_G 26 and 36 are blocks for calculating content key from the CCI and the title key respectively. The device keys 21 and 31 are identification numbers issued for each apparatus maker or each application software vendor. A device key is information unique to a valid electronic apparatus or valid application software assigned by a licenser. The MKB 12 and the device key 21 reproduced from the DVD medium 1 are calculated by the process MKB 22 so as to determine whether or not the electronic apparatus or application software has been revoked. Like the recorder 2, in the player 3, the MKB 12 and the device key 31 are calculated by the process MKB 32 so as to determine whether or not the player 3 has been revoked. The processes MKB 22 and 32 each calculate a medium key with the MKB 12 and the device keys 21 and 31. When the MKB 12 does not contain a device key of the recorder 2 or the player 3 and the calculated result matches a predetermined value for example 0, it is determined that the recorder 2 or player 3 that has the device key is not valid. In other words, the recorder 2 or player 3 is revoked. The C2_G 23 and the C2_G 33 are processes each of which calculates a medium key and a medium ID and obtains a medium unique key. The random number generator (RNG) 24 is used to generate a title key. A title key generated by the random number generator 24 is input to the C2_E 25. The title key is encrypted with a medium unique key. The encrypted title key 14 is recorded on the DVD medium 1. In the player 3, the encrypted title key 14 and the medium unique key reproduced from the DVD medium 1 are supplied to the C2_D 35. The encrypted title key is decrypted with the medium unique key. As a result, the title key is obtained. In the recorder 2, the CCI and the title key are supplied to the C2_G 26. The C2_G 26 obtains a content key. The content key is supplied to the C2_ECBC 27. The C2_ECBC 27 encrypts a content with the content key. The encrypted content 13 is recorded on the DVD medium 1. In the player 3, the CCI and the title key are supplied to the C2_G 36. The C2_G 36 obtains a content key. The content key is supplied to the C2_ECBC 37. The encrypted content 13 reproduced from the DVD medium 1 is decrypted with the content key. In the structure shown in FIG. 1, a recording process for the recorder 2 will be described. The recorder 2 reads the MKB 12 from the DVD medium 1. The process MKB 22 calculates the device key 21 and the MKB 12 and obtains a medium key. When the calculated result matches a predetermined value, it is determined that the device key 21 (the apparatus or application of the recorder 2) has been revoked by the MKB. At that point, the recorder 2 stops the current process and prohibits a content from being recorded to the DVD medium 1. If the value of the medium key does not match the predetermined value, the recorder 2 continues the current process. The recorder 2 reads the medium ID 11 from the DVD medium 1 and inputs the medium ID and the medium key to the C2_G 23. The C2_G 23 calculates the medium ID and the medium key and obtains a medium unique key that is unique to each medium. The title key generated by the random number generator 24 is encrypted by the C2_E 25. The encrypted title key 14 is recorded on the DVD medium 1. The title key and the CCI information of the content are calculated by the C2_G 26. As a result, the C2_G 26 obtains a content key. The C2_ECBC 27 encrypts the content with the content key. The encrypted content 13 and the CCI 15 are recorded on the DVD medium 1. Next, a reproducing process of the player 3 will be described. First of all, the MKB 12 is read from the DVD medium 1. The device key 31 and the MKB 12 are calculated so as to determine whether or not the device key 31 has been revoked. When the device key 31 namely the apparatus or application of the player 3 has not been revoked, a medium unique key is calculated with the medium ID. With the encrypted title key 14 and the medium unique key, a title key is calculated. The title key and the CCI 15 are input to the C2_G 36. As a result, a content key is obtained. The content key is input to the C2_DCBC 37. The C2_DCBC 37 calculates the encrypted content 13 reproduced from the DVD medium 1 with the content key. As a result, the encrypted content 13 is decrypted. To obtain a content key necessary for decrypting a content, a unique medium ID is required for each DVD medium. Thus, even if an encrypted content on a medium is copied to another medium, since the medium ID of the other medium is different from the medium ID of the original medium, the copied content cannot be decrypted. As a result, the copyright of the content can be protected. The structure shown in FIG. 1 is a recording and reproducing apparatus. The present invention is applied to the case that the content protecting process for the DVD medium 1 is performed under a PC environment. Next, with reference to FIG. 2, roles shared by a PC and a drive according to a conventional system will be described. In FIG. 2, reference numeral 4 represents a DVD drive as a recording and reproducing apparatus that records and reproduces a content to and from a DVD medium 1 based on the foregoing CPRM standard will be described. Reference numeral 5 represents a host for example a PC as a data processing apparatus. The host 5 is an apparatus or application software that can handle a content that can be recorded to the DVD medium 1 and reproduced therefrom and that is connected to the DVD drive 4. The host 5 is composed of for example application software and a PC in which the application software is installed. The DVD drive 4 and the host 5 are connected with an interface 4a. The interface 4a is for example ATAPI (AT Attachment with Packet Interface), SCSI (Small Computer System Interface), USB (Universal Serial Bus), IEEE (Institute of Electrical and Electronics Engineers) 1394, or the like. On the DVD medium 1, a medium ID 11, a medium key block 12, and a ACC (Authentication Control Code) are pre-recorded. The ACC is data recorded on the DVD medium 1. The ACC causes the DVD drive 4 and the host 5 to authenticate each other uniquely for each DVD medium 1. The DVD drive 4 reads an ACC 16 from the DVD medium 1. The ACC 16 that is read from the DVD medium 1 is input to an AKE (Authentication and Key Exchange) 41 of the DVD drive 4. In addition, the ACC 16 is transferred to the host 5. The host 5 inputs the received ACC to an AKE 51. The AKEs 41 and 51 exchange random number data and generates a common session key (referred to as bus key in the structure shown in FIG. 2) that varies in each authenticating operation with the exchanged random numbers and the value of the ACC. The bus key is supplied to MAC (Message Authentication Code) calculating blocks 42 and 52. The MAC calculating blocks 42 and 52 are processes that calculate a medium ID and a MAC of the medium key block 12 with the obtained bus keys as parameters obtained by the AKEs 41 and 51. The host 5 uses the MAC calculating blocks 42 and 52 so as to determine whether or not the MKB and medium ID have integrity. A comparing portion 53 of the host 5 compares the MACs calculated by the MACs 42 and 52 and determines whether or not they match. When the values of the MACs match, it is confirmed that the MKB and the medium ID have integrity. A switch SW1 is controlled in accordance with the compared output. The switch SW1 turns on/off a signal path between a recording path or a reproducing path of the DVD medium 1 of the DVD drive 4 and an encrypting/(or) decrypting module 54 of the host 5. The switch SW1 represents on/off of the signal path. Actually, the switch SW1 represents that when the signal path is turned on, the process of the host 5 is continued and that when the signal path is turned off, the process of the host 5 is stopped. The encrypting/decrypting module 54 is a calculating block that calculates a content key with a medium unique key, an encrypted title key, and a CCI, encrypts a content with the content key, obtains an encrypted content 13 or decrypts the encrypted content 13 with the content key. A medium unique key calculating block 55 is a calculating block that calculates a medium unique key with the MKB 12, the medium ID, and a device key 56. Like the recorder or player shown in FIG. 1, the medium unique key calculating block 55 calculates a medium key with the device key and the MKB 12. The medium unique key calculating block 55 calculates a medium unique key with the medium key and the medium IC 11. When the medium key is a predetermined value, it is determined that the electronic apparatus or application software is not valid. As a result, the electronic apparatus or application software is revoked. Thus, the medium unique key calculating block 55 also functions as a revoke processing portion that revokes the electronic apparatus or application software. When a content is recorded, if the result of the comparing portion 53 has confirmed integrity, the switch SW1 is turned on. At that point, the encrypted content 13, the encrypted title key 14, and the CCI 15 are supplied from the encrypting/decrypting module 54 to the DVD drive 4 through the switch SW1. As a result, the encrypted content 13, the encrypted title key 14, and the CCI 15 are recorded to the DVD medium 1. When a content is reproduced, if the result of the comparing portion 53 has confirmed integrity, the SW1 is turned on. At that point, the encrypted content 13, the encrypted title key 14, and the CCI 15 reproduced from the DVD medium 1 are supplied to the encrypting/decrypting module 54 through the switch SW1. The encrypting/decrypting module 54 decrypts the encrypted content. FIG. 3 shows steps of a process for exchanging signals among the DVD medium 1, the DVD drive 4, and the host 5 in the system using the DVD medium under the conventional PC environment shown in FIG. 2. The host 5 sends a command to the DVD drive 4. The DVD drive 4 performs an operation in accordance with the command. In response to the command received from the host 5, the ACC of the DVD medium 1 is sought and read (at step Si). At the next step S2, the ACC is input to the AKE 41. In addition, the ACC is transferred to the host 5. In the host 5, the received ACC is input to the AKE 51. The AKEs 41 and 51 exchange random number data. The AKEs 41 and 51 generate a bus key as a session key that varies in each session with the exchanged random numbers and the value of the ACC 16. The bus key is shared by the DVD drive 4 and the host 5. When a mutual authentication has not been successful, the process is stopped. Whenever the disc is detected or the disc is changed after the power is turned on, an authenticating operation is performed. When a recording operation is performed with the recording button or a reproducing operation is performed with the play button, an authenticating operation may be performed. For example, when the record button or play button is pressed, an authenticating operation is performed. When authentication has been successful, at step S3, the host 5 requests the DVD drive 4 to read a MKB (medium key block) pack #0 from the DVD medium 1. MKB pack 0 to pack 15 of 16 sectors are recorded repeatedly 12 times in the lead-in area. The error correction code encoding process is-performed in the unit of one pack. At step S4, the DVD drive 4 reads the MKB pack #0. At step S5, the pack #0 is read. The DVD drive 4 returns a modified MKB to the host 5 (at step S6). When the DVD drive 4 reads an MKB, the DVD drive 4 calculates a MAC value with a bus key as a parameter, adds the MAC value to the MKB, and transfers the resultant data to the host 5. At steps S7 and S8, the requesting operation, the reading operation, and the transferring operation are repeatedly performed for the remaining MKB packs other than the pack #0 namely until for example the pack #15 is read and transferred to the host 5. The host 5 requests a medium ID of the DVD drive 4. The DVD drive 4 reads the medium ID from the DVD medium 1. At step S11, the medium ID is read. When the DVD drive 4 reads the medium ID from the DVD medium 1, the DVD drive 4 calculates the MAC value with the bus key as a parameter. At step S12, the DVD drive 4 adds a MAC value ml to the medium ID and transfers the resultant data to the host 5. The host 5 calculates the MAC value with parameters of the MKB 12 received from the DVD drive 4 and the bus key received from the medium ID 11. The comparing portion 53 compares the calculated MAC value with the MAC value received from the DVD drive 4. When they match, the host 5 determines that the received MKB and medium ID are valid and turns on the switch SW1 so as to cause the process to advance. In contrast, when they do not match, the host 5 determines that the received MKB and medium ID have been revoked and turns off the switch SW1 so as to cause the process to stop. At step S13, the host 5 requests an encrypted content of the DVD drive 4. At step S14, the DVD drive 4 reads the encrypted content from the DVD drive 4. At step S13, the encrypted content is transferred to the host 5. The medium unique key calculating block 55 of the host 5 calculates a medium unique key with the device key 56, the MKB 12, and the medium ID 11. The medium unique key is supplied to the encrypting/decrypting module 54. The encrypting/decrypting module 54 obtains a content key with the encrypted title key 14 and the CCI 15. The encrypting/decrypting module 54 decrypts the encrypted content that is read from the DVD medium 1 with the content key. The encrypting/decrypting module 54 encrypts a content that is recorded to the DVD medium 1. At step ST1 of a flow chart shown in FIG. 4, a MAC calculated value obtained with a bus key as a parameter by the MAC calculating block 42 is compared with a MAC calculated value obtained with a bus key as a parameter by the comparing portion 53. When they match, at step ST2, the switch SW1 is turned on. When they do not match, at step ST3, the switch SW1 is turned off and the process is stopped. The foregoing CPRM uses the same bus key generating method as the CSS, which is a copyright protection technology for the DVD-Video. Although the contents of the CSS authenticating system is supposed to be secret, it has been analyzed and can be operated by free software that has not been permitted by DVD-CCA, which is a CSS license management organization. In addition, a content protecting process is performed on the host side. In other words, all a revocation determining process, a medium key obtaining process, a medium unique key obtaining process, a title key generating process, a title key obtaining processes, a content key obtaining process, a content encrypting process, and a content decrypting process are performed on the host side. Thus, the reliability of the copyright protection technology deteriorates. An embodiment of the present invention is to solve such a problem. According to the embodiment, a structure for obtaining a title key in a content protecting process in a PC environment is disposed in a drive. After the drive and the PC mutually authenticates each other, the title key and the content key are transmitted to the PC. FIG. 5 is a block diagram showing a structure for performing the mutual authentication according to the embodiment. FIG. 6 is a flow chart showing a process on the drive side. FIG. 7 is a flow chart showing a process on the host side. In the following description, reference numeral 101 represents a medium for example an optical disc. Reference numeral 102 represents a drive for a medium. Reference numeral 103 represents a host connected to the drive 102 through a drive-host interface 104. On the medium 101, information similar to that of the foregoing DVD medium is pre-recorded. The medium 101 may be not only a recordable type, but a read-only type. The host 103 sends a predetermined command to the drive 102 so as to control the operation of the drive 102. Commands that are used are commands described in the foregoing non-patent related art reference 2, extended commands, a READ command for reading a content from the medium 101 as sector data, and a WRITE command for writing a content as sector data to the medium 101. The drive 102 has a device key 121 for the drive. The host 103 has a device key 131 for the host. The device key 121 is mainly placed in an LSI (Large Scale Integrated Circuit) and securely stored so that it cannot be read from the outside of the drive 102. The device key 131 may be securely stored in a software program or stored as hardware. To allow the drive 102 to be a valid drive that can handle the medium 101, the drive 102 requires secret information of the copyright protection technology such as a device key according to the embodiment. Thus, a clone drive that pretends to be an authorized drive without a proper license can be prevented from being produced. As shown in FIG. 5, the drive 102 has a process MKB 122 that inputs an MKB and the device key 121 and determines whether or not the device key of the drive has been revoked. Likewise, the host 103 has a process MKB 132. When the drive has not been revoked, a medium key Km is output from each of the process MKBs 122 and 132. After the revoke determining process has been performed and the medium key Km has been obtained an authenticating process is performed. Reference numerals 123, 124, and 125 represent MAC calculating blocks that calculate a MAC value using the medium key Km as a parameter. Reference numerals 126, 127, and 128 represent random number generators (RNGs). The random number generator 126 generates a random number Ra1. The random number generator 127 generates a random number Ra2. The random number generator 128 generates a random number Ra3. The random number generators 126, 127, and 128 are random number generators composed of for example an LSI. Thus, they can generate random numbers close to true random numbers in comparison with a method of which random numbers are generated by software. Although the random number generators may be composed of common hardware, random numbers Ra1, Ra2, and Ra3 are independent. The host 103 has MAC calculating blocks 133, 134, and 135 and random number generators 136, 137, an 138. The MAC calculating blocks 133, 134, and 135 calculate MAC values using the medium key Km as a parameter. The random number generator 136 generates a random number Rb1. The random number generator 137 generates a random number Rb2. The random number generator 138 generates a random number Rb3. The random number generators 136, 137, and 138 are normally software that generates random numbers. Alternatively, the random number generators 136, 137, and 138 may be hardware that generate random numbers. The random numbers generated in the drive 102 are exchanged with the random numbers generated in the host 103. In other words, the random number Ra1 and the random number Rb1 are input to each of the MAC calculating blocks 123 and 133. The random number Ra2 and the random number Rb2 are input to each of the MAC calculating blocks 124 and 134. The random number Ra3 and the random number Rb3 are input to each of the MAC calculating blocks 125 and 135. The MAC value calculated by the MAC calculating block 123 of the drive 102 and the MAC value calculated by the MAC calculating block 133 of the host 103 are compared by a comparing portion 139 of the host 103. The comparing portion 139 determines whether or not the two values are the same. In this example, the MAC value is denoted by eKm(Ra1 ∥ Rb1). eKm () represents that data in parentheses is encrypted using the medium key Km as a key. The symbol Ra1 ∥ Rb1 represents that two random numbers are combined so that the random number Ra1 is placed on the left side and the random number Rb1 is placed on the right side. When the compared result represents that the two values are the same, the host 103 has successfully authenticated the drive 102. Otherwise, the host 103 has not successfully authenticated the drive 102. The MAC value calculated by the MAC calculating block 134 of the host 103 and the MAC value calculated by the MAC calculating block 124 of the drive 102 are compared by a comparing portion 129 of the drive 102. The comparing portion 129 determines whether or not the two values are the same. The MAC value is denoted by eKm(Rb2 ∥ Ra2). When the compared result represents that the two values are the same, the drive 102 has successfully authenticated the host 103. Otherwise, the drive 102 has not successfully authenticated the host 103. When the comparing portions 139 and 129 have determined that the MAC values are the same and it has been confirmed that the drive 102 and the host 103 are valid, namely mutual authentication has been successfully performed, the MAC calculating blocks 125 and 135 generate a common session key eKm(Ra3 ∥ Rb3). Next, with reference to flow charts shown in FIG. 6 and FIG. 7, a process of the mutual authentication will be described. First of all, at step ST20 shown in FIG. 7, the host 103 issues a command REPORT KEY and requests the drive 102 for the MKB. At step ST10 shown in FIG. 6, the drive 102 reads the MKB 112 from the medium 101 and transfers the MKB 112 to the host 103. Thereafter, at step ST11, the drive 102 causes the process MKB 122 to calculate the medium key Km. At step ST21, the host 103 causes the process MKB 132 to calculate the medium key Km. In the calculating process, the drive 102 and the host 103 determine whether or not the device keys 121 and 31 represent that the drive 102 and the host 103 should be revoked (at step ST12 shown in FIG. 6 and step ST22 shown in FIG. 7). When the drive 102 and the host 103 should be revoked, they are revoked and the process is completed. When the host 103 should not be revoked, at step ST23, the host 103 transfers the random number Rb1 and the random number Rb2 generated by the random number generators 136 and 137 to the drive 102 using a command SEND KEY. When the drive 102 should not be revoked, at step ST13, the drive 102 receives the random numbers transferred from the host 103. Thereafter, the host 103 requests the drive 102 to transfer a response value of the MAC using the medium key Km of the drive 102 and the random number Ra1 generated by the random number generator 126 to the host 103 using a command REPORT KEY (at step ST24). This response value is denoted by eKm(Ra1 ∥ Rb1). eKm ( ) represents that data in parentheses is encrypted using the medium key Km as an encryption key. The symbol Ra1 ∥ Rb1 represents that two random numbers are combined so that the random number Ra1 is placed on the left side and the random number Rb1 is placed on the right side. After the drive 102 has received the command REPORT KEY from the host 103, at step ST14, the drive 102 transfers the MAC value eKm(Ra1 ∥ Rb1) and the random number Ra1 generated by the MAC calculating block 123 to the host 103. At step ST25, the host 103 causes the MAC calculating block 133 to calculate the MAC value and cause the comparing portion 139 to determine whether the calculated MAC value matches the MAC value received from the drive 102. When the received MAC value matches the calculated MAC value, the host 103 has successfully authenticated the drive 102. When the compared result at step ST25 represents that the MAC values do not match, the host 103 has not successfully authenticated the drive 102. As a result, a rejecting process is preformed. When the host 103 has successfully authenticated the drive 102, at step ST26, the host 103 sends the command REPORT KEY to the drive 102 so as to request the drive 102 to transfer the random number Ra2 and the random number Ra3 generated by the random number generators 124 and 125 of the drive 102 to the host 103. In response to the command, at step ST15, the drive 102 transfers these random numbers to the host 103. At step S27, the MAC calculating block 134 of the host 103 calculates a response value eKm(Rb2 ∥ Ra2) of MAC using the random number received from the drive 102 and the medium key Km of the host 103 and transfers the response value eKm(Rb2 ∥ Ra2) and the random number Rb3 to the drive 102 using the command SEND KEY. At step ST16, when the drive 102 has received the response value eKm(Rb2 ∥ Ra2) and the random number Rb3 from the host 103, the drive 102 calculates the MAC value by itself. At step ST17, the drive 102 causes the comparing portion 129 to determine whether or not the calculated MAC value matches the MAC value received from the host 103. When the received MAC value matches the calculated MAC value, the drive 102 has successfully authenticated the host 103. In this case, at step ST18, the MAC calculating block 125 generates the session key eKm(Rb3 ∥ Ra3) and transmits information that represents that the host 103 has been successfully authenticated to the host 103. Thereafter, the authenticating process is completed. The session key is varied whenever the authenticating process is performed. When the compared result at step ST17 represents that the MAC values do not match, the drive 102 has not successfully authenticated the host 103. At step ST19, error information that represents that the host 103 has not been successfully authenticated is transmitted to the host 103. In response to the command SEND KEY, the host 103 receives information that represents whether or not the host 103 has been successfully authenticated from the drive 102. At step ST28, in accordance with the received information, the host 103 determines whether or not the authenticating process has been completed. When the host 103 has received the information that represents that the authentication has been successful, the host 103 determines that the authenticating process has been completed. When the host 103 has received information that represents that the authentication has not been successful, the host 103 determines that the authenticating process has not been completed. When the authenticating process has been completed, at step ST29, the MAC calculating block 135 generates a session key eKm(Ra3 ∥ Rb3) (of for example 64 bits) that is in common with the drive side. When the authenticating process has not been completed, a rejecting process is performed. In the following description, the session key eKm(Ra3 ∥ Rb3) is denoted by Ks. In the mutual authentication according to the foregoing embodiment, the drive 102 is capable of having a revoking function. Thus, the drive 102 does not need a special authenticating key dedicated for authentication is not require. In addition, the drive 102 causes the comparing portion 129 to check the authentication result of the host 103. Thus, the drive 102 is capable of determining whether or not it has been mounted after it had been correctly licensed by the host 103. Next, with reference to FIG. 8, a structure of a recorder that incorporates a drive 102 and a host 103 that perform the foregoing mutual authentication according to an embodiment will be described. The recorder according to the embodiment securely transfers a medium unique key calculated by the drive 102 to the host 103 using a session key Ks generated by mutual authentication. A random number generator 143 of the drive 102 generates a title key. The drive 102 generates a content key using a title key and a CCI 232. The generated content key is securely transferred to the host 103 using a session key Ks. The host 103 encrypts a content using a decrypted content key and transfers the encrypted content to the drive 102. The drive 102 records the encrypted content, the encrypted title key, and the CCI 232 to the medium 101. A CCI recorded on the medium 101 is denoted by reference numeral 115. In other words, the drive 102 generates the medium unique key and the content key. The drive 102 that composes the recorder has structural elements of a device key 121, a process MKB 122, a C2_G2 141, a DES (Data Encryption Standard) encryptor 142, a random number generator 143, a C2_G 145, and a DES encryptor 146. The C2_G2 141 is a block that calculates a medium unique key using the medium ID and the medium key. The G2_G2 145 is a block that calculates the content key using the title key and the CCI 232. The process MKB 122 calculates an MKB 112 reproduced from the medium 101 and the device key 121. As a result, it is determined whether or not the drive 102 has been revoked. The process MKB 122 calculates the medium key using the MKB 112 and the device key 121. When the MKB 112 does not contain the device key 121 of the drive 102 and the calculated result matches a predetermined value for example zero, it is determined that the drive 102 that has the device key 121 is not valid. Thus, the drive 102 is revoked. The C2_G 141 is a process for calculating the medium key and a medium ID 111 and obtaining a medium unique key as a calculated result. The DES encryptor 142 encrypts the medium unique key using a session key Ks. In this example, as an encrypting system, DES CBC mode is used. An output of the DES encryptor 142 is transmitted to a DES decryptor 151 of the host 103. The random number generator 143 of the drive 102 generates a title key. The title key generated by the random number generator 143 is supplied to a C2_E 153 of the host 103. The C2 encrypts the title key using a medium unique key. The encrypted title key denoted by reference numeral 114 is recorded to the medium 101. The host 103 causes a MAC calculating block 158 to calculate a MAC value eKs(CCI) of a CCI using the session key Ks. The MAC value eKs(CCI) and a CCI 232 are transferred to the drive 102. The drive 102 causes an MAC calculating block 157 to calculate a MAC value eKs(CCI) using the CCI 232 received from the host 103 and the session key Ks. The calculated MAC value eKs (CCI) and the MAC value received from the host 103 are supplied to a comparing portion 159. When both the MAC values match, the comparing portion 159 determines that the CCI 232 received from the host 103 has not been tampered. As a result, the drive 102 turns on a switch SW2. In contrast, when the MAC values do not match, the comparing portion 159 determines that the CCI has been tampered. At that point, the drive 102 turns off the switch SW2 and stops the process. In the drive 102, the CCI 232 received from the host 103 and the title key are supplied to the C2_G 145. The C2_G 145 obtains a content key. The content key is supplied to a DES encryptor 146. The DES encryptor 146 encrypts the content key using the session key Ks. The encrypted content key is transferred to a DES decryptor 156 of the host 103. The content key decrypted by the DES decryptor 156 of the host 103 using the session key Ks is supplied to a C2_ECBC 155. The C2_ECBC 155 encrypts the content using the content key. The encrypted content denoted by reference numeral 113 is transferred to the drive 102. The drive 102 records the encrypted content 113 to the medium 101. FIG. 9 shows steps of a content recording procedure of the recorder according to the embodiment. First of all, the drive 102 seeks an MKB from the medium 101 and reads the MKB therefrom in accordance with a request from the host 103 (at step S61). At step S62, AKE (Authentication and Key Exchange) is performed. In other words, the foregoing revoking process and mutual authenticating operation of the drive 102 and the host 103 are performed. The mutual authenticating operation is always performed whenever the power of the recorder is turned on and a disc is detected or whenever the current disc is replaced with another disc. Alternatively, when the record button is pressed for the recording operation or the play button is pressed for the reproducing operation, the authenticating operation may be performed. For example, when the record button or the play button is pressed, the authenticating operation is performed. When the mutual authentication has not been successfully performed, the rejecting process is performed and the subsequent process of the recorder is stopped. When the mutual authentication has been successfully preformed, both the drive 102 and the host 103 generate a session key Ks and share it. At step S63, the host 103 requests the drive 102 for a medium unique key. The drive 102 seeks a medium ID of the medium 101 (at step S64) and reads a medium ID from the medium 101 (at step S65). The drive 102 calculates the medium key and the medium ID so as to generate a medium unique key. At step S66, the medium unique key is encrypted with the session key Ks. The encrypted medium unique key is transferred to the host 103. Next, at step S67, the host 103 requests the drive 102 for a title key. At step S68, the drive 102 transfers the title key to the host 103. The host 103 decrypts the encrypted medium unique key using the session key Ks. The host 103 encrypts the title key using the medium unique key and generates an encrypted title key. At step S69, the host 103 sends a CCI 232 to the drive 102. At that point, to prevent the CCI 232 from being tampered, the host 103 transfers a MAC value eKs(CCI) calculated as authentication data of the CCI 232 to the drive 102. After it has been determined that the CCI 232 had not been tampered, the drive 102 generates a content key using the title key and the CCI 232 and encrypts the content key using the session key Ks. At step S70, the host 103 requests the drive 102 for the content key. At step S71, the drive 102 sends the encrypted content key to the host 103. The host 103 decrypts the encrypted content key using the session key Ks and obtains the content key. The host 103 encrypts a content using the content key. At step S72, the host 103 transfers the encrypted title key, the encrypted content, and the CCI 232 to the drive 102. At step S73, the drive 102 records the encrypted title key, the encrypted content, and the CI 232 to the medium 101. In the recorder having the structure shown in FIG. 8, a true random number or a random number close thereto is generated by hardware for example an LSI of the drive 102. As a result, it becomes difficult to replace a generated random number with a fixed value. In addition, in the drive 102, a content key is generated by hardware. Thus, copyright protection can be securely implemented. FIG. 10 shows a structure of a player that integrates a drive 102 and a host 103 that perform the foregoing mutual authentication according to an embodiment. The player according to the embodiment securely transfers a medium unique key calculated by the drive 102 to the host 103 using a session key Ks generated as a result of the mutual authentication of a medium unique key calculated by the drive 102. The host 103 decrypts an encrypted title key using the medium unique key and decrypts a content using a content key obtained using the title key and a CCI 115. The drive 102 that composes the player has structural elements of a device key 121, a process MKB 122, a C2_G2 141, and a DES encryptor 142. The process MKB 122 calculates an MKB 112 reproduced from a medium 101 and the device key 121. As a result, it is determined whether or not the drive 102 has been revoked. The process MKB 122 obtains a medium key using the MKB 112 and the device key 121. The C2_G 141 is a process for calculating a medium key and a medium ID 111 and obtaining a medium unique key. The DES encryptor 142 encrypts the medium unique key using a session key Ks. In this example, as an encrypting system, DES CBS mode is used. An output of the DES encryptor 142 is transmitted to a DES descriptor 151 of the host 103. In the host 103, the DES descriptor 151 decrypts the medium unique key using a session key Ks. The medium unique key and an encrypted title key 114 are supplied to a C2_D 153. The C2_D 153 decrypts the encrypted title key using the medium unique key. The decrypted title key and a CCI 115 reproduced from the medium 101 are supplied to a C2_G 154. The C2_G 154 obtains a content key. A C2 decryptor 155 decrypts an encrypted content 113 reproduced from the medium 101 using the content key and obtains the content key. FIG. 11 shows steps of a content reproducing procedure. First of all, the drive 102 seeks an MKB from the medium 101 in accordance with a request from the host 103 and reads the MKB therefrom (at step S41). An MKB is read for each pack. At step S42, AKE is performed. In other words, the foregoing revoking process and mutual authenticating operation of the drive 102 and the host 103 are preformed. When the mutual authentication has not been successfully performed, a rejecting process is performed and for example the subsequence process is stopped. When the mutual authentication has been successfully performed, the drive 102 and the host 103 generate a session key Ks and share it. At step S43, the host 103 requests the drive 102 for a medium unique key. The drive 102 seeks a medium ID of the medium 101 (at step S44). The drive 102 reads the medium ID from the medium 101 (at step S45). The drive 102 calculates the medium key and a medium ID and generates a medium unique key. At step S46, the medium unique key is encrypted using the session key Ks. The encrypted medium unique key is transferred to the host 103. Thereafter, at step S47, the host 103 requests the drive 102 for an encrypted title key, a CCI, and an encrypted content. At step S48, the drive 102 reads an encrypted title key 114, a CCI 115, and an encrypted content 113 from the medium 101. At step S49, the drive 102 reads the encrypted title key 114, the CCI 115, and the encrypted content 113. At step S50, the drive 102 transfers the encrypted title key 114, the CCI 115, and the encrypted content 113 to the host 103. The host 103 decrypts the title key and obtains a content key using the title key and the CCI 115. The host 103 decrypts the encrypted content using the content key. In the player having the structure shown in FIG. 10, the host 103 has the decryptor C2_D 153 that decrypts an encrypted title key. Alternatively, the drive 102 may have a decryptor that decrypts an encrypted title key. In this case, a decrypted title key is securely transferred to the C2_G 154 of the host 103. The C2_G 154 generates a content key. Alternatively, the drive 102 may have the content key generating device C2_G so as to generate the content key using the decrypted title key and the CCI. In this case, the decrypted content key is securely transferred to the C2 decryptor 155 of the host 103. Next, with reference to FIG. 12 and FIG. 13, a recorder and a player according to another embodiment of the present invention will be described. In the embodiment, a medium unique key is generated by the drive. A parameter with which a content key is generated is used (a system of which the CPRM is extended). In the system of which the CPRM is extended, a parameter A with which a medium unique key is calculated and a parameter B for which an encrypting/decrypting process is performed are used. The parameters A and B may be recorded on the host side, on the drive side, or recorded on a medium and read by the host. When the parameters. A and B are sent and received through an interface, they may be encrypted so as to securely transfer them. FIG. 12 shows a structure of the recorder according to the embodiment. In FIG. 12, reference numeral 201 represents a recordable medium. On the medium 201, an EKB 211, en encrypted disc key Em(Kd) 212, a disc ID 213, and a unit key generation value Vu 214 are pre-recorded. Next, terminology of key information shown in FIG. 12 will be described. The EKB 211 is a key bundle of which a medium key is distributed to each device key. The EKB 211 corresponds to a medium key block MKB according to the foregoing embodiment. A medium key Km is key information unique to each medium. When a medium key is not found from the EKB, it represents that the device key has been revoked. A disc key Kd is key information that differs in at least each content. A disc key Kd may differ in each master disc. The encrypted disc key Em(Kd) 212 is an encryption key of which a disc key Kd is encrypted with a medium key Km. The encrypted disc key Em(Kd) 212 is recorded on the medium 201. The encrypted disc key Em (Kd) 212 is used for the drive 102 to generate an embedded key Ke that differs in each medium. The unit key generation value Vu 214 is a parameter that can be defined in each encrypted unit. Each encrypted unit is composed of data of a plurality of sectors. The unit key generation value Vu 214 is used for the host 103 to generate a unit key Ku as an encryption key with which a content is encrypted. The disc ID 213 is an ID that doffers in each stamper. The disc ID 213 corresponds to the medium ID 111 of the foregoing embodiment. The embedded key Ke is key information that differs in each medium. The embedded key Ke corresponds to the medium unique key according to the foregoing embodiment. A process EKB 222 obtains a medium key Km using a device key 221 of the drive 102 and the EKB 211 of the medium 201. An AES_D 223 decrypts a disc key Kd using the medium key Km and the encrypted disc key Em(Kd) 212 of the medium 201. An AES_G 224 obtains an embedded key Ke using the disc key Kd and the disc ID 213. The unit key Ku is a key with which a content is encrypted. The unit key Ku is obtained using the embedded key Ke, the unit key generation value Vu, and copy control information CCI 232. The unit key Ku corresponds to the content key of the foregoing embodiment. Next, the operation of the recorder according to the other embodiment will be described. First of all, AKEs 225 and 227 authenticate each other. When they have successfully authenticated each other, they generates a session key Ks. A parameter for the authentication (not shown in FIG. 12) is supplied to at least one of the AKEs 225 and 227. The drive 102 reads the EKB 211 from the medium 201. The process EKB 222,of the drive 102 calculates the EKB 211 of the medium 201 and the device key 221 and obtains the medium key Km. When the calculated result is for example 0, the device key is revoked. The device key 221 of the drive 102 is a key unique to each drive model. The drive 102 reads the encrypted disc key Em(Kd) 212 from the medium 201. The AES_D 223 obtains the disc key Kd using the medium key Km. The AES (Advanced Encryption Standard) is an encrypting method that the United States Government has employed as a new encrypting standard that is a successor of the DES. In addition, the drive 102 reads the disc ID 213 from the medium 201. The AES_G 224 calculates the disc ID and the disc key Kd and obtains the embedded key Ke. After the authentication of the drive 102 and the host 103 have successfully performed and the session key Ks has been obtained, the host 103 requests the drive 102 for the embedded key Ke. When the drive 102 transfers Ke to the host 103 through the interface 104, the AES encryptor 226 encrypts Ke using the session key Ks. The host 103 causes the AES decryptor 228 to decrypt the encrypted Ke and obtains Ke. The AES encryptor 226 and the AES decryptor 228 perform a process of for example CBC (Cipher Block Chaining) mode. The host 103 process the content in each encrypted unit. The host 103 reads the unit key generation value Vu 214 as the encrypted unit from the drive 102. The AES_G 229 calculates the unit key Ku using the embedded key Ke, the unit key generation value Vu 214, and the CCI 232. Since the unit key Ku is generated using the CCI 232, copyright of the content can be more securely protected. The host 103 causes the encrypting module 230 to encrypt the content using the unit key Ku. The encrypted content 113 is transferred to the drive 102. The encrypted content 113 is recorded to the recordable medium 201. Next, with reference to FIG. 13, a player according to the other embodiment of the present invention will be described. The player reproduces data from a ROM type medium 210 for example a ROM disc. A content is pre-recorded on the ROM type medium 210. A host 103 does not need to perform an encrypting process. The host 103 uses a decrypting module 231. An encrypted content is read from the medium 210 and decrypted by the decrypting module 231. As a result, an AV content is obtained. In the case of the ROM type medium 210, a medium key Km and a disc key Kd are key information unique to each content. Each content is composed of at least one encrypted unit. An embedded key generation value Ve 215 is pre-recorded on the medium 210. The embedded key generation value Ve 215 is a non-zero value recoded for each stamper (which is a disc original of which photo resist is developed or a first stamper produced using a disc original). The embedded key generation value Ve 215 is recorded as a physical watermark on the disc by other than the regular data recording means. An embedded key Ke corresponds to the medium unique key of the foregoing embodiment. The embedded key generation value Ve 215 for generating the embedded key Ke is a kind of a medium ID. The recorder shown in FIG. 13 performs a process similar to the player shown in FIG. 12. First, AKEs 225 and 227 authenticate each other and generate a session key Ks. A process EKB 222 of the drive 102 calculates an EKB 211 and a device key 221 that have been read, obtains a medium key Km, and performs a revoking process. An AES_D 223 decrypts a disc key Kd using the medium key Km. An AES_G 224 obtains an embedded key Ke. An AES encryptor 226 encrypts Ke using a session key Ks. The host 103 causes an AES decryptor 228 to decrypt the encrypted Ke and obtains Ke. The host 103 reads a unit key generation value Vu 214 of an encrypted unit to be read and copy control information CCI from the drive 102. An AES_G 229 calculates a unit key Ku. A decrypting module 231 of the host 103 decrypts sector data of the encrypted unit requested by the host 103 using the unit key Ku of the encrypted unit. According to the present invention, since information unique to an electronic device or application software for example a device key as secret information of a copyright protection technology is implemented in a recording and reproducing apparatus, application software that is installed in a DVD processing apparatus does not need to have secret information of a copyright protection technology. Thus, the software can withstand an analysis using reverse engineering. As a result, the safety of the copyright protection technology can be secured. A device key that is information unique to an electronic apparatus or application software is divided into two portions that are shared by the recording and reproducing apparatus and the data processing apparatus. Thus, both the recording and reproducing apparatus and the application software can be revoked. According to the present invention, a part of an algorithm of a copyright protection technology, for example a calculating portion for a medium unique key is implemented in the recording and reproducing apparatus. Thus, the application software of the data processing apparatus needs to have only a part of the algorithm. As a result, the software is capable of withstanding an analysis using reverse engineering. Consequently, the safety of the copyright protection technology can be secured. Although the present invention has been shown and described with respect to a best mode embodiment thereof, it should be understood by those skilled in the art that the foregoing and various other changes, omissions, and additions in the form and detail thereof may be made therein without departing from the spirit and scope of the present invention. For example, a title key is a key for each title. However, according to the present invention, as long as the title key is random number information, the title key does not need to differ in each title. The foregoing description exemplifies the CPRM as a copyright protection technology and an extended CPRM. However, the present invention can be applied to other than the CPRM as a copyright protection technology. For example, the present invention can be applied to a copyright protection technology based on a tree-type key distribution structure as proposed in for example Japanese Patent Laid-Open Publication No. 2001-352322. In addition, the present invention can be applied to a PC based system. However, it should be noted that the present invention is not limited to a structure of which a PC and a drive are combined. For example, the present invention can be applied to a portable moving picture or still picture camera having an optical disc as a medium, a drive that drives the medium, and a microcomputer that controls the drive. According to the present invention, the reproducing apparatus side generates a content key. The content key is transmitted to the information processing apparatus. The information processing apparatus side encrypts a content using the content key. Since the reproducing apparatus generates key information with which copyright of a content is protected, the content key can be generated by hardware. As a result, tamper-resistance for secret information is improved. In addition, since the reproducing apparatus generates a random number as an intermediate key, a true random number or a random number close thereto can be generated by hardware for example an LSI in the reproducing apparatus. Thus, it becomes difficult to replace a generated random number with a fixed value. As a result, according to the present invention, it is not necessary for application software installed in the information processing apparatus to have all secret information of a copyright protection technology. Thus, the system according to the present invention is capable of having tamper-resistance for secret information against reverse-engineering for software and securing safety of the copyright protection technology. In addition, since encrypted data that is read from the disc can be prevented from being decrypted by decrypting software such as “DeCSS” and non-encrypted clear content from being repeatedly copied without copy restriction. Thus, safety of the copyright protection technology can be secured. Since the recording and reproducing apparatus has a device key as information unique to an electronic device, the recording and reproducing apparatus itself can be revoked. According to the present invention, since random number information necessary for calculating a content key in the information processing apparatus can be generated by for example an LSI in the recording and reproducing apparatus, a true random number or a random number close thereto can be generated in comparison with the case that a random number is generated by software in a PC. Thus, the risk of which a random number is replaced with a fixed value can be suppressed.

<SOH> BACKGROUND ART <EOH>On one recording medium such as a DVD (Digital Versatile Disc), which has been recently developed, a large capacity of data for one movie can be recorded as digital information. When video information and so forth can be recorded as digital information, it will become important to protect copyright of digital information against illegal copies. In DVD-Video, as a copy protection technology, CSS (Content Scrambling System) has been employed. The use of the CSS is permitted for only DVD-ROM media, not recordable DVDs such as a DVD−R, a DVD−RW, a DVD+R, a DVD+RW, and so forth due to CSS contract. Thus, the CSS contract does not permit the user to copy the contents of a DVD-Video disc that has been copyright-protected in accordance with the CSS system to a recordable DVD (so-called bit-by-bit copy). However, there was a serious situation of which the CSS encrypting system was broken. Illegal software called “DeCSS” that is capable of easily decrypting contents that has been encrypted in accordance with the CSS encryption system and copying the decrypted contents to a hard disk was published on the Internet. As a background of the advent of “DeCSS”, reproduction software was designed with a CSS decryption key that was not anti-tampered although it was supposed to be anti-tampered. The reproduction software was reverse-engineered and the encryption key was decrypted. As a result, all the CSS algorithm was decrypted. As a successor of the CSS, CPPM (Content Protection for Pre-Recorded Media) as a copyright protection technology for DVD-ROMs such as a DVD-Audio disc and CPRM (Content Protection for Recordable Media) as a copyright protection technology for recordable DVDs and memory cards have been proposed. In these systems, even if there is a problem about encryption for contents, storage of management information, and so forth, the systems can be updated. Even if data of a whole disc is copied, the reproduction can be restricted. A method for protecting copyright for DVDs is described in the following non-patent related art reference 1 . The CPRM is described in the following document distributed by its licenser, 4C Entity, LLC, USA. “Spreading-out Copyright Protection Space Starting from DVD”, Yamada, Nikkei Electronics, pp. 143-153, 2001.8.13. “Content Protection for Recordable Media Specification DVD Book”, Internet <URL: http:// www.4Centrity.com/> In a personal computer (hereinafter, sometimes abbreviated as PC) environment, since a PC and a drive are connected with a standard interface, secret data may be leaked out or tampered at the standard interface. As a result, there is a risk of which application software may be reverse-engineered and secret information may be stolen or tampered. Such a risk hardly occurs in an electronic apparatus that has a recording and reproducing apparatus that is integrated thereinto. When a copyright protection technology is implemented to an application program that is executed on a PC, to prevent the copyright protection technology from being analyzed, the application program is generally anti-tampered. However, there is no index that represents the strength of tamper-resistance. As a result, countermeasures against reverse-engineering depend on the decision and capability of each implementer. Thus, the CSS was broken. The copyright protecting technologies CPPM and CPRM for recordable DVDs, which were proposed as a successor of the CSS are based on the known CSS and have new additional functions. In addition, most of algorithms of copyright protection technologies depend on implementation to a PC. Thus, it cannot be said that they have strong content protection functions. In other words, an encrypting system would be broken by analyzing secret information of a copyright protection technology for example reverse-engineering using application software. Encrypted content read as data from a disc by a PC would be decrypted by decrypting software such as “DeCSS”. The decrypted data would be repeatedly copied as a clear content in non-copy-protection state. Thus, there was a risk of which the copyright protection would not work. An object of the present invention is to provide a mutual authenticating method, a program, a recording medium, a signal processing system, a reproducing apparatus, and an information processing apparatus that allow safety of a copyright protection technology in a PC environment to be secured.

<SOH> BRIEF DESCRIPTION OF DRAWINGS <EOH>FIG. 1 is a block diagram describing a proposed system composed of a recorder, a player, and a DVD medium. FIG. 2 is a block diagram describing a PC based DVD medium recording and reproducing system. FIG. 3 is a schematic diagram describing steps of processes of a DVD drive 4 and a host 5 of the system shown in FIG. 2 . FIG. 4 is a flow chart describing an authenticating operation of the system shown in FIG. 2 . FIG. 5 is a block diagram showing a structure for performing mutual authentication according to an embodiment of the present invention. FIG. 6 is a flow chart describing steps of a process of an authenticating operation of the drive according to the embodiment of the present invention. FIG. 7 is a flow chart describing steps of a process of an authenticating operation of the host according to the embodiment of the present invention. FIG. 8 is a block diagram showing an example of a structure of a recorder that integrates the drive and the host according to the embodiment of the present invention. FIG. 9 is a schematic diagram describing an example of steps of a communicating procedure of the recorder. FIG. 10 is a block diagram showing an example of a structure of a player that integrates the drive and the host according to the embodiment of the present invention. FIG. 11 is a schematic diagram describing an example of steps of a communicating procedure of the player. FIG. 12 is a block diagram showing an example of a structure of a recorder that integrates a drive and a host according to another embodiment of the present invention. FIG. 13 is a block diagram showing an example of a structure of a player that integrates the drive and the host according to the other embodiment of the present invention. detailed-description description="Detailed Description" end="lead"?

20040831

20080902

20050428

98704.0

CALLAHAN, PAUL E

SIGNAL PROCESSING SYSTEM, RECORDING METHOD, PROGRAM, RECORDING MEDIUM, REPRODUCTION DEVICE AND INFORMATION PROCESSING DEVICE

UNDISCOUNTED

ACCEPTED

ACCEPTED

Process for the preparation of a functionalized polymer intermediate products, compositions and shaped parts

Process for the preparation of a functionalized polymer containing an additive, in which process there is formed a compound that contains, besides at least one blocked isocyanate group, a free amino, hydroxy or carboxy group; this compound is linked to an additive via the free amino, hydroxy or carboxy group in the additive; this additive linked to the compound mentioned is contacted with a polymer that contains at least one free amino or hydroxyl group, at a temperature above the polymer's melting point and at least above (150)° C., such that the blocked isocyanate group reacts with the free amino or hydroxy group of the polymer to form the functionalized polymer. The invention also relates to the intermediate products formed in the process and in the preparation thereof. Lasdy, the invention relates to functionalized polymers and polymer compositions containing the functionalized polymer.

1. Process for the preparation of a functionalized polymer wherein a. a first compound, containing at least a primary amino group and at least a group chosen from a first series comprising a secondary amino group, an amino group attached to a secondary carbon atom and a primary hydroxyl group or a group chosen from a second series comprising a hydroxyl group attached to a secondary carbon atom and a carboxy group, or a first compound containing at least a group chosen from the first series and also contains at least a group chosen from the second series whereby optionally said first or second series furthermore comprise a double or triple bond, is contacted with an amount of carbonyl bislactam at a temperature below 150° C. and with the amount of carbonyl bislactam being at least equimolar to the number of primary amino groups or at least equimolar to the number of groups chosen from the first series and with the molar amount of carbonyl bislactam being lower than the sum of the molar number of primary amino groups and groups chosen from the first or second series or lower than the sum of the molar number of groups chosen from the first series and chosen from the second series, as a result of which a first intermediate compound is formed which contains, besides at least one blocked isocyanate group, a free amino group, hydroxy group, carboxy group or a double or triple bond; b. the first intermediate compound is contacted, at a temperature preferably below 150° C., with an additive such that a link is established via the free amino, hydroxy or carboxy group or via a double or triple bond to form a second intermediate compound. c. the second intermediate compound is contacted with a polymer having at least one free amino group or hydroxyl group at a temperature above the melting point of the polymer and at least above 150° C., such that the blocked isocyanate group reacts with the free amino group or hydroxy group of the polymer to form the functionalized polymer. 2. Process according to claim 1 wherein the carbonylbislactam is carbonylbiscaprolactam. 3. Process according to claim 1 wherein the polymer is chosen from the series of polyamides, polyesters, copolyesters, polyethers, polyacrylates, cellulose and hydroxy or amino functionalized polymers. 4. First intermediate compound comprising at least one blocked isocyanate group and a free amino, hydroxy or carboxy group, or a double or triple bond. 5. Process for the preparation of the compound of claim 4, wherein: a. a first compound, containing at least a primary amino group and at least a group chosen from a first series comprising a secondary amino group, an amino group attached to a secondary carbon atom and a primary hydroxyl group or a group chosen from a second series comprising a hydroxyl group attached to a secondary carbon atom and a carboxy group, or a first compound containing at least a group chosen from the first series and also contains at least a group chosen from the second series whereby optionally said first or second series furthermore comprise a double or triple bond, is contacted with an amount of carbonyl bislactam at a temperature below 150° C. and with the amount of carbonyl bislactam being at least equimolar to the number of primary amino groups or at least equimolar to the number of groups chosen from the first series and with the molar amount of carbonyl bislactam being lower than the sum of the molar number of primary amino groups and groups chosen from the first or second series or lower than the sum of the molar number of groups chosen from the first series and chosen from the second series, as a result of which a first intermediate compound is formed which contains, besides at least one blocked isocyanate group, a free amino group, hydroxy group, carboxy group or a double or triple bond; b. the first intermediate compound is contacted, at a temperature preferably below 150° C., with an additive such that a link is established via the free amino, hydroxy or carboxy group or via a double or triple bond to form a second intermediate compound. 6. Second intermediate compound comprising an additive that is linked to the first intermediate compound in claim 4 via the free amino, hydroxy or carboxy group, or a double or triple bond present in the first intermediate compound. 7. Second intermediate compound according to claim 6 wherein the additive is chosen from the series of stabilizers, flame retardants, bactericides, fungicides, surfactants, anti-fouling agents, colouring agents, antistatic agents and lubricants. 8. Process for the preparation of the second intermediate compound of claim 6 wherein: a. a first compound, containing at least a primary amino group and at least a group chosen from a first series comprising a secondary amino group, an amino group attached to a secondary carbon atom and a primary hydroxyl group or a group chosen from a second series comprising a hydroxyl group attached to a secondary carbon atom and a carboxy group, or a first compound containing at least a group chosen from the first series and also contains at least a group chosen from the second series whereby optionally said first or second series furthermore comprise a double or triple bond, is contacted with an amount of carbonyl bislactam at a temperature below 150° C. and with the amount of carbonyl bislactam being at least equimolar to the number of primary amino groups or at least equimolar to the number of groups chosen from the first series and with the molar amount of carbonyl bislactam being lower than the sum of the molar number of primary amino groups and groups chosen from the first or second series or lower than the sum of the molar number of groups chosen from the first series and chosen from the second series, as a result of which a first intermediate compound is formed which contains, besides at least one blocked isocyanate group, a free amino group, hydroxy group, carboxy group or a double or triple bond. 9. Process for the preparation of a functionalized polymer by a. reacting an additive comprising at least one amino group or a hydroxyl group with carbonylbislactam at a temperature below 150° C. such that a link is established via the amino group or hydroxyl group of the additive, thereby forming an intermediate product A, b. contacting the intermediate product A with a polymer having at least one free amino group or hydroxyl group at a temperature above the melting point of the polymer and at least above 150° C., such that the blocked isocyanate group reacts with the free amino group or hydroxy group of the polymer to form a functionalized polymer. 10. Intermediate product A comprising an additive provided with a lactam blocked isocyanate group. 11. Process for the preparation of an intermediate product A according to claim 10, wherein: a. reacting an additive comprising at least one amino group or a hydroxyl group with carbonylbislactam at a temperature below 150° C. such that a link is established via the amino group or hydroxyl group of the additive, thereby forming an intermediate product A. 12. Functionalized polymer obtainable according to the process of claim 1. 13. Polymer composition containing a functionalized polymer according to claim 12. 14. Shaped article comprising the polymer composition of claim 13. 15. Shaped article according to claim 14 wherein the shaped article is a film, fibre, monofilament or strapping. 16. Coating composition comprising the second intermediate compound of claim 6. 17. Substrate comprising a coating based on the coating composition according to claim 16. 18. Coating composition comprising the second intermediate compound of claim 7.

The invention relates to a process for the preparation of a functionalised polymer. The invention also relates to intermediate products, processes for the preparation thereof, a functionalized polymer and a polymer composition containing a functionalized polymer as well as shaped parts. A functionalized polymer may be prepared by adding an additive to a polymer. Certain properties of the polymer are improved in this way. A stabilizer, for example, is added in order to improve the stability of a polymer. Additives blended in polymers generally tend to migrate out of the polymer. This is also known as the “bleeding” of additives. An additive that bleeds out of a polymer accumulates on the surface of the polymer. This means not only the loss of a valuable additive from the polymer, but there also develops a deposit on the polymer surface. Such a deposit on the surface of a polymer is undesirable for many applications. Furthermore, the additive, while migrating out of the polymer, may cause deposits in polymer processing equipment. In injection moulding of polymers, for example, the additive may deposit in a mould. As a consequence, the injection moulding operation needs to be interrupted in order to clean the mould. Such interruptions of production processes are undesirable from a cost viewpoint. Furthermore, additives may bleed out of coatings. Additives that are added to a coating composition or paint may migrate to the surface. As a result, the performance of the additive present on the surface may be lost, which is undesirable. In a known method of preparing a functionalized polymer, the molecular weight of the additive is first increased and then the additive is blended in a polymer. This reduces the bleeding of additives out of polymers. Another manner of preparing functionalized polymers is described by Wolfe in Rubber Chemistry and Technology (vol. 54, p. 988-995). Here, during the polymerization of segmented polyether ester elastomers, antioxidants are co-polymerized by utilizing bifunctional monomers with antioxidant properties, in this application also referrred to as antioxidant. This prevents the antioxidant from bleeding out of the polymer. Dimethyl 5-(3,5-di-t-butyl4-hydroxybenzenepropanamido)-isophthalate, among other substances, is mentioned as a bifunctional antioxidant. A drawback of this method as described by Wolfe is that it can only be applied during the polymerization of the polymer. The invention aims to provide a process for the preparation of functionalized polymers that is not limited to the polymerization of the polymer and that prevents the additive from migrating. This is achieved according to the invention in that a. a first compound, containing at least one primary amino group and at least a group chosen from a first series comprising a secondary amino group, an amino group on a secondary carbon atom and a primary hydroxyl group or a group chosen from a second series comprising a hydroxyl group on a secondary carbon atom and a carboxy group, or a first compound containing at least one group chosen from the first series and also contains at least a group chosen from the second series whereby optionally said first or second series furthermore comprise a double or triple bond, is contacted with an amount of carbonylbislactam (CBL) at a temperature below 150° C. and with the amount of carbonyl bislactam being at least equimolar to the number of primary amino groups or at least equimolar to the number of groups chosen from the first series and with the molar amount of carbonyl bislactam being lower than the sum of the molar number of primary amino groups and groups chosen from the first or second series or lower than the sum of the molar number of groups chosen from the first series and chosen from the second series, as a result of which a first intermediate compound is formed which contains, besides at least one blocked isocyanate group, a free amino, hydroxy, carboxy group or a double or triple bond; b. the first intermediate compound is contacted, at a temperature preferably below 150° C., with an additive such that a link is established via the free amino, hydroxy, carboxy group or the double or triple bond, resulting in the formation of a second intermediate compound; c. the second intermediate compound is contacted with a polymer having at least one free amino group or hydroxyl group at a temperature above the melting point of the polymer and at least above 150° C., such that the blocked isocyanate group reacts with the free amino or hydroxy group of the polymer to form the functionalized polymer. The invention provides a process for the preparation of functionalized polymers, which process is not limited to the polymerization of this polymer and prevents an additive from bleeding. Large amounts of polymer are usually continuously produced during polymerization. This means that when an additive is added during the polymerization of the polymer, large amounts of a functionalized polymer, comprising said additive, are produced. The process according to the invention allows smaller batches of functionalised polymer to be produced more easily in, for example, a compounding process. By adding an additive not during polymerization but later, for example during compounding in an extruder or during injection moulding in an injection moulding machine, greater flexibility is obtained than during the production of a polymer or a polymer composition. In addition, the continuous polymerization process is not disturbed in this manner. In the process according to the invention a first reaction is carried out as mentioned under a. By way of an example of a first reaction, a reaction A) is shown below, in which a first compound, I, contains two primary amine groups and a secondary amine group and in which carbonylbiscaprolactam, CBC, is used as exemplary CBL. In reaction equation A), the first compound reacts with two moles of CBC to form the first intermediatecompound, II, with two moles of caprolactam being split off. The reaction may be carried out ‘in bulk’, with the compound having the secondary amine, hydroxy or carboxy group and the CBL being contacted directly, but the reaction may also be carried out in solution. A catalyst may optionally be applied in order to accelerate the reaction. Preferably a catalyst is applied for a reaction with a hydroxyl group. In that case the reaction is significantly accelerated. Suitable catalysts include acids, including Lewis acids, and bases, including Lewis bases. Examples of acids, including Lewis acids, that are suitable as a catalyst are LiX, Sb2O3, GeO2 en As2O3, BX3, MgX2, BiX3, SnX4, SbX5, FeX3, GeX4, GaX3, HgX2, ZnX2, AlX3, TiX4, MnX2, ZrX4, R4NX, R4PX, HX, where X=I, Br, Cl, F, OR, acetylacetonate, or a compound according to formula (a) in which formula R″ and R′″ are independently chosen from the series comprising alkyl, aryl, alkoxy and aryloxy. and R=alkyl or aryl. Brönstedt acids such as H2SO4, HNO3, HX′ (where X′=I, Br, Cl, F), H3PO4, H3PO3, RH2PO2, RH2PO3, R[(CO)OH]n, where n=1-6 are also suitable. Examples of bases, including Lewis bases, that are suitable as a catalyst are MHn, M(OH)n, (R′O)nM (M=Alkali or earth alkali, R′=alkyl with C1-C20 or aryl), NR′nH4-nOH (R′=alkyl with C1-C20 or aryl), triamines such as triethylamine, tributyl amine, trihexylamine, trioctylamine and cyclic amines such as diazobicyclo[2,2,2]octane (DABCO), dimethylaminopyridine (DMAP), guanidine, morfoline. It is also possible to accelerate the reaction in the presence of another compound such as an acid scavenger. If a solvent is used, preferrably an aprotic solvent is used. This prevents unwanted reactions with the solvent. Suitable aprotic solvents are for example aliphatic or aromatic hydrocarbons such as toluene or xylene. The reaction of step a. of the invention is carried out at a temperature below 150° C. Undesirable side reactions may take place above 150° C., potentially resulting in a compound with less or no blocked isocyante anymore. The reaction is preferably carried out at a temperature below 125° C. If the boiling point of the chosen solvent is lower than the desired reaction temperature, the reaction may, if desired, be carried out under pressure and/or reflux. In general the reaction is carried out at a temperature above room temperature, preferably above 50° C. Long reaction times are prevented in this manner. A suitable first compound is one containing at least one primary amino group and at least a group chosen from a first series comprising a secondary amino group, an amino group on a secondary carbon atom, a primary hydroxyl group or a group chosen from a second series comprising a hydroxyl group on a secondary carbon atom and a carboxy group, or a first compound containing at least one group chosen from the first series and also at least one group chosen from the second series. The chosen groups may be mutually bonded by one or more aliphatic, cycloaliphatic or aromatic units chosen independently of one another. Examples of suitable first compounds are for example bishexamethylenetriamine, bisethylenetriamine, bispropylenetriamine, 2-(ethylamino)ethylamine, 3-(methylamino)propylamine, 3-(cylohexylamino)propylamine, 1,2-propanediamine, N,N′-1,2-ethanediylbis-(1,3-propanediamine), N-(aminoethyl)benzylamine. Examples of a first compound containing amino and hydroxy groups are for example ethanolamine, propanolamine, isopropanolamine, 2-(2-aminoethyoxy)ethanol, N-(2-aminoethyl)ethanolamine, N-methylethanolamine, diethanolamine, chitin. Further examples of a first compound comprising a primary hydroxy group and a hydroxy group on a secondary carbon atom are glycerol, 1,2-pentanediol,1,2,4-butanetriol or glucose. Examples of first compounds containing amino and carboxy groups are glycine, asparagine, lysine, glutamine or γ-aminocapronic acid. Various types may be used as CBL. Preferably carbonylbiscaprolactam, CBC, is used because of its commercial availability. In the reaction of the invention referred to under b., the first intermediate compound is contacted, preferably at a temperature below 150° C., with an additive such that a link is established via the free amino, hydroxy or carboxy group or via a double or triple bond to form a second intermediate compound. The additive's linkage to the first intermediate compound takes place via a reactive group that is present on the additive. An example of this link is shown in the reaction equation B) below, which is based on the reaction product of reaction A) and wherein YFn symbolizes the additive containing a reactive group Y. If the first intermediate compound contains several reactive groups per molecule, then several molecules of the additive per molecule of the first intermediate compound may be linked. The linkage may take place if the additive contains a reactive group Y capable of reacting directly with a group of the first intermediate compound. Reactive groups on the additive may be an amino, hydroxyl or carboxy group, or a halide, an ester, an isocyanate, an epoxy, an aldehyde or an anhydride. In some cases the linkage cannot take place directly, for example because both the first intermediate compound and the additive contain groups that do not react directly with one another, for example when both contain a hydroxyl, amino or carboxy group. In such cases the linkage may take place via a so-called linking unit. This linking unit contains one reactive group capable of reacting with the reactive group of the first intermediate compound and one reactive group capable of reacting with the reactive group present in the additive. If the linking unit is to link with a hydroxyl group, the linking unit preferably contains an acid group, an isocyanate, a dihalogenide or a cyclic anhydride. If the linking unit is to link with an amino group, it preferably contains an acid group, an isocyanate, an aldehyde or a cyclic anhydride, or carbonylbislactam. In using this latter compound the reaction has to be carried out at a temperature above 150° C. If the linking unit is to link with a carboxy group, it preferably contains an amino group or hydroxy group. Suitable linking units may be cyclic anhydrides, diisocyanates or aldehydes. Examples of cyclic anhydrides are for example succinic anhydride, maleic anhydride or phthalic anhydride. A diisocyanate that may be suitable is for example isoferondiisocyanate (IPDI) or toluenediisocyanate (TDI). Examples of aldehydes are for example formaldehyde, acetaldehyde, benzaldehyde or glyoxal. If a linking unit is used, it is preferably first reacted with the first intermediate compound or the additive and the formed product is subsequently, in a next reaction step, reacted with the additive or the first intermediate compound respectively. An additive in this invention is understood to be an antioxidant, a flame retardant, a bactericide, a fungicide, a dying agent, a surfactant, an anti-fouling agent, a colouring agent, an antistatic agent or a lubricant, or a combination thereof. The reaction is preferably carried out at a temperature below 150° C., because otherwise undesirable side reactions may take place. In general the reaction is carried out at a temperature above room temperature, preferably above 50° C. Long reaction times are prevented in this manner. In the reaction referred to under c. above, the second intermediate compound is contacted with a polymer having at least one free amino group or hydroxyl group such that the blocked isocyanate group of the second intermediate compound reacts with the free amino group or hydroxy group of the polymer. In the process according to the invention the second intermediate compound is preferably added to the polymer in an extruder or injection moulding machine. In this manner, the second intermediate compound is rapidly blended with the polymer and a quick reaction takes place at the high temperatures during extrusion or injection moulding. Under these conditions the reaction will usually be complete in a few minutes. The second intermediate compound may also be added during the production of coating compositions. The second intermediate compound may be metered directly to the extruder or may be added to the extruder or injection moulding machine pre-blended with the polymer or other additives. If the second intermediate compound is liquid, it may also be added to the extruder or injection moulding machine with a liquid metering system. It is also possible to add additives that react with acid groups, if present, such as phenylenebisoxazoline, phenylenebisoxazine, (di)epoxides and carbodiimides. During the reaction of the blocked isocyanate group of the second intermediate compound with a free amino or hydroxy group of the polymer caprolactam is split off, which caprolactam may be removed from the extruder or injection moulding machine or polymer through devolatization. If the second intermediate compound contains one blocked isocyanate group, the second intermediate compound may be linked to the end of the polymer chain. If the second intermediate compound contains several blocked isocyanate groups, it may also be incorporated in the polymer. If the second intermediate compound links two polymer chains, chain extension may occur. This is manifested by an increase in the molar mass of the polymer. An extra advantage of the invention is that additives having only one functional group may also be used. In the publication by Wolfe cited above this is not possible since the addition of a monofunctional compound during the polymerization may result in chain termination, as a result of which the polymer's molecular mass is limited. Also, the addition, via the process of the invention, of the additives cited by Wolfe will not result in a functionalized polymer in which additives do not bleed, since in general the additives cited by Wolfe react only slowly. Consequently, over the relatively short reaction time in an extruder, practically no reaction takes place with the polymer, so allowing the additives still to bleed out of the polymer. The second intermediate compound is contacted with the polymer containing at least one free amino or hydroxy group at a temperature above the melting point of the polymer and at least at 150° C. At lower temperatures the reaction will proceed more slowly and will not run to completion during the residence time in the extruder. The upper temperature limit is not subject to any further limitation than the temperature customary for melt processing of the polymers in question. Polymers that contain a free amino or hydroxy group are for example polyamides, polyesters, copolyesters, polyethers, polyacrylates, cellulose and amine or hydroxy functionalized polymers or copolymers or blends thereof. Exemplary polyamides are polyamides and copolyamides that are derived from diamines and dicarboxylic acids and/or from aminocarboxylic acids or the corresponding lactams, such as polyamide 4, polyamide 6, polyamide 11, polyamide 12, polyamide 6/6, 4/6, partially aromatic (co)polyamides, for example polyamides based on an aromatic diamine and adipic acid; polyamides produced from an alkylenediamine and isophthalic and/or terephthalic acid and copolyamides thereof. Exemplary polyesters are polyesters derived from dicarboxylic acids as e.g terephthalic acid, isophthalic acid and trimellitic acid, and dialcohols as e.g. ethylene glycol, propane diol, butanediol, neopentyl glycol and/or from hydroxycarboxylic acids or the corresponding lactones including polyethyleneterephthalate, polypropyleneterephthalate, polybutyleneterephthalate, poly-1,4-dimethylolcyclohexaneterephthalate, polycaprolacton and copolyesters thereof or thermosetting polyesters derived of any one of the above mentioned monomers. Exemplary polyethers are polytetrahydrofuran, polypropyleneglycol, polyethyleneglycol and polyoxymethylene and copolyethers thereof or copolymers containing the abovementioned polyesters, in particular copolyesters including Arnitel®. Examples of amine functionalized polymers are for example amine functionalized polyethers including Jeffamines and amino terminated acrylonitrilebutadiene copolymers (ATBN). An exemplary hydroxy functionalized polymer is for example hydroxyfunctional polybutadiene. The amount of the second intermediate compound to be added to the polymer may be freely chosen. Preferably the amount of the additive is chosen to be equal to or lower than the amount of free amino or hydroxy groups. These groups may be determined by techniques known to those skilled in the art. In general, a polymer with a lower molar mass contains more free amino or of hydroxy groups so that a larger amount of the second intermediate compound may be linked to a polymer with a lower molar mass. The amount of the second intermediate compound is preferably so chosen that the amount of additive to be introduced in the polymer is equal to the desired dosage of the additive in the polymer composition. If a larger amount of additive is to be added to the polymer via the second intermediate compound than the available terminal groups in this polymer, this may be accomplished by using a second intermediate compound to each molecule of which more than one molecule of the additive is linked. If desired, fillers may be added during compounding. In general, there may be added glass fibres, glass spheres, glass lamellae, mineral fillers including for example, mica, talcum, chalk or gypsum, rubbers, including for example halogenated polymer systems and synergists such as antimonetrioxide, sodiumantimonate or zinc borate. The invention also relates to a first intermediate compound comprising at least one blocked isocyanate group and a free amino, hydroxy or carboxy group. The invention further relates to a second intermediate compound comprising an additive that is linked to a compound containing at least one blocked isocyanate group. In this second intermediate compound the additive may be linked to the first intermediate compound via the free amino, hydroxy or carboxy group or via a double or triple bond present in the first intermediate compound. Furthermore, the invention relates to a process for obtaining the said intermediate compounds and product. It concerns a process for the preparation of the first intermediate compound, wherein the process comprises step a. of the process of the invention. In this process the additive is chosen from the series of stabilizers, flame retardants, bactericides, fungicides, dying agents, surfactants, anti-fouling agents, colouring agents, antistatic agents and lubricants. The invention further relates to a process for the preparation of the second intermediate compound wherein the process comprises steps mentioned under a. and b. of the process of the invention. The invention further relates to an alternative route to produce a functionalised polymer using an additive comprising a lactam blocked isocyanate groups. Such process comprises a. reacting an additive comprising at least one amino group or a hydroxyl group with carbonylbislactam at a temperature below 150° C. such that a link is established via the amino group or hydroxyl group of the additive, thereby forming an intermediate product A, b. contacting the intermediate product A with a polymer having at least one free amino group or hydroxyl group at a temperature above the melting point of the polymer and at least above 150° C., such that the blocked isocyanate group reacts with the free amino group or hydroxy group of the polymer to form a functionalized polymer. In this process an intermediate product A is formed. The invention therefore also relates to an intermediate product A comprising an additive provided with a lactam blocked isocyanate group as well as the process for the preparation of an intermediate product A, which comprises step a. of the above mentioned alternative process according to the invention. In the case of intermediate product A which contains only one blocked isocyanate, an additive comprising an amino group or a hydroxyl group is reacted with CBL at a temperature preferably below 150° C., with said additive such that a link is established via the amino group or hydroxyl group of the additive. The invention also provides a functionalised polymer obtainable by the process of the invention. Such a functionalized polymer may also be added to other polymers, this group of other polymers not necessarily being limited to the group of polymers that contain a free amino or hydroxy group. The invention therefore also provides polymer compositions containing also a functionalized polymer with an additive that does not bleed. Said functionalized polymers or polymer compositions according to the invention can also be applied in coating compositions. The invention therefore also provides a coating composition comprising functionalized polymers according to the invention or shaped articles comprising a functionalised polymer composition according to the invention The coating composition can further comprise the usual fillers applied in coating chemistry. Upon curing of the coating composition according to the invention a coating is obtained on a substrate. The invention therefore furthermore provides substrates comprising a coating based on the coating composition according to the invention. Furthermore the invention relates to shaped articles comprising functionalized polymers according to the invention or shaped articles comprising functionalised polymer compositions according to the invention. The shaped articles can be produced by the known methods as e.g. injection moulding or extrusion. Consequently shaped articles comprise moulded parts extruded parts, films, strapping and fibres. The invention is elucidated by the following non-limiting examples. EXAMPLE I Preparation of a First Intermediate Ompound Containing an Amino Group and Two Blocked Isocyanate Groups 10.3 g (0.1 mol) of bisethylenetriamine and 50.4 g (0.2 mol) of carbonylbiscaprolactam (CBC) are dissolved in 100 ml of toluene. The solution is heated to 70° C. for 1 hour. After the mixture has cooled down to room temperature, caprolactam liberated in the reaction is extracted twice with 50 ml of water. The product, the caprolactam blocked diisocyanate of bisethylenetriamine, has formed virtually quantitatively and can be isolated by distilling off toluene. EXAMPLE II Preparation of a First Intermediate Ompound Containing an Amino Group and Two Blocked Isocyanate Groups 21.5 g (0.1 mol) of bishexamethylenetriamine and 50.4 g (0.2 mol) of carbonylbiscaprolactam (CBC) are dissolved in 100 ml of toluene. The solution is heated to 70° C. for 1 hour. After the mixture has cooled down to room temperature, caprolactam liberated in the reaction is extracted twice with 50 ml of water. The product, the caprolactam blocked diisocyanate of bishexamethylenetriamine, has formed virtually quantitatively and can be isolated by distilling off toluene. EXAMPLE III Preparation of an Intermediate Product A Containing an Amino Group and One Blocked Isocyanate Ground 15.0 g (0.1 mol) of (2-aminoethyl) benzylamine and 25.2 g (0.1 mol) of carbonylbiscaprolactam (CBC) are dissolved in 100 ml of toluene. The solution is heated to 70° C. for 1 hour. After the mixture has cooled down to room temperature, caprolactam liberated in the reaction is extracted twice with 50 ml of water. The product, the caprolactam blocked mono-isocyanate of (2-aminoethyl) benzylamine, has formed virtually quantitatively and can be isolated by distilling off toluene. EXAMPLE IV Preparation of an Intermediate Product A Containing an Amino Group and One Blocked Isocyanate Group 16.8 g (0.1 mol) of 1,1-dimethyl, 3,3-dimethyl, 5-aminopiperidine and 25.2 g (0.1 mol) of carbonylbiscaprolactam (CBC) are dissolved in 100 ml of toluene. The solution is heated to 70° C. for 1 hour. After the mixture has cooled down to room temperature, caprolactam liberated in the reaction is extracted twice with 50 ml of water. The product, the caprolactam blocked mono-isocyanate of 1,1-dimetyl, 3,3-dimethyl, 5-aminopiperidine, has formed virtually quantitatively and can be isolated by distilling off toluene EXAMPLE V Preparation of a Second Intermediate Compound that Contains the Additive Dimethylphosphite Linked to the Fist Intermediate Compound in Example I via a Formaldehyde Linking Unit 91.9 g (0.25 mol) of caprolactam blocked diisocyanate of bisethylenetriamine (obtained in Example I), 7.5 g of formaldehyde (0.25 mol) as a linking unit and 100 ml of methanol are heated to 60° C. for 1 hour. In a second step 27.5 g (0.25 mol) of the additive dimethylphosphite are added in the presence of 0.5 g of NaOH as a catalyst. After two hours the excess of methanol is distilled off and the product is washed once with 50 ml of water. The product is a phosphorus modified caprolactam blocked diisocyanate of bisethylenetriamine, that cab be used to prepare a flame retardant polymer that dos not bleed. EXAMPLE VI Preparation of a Second Intermediate Compound that Contains an Additive, the Acid Chloride of Perfluorododecanoic Carboxylic Acid, Linked to the First Intermediate of Example I via an Amino Group 91.9 g (0.25 mol) of caprolactam blocked diisocyanate of bisethylenetriamine (see Example I) and 25 g (0.25 mol) of triethylamine (as acid scavenger) are dissolved in 400 ml of toluene. A solution of 158 g (0.25 mol) of the additive, the acid chloride of perfluordodecanoic carboxylic acid, in 200 ml of toluene, is added at room temperature. After that, the solution is heated to 40° C. for 2 hours. Next, the formed triethylamine.HCl salt is filtered off and the filtrate is concentrated by evaporation. The product is the amide of perfluorododecanoic carboxylic acid and the caprolactam blocked diisocyanate of bisethylenetriamine, which can be used to form a functionalised polymer with a built in fouling agent. EXAMPLE VII Preparation of a Functionalized Polymer A mixture of 5 wt % of the phosphorus modified caprolactam blocked diisocyanate of bisethylenetriamine as obtained in Example V and 95 wt % of nylon-6 are added to the hopper of an extruder. The extruder temperature is adjusted to 260° C. and the residence time is approx. 2 minutes. The strands of the polymer composition thus obtained are chopped to form a granulate. The granulate is processed in an injection moulding machine at 260° C. and a mould temperature of 85° C. into test bars of 3*6*75 mm and tested in terms of flame retardance through LOI, limiting oxygen index. The LOI of the test bars was measured to ASTM D2863 and amounted to 26. This is substantially higher than that of test bars obtained without the compound in Example V, where the LOI amounted to 21. While injection moulding 500 test bars, the mould did not exhibit any deposit from the phosphorus compound bleeding out of the polymer. EXAMPLE VIII Preparation of an Intermediate Product A Comprising One Caprolactam Blocked Isocyanate Group and a Fluorine Containing Additive. A commercially available per-fluorine alkyl alcohol (see reaction below, n=7) was reacted with carbonyl biscaprolactam in equimolar amounts in the presence of MgBr2 as catalyst for two hours at 125° C., according to the reaction below. EXAMPLE IX Preparation of Coating Comprising the Additive of Example VIII on a Substrate A coating composition was made by blending a hydroxy functional polyester resin according to the following formula C2H5C[CH2{OC(O)RC(O)O(CH2)nO}mH]3 in which n=4 and m=1, the per-fluorine alkyl blocked isocyanate of example VIII, and a tri-functional blocked isocyanate Desmodur® BL-3272 (Bayer). The overall OH/NCO molar ratio was maintained slightly higher than 1. The ratio of per-fluorine alkyl blocked isocyanate to BL-3272 was chosen such that the fluorine content was 3% by weight of the film. The coating composition was applied on clean aluminum panels in such an amount as to obtain a coating thickness of about 20 μm and then cured at 200° C. for 0.5 hour. The thickness of the cured coating on the aluminium substrate was found to be 20 μm, as measured using a Twin-Check thickness gauge by List-Magnetic GmbH. Contact angles were measured with deionized water and hexadexane (>99%, Merck) on a contact angle microscope (G10, Krüss, Hamburg-Germany) and amounted to 80° and 125° with hexadexane and water, respectively. From these contact angles surface energy of the coating was calculated according to methods known to the skilled man. This surface energy of the coating was 9 mN/m, which is significantly lower that the surface energy of 40 mN/m measured at the same coating not comprising the intermediate product A of Example VIII. The fact that the surface energy of the coating was very low can also be seen by comparing with the value for Teflon, which was measured to be 20 mN/m. The coating according to the invention therefore has a lower surface energy than Teflon which is well known for its low surface energy. Due to the low surface energy of the coating of 9 mN/m, the coating showed very good anti fouling and non staining properties. Furthermore extraction tests were done with aceton to verify whether the intermediate product A of Example VIII could be removed from the coating. It was not possible to remove the intermediate product A of example VIII from the coating through the aceton treatment. Thus the intermediate product A of example VIII is chemically fixed at the coating. EXAMPLE X Preparation of Functionalised Polymer Comprising the Intermediate Product A of Example IV The additive as obtained through Example IV was fed to a twinscrew extruder of diameter 30 mm together with polyamide 6, (PA6). The amount of the intermediate product A of Example IV was 0.7% by weight of the amount of polyamide 6. The temperature of the extruder barrel was set to 265° C. and a functionalized polymer was obtained upon meltmixing the PA6 with the intermediate product A of Example IV. After leaving the extruder, the functionalized polymer was cut into pellets and dried to a moisture amount of less than 0.05 w %. Of the dried polymer fibers were spun and compared with that of a polyamide 6, not comprising the intermediate product A according to Example IV. It was seen that the melt degradation of the polymer obtained according to Example X, upon melt processing, was less than that of a polyamide 6, not comprising the intermediate product A according to Example IV. Dyability of the fibres of both the polyamide 6 with or without the intermediate product A of Example IV were comparable.

20050310

20070925

20050721

76856.0

BLAND, ALICIA

PROCESS FOR THE PREPARATION OF A FUNCTIONALIZED POLYMER INTERMEDIATE PRODUCTS, COMPOSITIONS AND SHAPED PARTS

UNDISCOUNTED

ACCEPTED

ACCEPTED

Intelligent ink cartridge and method for manufacturing the same

This relates to an intelligent ink cartridge and method for manufacturing the same. The ink cartridge comprises at least one ink chamber for containing ink, an electronics module for storing identification information of the ink cartridge and ink remaining data. The electronics module comprises a microcontroller with embedded non-volatile memory, for storage, controlling, calculation and accessing of ink remaining data, so that the maximum ink capacity of the ink cartridge for use with the printer can be improved.

1. An intelligent ink cartridge comprising, at least one ink chamber for storing ink therein; an electronics module adapted to store identification information data of the ink cartridge and ink remaining data, wherein, the electronics module is a micro-controller with embedded non-volatile memory storing a program executable to control access and processing of ink remaining data in the ink cartridge to improve the maximum of ink volume of the ink cartridge. 2. An intelligent ink cartridge according to claim 1, wherein said non-volatile memory is an EEPROM. 3. An intelligent ink cartridge according to claim 1, wherein said micro-controller is an 8-bit CMOS RISC micro-controller. 4. An intelligent ink cartridge according to claim 1 wherein said micro-controller includes: an ALU (arithmetic and logic unit) connected with a data bus; an EEPROM memory for storing said identification information data of the ink cartridge and said ink remaining data, plural registers, an interrupt unit, a serial periphery interface unit, a timer, an analog comparator, an I/O interface, and a program memory connected to said ALU by said register for storing a program controlling reading and writing operations and calculation of ink remaining data. 5. An intelligent ink cartridge according to claim 4, further comprising a R-C control circuit defining a preselected time constant value, used to distinguish a checking read cycle of said cartridge and a normal read cycle of said cartridge, wherein, said R-C control circuit is connected to the input interface of said micro-controller. 6. A method of manufacturing an intelligent ink cartridge of the type including at least one ink cartridge for storing ink therein; and an electronics module adapted to store identification information data of the ink cartridge and ink remaining data, wherein the electronics module is a micro-controller with embedded non-volatile memory storing a program executable to control access and processing of ink remaining data in the ink cartridge to improve the maximum of usable ink volume of the ink cartridge, the method comprising: disposing a micro-controller on the ink cartridge; writing i) identification information of the ink cartridge and ii) a program controlling access and process operations of ink remaining data into the non-volatile memory of the micro-controller; and, executing said program so that it can meet the requirement of control and reading and writing operations of ink remaining data by an associated ink jet apparatus when ink capacity of ink cartridge is increased. 7. A method of manufacturing an intelligent ink cartridge according to claim 6, wherein, said identification information of the ink cartridge and said ink remaining data is stored into an EEPROM memory in the micro-controller, and said program for controlling access and process operation of ink remaining data is stored into a fast flash memory in said micro-controller. 8. A method of manufacturing an intelligent ink cartridge according to claim 7, wherein, said program is adapted to execute the steps of: transferring an ink utilization percentage stored in EEPROM to register temp1 in said micro-controller during printer power on or when the ink cartridge is installed on the associated ink jet apparatus and moved to normal position; transferring said ink utilization percentage into said ink jet apparatus from said register temp1 when a control signal of the associated ink jet apparatus is received; updating the ink utilization percentage at the associated ink jet apparatus during printing; storing the updated ink utilization percentage written into the ink cartridge from the associated ink jet apparatus into the register temp2 in said micro-controller during printer power off or when the ink cartridge is moved to installation position; executing steps in said micro controller micro-controller of:, temp3=temp2=temp1; temp3−temp3/(1+x %), wherein, x % is the targeted increment in ink capacity of said ink cartridge; temp1=temp1+temp3; and, storing ink utilization percentage updated to EEPROM from said register temp1 and using it as the output from cartridge to the associated ink jet apparatus for the next printer power on read cycle. 9. A method of manufacturing an intelligent ink cartridge according to claim 7 further comprising a check step for checking whether updated ink utilization percentage is larger than predetermined value y, and adjusting the ink utilization percentage if no previous adjustments had been performed wherein x % is the targeted increment in ink capacity and a % is the additional consumption due to an additional head cleaning operation, so as to check whether ink utilization has been adjusted when ink utilization percentage is higher than (x+a) % and the ink utilization is updated, wherein, adj=0 means ink utilization has been not adjusted and adj=1 means it ink utilization has been done. 10. A method of manufacturing an intelligent ink cartridge according to claim 9, wherein, the check step for checking whether said micro-controller has adjusted ink utilization percentage of a new ink cartridge includes: setting an initial status flag into EEPROM of a new ink cartridge; reading and judging said status flag; and, subtracting (x+a) from the updated ink utilization percentage before storage to EEPROM should the status flag has been not adjusted and updated ink utilization percentage be higher than (x+a) %, and change the flag to signify ink utilization percentage had been adjusted. 11. A method of manufacturing an intelligent ink cartridge according to claim 9, another including an additional check step for distinguishing a first read cycle immediately following a write cycle during printer power off from a second read cycle performed during printer power on. 12. A method of manufacturing an intelligent ink cartridge according to claim 6 further including: providing an R-C circuit with a time constant of appropriate value is connected with an input port of said micro-controller for distinguishing a checking read cycle from a normal read cycle. 13. An electronics module of an intelligent ink cartridge for use with an associated ink jet printer apparatus, the electronics module storing identification information of the ink cartridge and ink remaining data, wherein, the electronics module is a micro-controller with embedded non-volatile memory storing a program executable to control access and process operations of said ink remaining data in the ink cartridge for improving the maximum ink capacity utilization of the ink cartridge. 14. An electronics module according to claim 13, wherein, said non-volatile memory in said micro-controller stores said identification information of said ink cartridge and the program for controlling access and process operations of ink remaining data is stored in a one of a flash memory and a ROM memory, so as to X meet the requirement of controlling and reading/writing ink remaining data by said ink jet apparatus when said program is carried out and ink capacity of said ink cartridge is improved. 15. An ink cartridge apparatus for use with an associated printing device, the ink cartridge apparatus comprising: a housing holding ink therein; a micro-controller having a memory storing ink remaining data indicating a relative amount of ink remaining in the cartridge apparatus; and, a computer program, performed by the micro-controller for, in response to receiving signals from the associated printing device, manipulating said ink remaining data for increasing a utilization of ink from the ink cartridge apparatus. 16. The ink cartridge apparatus according to claim 15 wherein said computer program is executable by said micro-controller for manipulating said ink remaining data for increasing said utilization of ink from the ink cartridge apparatus by: transferring ink utilization percentage data stored in a register temp1 in said micro-controller i) during a power on cycle of said associated printing device and ii) when the ink cartridge apparatus is installed on the associated printing device and moved to a normal position; transferring the ink utilization percentage data into the associated printing device from register temp1 in response to a control signal received from the associated printing device is received; updating the ink utilization percentage data after a printing operation; storing the ink utilization percentage data written into the ink cartridge apparatus from the associated printing device into a register temp2 in said micro-controller during a power off of said associated printing device or when said ink cartridge apparatus is moved to an installation position relative to said associated printing device; subtracting the previously stored ink utilization percentage data in register temp1 from the updated ink utilization percentage data in register temp2 and storing the result of said subtracting into a register temp3; dividing a value temp3=temp2−temp1 obtained in the subtracting step by a divisor (1+x %) to generate a quotient value and storing the quotient value in register temp3; adding the quotient value in register temp3 obtained in said dividing step to said previously stored ink utilization percentage data in register temp1 as temp1=temp3+temp1; storing the value in register temp1 in a memory of said micro-controller; and, using the value temp1 stored in said register as an output from said ink cartridge apparatus to said associated printing device during a subsequent power on read cycle of said associated printing device. 17. The ink cartridge apparatus according to claim 16 wherein said micro-controller is a reduced instruction set controller (RISC) and said computer program is stored in a memory of the micro-controller. 18. The ink cartridge apparatus according to claim 15 wherein said computer program is executable by said microcontroller for manipulating said ink remaining data for increasing said utilization of ink from the ink cartridge apparatus by: using a software flag (adj) stored in a memory of said micro-controller on said ink cartridge apparatus to signify whether said ink utilization data had been adjusted by the micro-controller using an initial logical value of “0” to signify an unadjusted state; transferring said ink utilization data stored in said memory to a register reg1 when receiving a power signal from said associated printing device or when mounting said ink cartridge apparatus during a power on cycle of said associated printing device; sending said ink utilization data to said associated printing device from reg1 under control of said associated printing device upon a power on cycle of said associated printing device; permitting a printing operation by said associated printing device; storing said updated ink utilization data written to said ink cartridge apparatus into register reg1 during a power off cycle of said associated printing device or during a removal of the ink cartridge apparatus from the associated printing device; transferring, when the value stored in register reg1 is less than a predetermined value y and the logical value of the flag adj is “0”, the updated ink utilization percentage data as stored in register reg1 into a predetermined memory location in said micro-controller during a power off cycle of said associated printing device; and, subtracting, when the logical value stored in register reg1 is less than said predetermined value y and said logical value of the flag adj is “0”, (x+a) from register reg1 and storing the result back to register reg1, where x % is a targeted increment in ink capacity and a % is an additional consumption due to additional head cleaning operations performed by said associated printing device. 19. The ink cartridge apparatus according to claim 18 wherein said micro-controller is a reduced instruction set controller (RISC) and said computer program is stored in a memory of the micro-controller. 20. The ink cartridge apparatus according to claim 15 wherein said computer program is executable by said micro-controller for manipulating said ink remaining data for increasing said utilization of ink from the ink cartridge apparatus by: using a software flag (adj) stored in a memory location in said micro-controller to signify whether said ink utilization data had been adjusted by the micro-controller with an initial logical value of “0” to signify an unadjusted state; transferring the updated ink utilization data stored in said memory location of said micro-controller to a register reg1 upon a power on cycle of said associated printing device or upon an installation of said ink cartridge onto said associated printing device; sending said ink utilization percentage data in register reg1 to said associated printing device upon a power on cycle of said printing device when a one of: i) an external signal TP1 is received by said micro-controller indicating a normal read cycle logic level TP1=0, ii) when a value stored in register reg1 is less than a predetermined value y, and iii) when said ink utilization percentage data had been modified as determined based on the value of the software flag adj being a logic level 1 value; subtracting (x+a) from register reg1 and storing the result in register reg1 when i) said software flag adj has a logic value of “0”, ii) the value stored in register reg1 is greater than said predetermined value y, and iii) the external signal TP1 received indicates a checking read cycle logic level TP1=I and changing said software flag adj to a logic level of “1” and sending the value in reg1 to the associated printing device upon a power on cycle where x % is a targeted increment in ink capacity and a % is an additional consumption due to an additional head cleaning operation in said associated printing device; permitting a printing operation in said associated printing device; storing the updating ink utilization percentage data written to said micro-controller from said associated printing device to register reg1 upon a power off cycle of said associated printing device or upon a moving of said ink cartridge apparatus to an installation position for removal relative to said associated printing device; and, updating the ink utilization percentage data stored in a memory of said micro-controller with the value stored in register reg1. 21. The ink cartridge apparatus according to claim 20 wherein said micro-controller is a reduced instruction set controller (RISC) and said computer program is stored in a memory of the micro-controller.

FIELD OF THE INVENTION The present invention relates to an ink cartridge for use with an ink jet printer or a plotter and method for manufacturing the same. In particularly, it relates to an intelligent ink cartridge that can provide a user ink amount data of the ink cartridge, and method for manufacturing the same. BACKGROUND OF THE INVENTION In the ink jet apparatuses using intelligent ink cartridges, in recent years, passive memory, usually in the form of serial EEPROM, has being used as electronics modules in ink cartridges, for example, EPSON printer cartridges. Such passive memory stores fixed data such as manufacturer name, manufacturing date, type of ink, capacity, cartridge model number, etc, as well as rewritable operational data such as date of first installation, ink volume remaining in the cartridge, etc. Data stored in electronics module of a particular intelligent ink cartridge can be read by printer on demand. Updated data concerning ink volume remaining are usually being written back to the electronics module during printer power off or removal of ink cartridge from printer. Usually, the printer controls the ink volume updating while the passive memory in intelligent ink cartridge just stores faithfully the updated data issued from the printer. For example, Chinese patent application, pub. No. CN1257007A, has disclosed an intelligent ink cartridge, using a 8-bit EEPROM to store data concerning ink remaining of ink cartridge. It is by the printer or by IC and storage member on the ink cartridge carrier of the printer that data of EEPROM is accessed. For ink cartridge using passive memory as electronics module, the hardware architecture can be classified mainly into independent interfacing for each cartridge and multi-drop common bus in which more than one cartridge are connected to the bus between electronics modules of ink cartridges and the printer, as shown respectively in FIG. 1 to FIG. 4. It should be noted that the hardware architecture as shown in FIG. 1 can be replicated for different color ink cartridges. As for FIG. 2, there may exist more than 2 cartridges connecting to the common bus. As shown in FIGS. 1 to 4, data transfer between printer and ink cartridges is initiated and controlled by the printer. Data is read from cartridges during power on of printer or installation of cartridge to the printer. Data is written to ink cartridges during power off of printer, or moving cartridge holder to unload position, or marking the first use of a new cartridge after read operation. For individually controlled hardware architecture, data transfer between printer and each individual cartridge takes place simultaneously. For multi-drop common bus architecture, printer addresses (address embedded with read/write command) each cartridge for data transfer in sequence. Data strings read from ink( cartridges are normally longer than data being written to ink cartridges. This is due to the fact that data written to cartridges are just variables related to ink volume, date installed, etc, while data read contain fixed information such as cartridge code and type, capacity, manufacturer and manufacturing date, etc. Typical communication protocol for exchange of data between printer and ink cartridges for individually controlled architecture is shown in FIG. 3. For read cycle (R/W=0), data flow direction is from ink cartridge to printer. For write cycle (R/W=1), data flow direction is from printer to ink cartridge. Typical communication protocol for exchange of data between printer and an ink cartridge for multi-drop common bus architecture is shown in FIG. 4. As an example, a common code may be used in which 3 bits are serving as the address for addressing up to 8 cartridges and 1 bit is used to signify read or write operations. Read operation after write cycle can be added to ensure data written to cartridges correctly stored. Usually ink capacity of the ink cartridge is being basically constant, and it is little, so the user has to change frequently the ink cartridge after it runs out. This frequent change of ink cartridges not only spends much time, but waste the resources such as ink. As data updating of electronics module in ink cartridges is controlled by the printer, the manufacturers of ink cartridges have to design electronics module compatible with the printer. That is, it is very difficult for the remanufacturers to come up with a much higher ink volume cartridge. And actually, there are much ink remained in the ink cartridge when the printer alerts the user with the ink out condition. Thus, inks are not used fully in the cartridge and then a user replaces it for a new one, as a result, much ink is thrown away. Accordingly, an improved ink cartridge with higher ink capacity and compatible with different inks that address these problems and others would be desirable. SUMMARY OF THE INVENTION According to one aspect of the present invention there is provided an intelligent ink cartridge with an electronics module, which can access, and in addition, control the EEPROM built in, and as a result, design out an ink cartridge with higher ink capacity. According to another aspect of the present invention there is provided an electronics module which controls accessing and processing operations of ink remaining data, as a result, to improve ink capacity of the ink cartridge for use with the printer, and improve the volumetric efficiency of ink. The present invention provides an intelligent ink cartridge, comprising at least one ink chamber storing ink, an electronics module storing identification information of ink cartridge and ink remaining data. The electronics module is a micro-controller with a non-volatile memory for controlling calculation and access of ink remaining data in the ink cartridge to improve the maximum ink volume of the ink cartridge for use with the printer. According to the intelligent ink cartridge, the non-volatile memory is an EEPROM that is serially accessed. According to the intelligent ink cartridge, the micro-controller is a RISC 8-bit micro-controller of CMOS, comprising: an ALU(arithmetic and logic unit) connected to a 8-bit data bus, an EEPROM memory storing identification information of ink cartridge and ink remaining data, plural registers, interrupt unit, serial periphery interface unit, timer, analog comparator, I/O interface, and a fast flash connected to the ALU by the register, storing a program controlling reading and writing operations and calculation of ink remaining data. The intelligent ink cartridge further comprises a R-C control circuit with appropriate time constant, used to distinguish the checking read cycle and the normal read cycle, and the R-C control circuit is connected to the input interface of the micro-controller. The present invention also provides a method of manufacturing an intelligent ink cartridge, which comprises at least one ink chamber for storing ink, an electronics module storing identification information of ink cartridge and ink remaining data. According to the method, the electronics module is made according to the following steps: to set a special-purpose micro-controller in the ink cartridge; to write identification information of ink cartridge and the program controlling access and process operations of ink remaining data into the non-volatile memory of the special-purpose micro-controller; and to carry out the program so that it can meet the requirement of an ink jet apparatus's controlling and reading/writing ink remaining data when ink capacity of ink cartridge is increased. According to the method of manufacturing the intelligent ink cartridge, identification information of ink cartridge and ink remaining data is stored into an EEPROM memory in the special-purpose micro-controller, and the program controlling access and process operations of ink remaining data is stored into a fast flash in the micro-controller. (Process operations can also be stored in any other micro-controllers having equal or higher computational ability and storage capacities). According to a further aspect of the present invention there is provided a special-purpose electronics module of an intelligent ink cartridge, which is used to store identification information of the ink cartridge and ink remaining data, and the electronics module is a micro-controller with embedded non-volatile memory and the micro-controller is used to control calculation and access of ink remaining data in the ink cartridge to improve the maximum ink volume of the ink cartridge for use with the printer. According to the electronics module of the intelligent ink cartridge, the non-volatile memory in the micro-controller stores identification information and the program controlling access and process operations of ink remaining data. By carrying out the program it can meet the requirement of an ink jet apparatus's controlling and reading/writing ink remaining data when ink capacity of ink cartridge is increased. BRIEF DESCRIPTION OF THE DRAWINGS The beneficial effect will be more apparent by reference to following detailed specification of preferred embodiments combined with the drawings, in which: FIG. 1 is a view showing the interface for ink cartridges with individual control architecture. FIG. 2 is a view showing the interface for ink cartridges with multi-drop common bus architecture. FIG. 3 shows data exchange protocol for individually controlled architecture in FIG. 1. FIG. 4 shows data exchange protocol for multi-drop common bus architecture in FIG. 2. FIG. 5 is a perspective view showing an intelligent ink cartridge of the present invention. FIG. 6 is a circuit diagram for individually controlled architecture. FIG. 7 is a circuit diagram for multi-drop common bus architecture. FIG. 8 is a block diagram of micro-controller in the intelligent ink cartridge in FIG. 5. FIG. 9 is a normal read cycle & checking read cycle detection circuit. FIG. 10 is a flowchart for the first embodiment of the invention. FIG. 11 is a flowchart for the second embodiment of the invention. FIG. 11A is a flowchart for a supplementary design for the second embodiment of the invention. FIG. 12 is a flowchart for the third embodiment of the invention. DETAILED DESCRIPTION OF THE INVENTION As shown in FIGS. 1 to 4, an intelligent ink cartridge has been disclosed, but only an EEPROM is set on the cartridge and accessing ink remaining data is controlled by IC in ink jet printer. An intelligent ink cartridge brought by the present invention replaces the passive serial EEPROM with a micro-controller with an embedded EEPROM as electronics module to improve the maximum of ink volume of the ink cartridge, as shown in FIGS. 5 to 9. As shown in FIG. 5, the intelligent ink cartridge of the present invention consists of ink chamber 1 and electronics module 2. Electronics module 2 is a micro-controller with an embedded EEPROM. As for data exchange between the ink cartridge with individual control architecture and the printer, the protocol of data communication between electronics module 2 in the intelligent ink cartridge and the printer is the same as the prior art, as illustrated in FIG. 6. And as shown in FIG. 7, as for data exchange between the ink cartridge with multi-drop common bus architecture and the printer, the protocol of data communication between electronics module 2 in the intelligent ink cartridge and the printer is also the same as the prior art. As shown in. FIG. 8, the electronics module 2 in the intelligent ink cartridge provided by the present invention is a general-purpose micro-controller, comprising the hardware structure and the control software embedded therein. The hardware comprises a RISC 8-bit micro-controller of CMOS, which comprises ALU 21 connected by 8-bit data bus, EEPROM memory 22 storing identification information of ink cartridge, 32×18 general-purpose register 23, interrupt unit 24, serial periphery interface unit 25, 8-bit timer 26, analog comparator 27, six I/O lines 28, and a fast flash 29 connected to the general-purpose register 23, which is being connected to ALU 21. And the software portion comprises a program controlling calculation and reading/writing operations of ink remaining data and which is embedded in the fast flash 29. There are several embodiments as follows based on the control method of the software. The implementation of the present invention can be done in several different ways, depending on the hardware structure as well as the protocol between ink cartridges and printers. Assuming that the variable related to ink volume is the ink being utilized in percentage (i.e. 0% for new cartridge and 100% for empty cartridge), then the printer will update the inlk volume every time the printer is powered off or when the cartridge is moved to cartridge installation position. In the first embodiment of the invention the flowchart is shown in FIG. 10. To increase the capacity by approximately x %, the simplest approach is: to carry out the instructions as follows, as shown at step 100: to transfer ink utilization percentage stored in EEPROM register temp1 in the micro-controller during printer power on or when the ink cartridge is installed on the ink jet apparatus and moved to normal position; to transfer the ink utilization percentage into the ink jet apparatus from register temp1 when control signal of the inkjet apparatus is received; to update the ink utilization percentage after printing; to store the ink utilization percentage written into the ink cartridge from the ink jet apparatus into register temp2 in the micro-controller during printer power off or when the ink cartridge is moved to installation position. 1to subtract the previously stored ink utilization percentage temp1 from updated ink utilization percentage temp2 written to the cartridge from the printer during power off, and store the result into temp3, as shown at step 101; to divide the value temp3=temp2−temp1 obtained in step 101 by (1+x %), as shown at step 102; to add the value temp3 obtained in step 102 to previously stored ink utilization percentage temp1, that is, temp1=temp3+temp1, as shown at step 103; to store the value obtained from step 103 to EEPROM as shown at step 104; and to use the value temp1 stored in step 104 as the output from cartridge for the next printer power on read cycle, as shown at step 101. However, should the printer checks the value read from ink cartridge against that being written to ink cartridge from the previous power off during power on and initiates a head cleaning operation if these values not identical, a certain ink utilization percentage will be deducted for the head cleaning operating. If that percentage exceeds the increment obtained from the scaling computation as discussed above, this design approach cannot be applied. To overcome the limitation of embodiment 1, the following approach in the second embodiment is devised: (as shown in FIG. 11). to use a software flag (adj) stored in EEPROM in the ink cartridge electronics to signify whether the ink utilization percentage had been adjusted by the micro-controller firmware, with initial value of ‘0’ to signify unadjusted, as shown at step 201; to transfer ink utilization data stored in EEPROM to register reg1 when receiving power signal from the printer or mounting the ink cartridge during printer power on; to send ink utilization data to the printer from reg1 under the control of the printer upon printer power on; to print by printer; to store the updated ink utilization percentage written to the ink cartridge into reg1 during printer power off or removal of the ink cartridge; to check whether the value stored in register reg1 is greater than a predetermined value y (e.g. 50) as in step 202; to go to step 205 if the result of step 202 is yes; to check if the value of the flag adj is 0 if the result of step 202 is no as in step 203; to go to step 205 if the value of the flag adj as obtained in step 203 is not 0; to subtract (x+a) from reg1 and store the result back to reg1 if the value of the flag adj in step 203 is 0 (where x % is the targeted increment in ink capacity and a % is the additional consumption due to the additional head cleaning operation), as shown at step 204; to change the value of the flag adj to 1; to transfer the updated ink utilization percentage as stored in register reg1 into appropriate EEPROM location during printer power off as in step 205; and end, as shown at step 206. As an alternative, as shown in FIG. 11A, the following approach may also be used: to use a software flag (adj) stored in EEPROM in the ink cartridge electronics to signify whether the ink utilization percentage had been adjusted by the micro-controller firmware, with initial value of ‘0’ to signify unadjusted (for new ink cartridge), as shown at step 211; to transfer the utilization percentage as stored in EEPROM of the micro-controller to register reg1 upon printer power up or installation of cartridge to printer as shown at step 212; to check if the value in reg1 is less than a pre-determined value y as in step 213; to go to step 216 if the value in reg1 as in step 213 is less than y; to check if ink value had been adjusted previously by checking if the status flag adj is 0 as in step 214; to go to step 216 if the status flag as in step 214 is not 0; to subtract (x+a) from register reg1 and store the result in reg1 if the flag adj in step 214 is 0, and change the flag adj to 1, and send the value in reg1 to the printer as controlled by the printer upon power on as in step 215 (where x % is the targeted increment in ink capacity and a % is the additional consumption due to the additional head cleaning operation); to skip the next step; to send ink utilization percentage in reg1 to printer as controlled by the printer upon printer power on as in step 216; to print and update ink utilization percentage in printer by printer; to store the updated ink utilization percentage written to the ink cartridge electronics from the printer to register reg1 upon printer power off or moving of cartridge holder to installation position for removal; to update the ink utilization percentage stored in EEPROM with the value in register reg1 in the previous step; and end, as shown at step 217. However, should the printer initiates an additional read cycle after the write cycle to update the ink utilization percentage during power off as checking and lock up if the value obtained from the read cycle differs from that written to the cartridge, this design implementation is not applicable. To overcome the limitation of embodiment 2, in the third embodiment, a method to identify the difference between the read cycle that immediately follows a write cycle during printer power off and the read cycle during printer power on is required. Normally, the DC power (Vcc) cycle provided by the printer to the ink cartridge electronics for the checking read cycle that follows the write cycle at printer power off is separated from the Vcc cycle for the previous write cycle by tens of millisecond in time. As for the read cycle during printer power on, the Vcc normally had been off in the order of seconds or more. Therefore, a R-C circuit with a time constant of approximate 1 second or other selected appropriate value connected to an input port (hereinafter called TP1) will provide the information required to distinguish the checking read cycle and the normal read cycle. This is achieved by reading the TP1 at the beginning of each Vcc cycle. For checking read cycle, the sampled TP1 is ‘1’. For the normal read cycle, the sampled TP1 is ‘0’. The circuit is shown in FIG. 9. The following further illustrates the firmware algorithm for implementing the desired feature, as shown in FIG. 12: to use a software flag (adj) stored in EEPROM in the ink cartridge electronics to signify whether the ink utilization percentage had been adjusted by the micro-controller firmware, with initial value of ‘0’ to signify unadjusted, as shown at step 301; to transfer the updated ink utilization percentage stored in EEPROM of the micro-controller to register reg1 upon printer power on or installation of cartridge as in step 302; to check if the value of the pin TP1 is 0 as in step 303; to go to step 307 if the TP1 is not 0 in step 303; to check if the value in register reg1 is less than a pre-determined value y as instep 304; to go to step 307 if the value in register reg1 is less than y in step 304; to check if the ink utilization percentage had been modified by checking if the value of the flag adj is 0 as in step 305; to go to step 307 if the value of the flag is not 0 as in step 305; to subtract (x+a) from register reg1 and store the result in reg1 if the flag adj in step 305 is 0, and change the flag adj to 1, and send the value in reg1 to the printer as controlled by the printer upon power on as in step 306(where x % is the targeted increment in ink capacity and a% is the additional consumption due to the additional head cleaning operation); to skip the next step; to send ink utilization percentage in reg1 to printer as controlled by the printer upon printer power on as in step 307; to print and update ink utilization percentage in printer by printer; to store the updated ink utilization percentage written to the ink cartridge electronics from the printer to register reg1 upon printer power off or moving of cartridge holder to installation position for removal; to update the ink utilization percentage stored in EEPROM with the value in register reg1 in the previous step; and end, as shown at step 308. The design implementations are carried out by computer programs, which are embedded in the electronics module 2 in the intelligent ink cartridge. The electronics module 2 replaces prior passive serial EEPROM to improve the maximum of ink volume of the ink cartridge. Considering the defect of accessing ink remaining data totally controlled by the printer, the invention uses a special-purpose micro-controller to access ink remaining data in the ink cartridge to improve the ink cartridge with higher ink capacity. While the present invention has been described with respect to what is presently considered to be the preferred embodiments, it is to be understood that the invention is not limited to the disclosed embodiments. To the contrary, the invention is intended to cover various modifications and equivalent arrangements comprised within the spirit and scope of the appended claims. The scope of the following claims is to be accorded the broadest interpretation, so as to encompass all such modifications and equivalent structures and functions.

<SOH> BACKGROUND OF THE INVENTION <EOH>In the ink jet apparatuses using intelligent ink cartridges, in recent years, passive memory, usually in the form of serial EEPROM, has being used as electronics modules in ink cartridges, for example, EPSON printer cartridges. Such passive memory stores fixed data such as manufacturer name, manufacturing date, type of ink, capacity, cartridge model number, etc, as well as rewritable operational data such as date of first installation, ink volume remaining in the cartridge, etc. Data stored in electronics module of a particular intelligent ink cartridge can be read by printer on demand. Updated data concerning ink volume remaining are usually being written back to the electronics module during printer power off or removal of ink cartridge from printer. Usually, the printer controls the ink volume updating while the passive memory in intelligent ink cartridge just stores faithfully the updated data issued from the printer. For example, Chinese patent application, pub. No. CN1257007A, has disclosed an intelligent ink cartridge, using a 8-bit EEPROM to store data concerning ink remaining of ink cartridge. It is by the printer or by IC and storage member on the ink cartridge carrier of the printer that data of EEPROM is accessed. For ink cartridge using passive memory as electronics module, the hardware architecture can be classified mainly into independent interfacing for each cartridge and multi-drop common bus in which more than one cartridge are connected to the bus between electronics modules of ink cartridges and the printer, as shown respectively in FIG. 1 to FIG. 4 . It should be noted that the hardware architecture as shown in FIG. 1 can be replicated for different color ink cartridges. As for FIG. 2 , there may exist more than 2 cartridges connecting to the common bus. As shown in FIGS. 1 to 4 , data transfer between printer and ink cartridges is initiated and controlled by the printer. Data is read from cartridges during power on of printer or installation of cartridge to the printer. Data is written to ink cartridges during power off of printer, or moving cartridge holder to unload position, or marking the first use of a new cartridge after read operation. For individually controlled hardware architecture, data transfer between printer and each individual cartridge takes place simultaneously. For multi-drop common bus architecture, printer addresses (address embedded with read/write command) each cartridge for data transfer in sequence. Data strings read from ink( cartridges are normally longer than data being written to ink cartridges. This is due to the fact that data written to cartridges are just variables related to ink volume, date installed, etc, while data read contain fixed information such as cartridge code and type, capacity, manufacturer and manufacturing date, etc. Typical communication protocol for exchange of data between printer and ink cartridges for individually controlled architecture is shown in FIG. 3 . For read cycle (R/W=0), data flow direction is from ink cartridge to printer. For write cycle (R/W=1), data flow direction is from printer to ink cartridge. Typical communication protocol for exchange of data between printer and an ink cartridge for multi-drop common bus architecture is shown in FIG. 4 . As an example, a common code may be used in which 3 bits are serving as the address for addressing up to 8 cartridges and 1 bit is used to signify read or write operations. Read operation after write cycle can be added to ensure data written to cartridges correctly stored. Usually ink capacity of the ink cartridge is being basically constant, and it is little, so the user has to change frequently the ink cartridge after it runs out. This frequent change of ink cartridges not only spends much time, but waste the resources such as ink. As data updating of electronics module in ink cartridges is controlled by the printer, the manufacturers of ink cartridges have to design electronics module compatible with the printer. That is, it is very difficult for the remanufacturers to come up with a much higher ink volume cartridge. And actually, there are much ink remained in the ink cartridge when the printer alerts the user with the ink out condition. Thus, inks are not used fully in the cartridge and then a user replaces it for a new one, as a result, much ink is thrown away. Accordingly, an improved ink cartridge with higher ink capacity and compatible with different inks that address these problems and others would be desirable.

<SOH> SUMMARY OF THE INVENTION <EOH>According to one aspect of the present invention there is provided an intelligent ink cartridge with an electronics module, which can access, and in addition, control the EEPROM built in, and as a result, design out an ink cartridge with higher ink capacity. According to another aspect of the present invention there is provided an electronics module which controls accessing and processing operations of ink remaining data, as a result, to improve ink capacity of the ink cartridge for use with the printer, and improve the volumetric efficiency of ink. The present invention provides an intelligent ink cartridge, comprising at least one ink chamber storing ink, an electronics module storing identification information of ink cartridge and ink remaining data. The electronics module is a micro-controller with a non-volatile memory for controlling calculation and access of ink remaining data in the ink cartridge to improve the maximum ink volume of the ink cartridge for use with the printer. According to the intelligent ink cartridge, the non-volatile memory is an EEPROM that is serially accessed. According to the intelligent ink cartridge, the micro-controller is a RISC 8-bit micro-controller of CMOS, comprising: an ALU(arithmetic and logic unit) connected to a 8-bit data bus, an EEPROM memory storing identification information of ink cartridge and ink remaining data, plural registers, interrupt unit, serial periphery interface unit, timer, analog comparator, I/O interface, and a fast flash connected to the ALU by the register, storing a program controlling reading and writing operations and calculation of ink remaining data. The intelligent ink cartridge further comprises a R-C control circuit with appropriate time constant, used to distinguish the checking read cycle and the normal read cycle, and the R-C control circuit is connected to the input interface of the micro-controller. The present invention also provides a method of manufacturing an intelligent ink cartridge, which comprises at least one ink chamber for storing ink, an electronics module storing identification information of ink cartridge and ink remaining data. According to the method, the electronics module is made according to the following steps: to set a special-purpose micro-controller in the ink cartridge; to write identification information of ink cartridge and the program controlling access and process operations of ink remaining data into the non-volatile memory of the special-purpose micro-controller; and to carry out the program so that it can meet the requirement of an ink jet apparatus's controlling and reading/writing ink remaining data when ink capacity of ink cartridge is increased. According to the method of manufacturing the intelligent ink cartridge, identification information of ink cartridge and ink remaining data is stored into an EEPROM memory in the special-purpose micro-controller, and the program controlling access and process operations of ink remaining data is stored into a fast flash in the micro-controller. (Process operations can also be stored in any other micro-controllers having equal or higher computational ability and storage capacities). According to a further aspect of the present invention there is provided a special-purpose electronics module of an intelligent ink cartridge, which is used to store identification information of the ink cartridge and ink remaining data, and the electronics module is a micro-controller with embedded non-volatile memory and the micro-controller is used to control calculation and access of ink remaining data in the ink cartridge to improve the maximum ink volume of the ink cartridge for use with the printer. According to the electronics module of the intelligent ink cartridge, the non-volatile memory in the micro-controller stores identification information and the program controlling access and process operations of ink remaining data. By carrying out the program it can meet the requirement of an ink jet apparatus's controlling and reading/writing ink remaining data when ink capacity of ink cartridge is increased.

20040820

20080318

20050428

59579.0

FIDLER, SHELBY LEE

INTELLIGENT INK CARTRIDGE AND METHOD FOR MANUFACTURING THE SAME

UNDISCOUNTED

ACCEPTED

ACCEPTED

Dynamic frequency spectrum re-allocation

A method of dynamically re-allocating a frequency spectrum to a plurality of radio networks (RNs; 16) in accordance with a predefined spectrum allocation scheme is described. A spectrum resource is previously allocated to each RN (16) or group of RNs (16, 16′). An electronic spectrum request for a RN (16) or a group of RNs (16, 16′) is generated and transmitted via a communications network (18) to a server infrastructure (12) which also receives electronic spectrum requests for other RNs (16), the server infrastructure (12) processing the received electronic spectrum requests in accordance with the spectrum re-allocation scheme to re-allocate the spectrum resources to the plurality of RNs (16).

1. A method of dynamically re-allocating a frequency spectrum to a plurality of radio networks in accordance with a predefined spectrum allocation scheme, wherein a spectrum resource has previously been allocated to each RN or group of RNs comprising: generating an electronic spectrum request for a RN or a group of RNs; and transmitting the electronic spectrum request via a communications network to a server infrastructure which also receives electronic spectrum requests for other RNs, the server infrastructure processing the received electronic spectrum requests in accordance with the spectrum re-allocation scheme to reallocate the spectrum resources to the plurality of RNs. 2. The method of claim 1, wherein the re-allocation is performed continuously or wherein the re-allocation is performed quasi-continuously. 3. The method of claim 2, further comprising determining a service quality of one of the RNs taking into account the actual or predicted traffic on the RN's spectrum resource and generating the electronic spectrum request in dependence of the service quality. 4. The method of claim 3, wherein the whole frequency spectrum is re-allocated. 5. The method of claim 3, wherein only a portion of the frequency spectrum is re-allocated and wherein the portion of the frequency spectrum to be re-allocated is taken from the individual RNs' spectrum resources according to a predefined contribution scheme. 6. The method of claim 5, wherein the spectrum allocation scheme is based on spectrum credits relating to elementary spectrum units. 7. The method of claim 6, wherein each RN or group of RNs is assigned the same or an individual first number of spectrum credits and wherein an electronic spectrum request for an RN comprises a specification of a second number of spectrum credits representative of the requested spectrum resource. 8. The method of claim 7, wherein the communications network allows to reassign the spectrum credits among the plurality of RNs. 9. The method of claim 8, wherein the spectrum credits have a limited temporal validity. 10. The method of claim 9, wherein the spectrum re-allocation scheme is auction-based and wherein the electronic spectrum requests comprise electronic bids submitted via the communications network. 11. The method of claim 10, wherein the electronic bids relate to one or more frequency bundles comprised within the frequency spectrum and wherein a specific frequency bundle is re-allocated to the RN associated with the best electronic bid. 12. The method of claim 11, wherein, prior to the next re-allocation process for all RNs, the specific frequency bundle or a part thereof re-allocated to the RN or group of RNs associated with the best electronic bid is allocated to another RN or group of RNs. 13. The method of claim 10, wherein the frequency spectrum to be re-allocated is partitioned bid-proportionally. 14. The method of claim 13, wherein the electronic bids are submitted iteratively. 15. A computer program product for dynamically re-allocating a frequency spectrum to a plurality of radio networks in accordance with a predefined spectrum allocation scheme, wherein a spectrum resource has previously been allocated to each RN or group of RNs, comprising program code portions for: generating an electronic spectrum request for a RN or a group of RNs and transmitting the electronic spectrum request via a communications network to a server infrastructure which also receives electronic spectrum requests for other RNs, the server infrastructure processing the received electronic spectrum requests in accordance with the spectrum re-allocation scheme to reallocate the spectrum resources to the plurality of RNs. 16. (canceled) 17. A system for dynamically re-allocating a frequency spectrum to a plurality of radio networks in accordance with a predefined spectrum re-allocation scheme, wherein a spectrum resource has previously been allocated to each RN or group of RNs, comprising: a communications network; at least one RN infrastructure with one or more RNs, means for generating an electronic spectrum request, and means for transmitting the electronic spectrum request via the communications network; and a server infrastructure in communication via the communications network with the at least one RN infrastructure, the server infrastructure having means for receiving electronic spectrum requests and means for processing the received electronic spectrum requests in accordance with the spectrum re-allocation scheme to re-allocate the spectrum resources to the plurality of RNs. 18. The system of claim 18, configured as an electronic auction network. 19. A server infrastructure for dynamically reallocating a frequency spectrum to a plurality of radio networks in accordance with a predefined spectrum re-allocation scheme, wherein a spectrum resource has previously been allocated to each RN or group of RNs, comprising: means for receiving electronic spectrum requests in communication via a communications network with at least one RN infrastructure; and means for processing the received electronic spectrum requests in accordance with the spectrum re-allocation scheme to re-allocate the spectrum resources to the plurality of RNs. 20. A radio network infrastructure utilizing a previously allocated spectrum resource, comprising: at least one RN; and a device for generating an electronic spectrum request and for transmitting the electronic spectrum request via a communications network to a server infrastructure which also receives electronic spectrum requests for other RNs, the server infrastructure processing the received spectrum requests in accordance with a predefined spectrum re-allocation scheme to re-allocate a spectrum resources to the at least one RN.

BACKGROUND OF THE INVENTION 1. Technical Field The invention relates to the field of allocating a frequency spectrum to a plurality of radio networks. More particularly, the invention departs from the situation that a spectrum resource has previously been allocated to each radio network or to a group of radio networks and proposes a method and a system for dynamically re-allocating the frequency spectrum. 2. Technical Background In recent years wireless communications expanded rapidly and the current development shows clear signs of accelerated future growth. However, future growth is limited by the fact that the total frequency spectrum that is made available for wireless communications cannot keep pace with the increasing demands. There have thus been various approaches like channel splitting or advanced speech and data coding to improve spectrum efficiency. Additionally, technical improvements enable wireless communications to advance into increasingly higher frequency regions. In spite of all these attempts, spectrum resources have become scarce. Due to the steadily increasing spectrum demands spectrum allocation has become an important topic. Basically, spectrum allocation belongs to the category of problems that concern the distribution of a scarce resource to a set of individuals having different demand for the resource. In the past several approaches like beauty contests and auctions have been employed in order to allocate a frequency spectrum to a certain number of competing spectrum applicants (e.g. operators) for usage by their radio networks (RNs). A beauty contest is a spectrum allocation scheme which is generally based on the spectrum applicant's prospects of the spectrum usage over several years and also on the related interests of governments. The complex nature of such beauty contests requires a long-term allocation of the spectrum resources. As an alternative to beauty contests many governments have made use of auctioning schemes. Such schemes involve the auctioning of a plurality of spectrum licenses for typical license periods ranging from ten to twenty years. The settlement price of such auctions reflects the expected earnings from the services provided in the licensed spectrum over the license period. As has become apparent from the above, the currently practiced long-term spectrum allocation schemes are not appropriate for dynamic spectrum allocation. If for example technical developments necessitate short-term re-allocations of the frequency spectrum allocated by means of the spectrum allocation schemes discussed above, such re-allocations cannot be dynamically performed today. There is, therefore, a need for a method and a system for dynamically re-allocating a frequency spectrum to a plurality of RNs, which is more flexible and can easily be adapted to the ever-changing demand for spectrum resources. SUMMARY OF THE INVENTION According to the invention this need is satisfied by a method of dynamically re-allocating an at least partially continuous frequency spectrum to a plurality of RNs in accordance with a pre-defined spectrum re-allocation scheme, wherein a spectrum resource has previously been allocated to each RN and wherein the method comprises generating an electronic spectrum request for a RN and transmitting the electronic spectrum request via a communications network to a server infrastructure which also receives electronic spectrum requests for other RNs, the server infrastructure processing the received electronic spectrum requests in accordance with the spectrum re-allocation scheme in order to re-allocate the spectrum resources to the plurality of RNs. In contrast to dynamic frequency re-allocation schemes like Dynamic Frequency Selection (DFS), which re-allocate a single frequency within the spectrum resource available to a single RN, the invention proposes to dynamically re-allocate a continuous frequency spectrum. This continuous frequency spectrum is re-allocated among two or more RNs. The invention departs from the situation that a frequency spectrum has already been allocated to a plurality of RNs, for example by means of one of the long-term spectrum allocation schemes known in the art or any other allocation scheme, and proposes to continue with a dynamic spectrum re-allocation scheme that is based on electronic spectrum requests submitted to a central authority via a communications network. The central authority evaluates the received spectrum requests preferably in real-time and re-allocates spectrum resources to individual RNs or individual groups of RNs. The use of electronic spectrum requests and the automated evaluation thereof constitutes the framework which enables the implementation of dynamic, i.e. short-term, re-allocations of a frequency spectrum. According to the dynamic nature of this invention, re-allocations may be performed continuously, for example on a day-to-day basis, or at least quasi-continuously like during scheduled re-allocation periods. Compared to the current re-allocation periods ranging between ten and twenty years the quasi-continuous re-allocations are performed in much shorter intervals of preferably one year or less. In the case re-allocation is performed quasi-continuously, specific submission periods may be defined during which the electronic spectrum requests may be submitted to or are accepted by the server infrastructure. Such submission periods may range between one or more days and several weeks or months. Due to the dynamic nature of the spectrum re-allocation, technical needs of RNs and economical needs of RN operators can be satisfied almost in real-time in the case the re-allocation is performed continuously. If the re-allocation is performed quasi-continuously, the operators may still plan more flexibly because they basically have only to consider their spectrum needs until the next spectrum re-allocation process. The electronic spectrum request submitted to the server infrastructure may comprise an indication of the specific size of the spectrum resource requested for a particular RN. Alternatively, it may simply indicate that a spectrum resource is needed for a particular RN without specifying the size. The electronic spectrum request is generated on the basis of various considerations. One of those considerations may be the service quality of a RN, which also depends on the actual or predicted traffic on the RN's spectrum resource. The electronic spectrum request may thus be generated in dependence of the service quality. This means that if for example the operator of a RN expects increasing traffic on his RN, he may submit an electronic spectrum request that takes this additional traffic into consideration and vice versa. Apart from the service quality, or in addition to the service quality, aspects like improved spectrum efficiency of a particular RN or strategic considerations may also form the basis for a specific electronic spectrum request. In most cases the spectrum resource available to a particular RN can only be increased at the expense of the spectrum resource currently allocated to one or more other RNs. Re-allocation therefore necessitates that the whole frequency spectrum or at least a portion thereof is dynamically reallocated among the RNs. If only a portion of the frequency spectrum is to be reallocated, a specific re-allocation ratio may be defined. This re-allocation ratio indicates the portion of the previously allocated frequency spectrum that is to be dynamically re-allocated, whereas the remaining portion of the total frequency spectrum is not subjected to the re-allocation process. In the case only a portion of the frequency spectrum is reallocated, this portion has to be taken from the individual RNs' spectrum resources. This is preferably done in accordance with a predefined contribution scheme. This predefined contribution scheme may for example define that each RN has to contribute the same spectrum amount or that each RN contributes a spectrum amount that is proportional to the spectrum resource currently allocated to this RN. The spectrum re-allocation scheme underlying the dynamic re-allocation process has to be chosen such that short-term allocation is rendered possible. Various re-allocation schemes fulfill this requirement. According to a first exemplary variant, the spectrum re-allocation scheme is based on spectrum credits that relate to elementary spectrum units. According to this spectrum re-allocation scheme, each RN or group of RNs may be assigned the same or an individual number of spectrum credits that are exchangeable into a specific spectrum resource. An electronic spectrum request in this spectrum re-allocation scheme may thus comprise a specification of a particular number of spectrum credits representative of the requested spectrum resource. Preferably, the communications network linking the RN to the server's infrastructure (and, if required, additionally linking individual RNs) and the system as a whole are configured such that they allow to reassign the spectrum credits among the plurality of RNs. Such an implementation enables spectrum credit trading and thus guarantees an economically equitable access to spectrum resources. In order to prevent specific RNs from blocking other RNs, the spectrum credits may have a limited temporal validity. Furthermore, the number of spectrum credits that may be allocated to a specific RN could be limited. According to a second exemplary embodiment, the re-allocation scheme may be auction-based such that the electronic spectrum requests submitted via the communications network comprise electronic bids. The frequency spectrum to be re-allocated may be auctioned as a single bundle or it may be divided into a plurality of frequency bundles which are auctioned separately. The electronic bids may relate to one or more frequency bundles comprised within the frequency spectrum. A specific frequency bundle may be re-allocated to this RN or this group of RNs associated with the best electronic bid. The best electronic bid need not necessarily be the bid specifying the highest price. Instead, the best electronic bid may be determined on the basis of one or more further parameters like the RN's previous quality of service. Once one or more specific frequency bundles have been auctioned by the RN associated with the best electronic bid, it might become necessary to re-allocate these one or more frequency bundles, or a part thereof, prior to the next (scheduled) re-allocation process in which all RNs take part. Such a situation may arise for example if the RN associated with the best electronic bid is not willing to use or not capable of using the obtained spectrum resource adequately because the spectrum resource was primarily acquired to block other RNs. In order to prevent sub-optimal quality of service, one or more frequency bundles might be de-associated from this RN in exchange for a predefined penalty or restitution. The penalty may be of a financial nature. According to a further aspect of the auctioning scheme the frequency spectrum to be auctioned may be partitioned bid-proportionally. This means that a larger spectrum resource is re-allocated to a RN associated with a better bid and vice versa. In order to avoid fragmentation, a minimum quantity for an acceptable electronic bid or a minimum partition size may be defined or dynamically specified. The submission of the electronic bids may be performed in a single round or in a plurality of subsequent rounds. In the latter case the electronic bids submitted by an operator of a specific RN are submitted iteratively in response to previous electronic bids submitted by operators of other RNs. The invention can be implemented as a hardware solution or as a software solution. The software solution includes a computer program product comprising program code portions for performing the method set out above. The computer program product may be stored on a computer readable recording medium like a hard disc, a CD-ROM, a floppy disk or on any other storage device. The hardware solution is constituted by a system for dynamically re-allocating a frequency spectrum to a plurality of RNs, the system including a communications network and at least one RN infrastructure with one or more RNs, means for generating an electronic spectrum request, and means for transmitting the electronic spectrum request via the communications network. The system further includes a server infrastructure in communication via the communications network with the at least one RN infrastructure, the server infrastructure having means for receiving electronic spectrum requests and means for processing the received electronic spectrum requests in accordance with the spectrum re-allocation scheme to re-allocate the spectrum resources to the plurality of RNs. Preferably, the system is configured as an electronic auction network. The invention may also be realized in the form of a RN infrastructure configured to communicate with a server infrastructure and vice versa BRIEF DESCRIPTION OF THE DRAWINGS Further advantages of the invention will become apparent upon reference to the following description of preferred embodiments of the invention in the light of the accompanying drawings, in which: FIG. 1 shows a schematic view of a system according to the invention for dynamically re-allocating a frequency spectrum; FIG. 2 schematically shows the course of a quasi-continuous spectrum re-allocation according to the invention (time axis); and FIG. 3 schematically shows the frequency spectrum to be re-allocated to a plurality of radio network infrastructures (frequency axis). DESCRIPTION OF PREFERRED EMBODIMENTS In the following the invention is exemplarily set forth with respect to RNs operating in licensed spectrum bands. The RNs can be constituted by mobile radio networks (GSM, TDMA, PDC, CDMA, EDGE, WCDMA etc.), broadcast networks (DVB, DAB, etc.) or fixed access networks (LDMS etc.). In FIG. 1 a system 10 according to the invention for dynamically re-allocating a frequency spectrum to a plurality of RNs 16, 16′ in accordance with a predefined spectrum re-allocation scheme is depicted. The system 10 comprises a server infrastructure 12 associated with a plurality of RN infrastructures A, B, C, D. The number of RN infrastructures associated with the server infrastructure 12 may be limited, preferably to a maximum number of ten RN infrastructures. In the embodiment depicted in FIG. 1, the server infrastructure 12 is associated with four RN infrastructures A, B, C, D. Each of the RN infrastructures A, B, C, D depicted in FIG. 1 is operated by a different RN operator and comprises a client component 14 and at least one RN 16, 16′. The client component 14 allows to generate an electronic spectrum request and includes an interface device for transmitting the generated electronic spectrum request to the server infrastructure 12. The client components 14 and the server infrastructure 12 communicate via a communications network 18. The communications network 18 may be a public network like the Internet or a dedicated internal network for frequency spectrum re-allocation purposes. If the communications network 18 is constituted by a public network, security requirements may necessitate an encrypted communication between the client components 14 and the server infrastructure 12. Additional components like firewalls, proxy servers and demilitarized zones (DMZ) could be used to prevent unauthorized access to the client components 14 or the server infrastructure 12. In order to improve authorization security, each client component 14 could be provided with smart card technology including a secure and user-controllable card reader (not depicted in FIG. 1). It should be noted that in the embodiment depicted in FIG. 1 the client components 14 can communicate with each other via the communications network 18 and the server component 12. The server component 12 functions as a central authority that controls the communication among the client components 14. In principle, the client components 14 could communicate directly with each other if direct communication links between the client components 14 are provided. Any electronic spectrum requests transmitted from the client components 14 via the communications network 18 to the server infrastructure 12 are received by an appropriately configured interface device of the server infrastructure 12 and are processed in accordance with a predefined spectrum re-allocation scheme by a processing device of the server infrastructure 12. In the course of this processing, spectrum re-allocation information is generated and transmitted back via the communications network 18 to the client components 14. Prior to considering some exemplary dynamic spectrum re-allocation schemes in more detail, some exemplary generic aspects of all schemes will be considered with reference to FIGS. 2 and 3. In FIG. 2 an exemplary quasi-continuous re-allocation scheme is described with reference to a time axis t. At an initial point in time t0 it is assumed that the frequency spectrum is already completely or at least partially allocated to the four RN infrastructures A, B, C, D depicted in FIG. 1. The operators of the RN infrastructures A, B, C, D have been informed that the frequency spectrum or at least a part thereof is re-allocated starting from a point in time t5 and that electronic spectrum requests for desired spectrum resources may validly be transmitted, and are accepted by the server infrastructure 12, during a time interval Δt1 preceding t5. The next re-allocation takes place at t9 and electronic spectrum requests relating to t9 may be validly submitted during Δt2. Starting from t5, the re-allocation is performed quasi-continuously in constant time intervals of four time units, i.e. t9−t5. One time unit (ti−ti-1) may correspond to for example one week or one month. According to an embodiment not shown in the drawings the re-allocation process could also take place continuously and may for example involve only two of the RN infrastructures A, B, C, D depicted in FIG. 1. For example an RN infrastructure which requires a larger spectrum resource may at any point in time transmit a corresponding electronic spectrum request to the server infrastructure 12, which forwards the electronic spectrum request or processes the electronic spectrum request and forwards the processed electronic spectrum requests to one or more of the further RN infrastructures. Should one or more RNs infrastructures be willing to abandon a part of their spectrum resources, they may notify the server infrastructure 12 accordingly via the communications network 18. The server infrastructure 12 may then immediately (i.e. not bound by fixed points in time ti) re-allocate the spectrum resources appropriately between the RN infrastructure requesting the spectrum resource and the one or more RNs infrastructure willing to abandon their spectrum resources. In FIG. 3 a possible outcome of a re-allocation process is exemplarily depicted. In the embodiment shown in FIG. 3 the frequency spectrum Δf to be dynamically re-allocated is arranged between the lower frequency limit f0 and the upper frequency limit f1. It is assumed that the frequency spectrum Δf has been divided into equidistant frequency blocks Δf1, Δf2 . . . which in the exemplary embodiment depicted in FIG. 3 constitute elementary spectrum units. Of course, the frequency spectrum Δf could also be divided non-equidistantly. As becomes apparent from FIG. 3, RN infrastructure D of FIG. 1 has been allocated two elementary spectrum units, namely Δf1 and Δf2. RN infrastructure B of FIG. 1 has been allocated three elementary spectrum units, and the remaining RN infrastructures A and C share the remaining elementary spectrum units not explicitly shown in FIG. 3. In principle, the frequency spectrum Δf could also be fragmented. However, it is assumed here that such a fragmentation can be removed by appropriate defragmentation processes. In the following description, two dynamic spectrum re-allocation schemes, namely a short-term auctioning scheme and a spectrum credit based scheme, will be described in more detail. 1. Short-Term Auctioning Scheme According to the short-term auctioning scheme, the operators of the RN infrastructures A, B, C, D of FIG. 1 participate in an electronic auction by submitting electronic spectrum requests in the form of electronic bids. The electronic bids can be submitted in a single round or iteratively in multiple rounds. As depicted in FIG. 2, bidding is performed during predetermined periods of time Δti. The spectrum resources to be auctioned during Δti are taken from spectrum resources the operators have obtained prior to the beginning of Δti. The size of the total spectrum resources available for auctioning is not discussed here further. 1.1 Bid-Proportional Spectrum Partitioning In the following a bid-proportional re-allocation of the spectrum resources available for bidding is described. According to this embodiment, the entire frequency spectrum that is available for dynamic re-allocation is auctioned during each scheduled auctioning interval Δti. During each interval Δti each operator places bids for a portion of the available frequency spectrum. In the case all participating operators refrain from revising their bids further, or in the case the time interval Δti has expired, the total amount of the offered frequency spectrum is partitioned directly in proportion to the bids of the individual operators and distributed to the operators accordingly. However, in order to avoid fragmentation effects, the total number of partitions is limited and a specific minimum size of each partition is to be specified. During the bidding process, each operator i can determine the spectrum partition Si he would get from the total amount of dynamically re-allocated frequency spectrum S for his bid Bi if the other operators j would stick to their bids Bj in accordance with the following exemplary formula: S i = f ⁡ ( B i ) = B i B i + ∑ j ≠ i ⁢ B j ⁢ S The price Bi an operator is willing to pay thus directly determines the size of the spectrum resource the operator will receive. Each operator will consider in his bids the individual revenue he expects to get from the spectrum resource he desires in the time interval between two subsequent re-allocations. At the end of the auction the operators are informed of the spectrum resource re-allocated to their respective RN and requested to pay in accordance with their (last) bid. The total amount paid or a fraction thereof may be refunded to the operators at the end of each auctioning process or to third parties such as the government. The scheme according to which the amount is returned to the operators is preferably configured such that an individual operator cannot predict how much he will get back. The reason therefore is the fact that if the operator could predict the refunding, he would take this into account when placing his bids, which is not desirable. 1.2 Bidding for Predefined Frequency Bundles According to a further variant, the frequency spectrum to be dynamically re-allocated is divided into one or more frequency bundles that are individually auctioned among the operators. The frequency bundles may have all the same size or different sizes. For example each frequency bundle to be auctioned may correspond to a frequency block Δfi as depicted in FIG. 3 or a multiple thereof. The operators place electronic bids during predetermined submission periods Δti (see FIG. 2) for individual frequency bundles Δfi (see FIG. 3). The price an operator is willing to pay for a frequency bundle is influenced by his individual business case and other prospects from the usage of the frequency bundle between two subsequent re-allocations. According to an important aspect of this embodiment, the effects of electronic bids placed by operators aiming solely at driving the price are alleviated after the auction process has ended and prior to the subsequently scheduled auctioning process. This will now be illustrated in more detail. Generally, the operator with the best (for example the highest) final bid for a specific frequency bundle has the right to buy this frequency bundle. If he exploits his right, the amount he pays might be given to the remaining but out-bidded operators or to third parties. On the other hand, if the operator with the best final bid is not interested in actually buying the frequency bundle this operator is given the possibility to refrain from buying the frequency bundle in order to avoid the situation that spectrum resources remain unused that are required by other operators to ensure optimal quality of service. However, the operator may only refrain from buying the frequency bundle if he pays a certain fine. This fine should be lower than the loss the operator would face if he had bought the frequency bundle because if the fine were higher, the operator would rather buy the frequency bundle than paying the fine. However, if the operator would rather buy the frequency bundle than paying the fine, the frequency bundle is not optimally used. This can be avoided by appropriately selecting the amount of the fine. The amount of the fine should be set so large that the operator is just expected to select the fine with a high probability. Preferably, the amount of the fine is a certain fraction of the operator's bit. The fine paid by an operator can be distributed among the other, out-bided operators according to a specific distribution scheme. If the operator with the best bid chooses not to buy a frequency bundle, the operator with the second best bid is given two alternatives: The operator with the second best bid may either buy this frequency bundle at the price of his last bid or he may not buy this frequency bundle and pass the frequency bundle to the operator with the third best bid. The operator with the third best bid then has the same alternatives like the operator with the second best bid. The remaining operators that have bided may thus also decline from buying the frequency bundle, but in contrast to the operator with the best bid they are not fined for declining. The reason for this is the fact that the fine is only needed to discourage each operator from placing a better bid than the current best bid if the value of the auctioned frequency bundle to him is less than the amount of the bid placed by him. 2. Spectrum Credit Based Re-Allocation Scheme This spectrum re-allocation scheme is based on spectrum credits that relate to elementary spectrum units, for example the frequency intervals Δfi depicted in FIG. 3. In this scheme each operator, i.e. each RN infrastructure A, B, C, D depicted in FIG. 1, can acquire or simply receives from the server infrastructure 12, which acts as spectrum broker, a specific amount of spectrum credits. The obtained amount of spectrum credits enables using on the average a certain spectrum resource Mi when a certain spectrum (see for example Δf in FIG. 3) is dynamically re-allocated. The temporal validity of the spectrum credits is limited by introducing a validity period T. The spectrum credits SC(Mi) are given to each operator i at the beginning of each period T and expire at the end of T. If it is assumed that Mi represents a fraction of the spectrum to be re-allocated and further that n RN infrastructures participate in the re-allocation process, the sum of all Mi (1≦i≦n) equals 1. This means that all operators i may use exactly the spectrum resource Mi in T without any conflict. In an enhanced scheme, also larger sums than 1 are possible. If for example an operator i wants to use a spectrum resource Ni of the frequency spectrum Δf during a period t′<T, the operator i must spend SC(Ni)=(Ni/Mi)*(t′/T)*SC(Mi) spectrum credits. The operator i thus has enough spectrum credits in order to use either constantly the spectrum resource Mi during T, or to use a larger spectrum resource for a shorter period t′<T and a smaller spectrum resource in the remaining duration of T. Spectrum credits that have not been spent at the end of T are invalidated and cannot be used in a subsequent period T. Conflicts that may arise in the case where several or all operators want to spend in t′ more spectrum credits, i.e. want to use a larger spectrum amount, than available in Δf. Such conflicts must be resolved in a predetermined manner, for example according to the first-come-first-served principle, according to the short term auctioning mechanism described above or according to other schemes. Spectrum credits can be re-assigned among the client components 14 via the server infrastructure 12 depicted in FIG. 1 or directly between the client components 14. For example, a RN infrastructure may acquire spectrum credits from another RN infrastructure, thus increasing its future spectrum resources. Of course, the spectrum resources of the further RN infrastructure will decrease accordingly. This corresponds to a trading of spectrum credits. Misbehavior of operators has to be prevented. This can be accomplished by setting upper limits on the number of spectrum credits that can be assigned to an individual RN infrastructure. It can thus be prevented that one operator which has saved or acquired more spectrum credits than other operators prevents the other operators in t′ from using any spectrum resources. The embodiments described above ensure fair spectrum usage policies, especially on a spectrum market with a small number of participants. The spectrum re-allocation scheme of short-term auctioning achieves that the operators can aim at the exact amount of spectrum resource that is needed, while ensuring that the totally available spectrum resource is allocated such that it is used in the most efficient way. The spectrum re-allocation scheme of spectrum credits, that can be spent, saved or traded, ensures that an RN can always use a specific spectrum resource. Modification and alternative embodiments of the invention are contemplated which do not depart from the spirit and the scope of the invention as defined by the foregoing teaching and appended claims. It is intended that the claims cover all such modifications that fall within their scope.

<SOH> BACKGROUND OF THE INVENTION <EOH>1. Technical Field The invention relates to the field of allocating a frequency spectrum to a plurality of radio networks. More particularly, the invention departs from the situation that a spectrum resource has previously been allocated to each radio network or to a group of radio networks and proposes a method and a system for dynamically re-allocating the frequency spectrum. 2. Technical Background In recent years wireless communications expanded rapidly and the current development shows clear signs of accelerated future growth. However, future growth is limited by the fact that the total frequency spectrum that is made available for wireless communications cannot keep pace with the increasing demands. There have thus been various approaches like channel splitting or advanced speech and data coding to improve spectrum efficiency. Additionally, technical improvements enable wireless communications to advance into increasingly higher frequency regions. In spite of all these attempts, spectrum resources have become scarce. Due to the steadily increasing spectrum demands spectrum allocation has become an important topic. Basically, spectrum allocation belongs to the category of problems that concern the distribution of a scarce resource to a set of individuals having different demand for the resource. In the past several approaches like beauty contests and auctions have been employed in order to allocate a frequency spectrum to a certain number of competing spectrum applicants (e.g. operators) for usage by their radio networks (RNs). A beauty contest is a spectrum allocation scheme which is generally based on the spectrum applicant's prospects of the spectrum usage over several years and also on the related interests of governments. The complex nature of such beauty contests requires a long-term allocation of the spectrum resources. As an alternative to beauty contests many governments have made use of auctioning schemes. Such schemes involve the auctioning of a plurality of spectrum licenses for typical license periods ranging from ten to twenty years. The settlement price of such auctions reflects the expected earnings from the services provided in the licensed spectrum over the license period. As has become apparent from the above, the currently practiced long-term spectrum allocation schemes are not appropriate for dynamic spectrum allocation. If for example technical developments necessitate short-term re-allocations of the frequency spectrum allocated by means of the spectrum allocation schemes discussed above, such re-allocations cannot be dynamically performed today. There is, therefore, a need for a method and a system for dynamically re-allocating a frequency spectrum to a plurality of RNs, which is more flexible and can easily be adapted to the ever-changing demand for spectrum resources.

<SOH> SUMMARY OF THE INVENTION <EOH>According to the invention this need is satisfied by a method of dynamically re-allocating an at least partially continuous frequency spectrum to a plurality of RNs in accordance with a pre-defined spectrum re-allocation scheme, wherein a spectrum resource has previously been allocated to each RN and wherein the method comprises generating an electronic spectrum request for a RN and transmitting the electronic spectrum request via a communications network to a server infrastructure which also receives electronic spectrum requests for other RNs, the server infrastructure processing the received electronic spectrum requests in accordance with the spectrum re-allocation scheme in order to re-allocate the spectrum resources to the plurality of RNs. In contrast to dynamic frequency re-allocation schemes like Dynamic Frequency Selection (DFS), which re-allocate a single frequency within the spectrum resource available to a single RN, the invention proposes to dynamically re-allocate a continuous frequency spectrum. This continuous frequency spectrum is re-allocated among two or more RNs. The invention departs from the situation that a frequency spectrum has already been allocated to a plurality of RNs, for example by means of one of the long-term spectrum allocation schemes known in the art or any other allocation scheme, and proposes to continue with a dynamic spectrum re-allocation scheme that is based on electronic spectrum requests submitted to a central authority via a communications network. The central authority evaluates the received spectrum requests preferably in real-time and re-allocates spectrum resources to individual RNs or individual groups of RNs. The use of electronic spectrum requests and the automated evaluation thereof constitutes the framework which enables the implementation of dynamic, i.e. short-term, re-allocations of a frequency spectrum. According to the dynamic nature of this invention, re-allocations may be performed continuously, for example on a day-to-day basis, or at least quasi-continuously like during scheduled re-allocation periods. Compared to the current re-allocation periods ranging between ten and twenty years the quasi-continuous re-allocations are performed in much shorter intervals of preferably one year or less. In the case re-allocation is performed quasi-continuously, specific submission periods may be defined during which the electronic spectrum requests may be submitted to or are accepted by the server infrastructure. Such submission periods may range between one or more days and several weeks or months. Due to the dynamic nature of the spectrum re-allocation, technical needs of RNs and economical needs of RN operators can be satisfied almost in real-time in the case the re-allocation is performed continuously. If the re-allocation is performed quasi-continuously, the operators may still plan more flexibly because they basically have only to consider their spectrum needs until the next spectrum re-allocation process. The electronic spectrum request submitted to the server infrastructure may comprise an indication of the specific size of the spectrum resource requested for a particular RN. Alternatively, it may simply indicate that a spectrum resource is needed for a particular RN without specifying the size. The electronic spectrum request is generated on the basis of various considerations. One of those considerations may be the service quality of a RN, which also depends on the actual or predicted traffic on the RN's spectrum resource. The electronic spectrum request may thus be generated in dependence of the service quality. This means that if for example the operator of a RN expects increasing traffic on his RN, he may submit an electronic spectrum request that takes this additional traffic into consideration and vice versa. Apart from the service quality, or in addition to the service quality, aspects like improved spectrum efficiency of a particular RN or strategic considerations may also form the basis for a specific electronic spectrum request. In most cases the spectrum resource available to a particular RN can only be increased at the expense of the spectrum resource currently allocated to one or more other RNs. Re-allocation therefore necessitates that the whole frequency spectrum or at least a portion thereof is dynamically reallocated among the RNs. If only a portion of the frequency spectrum is to be reallocated, a specific re-allocation ratio may be defined. This re-allocation ratio indicates the portion of the previously allocated frequency spectrum that is to be dynamically re-allocated, whereas the remaining portion of the total frequency spectrum is not subjected to the re-allocation process. In the case only a portion of the frequency spectrum is reallocated, this portion has to be taken from the individual RNs' spectrum resources. This is preferably done in accordance with a predefined contribution scheme. This predefined contribution scheme may for example define that each RN has to contribute the same spectrum amount or that each RN contributes a spectrum amount that is proportional to the spectrum resource currently allocated to this RN. The spectrum re-allocation scheme underlying the dynamic re-allocation process has to be chosen such that short-term allocation is rendered possible. Various re-allocation schemes fulfill this requirement. According to a first exemplary variant, the spectrum re-allocation scheme is based on spectrum credits that relate to elementary spectrum units. According to this spectrum re-allocation scheme, each RN or group of RNs may be assigned the same or an individual number of spectrum credits that are exchangeable into a specific spectrum resource. An electronic spectrum request in this spectrum re-allocation scheme may thus comprise a specification of a particular number of spectrum credits representative of the requested spectrum resource. Preferably, the communications network linking the RN to the server's infrastructure (and, if required, additionally linking individual RNs) and the system as a whole are configured such that they allow to reassign the spectrum credits among the plurality of RNs. Such an implementation enables spectrum credit trading and thus guarantees an economically equitable access to spectrum resources. In order to prevent specific RNs from blocking other RNs, the spectrum credits may have a limited temporal validity. Furthermore, the number of spectrum credits that may be allocated to a specific RN could be limited. According to a second exemplary embodiment, the re-allocation scheme may be auction-based such that the electronic spectrum requests submitted via the communications network comprise electronic bids. The frequency spectrum to be re-allocated may be auctioned as a single bundle or it may be divided into a plurality of frequency bundles which are auctioned separately. The electronic bids may relate to one or more frequency bundles comprised within the frequency spectrum. A specific frequency bundle may be re-allocated to this RN or this group of RNs associated with the best electronic bid. The best electronic bid need not necessarily be the bid specifying the highest price. Instead, the best electronic bid may be determined on the basis of one or more further parameters like the RN's previous quality of service. Once one or more specific frequency bundles have been auctioned by the RN associated with the best electronic bid, it might become necessary to re-allocate these one or more frequency bundles, or a part thereof, prior to the next (scheduled) re-allocation process in which all RNs take part. Such a situation may arise for example if the RN associated with the best electronic bid is not willing to use or not capable of using the obtained spectrum resource adequately because the spectrum resource was primarily acquired to block other RNs. In order to prevent sub-optimal quality of service, one or more frequency bundles might be de-associated from this RN in exchange for a predefined penalty or restitution. The penalty may be of a financial nature. According to a further aspect of the auctioning scheme the frequency spectrum to be auctioned may be partitioned bid-proportionally. This means that a larger spectrum resource is re-allocated to a RN associated with a better bid and vice versa. In order to avoid fragmentation, a minimum quantity for an acceptable electronic bid or a minimum partition size may be defined or dynamically specified. The submission of the electronic bids may be performed in a single round or in a plurality of subsequent rounds. In the latter case the electronic bids submitted by an operator of a specific RN are submitted iteratively in response to previous electronic bids submitted by operators of other RNs. The invention can be implemented as a hardware solution or as a software solution. The software solution includes a computer program product comprising program code portions for performing the method set out above. The computer program product may be stored on a computer readable recording medium like a hard disc, a CD-ROM, a floppy disk or on any other storage device. The hardware solution is constituted by a system for dynamically re-allocating a frequency spectrum to a plurality of RNs, the system including a communications network and at least one RN infrastructure with one or more RNs, means for generating an electronic spectrum request, and means for transmitting the electronic spectrum request via the communications network. The system further includes a server infrastructure in communication via the communications network with the at least one RN infrastructure, the server infrastructure having means for receiving electronic spectrum requests and means for processing the received electronic spectrum requests in accordance with the spectrum re-allocation scheme to re-allocate the spectrum resources to the plurality of RNs. Preferably, the system is configured as an electronic auction network. The invention may also be realized in the form of a RN infrastructure configured to communicate with a server infrastructure and vice versa

20050201

20081014

20050616

67320.0

NGUYEN, SIMON

DYNAMIC FREQUENCY SPECTRUM RE-ALLOCATION

UNDISCOUNTED

ACCEPTED

ACCEPTED

Method for producing 2-chloromethylphenyl acetic acid derivatives

A process for preparing 2-(chloromethyl)phenylacetic acid derivatives of the formula I, where X is C1-C4-alkoxy or methylamino, by ether cleavage of compounds of the formula II, where R is C1-C4-alkyl, C1-C4-alkoxy, C1-C2-haloalkyl, C1-C4-alkylcarbonyl, C1-C4-alkylcarbonyloxy, halogen, nitro or cyano and X is as defined above comprises carrying out the reaction in the presence of hydrogen chloride and an inert solvent, and adding a catalyst to the reaction mixture selected from the group consisting of iron, indium and halides, oxides and triflates thereof.

1-5. (canceled) 6. A process for preparing a 2-(chloromethyl) phenylacetic acid derivative of formula I, where X is C1-C4-alkoxy or methylamino, said process comprising ether cleaving a compound of formula II, where R is C1-C4-alkyl, C1-C4-alkoxy, C1-C2-haloalkyl, C1-C4-alkylcarbonyl, C1-C4-alkylcarbonyloxy, halogen, nitro or cyano and X is as defined above, with hydrogen chloride, in the presence of an inert solvent and a catalyst. 7. The process of claim 6 wherein said catalyst is selected from the group consisting of iron, indium and halides, oxides and triflates thereof. 8. The process of claim 6, wherein said catalyst is iron (III) chloride. 9. The process of claim 6, wherein said catalyst is iron. 10. The process of claim 6, wherein said catalyst is indium (III) chloride. 11. The process of claim 6, wherein said catalyst is iron (III) oxide. 12. The process of claim 6, wherein said catalyst has a concentration in the components of the ether cleaving reaction of about 0.001 to 0.5 mol equivalents. 13. The process of claim 6, wherein said catalyst has a concentration in the components of the ether cleaving reaction of about 0.01 to 0.2 mol equivalents. 14. The process of claim 6, wherein said hydrogen chloride has a concentration in the components of the ether cleaving reaction of about 1 to 25 mol equivalents. 15. The process of claim 6, wherein said hydrogen chloride has a concentration in the components of the ether cleaving reaction of about 1 to 10 mol equivalents. 16. The process of claim 6, wherein said hydrogen chloride has a concentration in the components of the ether cleaving reaction of about 3 to 5 mol equivalents. 17. The process of claim 6, wherein said inert solvent is an aromatic hydrocarbon. 18. The process of claim 6, wherein said inert solvent is an aliphatic (halogenated) hydrocarbon. 19. The process of claim 6 wherein said hydrogen chloride is passed into the ether cleaving reaction mixture in gaseous form. 20. The process of claim 6 wherein said hydrogen chloride is condensed into said ether cleaving reaction. 21. The process of claim 6 further comprising adding at least one Lewis base to the said ether cleaving reaction. 22. The process of claim 16 wherein said Lewis base is pyridine. 23. The process of claim 16 wherein said Lewis base is N,N-dimethylaniline. 24. The process of claim 16 wherein said Lewis base is ethanethiol. 25. The process of claim 6 further comprising adding trimethylsilyl chloride to said ether cleaving reaction. 26. The process of claim 6 further comprising conducting said ether cleaving reaction in a biphasic system in the presence of a phase transfer catalyst. 27. The process of claim 6 further comprising performing said ether cleaving reaction under a protective gas atmosphere. 28. The process of claim 6 wherein said ether cleaving reaction temperature is between about 0 to 100° C. 29. The process of claim 6 wherein said ether cleaving reaction temperature is between about 30 to 70° C. 30. The process of claim 6 wherein said ether cleaving reaction pressure is from about 0 to 6 bar. 31. The process of claim 6 wherein said ether cleaving reaction pressure is atmospheric pressure.

The present invention relates to a process for preparing 2-(chloromethyl)phenylacetic acid derivatives of the formula I, where X is C1-C4-alkoxy or methylamino, by ether cleavage of compounds of the formula II, where R is C1-C4-alkyl, C1-C4-alkoxy, C1-C2-haloalkyl, C1-C4-alkylcarbonyl, C1-C4-alkylcarbonyloxy, halogen, nitro or cyano and X is as defined above. J. Chem. Research (S) 232-3 (1985) and J. Org. Chem. 64, 4545 (1981) disclose methods for cleaving benzyl ethers in the presence of specific Lewis acids such as sodium iodide/boron trifluoride or iron(III) chloride on silica. The Lewis acids are used in greater than stoichiometric quantities, which makes the process uneconomical. Synlett (10), 1575-6 (1999) describes a process for cleaving 4-nitrobenzyl ethers in the presence of indium and aqueous ammonium chloride. Indium is used in an excess of more than 8 equivalents based on the ether to be cleaved. A process for preparing 2-(chloromethyl)phenyl acetic acid derivatives of the formula I by cleaving the appropriate benzyl ethers II is described in WO-A 97/21686. This involves admixing the benzyl ether II with an excess of two or more mol equivalents of boron trichloride. The prior art processes use greater than stoichiometric quantities of Lewis acids. The handling of Lewis acids used is additionally problematic and the majority thereof are highly corrosive. It is an object of the present invention to provide a catalytic process for preparing 2-(chloromethyl)phenylacetic acid derivatives of the formula I from the appropriate benzyl ethers in high yield and selectivity which does not have the abovementioned disadvantages. Care also had to be taken that the benzyl ether II was cleaved with high selectivity, i.e. that the methoxyiminophenylglyoxylic acid unit in the target compound I was retained. We have found that this object is achieved by carrying out the ether cleavage in the presence of hydrogen chloride and an inert solvent, and adding a catalyst to the reaction mixture selected from the group consisting of iron, indium and halides, oxides and triflates thereof. The hydrogen chloride is generally passed into the reaction mixture in gaseous form. However, it is also possible to condense in the hydrogen chloride. In general, the hydrogen chloride is used in a molar ratio relative to the benzyl ether of from 1 to 25, preferably from 1 to 10 and more preferably from 3 to 5 mol equivalents. Useful catalysts include Lewis acids selected from the group consisting of iron, indium and halides, oxides and triflates thereof. Preferred catalysts are iron and indium(III) chloride and also in particular iron(III) oxide and iron(III) chloride. The catalyst is used in a concentration of from 0.001 to 0.5 and preferably from 0.01 to 0.2 mol equivalents. Useful solvents include aromatic (halogenated) hydrocarbons, e.g. benzene, toluene, xylene, chlorobenzene, dichlorobenzene, bromobenzene and benzotrifluoride; aliphatic (halogenated) hydrocarbons, e.g. pentane, heptane, dichloromethane, chloroform, 1,2-dichloroethane and carbon tetrachloride; cycloaliphatic hydrocarbons, e.g. cyclohexane and cyclopentane; ethers, e.g. dimethoxyethane, diethyl ether and di-isopropyl ether; and esters, e.g. ethyl acetate and butyl acetate. Mixtures of these solvents may also be used. Preferred solvents are aromatic (halogenated) hydrocarbons and aliphatic (halogenated) hydrocarbons. It may possibly be advantageous to add Lewis bases, e.g. pyridine, N,N-dimethylaniline or ethanethiol and/or further auxiliaries such as trimethylsilyl chloride, to the reaction mixture. It may also be advantageous to work in a biphasic system in the presence of a phase transfer catalyst, e.g. tetrabutylammonium chloride, tetrahexylammonium chloride, tetrabutylphosphonium chloride, bis(triphenylphosphoranylidene) ammonium chloride, trimethylbenzylammonium chloride, triethylbenzylammonium chloride or triphenylbenzylammonium chloride. The reaction temperature is customarily from 0 to 100° C. and preferably from 30 to 70° C. The reaction pressure is customarily from 0 to 6 bar. Preference is given to carrying out the reaction under atmospheric pressure. It is also advantageous to perform the ether cleavage under a protective gas atmosphere. Useful starting materials for the ether cleavage include the benzyl ethers II mentioned at the outset. They are accessible by literature methods (EP-A 253 213, EP-A 254 426, EP-A 398 692 or EP-A 477 631). In particular, the crop protection agents currently on the market are suitable, for example methyl 2-methoxyimino-2-[(2-methylphenyloxymethyl)phenyl] acetate (Kresoxim-methyl, EP-A 253 213). After the ether cleavage, the reaction mixture is generally worked up by extraction. Catalyst impurities may be removed, for example, by extraction using aqueous mineral acid such as hydrochloric acid. The phenol cleavage product may advantageously be removed by extraction using aqueous alkali such as sodium hydroxide. The 2-(chloromethyl)phenylacetic acid derivative obtained may be further processed directly, dissolved in the inert solvent, or as a melt after distillative removal of the solvent. The crude product can be further purified by recrystallization in alcohols such as methanol, ethanol, n-butanol or mixtures thereof or mixtures of alcohols and dimethylformamide. The crude product can also be purified by melt crystallization. PROCESS EXAMPLES Inventive Example 1 7.5 g (24 mmol) of kresoxim-methyl were dissolved in 150 ml of chlorobenzene. 0.32 g (2.4 mmol) of iron(III) chloride were then added and 2.6 g (72 mmol) of hydrogen chloride were gassed in within 1 h, during the heating phase to 50° C. The reaction mixture was held at 50° C. for a further 2 hours with stirring and the conversion was then monitored by means of HPLC. After the reaction had ended, the reaction solution was cooled and admixed with 10 ml of methanol. The reaction mixture was extracted, first with hydrochloric acid and then with sodium hydroxide. The organic phase was washed to neutrality and then freed of solvent. The yield of methyl 2-methoxyimino-2-[(2-chloromethyl)phenyl]acetate was 75%. Inventive Example 2 7.5 g (24 mmol) of kresoxim-methyl were dissolved in 150 ml of toluene. 0.53 g (2.4 mmol) of indium(III) chloride were then added and 2.6 g (72 mmol) of hydrogen chloride were gassed in within 1 h, during the heating phase to 40° C. The reaction mixture was held at 40° C. for a further 4 hours with stirring and then worked up as in inventive example 1. The yield of methyl 2-methoxyimino-2-[(2-chloromethyl)phenyl]acetate was 80%. Inventive Example 3 The ether cleavage of inventive example 1 was repeated in 150 ml of 1,2-dichloroethane. 4.1 g (112 mmol) of hydrogen chloride were gassed in within 1 h, during the heating phase to 100° C., and the reaction mixture was held at 100° C. for a further 5 hours. The yield of product of value was 80%. Comparative Example 4 7.5 g (24 mmol) of kresoxim-methyl were dissolved in 150 ml of toluene. 0.32 g (2.4 mmol) of aluminum chloride were then added and 2.6 g (72 mmol) of hydrogen chloride were gassed in within 1 h, during the heating phase to 100° C. The reaction mixture was held at 100° C. for a further 2 hours with stirring and then worked up as in inventive example 1. The yield of product of value was 30%. Comparative Example 5 7.5 g (24 mmol) of kresoxim-methyl were dissolved in 150 ml of 1,2-dichloroethane. 0.63 g (2.4 mmol) of tin tetrachloride were then added and 2.6 g (72 mmol) of hydrogen chloride were gassed in within 1 h, during the heating phase to 85° C. The reaction mixture was held at 85° C. for a further 4 hours with stirring and then worked up as in Inventive Example 1. The yield of product of value was 30%.

20040824

20090210

20050526

94511.0

OH, TAYLOR V

METHOD FOR PRODUCING 2-CHLOROMETHYLPHENYL ACETIC ACID DERIVATIVES

UNDISCOUNTED

ACCEPTED

ACCEPTED

Rack-and-pinion steering system for motor vehicles

A rack-and-pinion steering system for motor vehicles includes a rack, which is mounted in a housing such that it is longitudinally displaceable and kept in constant engagement with a pinion by a pressure piece, is connected at both ends to in each case one steering tie rod in an articulated manner, sealing bellows being fastened on one side to the housing and on the other side to the longitudinally displaceable steering rods. The steering system has a pressure compensation element integrated in the pressure piece.

1-10. (canceled) 11. A rack-and-pinion steering system for motor vehicles, comprising: a pinion; a rack longitudinally displaceably arranged in a steering mechanism housing, the rack including two ends, each end articulatedly connected to a respective steering tie rod; a pressure piece configured to maintain the pinion and the rack in constant engagement; a sealing bellows fastened on one side to the housing and on another side to the steering tie rods; and at least one pressure compensation element integrated in the steering mechanism housing, the pressure compensation element integrated in the pressure piece. 12. The rack-and-pinion steering system according to claim 11, wherein an adjusting screw of the pressure piece includes the pressure compensation element. 13. The rack-and-pinion steering system according to claim 11, wherein the pressure compensation element is formed of a porous sintered material. 14. The rack-and-pinion steering system according to claim 13, wherein an adjusting screw of the pressure piece is formed of a porous sintered material. 15. The rack-and-pinion steering system according to claim 1, wherein the pressure compensation element is configured as a porous sintered plastic insert. 16. The rack-and-pinion steering system according to claim 15, wherein one of (a) the housing and (b) the adjusting screw of the pressure piece includes a cutout adapted to dimensions of the sintered plastic insert and arranged to accommodate the sintered plastic insert. 17. The rack-and-pinion steering system according to claim 15, wherein the sintered plastic insert is arranged as a pressed pellet is pressable into the cutout. 18. The rack-and-pinion steering system according to claim 17, wherein the pressed pellet is formed from ground granules joined to one another by sintering. 19. The rack-and-pinion steering system according to claim 18, wherein at least one of (a) air permeability values and (b) liquid retention capacity is influenceable by at least one of (a) a size and (b) a shape of the granules. 20. The rack-and-pinion steering system according to claim 11, wherein the pressure compensation element is arranged as one of (a) a disk and (b) a diaphragm. 21. A rack-and-pinion steering system for motor vehicles, comprising: a pinion; a rack longitudinally displaceably arranged in a steering mechanism housing, the rack including two ends, each end articulatedly connectable to a respective steering tie rod; a pressure piece configured to maintain the pinion and the rack in constant engagement; a sealing bellows fastened on one side to the housing and fastenable on another side to the steering tie rods; and at least one pressure compensation element integrated in the steering mechanism housing, the pressure compensation element integrated in the pressure piece. 22. A rack-and-pinion steering system for motor vehicles, comprising: pinion means; rack means longitudinally displaceably arranged in a steering mechanism housing means, the rack means including two ends, each end articulatedly connected to a respective steering tie rod means; means for maintaining the pinion means and the rack means in constant engagement; sealing bellows means arranged on one side to the housing means and on another side to the steering rod means; and at least one pressure compensating means integrated in the steering mechanism housing means, the pressure compensating means integrated in the maintaining means.

FIELD OF THE INVENTION The present invention relates to a rack-and-pinion steering system for motor vehicles, the rack of which is mounted in a housing such that it is longitudinally displaceable, is connected at both ends to in each case one steering rod in an articulated manner, sealing bellows being fastened on one side to the housing and on the other side to the longitudinally displaceable steering rods. The bellows made from a flexible material serve to protect the articulated connection and the rack against dust, other solid bodies and humidity. BACKGROUND INFORMATION During driving operation, what is referred to as a pump effect occurs on account of the axial displacement movement of the rack, the pump effect widening the bellows as a result of the intake of air but also as a result of temperature-induced air expansion, and therefore subjecting them to an additional load. Secondly, a reduced pressure compared with atmosphere can occur in the bellows, which can lead to the annular folds bending inwardly. A device for compensation must be provided for the changes in volume occurring in the bellows or also within the housing. German Published Patent Application No. 29 00 026 describes a ventilation apparatus for a shaft joint having bellows sealing, which has a slotted sleeve as a flow connection which is integrated between the shaft and the fastening sleeve of the bellows and allows air to pass. A disadvantage of such a solution is that, in the event of a wet roadway, water and dirt can penetrate through this opening into the joint space as a consequence of the proximity of the wheel and heavy occurrence of water spray, and therefore the components to be protected are subjected to increased wear. U.S. Pat. No. 3,927,576 describes an articulated connection protected by a bellows, in which this disadvantage is eliminated by integrating solids filters in the fastening collar of the bellows or in adjoining regions of, the housing, which filters, in addition to pressure compensation between the interior and atmosphere, also prevent the penetration of moisture and dirt. However, a change to the bellows is necessary here, so that specially manufactured bellows become necessary rather than commercially available ones. The integration of the solid body filter in special ventilation openings of the housing permits subsequent installation into steering systems which are already in service only in conjunction with increased expenditure. SUMMARY According to an example embodiment of the present invention, a rack-and-pinion steering system is provided, in which the required pressure compensation between the interior of the bellows or of the steering mechanism housing and atmosphere may be ensured and, independently of the respective deployment situation and loading of the bellows, reliable sealing of the same may be achieved. A pressure compensation element may be integrated in the pressure piece which keeps the rack in constant engagement with the pinion. The components to be protected may be reliably sealed using a simple arrangement and with continuous pressure compensation, and the properties of their translational movement may remain preserved without changes to the elastic bellows or to the steering mechanism housing becoming necessary. According to an example embodiment of the present invention, a rack-and-pinion steering system for motor vehicles includes: a pinion; a rack longitudinally displaceably arranged in a steering mechanism housing, the rack including two ends, each end articulatedly connected to a respective steering tie rod; a pressure piece configured to maintain the pinion and the rack in constant engagement; a sealing bellows fastened on one side to the housing and on another side to the steering tie rods; and at least one pressure compensation element integrated in the steering mechanism housing, the pressure compensation element integrated in the pressure piece. According to an example embodiment of the present invention, a rack-and-pinion steering system for motor vehicles includes: a pinion; a rack longitudinally displaceably arranged in a steering mechanism housing, the rack including two ends, each end articulatedly connectable to a respective steering tie rod; a pressure piece configured to maintain the pinion and the rack in constant engagement; a sealing bellows fastened on one side to the housing and fastenable on another side to the steering tie rods; and at least one pressure compensation element integrated in the steering mechanism housing, the pressure compensation element integrated in the pressure piece. According to an example embodiment of the present invention, a rack-and-pinion steering system for motor vehicles includes: pinion means; rack means longitudinally displaceably arranged in a steering mechanism housing means, the rack means including two ends, each end articulatedly connected to a respective steering tie rod means; means for maintaining the pinion means and the rack means in constant engagement; sealing bellows means arranged on one side to the housing means and on another side to the steering rod means; and at least one pressure compensating means integrated in the steering mechanism housing means, the pressure compensating means integrated in the maintaining means. An exemplary embodiment of the present invention is illustrated in the appended Figures and explained in the following text in greater detail. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a schematic view of an electrically assisted power steering system. FIG. 2 is a cross-sectional view of a pressure compensation element integrated in a pressure piece. DETAILED DESCRIPTION Although an example embodiment of the present invention is described with reference to a rack-and-pinion steering system 1 having electrical power assistance, it may also be used in rack-and-pinion steering systems 1 having hydraulic power assistance or without power assistance or in steering systems having external power assistance, etc. In a rack-and-pinion steering system 1 of this type, a pinion 9 bears an input shaft 2 which, in the exemplary embodiment illustrated in FIG. 1, is operatively connected to a steering wheel 4 via a steering column 3 provided with universal joints. Together with two steering rods 5 and 6 whose articulated connections to the rack 12 are enclosed in a protective manner by the bellows 19 and 20, the rack of the rack-and-pinion steering system 1 forms on the output element which is operatively connected to wheels which are to be steered. Moreover, the rack 12 forms the driven part of the steering system. Using a power assisted steering system of this type, it is possible to transmit the steering torque from the steering wheel 4 to the wheels to be steered. An assisting force may be exerted on the input shaft 2 by an electric motor 7. In this exemplary embodiment, the electric motor 7 is arranged such that its axis is perpendicular with respect to the axis of the input shaft 2 and therefore of the pinion (9). However, it is also possible for its axis to be at a different angle to the axis of the input shaft 2, for example at an angle of from 60° to 130°. With an identical or similar effect, the electric motor 7 may be arranged such that its axis is arranged parallel to the axis of the input shaft 2 and therefore of the pinion 9 or parallel to the axis of another part of the steering column 3. In the two previously described manners of arranging the electric motor 7, the latter acts on the input shaft 2 and the pinion 9 of the rack-and-pinion steering system 1. It is possible for the electric motor 7 to be arranged such that its axis is parallel to, or at an angle to, or coaxially with respect to the axis of the rack 12 of the rack-and-pinion steering system 1. In the cross-sectional view illustrated in FIG. 2, a pinion 9 is rotatably mounted in two bearings 10 and 11. The toothing of the pinion 9 engages with a rack 12 which is guided in the steering housing 8 in an axially displaceable manner. The rack 12 may be pressed against the toothing of the pinion 9 in a conventional manner using a spring-loaded pressure piece 13. The rack 12 has a longitudinal groove 16 in its toothing region on the outer circumferential surface on the opposite side from the toothing. The longitudinal groove 16 interacts with a longitudinal lug 17 which is integrally formed on the pressure piece 13. The rack 12 is prevented from tilting during operation by the interaction of the longitudinal groove 16 and the longitudinal lug 17. It is possible for these two elements to be interchanged with an identical effect, so that the longitudinal lug is arranged on the rack 12 and the longitudinal groove is arranged on the pressure piece 13 A pressure compensation element 14 designed to be air and liquid permeable is integrated in the adjusting screw 18 of the pressure piece 13 for pressure compensation in the interior of the mechanism housing 8 of the rack-and-pinion steering system 1. The adjusting screw 18, arranged as a screw cap, serves to adjust the play of the pressure piece, which play may be adjusted by the amount by which the screw cap is screwed in. For example, the pressure compensation element 14 is configured as a porous sintered plastic insert which is arranged in a cutout 15 of the adjusting screw 18, the cutout 15 being adapted to the dimensions of the sintered plastic insert. The sintered plastic insert is configured as a pressed pellet composed of PTEE material. Here, the pressed pellet is formed from ground granules which are present, for example, in the form of small balls, the granules being joined to one another under pressure and temperature. The varied density of the sintered material, which may be critical for the air permeability value, may be influenced in a simple manner by the size and/or shape of the granules. Here, the air permeability of the pressed pellet decreases in a manner corresponding to the magnitude of the applied pressing pressure. The property of the pressed pellet of allowing air to permeate and preventing the penetration of moisture may therefore be determined in a simple manner by the granules or the pressure and the temperature of the sintering process. The pressure compensation element 14 may also be composed of another sintered material, such as sintered bronze or another moisture tight and air permeable solids filter which may be configured as a thin disk or diaphragm. The entire adjusting screw 18 may be composed of porous sintered material. The introduction of a pressed pellet into the adjusting screw 18 if the pressure piece 13 may make it simple to retrofit a pressure compensation element 14 to a steering mechanism 18 already in service, by exchanging the existing adjusting screw for one having a pressure compensation element 14. LIST OF REFERENCE NUMERALS USED Rack-and-pinion steering system Input shaft 3 Steering column 4 Steering wheel 5 Steering rod 6 Steering rod 7 Electric motor Steering housing Pinion Bearing Bearing Rack Pressure piece Pressure compensation element Cutout 16 Longitudinal groove 17 Longitudinal lug Adjusting screw Bellows 20 Bellows

<SOH> BACKGROUND INFORMATION <EOH>During driving operation, what is referred to as a pump effect occurs on account of the axial displacement movement of the rack, the pump effect widening the bellows as a result of the intake of air but also as a result of temperature-induced air expansion, and therefore subjecting them to an additional load. Secondly, a reduced pressure compared with atmosphere can occur in the bellows, which can lead to the annular folds bending inwardly. A device for compensation must be provided for the changes in volume occurring in the bellows or also within the housing. German Published Patent Application No. 29 00 026 describes a ventilation apparatus for a shaft joint having bellows sealing, which has a slotted sleeve as a flow connection which is integrated between the shaft and the fastening sleeve of the bellows and allows air to pass. A disadvantage of such a solution is that, in the event of a wet roadway, water and dirt can penetrate through this opening into the joint space as a consequence of the proximity of the wheel and heavy occurrence of water spray, and therefore the components to be protected are subjected to increased wear. U.S. Pat. No. 3,927,576 describes an articulated connection protected by a bellows, in which this disadvantage is eliminated by integrating solids filters in the fastening collar of the bellows or in adjoining regions of, the housing, which filters, in addition to pressure compensation between the interior and atmosphere, also prevent the penetration of moisture and dirt. However, a change to the bellows is necessary here, so that specially manufactured bellows become necessary rather than commercially available ones. The integration of the solid body filter in special ventilation openings of the housing permits subsequent installation into steering systems which are already in service only in conjunction with increased expenditure.

<SOH> SUMMARY <EOH>According to an example embodiment of the present invention, a rack-and-pinion steering system is provided, in which the required pressure compensation between the interior of the bellows or of the steering mechanism housing and atmosphere may be ensured and, independently of the respective deployment situation and loading of the bellows, reliable sealing of the same may be achieved. A pressure compensation element may be integrated in the pressure piece which keeps the rack in constant engagement with the pinion. The components to be protected may be reliably sealed using a simple arrangement and with continuous pressure compensation, and the properties of their translational movement may remain preserved without changes to the elastic bellows or to the steering mechanism housing becoming necessary. According to an example embodiment of the present invention, a rack-and-pinion steering system for motor vehicles includes: a pinion; a rack longitudinally displaceably arranged in a steering mechanism housing, the rack including two ends, each end articulatedly connected to a respective steering tie rod; a pressure piece configured to maintain the pinion and the rack in constant engagement; a sealing bellows fastened on one side to the housing and on another side to the steering tie rods; and at least one pressure compensation element integrated in the steering mechanism housing, the pressure compensation element integrated in the pressure piece. According to an example embodiment of the present invention, a rack-and-pinion steering system for motor vehicles includes: a pinion; a rack longitudinally displaceably arranged in a steering mechanism housing, the rack including two ends, each end articulatedly connectable to a respective steering tie rod; a pressure piece configured to maintain the pinion and the rack in constant engagement; a sealing bellows fastened on one side to the housing and fastenable on another side to the steering tie rods; and at least one pressure compensation element integrated in the steering mechanism housing, the pressure compensation element integrated in the pressure piece. According to an example embodiment of the present invention, a rack-and-pinion steering system for motor vehicles includes: pinion means; rack means longitudinally displaceably arranged in a steering mechanism housing means, the rack means including two ends, each end articulatedly connected to a respective steering tie rod means; means for maintaining the pinion means and the rack means in constant engagement; sealing bellows means arranged on one side to the housing means and on another side to the steering rod means; and at least one pressure compensating means integrated in the steering mechanism housing means, the pressure compensating means integrated in the maintaining means. An exemplary embodiment of the present invention is illustrated in the appended Figures and explained in the following text in greater detail.

20040823

20061212

20050721

67930.0

LUM VANNUCCI, LEE SIN YEE

RACK-AND-PINION STEERING SYSTEM FOR MOTOR VEHICLES

UNDISCOUNTED

ACCEPTED

ACCEPTED

Method and system for providing a single unified channel quieting/measurement request element in an 802.11 wireless local area network

A channel quieting/measurement request element is provided for use in a wireless local area network. The unified element of the invention integrates a dual capability for performing channel quieting and for making measurement requests of one or more stations in the network. According to another aspect of the invention, a conventional channel quieting element is modified to include provisions for defining an offset time and an offset duration interval for performing channel quieting.

1. In a system including a wireless local area network (200), the network (200) including a source node (205) and a plurality of destination nodes (210), a unified channel quieting/measurement request element, comprising: means for quieting a current channel of operation; and means for making a measurement request of at least one of said plurality of destination nodes wherein said means for quieting and said means for making a measurement request may be performed simultaneously or independently. 2. The system of claim 1, wherein said source node is an access point (205) and said plurality of destination nodes are stations (STAs) (210) associated with said access point (205). 3. The system of claim 1, wherein said element is defined by a single protocol at a MAC layer. 4. The system of claim 1, wherein said element further includes means for defining a number of beacon interval periods over which said means for quieting and said means for making a measurement request are performed. 5. The system of claim 4, wherein said element further includes means for defining an offset time which must first elapse in each of said beacon interval periods prior to initiating said channel quieting means and/or said measurement request means. 6. The system of claim 5, wherein said request element further includes means for defining a quiet time interval inside of which said channel quieting means are performed in each of said beacon interval periods. 7. The system of claim 1, wherein said element further includes means for defining one or more additional channels in which said quieting means and/or said measurement request means are performed. 8. The system of claim 1, wherein said means for making a measurement request further includes means for defining one or more measurements. 9. The system of claim 1, wherein the system operates in accordance with the IEEE 802.11(h) specification. 10. A method for performing channel quieting and/or making measurement requests via a single unified channel quieting/measurement request element (202) in a wireless local area network (WLAN) (200), the method comprising the steps of: (a) transmitting said element from a source node (205) to at least one destination node (210) in said WLAN (200); Upon receiving said element at said at least one destination node (210): (b) determining from a first parameter (43a) included in said element (202), a number of beacon interval periods in which said channel quieting and/or making measurement requests are to be performed; (c) determining from a second parameter (43b) included in said element (202), an offset time defining a time which must first expire prior to performing said channel quieting and/or making measurement requests; (d) determining from a third parameter (43c) included in said element (202), a quiet time defining a time duration over which said channel is quieted and/or measurements are performed; (e) determining from at least a fourth parameter (47) included in said element (202) at least one measurement identifier for determining at least one measurement to be performed in accordance with making said measurement requests; and (f) performing the operations of channel quieting and/or measurement requests in accordance with said first, second, third and said at least fourth parameters. 11. The method of claim 10, wherein said offset time is defined in transmission units (TUs) and is measured from a target beacon transmission time (TBTT) in said number of determined beacon interval periods. 12. The method of claim 10, wherein said quiet time is defined in transmission units (TUs). 13. The method of claim 10, wherein said request element further includes a channel list (45) defining at least one additional channel in which said channel quieting and/or measurements are to be performed. 14. The method of claim 10, wherein said parameters are reset in a subsequently transmitted element from said source node (205). 15. A method for performing channel quieting in a wireless local area network (WLAN (200), the method comprising the steps of: (a) transmitting, from a source node (205) to at least one destination node (210) in said WLAN (200), a management frame (202) including a channel quieting element (202), wherein said channel quieting element (202) further includes one or more parameters for performing channel quieting in a current channel of operation; at said at least one destination node: (b) determining from a first parameter in said transmitted channel quieting element (202) a prescribed number of beacon interval periods for performing said channel quieting; (c) determining from a second parameter in said transmitted channel quieting element (202) an offset time for delaying the start of said channel quieting in each of said prescribed number of beacon interval periods; (d) determining from a third parameter in said transmitted channel quieting element (202) a quiet time interval for determining a length of time in which said channel quieting is performed in each of said prescribed number of beacon interval periods; and (e) performing channel quieting in accordance with said first, second, and third parameters. 16. A channel quieting element transmitted as part of a management frame in a wireless local area network (WLAN), the channel quieting element comprising: means for defining an offset time which must first elapse in a beacon interval prior to the start of said channel quieting; and means for defining a channel quiet time in which said channel quieting is performed in said beacon interval subsequent to the expiration of said offset time.

The present invention relates to wireless local area networks (WLANs). More particularly, the present invention relates to a method and system for providing a single unified measurement/quiet request element at the MAC layer in a WLAN. A current mechanism defined in the IEEE 802.11h D1.1draft standard, January 2002, for performing measurements in an 802.11 based wireless local area network (WLAN) is shown and described in FIGS. 1a-c. FIG. 1a illustrates the format of a channel measurement request frame 10 which is included as part of a spectrum management frame, for making measurement requests in a wireless local area network (WLAN). The channel measurement request frame 10 includes, inter alia, a ‘channel measurement method’ element field for specifying a measurement request element. Two types of measurement request elements are shown in FIGS. 1b and 1c, respectively. FIG. 1b illustrates a basic measurement request element 20 and FIG. 1c illustrates a CF type measurement request element 30. Presently, the IEEE 802.11 standard provides for a quiet channel element which defines an interval during which no transmission shall occur on the current operating channel. This interval may be used to assist in making channel measurements, like those specified in FIGS. 1b and 1c, without interference from other STAs in the BSS or IBSS. For example, the quiet channel element may be used to allow a channel to be tested more easily for primary users without interference. One drawback of the present scheme for quieting the channel is that the channel quiet element may only be transmitted as part of a beacon transmission. This is restrictive in the sense that it may be necessary to modify a most recently transmitted channel quiet element or otherwise transmit a new channel quiet element between successive beacon transmissions so as to satisfy European DFS regulatory requirements for operation in the 5 GHz band. Another drawback of the current quiet channel element is that the quiet time specified in the element always starts immediately after the beacon transmission. It would be desirable, in certain cases, to start the quiet time sometime after the start of a beacon transmission at a time when radar transmissions are expected. In this way, it would not be necessary to quiet the channel for the entire beacon interval. An additional drawback of the current channel quieting mechanism is that it is not integrated or tied to the channel measurement element of FIG. 1a. This is problematic in that two frame requests are required, requiring synchronization in their respective transmissions. It would therefore be desirable to add a capability to provide an offset time to schedule channel quieting within a beacon interval thereby overcoming the restriction of having channel quieting always begin immediately at the start of a beacon transmission. It would also be desirable to integrate the channel quiet element and channel measurement element into a single unified element thereby simplifying the MAC protocol and providing a more streamlined means of making ‘clean’ measurements in the channel. The present invention addresses the foregoing needs by providing a unified element for use in a WLAN, the element uniquely integrating capabilities for quieting the channel and/or making measurement requests of stations (STAs) in the network. These features are at present, separately provided in a channel quieting element and a measurement request (MRQ) element, respectively. The format of the unified element of the invention, according to one embodiment, includes a number of fields including: a “count” field for specifying a number of beacon intervals that the channel quieting and/or measurement requests shall be repeated over. A second field referred to as an “offset” field which specifies, for each beacon interval specified in the “count” field, a time interval (i.e., offset period) measured from the start of the beacon interval after which the STA shall halt transmissions and/or make measurement requests. A third field, used in conjunction with the offset field, referred to as a “quiet time” field for specifying a time interval whose start time is measured from the end of the specified “offset” time. The quiet time specifies a time interval inside of which the STA shall halt transmissions and/or make measurement requests. Additional fields of the single unified element of the invention include a “measurement ID” field for specifying specific measurements to be requested and a “Channel List” for specifying one or more channels in which channel quieting and/or measurement requests will be performed. One advantage of the unified element of the invention is that, by combining both channel quieting and measurement request provisions in a single unified element, the MAC protocol is simplified. Another advantage is the ability to transmit the unified element independent of the beacon interval thereby reducing latencies which are normally associated with channel quieting/measurement methods of the prior art. By reducing these latencies, European DFS regulatory requirements for WLANs operating in the 5 GHz band are more easily satisfied. According to another aspect of the invention, there is provided a channel quieting element which includes an offset feature. The channel quieting element is essentially a conventional channel quieting element modified to incorporate an offset capability. Specifically, the channel quieting element includes two parameters not available for use with the conventional channel quieting element. A first parameter referred to herein as an “offset” parameter for defining an offset time which must first expire in each specified beacon interval before channel quieting can occur. A second parameter referred to herein as an “quiet time” parameter defining a time interval, starting from the expiration of the offset time, in which channel quieting is performed. The combination of the offset time parameter and the quiet time parameter essentially define a ‘window’ inside of which channel quieting is performed in each beacon interval. An advantage of the channel quieting element of the invention is that channel quieting is more flexibly performed. That is, the offset feature provides a capability for performing channel quieting at any point after the start of a beacon transmission. This capability may be used to quiet the channel at a time when radar transmissions are expected (e.g., near the end of a beacon interval) without the associated drawback of quieting the channel for the entire beacon interval as is required in a conventional channel quieting element. It is noted, that while the invention finds suitable application for use with WLANS operating in the 5 GHz band, it is equally applicable for use in other bands such as the 2.4 GHz band. A more complete understanding of the method and apparatus of the present invention may be had by reference to the following detailed description when taken in conjunction with the accompanying drawings wherein: FIG. 1a illustrates the format of a channel measurement request frame which is included as part of a spectrum management frame; FIG. 1b illustrates a basic measurement request element; FIG. 1c illustrates a CF type measurement request element; FIG. 2 illustrates a representative network whereto embodiments of the present invention are to be applied; FIG. 3 illustrates a simplified block diagram of an access point (AP) and each station (STA) according to an embodiment of the present invention; FIG. 4 illustrates the format of a measurement/quiet request (MRQ) element according to an embodiment of the invention; FIGS. 5(a)-(e) illustrate partial timelines for illustrating the effect of transmitting a unified element for the purpose of performing channel quieting and/or making measurement requests, according to an embodiment of the invention; and FIG. 6 illustrates the offset parameter for use with the channel quieting element. In the following description, for purposes of explanation rather than limitation, specific details are set forth such as the particular architecture, interfaces, techniques, etc., in order to provide a thorough understanding of the present invention. For purposes of simplicity and clarity, detailed descriptions of well-known devices, circuits, and methods are omitted so as not to obscure the description of the present invention with unnecessary detail. The unified channel quieting/measurement/request element, as its name implies, contains parameters for performing channel quieting and/or making measurement requests in a wireless local area network (WLAN). In accordance with the unified element of the invention, a single channel element provides a dual capability for quieting the channel for a prescribed number of beacon intervals and for a prescribed start time and duration inside each beacon interval and/or for making measurement requests for a prescribed number of beacon intervals and for a prescribed start time and duration inside each beacon interval. FIG. 2 illustrates a representative network 200 whereto embodiments of the present invention are to be applied. According to the principles of the present invention, there is provided a single unified element 202 which may be transmitted by the AP 205 to one or more STAs 210 associated with the AP 205, to request measurements and/or to quiet the STAs 210 for some number of beacon intervals. It should be noted that the network shown in FIG. 2 is small for purposes of illustration. In practice, most networks would include a much larger number of mobile STAs 210. Referring to FIG. 3, the AP 205 and each STA 210 within the WLAN 200 shown in FIG. 2 may include a system with an architecture that is illustrated in the block diagram of FIG. 3. Both the AP 205 and STA 210 may include a display 30, a CPU 32, a transmitter/receiver 34, an input device 36, a storage module 38, a random access memory (RAM) 40, a read-only memory (42), and a common bus 41. Although the description may refer to terms commonly used in describing particular computer systems, the description and concepts equally apply to other processing systems, including systems having architectures dissimilar to that shown in FIG. 3. The transmitter/receiver 34 is coupled to an antenna (not shown) to transmit desired data and its receiver converts received signals into corresponding digital data. The CPU 32 operates under the control of an operating system contained in the ROM 42 and utilizes RAM 40 to perform the frequency selection within a wireless local area network (WLAN), by enabling the AP to provide a new channel or wireless link for all stations (STAs) associated with its BSS. With continued reference to FIG. 2, to make a channel quieting and/or measurement requests in accordance with the present invention, a management frame including the unified element of the invention is transmitted by the AP 205 to one or more STAs 210 in the network, which are associated with the AP 205. The unified element 202 contains parameter values for instructing the STAs 210 on how to perform channel quieting and/or make measurements. The format of the unified element 202 of the invention will be now be described in greater detail. In part II, a description is provided of a conventional channel quieting element, modified to incorporate an offset feature, as will be described. I. Unified Element Description Referring now to FIG. 4, the format of the element 202 of the invention is shown. In addition to the “Element ID” and “Length” fields, the unified element 202 includes a “measurement time” field 43 which is comprised of three sub-fields: a “count” sub-field 43a for specifying the number of beacon intervals that the measurement shall be repeated over, an “offset” sub-field 43b for specifying the time interval in TUs (time units) starting from target beacon transmission time (TBTT) after which the station (STA) shall not transmit, and a “quiet time” sub-field 43c for specifying the time interval in TUs starting from the end of the ‘offset’ that the STA shall not transmit. The unified element 202 also includes a channel list field 45 for selecting one or more channels in the network in which to make measurements, and a “Measurement ID” field 47 for specifying the one or more measurements to be made. Examples of Unified Element Use A number of exemplary general cases are described below which broadly illustrate the functionality of the unified element 202 of the invention. In particular, the specific cases were chosen to illustrate the inherent flexibility in making measurement requests and performing channel quieting by varying one or more of the parameter values included in the unified element 202 of the invention. It is to be understood, however, that the specific cases are not limiting, rather they are provided as exemplary to facilitate a more complete understanding of the invention. 1st case: In the first case, the unified element 202 of the invention is used only to perform channel quieting in a single beacon interval without making any associated measurement requests. With reference now to FIG. 5a, there is shown a partial timeline illustrating the result of transmitting the unified element 202 for the purpose of performing channel quieting over an entire single beacon interval without including a measurement request. In the present case, the current channel is quieted for an entire single beacon interval. A single beacon interval is selected by setting the “count” field 43a of the Unified element 202 to one (‘1’). For ease of explanation, the second beacon interval 55 is arbitrarily selected as the interval to be quieted. In the present case, the current channel is quieted for the entire beacon interval. This is achieved by setting two parameters. The first parameter, referred to above as the “offset” field 43b must be set to zero (‘0’). In so doing, channel quieting begins at a point coincident with the start of the beacon interval (Point “A”). The second parameter, referred to above as the “quiet time” field 43c is set to a value equal to the duration of the beacon interval in time units (TUs), which is 100 TU in the present case. In the present case, no measurement requests are made. As such, the “Measurement ID” element 47 of FIG. 4 is not included. The pertinent parameter settings for the 1st case, discussed above and illustrated in FIG. 5a, are summarized in the table below. Measurement Time Channel List Channel Channel Count Offset Quiet Time Length Number . . . Number 1 0 100 TU 0 N/A N/A N/A 100 TU is assumed to be the length of the beacon interval 2nd case: In the second case, the unified element of the invention is used only to perform channel quieting in a single beacon interval without making associated measurement requests. The present case is distinguishable from the first in that channel quieting is performed only in a portion of the single beacon interval. With reference now to FIG. 5b, there is shown a partial timeline illustrating the result of transmitting the unified element 202 for performing channel quieting over a partial single beacon interval without making a measurement request. Similar to that described above, to select a single beacon interval, the “count” field 43a is set to one (“1”). To perform quieting only over a partial interval of the beacon interval, a non-zero offset value 43b is required. The offset value can be any value in the range, 0<offset<length of the beacon interval (e.g., 100 TU). For ease of explanation, an arbitrary non-zero offset value may be calculated as some fraction of the beacon interval: Offset value=0.2*Beacon interval=0.2*100=20 (1) When an offset value is utilized in the unified element 202 of the invention, a corresponding parameter, referred to herein as the “quiet time” parameter must be defined. For ease of explanation, an arbitrary quiet time parameter value may be calculated as some fraction of the beacon interval as: Quiet time=0.4*Beacon interval=0.4*100=40 TU (2) It should be noted that the combination of the offset time parameter and quiet time parameter essentially define a window (e.g., start time and duration) inside of which channel quieting is performed in the beacon interval. This window is labeled as “B” in FIG. 5b. The parameter settings for the exemplary 2nd case, discussed above and illustrated in FIG. 5b, are summarized in the table below. Measurement Time Channel List Channel Channel Count Offset Quiet Time Length Number . . . Number 1 20 40 0 N/A N/A N/A 100 TU is assumed to be the length of the beacon interval In the present case, no measurement requests are made and as such the measurement ID element 47 of FIG. 4 is not included. 3rd case: The present case is distinguishable from the first two in that channel quieting is performed for an infinite number of beacon intervals. That is, once a unified element 202 is broadcast including a directive to perform channel quieting and/or measurements in an infinite number of intervals, that request will be carried out in every beacon interval thereafter until such time as a subsequent unified element 202 is broadcast having a different directive. With reference now to FIG. 5c, there is shown a partial timeline illustrating the result of transmitting an unified element 202 for performing continuous channel quieting over an infinite number of beacon interval without making a measurement request. It is noted that FIG. 5c is provided primarily to illustrated that the operations specified are to be performed in each and every beacon interval until a subsequent unified element 202 is received indicating otherwise. In the present example, the operation of performing channel quieting over a partial interval without making associated measurements is shown, solely for purposes of illustration. To perform the channel quieting in a succession of beacon intervals, the “count” field 43a is set to hex 0×FF in the illustrative embodiment. The remaining parameters are otherwise identical with those described for the 2nd case for ease of explanation and will therefore not be further described. The pertinent field settings for the 3rd case, discussed above and illustrated in FIG. 5c, are summarized in the table below. Measurement Time Channel List Channel Channel Count Offset Quiet Time Length Number . . . Number 0xFF 20 40 0 N/A N/A N/A In the present case, no measurement requests are made and as such the measurement ID element 47 of FIG. 4 is not included. 4th case: In the fourth case, the unified element 202 of the invention is used to perform both channel quieting and making measurement requests. The dual operations highlight the novelty of the inventive unified element 202. In the illustrative example, the dual operations are performed in an infinite number of beacon intervals over a portion of each beacon interval. With reference now to FIG. 5d, there is shown a partial timeline illustrating the effect of transmitting a unified element 202 for performing channel quieting over a partial beacon interval while making one or more measurement requests. Whenever a measurement request is made, the measurement ID element 47 shown in FIG. 4 is included in the unified element 202. The parameter settings are identical with those shown above for the second case, however, there is also shown some exemplary settings for the channel list and measurement ID element. Measurement Time Channel List Channel Channel Count Offset Quiet Time Length Number . . . Number 0Xff 0.2*BI 0.4*BI 1 1 N/A N/A Measurement Measurement ID . . . . . . ID . . . 1 N 1 N Making Measurements Without Performing Channel Quieting In order to exclusively make measurements without performing channel quieting, the quiet time parameter must be set to a value of zero (“0”). To specify one or more measurement requests, one or more measurement identifiers must be included in the “Measurement ID” field of the Unified element 202. In summation, advantages of the Unified element 202 of the invention over prior art methods for performing channel measurement/quieting include a simplified MAC protocol, higher reliability in transmission by transmitting one frame instead of two dedicated frames (a quieting frame and a management frame), flexibility for performing measurements and flexibility in scheduling quiet times. Furthermore, by providing a unified element with flexible measurement and/or channel quieting options, the possible existence of pre-existing primary users in the channel may be more readily determined. This capability would facilitate meeting the requirements imposed by the European Radio communications Committee (ERC) and it would enhance the performance of an 802.11 WLAN operation in the 5 GHz band or other band range, i.e., 2.4 GHz. It should be apparent to those skilled in the art that this invention can be easily extended to other frequency bands, such as 2.4 GHz, using different physical layer specifications, such as IEEE 802.11b PHY specification. II. Modified Conventional Channel Quieting Element As described above, the unified element 202 of the invention provides advantages of making flexible measurements by virtue of being able to specify a variable offset time for either performing channel quieting and/or making measurement requests. Presently, this capability does not exist in the conventional channel quieting element as defined by the IEEE 802.11 standard. However, an offset time capability would be desirable to incorporate into the conventional channel quieting element. Therefore, the present application further provides a ‘modified’ channel quieting element that provides an offset capability as described above with respect to the unified element 202. In other words, the conventional channel quieting element is modified to the extent of incorporating two parameters, an offset parameter and a quiet time parameter, as described above, to essentially provide a capability of generating a channel quieting ‘window’ in each beacon interval. In so doing, the channel may be quieted at a time when radar transmissions are expected (e.g., near the end of a beacon interval) without the associated drawback of quieting the channel for an entire beacon interval as is required in a conventional channel quieting element. FIG. 6 illustrates a partial timeline illustrating such an offset capability in a modified conventional channel quieting element. In the illustrated example, channel quieting is performed over a partial single beacon interval (e.g. the 2nd beacon interval). The offset time is defined identically to that described above. That is, the offset time defines a time which must first expire in the beacon interval before channel quieting may begin. The offset time is labeled “A” in FIG. 6, and is included in the modified channel quieting element as a single parameter having a value in the range of the beacon interval. A corresponding “quiet time” parameter defines the length of the channel quieting ‘window’, labeled “B” in FIG. 6. The modified channel quieting element of the invention, incorporating offset and quiet time parameters provides similar advantages to those described above with regard to the unified element. Specifically, the conventional channel quieting element as modified provides flexible channel quieting options by providing an offset feature embodied as two offset related parameters. Specifically, the offset parameters define an offset time and quiet time duration parameter which collectively define a channel quieting “window” providing a capability for performing channel quieting over any portion of the beacon interval where radar transmissions are expected without the associated drawback of quieting the entire interval. The foregoing is to be constructed as only being an illustrative embodiment of this invention. Persons skilled in the art can easily conceive of alternative arrangements providing a functionality similar to this embodiment without any deviation from the fundamental principles or the scope of this invention.

20040825

20091117

20050526

97266.0

AJAYI, JOEL

METHOD AND SYSTEM FOR PROVIDING A SINGLE UNIFIED CHANNEL QUIETING/MEASUREMENT REQUEST ELEMENT IN AN 802.11 WIRELESS LOCAL AREA NETWORK

UNDISCOUNTED

ACCEPTED

ACCEPTED

Light emitting module

The present invention provides a light emitting module, comprising: a plurality of thin plate-shaped conductors (2) spaced apart from each other in a first direction; at least one light source (4) connected between at least one pair of adjoining ones of said conductors; and at least one insulating joint member (4) for mechanically joining said plurality of conductors, wherein said at least one insulating joint member exposes both sides of at least a portion of said conductors where said light source is mounted.

1. A light emitting module, comprising: a plurality of thin plate-shaped conductors spaced apart from each other in a first direction; at least one light source connected between at least one pair of adjoining ones of said conductors; and at least one insulating joint member for mechanically joining said plurality of conductors, wherein said at least one insulating joint member exposes both sides of at least a portion of said conductors where said light source is mounted. 2. A light emitting module, comprising: a plurality of thin plate-shaped conductors spaced apart from each other in a first direction; at least one light source connected between at least one pair of adjoining ones of said conductors; and at least one insulating joint member for mechanically joining said plurality of conductors, wherein said at least one insulating joint member has an opening exposing at least one side of a portion of said conductors, and said light source is inserted into said opening to be connected to said exposed portion of the conductors. 3. A light emitting module according to claim 2, wherein said opening exposes both sides of said conductors. 4. A light emitting module according to claim 3, wherein said opening has a first opening into which said light source is inserted, and a second opening located at an opposite position with respect to said conductors, wherein said second opening diverges in a direction away from said conductors. 5. A light emitting module according to claim 2, wherein dimensions of said opening are determined so as to substantially match those of said light source such that said insulating joint member having the opening serves as a socket for said light source. 6. A light emitting module according to claim 3, wherein said light source comprises a chip-type LED, and said portion of said conductors exposed by said opening of said insulating joint member is provided with extensions for resiliently contact electric connection terminals of said chip-type LED. 7. A light emitting module according to claim 6, wherein said insulating joint member has side walls for defining said opening, and a portion of said side walls is formed with an engagement finger for engaging with an upper surface of said chip-type LED when the chip-type LED is inserted into said opening. 8. A light emitting module according to claim 3, wherein said light source comprises a bullet-type LED having a pair of substantially parallel extending leads, wherein said insulating joint member has a partition wall within said opening into which said bullet-type LED is inserted, said partition wall extending across said opening in a second direction substantially perpendicular to said first direction, wherein said portion of said conductors which is exposed by said opening of said insulating joint member and to which said bullet-type LED is mounted has extensions each extending in said first direction to contact said partition wall or to form a small gap between said partition wall and said extensions, and wherein said pair of leads of said bullet-type LED are pushed in between said partition wall and said extensions and cramped by them. 9. A light emitting module, comprising: at least three thin plate-shaped conductors spaced apart from each other in a first direction; a plurality of electric elements each connected between associated pair of said conductors such that said plurality of electric elements are connected in series; and an insulating joint member mechanically joining said at least three conductors, wherein said electric elements comprise at least one light source. 10. A light emitting module according to claim 9, wherein said insulating joint member exposes a portion of said at least three conductors, and said exposed portion is formed with holes or grooves extending in a second direction substantially perpendicular to said first direction whereby said conductors can be bent along said holes or grooves. 11. A light emitting module according to claim 9, comprising a plurality of said insulating joint members, wherein said insulating joint members are spaced apart in said first direction such that said conductors are exposed between adjoining ones of said insulating joint members. 12. A light emitting module, comprising: a plurality of thin plate-shaped conductors spaced apart from each other in a first direction and extending in a second direction substantially perpendicular to said first direction; at least one light source connected between at least one pair of adjoining ones of said conductors; and a plurality of insulating joint members for mechanically joining said plurality of conductors, wherein said insulating joint members are spaced apart from each other in said second direction such that said conductors are exposed between adjoining ones of said insulating joint members. 13. A light emitting module, comprising: a plurality of thin plate-shaped conductors spaced apart from each other in a first direction and extending in a second direction substantially perpendicular to said first direction; a plurality of light sources each connected between an associated pair of said conductors such that said plurality of light sources are arranged in a matrix pattern; and a plurality of insulating joint members for mechanically joining said plurality of conductors, wherein said plurality of insulating joint members are spaced apart in both of said first and second directions whereby said conductors are exposed between adjoining ones of said insulating joint members. 14. A light emitting module, comprising: a plurality of thin plate-shaped conductors spaced apart from each other in a first direction and extending in a second direction substantially perpendicular to said first direction; at least one light source each connected between an associated pair of said conductors; and a plurality of insulating joint members for mechanically joining said plurality of conductors, wherein a resistor is connected in series with each of said at least one light source. 15. A light emitting module according to claim 14, wherein said insulating joint members are provided one for each of said at least one light source, and each of said insulating joint members is formed with openings for receiving an associated light source and resistor connected in series to said light source. 16. A light emitting module according to claim 14, wherein a conductive piece is provided between adjoining ones of said plurality of thin plate-shaped conductors such that said series-connected at least one light source and resistor are connected to each other via said conductive piece, and wherein said insulating joint member mechanically joins said conductive piece and said conductors. 17. A light emitting module according to claim 14, wherein said at least one light source comprises a bare-chip LED. 18. A light emitting module, comprising: a plurality of thin plate-shaped conductors spaced apart from each other in a first direction and extending in a second direction substantially perpendicular to said first direction; a plurality of conductive pieces disposed between adjoining ones of said conductors so as to be spaced apart from each other in said second direction; a plurality of light sources connected between adjoining ones of said conductive pieces; a plurality of resistors for connecting selected ones of said conductive pieces to one or the other of a pair of said conductors interposing said selected conductive pieces therebetween; and at least one insulating joint member for mechanically joining said plurality of conductors and said conductive pieces. 19. A light emitting module, comprising: first and second conductors spaced apart from each other in a first direction and extending in a second direction substantially perpendicular to said first direction; and at least one light source connected between said first and second conductors, wherein said first conductor has a widthwise recess in which a conductive piece is disposed such that said conductive piece is spaced apart from a portion of said first conductor in said second direction, and wherein said at least one light source is connected to said conductive piece and said portion of said first conductor which are spaced apart from each other in said second direction, and said conductive piece is connected to said second conductor via a resistor. 20. A light emitting module according to claim 19, wherein said widthwise recess of said first conductor is provided on a side facing away from said second conductor, and said resistor strides across said first conductor to connect said conductive piece to said second conductor. 21. A light emitting module according to claim 19, further comprising at least one insulating joint member for mechanically joining said first and second conductors and said conductive piece.

TECHNICAL FIELD The present invention relates to a light emitting module comprising one or more light sources and a method for manufacturing the light emitting module. BACKGROUND OF THE INVENTION It is conventionally known to provide a light emitting module comprising one or more light sources without using a printed circuit board, where the light sources are attached directly between a plurality of conductors extending substantially in parallel (see, e.g., U.S. Pat. No. 5,519,596). In the light emitting module shown in U.S. Pat. No. 5,519,596, a plurality of bus bar pairs are connected via electroconductive extendable joints, and a plurality of LEDs serving as light sources are connected between each bus bar pair by clinching, soldering, spot-welding or the like, to form a so-called matrix circuit comprising a plurality of LED parallel-connections that in turn are connected in series. Before attachment of the LEDs, the bus bars in each pair are connected to each other by integral connection pieces, which, after the attachment of the LEDs, are cut off so as not to short-circuit the LEDs. The light emitting module fabricated by attaching the LEDs directly onto the conductive bus bars can obviate the use of a printed circuit board, and thus can be manufactured at a reduced cost. Further, the light emitting module has a favorable heat dissipation property because heat can be dissipated efficiently from the exposed bus bars and extendable joints. However, in such a light emitting module, the bus bars in each bus bar pair are mechanically connected to each other by the LEDs, and this can result in stress being imposed upon electrical connections between the bus bars and the LEDs and may undesirably lead to faulty electrical connections. Such a problem tends to be caused particularly when the light emitting module is being carried and thus makes the handling of the module cumbersome. Japanese Patent Application Laid-Open (kokai) No. 2000-260206 has disclosed processing a metallic sheet into a plurality of bus bar pairs extending in parallel and connected together by joint portions at either ends, attaching light emitting elements mechanically and electrically between each pair of bus bars at predetermined positions by means of clamping, for example, and cutting off part of the joint portions connecting the bus bar pairs to form a flexible light emitting module. In thus formed light emitting module also, the bus bars in each bus bar pair are connected to each other by the light emitting elements (LEDs), and therefore, contains a problem that the stress imposed on the electric connections between the bus bars and the light emitting elements can cause faulty electric connection. Japanese Patent Application Laid-Open (kokai) No. 2000-10507 has disclosed punching a metallic sheet by means of a punch press machine or the like to form a lead frame comprising a plurality of electrode terminals, to which LED chips are attached, where the electrode terminals are spaced apart from each other at a predetermined interval, subsequently molding a box-shaped reflection case onto the lead frame such that the reflection case covers top and under sides of the lead frame while exposing surfaces of the electrode terminals, and mounting LED chips onto the electrode terminal surfaces by die bonding to whereby manufacture a light emitting display device. In order to prevent warp of the lead frame when molding the box-shaped reflection case, an upper surface of the reflection case is formed with a plurality of pairs of arcuate projections such that each projection pair is aligned with a corresponding LED chip and interposes the LED chip therebetween, and a lower surface of the reflection case is formed with notches at positions between the projections. In this device, the reflection case serves to mechanically support the lead frame, and thus reduces an amount of stress imposed on electric connections between the LED chips and the lead frame. However, the reflection case extending an entire length of the light emitting display device and covering the top and under surfaces of the lead frame hinders heat dissipation as well as makes the device difficult to bend or curve. Further, the light emitting display device uses wire bonding to achieve attachment of the LED chips, and this makes it difficult to achieve attachment of a chip-type LED (or surface mount-type LED), which has electric connection terminals integral with a substantially box-shaped main body and thus has no leads. BRIEF SUMMARY OF THE INVENTION In view of such problems of the prior art, a primary object of the present invention is to provide a light emitting module which has an improved heat dissipation property and allows easy handling without imposing stress on connections between light sources and conductors. A second object of the present invention is to provide a light emitting module which can be bent easily and allows easy handling without imposing stress on connections between light sources and conductors. A third object of the present invention is to provide a light emitting module that can be manufactured easily and efficiently even when chip-type LEDs are used as light sources. A fourth object of the present invention is to provide such a light emitting module at low cost and with simple structure. A fifth object of the present invention is to provide a method for manufacturing such a light emitting module. A sixth object of the present invention is to provide a method for easily and efficiently manufacturing a light emitting module comprising a desired number of light sources. A seventh object of the present invention is to provide a light emitting module that can be easily divided into smaller light emitting modules and allows thus-formed smaller light emitting modules to be used without need for additional current-limiting resistors. According to the present invention, such objects can be accomplished by providing a light emitting module, comprising: a plurality of thin plate-shaped conductors spaced apart from each other in a first direction; at least one light source connected between at least one pair of adjoining ones of the conductors; and at least one insulating joint member for mechanically joining the plurality of conductors, wherein the at least one insulating joint member exposes both sides of at least a portion of the conductors where the light source is mounted. According to such a structure, because the conductors are joined by the insulating joint member, it is possible to keep stress from being placed upon the connections between the light source and the conductors. Further, because the both sides of the light source mount portion of the conductors are exposed, heat generated by the light source can be quickly dissipated. The insulating joint member can be preferably formed by molding a resin material. According to another aspect of the present invention, there is provided a light emitting module, comprising: a plurality of thin plate-shaped conductors spaced apart from each other in a first direction; at least one light source connected between at least one pair of adjoining ones of the conductors; and at least one insulating joint member for mechanically joining the plurality of conductors, wherein the at least one insulating joint member has an opening exposing at least one side of a portion of the conductors, and the light source is inserted into the opening to be connected to the exposed portion of the conductors. The portion of the conductors exposed by the opening of the insulating joint member is hard to deform because it is surrounded by the insulating joint member, whereby preventing stress from being applied on the connections between the light source and the conductors. It will be preferred if the opening of the insulating joint member exposes both sides of the conductors, because, as described above, it can allow the heat from the light source to be dissipated quickly. Also, it will be preferred if the opening has a first opening into which the light source is inserted, and a second opening located at an opposite position with respect to the conductors, wherein the second opening diverges in a direction away from the conductors because when the light source is laser welded to the conductors, the irradiation of laser onto the conductors through the second opening can be achieved easily, facilitating the mounting of the light source to the conductors. Further preferably, dimensions of the opening are determined so as to substantially match those of the light source such that the insulating joint member having the opening serves as a socket for the light source. When the light source comprises a chip-type LED, it will be preferred if the portion of the conductors exposed by the opening of the insulating joint member is provided with extensions for resiliently contact electric connection terminals of the chip-type LED because this can achieve a reliable electric contact between the LED and the conductors. Further, if the insulating joint member has side walls for defining the opening, and a portion of the side walls is formed with an engagement finger for engaging with an upper surface of the chip-type LED when the chip-type LED is inserted into the opening, the mechanical and electrical attachment of the LED can be easily achieved without using laser-welding. When the light source comprises a bullet-type LED having a pair of substantially parallel extending leads, it will be favorable if the insulating joint member has a partition wall within the opening into which the bullet-type LED is inserted, the partition wall extending across the opening in a second direction substantially perpendicular to the first direction, and the portion of the conductors which is exposed by the opening of the insulating joint member and to which the bullet-type LED is mounted has extensions each extending in the first direction to contact the partition wall or to form a small gap between the partition wall and the extensions. In this way, it is possible to achieve quick and reliable attachment of the bullet-type LED by pushing in the pair of leads of the bullet-type LED between the partition wall and the extensions to thereby cramp them therebetween. According to another aspect of the present invention, there is provided a light emitting module, comprising: at least three thin plate-shaped conductors spaced apart from each other in a first direction; a plurality of electric elements each connected between associated pair of the conductors such that the plurality of electric elements are connected in series; and an insulating joint member mechanically joining the at least three conductors, wherein the electric elements comprise at least one light source. The electric elements may include a resistor for preventing an excessive current from flowing through the light source. When the electric elements include a resistor, it is possible to adjust the resistance of the resistor to allow the light emitting module to be directly connected to the power source to be used without need for a step-down transformer or the like. Further, if the light sources consist of LEDs, it is possible to prevent an overcurrent from flowing through the LEDs. In such a light emitting module also, because the mechanical joint of the conductors is achieved by the insulating joint members, stress can be kept from being applied upon the connections between the light sources and the conductors. It may be also possible to short-circuit between an arbitrary pair of conductors to prevent light emission at a position corresponding to the short-circuited pair of conductors. Preferably, the insulating joint member exposes a portion of the at least three conductors, and the exposed portion is formed with holes or grooves extending in a second direction substantially perpendicular to the first direction, because this can allow the conductors to be cut or bent easily along the holes or grooves. Further preferably, the light emitting module comprises a plurality of the insulating joint members, wherein the insulating joint members are spaced apart in the first direction such that the conductors are exposed between adjoining ones of the insulating joint members. In this way, heat can be dissipated efficiently from the exposed conductors. Further, the exposed conductors can be easily bent or flexed, making it possible to change the shape of the light emitting module depending on the place where the module is to be installed or to vary the directions of lights emitted from the light sources. In a preferred embodiment of the present invention; the light-emitting module further comprises an additional conductor extending in the first direction and spaced apart from the at least three conductors, wherein one end of the additional conductor is connected to one of the at least three conductors that is positioned at one end in the first direction, and the other end of the additional conductor is located at substantially the same position as one of the at least three conductors that is positioned at the other end in the first direction. In such a structure, it is possible to supply electricity to the light emitting module by connecting a power source to one of the at least three conductors that is positioned at the other end in the first direction and to the other end of the additional conductor, and thus the connection with the power source is easy. The one end of the additional conductor may be connected to the conductor positioned at the one end in the first direction via a resistor. According to another aspect of the present invention, there is provided a light emitting module comprising: a plurality of thin plate-shaped conductors spaced apart from each other in a first direction and extending in a second direction substantially perpendicular to the first direction; at least one light source connected between at least one pair of adjoining ones of the conductors; and a plurality of insulating joint members for mechanically joining the plurality of conductors, wherein the insulating joint members are spaced apart from each other in the second direction such that the conductors are exposed between adjoining ones of the insulating joint members. In this way, it is possible to efficiently dissipate heat from the exposed conductors as well as bend or flex the exposed portions of the conductors easily. A light source may be mounted to the portion of the conductors exposed between adjoining insulating joint members. If holes or grooves extending in the first direction are formed in the portion of the conductors exposed between adjoining insulating joint members, the conductors can be preferably cut or bent along the holes or, grooves. Further preferably, each of the portions of the conductors exposed between adjoining joint members is formed with a hole for electrical connection to an outer device such that when the light emitting module is cut to form a smaller light emitting module, it is possible, irrespective of the position to be cut, to leave portions of the conductors containing the holes for electrical connection to the outer device, to whereby make electric connection terminals for the outer device in the resulting smaller light emitting module. According to yet another aspect of the present invention, there is provided a light emitting module, comprising: a plurality of thin plate-shaped conductors spaced apart from each other in a first direction and extending in a second direction substantially perpendicular to the first direction; a plurality of light sources each connected between an associated pair of the conductors such that the plurality of light sources are arranged in a matrix pattern; and a plurality of insulating joint members for mechanically joining the plurality of conductors, wherein the plurality of insulating joint members are spaced apart in both of the first and second directions whereby the conductors are exposed between adjoining ones of the insulating joint members. In such a lighting module also, the conductors are joined by the insulating joint members, which can prevent stress from being imposed on the connections between the light sources and the conductors. Further, the heat from the light sources can be quickly dissipated from the portions of the conductors exposed between adjoining joint members, as well as the exposed portions of the conductors can be bent or flexed easily. In the light emitting module as above, the insulating joint member preferably has a portion extending through a portion of at least one of the conductors in a direction of thickness of the conductors. This can prevent shift between the insulating joint member and the conductors. In one embodiment, the portion of at least one of the conductors through which the insulating joint member extends comprises a through-hole extending in the direction of thickness. Also preferably, at least one joint member has a through-hole extending in the direction of thickness of the conductors. This can allow a bolt or the like for securing the light emitting module to a support member to be passed through the through-hole. According to another aspect of the present invention, there is provided a method for manufacturing a light emitting module, comprising the steps of: mechanically joining a plurality of conductors which are spaced apart from each other in a first direction by means of at least one insulating joint member; and mounting at least one light source between at least one pair of adjoining ones of said conductors, wherein in the step of joining the conductors, the insulating joint member exposes both sides of at least a portion of the conductors to which the light source is mounted. In this way, because the joint of the conductors is achieved by the insulating joint member, no stress will be imposed upon the connections between the light source and the conductors. Further, because the both sides of the conductors where the light source is mounted are exposed, the heat generated by the light source can be dissipated quickly. Preferably, the conductors are electrically separated from each other before the light source mounting step, and the method further comprises a step of conducting a conductivity test every time a light source is attached to the conductors. In this way, it is possible to find out a faulty light source or faulty connection between the light source and the conductors, whereby minimizing a later work for fixation and thus improving the work efficiency. According to another aspect of the present invention, there is provided a method for manufacturing a light emitting module, comprising the steps of: mechanically joining a plurality of conductors which are spaced apart from each other in a first direction and extending in a second direction substantially perpendicular to the first direction by means of a plurality of insulating joint members while transporting the conductors in the second direction; and mounting a plurality of light sources between at least one pair of adjoining ones of said conductors such that the light sources are arranged in the second direction, wherein the insulating joint members are spaced apart from each other in the second direction so that the conductors are exposed between adjoining ones of the joint members. In this way, it is possible to form a light emitting module comprising an arbitrary number of light sources arranged in the second direction (or in the direction of extension of the conductors) and connected between an associated pair of conductors. Because the conductors are joined by the insulating joint members, stress can be kept from being placed upon the connections between the light sources and the conductors. Further, heat generated by the light sources can be quickly dissipated from the portions of the conductors exposed between adjoining joint members In the step of joining the conductors, the conductors which are spaced apart from each other may be individually transported in the second direction. Alternatively, it is also possible that in the step of joining the conductors, the conductors are transported in a state that they are connected to each other via connection pieces to form an integral patterned conductor and insulating joint members are formed so as to expose the connection pieces, and the method further comprises, after the step of joining the conductors, a step of cutting off the connection pieces to separate the conductors from each other. In the case that the conductors separated apart from each other are individually transported, wasted material can be reduced because there is no part to be cut off. On the other hand, in the case that the conductors are connected via the connection pieces to form a unitary patterned conductor, easier handling thereof can be achieved. Further, when at least one of the conductors is provided with pilot holes arranged at prescribed intervals in the second direction for engagement with pilot pins of a progressive manufacturing line for transporting the patterned conductor, it is not necessary for each conductor to be provided with the pilot holes because they can be transported integrally with the conductor provided with the pilot holes. Such a patterned conductor can be preferably formed by press-working a metallic thin plate. According to still another aspect of the present invention, there is provided a method for manufacturing a light emitting module, comprising the steps of: mechanically joining a plurality of conductors which are spaced apart from each other in a first direction by means of a plurality of insulating joint members while transporting the conductors in the first direction; and mounting a plurality of light sources between an associated pair of said conductors, wherein at least some of the light sources are connected in series via the conductors and the insulating joint members are spaced apart in the first direction such that the conductors are exposed between adjoining ones of the insulating joint members. This can allow an arbitrary number of conductors to be transported and hence, the number of light sources that are connected in series via the conductors is not limited. Therefore, it is possible, for example, to easily form a light emitting module comprising a number of light sources that match the voltage of a power supply to be connected or a number of light sources that are required for a place where the light source is to be installed. In this case also, the conductors are joined by the insulating joint members and thus, no stress will be imposed upon the connections between the light sources and conductors. Further, the heat generated by the light sources can be swiftly dissipated from the portions of the conductors exposed between adjoining joint members. In the step of joining the conductors, the conductors are preferably transported in a state that they are connected to each other via connection pieces to form an integral patterned conductor and the insulating joint members are formed so as to expose the connection pieces, and the method further comprises, after the step of joining the conductors, a step of cutting off the connection pieces to separate the conductors from each other. The use of the patterned conductor can make the handling easier because the conductors are integral to each other. Further, in the case that the direction of transportation of the patterned conductor coincides with the first direction, it will be preferable if the patterned conductor comprises an additional conductor extending in the first direction and connected to the plurality of conductors via connection pieces, and the method further comprises the step of: joining the additional conductor to the plurality of conductors by means of an insulating joint member; cutting off the connection pieces connecting the additional conductor to the plurality of conductors; and connecting an end of the additional conductor to one of the plurality of conductors at one end of the light emitting module via an electric element (such as a resistor). In this way, an end of the additional conductor and one of the plurality of conductors at the other end of the light emitting module can be used for connection to a power source. In other words, the terminals for connection to the power source can be provided at the same end of the light emitting module, thereby facilitating the connection to the power source. According to another aspect of the present invention, there is provided a method for manufacturing a light emitting module, comprising the steps of: mechanically joining a plurality of conductors which are spaced apart from each other in a first direction and extending in a second direction substantially perpendicular to the first direction by means of a plurality of insulating joint members; mounting a plurality of light sources between at least one pair of adjoining ones of the conductors; and after the light source mounting step, cutting the conductors along a line extending substantially in the first direction at a prescribed position in the second direction. This can form a light emitting module comprising a desired number of light sources arranged in the second direction. Further, the conductors are joined by the insulating joint members to prevent stress from being upon the connections between the light sources and the conductors. According to yet another aspect of the present invention, there is provided a method for manufacturing a light emitting module, comprising the steps of: mechanically joining more than two conductors which are spaced apart from each other in a first direction and extending in a second direction substantially perpendicular to the first direction by means of a plurality of insulating joint members; mounting a plurality of light sources between at least two pairs of adjoining ones of the conductors such that the light sources are arranged in the first direction; and after the light source mounting step, cutting the conductors along a line extending substantially in the second direction, which is perpendicular to the first direction, at a prescribed position in the first direction. This can form a light emitting module comprising a desired number of light sources arranged in the first direction. Further, the conductors are joined by the insulating joint members to prevent stress from being upon the connections between the light sources and the conductors. According to another aspect of the present invention, there is provided a light emitting module, comprising: a plurality of thin plate-shaped conductors spaced apart from each other in a first direction; at least one light source connected between at least one pair of adjoining ones of the conductors; at least one insulating joint member for mechanically joining the plurality of conductors; and an additional conductor spaced apart from the plurality of conductors and extending in the first direction, wherein one end of the additional conductor is connected to one of the plurality of conductors located at one end in the first direction while the other end of the additional conductor is disposed substantially at the same position as one of the plurality of conductors located at the other end in the first direction, and wherein the at least one insulating joint member has an opening exposing at least one side of a portion of the plurality of conductors and the light source is inserted into the opening to be connected to the portion of the conductors exposed by the opening. In this way, the one of the plurality of conductors located at the other end in the first direction and the other end of the additional conductor are positioned close to each other, whereby it is easily achieved to connect them to a power source so as to supply electric power to the light emitting module. Further, because the light source is inserted into the opening of the insulating joint member, it is possible to keep stress from being placed upon the connections between the light source and the conductors and thus easy handling can be achieved. In such a light emitting module, it is possible that a plurality of electric elements including at least one light source are connected in series via the plurality of conductors. Preferably, the connection between the other end of the additional conductor and the one of the plurality of conductors located at the other end in the first direction is achieved via a resistor although the connection may be also achieved by a conductive member such as a jumper wire. Further, it will be favorable if the insulating joint member also joins the additional conductor and the conductor located at the other end in the first direction to each other because it can increase the mechanical strength. Preferably, the insulating joint member has an additional opening in which the resistor is inserted. This keeps stress from being placed upon the connections between the resistor and the conductors, to whereby prevent undesirable detachment of the resistor or faulty connection. Aligning the opening for receiving the light source and the opening for receiving the resistor with each other in the first direction can position the openings close to each other, and thus the openings can be formed in the insulating joint member efficiently. According to yet another aspect of the present invention, there is provided a light emitting module, comprising: a plurality of thin plate-shaped conductors spaced apart from each other in a first direction and extending in a second direction substantially perpendicular to the first direction; at least one light source each connected between an associated pair of the conductors; and a plurality of insulating joint members for mechanically joining the plurality of conductors, wherein a resistor is connected in series with each of the at least one light source. Such provision of resistors which are series-connected to respective light sources can allow a resistance of each resistor to be determined depending on the characteristics of an associated light source so that when a predetermined voltage (e.g., 4V) is applied upon a light source (e.g., LED), a predetermined rated current flows through the light source. This can allow a single light emitting module to contain a plurality of light sources having different characteristics, for example. Further, in a case that such a light source is cut at desired portions to form a smaller light source(s), the resulting smaller light source automatically contains resistors having suitable resistances that match the light sources contained and thus, external resistors are not separately needed. Therefore, it is easy for a user to cut the light emitting module as desired to form smaller light emitting modules and to arrange them in various patterns. Preferably, the insulating joint members are provided one for each of the at least one light source, and each of the insulating joint members is formed with openings for receiving an associated light source and resistor connected in series to the light source. In this way, the insulating joint members can serve as an integral socket for the light source and resistor for steadily holding the same. This makes carrying or cutting of the light emitting module easier. In one embodiment, a conductive piece is provided between adjoining ones of the plurality of thin plate-shaped conductors such that the series-connected at least one light source and resistor are connected to each other via the conductive piece, and the insulating joint member mechanically joins the conductive piece and the conductors. Further, the light emitting module may include, as light sources, not only a bullet-type LED or chip-type LED but also a bare-chip LED. According to still another aspect of the present invention, there is provided a light emitting module, comprising: a plurality of thin plate-shaped conductors spaced apart from each other in a first direction and extending in a second direction substantially perpendicular to the first direction; a plurality of conductive pieces disposed between adjoining ones of the conductors so as to be spaced apart from each other in the second direction; a plurality of light sources connected between adjoining ones of the conductive pieces; a plurality of resistors for connecting selected ones of the conductive pieces to one or the other of a pair of the conductors interposing the selected conductive pieces therebetween; and at least one insulating joint member for mechanically joining the plurality of conductors and the conductive pieces. In such a light emitting module, a plurality of light source series-connections each comprising light sources connected in series via conductive pieces can be connected in parallel between an associated conductors via resistors, to thereby form a so-called series-parallel connection. The number of light sources contained in each light source series-connection may be arbitrarily selected by choosing the position of the resistors for connecting the conductive pieces to the conductors. As a particular case thereof, when each light source series-connection comprises only a single light source, the light sources are connected in parallel between the pair of conductors. Alternatively, only a single light source series-connection may be connected between the pair of conductors. Thus, in this light emitting module, it is possible to connect the light sources in any of series, parallel or series-parallel connections by changing the attachment positions of the resistors or the like. According to yet another aspect of the present invention, there is provided a light emitting module, comprising: first and second conductors spaced apart from each other in a first direction and extending in a second direction substantially perpendicular to the first direction; and at least one light source connected between the first and second conductors, wherein the first conductor has a widthwise recess in which a conductive piece is disposed such that the conductive piece is spaced apart from a portion of the first conductor in the second direction, and wherein the at least one light source is connected to the conductive piece and the portion of the first conductor which are spaced apart from each other in the second direction, and the conductive piece is connected to the second conductor via a resistor. In such a light emitting module, the light source is connected between the conductive piece and the portion of the first conductor spaced apart in the second direction and thus, when a side-view LED having a light emitting surface on its side is used as a light source, it is possible to emit light in a direction perpendicular to the direction of extension of the first and second conductors. Further, provision of a resistor connected in series to each light source can allow the resistance of each resistor to be determined depending on the characteristics of an associated light source. Preferably, the widthwise recess of the first conductor is provided on a side facing away from the second conductor, and the resistor strides across the first conductor to connect the conductive piece to the second conductor. In this way, when the light source consists of a side-view LED, it is possible to mount the light source such that the light emitting surface of the light source is substantially aligned with a widthwise edge of the first conductor away from the second conductor, so as to prevent the conductor to interfere with the light emitted from the light source. Further preferably, the light emitting module may further comprise at least one insulating joint member for mechanically joining the first and second conductors and the conductive piece. This can prevent stress from being placed upon the electric connections between the light source and the conductive piece or conductor. Other and further objects, features and advantages of the invention will appear more fully from the following description. BRIEF DESCRIPTION OF THE DRAWINGS Now the present invention is described in the following with reference to the appended drawings, in which: FIG. 1 is a partial perspective view showing a preferred embodiment of a light emitting module according to the present invention; FIG. 2 is a partial plan view of a patterned conductor used in a preferred embodiment of a process for manufacturing the light emitting module shown in FIG. 1; FIG. 3 is a partial plan view showing a state that insulating joint members are formed on the patterned conductor shown in FIG. 2; FIG. 4 is a partial plan view showing a light emitting module manufactured in accordance with a preferred embodiment of a method for manufacturing a light emitting module of the present invention; FIG. 5a is a plan view of a light emitting module formed by cutting the patterned conductor along the line A in FIG. 4 while FIG. 5b is a plan view of a light emitting module formed by cutting the patterned conductor along the line B in FIG. 4; FIG. 6 is a partial plan view showing another embodiment of a light emitting module according to the present invention; FIGS. 7a and 7b show different ways of bending of the light emitting module shown in FIG. 6; FIG. 8a is a cross-sectional view taken along the line VIII-VIII in FIG. 6, while FIG. 8b is a view similar to FIG. 8a and shows the light emitting module in a flexed state; FIG. 9 is a partial perspective view showing another embodiment of a light emitting module according to the present invention; FIG. 10 is a partial plan view of the light emitting module shown in FIG. 9; FIG. 11 is a partial cross-sectional view taken along the line XI-XI in FIG. 10; FIG. 12a is a plan view of a light emitting module formed by cutting the patterned conductor along the line C in FIG. 10, while FIG. 12b is a plan view of a light emitting module formed by cutting the patterned conductor along the line D in FIG. 10; FIG. 13 is a partial plan view showing a modified embodiment of a light source mount portion of the light emitting module shown in FIG. 9; FIG. 14 is a partial cross-sectional view taken along the line XIV-XIV in FIG. 13; FIG. 15 is a partial cross-sectional view taken along the line XV-XV in FIG. 13; FIG. 16 is a partial plan view showing a patterned conductor which is used in another preferred embodiment of a method for manufacturing a light emitting module according to the present invention; FIG. 17 is a partial plan view showing the patterned conductor of FIG. 16 attached with insulating joint members; FIG. 18 is a plan view showing a light emitting module formed by using the patterned conductor shown in FIG. 16; FIG. 19 is a plan view showing a light emitting module formed by cutting the conductor along the line E in FIG. 18; FIG. 20a is a partial plan view showing a light source mount structure suitable for a bullet-type LED, and FIG. 20b is a partial cross-sectional view taken along the line XXb-XXb in FIG. 20a; FIG. 21 is a partial plan view showing another embodiment of a light emitting module according to the present invention; FIG. 22 is a partial enlarged view showing the light emitting module of FIG. 21 with the joint member being omitted; FIG. 23a is a partial plan view of a light emitting module formed by cutting the light emitting module of FIG. 22 along the line F, while FIG. 23b is a plan view of a light emitting module formed by cutting the conductor along the line G in FIG. 22; FIG. 24 is a partial plan view showing a patterned conductor suitable for forming the light emitting module shown in FIG. 21; FIG. 25 is a partial plan view showing the patterned conductor of FIG. 24 attached with joint members; FIG. 26 is a partial enlarged plan view showing another embodiment of a light source mount portion of the patterned conductor shown in FIG. 24; FIG. 27 is a partial plan view showing another embodiment of a light emitting module according to the present invention; FIG. 28 is an enlarged plan view showing a portion encircled by broken lines in FIG. 27 with joint members 203 being omitted; FIG. 29 is a partial plan view of a light emitting module formed by cutting the conductor 202 along the line H in FIG. 27; FIG. 30 is a partial plan view showing a patterned conductor suitable for forming the light emitting module of FIG. 27; FIG. 31 is a partial plan view showing a state of the patterned conductor of FIG. 30 attached with joint members; FIG. 32 is a partial plan view showing another embodiment of a light emitting module according to the present invention; FIG. 33 is a partial plan view of the light emitting module of FIG. 32 with joint members being omitted; and FIG. 34 is a partial plan view showing a patterned conductor suitable for forming the light emitting module of FIG. 32. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS In the following, preferred embodiments of the present invention will be described with reference to the drawings. FIG. 1 is a partial perspective view showing one preferred embodiment of a light emitting module according to the present invention. As shown in the drawing, the light emitting module 1 comprises: a plurality (six in this embodiment) of thin plate-shaped conductors 2 spaced apart from each other in a first direction (in a direction of x-axis in FIG. 1) and extending in a second direction (in a direction of y-axis in FIG. 1) substantially perpendicular to the first direction; a plurality of insulating joint members 3 for mechanically joining the conductors 2; a plurality of in LEDs 4 mounted between adjoining conductors 2 to serve as light sources. The LEDs 4 are generally arranged in a matrix pattern at predetermined intervals in the first and second directions. The x-axis direction may sometimes be referred to as a column direction while the y-axis direction may be referred to as a row direction. In this embodiment, the LEDs 4 comprise so-called bullet-type LEDs (or lamp-type LEDs) 5 having a pair of substantially parallel leads 5a serving as electric connection terminals as well as so-called chip-type LEDs 6 having electric connection terminals 6a integral with a main body. Of course, the LEDs 4 may comprise LEDs of only one type. The chip-type LED 6 can have significantly reduced lengthwise, widthwise and height-wise dimensions such as 3.5 mm×2.5 mm×2.3 mm. The chip-type LEDs 6 shown in FIG. 1 have a light emitting surface on their top. Other light sources such as incandescent lamps may also be used. The LEDs 4 are connected to exposed portions of the conductors 2 that are not covered by the insulating joint members 3. Each bullet-type LED 5 is attached to the associated conductors 2 with the leads 5a being inserted into lead insertions holes 7 formed in exposed portions of the conductors 2. The chip-type LEDs 6 can be attached to the conductors 2 by laser welding or spot welding, for example. In the light emitting module 1, the LEDs 4 aligned in the second direction are connected in parallel between the associated pair of conductors to form an LED parallel-connection. It should be appreciated that since the conductors other than those positioned at either end are used commonly in different conductor pairs, five conductor pairs are formed in the light emitting module 1 of FIG. 1, four of which are used to form LED parallel-connections, and the conductors in the remaining conductor pair positioned at an end is used to connect a plurality of resistors 8 in parallel therebetween in the same manner that the LEDs 4 are connected. The attachment of the resistors 8 to the conductors 2 can be also achieved easily by inserting leads 8a of the resistors 8 into lead insertion holes 7 formed in the conductors 2 beforehand. It may be also possible to use chip-type resistors (not shown) having no leads 8a. The four LED parallel-connections and one resistor parallel-connection are connected in series in the first direction via conductors 2 to form a matrix circuit as a whole. Thus, application of voltage across the end conductors 2 can cause an electric current to flow through the LEDs 4 to make them emit light. Because the resistors are connected in series to the LEDs 4, it is possible, upon application of a certain voltage, to prevent an excessive voltage from being applied to the LEDs 4 without using a step-down transformer or the like. It should be understood that the resistors 8 may be connected between the conductors of a conductor pair other than that positioned at an end so long as the resistors 8 are connected in series to the LED parallel connections. Another element such as a switch or a positive temperature coefficient thermistor may be used instead of or in addition to the resistors 8. It is also possible to use an electroconductive member such as a jumper wire in place of the LEDs 4 at a certain row of the matrix to short-circuit the adjoining conductors, to thereby prevent light emission at the row. In this embodiment, the insulating joint members 3 that join the conductors 2 each extend in the first direction from the conductor 2 at one end to the conductor 2 at the other end. The insulating joint members 3 are spaced apart from each other in the second direction to expose both sides of portions of the conductors 2 between adjoining joint members 3. As mentioned above, the LEDs 4 are attached to the exposed portions of the conductors 2. The insulating joint members 3 are preferably made of resin and can be formed by molding (e.g., insert molding). Each insulating joint member is formed with a plurality of through-holes 9 such that a bolt or screw (not shown) may be inserted into at least one of the through-holes 9 to secure the light emitting module 1 to a support member (not shown). Portions of each conductor 2 aligned with the through-holes 9 of the insulating joint member 3 are formed with a hole 22 (see FIG. 2) having a larger diameter than the through-hole 9 so that the conductor 2 is not exposed in the through hole 9 when the joint member 3 is formed. This can prevent a voltage from being applied to a metallic bolt inserted into the through-hole 9. Further, because the insulating joint member 3 extends through the holes 22 of the conductor 2 in a direction of thickness of the conductor 2 (z-axis direction in FIG. 1), it is possible to prevent the insulating joint member 3 from inadvertently sliding with respect to the conductor 2. In the light emitting module 1 having the above structure, because the mechanical joint of the plurality of conductors 2 is achieved by the insulating joint members 3 formed by molding, it is possible to keep stress from being imposed upon connections between the LEDs 4 and the conductors 2. Therefore, when the light emitting module 1 is being carried or when the light emitting module 1 is used in an environment such as in an automobile where the module 1 tends to be applied with substantial oscillations, there is no concern about undesirable open circuit. The insulating joint members 3 expose both sides of various portions of the conductors 2 inclusive of the portions where the LEDs 4 are mounted, and the thickness of the joint members 3 serves to ensure that a space is created between the conductors 2 and the support member (not shown) when the light emitting module 1 is secured to the support member, whereby achieving favorable heat dissipation characteristics. Further, because the conductors 2 are of a thin plate-shape, they can be easily bent or flexed at portions where the joint members 3 are not provided. Now, with reference to FIGS. 2-4, a preferred method for manufacturing the light emitting module 1 of FIG. 1 is described. It should be noted that in these drawings, component parts corresponding to those of FIG. 1 are denoted with the same reference numerals. According to the preferred embodiment of the present invention, first, a thin plate-shaped conductor (patterned conductor) 20 having a prescribed pattern as shown in the plan view of FIG. 2 is prepared. The patterned conductor 20 comprises: a plurality (e.g., six) of thin plate-shaped conductors 2 spaced apart from each other in the first direction (x-axis direction in the drawing) and extending in the second direction (y-axis direction in the drawing) substantially perpendicular to the first direction; and a plurality of connection pieces 21 connecting the conductors 2 in the first direction. The conductors 2 positioned at either end have a narrower width than the central four conductors 2. As described above, portions of each of the central four conductors 2 aligned with the through-holes 9 of the insulating joint members 3 are formed with holes 22 having a slightly larger diameter than the through-holes 9. Further, in the conductor 2 second to the bottom in FIG. 2 is formed with pilot holes 23 which are arranged at a predetermined interval in the second direction such that when the patterned conductor 20 is transported by a progressive manufacture line (not shown), which may include a progressive press machine or the like, the pilot holes 23 can engage pilot pins of a transportation mechanism of the progressive manufacture line. Thus, in this embodiment, the direction of transportation (or lengthwise direction) of the patterned conductor 20 is perpendicular to the first direction in which the conductors 2 are spaced apart from each other and coincides with the second direction in which the conductors 2 extend. In addition to the conductors 2 for mounting the light sources thereon, it may be possible to provide an additional conductor (side frame) extending in the second direction in parallel with the end conductor 2 and connected to the same via connection pieces and to form the pilot holes in the additional conductor. Further, as described above, in order to facilitate attachment of the LEDs 5 and resistors 8 having leads 5a, 8a, respectively, the patterned conductor 20 is formed with holes 7 for receiving the leads 5a, 8a at appropriate positions determined by taking into account a distance between the pair of leads of each element to be mounted. A surface (top surface) on the side of the patterned conductor 4 to which the LEDs 4 are mounted may be plated with a light-reflecting material to effectively serve as a reflector surface. The patterned conductor 20 as described above can be formed efficiently by press-working a tape-shaped metallic thin plate having the pilot holes 23 preformed therein while transporting it by the progressive press machine. The patterned conductor 20 thus formed is tape-shaped and can be wound into a roll. Instead of the press-working, the patterned conductor 20 may be formed by etching a metallic thin plate having an appropriate length. Next, as shown in FIG. 3, the insulating joint members 3 are formed by molding to join the conductors 2 in the first direction where the connection pieces 21 are exposed by the joint members 3. The molding can be carried out in the same progressive manufacturing line as that for performing the press-working. It may be also possible to roll up the patterned conductor 20 and carry it to another manufacturing line where the molding is carried out. After the molding, the connection pieces 21 are cut off by press-working or the like as shown by hatching in FIG. 3. This electrically separates the conductors 2 from each other but the joint members 3 keep the conductors 2 mechanically held together. Then, as shown in FIG. 4, elements such as the chip-type LEDs 6 and resistors 8 are attached to the conductors 2 to form the light emitting module 1. The attachment of the chip-type LEDs 6 to the conductors 2 can be achieved by laser welding, spot welding, soldering, etc. Because both of the upper and under sides of the light source mount portions of the conductors 2 are exposed, it is possible to place the chip-type LEDs on the upper side of the conductors 2 and carry out laser welding by irradiating laser onto the light source mount portion from underside. The resistors 8 having the leads 8a are attached to the conductors 2 by inserting the leads 8a into the holes 7 of the conductors 2. Though not shown in FIG. 4, if the LEDs 5 having leads 5a are used instead of the chip-type LEDs 6, the attachment of the LEDs 5 can be achieved easily by inserting the leads 5a into the holes 7 of the conductors 2 in the same fashion as in the attachment of the resistors 8. It is also possible to conduct laser welding or the like after the insertion of the leads 5a, 8a into the holes 7. In this embodiment, when the LEDs 6 are mounted to the conductors 2, the conductors 2 are electrically separated from each other and therefore, it is possible to perform an electric conduction test after each attachment of the LEDs 6, to thereby check the state of connection between the LEDs and conductors 2 and/or the integrity of the LEDs 6 themselves. This can allow a faulty LED 6 or a faulty connection between LEDs 6 and conductors 2 to be found at an earlier stage, minimizing a later work for fixation and thus improving the work efficiency. In the above embodiment, the insulating joint members 3 are formed by molding on the patterned conductor 20, in which the conductors 2 are connected together via integral connection pieces 21, to join the conductors 2 together. However, if each conductor 2 has a relatively short length, it is possible to simply arrange the conductors 2 at certain intervals and then join the conductors 2 by molding. Further, in the case that the conductors 2 are lengthy, if each conductor 2 is formed with the pilot holes 23 or the like and can be transported individually, it is possible to arrange the separated conductors 2 such that they are spaced apart from each other in the widthwise direction and then join the conductors 2 by molding while transporting the same. The light emitting module 1 having the LEDs 6 arranged in the matrix fashion as shown in FIG. 4 may be cut at appropriate positions to form a smaller light emitting module comprising the LEDs 6 in an arbitrary number of rows and columns. For instance, cutting along the line A in FIG. 4 provides a two-row, one-column light emitting module 1a comprising a series-connected single LED 6 and single resistor 8, as shown in FIG. 5a. Cutting along the line B in FIG. 4 provides a three-row, two-column light emitting module 1b comprising two pairs of parallel-connected LEDs 6 and a pair of parallel-connected resistor 8, with the two LED pairs and the resistor pair being connected in series. In these light emitting modules 1a, 1b also, the conductors 2 on which the LEDs 6 are mounted are mechanically joined by the joint members 3, preventing stress from being placed upon the connections between the LEDs 6 and the conductors 2. Further, because both sides of the conductors 2 are exposed between adjoining insulating members 3 and the LEDs 6 are mounted to the exposed portions, it is possible to quickly dissipate the heat from the LEDs 6 via the exposed conductors 2. FIG. 6 is a top plan view showing another embodiment of a light emitting module according to the present invention. In this drawing, the chip-type LEDs 6 and resistors 8 are shown in broken lines. Of course, bullet-type LEDs 5 may be used instead of the chip-type LEDs 6. Like the light emitting module 1 shown in FIG. 1, this light emitting module 31 comprises a plurality of conductors 32 spaced apart from each other in one direction and insulating joint members 33 for mechanically joining the conductors 32, where the LEDs 6 and resistors 8 are connected between adjoining conductors 32. In this embodiment, each insulating joint member 33 has a narrower width at portions overlapping the conductors 32, and thus through-holes 35 for inserting bolts or the like therein to secure the light emitting module to a support member (not shown) are formed in portions corresponding to spaces between adjoining conductors 32. Further, portions of each conductor 32 other than those where the LEDs 6 are to be mounted are provided with a narrower width, and widthwise (or column-wise) extending holes 36 are formed in portions of each conductor 32 near the insulating joint members 33. These allow easier bending or cutting of the light emitting module 31 along a column-wise extending line connecting the holes 36. Because the light emitting module 31 can be easily bent, it is possible to arrange the light emitting module 31 so as to conform to a shape of the setting place or to vary the direction of lights emitted from the LEDs 6 to improve the freedom of illumination design. For example, as shown in the side view of FIG. 7a, it is possible to direct the lights from the LEDs 6 in an oblique direction with respect to the direction of extension of the light emitting module 31. Alternatively, as shown in the side view of FIG. 7b, the light emitting module 31 can be bent such that the lights from the LEDs 6 are directed in two different oblique directions with respect to the direction of extension of the light emitting module 31. FIG. 8a is a cross-sectional view taken along the line VIII-VIII of FIG. 6. As clearly shown in FIG. 8a, a plurality of row-wise extending grooves 37 having a depth of 0.2-0.4 mm, for example, are formed on both of upper and under sides of each insulating joint member 33 at prescribed column-wise positions. As shown in the set of grooves 37 second to the left in FIG. 8a, the grooves 37 may extend to the conductors 32. Further, as seen in FIG. 6, a plurality of row-wise extending holes 38 are formed in portions of the conductors 32 exposed between adjoining insulating joint members 33 at positions column-wise aligned with the grooves 37. In this way, as shown in FIG. 8b, the light emitting module 31 can be easily bent or flexed along lines connecting the grooves 37 and holes 38 in the row direction. This can also contribute to increasing the freedom of illumination design. Further, the light emitting module 31 can be cut easily along such a line. FIG. 9 is a partial perspective view showing yet another embodiment of a light emitting module according to the present invention, FIG. 10 is a top plan view thereof, and FIG. 11 is a partial cross-sectional view taken along the line XI-XI of FIG. 10. It should be noted that FIG. 10 only shows chip-type LEDs 6 as light sources, and the right-end column shows a state where the chip-type LEDs 6 are yet to be mounted. Like the light emitting module 1 shown in FIG. 1, this light emitting module 51 also comprises: a plurality of conductors 52 spaced apart from each other in one direction; insulating joint members 53 for mechanically joining the conductors 52; and a plurality of LEDs 6 connected between adjoining conductors 52. Each insulating joint member 53 is formed with through-holes 55 through which bolts or the like for securing the light emitting module 51 to a support member are passed. In this embodiment, an upper side of each insulating joint member 53 mechanically joining the conductors 52 is formed with openings 56, each of which has a rectangular shape when seen in the plan view and exposes an upper surface of an associated pair of adjoining conductors 52. This allows a chip-type LED 6, for example, to be inserted into the opening 56 so that the LED 6 is attached to the exposed parts of the conductors 52. Further, as best shown in FIG. 11, openings 57 are formed in the underside of each insulating joint member 53 such that they align with the openings 56 and communicate with the same. The openings 57 not only expedite dissipation of heat from the LEDs 6 but also allow laser to be passed therethrough so that the LEDs can be laser-welded to the conductors 52 easily. The walls of the insulating joint member 53 defining each lower openings 57 are tapered so that the opening 57 diverges in the direction away from the conductors 52 so that in the laser-welding process, the laser can be irradiated onto the conductors 52 easily from the underside through the opening 57. Each upper opening 56 may have dimensions that match those of the chip-type LED 6 so that the insulating joint members 53 having such openings 56 can serve as sockets for positioning or holding the chip-type LEDs 6. Further, as seen in the bullet-type LEDs 5 widthwise second and third to the right in FIG. 9, the upper surface of the insulating joint member 53 can abut an underside of the main body of the bullet-type LEDs 5 to prevent the leads 5a of the LEDs 5 from bending to cause the LEDs 5 to incline in the soldering process, for example. This favorably eliminates a need for an additional skirt member for preventing the inclination of the LED 5. As best shown in the lowermost row in FIG. 10, instead of the LEDs 6, chip-type resistors 58 may be inserted into the openings 56 and attached to the conductors 52. Further, as shown in the rightmost column in FIG. 10, in order for permit attachment of elements having leads, such as the bullet-type LEDs 5 or resistors 8, portions of the pair of conductors 52 exposed by each opening 56 of the insulating joint member 53 are formed with holes 59 for receiving the leads 5a, 8a. The portions of the conductors 52 exposed by the openings 56, 57 of the insulating joint members 53 are each surrounded by an associated one of the insulating joint members 53, and thus are less deformable than the portions of the conductors 52 external of the insulating joint members 53. Therefore, attachment of the LEDs 5, 6 or resistors 8, 58 to the portions of the conductors 52 exposed by the openings 56, 57 can reduce the stress imposed upon the connections between such elements and the conductors 52. Referring to FIG. 10 again, in the light emitting module 51, portions of each conductor 52 between adjoining insulating joint members 53 are each formed with column-wise extensions 61 where holes 62 are provided. In this way, if, after the attachment of the LEDs 6, the conductors 52 are cut along the line C in FIG. 10 for example, to form a light emitting module 51a having electric elements of five rows by three columns (among which, one row constitutes of resistors 58) as shown in FIG. 12a, the conductor portions including the extensions 61 and holes 62 can be used as connection terminals for facilitating connection to an external device such as a power supply. The holes 62 can allow conductive leads or the like for connection with the external device to be passed therethrough, to whereby allow easy connection. It is also possible to bend the extensions 61 so as to make crimp contacts for connecting to the lead wires of the external device. If the cutting is made along the line D in FIG. 10, a light emitting module 51b comprising a single LED 6 and a single resistor 58 which are connected in series as shown in FIG. 12b. In such a case also, the extensions 61 with the holes 62 can be used as connection terminals. As described above, by forming the holes 62 in the portions of the conductors 52 exposed between the adjoining insulating joint members 53, it is possible that when the light emitting module 51 is cut to form a light emitting module 51a, 51b containing a desired number of LEDs 6, proper conductor portions having the holes 62 may be left uncut such that the conductor portions may be used in the resulting light emitting module 51a, 51b as connection terminals for electrical connection to the external device. It should be noted that the extensions 61 may not be necessarily provided so long as there is enough space ensured for forming the holes 62. Further, though in the embodiment shown in the drawings, the conductors 52 at either end are formed with the extensions 61 only on one lateral side, the extensions may be formed on both lateral sides. FIG. 13 is a partial enlarged view showing another embodiment of the light source mount portion in the light emitting module 51 shown in FIGS. 9-12. FIG. 14 is a cross-sectional view taken along the line XIV-XIV of FIG. 13, and FIG. 15 is a cross-sectional view taken along the line XV-XV of FIG. 15. This embodiment is suitable for mounting the chip-type LEDs 6 having a substantially parallelepiped shape with no leads. FIG. 13 shows a state in which the LED 6 is yet to be mounted, and FIG. 15 shows the mounted LED 6 in phantom lines. As shown in FIG. 13, in this embodiment, portions of the pair of conductors 52 exposed by the openings 56, 57 of the insulating joint member 53 for contacting the electric connection terminals 6a of the chip-type LED 6 have a pair of substantially parallel extensions 70 each of which extends to a vicinity of the opposing conductor 52, such that the extensions 70 can be bent in an upward direction to resiliently contact the terminals 6a on the underside of the chip-type LED 6. Each of the row-wise opposing pair of walls defining the upper opening 56 of the joint member 53 for receiving the chip-type LED 6 is formed with a pair of column-wise spaced slits 71 so that an upright engagement piece 72 is formed therebetween. The engagement pieces 72 can be flexed outwardly as shown by the arrows in FIG. 15 to facilitate the insertion of the chip-type LEDs 6 into the openings 56. An inward projection 73 is formed at a top end of each engagement piece 72 so that when the chip-type LED 6 is pushed into the opening 56, the inward projection 73 serves as a finger that presses the LED 6 from above to prevent inadvertent detachment of the LED 6 (see FIG. 15). In such a structure, it is possible by just pushing the chip-type LED 6 into the corresponding opening 56 to not only achieve quick mechanical attachment of the LED 6 but also achieve reliable electric contact between the LED 6 and the conductors 52 without using laser-welding or the like because the widthwise extensions 70 of the pair of conductors 52 resiliently contact the electric connection terminals 6a on the underside of the LED 6. Further, at four corners of each opening 56 of the insulating joint members 53 slightly above the conductors 52, inward projections 74 are formed to limit the insertion of the chip-type LED 6 into the opening 56. This prevents a single electric connection. Terminal 6a of the LED 6 from contacting both of the pair of extensions 70. In the manufacturing process of the light emitting module 1 described with reference to FIGS. 2-4, the direction of transportation (or lengthwise direction) of the tape-shaped patterned conductor 20, in which the plurality of spaced-apart conductors 2 are integrally connected via connection pieces 21, was perpendicular to the direction in which the conductors 2 are spaced apart (or first direction) and thus coincided with the direction in which the conductors 2 extend (or second direction). Therefore, the number of light sources such as LEDs 6 parallel-connected between adjoining conductors 2 could be arbitrarily selected but the number of light sources (or light source parallel connections) to be connected in series was limited (the maximum number was (number of conductors 2)-1, when no resistors are connected). However, it may be sometimes desirable that the number of light sources to be connected in series can be selected arbitrarily in accordance with various power supply voltages. FIGS. 16-18 show an embodiment of a method for manufacturing a light emitting module according to the present invention that allows arbitrary selection of the number of light sources to be connected in series. First, a patterned conductor 100 as shown in FIG. 16 is prepared. The patterned conductor 100 is transported from left to right in the drawing. The patterned conductor 100 comprises a plurality of conductors 101 which are spaced apart from each other in a direction of transportation of the patterned conductor 100, and each of the conductors 101 extends in a direction perpendicular to the transportation of the patterned conductor 100. Therefore, in this embodiment, the first direction in which the conductors 100 are spaced apart from each other coincides with the direction of transportation of the patterned conductor 100 while the second direction in which the conductors 100 extend is perpendicular to the direction of transportation of the patterned conductor 100. One end (upper end in the drawing) of each conductor 101 is connected via a connection piece 103 to a first side frame 102 that extends in the direction of transportation of the patterned conductor 100. The other end of each conductor 101 is connected via a connection piece 105 to a power supply connection bar 104 extending in the direction of transportation of the patterned conductor 100. The power supply connection bar 104 is in turn connected via connection pieces 107 to a second side frame 106, which also extends in the direction of transportation of the patterned conductor 100. The first and second side frames 102, 106 are formed with pilot holes 108 so as to be engageable with pilot pins of a progressive manufacturing line (not shown) to achieve transportation of the patterned conductor 100. Further, the other end (or lower end in the drawing) of each conductor 101 has an extension 109 that extends to a position substantially aligned with a space between adjoining conductors 101 such that resistors or the like can be mounted between the extension 109 and the power supply connection bar 104 as described later. The patterned conductor 100 is also provided with holes or grooves 110 which are aligned in the first direction as well as holes or grooves 111 which are aligned in the second direction for permitting easy cutting of the patterned conductor 100 and/or easy bending of a light emitting module 120 (FIG. 18) to be formed. Next, as shown in FIG. 17, a plurality of insulating joint members 113, 114 are formed by molding to join adjoining conductors 101 to each other. In this embodiment, first joint members 113 having an opening 15 for receiving the light source therein and second joint members 114 formed with a through-hole 116 through which a bolt or the like is passed to secure the resulting light emitting module 120 (FIG. 18) to a support member or the like are arranged alternately in a direction perpendicular to the direction of transportation of the patterned conductor 100 (i.e., in a direction of extension of the conductors 101) along a gap between adjoining conductors 101. It may be also possible to integrally form the first and second joint members 113, 114 which are aligned in the direction of extension of the conductors 101, but making them spaced apart from each other as shown in the drawing not only can save the amount of material and thereby reduce the manufacturing cost but also can facilitate bending the conductors 101 at a point between the joint members 113, 114 or cutting the conductors 101 to form a light emitting module of a desired size. Referring to FIG. 16 again, portions of each conductor 101 where the second joint members 114 are provided are formed with recesses 112 each having portions widening in the first and second directions. The second joint members 114 extend through the recesses 112 in the thickness direction of the conductors 101 and therefore the second joint member 114 and the conductors 101 are joined firmly to prevent shift therebetween in both the first and second directions. Further, owing to the provision of the recesses 112, the conductors 101 are not exposed within the through-holes 116 formed in the second joint members 114. As shown in FIG. 17, the first and second joint members 113, 114 are also spaced apart in the direction of transportation of the patterned conductor 100 (or in the first direction in this embodiment) to expose the conductors therebetween. This can allow heat dissipation from the exposed parts of the conductors 101 as well as easy bending or flexion of the conductors 101 at such exposed parts. Though not shown in the drawings, each first joint member 113 has lower openings as in the embodiment shown in FIGS. 9-11, whereby both the upper and under sides of the conductors 101 are exposed within the first joint member 113. The joint members 113 at the lowermost row in FIG. 17 not only join adjoining conductors 101 to each other but also join the power supply connection bar 104 to the conductors 101. These joint members 113 each comprise, in addition to the opening 115 for exposing portions of the conductors 101 where the LED is to be mounted, an opening 117 for exposing the extension 109 of the conductor 101 and a portion of the power supply connection bar 104 so that a resistor can be attached thereto. Because the extension 109 substantially extends to a point between the adjoining conductors 101, the opening 115 for receiving the LED and the opening 117 for receiving the resistor can be aligned in the first direction (or the direction in which the conductors 101 are spaced apart) and brought as close to each other as possible such that the openings 115, 117 are efficiently formed in the same insulating joint member 113. After forming the joint members 113, 114 by molding, the connection pieces 103, 105, 107 are cut off as indicated by hatching in FIG. 17. This electrically separates adjoining conductors 101 from each other but the joint members 113, 114 hold the conductors 101 together. Then, as shown in FIG. 18, light sources such as the chip-type LEDs 6 are inserted into the openings 115 of the first joint members 113 to mount them on the conductors 101, and a conductor 101 at an appropriate position is cut to form a light emitting module 120 comprising a desired number (five in the shown embodiment) of light source parallel connections, each of which has a plurality (five in the shown embodiment) of parallel-connected light sources, where the light source parallel connections are connected in series in the direction of transportation of the patterned conductor 100. It should be noted that by changing the position to cut the conductor 101, the number of light source parallel-connections that are connected in series can be arbitrarily selected. As shown in FIG. 18, on one end in the first direction (right end in the drawing) of the resulting light emitting module 120, two chip-type resistors 58 are inserted into the opening 117 of the lowermost joint member 113 to electrically connect the extension 109 of the conductor 101 and the power source connection bar 104. In this way, it is possible to connect a power supply to the conductor 101 and the power supply connection bar 104 on the other end (the left end in the drawing) to supply electric power to the light emitting module 120. Thus, the provision of the power supply connection bar 104 extending in the first direction can easily make a light emitting module 120 that can be supplied with electric power at its one end. In the above embodiment, it is possible to arbitrarily change the number of light source parallel-connections that are connected in series in accordance with an amount of voltage of a power supply or the like so that the light emitting module 120 can be directly connected to the power supply while suppressing the amount of electric power wastefully consumed by the resistors 58. Further, by cutting the light emitting module 120 along the line E in FIG. 18, it is possible to obtain a light emitting module 120a comprising only one row of series-connected LEDs 6 as shown in FIG. 19. It is also possible to form the light emitting module 120a by preparing another patterned conductor having a shape as obtained by cutting the patterned conductor 100 along the line E, and then performing the molding and LED mounting in the same way as described above. It may be possible to omit the first joint members 113 in the above embodiment. However, as described above with respect to the embodiment shown in FIGS. 9-12, attaching the light sources to the conductors 101 within the openings 115 of the first joint members 113 can contribute keeping stress from being placed upon connections between the light sources and the conductors 101. Further, when the through-holes 116 for passing bolts or the like therethrough for attaching the light emitting module to a support member are not needed, the second joint members 114 may be omitted. In such a case, however, in order to improve the strength of joint between the first joint members 113 and the conductors 101, the conductors 101 can be preferably formed with holes such that the first joint members 113 can extend therethrough in the direction of thickness of the conductors 101. FIGS. 13-15 have shown a preferred embodiment suitable for inserting the chip-type LEDs into the openings 56 formed in the insulating joint members 53 to connect them to the conductors 52, but LEDs may include bullet-type LEDs 5 having leads 5a. FIGS. 20a and 20b show an embodiment suitable for the bullet-type LEDs. FIG. 20a is a plan view showing an LED mount portion and FIG. 20b is a cross-sectional view taken along the line XXb-XXb in FIG. 20a. It should be noted that in FIG. 20a, the direction of the LED mount portion is rotated by 90 degrees with respect to FIG. 13. As shown, in this embodiment, an insulating joint member 53a joining the conductors 52 has an opening 121 at a position between the pair of conductors 52 to which the bullet-type LED 5 is to be connected, where the opening 121 is circular so as to conform to the shape of the bullet-type LED 5. The insulating joint member 53a further comprises a partition wall 123 extending across the opening 121 in a direction of extension of the conductors 52. Each of the pair of conductors 52 to which the bullet-type LED 5 is to be connected has an extension 122 that extends out toward the partition wall 123 so as to be exposed within the opening 121. As best shown in FIG. 20b, before the bullet-type LED is mounted, an end portion of each extension 122 of the conductors 52 is curved downward to form a small gap between the end portion and the partition wall 123. Preferably the gap is smaller than the lead 5a of the bullet-type LED 5. The end portion of the extension 122 may contact the partition wall 123. In this way, by pushing the leads 5a of the bullet-type LED 5 into the gaps between the extensions 122 and the partition wall 123, the leads 5a are cramped between the extensions 122 and the partition wall 123. Due to the resiliency of the extensions 122, the extensions 122 press the leads 5a against the partition wall 123, thus achieving reliable contact between the extensions 122 and the leads 5a. The downward curve of the end portion of each extension 122 allows the lead 5a to be pushed into the gap easily but when the lead 5a is being pulled out, a frictional force is generated between the lead 5a and the extension 122. Thus, without laser-welding or the like, the LED 5 can be held firmly and prevented from easily coming out of place. Further, because the shape (dimensions) of the opening 121 is determined so as to conform to that of the bullet-type LED 5, when the LED 5 is inserted into the opening 121, the wall of the insulating joint member 53a defining the opening 121 serves to hold the LED 5. The partition wall 123 abuts the underside of the LED 5 to limit the insertion of the LED 5 into the opening 121. Because the laser-welding is unnecessary, the opening 121 may not have to extend to the underside of the insulating joint member 53a to expose the underside of the extensions 122 of the conductors 52 although in view of heat dissipation, it is preferred that the underside of the extensions 122 is exposed. FIG. 21 is a partial plan view showing another embodiment of a light emitting module according to the present invention. As in the above embodiments, this light emitting module 151 comprises: a plurality (six in this embodiment) of thin plate-shaped conductors 152 spaced apart from each other in a first direction (or x-axis direction) and extending in a second direction (or y-axis direction) substantially perpendicular to the first direction; a plurality of insulating joint members 153 for mechanically joining the conductors 152; and a plurality of chip-type LEDs 156 connected between adjoining conductors 152 to serve as light sources. The LEDs 156 are arranged in a matrix pattern with predetermined intervals in the first and second directions. In this embodiment, a resistor 157 and a zener diode 158 are provided for each LED 156. The insulating joint members 153 are provided so as to correspond to individual LEDs 156, and each insulating joint member 153 is formed with three openings 173, 174, 175 for accommodating the LED 156, resistor 157 and zener diode 158, respectively (see FIG. 25). Such insulating joint members 153 can be preferably formed by molding. FIG. 22 is an enlarged top plan view showing a way of attachment of a single LED 156 and its associated resistor 157 and zener diode 158 between adjoining conductors 152, with the insulating joint member 153 being omitted. As shown, a conductive piece 159 is provided between the adjoining conductors 152. The LED 156 and the zener diode 158 are connected in parallel between the conductive piece 159 and one conductor 152, while the resistor 157 is connected between the conductive piece 159 and the other conductor 152. Therefore, the LED 156 and the resistor 157 are connected in series between the adjoining conductors 152. The zener diode 158 connected in parallel with the LED 156 functions to prevent an overvoltage from being applied to the LED 156. A resistance of the resistor 157 connected in series to the LED 156 is selected depending on the characteristics of the LED 156 such that when a predetermined voltage (e.g., 4V) is applied between the adjoining conductors 152, a predetermined rated current flows through the LED 156. In this way, the light emitting module 151 can comprise a plurality of LEDs 156 having different characteristics. The light emitting module 151 having the LEDs 156 arranged in a matrix pattern as shown in FIG. 21 can be cut at appropriate portions to form a smaller light emitting module comprising the LEDs 156 in an arbitrary rows and columns. For example, by cutting the light emitting module 151 along the line F in FIG. 21, a light emitting module 151a comprising an arbitrary number of parallel-connected LEDs 156 as shown in FIG. 23a can be provided. Alternatively, by cutting the light emitting module 151 along the line G in FIG. 21, a light emitting module 151b comprising five series-connected LEDs 156 as shown in FIG. 23b can be formed. Because in the light emitting module 151 each LED 6 is connected in series with a resistor having an appropriate resistance as described above, a smaller light emitting module obtained by cutting the light emitting module 151 automatically comprises resistors having appropriate resistances suitable for the LEDs 156 contained therein irrespective of the position where the cutting is done, and thus there is no need to provide additional outer resistors. Thus, it is easy for a user to cut the light emitting module 151 as desired to form smaller lighting modules, and arrange them in various patterns. As in the embodiments described above, in the light emitting module 151 also, the mechanical joint of the conductors 152 is achieved by the insulating joint members 153, and thus it is possible to keep stress from being placed upon electric connections between the conductors 152 and the LEDs 156. FIG. 24 is a plan view showing a patterned conductor 170 suitable for forming the light emitting module 151 shown in FIG. 21. As shown, in this patterned conductor 170, adjoining conductors 152 are connected to each other via a plurality of connection pieces 171. Further, the conductive pieces 159 located between adjoining conductors 152 are connected to one of the adjoining conductors 152 via connection pieces 172. Such a patterned conductor 170 can be formed easily by press-working a thin plate-shaped conductor such as a metal. As shown in FIG. 25, after forming the insulating joint members 153 by molding to hold adjoining conductors 152 together, the connection pieces 171, 172 are cut off as indicated by hatching in the drawing. Each insulating joint member 153 has openings 173, 174, 175 for receiving the associated LED 156, resistor 157 and zener diode 158, and the openings 173, 174, 175 expose portions of the conductors 152 and conductive piece 159. Subsequently, the LED 156, resistor 157 and zener diode 158 are inserted into the openings 175, 174, 175 of each insulating joint member 153 and attached to the conductors 152 and conductive piece 159 by laser welding, spot welding, soldering or the like to form the light emitting module 151. The light emitting module 151 of FIG. 21 uses the chip-type LEDs 156 as light sources, but it is preferable that bullet-type LEDs having leads (e.g., the LED 5 in FIG. 1) can be also used as light sources. For this reason, as shown in an enlarged partial view of FIG. 26, the light source mount portions of the patterned conductor 170 may be formed with holes 176 for receiving and holding the leads 5a of the LEDs 5. As shown, each hole 176 is formed as an H-shaped cut to define a pair of opposed extensions 177, 177 so that when the lead 5a is inserted between the extensions 177, 177, they flex to crimp the lead therebetween. FIG. 27 is a partial plan view showing another embodiment of a light emitting module according to the present invention. This light emitting module 201 comprises: a plurality (five in this embodiment) of thin plate-shaped conductors 202 spaced apart from each other in a first direction (or x-axis direction) and extending in a second direction (or y-axis direction) substantially perpendicular to the first direction; a plurality of insulating joint members 203 for mechanically joining the conductors 202; and a plurality of chip-type LEDs 206 connected between adjoining conductors 202 to serve as light sources. The LEDs 206 are arranged in a matrix pattern with predetermined intervals in the first and second directions. The insulating joint members 203 are provided for respective LEDs 206 and each insulating joint member 203 is formed with an opening 223 for accommodating the LED 206 therein. Such insulating joint members 203 can be preferably formed by molding a resin material. In the light emitting module of FIG. 27, a plurality of LED series-connections, each of which comprises a plurality (three in this embodiment) of series-connected LEDs 206, are connected between adjoining conductors 202 to form a so-called series-parallel connection. FIG. 28 is an enlarged plan view showing a portion encircled by broken lines in FIG. 27, with the insulating joint members 203 being omitted to show electric connection of a single LED series-connection. As shown, disposed between adjoining conductors 202 are a plurality of conductive pieces 209 which are spaced apart from each other in a direction of extension of the conductors 202, and each LED 206 is connected between an associated pair of conductive pieces 209. The conductive pieces 209 positioned at either end of each LED series-connection are connected to the conductors 202 via respective resistors 207. As shown in FIG. 27, each joint member 203 is formed with two openings 224 that can receive the resistors 207 in addition to the opening 223 for receiving the LED 6, and when the resistors 207 are not inserted, the openings 224 expose conductors 202 and conductive pieces 209. In the light emitting module 201 also, the conductors 202 are joined by the insulating joint members 203, and thus stress will not be imposed upon electric connections between the conductors 202 and the LEDs 206. Further, it is possible to cut the light emitting module 201 along the line H in FIG. 27, for example, to form a linear light emitting module 201a having the LEDs 206 arranged in a line as shown in FIG. 29. It is further possible to form a plurality of light emitting modules as above or of any other shapes and arrange them in a variety of patterns. FIG. 30 is a partial plan view showing a patterned conductor 220 suitable for forming the light emitting module 201 shown in FIG. 27. This patterned conductor 220 comprises a plurality of conductive pieces 209 which are disposed between adjoining conductors 202 and spaced apart in a direction of extension of the conductors 202, and each conductive piece 209 is connected to the conductors 202 via connection pieces 221. The relatively wide conductors 202 disposed at an intermediate position are formed with substantially rectangular holes 222. The insulating joint members 202 extend through the holes 222 in the direction of thickness of the conductors 202 so that a shift between the joint members 203 and the conductors 202 is prevented. As shown in FIG. 31, after the insulating joint members 203 are formed to hold the conductors 202 of the patterned conductor 210, the connection pieces 221 are cut off and the conductive pieces 209 positioned between adjoining LED series-connections are parted as indicated by hatching in the drawing. Subsequently, the LEDs 206 are inserted into the openings 223 of the insulating joint members (or sockets) 203 and resistors 207 are inserted into appropriate ones of the openings 224 of the insulating joint members 203, followed by attaching the LEDs 206 and resistors 207 to the conductors 202 and conductive pieces 209 to make the light emitting module 201 shown in FIG. 27. As will be appreciated, the number of series connected LEDs 206 in each LED series-connections connected between adjoining conductors 202 can be arbitrarily selected by changing the attachment positions of the resistors 207 and the conductive pieces 209 that are parted. As a specific example, when only a single LED 206 is included in each LED series-connection, the LEDs 206 are connected in parallel between the adjoining conductors 202. As another example, the number of LED series-connections connected between the adjoining conductors 202 may be one. Thus, according to this embodiment, it is possible to make light emitting modules 201 that connect the LEDs 206 between adjoining conductors 202 in arbitrary connection patterns, such as series, parallel or series-parallel connections, at low cost by using a common patterned conductor 210 and changing the attachment positions of the resistors 207 and the conductive pieces 209 to be parted. FIG. 32 is a partial plan view showing yet another embodiment of a light emitting module according to the present invention. This light emitting module 251 comprises: a pair of thin plate-shaped conductors 252 spaced apart from each other in a first direction (or x-axis direction) and extending in a second direction (or y-axis direction) substantially perpendicular to the first direction; a plurality of insulating joint members 253 for mechanically joining the conductors 252; and a plurality of side-view LEDs 256 arranged in the direction of extension of the conductors 252 to serve as light sources. The side-view LED 256 has a light emitting surface 256a on its side and electric connection terminals (not shown) on its underside. The insulating joint members 253 are provided for individual LEDs 256, and each joint member 253 is formed with an opening 273 for receiving the LED 256. Further, in order not to interfere with the light emitted from the side-view LED 256, part of the side walls defining the opening 273 of each insulating joint member 253 is removed to form a window 274. Such an insulating joint member 253 can be preferably formed by molding a resin material. FIG. 33 is a partial plan view omitting the insulating joint members 253 in order to show the way of connection of the LEDs 256 to the conductors 252. As shown, the upper conductor 252 in the drawing has widthwise (or in the first direction) recesses 261 on a side facing away from the lower conductor 252, and conductive pieces 259 are disposed in the recesses 261 where each LED 256 is connected between the associated conductive piece 259 and the conductor 252. Further, the conductive pieces 259 are connected to the lower conductor 252 via resistors 257 that stride across the upper conductor 252, as a result of which each LED 256 and its associated resistor 257 are connected in series between the conductors 252. The resistance of each resistor 257 can be determined appropriately depending on the characteristics of the corresponding LED 256. As shown in FIG. 32, each insulating joint member 253 is formed with an opening 274 for receiving the resistor in addition to the opening 274 for receiving the LED 256. Owing to such a structure, it is possible that the conductive piece 259 and a portion of the conductor 252 to which the terminals of the LED 256 are to be connected can be spaced apart in the direction of extension of the conductors 252 such that when the side-view LED 256 is attached, its light emitting surface 256a faces in the widthwise direction of the conductors 252. Further, by positioning the LED 256 such that its light emitting surface 256a is substantially aligned with an widthwise edge of the conductor 252, it can be prevented that the conductor 252 interferes with the light emitted from the LED 256. FIG. 34 is a partial plan view showing a patterned conductor 270 suitable for forming the light emitting module 251 as shown in FIG. 32. Such a patterned conductor 270 can be formed easily by press-working a thin plate-shaped conductor (such as a metal). After forming the insulating joint members 253 by molding a resin material onto the patterned conductor and cutting off the connection pieces 271, 272, the LEDs 256 and resistors 257 are attached to the conductors 252 and conductive pieces 259 to form the light emitting module 251 as shown in FIG. 32. The light emitting module 251 can be cut to form a smaller light emitting module(s). In this embodiment, the dimensions of the opening 273 of each insulating joint member 253 are determined such that not only the side-view LEDs 256 but also normal-view LEDs (or LEDs having a light emitting surface on their top) may be used. Although the present invention has been described in terms of preferred embodiments thereof the embodiments are presented for illustrative purposes only and the present invention should not be limited to the embodiments. It is obvious to a person having ordinary skill in the art that various alterations and modifications are possible without departing from the scope of the present invention which is set forth in the appended claims. For instance, in the above embodiments, bullet-type LEDs or chip-type LEDs, which are formed by bonding a bare-chip LED (or die) onto terminals for electric connection and encapsulating it by a resin, are used as light sources. However, the bare-chip LEDs before encapsulation may be used as light sources in the light emitting module of the present invention. Such bare-chip LEDs may be commercially available from Toyota Gosei Kabushiki Kaisha of Japan, for example. It is possible to bond a bare-chip LED onto the conductor 52 exposed by the opening 56 of the insulating joint member (socket) 53 shown in FIG. 9, for example, and then fill the opening 56 with a transparent resin for protecting the bare-chip LED. This can reduce the manufacturing cost of the light emitting module. Industrial Applicability In a light emitting module according to one aspect of the present invention, the conductors are joined by the insulating joint members so as to prevent stress from being imposed upon connections between the light sources and conductors, while the both sides of the portions of the conductors where the light sources are mounted are exposed so that the heat generated from the light sources can be quickly dissipated. In a light emitting module according to another aspect of the present invention, the conductors are joined by insulating joint members which are space apart from each other, and the conductors are exposed between adjoining joint members. This can prevent stress from being applied upon the connections between the light sources and the conductors, while allowing heat generated from the light sources to be dissipated from the exposed portions of the conductors. Further, it is possible to bend the exposed portions of the conductors to adjust the shape of the light emitting module in conformity with the shape of a support member or the like, or vary the direction of lights emitted from the light sources. In a light emitting module according to yet another aspect of the present invention, the insulating joint members for joining a plurality of conductors are each formed with an opening for exposing the conductors to which the light sources such as LEDs are mounted. The portions of the conductors exposed by the openings are each surrounded by the insulating joint member and thus are hard to deform. This can further reduce stress imposed upon the connections between the light sources and conductors. By determining the dimensions of the openings so as to match those of the light sources, the insulating joint members can serve as sockets to facilitate attachment of the light sources.

<SOH> BACKGROUND OF THE INVENTION <EOH>It is conventionally known to provide a light emitting module comprising one or more light sources without using a printed circuit board, where the light sources are attached directly between a plurality of conductors extending substantially in parallel (see, e.g., U.S. Pat. No. 5,519,596). In the light emitting module shown in U.S. Pat. No. 5,519,596, a plurality of bus bar pairs are connected via electroconductive extendable joints, and a plurality of LEDs serving as light sources are connected between each bus bar pair by clinching, soldering, spot-welding or the like, to form a so-called matrix circuit comprising a plurality of LED parallel-connections that in turn are connected in series. Before attachment of the LEDs, the bus bars in each pair are connected to each other by integral connection pieces, which, after the attachment of the LEDs, are cut off so as not to short-circuit the LEDs. The light emitting module fabricated by attaching the LEDs directly onto the conductive bus bars can obviate the use of a printed circuit board, and thus can be manufactured at a reduced cost. Further, the light emitting module has a favorable heat dissipation property because heat can be dissipated efficiently from the exposed bus bars and extendable joints. However, in such a light emitting module, the bus bars in each bus bar pair are mechanically connected to each other by the LEDs, and this can result in stress being imposed upon electrical connections between the bus bars and the LEDs and may undesirably lead to faulty electrical connections. Such a problem tends to be caused particularly when the light emitting module is being carried and thus makes the handling of the module cumbersome. Japanese Patent Application Laid-Open (kokai) No. 2000-260206 has disclosed processing a metallic sheet into a plurality of bus bar pairs extending in parallel and connected together by joint portions at either ends, attaching light emitting elements mechanically and electrically between each pair of bus bars at predetermined positions by means of clamping, for example, and cutting off part of the joint portions connecting the bus bar pairs to form a flexible light emitting module. In thus formed light emitting module also, the bus bars in each bus bar pair are connected to each other by the light emitting elements (LEDs), and therefore, contains a problem that the stress imposed on the electric connections between the bus bars and the light emitting elements can cause faulty electric connection. Japanese Patent Application Laid-Open (kokai) No. 2000-10507 has disclosed punching a metallic sheet by means of a punch press machine or the like to form a lead frame comprising a plurality of electrode terminals, to which LED chips are attached, where the electrode terminals are spaced apart from each other at a predetermined interval, subsequently molding a box-shaped reflection case onto the lead frame such that the reflection case covers top and under sides of the lead frame while exposing surfaces of the electrode terminals, and mounting LED chips onto the electrode terminal surfaces by die bonding to whereby manufacture a light emitting display device. In order to prevent warp of the lead frame when molding the box-shaped reflection case, an upper surface of the reflection case is formed with a plurality of pairs of arcuate projections such that each projection pair is aligned with a corresponding LED chip and interposes the LED chip therebetween, and a lower surface of the reflection case is formed with notches at positions between the projections. In this device, the reflection case serves to mechanically support the lead frame, and thus reduces an amount of stress imposed on electric connections between the LED chips and the lead frame. However, the reflection case extending an entire length of the light emitting display device and covering the top and under surfaces of the lead frame hinders heat dissipation as well as makes the device difficult to bend or curve. Further, the light emitting display device uses wire bonding to achieve attachment of the LED chips, and this makes it difficult to achieve attachment of a chip-type LED (or surface mount-type LED), which has electric connection terminals integral with a substantially box-shaped main body and thus has no leads.

<SOH> BRIEF SUMMARY OF THE INVENTION <EOH>In view of such problems of the prior art, a primary object of the present invention is to provide a light emitting module which has an improved heat dissipation property and allows easy handling without imposing stress on connections between light sources and conductors. A second object of the present invention is to provide a light emitting module which can be bent easily and allows easy handling without imposing stress on connections between light sources and conductors. A third object of the present invention is to provide a light emitting module that can be manufactured easily and efficiently even when chip-type LEDs are used as light sources. A fourth object of the present invention is to provide such a light emitting module at low cost and with simple structure. A fifth object of the present invention is to provide a method for manufacturing such a light emitting module. A sixth object of the present invention is to provide a method for easily and efficiently manufacturing a light emitting module comprising a desired number of light sources. A seventh object of the present invention is to provide a light emitting module that can be easily divided into smaller light emitting modules and allows thus-formed smaller light emitting modules to be used without need for additional current-limiting resistors. According to the present invention, such objects can be accomplished by providing a light emitting module, comprising: a plurality of thin plate-shaped conductors spaced apart from each other in a first direction; at least one light source connected between at least one pair of adjoining ones of the conductors; and at least one insulating joint member for mechanically joining the plurality of conductors, wherein the at least one insulating joint member exposes both sides of at least a portion of the conductors where the light source is mounted. According to such a structure, because the conductors are joined by the insulating joint member, it is possible to keep stress from being placed upon the connections between the light source and the conductors. Further, because the both sides of the light source mount portion of the conductors are exposed, heat generated by the light source can be quickly dissipated. The insulating joint member can be preferably formed by molding a resin material. According to another aspect of the present invention, there is provided a light emitting module, comprising: a plurality of thin plate-shaped conductors spaced apart from each other in a first direction; at least one light source connected between at least one pair of adjoining ones of the conductors; and at least one insulating joint member for mechanically joining the plurality of conductors, wherein the at least one insulating joint member has an opening exposing at least one side of a portion of the conductors, and the light source is inserted into the opening to be connected to the exposed portion of the conductors. The portion of the conductors exposed by the opening of the insulating joint member is hard to deform because it is surrounded by the insulating joint member, whereby preventing stress from being applied on the connections between the light source and the conductors. It will be preferred if the opening of the insulating joint member exposes both sides of the conductors, because, as described above, it can allow the heat from the light source to be dissipated quickly. Also, it will be preferred if the opening has a first opening into which the light source is inserted, and a second opening located at an opposite position with respect to the conductors, wherein the second opening diverges in a direction away from the conductors because when the light source is laser welded to the conductors, the irradiation of laser onto the conductors through the second opening can be achieved easily, facilitating the mounting of the light source to the conductors. Further preferably, dimensions of the opening are determined so as to substantially match those of the light source such that the insulating joint member having the opening serves as a socket for the light source. When the light source comprises a chip-type LED, it will be preferred if the portion of the conductors exposed by the opening of the insulating joint member is provided with extensions for resiliently contact electric connection terminals of the chip-type LED because this can achieve a reliable electric contact between the LED and the conductors. Further, if the insulating joint member has side walls for defining the opening, and a portion of the side walls is formed with an engagement finger for engaging with an upper surface of the chip-type LED when the chip-type LED is inserted into the opening, the mechanical and electrical attachment of the LED can be easily achieved without using laser-welding. When the light source comprises a bullet-type LED having a pair of substantially parallel extending leads, it will be favorable if the insulating joint member has a partition wall within the opening into which the bullet-type LED is inserted, the partition wall extending across the opening in a second direction substantially perpendicular to the first direction, and the portion of the conductors which is exposed by the opening of the insulating joint member and to which the bullet-type LED is mounted has extensions each extending in the first direction to contact the partition wall or to form a small gap between the partition wall and the extensions. In this way, it is possible to achieve quick and reliable attachment of the bullet-type LED by pushing in the pair of leads of the bullet-type LED between the partition wall and the extensions to thereby cramp them therebetween. According to another aspect of the present invention, there is provided a light emitting module, comprising: at least three thin plate-shaped conductors spaced apart from each other in a first direction; a plurality of electric elements each connected between associated pair of the conductors such that the plurality of electric elements are connected in series; and an insulating joint member mechanically joining the at least three conductors, wherein the electric elements comprise at least one light source. The electric elements may include a resistor for preventing an excessive current from flowing through the light source. When the electric elements include a resistor, it is possible to adjust the resistance of the resistor to allow the light emitting module to be directly connected to the power source to be used without need for a step-down transformer or the like. Further, if the light sources consist of LEDs, it is possible to prevent an overcurrent from flowing through the LEDs. In such a light emitting module also, because the mechanical joint of the conductors is achieved by the insulating joint members, stress can be kept from being applied upon the connections between the light sources and the conductors. It may be also possible to short-circuit between an arbitrary pair of conductors to prevent light emission at a position corresponding to the short-circuited pair of conductors. Preferably, the insulating joint member exposes a portion of the at least three conductors, and the exposed portion is formed with holes or grooves extending in a second direction substantially perpendicular to the first direction, because this can allow the conductors to be cut or bent easily along the holes or grooves. Further preferably, the light emitting module comprises a plurality of the insulating joint members, wherein the insulating joint members are spaced apart in the first direction such that the conductors are exposed between adjoining ones of the insulating joint members. In this way, heat can be dissipated efficiently from the exposed conductors. Further, the exposed conductors can be easily bent or flexed, making it possible to change the shape of the light emitting module depending on the place where the module is to be installed or to vary the directions of lights emitted from the light sources. In a preferred embodiment of the present invention; the light-emitting module further comprises an additional conductor extending in the first direction and spaced apart from the at least three conductors, wherein one end of the additional conductor is connected to one of the at least three conductors that is positioned at one end in the first direction, and the other end of the additional conductor is located at substantially the same position as one of the at least three conductors that is positioned at the other end in the first direction. In such a structure, it is possible to supply electricity to the light emitting module by connecting a power source to one of the at least three conductors that is positioned at the other end in the first direction and to the other end of the additional conductor, and thus the connection with the power source is easy. The one end of the additional conductor may be connected to the conductor positioned at the one end in the first direction via a resistor. According to another aspect of the present invention, there is provided a light emitting module comprising: a plurality of thin plate-shaped conductors spaced apart from each other in a first direction and extending in a second direction substantially perpendicular to the first direction; at least one light source connected between at least one pair of adjoining ones of the conductors; and a plurality of insulating joint members for mechanically joining the plurality of conductors, wherein the insulating joint members are spaced apart from each other in the second direction such that the conductors are exposed between adjoining ones of the insulating joint members. In this way, it is possible to efficiently dissipate heat from the exposed conductors as well as bend or flex the exposed portions of the conductors easily. A light source may be mounted to the portion of the conductors exposed between adjoining insulating joint members. If holes or grooves extending in the first direction are formed in the portion of the conductors exposed between adjoining insulating joint members, the conductors can be preferably cut or bent along the holes or, grooves. Further preferably, each of the portions of the conductors exposed between adjoining joint members is formed with a hole for electrical connection to an outer device such that when the light emitting module is cut to form a smaller light emitting module, it is possible, irrespective of the position to be cut, to leave portions of the conductors containing the holes for electrical connection to the outer device, to whereby make electric connection terminals for the outer device in the resulting smaller light emitting module. According to yet another aspect of the present invention, there is provided a light emitting module, comprising: a plurality of thin plate-shaped conductors spaced apart from each other in a first direction and extending in a second direction substantially perpendicular to the first direction; a plurality of light sources each connected between an associated pair of the conductors such that the plurality of light sources are arranged in a matrix pattern; and a plurality of insulating joint members for mechanically joining the plurality of conductors, wherein the plurality of insulating joint members are spaced apart in both of the first and second directions whereby the conductors are exposed between adjoining ones of the insulating joint members. In such a lighting module also, the conductors are joined by the insulating joint members, which can prevent stress from being imposed on the connections between the light sources and the conductors. Further, the heat from the light sources can be quickly dissipated from the portions of the conductors exposed between adjoining joint members, as well as the exposed portions of the conductors can be bent or flexed easily. In the light emitting module as above, the insulating joint member preferably has a portion extending through a portion of at least one of the conductors in a direction of thickness of the conductors. This can prevent shift between the insulating joint member and the conductors. In one embodiment, the portion of at least one of the conductors through which the insulating joint member extends comprises a through-hole extending in the direction of thickness. Also preferably, at least one joint member has a through-hole extending in the direction of thickness of the conductors. This can allow a bolt or the like for securing the light emitting module to a support member to be passed through the through-hole. According to another aspect of the present invention, there is provided a method for manufacturing a light emitting module, comprising the steps of: mechanically joining a plurality of conductors which are spaced apart from each other in a first direction by means of at least one insulating joint member; and mounting at least one light source between at least one pair of adjoining ones of said conductors, wherein in the step of joining the conductors, the insulating joint member exposes both sides of at least a portion of the conductors to which the light source is mounted. In this way, because the joint of the conductors is achieved by the insulating joint member, no stress will be imposed upon the connections between the light source and the conductors. Further, because the both sides of the conductors where the light source is mounted are exposed, the heat generated by the light source can be dissipated quickly. Preferably, the conductors are electrically separated from each other before the light source mounting step, and the method further comprises a step of conducting a conductivity test every time a light source is attached to the conductors. In this way, it is possible to find out a faulty light source or faulty connection between the light source and the conductors, whereby minimizing a later work for fixation and thus improving the work efficiency. According to another aspect of the present invention, there is provided a method for manufacturing a light emitting module, comprising the steps of: mechanically joining a plurality of conductors which are spaced apart from each other in a first direction and extending in a second direction substantially perpendicular to the first direction by means of a plurality of insulating joint members while transporting the conductors in the second direction; and mounting a plurality of light sources between at least one pair of adjoining ones of said conductors such that the light sources are arranged in the second direction, wherein the insulating joint members are spaced apart from each other in the second direction so that the conductors are exposed between adjoining ones of the joint members. In this way, it is possible to form a light emitting module comprising an arbitrary number of light sources arranged in the second direction (or in the direction of extension of the conductors) and connected between an associated pair of conductors. Because the conductors are joined by the insulating joint members, stress can be kept from being placed upon the connections between the light sources and the conductors. Further, heat generated by the light sources can be quickly dissipated from the portions of the conductors exposed between adjoining joint members In the step of joining the conductors, the conductors which are spaced apart from each other may be individually transported in the second direction. Alternatively, it is also possible that in the step of joining the conductors, the conductors are transported in a state that they are connected to each other via connection pieces to form an integral patterned conductor and insulating joint members are formed so as to expose the connection pieces, and the method further comprises, after the step of joining the conductors, a step of cutting off the connection pieces to separate the conductors from each other. In the case that the conductors separated apart from each other are individually transported, wasted material can be reduced because there is no part to be cut off. On the other hand, in the case that the conductors are connected via the connection pieces to form a unitary patterned conductor, easier handling thereof can be achieved. Further, when at least one of the conductors is provided with pilot holes arranged at prescribed intervals in the second direction for engagement with pilot pins of a progressive manufacturing line for transporting the patterned conductor, it is not necessary for each conductor to be provided with the pilot holes because they can be transported integrally with the conductor provided with the pilot holes. Such a patterned conductor can be preferably formed by press-working a metallic thin plate. According to still another aspect of the present invention, there is provided a method for manufacturing a light emitting module, comprising the steps of: mechanically joining a plurality of conductors which are spaced apart from each other in a first direction by means of a plurality of insulating joint members while transporting the conductors in the first direction; and mounting a plurality of light sources between an associated pair of said conductors, wherein at least some of the light sources are connected in series via the conductors and the insulating joint members are spaced apart in the first direction such that the conductors are exposed between adjoining ones of the insulating joint members. This can allow an arbitrary number of conductors to be transported and hence, the number of light sources that are connected in series via the conductors is not limited. Therefore, it is possible, for example, to easily form a light emitting module comprising a number of light sources that match the voltage of a power supply to be connected or a number of light sources that are required for a place where the light source is to be installed. In this case also, the conductors are joined by the insulating joint members and thus, no stress will be imposed upon the connections between the light sources and conductors. Further, the heat generated by the light sources can be swiftly dissipated from the portions of the conductors exposed between adjoining joint members. In the step of joining the conductors, the conductors are preferably transported in a state that they are connected to each other via connection pieces to form an integral patterned conductor and the insulating joint members are formed so as to expose the connection pieces, and the method further comprises, after the step of joining the conductors, a step of cutting off the connection pieces to separate the conductors from each other. The use of the patterned conductor can make the handling easier because the conductors are integral to each other. Further, in the case that the direction of transportation of the patterned conductor coincides with the first direction, it will be preferable if the patterned conductor comprises an additional conductor extending in the first direction and connected to the plurality of conductors via connection pieces, and the method further comprises the step of: joining the additional conductor to the plurality of conductors by means of an insulating joint member; cutting off the connection pieces connecting the additional conductor to the plurality of conductors; and connecting an end of the additional conductor to one of the plurality of conductors at one end of the light emitting module via an electric element (such as a resistor). In this way, an end of the additional conductor and one of the plurality of conductors at the other end of the light emitting module can be used for connection to a power source. In other words, the terminals for connection to the power source can be provided at the same end of the light emitting module, thereby facilitating the connection to the power source. According to another aspect of the present invention, there is provided a method for manufacturing a light emitting module, comprising the steps of: mechanically joining a plurality of conductors which are spaced apart from each other in a first direction and extending in a second direction substantially perpendicular to the first direction by means of a plurality of insulating joint members; mounting a plurality of light sources between at least one pair of adjoining ones of the conductors; and after the light source mounting step, cutting the conductors along a line extending substantially in the first direction at a prescribed position in the second direction. This can form a light emitting module comprising a desired number of light sources arranged in the second direction. Further, the conductors are joined by the insulating joint members to prevent stress from being upon the connections between the light sources and the conductors. According to yet another aspect of the present invention, there is provided a method for manufacturing a light emitting module, comprising the steps of: mechanically joining more than two conductors which are spaced apart from each other in a first direction and extending in a second direction substantially perpendicular to the first direction by means of a plurality of insulating joint members; mounting a plurality of light sources between at least two pairs of adjoining ones of the conductors such that the light sources are arranged in the first direction; and after the light source mounting step, cutting the conductors along a line extending substantially in the second direction, which is perpendicular to the first direction, at a prescribed position in the first direction. This can form a light emitting module comprising a desired number of light sources arranged in the first direction. Further, the conductors are joined by the insulating joint members to prevent stress from being upon the connections between the light sources and the conductors. According to another aspect of the present invention, there is provided a light emitting module, comprising: a plurality of thin plate-shaped conductors spaced apart from each other in a first direction; at least one light source connected between at least one pair of adjoining ones of the conductors; at least one insulating joint member for mechanically joining the plurality of conductors; and an additional conductor spaced apart from the plurality of conductors and extending in the first direction, wherein one end of the additional conductor is connected to one of the plurality of conductors located at one end in the first direction while the other end of the additional conductor is disposed substantially at the same position as one of the plurality of conductors located at the other end in the first direction, and wherein the at least one insulating joint member has an opening exposing at least one side of a portion of the plurality of conductors and the light source is inserted into the opening to be connected to the portion of the conductors exposed by the opening. In this way, the one of the plurality of conductors located at the other end in the first direction and the other end of the additional conductor are positioned close to each other, whereby it is easily achieved to connect them to a power source so as to supply electric power to the light emitting module. Further, because the light source is inserted into the opening of the insulating joint member, it is possible to keep stress from being placed upon the connections between the light source and the conductors and thus easy handling can be achieved. In such a light emitting module, it is possible that a plurality of electric elements including at least one light source are connected in series via the plurality of conductors. Preferably, the connection between the other end of the additional conductor and the one of the plurality of conductors located at the other end in the first direction is achieved via a resistor although the connection may be also achieved by a conductive member such as a jumper wire. Further, it will be favorable if the insulating joint member also joins the additional conductor and the conductor located at the other end in the first direction to each other because it can increase the mechanical strength. Preferably, the insulating joint member has an additional opening in which the resistor is inserted. This keeps stress from being placed upon the connections between the resistor and the conductors, to whereby prevent undesirable detachment of the resistor or faulty connection. Aligning the opening for receiving the light source and the opening for receiving the resistor with each other in the first direction can position the openings close to each other, and thus the openings can be formed in the insulating joint member efficiently. According to yet another aspect of the present invention, there is provided a light emitting module, comprising: a plurality of thin plate-shaped conductors spaced apart from each other in a first direction and extending in a second direction substantially perpendicular to the first direction; at least one light source each connected between an associated pair of the conductors; and a plurality of insulating joint members for mechanically joining the plurality of conductors, wherein a resistor is connected in series with each of the at least one light source. Such provision of resistors which are series-connected to respective light sources can allow a resistance of each resistor to be determined depending on the characteristics of an associated light source so that when a predetermined voltage (e.g., 4V) is applied upon a light source (e.g., LED), a predetermined rated current flows through the light source. This can allow a single light emitting module to contain a plurality of light sources having different characteristics, for example. Further, in a case that such a light source is cut at desired portions to form a smaller light source(s), the resulting smaller light source automatically contains resistors having suitable resistances that match the light sources contained and thus, external resistors are not separately needed. Therefore, it is easy for a user to cut the light emitting module as desired to form smaller light emitting modules and to arrange them in various patterns. Preferably, the insulating joint members are provided one for each of the at least one light source, and each of the insulating joint members is formed with openings for receiving an associated light source and resistor connected in series to the light source. In this way, the insulating joint members can serve as an integral socket for the light source and resistor for steadily holding the same. This makes carrying or cutting of the light emitting module easier. In one embodiment, a conductive piece is provided between adjoining ones of the plurality of thin plate-shaped conductors such that the series-connected at least one light source and resistor are connected to each other via the conductive piece, and the insulating joint member mechanically joins the conductive piece and the conductors. Further, the light emitting module may include, as light sources, not only a bullet-type LED or chip-type LED but also a bare-chip LED. According to still another aspect of the present invention, there is provided a light emitting module, comprising: a plurality of thin plate-shaped conductors spaced apart from each other in a first direction and extending in a second direction substantially perpendicular to the first direction; a plurality of conductive pieces disposed between adjoining ones of the conductors so as to be spaced apart from each other in the second direction; a plurality of light sources connected between adjoining ones of the conductive pieces; a plurality of resistors for connecting selected ones of the conductive pieces to one or the other of a pair of the conductors interposing the selected conductive pieces therebetween; and at least one insulating joint member for mechanically joining the plurality of conductors and the conductive pieces. In such a light emitting module, a plurality of light source series-connections each comprising light sources connected in series via conductive pieces can be connected in parallel between an associated conductors via resistors, to thereby form a so-called series-parallel connection. The number of light sources contained in each light source series-connection may be arbitrarily selected by choosing the position of the resistors for connecting the conductive pieces to the conductors. As a particular case thereof, when each light source series-connection comprises only a single light source, the light sources are connected in parallel between the pair of conductors. Alternatively, only a single light source series-connection may be connected between the pair of conductors. Thus, in this light emitting module, it is possible to connect the light sources in any of series, parallel or series-parallel connections by changing the attachment positions of the resistors or the like. According to yet another aspect of the present invention, there is provided a light emitting module, comprising: first and second conductors spaced apart from each other in a first direction and extending in a second direction substantially perpendicular to the first direction; and at least one light source connected between the first and second conductors, wherein the first conductor has a widthwise recess in which a conductive piece is disposed such that the conductive piece is spaced apart from a portion of the first conductor in the second direction, and wherein the at least one light source is connected to the conductive piece and the portion of the first conductor which are spaced apart from each other in the second direction, and the conductive piece is connected to the second conductor via a resistor. In such a light emitting module, the light source is connected between the conductive piece and the portion of the first conductor spaced apart in the second direction and thus, when a side-view LED having a light emitting surface on its side is used as a light source, it is possible to emit light in a direction perpendicular to the direction of extension of the first and second conductors. Further, provision of a resistor connected in series to each light source can allow the resistance of each resistor to be determined depending on the characteristics of an associated light source. Preferably, the widthwise recess of the first conductor is provided on a side facing away from the second conductor, and the resistor strides across the first conductor to connect the conductive piece to the second conductor. In this way, when the light source consists of a side-view LED, it is possible to mount the light source such that the light emitting surface of the light source is substantially aligned with a widthwise edge of the first conductor away from the second conductor, so as to prevent the conductor to interfere with the light emitted from the light source. Further preferably, the light emitting module may further comprise at least one insulating joint member for mechanically joining the first and second conductors and the conductive piece. This can prevent stress from being placed upon the electric connections between the light source and the conductive piece or conductor. Other and further objects, features and advantages of the invention will appear more fully from the following description.

20040827

20070410

20051027

71141.0

ULANDAY, MEGHAN K

LIGHT EMITTING MODULE

SMALL

ACCEPTED

ACCEPTED

Honeycomb structural body and canning structural body storing the honeycomb structural body

A honeycomb structure according to the present invention has partition walls, and a number of through-holes divided from each other by the partition walls and extending in an axial direction. The honeycomb structure contains silicon carbide (SiC) or a composite material having silicon carbide (SiC) as a main crystal phase, and has a cylindrical shape. A circularity of a periphery of the honeycomb structure is in a range of 1.0 to 2.5 mm. The honeycomb structure can be contained in a metal container in stable state and hardly has problems such as breakage or breakdown.

1-12. (canceled) 13. A honeycomb structure comprising: partition walls; and a number of through-holes divided from each other by the partition walls and extending in an axial direction; the honeycomb structure containing silicon carbide (SiC) or a composite material having silicon carbide (SiC) as a main crystal phase; and having a cylindrical shape; wherein a circularity of a periphery of the honeycomb structure is in a range of 1.0 to 2.5 mm, or a cylindricality of a periphery of the honeycomb structure is in a range of 1.0 to 3.0 mm. 14. The honeycomb structure according to claim 13, wherein a second phase of the composite material having silicon carbide (SiC) as a main crystal phase is at least one selected from the group consisting of metallic silicon (Si), metal oxide, metal nitride, metal boride and metal carbide. 15. The honeycomb structure according to claim 14, wherein the metal oxide is at least one selected from the group consisting of SiO2, Al2O3 and MgO. 16. The honeycomb structure according to claim 13, wherein the honeycomb structure is used for purifying automotive exhaust gas. 17. The honeycomb structure according to any of claim 13, wherein the honeycomb structure is used as a diesel particulate filter. 18. A canning structure comprising: a honeycomb structure; and a metal container housing the honeycomb structure; wherein the honeycomb structure is housed in the container in a held state by disposing, in a compressed state, a compressible elastic member having thermal resistance and cushioning ability between a peripheral portion of the honeycomb structure and the container; the honeycomb structure comprising: partition walls; and a number of through-holes divided from each other by the partition walls and extending in an axial direction; the honeycomb structure containing silicon carbide (SiC) or a composite material having silicon carbide (SiC) as a main crystal phase; and having a cylindrical shape; a circularity of a periphery of the honeycomb structure being in a range of 1.0 to 2.5 mm, or a cylindricality of a periphery of the honeycomb structure being in a range of 1.0 to 3.0 mm. 19. The canning structure according to claim 18, wherein the metal has a coefficient of thermal expansion of 8×10−7 to 13×10−7. 20. The canning structure according to claim 18, wherein the metal is a ferrite-based stainless steel and/or a low thermally-expansible special alloy. 21. The canning structure according to claim 18, wherein the compressible elastic member is a ceramic fiber mat. 22. The canning structure according to claim 21, wherein the ceramic fiber mat is a non-intumescent mat. 23. The canning structure according to claim 18, wherein the honeycomb structure is housed in the container by stuffing, tourniquet, clamshell, swaging, and rotational forging.

TECHNICAL FIELD The present invention relates to a honeycomb structure and a canning structure containing the honeycomb structure. BACKGROUND ART While the recently tightened regulation on exhaust gas has been improving in reducing discharged amounts of harmful substances such as hydrocarbons (HC), carbon monoxide (CO), and nitrogen oxides (NOx) from an engine itself; a three-way catalyst, which is the main current at present, has also been improving. Both of them have been effective in reducing a discharged amount of harmful substances. However, an amount of harmful substances discharged right after an engine has started is highlightened, while discharged substances are reduced extending over the whole running condition of an engine as the improvement according to tightening of exhaust gas regulations. For example, in FTP-75 cycle, which is a regulated running cycle in U.S., 60-80% of total emission discharged in the whole running cycle is discharged in the Bag-1 mode for 140 second right after the engine has started. This is because a catalyst is not sufficiently activated since temperature of exhaust gas is low right after an engine has started (Bag-1A), thereby passing harmful substances through the catalyst. Therefore, some measures are employed, for example, putting a catalyst as close to an engine as possible in a place where exhaust gas has high temperature to raise temperature of the catalyst right after an engine has started, thinning the cell partition walls to decrease heat capacity of a catalyst itself, and increasing cell density of a carrier to quickly absorb heat of exhaust gas and to increase a contact area of a catalyst with exhaust gas. As a catalyst, there is generally used a catalyst produced by loading γ-alumina of a fine porous structure having a high surface area on the surface of cell partition walls of a ceramic honeycomb structure, which is one of cell structures, and then noble metals such as platinum, palladium, and rhodium are loaded, as catalyst components, on the alumina. Further, to these noble metals are added ceria, zirconia, and the like, to store and release oxygen contained in exhaust gas. Such noble metals and oxygen-storing substances are present in a dispersed state in the pores in the γ-alumina layer loaded on the surface of porous cell partition walls (rib) of the carrier. A honeycomb structure is generally used in such a condition that it is housed (canned) in a container made of metal such as stainless steel with being held by the container. In addition, a honeycomb filter obtained by alternately plugging the honeycomb structure at each end face in such a way that it looks checkerboard patterns is suitably used also as a filter for capturing and removing particulate matters contained in dust-containing fluid such as diesel engine exhaust gas (such a filter may hereinbelow be referred to as “DPF.”), and the filter is disposed in a predetermined place after being canned similarly to the case of the aforementioned honeycomb structure. Upon canning, an appropriate compressible elastic member is disposed in a gap between the container and a peripheral surface of the honeycomb structure to impart an adequate compressing surface pressure to the honeycomb structure. An example of related prior art is a method of canning a honeycomb structure in a metal container with holding the honeycomb structure with a mat of an intumescent material containing vermiculite (see U.S. Pat. Nos. 5,207,989 and 5,385,873). However, in the case of the method disclosed in the above U.S. Pat. Nos. 5,207,989 and 5,385,873, compressing surface pressure is rapidly raised by intumescence. Therefore, the rapidly raised compressing surface pressure tends to exceed strength (isostatic strength) of a honeycomb structure having thin walls with low strength, and the honeycomb structure is liable to break. In addition, since compressibility of an intumescent mat is quickly deteriorated from about 800 degree C., compressing surface pressure disappears at about 1000 degree C., and it becomes impossible to hold the honeycomb structure. Whereas, in a non-intumescent mat not containing vermiculite (see U.S. Pat. Nos. 5,580,532 and 2,798,871), the change in surface pressure according to temperature-rise is very small, and the honeycomb structure can be held with surface pressure being hardly decreased even at 1000 degree C. A honeycomb structure having thin walls has conventionally been held using a non-intumescent mat in place of an intumescent mat. However, when a honeycomb structure is wound with a mat serving as a holding member followed by being canned in a metal container, slippage tends to be caused at the joint of the mat, and surface pressure tends to be increased. Further, when a honeycomb structure having a mat wound thereon is stuffed in a metal container, the mat tends to have rumples, and surface pressure tends to be increased at that point. These cause non-uniform distribution of compressing surface pressure acting on a peripheral surface of the honeycomb structure. When partially heightened compressing surface pressure exceeds isostatic strength of the honeycomb structure, the cell structure breaks. In addition, because of the non-uniform distribution of the surface pressure, the cell structure tends to slip due to vibrations of an engine or pressure of exhaust gas in practical use. Incidentally, “isostatic strength” of a honeycomb structure means a value measured by “isostatic fracture strength test” provided for by the automobile standards JASO standard M505-87 published by Society of Automotive Engineers of Japan, Inc. Specifically, the test is conducted in such a manner that a cell structure as a carrier is put in a rubber tube, and the container is capped and subjected to isotropic pressure compression, which imitates compression load in the case that a carrier is held at a peripheral surface thereof by a can of a converter. The isostatic strength is shown by a value of pressure at the time of breakage of a carrier. A catalyst converter for purifying automotive exhaust gas generally employs a canning structure in which a carrier is held at a peripheral surface thereof. It is a matter of course that high isostatic strength is preferable in view of canning. When the actual surface pressure becomes higher than the intended surface pressure planned upon design of canning, the structure may break at the point if the surface pressure exceeds isostatic strength of the honeycomb structure. According as thickness of cell partition walls decreases and strength of the structure is lowered, it is necessary to decrease the intended surface pressure, and it is necessary to minimize fluctuation of the surface pressure by suppressing extraordinary increase of actual canning surface pressure. It is ideal that the actual surface pressure is equal to the intended surface pressure because it makes possible the canning design just as aimed. Further, a honeycomb structure may break because of varied gap between the honeycomb structure and the metal container due to precision of an external shape of the honeycomb structure or because of uneven compression pressure act on the peripheral portion of the honeycomb structure and high holding surface pressure acts partially as a result of slippage of a holding member caused when the honeycomb structure is housed in a metal container. As the partition walls of a honeycomb structure are made thinner, the isostatic strength level of the honeycomb structure becomes lower, which requires to make compressing surface pressure of the honeycomb structure as low as possible with keeping the minimum surface pressure required for holding a honeycomb structure. As the level of compressing surface pressure is lowered, it is necessary to make variance in surface pressure smaller, i.e., to give more uniform distribution of surface pressure. The present invention has been made in view of the problems of the prior art and aims to provide a honeycomb structure which is capable of being housed in a metal container under a safely held condition and which hardly has problems such as breakage or breakdown, as well as a canning structure which has a metal container housing the honeycomb structure and which is superior in vibration resistance particularly under high temperature conditions. DISCLOSURE OF THE INVENTION According to the present invention, there is provided a honeycomb structure comprising: partition walls; and a number of through-holes divided from each other by the partition walls and extending in an axial direction; the honeycomb structure containing silicon carbide (SiC) or a composite material having silicon carbide (SiC) as a main crystal phase; and having a cylindrical shape, wherein a circularity of a periphery of the honeycomb structure is in a range of 1.0 to 2.5 mm. According to the present invention, there is also provided a honeycomb structure comprising: partition walls; and a number of through-holes divided from each other by the partition walls and extending in an axial direction; the honeycomb structure containing silicon carbide (SiC) or a composite material containing silicon carbide (SiC) as a main crystal phase; and having a cylindrical shape, wherein a cylindricality of a periphery of the honeycomb structure is in a range of 1.0 to 3.0 mm. In the present invention, it is preferable that a second phase of the composite material having silicon carbide (SiC) as a main crystal phase is at least one selected from the group consisting of metallic silicon (Si), metal oxide, metal nitride, metal boride and metal carbide and that the metal oxide is at least one selected from the group consisting of SiO2, Al2O3 and MgO. The honeycomb structure is preferably used for purification of exhaust gas of automobile, and more preferably used as a filter for capturing diesel particulate matter. According to the present invention, there is further provided a canning structure comprising: the honeycomb structure described above, and a metal container housing the honeycomb structure; wherein the honeycomb structure is housed in the container in a held state by disposing, in a compressed state, a compressible elastic member having thermal resistance and cushioning ability between a peripheral portion of the honeycomb structure and the container. In the present invention, it is preferable that the metal has a coefficient of thermal expansion of 8×10−7 to 13×10−7 and that the metal is a ferrite-based stainless steel and/or a low thermally-expansible special alloy. In the present invention, it is preferable that the compressible elastic member is a ceramic fiber mat and that the ceramic fiber mat is a non-intumescent mat. Further, in the present invention, it is preferable that a honeycomb structure is housed in the container by any of stuffing, tourniquet, clamshell, swaging, and rotational forging. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a partially cut-away view showing one example of the stuffing method used for housing a honeycomb structure in a metallic container. FIG. 2 is a perspective view showing one example of the tourniquet method used for housing a honeycomb structure in a metallic container. FIG. 3 is a perspective view showing one example of the clamshell method used for housing a honeycomb structure in a metallic container. FIG. 4 is a sectional view parallel to the direction of through-holes, showing one example of the swaging method used for housing a honeycomb structure in a metallic container. FIG. 5 is a sectional view parallel to the direction of through-holes, showing one example of the swaging method used for housing a honeycomb structure in a metallic container. FIG. 6 is a schematic view showing a high-temperature gas generator and a vibration generator connected with the high-temperature gas generator. BEST MODE FOR CARRYING OUT THE INVENTION Embodiments of the present invention will hereinbelow be described. However, the present invention is by no means limited to the embodiments, and it should be understood that modification in design, improvement, etc., may be adequately performed on the basis of those skilled in the art in a range not deviating from the gist of the present invention. The first aspect of the present invention is a honeycomb structure comprising: partition walls; and a number of through-holes divided from each other by the partition walls and extending in an axial direction; the honeycomb structure containing silicon carbide (SiC) or a composite material containing silicon carbide (SiC) as a main crystal phase; and having a cylindrical shape, wherein a circularity of a periphery of the honeycomb structure is in a range of 1.0 to 2.5 mm. The details will hereinbelow be described. As mentioned above, to use a honeycomb structure for purification of automotive exhaust gas, it is general to prepare a canning structure by housing (canning) the honeycomb structure in a container made of metal such as stainless steel with being held by the container. A honeycomb structure of the present invention has a circularity of a periphery of 1.0 to 2.5 mm. That is, the shape of a section perpendicular to the direction of through-holes is not exactly circle and the structure, which is cylindrical, has a little distortion. Therefore, when a honeycomb structure is used in a canning structure, compressing surface pressure is applied to hold not the whole peripheral surface of the honeycomb structure, but a partial peripheral surface. A honeycomb structure of the present invention contains silicon carbide (SiC) or a composite material having silicon carbide (SiC) as a main crystal phase. Its coefficient of thermal expansion is higher in comparison with, for example, cordierite (silicon carbide: 4×10−7, cordierite: 0.5×10−7 to 1.2×10−7) and closer to a coefficient of thermal expansion of a metal constituting a container (stainless steel: 8×10−7 to 13×10−7). Therefore, it is possible to set lower compressing surface pressure upon canning a honeycomb structure of the present invention in comparison with the case of a honeycomb structure of cordierite. Accordingly, since a canning structure of the present invention has a structure of applying the compressing surface pressure to hold not the whole peripheral surface but a part of the surface, it is very effective in inhibiting a honeycomb structure from slipping between the structure and a container or from falling off from the container due to a temperature difference in a place where the canning structure is placed or in suppressing breakage of the honeycomb structure due to high compressing surface pressure as well as it has high vibration resistance under a condition of high temperature. Further, to obtain higher effects in inhibiting slippage, falling off, breakage, and the like, it is preferable that the peripheral portion has circularity of 1.5 to 2.5 mm, more preferably 1.5 to 2.0 mm. Incidentally, “circularity” mentioned in the present invention means a value indicated by a difference in diameter in a measured section of a cylindrical honeycomb structure to show an extent of roundness. The measurement is performed by automatic measurement using a laser measuring device, digital calipers, or the like. The second aspect of the present invention is a cylindrical honeycomb structure having partition walls and a number of through-holes divided from each other by the partition walls and extending in an axial direction, containing silicon carbide (SiC) or a composite material having silicon carbide (SiC) as a main crystal phase, wherein a cylindricality of a periphery of the honeycomb structure is in a range of 1.0 to 3.0 mm. In a honeycomb structure of the present invention, a cylindricality of the periphery is specified in the rage of 1.0 to 3.0 mm. That is, a section in parallel with the direction of through-holes is not exactly rectangular and the honeycomb structure, which is cylindrical, has a little distortion. Therefore, like the first aspect of the present invention, i.e., a honeycomb structure whose periphery has a circularity of a predetermined range, compressing surface pressure upon canning is applied to hold not the whole peripheral surface of the honeycomb structure but a partial peripheral surface in the case that the honeycomb structure is used in a canning structure. Since a honeycomb structure of the present invention contains silicon carbide (SiC) or a composite material having silicon carbide (SiC) as a main crystal phase, it is possible to set lower compressing surface pressure upon canning a honeycomb structure of the present invention in comparison with the case of a honeycomb structure of cordierite. Accordingly, since a canning structure of the present invention has a structure of applying the compressing surface pressure to hold not the whole peripheral surface but a part of the surface, it is very effective in inhibiting a honeycomb structure from slipping between the structure and a container or from falling off from the container due to a temperature difference in a place where the canning structure is placed or in suppressing breakage of the honeycomb structure due to high compressing surface pressure as well as it has high vibration resistance under a condition of high temperature. Further, to obtain higher effects in inhibiting slippage, falling off, breakage, and the like, it is preferable that the peripheral portion has cylindricality of 1.5 to 2.5 mm. Incidentally, “cylindricality” mentioned in the present invention means a value indicated by a difference in diameters of two coaxial geometrical cylinders (standard cylinders) in the case of forming the minimum gap formed when a honeycomb structure is sandwiched by the coaxial geometrical cylinders (standard cylinders) to show if its a geometric cylinder or not. The measurement is performed by automatic measurement using a laser measuring device, digital calipers, or the like, similarly to the case of measurement for circularity. For the second phase of the composite material having silicon carbide (SiC) as a main crystal phase, there is preferably used at least one selected from the group consisting of metallic silicon (Si), metal oxide, metal nitride, metal boride and metal carbide from the viewpoint of low thermal expansion, heat resistance, oxidation resistance, and the like. Specifically, as the above metal oxide, at least one selected from the group consisting of SiO2, Al2O3 and MgO is preferably employed in view of practicability. Incidentally, in the present invention, a minute phase inevitably coexist in view of production may be contained besides the above main crystal phase and the second phase. As described above, a honeycomb structure of the present invention is preferably used as a filter for purifying automotive exhaust gas or further for capturing diesel particulate matter by taking advantage of features such as high vibration resistance under a condition of high temperature. A honeycomb structure of the present invention will hereinbelow described in more detail with an example of a method for production thereof. In the first place, silicon carbide (SiC) is prepared to produce a honeycomb structure. Silicon carbide (SiC) sometimes contains minute impurities such as Fe, Al, and Ca. Such silicon carbide may be used as it is or subjected to a chemical treatment such as chemical washing to purify. To the silicon carbide (SiC) may be added, as a material for forming the second phase, at least one of metallic silicon (Si), metal oxides such as SiO2, Al2O3, and MgO, non-oxides such as metal nitride, metal boride, and metal carbide, and the like. For smooth extrusion of clay into a honeycomb shape, it is preferable that at least one suitable organic binder is added in an appropriate amount. Further, water and the like are added to the material, followed by mixing and kneading to obtain clay for forming. When partition walls (cell partition walls) constituting cells of the honeycomb structure are used as a filter, a pore former is added to the material for preparing clay to raise the porosity. In this case, since pores are formed at the space where the pore former disappears after the burning, it is preferable to use a pore former having the average particle diameter within the range from 100 to 150% with respect to the intended average pore diameter after being fired. The clay obtained by mixing and kneading the above material by an ordinary method is formed into a honeycomb structure having a desired cell shape by extrusion or the like. As to a cell shape, it is general that a honeycomb structure used as a DPF has a square cell shape. However, in a honeycomb structure of the present invention, a cell shape is not restricted to a square and may be a rectangle, a triangle, a hexagon, a circle, or the like. When a honeycomb structure is used as a catalyst carrier for purification of automotive exhaust gas or as a DPF, the cell partition walls may have a thickness of 0.11 to 0.17 mm, and a cell density may be 300 to 1200 cpsi, or the cell partition walls may have a lower thickness of 0.02 to 0.10 mm. A honeycomb structure used for a heat-exchanger may have a structure having a high cell density of 1200 cpsi or more. Incidentally, a cell structure is specified by a cell wall thickness and a cell density, and a cell density is generally shown by cpsi. For example, a cell density of 400 cpsi means presence of 400 cells per square inch, and “cpsi” is an abbreviation of “cells per square inch”. Cell partition wall thickness is also called as rib thickness, and it has conventionally shown with a unit “mil”. One mil is 1×10−3 inch, and it is about 0.025 mm. The formed body obtained above is calcined to remove an organic binder contained in the formed body, and then subjected to firing. It is preferable that the calcination is performed at a temperature lower than a temperature at which metallic silicon melts. Specifically, it may temporarily be kept at a predetermined temperature of about 150 to 700 degree C. Alternatively, calcination may be conducted at a heating rate of 50 degree C./hr or less within the predetermined temperature range. In the manner of temporarily keeping the formed body at a predetermined temperature, the formed body may be kept at one temperature level or at plural temperature levels. When the formed body is kept at plural temperature levels, the time for keeping the temperature may be the same or different from each other. Similarly, as to a manner of making slower a heating rate, the heating rate may be made slower in a certain temperature range or in plural temperature ranges. When the heating rate is made slower in plural ranges, the rate may be the same or different from each other. The calcination may be performed in an oxidization atmosphere. However, in the case that a large amount of organic binder(s) is contained in the formed body, the organic binder(s) sometimes burn(s) furiously with oxygen to raise temperature of the formed body rapidly during the calcination. Therefore, in such a case, it is also preferable to perform the calcination in an inert atmosphere such as N2 and Ar to suppress extraordinary temperature rise of the formed body. The calcination and the following main firing may be performed in the same furnace or different furnaces as different steps. Alternatively, they may be performed in the same furnace as successive steps. The former manner is also preferable when the calcination and the main firing are performed in different atmospheres. However, the latter manner is also preferable from the viewpoint of total firing time, running cost of a furnace, and the like. The optimum firing temperature during the main firing is determined depending on a micro-structure and properties, and the temperature of 1400 to 1800 degree C. is appropriate in general. As to an atmosphere of the main firing, a non-oxidizing atmosphere such as N2 and Ar is preferable to avoid oxidation of silicon carbide at high temperature. When the honeycomb structure of the present invention is used as a carrier for catalyst in an internal combustion engine, a boiler, a chemical reactor, a fuel cell reformer, or the like, the honeycomb segments used therein are allowed to load thereon a metal having a catalytic activity. As representative metals having a catalytic activity, there are mentioned Pt, Pd, Rh, K, Na, Li, etc. It is preferred that at least one selected from these metals is loaded on the honeycomb segments. On the other hand, when the honeycomb structure of the present invention is used as a filter for capturing particulate matter in exhaust gas such as DPF, cell walls are made to a filter by plugging cells alternately at each end face so that the end faces show checkerboard pattern. When exhaust gas containing particulate matter is taken into a honeycomb structure constituted by such honeycomb segments, from its one end face, the exhaust gas enters the inside of the honeycomb structure from those openings not plugged at the one end face, passes through porous cell walls having a filtration ability, and is discharged from the openings not plugged at the other end. When the exhaust gas passes through the cell walls, the particulate matter present in the exhaust gas is captured by the partition walls. As the captured particulate matter builds up on cell walls, pressure loss increases rapidly, an engine load increases, fuel consumption and drivability deteriorate; hence, the particulate matter is burnt and removed periodically by a heating means such as a heater, to regenerate ability of the filter. In order to promote the combustion during the regeneration, metal having a catalytic activity such as mentioned above may be loaded on the honeycomb structure. Next, description is made on the third aspect of the present invention. The third aspect of the present invention is a canning structure comprising: any of the honeycomb structure mentioned above, and a metal container housing the honeycomb structure; wherein the honeycomb structure is housed in the container in a held state by disposing, in a compressed state, a compressible elastic member having thermal resistance and cushioning ability between a peripheral portion of the honeycomb structure and the container. The details will hereinbelow be described. As described above, since a peripheral portion of a honeycomb structure of the present invention has a predetermined circularity or cylindricality, a canning structure of the present invention obtained by using the honeycomb structure of the present invention hold not the whole peripheral surface of the honeycomb structure but a part of the peripheral surface by compressing surface pressure applied when the honeycomb structure is canned with a compressible heat-insulating material being disposed between a peripheral portion of the honeycomb structure and a metal container. Since the honeycomb structure to be housed in the container is constituted by silicon carbide (SiC), the structure has a coefficient of thermal expansion higher than that of cordierite (silicon carbide: 4×10−7, cordierite: 0.5×10−7 to 1.2×10−7) and the coefficient of thermal expansion is close to that of the metal constituting the container (stainless steel: about 10×10−7). Therefore, as to a canning structure of the present invention, it is possible to set lower compressing surface pressure upon canning a honeycomb structure of the present invention in comparison with the case of a honeycomb structure of cordierite. Accordingly, since a canning structure of the present invention has a structure of applying the compressing surface pressure to hold not the whole peripheral surface but a part of the surface, it is very effective in inhibiting a honeycomb structure from slipping between the structure and a container or from falling off from the container due to a temperature difference in a place where the canning structure is placed or in suppressing breakage of the honeycomb structure due to high compressing surface pressure as well as it has high vibration resistance under a condition of high temperature. Further, it is preferable that the metal constituting the container for housing the honeycomb structure has a coefficient of thermal expansion of 8×10−7 to 13×10−7, more preferably 8×10−7 to 1×10−7. A canning structure with a container of a metal having a coefficient of thermal expansion within the above range shows superior characteristics such as vibration resistance under a condition of high temperature from the relation among a coefficient of thermal expansion of 4×10−7 of silicon carbide (SiC) constituting the honeycomb structure, circularity, and cylindricality. In addition, it is preferable that the metal constituting the container for housing the honeycomb structure is a ferrite-based stainless steel and/or a low thermally-expansible special alloy. Each of these metals has a coefficient of thermal expansion suitable for constituting a container of a canning structure showing superior characteristics such as vibration resistance under a condition of high temperature from the relation among a coefficient of thermal expansion of silicon carbide (SiC) constituting a honeycomb structure, circularity and cylindricality of a peripheral portion of the honeycomb structure. In the present invention, it is preferable that the compressible elastic member is a ceramic fiber mat. This is because a ceramic fiber mat has sufficient heat resistance and cushioning ability as well as it can easily be obtained and processed. A preferable ceramic fiber mat is a non-intumescent mat substantially not containing vermiculite, a low-intumescent mat containing a small amount of vermiculite, or the like, and contains as the main component, ceramic fibers comprising alumina, high-alumina, mullite, silicon carbide, silicon nitride, zirconia, titania, or a mixture thereof. Among these, further preferable is a non-intumescent mat substantially not containing vermiculite and containing, as the main component, alumina or mullite. Next, a canning structure of the present invention is hereinbelow described in more detail with an example of a method for production thereof. A canning structure can be obtained by housing, in a metal container, a honeycomb structure of the present invention obtained in the aforementioned method of production. In the present invention, the preferable methods to impart compressing surface pressure to the honeycomb structure by means of housing of the honeycomb structure in the container and a compressible elastic member is as follows. That is, there are suitably used a stuffing method shown in FIG. 1, using a guide 17; a tourniquet method shown in FIG. 2, which comprises winding a metallic plate 11c around a honeycomb structure, pulling the plate to impart a pressure to the outer surface of the honeycomb structure, and welding and fixing the to-be-jointed areas of the metallic plate 11c; and a clamshell method shown in FIG. 3, which comprises interposing a honeycomb structure between two metallic container parts 11a and 11b with applying a load to the parts 11a and 11b, and welding the to-be-bonded areas (flanges) 16a and 16b of the parts 11a and 11b to obtain a bonded container. There is also suitably used a swaging method utilizing metal forming technology, shown in FIG. 4, which comprises applying a compression force to a metallic container 11 from the outside via a tap (of pressure type) to reduce the outer diameter of the metallic container 11. Further, there can also be suitably used a swaging method as shown in FIG. 5, which comprises spinning the outer surface of a metallic container 11 by metal forming process using a processing jig 18 with the metallic container 11 being rotated, to reduce the outer diameter of a metallic container, and thereby imparting a pressure to the outer surface of a honeycomb structure in the metallic container. Incidentally, in FIG. 1, the reference numeral 1 denotes a honeycomb structure, the reference numeral 5 denotes a compressible elastic body B, and the reference numeral 11 denotes a metal container. Even in the other drawings, the same reference numerals denote the same portions. The concrete results of the present invention performed are hereinbelow described. EXAMPLES 1 TO 33, COMPARATIVE EXAMPLES 1 TO 14 A silicon carbide powder was used as a raw material. Thereto were added methyl cellulose, hydroxypropoxylmethyl cellulose, a surfactant and water to prepare clay having plasticity. The clay was subjected to extrusion to give a honeycomb shape, followed by drying, and then both end faces were alternately plugged with a plugging material of the same material as the honeycomb structure so that the end faces show checkerboard pattern. After heat-degreasing the honeycomb shaped clay in a N2 atmosphere, it was fired in an Ar atmosphere to obtain a cylindrical honeycomb structure having a diameter of 5.66 inches, a length of 6 inches, and a thickness of 15 mil/cell density of 300 cpi. Incidentally, each of the honeycomb structures obtained was measured for porosity and average pore diameter using a mercury porosimeter, and for circularity and cylindricality by the method described above. The results are shown in Tables 1 and 2. A ceramic non-expansible mat having a thickness of 6.8 mm is wound around the peripheral portion of each of the honeycomb structures obtained above, and each of the honeycomb structures was pressed in a SUS409 can for canning to obtain a canning structure. Incidentally, the ceramic non-intumescent mat had a thickness of 4 mm after being pressed in the can. (Evaluation of Durability) A canning structure was evaluated for durability using a high-temperature gas generator 23 shown in FIG. 6 and a vibration generator 21 connected with the high-temperature gas generator 23. After the canning structure 20 was set at the vibrating portion 22 of the vibration generator 21, a high-temperature gas generated from the high-temperature gas generator 23 was sent in the honeycomb structure from the lower end face (exhaust gas flow-in end face) and discharged from the upper end face (exhaust gas flow-out end face), with operating the vibration generator 21 to generate vertical vibrations. Incidentally, the durability test time was 100 hours, the temperature of the high-temperature gas was 700 degree C., and the vibrations applied was 100 Hz at 60 G. After the durability test time passed, the canning structure was taken out, and conditions of the honeycomb structure were evaluated. The results are shown in Tables 1 and 2. Incidentally, the evaluations of the durability were given with “bad” in the case that both slipping and breakage of the honeycomb structure were caused, “fair” in the case that breakage of the honeycomb structure was caused, “good” in the case of a honeycomb structure with a little slipping (1 mm or less), and “excellent” in the case of the honeycomb structure having no problem. Incidentally, in FIG. 6, the reference numeral 30 denotes an exhaust port, the reference numeral 31 denotes a flowmeter, and the reference numeral 32 denotes a burner. TABLE 1 Porosity Average pore Circularity (%) diameter (μm) (mm) Durability Example 1 38 10 2 Excellent Example 2 44 14 2 Excellent Example 3 47 20 2 Excellent Example 4 38 11 1.5 Excellent Example 5 44 15 1.5 Excellent Example 6 47 20 1.5 Excellent Example 7 38 11 2.5 Good Example 8 44 14 2.5 Excellent Example 9 47 20 2.5 Excellent Example 10 38 9 1 Good Example 11 47 20 1 Excellent Example 12 44 16 1 Excellent Example 13 58 25 2.5 Good Example 14 58 26 2 Excellent Example 15 58 25 1.5 Excellent Example 16 58 24 1 Excellent Comp. Ex. 1 38 10 0.5 Bad Comp. Ex. 2 44 16 0.5 Bad Comp. Ex. 3 47 21 0.5 Fair Comp. Ex. 4 38 10 3 Fair Comp. Ex. 5 44 16 3 Bad Comp. Ex. 6 47 19 3 Bad TABLE 2 Porosity Average pore Cylindricality (%) diameter (μm) (mm) Durability Example 17 38 10 2 Excellent Example 18 44 16 2 Excellent Example 19 47 19 2 Excellent Example 20 38 11 1.5 Excellent Example 21 44 16 1.5 Excellent Example 22 47 21 1.5 Excellent Example 23 38 11 2.5 Excellent Example 24 44 15 2.5 Excellent Example 25 47 20 2.5 Excellent Example 26 58 26 2.5 Excellent Example 27 58 25 1 Good Example 28 58 25 1.5 Excellent Example 29 58 24 2 Excellent Example 30 58 24 3 Excellent Example 31 38 11 3 Good Example 32 47 19 3 Excellent Example 33 44 16 3 Excellent Comp. Ex. 7 38 11 0.5 Bad Comp. Ex. 8 44 16 0.5 Bad Comp. Ex. 9 47 20 0.5 Bad Comp. Ex. 10 38 9 3.5 Fair Comp. Ex. 11 44 15 3.5 Fair Comp. Ex. 12 47 21 3.5 Fair Comp. Ex. 13 58 26 0.5 Fair Comp. Ex. 14 58 25 3.5 Bad As obvious from the results shown in Tables 1 and 2, with regard to canning structures each showing a circularity within the range from 1.0 to 2.5 mm in Examples 1 to 16 and canning structures each showing a cylindricality within the range from 1.0 to 3.0 mm in Examples 17 to 33, no problem such as slipping or breakage of the honeycomb structure was caused, and this made clear that these canning structures shows superior high-temperature vibration resistance to the canning structures each canned with a similar compressing surface pressure in Comparative Examples 1 to 14. INDUSTRIAL APPLICABILITY As described above, since a honeycomb structure of the present invention has a predetermined circularity and cylindricality, it can be housed in a metal container under a safely held condition and hardly has problems such as breakage or break down. In addition, since a canning structure of the present invention has a metal container housing the above honeycomb structure, it is superior in vibration resistance particularly under high temperature conditions.

<SOH> BACKGROUND ART <EOH>While the recently tightened regulation on exhaust gas has been improving in reducing discharged amounts of harmful substances such as hydrocarbons (HC), carbon monoxide (CO), and nitrogen oxides (NO x ) from an engine itself; a three-way catalyst, which is the main current at present, has also been improving. Both of them have been effective in reducing a discharged amount of harmful substances. However, an amount of harmful substances discharged right after an engine has started is highlightened, while discharged substances are reduced extending over the whole running condition of an engine as the improvement according to tightening of exhaust gas regulations. For example, in FTP-75 cycle, which is a regulated running cycle in U.S., 60-80% of total emission discharged in the whole running cycle is discharged in the Bag-1 mode for 140 second right after the engine has started. This is because a catalyst is not sufficiently activated since temperature of exhaust gas is low right after an engine has started (Bag-1A), thereby passing harmful substances through the catalyst. Therefore, some measures are employed, for example, putting a catalyst as close to an engine as possible in a place where exhaust gas has high temperature to raise temperature of the catalyst right after an engine has started, thinning the cell partition walls to decrease heat capacity of a catalyst itself, and increasing cell density of a carrier to quickly absorb heat of exhaust gas and to increase a contact area of a catalyst with exhaust gas. As a catalyst, there is generally used a catalyst produced by loading γ-alumina of a fine porous structure having a high surface area on the surface of cell partition walls of a ceramic honeycomb structure, which is one of cell structures, and then noble metals such as platinum, palladium, and rhodium are loaded, as catalyst components, on the alumina. Further, to these noble metals are added ceria, zirconia, and the like, to store and release oxygen contained in exhaust gas. Such noble metals and oxygen-storing substances are present in a dispersed state in the pores in the γ-alumina layer loaded on the surface of porous cell partition walls (rib) of the carrier. A honeycomb structure is generally used in such a condition that it is housed (canned) in a container made of metal such as stainless steel with being held by the container. In addition, a honeycomb filter obtained by alternately plugging the honeycomb structure at each end face in such a way that it looks checkerboard patterns is suitably used also as a filter for capturing and removing particulate matters contained in dust-containing fluid such as diesel engine exhaust gas (such a filter may hereinbelow be referred to as “DPF.”), and the filter is disposed in a predetermined place after being canned similarly to the case of the aforementioned honeycomb structure. Upon canning, an appropriate compressible elastic member is disposed in a gap between the container and a peripheral surface of the honeycomb structure to impart an adequate compressing surface pressure to the honeycomb structure. An example of related prior art is a method of canning a honeycomb structure in a metal container with holding the honeycomb structure with a mat of an intumescent material containing vermiculite (see U.S. Pat. Nos. 5,207,989 and 5,385,873). However, in the case of the method disclosed in the above U.S. Pat. Nos. 5,207,989 and 5,385,873, compressing surface pressure is rapidly raised by intumescence. Therefore, the rapidly raised compressing surface pressure tends to exceed strength (isostatic strength) of a honeycomb structure having thin walls with low strength, and the honeycomb structure is liable to break. In addition, since compressibility of an intumescent mat is quickly deteriorated from about 800 degree C., compressing surface pressure disappears at about 1000 degree C., and it becomes impossible to hold the honeycomb structure. Whereas, in a non-intumescent mat not containing vermiculite (see U.S. Pat. Nos. 5,580,532 and 2,798,871), the change in surface pressure according to temperature-rise is very small, and the honeycomb structure can be held with surface pressure being hardly decreased even at 1000 degree C. A honeycomb structure having thin walls has conventionally been held using a non-intumescent mat in place of an intumescent mat. However, when a honeycomb structure is wound with a mat serving as a holding member followed by being canned in a metal container, slippage tends to be caused at the joint of the mat, and surface pressure tends to be increased. Further, when a honeycomb structure having a mat wound thereon is stuffed in a metal container, the mat tends to have rumples, and surface pressure tends to be increased at that point. These cause non-uniform distribution of compressing surface pressure acting on a peripheral surface of the honeycomb structure. When partially heightened compressing surface pressure exceeds isostatic strength of the honeycomb structure, the cell structure breaks. In addition, because of the non-uniform distribution of the surface pressure, the cell structure tends to slip due to vibrations of an engine or pressure of exhaust gas in practical use. Incidentally, “isostatic strength” of a honeycomb structure means a value measured by “isostatic fracture strength test” provided for by the automobile standards JASO standard M505-87 published by Society of Automotive Engineers of Japan, Inc. Specifically, the test is conducted in such a manner that a cell structure as a carrier is put in a rubber tube, and the container is capped and subjected to isotropic pressure compression, which imitates compression load in the case that a carrier is held at a peripheral surface thereof by a can of a converter. The isostatic strength is shown by a value of pressure at the time of breakage of a carrier. A catalyst converter for purifying automotive exhaust gas generally employs a canning structure in which a carrier is held at a peripheral surface thereof. It is a matter of course that high isostatic strength is preferable in view of canning. When the actual surface pressure becomes higher than the intended surface pressure planned upon design of canning, the structure may break at the point if the surface pressure exceeds isostatic strength of the honeycomb structure. According as thickness of cell partition walls decreases and strength of the structure is lowered, it is necessary to decrease the intended surface pressure, and it is necessary to minimize fluctuation of the surface pressure by suppressing extraordinary increase of actual canning surface pressure. It is ideal that the actual surface pressure is equal to the intended surface pressure because it makes possible the canning design just as aimed. Further, a honeycomb structure may break because of varied gap between the honeycomb structure and the metal container due to precision of an external shape of the honeycomb structure or because of uneven compression pressure act on the peripheral portion of the honeycomb structure and high holding surface pressure acts partially as a result of slippage of a holding member caused when the honeycomb structure is housed in a metal container. As the partition walls of a honeycomb structure are made thinner, the isostatic strength level of the honeycomb structure becomes lower, which requires to make compressing surface pressure of the honeycomb structure as low as possible with keeping the minimum surface pressure required for holding a honeycomb structure. As the level of compressing surface pressure is lowered, it is necessary to make variance in surface pressure smaller, i.e., to give more uniform distribution of surface pressure. The present invention has been made in view of the problems of the prior art and aims to provide a honeycomb structure which is capable of being housed in a metal container under a safely held condition and which hardly has problems such as breakage or breakdown, as well as a canning structure which has a metal container housing the honeycomb structure and which is superior in vibration resistance particularly under high temperature conditions.

<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>FIG. 1 is a partially cut-away view showing one example of the stuffing method used for housing a honeycomb structure in a metallic container. FIG. 2 is a perspective view showing one example of the tourniquet method used for housing a honeycomb structure in a metallic container. FIG. 3 is a perspective view showing one example of the clamshell method used for housing a honeycomb structure in a metallic container. FIG. 4 is a sectional view parallel to the direction of through-holes, showing one example of the swaging method used for housing a honeycomb structure in a metallic container. FIG. 5 is a sectional view parallel to the direction of through-holes, showing one example of the swaging method used for housing a honeycomb structure in a metallic container. FIG. 6 is a schematic view showing a high-temperature gas generator and a vibration generator connected with the high-temperature gas generator. detailed-description description="Detailed Description" end="lead"?

20040831

20070925

20050505

68072.0

TURNER, ARCHENE A

HONEYCOMB STRUCTURAL BODY AND CANNING STRUCTURAL BODY STORING THE HONEYCOMB STRUCTURAL BODY

UNDISCOUNTED

ACCEPTED

ACCEPTED

Aqueous liquid formulations of pyrazoline brighteners

The claimed liquid formulations contain an organic acid and a branched mono- or di-alcohol. The addition of the alcohol improves the storage stability of the liquid formulations.

1. An aqueous liquid formulation comprising an organic acid, a branched mono- or di-alcohol and a pyrazoline brightener of the formula where X is O, SO2, SO2NZ or a direct bond, Y is an alkylene chain, Z is H or alkyl, R1 and R2 are singly an alkyl, cycloalkyl or aralkyl radical or together the remaining members of an N-heterocycle, Z1 is H or alkyl, Z2 is H, alkyl or aryl, and A is an anion of an organic acid. 2. The aqueous liquid formulation according to claim 1, wherein the pyrazoline brightener is a compound of the formula where D is —CH2CH2—, —CH2CH2CH2—, —CH2CH2—OCH2CH2, R1′ and R2′ stand are independently C1-C2-alkyl, and T1, T2, T3 stand are independently H, CH3 or Cl. 3. The aqueous liquid formulation according to claim 1, wherein the organic acid is lactic acid, formic acid, or acetic acid or mixtures thereof. 4. The aqueous liquid formulation according to claim 1, wherein the branched mono- or di-alcohol is neopentylglycol or tertiary butanol. 5. The aqueous liquid formulation according to claim 1, further comprising 20% to 60% by weight of the organic acid. 6. The aqueous liquid formulation according to claim 1, further comprising 15% to 40% by weight of the branched mono- or di-alcohol. 7. The aqueous liquid formulation according to claim 1, further comprising 1% to 60% by weight of the pyrazoline brightener. 8. The aqueous liquid formulation according to claim 1, further comprising at least one customary auxiliary. 9. (canceled) 10. The aqueous liquid formulation according to claim 1, wherein Y is an alkylene chain interrupted by O, S, CONH. 11. The aqueous liquid formulation according to claim 2, wherein D is 12. The aqueous formulation according to claim 2, wherein A is lactate or formate. 13. A method for brightening an acrylic fiber comprising the step of incorporating an aqueous formulation according to claim 1 in the wet-spinning process or exhaust process for the acrylic fiber. 14. An acrylic fiber made in accordance with the method of claim 13. 15. A method for brightening an acrylic fiber comprising the step of brightening the acrylic fiber with an aqueous formulation as claimed in claim 1. 16. An acrylic fiber made in accordance with the method of claim 15.

It is known to use certain pyrazoline brighteners, which bear basic groups and are present in the form of their salts with lactic acid, for brightening acrylic fibers (DE 3 134 942). A commercially available aqueous liquid formulation of such a brightener contains lactic acid, formic acid and methoxypropanol as well as the brightener. However, this formulation is still in need of improvement with regard to its stability in storage. It is thus an object of the present invention to provide aqueous liquid formulations of pyrazoline brighteners that have improved stability in storage. It has now been found that this object is achieved when a branched mono- and di-alcohol is added to the formulation of this brightener type. The invention accordingly provides aqueous liquid formulations of pyrazoline brighteners of the formula where X is O, SO2, SO2NZ or a direct bond, Y is an alkylene chain which may be interrupted by O, S or CONH, Z is H or alkyl, R1 and R2 are singly an alkyl, cycloalkyl or aralkyl radical or together the remaining members of an N-heterocycle, Z1 is H or alkyl, Z2 is H, alkyl or aryl, and A is an anion of an organic acid, wherein these liquid formulations contain an organic acid and a branched mono- or di-alcohol as well as a pyrazoline brightener of the above formula. Suitable alkyl radicals R1 and R3 are especially those having 1 to 4 carbon atoms, which may be substituted by halogen such as fluorine, chlorine and bromine hydroxyl groups, cyano groups, C1-C4-alkoxy groups, phenoxy groups, C2-C5-alkylcarbonyloxy groups or C2-C5-alkoxycarbonyloxy groups. Suitable cycloalkyl radicals R1 and R2 are cyclopentyl and cyclohexyl radicals. Suitable aralkyl radicals R1 and R2 are especially benzyl and phenylethyl radicals. Suitable heterocyclic radicals which can be formed by R1 and R2 combining with the nitrogen atom are for example pyrrolidine, piperidine, imidazole, morpholine and thiomorpholine radicals. Suitable alkyl radicals Z, Z1 and Z2 are especially unsubstituted alkyl radicals having 1 to 4 carbon atoms. Suitable aryl radicals Z2 are in particular phenyl radicals, which may be substituted by one or more halogen atoms, C1-C4-alkyl groups, C1-C4-alkoxy groups, cyano groups, carboxylic ester groups and carboxamide groups. Useful alkylene radicals Y are especially those having 2 to 4 carbon atoms such as The anion A(−) may be an anion of a low molecular weight organic acid, examples being formate and lactate. Preferred pyrazoline brighteners are those of the formula where D is —CH2CH2—, —CH2CH2CH2—, —CH2CH2OCH2CH2, R1′ and R2′ are each C1-C2-alkyl, T1, T2, T3 are H, CH3 or Cl and A is lactate or formate. Preferably, T1-T3 do not represent C1 or CH3 at one and the same time. The amount of these pyrazoline brighteners in the ready-prepared liquid formulation can be 1% to 60% and preferably 5% to 30% by weight. The pyrazoline bases which underlie the brightener salts defined above are known and are described for example directly or indirectly (as quaternary salts) in the following patent literature: DE-A 1 155 418, 1 237 124, 1 469 222, 1 904 424, 2 011 552, 2 050 725, 2 248 772, 2 534 180 and 2 700 996 and U.S. Pat. No. 3,131,079 and also 3 135 742. As well as the brightener salt, the liquid formulations of the invention additionally contain organic acids and branched mono- or di-alcohols. Useful organic acids include low molecular weight organic acids of the kind which are customary for salt formation of pyrazoline bases, for example formic acid, acetic acid or lactic acid or mixtures of such acids. The amount of these acids based on the ready-prepared liquid formulation is generally in the range from 20% to 60% and preferably from 30% to 50% by weight. The fraction of branched mono- or di-alcohol in the ready-prepared liquid formulation can be 15% to 40% and preferably 20% to 30% by weight. Preferred mono- or di-alcohols are neopentylglycol and tertiary butanol. In addition, the liquid formulations of the invention can contain the auxiliaries customary for optical brighteners, such as for example hydrotropic agents (urea for example), solution-stabilizing agents (ethylene glycol diacetate for example), preservatives, water-soluble cationic shading dyes, each in amounts of up to 10% by weight. The liquid formulations of the invention are preferably prepared by adding the individual components of the formulation in the following order and mixing them in a suitable manner: organic acid, branched mono- or di-alcohol, brightener salt, water. Instead of the brightener salt it is also possible to start from the underlying base and to increase the amount of organic acid by the amount needed for salt formation. The liquid formulations of the invention have an improved stability in storage compared with the hitherto customary commercial form. This improved storage stability shows itself in that the color coordinates of these formulations rise distinctly less on prolonged storage in particular. The liquid formulations of the invention are used in a conventional manner for incorporation into spinning dopes for the production of polyacrylonitrite fibers in the so-called wet-spinning process or for brightening ready-prepared acrylic fibers in an exhaust process. EXAMPLES A liquid formulation was prepared by intensively mixing the following components at room temperature in this order: 40 g of lactic acid; 6 g of formic acid; 23.3 g of neopentylglycol (90% pure); 19.2 g of brightener (about 79% pure); 11.5 g of water. The brightener used has the formula This liquid formulation was tested for storage stability (measurement of the color coordinates x and y) together with a commercially available liquid formulation of the same brightener. The commercially available liquid formulation contains 21 g of methoxypropanol and 13.8 g of water instead of 23.3 g of neopentylglycol and 11.5 g of water with the composition otherwise identical to that of the formulation of the invention. The following x and y values were measured as a measure of stability for both formulations: Inventive Commercial formulation material x value y value x value y value At the start 0.353 0.390 0.354 0.392 After 4 weeks' 0.362 0.404 0.368 0.401 storage RT/dark After 4 weeks' 0.363 0.402 0.402 0.425 storage 50° C./dark After 10 weeks' 0.383 0.433 0.390 0.433 storage RT/dark After 10 weeks' 0.386 0.428 0.449 0.466 storage 50° C./dark These values show that the color coordinates rise distinctly less for the formulation of the invention compared with the commercial material. This indicates superior stability for the inventive formulation, which contains neopentylglycol.

20050525

20071127

20051117

81101.0

NOLAN, JASON MICHAEL

AQUEOUS LIQUID FORMULATIONS OF PYRAZOLINE BRIGHTENERS

UNDISCOUNTED

ACCEPTED

ACCEPTED

Apparatus and method for mounting photovoltaic power generating systems on buildings

Rectangular PV modules (6) are mounted on a building roof (4) by mounting stands that are distributed in rows and columns. Each stand comprises a base plate (10) that rests on the building roof (4) and first and second brackets (12, 14) of different height attached to opposite ends of the base plate (10). Each bracket (12, 14) has dual members for supporting two different PV modules (6), and each PV module (6) has a mounting pin (84) adjacent to each of its four corners. Each module (6) is supported by attachment of two of its mounting pins (84) to different first brackets (12), whereby the modules (6) and their supporting stands are able to resist uplift forces resulting from high velocity winds without the base plates (10) being physically attached to the supporting roof structure (4). Preferably the second brackets (14) have a telescoping construction that permits their effective height to vary from less than to substantially the same as that of the first brackets (12).

1. A photovoltaic assembly in combination with a building roof, said assembly comprising: a plurality of PV modules; and a plurality of PV module mounting stands distributed on said roof, each of said mounting stands comprising a base plate resting on said roof and four module mounting means extending upwardly from the base plate, each of said module mounting means having an outer end that is adapted for attachment to a PV module, characterized in that each PV module is supported in vertical spaced relation to said roof surface by module mounting means of four different PV module mounting stands. 2. Apparatus according to claim 1 wherein said PV module mounting stands are distributed on said roof in rows and columns, and each of said PV modules is supported by two PV module mounting stands in one row and two PV module mounting stands in an adjacent row. 3. Apparatus according to claim 1 further characterized in that each PV module mounting stand has first and second brackets attached to its base plate, with each bracket comprising two of said module mounting means. 4. Apparatus according to claim 3 wherein said module mounting means are in the form of arms that are part of the first and second brackets, with each arm having an outer end characterized by means for interlocking with attachment means on said modules. 5. Apparatus according to claim 4 wherein the arms of said first brackets are longer than the arms of said second brackets, whereby said PV modules are tilted relative to said roof. 6. Apparatus according to claim 4 wherein the arms of said first brackets are of fixed length and the arms of said second brackets are of adjustable length. 7. Apparatus according to claim 4 wherein each PV module has a rectangular configuration and further characterized in that each arm of each bracket is attached to a different PV module. 8. Apparatus according to claim 1 wherein the four module mounting means of each stand are in the form of arms that have a first end attached to the base plate and a second end that is spaced from the base plate and is adapted for attachment to a PV module. 9. Apparatus according to claim 1 further characterized in that each PV module mounting stand has first and second U-shaped brackets attached to Its base plate in spaced relation to one another, with each bracket having a base portion attached to the base plate and two mutually spaced arms attached to the base plate, said arms constituting the module mounting means of the PV module mounting stand, and each of said arms being connected to and supporting a different PV module. 10. Apparatus according to claim 9 wherein the second brackets are adjustably secured to the base plates so that they can be moved to vary the distance between them and the first brackets. 11. Apparatus according to claim 1 wherein said base plates are not fastened to said roof. 12. A photovoltaic assembly in combination with a building roof, said assembly comprising: a plurality of PV module mounting stands resting on said roof; each of said PV module mounting stands comprising a base plate resting on said roof and first and second U-shaped brackets each comprising a base portion attached to said base plate and first and second arms attached to the base portion and extending upwardly from the base portion and the base plate, each of said first and second arms having means for attachment to a PV module; and a plurality of rectangular PV modules having four attachment means at its periphery arranged in a rectangle; each of said PV modules having two of its four attachment means attached to first and second arms of two different first brackets and the other two of its four attachment means attached to first and second arms of two different second brackets, whereby each PV module is supported in vertical spaced relation to said roof by four different PV mounting stands. 13. Apparatus according to claim 12 wherein the arms of said first brackets have a fixed length and the arms of said second brackets are adjustable in length. 14. Apparatus according to claim 13 wherein each of said second brackets comprises three parts, a first part having a base portion secured to the base plate and first and second arms extending upwardly from said base portion, and second and third parts that are slidably coupled to said first and second arms of said first part so as to form telescoping extensions of said first and second arms of said first part, and further wherein the two arms of each of the first brackets are attached to different PV modules and the second and third parts of each of the second brackets are attached to different PV modules. 15. Apparatus according to claim 12 wherein said PV module mounting stands are distributed on said roof in rows and columns, and each of said PV modules is supported by two stands in one row and two stands in another adjacent row. 16. Apparatus according to claim 12 wherein each module has connecting pins projecting at four sides thereof, and further wherein said arms have openings in which said connecting pins are received so as to lock said PV modules to said brackets. 17. A photovoltaic assembly in combination with a building roof surface, said assembly comprising: a plurality of PV module assemblies, each of said assemblies comprising at least two PV modules that are electrically interconnected and mechanically ganged together; and a plurality of mounting stands distributed on said roof surface, each of said mounting stands comprising a base plate resting on said roof surface, and first and second brackets mounted to said base plate in spaced relation to one another, each of said brackets comprising first and second arms extending upwardly from the base plate away from the roof surface, each of said first and second arms of said first and second brackets being attached to a different one of said PV module assemblies so that each PV module assembly is supported in vertical spaced relation to said roof surface by (a) first and second arms of two different first brackets and (b) first and second arms of two different second brackets. 18. Apparatus according to claim 17 wherein the stands are distributed on said roof surface in rows and columns, and each PV module assembly is supported by two stands in one row and two stands in another adjacent row. 19. Apparatus according to claim 17 wherein each of said second brackets comprises three parts, a first part having a bottom portion secured to said one base plate and first and second arms extending upwardly from said bottom portion, and second and third parts that are slidably coupled to said first and second arms of said first part so as to form telescoping extensions of said first and second arms of said first part, and further wherein said two arms of each of said first brackets are attached to different PV modules and said second and third parts of each of said second brackets are attached to different PV modules. 20. Apparatus according to claim 19 wherein said first and second arms of said first brackets extend for a first distance from said base plates, and said second and third parts are movable between a first position in which they extend for a second distance from said base plate that is less than said first distance and a second position in which they extend for a third distance from said base plate that is substantially the same as the first distance. 21. Apparatus according to claim 19 wherein when said second and third parts of said second brackets are movable between a first retracted position and a second extended position, and further wherein said PV module assemblies are inclined relative to said roof when said second and third parts are in said first retracted position and are substantially parallel to said roof when said second and third parts are in said second extended position. 22. Apparatus according to claim 17 wherein said first or second brackets are movable on said base plates, whereby to adjust the distance between said first and second brackets on said base plates. 23. Apparatus according to claim 17 wherein said base plates are elongate and have a longitudinal axis, and further wherein said brackets are U-shaped members and said arms of said brackets are flat members that extend parallel to the longitudinal axis of the base plate to which the brackets are attached.

This application claims the benefit of the filing date of U.S. Provisional Application Ser. No. 60/371,576, filed 11 Apr. 2002 by Miles C. Russell for “Corner-Jack Photovoltaic Mounting System”. FIELD OF THE INVENTION This invention relates generally to installation of photovoltaic power generating systems and in particular to a novel approach for mounting photovoltaic modules on the roofs of buildings. BACKGROUND OF THE INVENTION As used herein the term “PV module” identifies a photovoltaic power generating unit in the form of an integrated structure comprising a plurality of electrically interconnected photovoltaic cells and means for supporting and protecting the cells, and the term “PV module assembly” identifies a structure comprising two or more PV modules that are mechanically ganged together and electrically interconnected to form a unitary power source. A variety of systems and methods have been devised for mounting PV modules and associated components of solar electric (PV) power generating systems on buildings. The market for solar electric power generating systems that operate in parallel with existing grid electricity supply and that can be safely and simply installed on the rooftops of businesses, factories, schools, hospitals, commercial establishments and the like, is growing rapidly in the United States and elsewhere. As the cost per watt has dropped in recent years for photovoltaic units, the need for improving methods of mounting photovoltaic modules to building roofs has become more critical. More precisely, as the cost of solar cells per se has declined, the non-solar cell components required for installing a functioning photovoltaic system become more critical with respect to overall system costs. However, care must be taken to insure that photovoltaic systems are installed with due respect to environmental factors such as wind-loading and environmental stresses, and preserving building integrity, notably, avoiding the use of mechanical fasteners that penetrate the roof. A number of different approaches have been taken with respect to providing means for supporting photovoltaic panels on a roof. These prior methods are exemplified by the inventions described in U.S. Pat. No. 4,886,554, issued Dec. 12, 1989 to Woodring et al for “Solar Roofing Assembly”; U.S. Pat. No. 5,746,839, issued May 5, 1998 to Thomas L. Dinwoodie for “Lightweight, Self-Ballastng Photovoltaic Roofing Assembly”; and U.S. Pat. No. 6,148,570, issued Nov. 21, 2000 to Thomas L. Dinwoodie et al for “Photovoltaic Building Assembly With Continuous Insulation Layer”. U.S. Pat. No. 6,148,570 discloses a photovoltaic building assembly comprising the use of a plurality of PV module support assemblies to support photovoltaic modules in close proximity to one another on a roof or other building support surface on which the photovoltaic building assembly is installed. Each of the PV module support assemblies comprises a base located on the building support surface, and an outwardly extending portion that projects through a continuous insulation layer, preferably in the form of a sprayed-on foam insulation layer, that covers the building support surface and the base of the PV module support assembly. The PV modules are mounted to and supported by the outwardly extending portions of the module support assemblies above the insulation layer. The base of the PV module support assembly may be made of concrete pavers or other heavy material to help counteract wind-induced uplift and sliding forces by their weight alone. U.S. Pat. No. 6,148,570 also teaches that by having their bases embedded within the insulation layer, and also by being fastened to the building support surfaces by adhesive or through the use of mechanical fasteners which may, or may not penetrate the building support surface, additional stability and mounting strength is achieved. The patent also suggests that the base portions may be sized so that embedding them within the insulation layer may be all that is needed to secure the PV module support assemblies to the building support surface. A characterizing aspect of the photovoltaic building assembly disclosed in U.S. Pat. No. 6,148,570 is that each PV module support assembly extends horizontally parallel to and in supporting relation to the mutually confronting edges of two adjacent modules, with each side of each module being supported by a different PV module assembly and adjacent modules being close to one another so as to form a covering for the supporting roof structure. OBJECTS AND SUMMARY OF THE INVENTION A primary object of the invention is to provide a new and improved method and apparatus for mounting PV modules to a building roof. A more specific object is to provide an improved system for mounting PV modules to flat roofs typical of commercial buildings that is economical, requires no special tools for installation and can be used with a variety of roofing surfaces. Another specific object of the invention is to provide a system for mounting solar modules on a building roof that eliminates the need for mechanically or adhesively attaching the module-mounting structure to the building roof, whereby to preserve the integrity and waterproof characteristics of the supporting roof structure. A further object of the invention is to provide a new and improved system for mounting solar modules on roofs that provides for walkways between rows of solar modules for easy access for servicing and repair. Still another object is to provide a photovoltaic module mounting system that is adapted to mount PV modules at a selected tilt angle, e.g., in the range of 0°-15°, to benefit annual energy production. A further object is to provide improved means for mounting a plurality of PV modules on a roof that allows the PV modules to shift from a tilt position to a near horizontal position in response to pressure differentials caused by extreme winds, whereby to release wind pressure and reduce or substantially eliminate wind uplift forces. These and other objects are achieved by providing a mounting system for PV modules and PV module assemblies in the form of a plurality of mounting stands that are intended to rest on a supporting roof, with each mounting stand consisting of a base plate, and first and second brackets attached to the base plate. The base plate rests on the supporting roof and is sized to introduce a defined separation distance between rows of PV modules to minimize row-to-row shading. The base plate also is sized also to distribute the dead load and to reduce the downward pressure on the supporting roof structure. The first and second brackets are secured at opposite ends of the base plate. These mounting stands are distributed in spaced relation to one another on a supporting roof in a row and column arrangement. The first and second brackets may be of fixed height, with one bracket being taller than the other. Preferably, however, one bracket has a fixed height and the second bracket is constructed to permit its effective height to vary from a first minimum value that is less than that of the first bracket to a second maximum value that is substantially the same as that of the first bracket. In the preferred embodiment, each bracket has dual members for supporting two different PV modules or PV module assemblies. The PV modules are rectangular or square and are supported by the mounting stands by attaching a corner of each module to a different mounting bracket. More specifically, two corners of each module are mounted to different first brackets and the other two corners of each module are attached to different second brackets. The first and second brackets of each mounting stand introduce a controlled gap between adjacent PV modules in a row. The distributed mounting stands and the supported PV modules provide sufficient weight to resist movement by wind uplift forces resulting from wind velocities of up to about 70 miles per hour. Under higher velocity winds, e.g., winds up to about 110 miles per hour, the ability of the mounting stands and the supported PV modules to withstand movement is enhanced and preserved by the ability of the second brackets to extend their heights so as to shift the modules to a near horizontal position, thereby releasing wind pressure on the modules and reducing wind uplift forces. Depending on the size of the modules, several modules may be ganged together to form a discrete PV module assembly, with each PV module assembly being supported at two spaced apart points by separate first brackets and at two other points by separate second brackets. Other features and advantages of the invention are disclosed or rendered obvious by the following detailed description which is to be considered together with the accompanying drawings. THE DRAWINGS FIG. 1 is a plan view illustrating a number of PV modules and apparatus embodying the present invention for mounting the modules on a roof, with certain of the PV modules being broken away for illustrative purposes only; FIGS. 2 and 3 are fragmentary sectional views in side elevation illustrating how the preferred form of mounting apparatus is adapted to permit the PV modules to change positions; FIG. 4 is a fragmentary cross-sectional view of one of the PV modules showing one form of mounting stud arrangement; FIG. 5 is a front elevational view showing one of the taller brackets for supporting a solar module mounted on a base plate; FIG. 6 is a side view in elevation of the same bracket; FIG. 7 is a plan view of the same bracket; FIG. 8 is a front view in elevation of the bottom part of the adjustable bracket assembly; FIG. 9 is a side view in elevation of the member shown in FIG. 9; FIG. 10 is a plan view of the bottom portion of the adjustable bracket assembly; FIG. 11 is a sectional view taken along line 11-11 of FIG. 10; FIG. 12 is a side view in elevation of one of the slide members of the adjustable bracket assembly; FIG. 13 is a side elevational view illustrating the adjustable bracket assembly in extended position; FIG. 14 is a side view in elevation of a junction box adapted for attachment to the PV mounting apparatus of the present invention; and. FIG. 15 is a plan view of the same junction box. In the several figures, like components are identified by like numerals. SPECIFIC DESCRIPTION OF THE INVENTION Referring to FIGS. 1, 2 and 3, the invention comprises a set of mounting stands 2 that are distributed on a supporting roof structure 4 and support a plurality of PV modules 6, with each stand consisting of a base plate 10 and two mutually spaced brackets 12 and 14 that are attached to opposite ends of the base plate. The brackets 12 are of fixed height. The other brackets 14 also may be of fixed height and shorter than brackets 12 in order to provide a selected angle of tilt to PV modules. Preferably, however, the brackets 14 are adjustable in height, as hereinafter described. The mounting stands are laid out on a flat roof in a rectangular grid pattern of rows and columns as shown in FIG. 1, with the row and column spacing being determined by the dimensions of the solar modules panels to be mounted as well as the tilt angle and site latitude. Preferably the base plates 10 of the mounting stands are sized to introduce a defined separation distance between the rows of PV modules 6, with that separation distance being set to minimize row-to-row shading and also to provide spaces 16 between adjacent rows of modules that are wide enough to serve as walkways for easy access to the modules for service and repair. Base plates 10 also are sized so as to distribute the dead load and reduce the downward pressure on the roof from the weight of the mounting stands and the modules supported by the mounting stands. In the preferred embodiment of the invention, the base plates and the brackets are made of sheet metal, e.g., aluminum, but they could be made of some other material. If desired, the base plates may be provided with an adhered cushioning material on their undersides to protect the roof surface. Such a cushioning material may be desirable where the base plates rest on a waterproofing diaphragm covering a roof surface. The base plates 10 are provided with fastener elements for securing the brackets in place. Preferably, but not necessarily, the fasteners are in the form of vertically-projecting threaded studs 18 (FIGS. 5, 7) that are permanently secured to the base plates. Of course, the fastener elements could take other forms, e.g., they may be separate screw fasteners inserted into holes in the base plate, with those holes being countersunk to accommodate the heads of the fasteners, so as to prevent the fastener heads from injuring the underlying roof surface. Referring to FIGS. 5-7, the taller brackets 12 of U-shaped configuration, comprising a flat base portion 20 and a pair of vertically-extending arms 22A and 22B. The flat base portion 20 is provided with a plurality of openings 24 to accommodate the threaded studs 18 of the associated base plate. Nuts 19 are threaded onto studs 18 to releasably anchor brackets 12 to base plates 10. The upper ends of arms 22A and 22B are provided with identical L-shaped slots 26 comprising horizontal portions 26A and vertical entry portions 26B that are used to receive mounting pins(described hereinafter) on the PV modules (or the PV module assemblies). Additionally, the arms 22A and 22B of brackets 12 may be provided with enlarged openings 30 to accommodate a nipple 32 (shown in phantom in FIG. 5) that serves as a protective conduit for electrical wires (not shown) that are used to interconnect the modules. The nipples are secured to brackets 12 by means of bushings 34 (also shown in phantom) that are attached to the opposite ends of the nipples by screw connections or some other suitable connecting means. Referring now to FIGS. 8-13, it is preferred that the other brackets 14 be adjustable in height. In their preferred form, each bracket 14 comprises a U-shaped bottom part or anchor member 38 and two identical slidable parts or slides 40A and 40B. The anchor member 38 comprises a transversely-extending base 42 and two parallel arms 44A and 44B that extend vertically upward from base 42. The base 42 is provided with two elongate holes 45 to accommodate threaded studs (not shown but like studs 18) that project upwardly from the base plate in the same manner as studs 18 secure brackets 12. Each of the arms 44A and 44B is bent back along its two opposite side edges as shown at 46, so that the end faces of those edges confront the adjacent inner surface 48 of the arm. The end faces of those edges are spaced from surfaces 48 so as to form a channel to receive the slides 40A and 40B. Nuts (not shown but like nuts 19) are threaded onto the upwardly-projecting studs or fasteners to anchor the bottom parts 38 of anchor members 14 to base plates 10. Additionally, each of the arms 44A and 44B of anchor members 38 are provided with a vertically elongate hole 50. Referring now to FIGS. 10, 12 and 13, the slidable parts or slides 40A and 40B have a thickness substantially the same as arms 22A and 22B, and are provided at their top ends with identical L-shaped slots 52, comprising horizontal portions 52A and vertical entry portions 52B, that receive mounting pins on the PV modules (or on PV module assemblies). Each of the slides 40A and 40B also is formed with a hole 56 (FIG. 12) and anchored in that hole is a laterally projecting stud 58 (FIG. 13) which is sized to make a sliding fit in the elongate hole 50 of one of the arms 44A and 44B. As seen in FIG. 10, each of the slides 40A and 40B has a thickness that is slightly less than the gap between the end faces of the bent edges of arms 44A and 44B and their inner surfaces 48, whereby to simultaneously enable the slidable parts 40A and 40B to move up and down relative to the bottom part 38 with only minimal play in a direction perpendicular to inner surfaces 48. The length of elongate holes 50 determines the extent to which the slides may be moved up and down relative to anchor member 38. Also the lengths of slides 40A and 40B, arms 44A and 44B and holes 50, and the positions of the L-shaped slots 52 are set so as to assure (1) a selected tilt angle for the modules supported by brackets 12 and 14 when the slides are in their bottommost position and (2) a substantially horizontal position for the same modules when slides 40A and 40B are extended to the uppermost position determined by studs 58 reaching the top ends of elongate holes 50. Brackets 12 and 14 are oriented on base plates 10 so that the ends of horizontal portions 26A and 52A of slots 26 and 52 remote from vertical entry portions 26B and 52B face away from each other, as shown in FIGS. 2 and 3. FIG. 4 illustrates how a PV module is adapted for the present invention. The form of PV module is not critical to this invention and may take various forms well known in the art. For that reason, and also for convenience of illustration, the internal structure of the module is not illustrated. Suffice it to say that the module has a square or rectangular configuration. By way of example but not limitation, PV modules commonly are in the form of a laminated sandwich that comprises a front panel made of transparent glass, a back panel made of glass, Tedlar®, or some other material, and a plurality of interconnected photovoltaic cells and a transparent encapsulant disposed between the front and back panels in a hermetically sealed arrangement. A frame may be provided to protect the edges of the laminated components and also to facilitate handling and mounting. This form of PV module is described and illustrated in U.S. Pat. No. 5,228,924, issued Jul. 20, 1993 to James M. Barker et al., and, U.S. Pat. No. 5,478,402, issued Dec. 26, 1995 to Jack I. Hanoka. U.S. Pat. No. 5,228,924 also shows how a plurality of PV modules can be ganged together to form a multi-module assembly. In FIG. 4, the PV module is provided at its margins with a protective frame 76 which preferably, but not necessarily, is made of a metal such as aluminum or stainless steel and defines a channel 78 that is sized to make a close fit with the module. A suitable sealant or gasket 80 may be provided between the edges of the module and the frame. In this illustrated embodiment, the frame has a standoff portion 82 with a depth sufficient to accommodate mounting pin assemblies for connecting the PV module to the brackets 12 and 14. The mounting pin assemblies may take various forms. A preferred form of mounting pin assembly comprises a threaded pin or stud 84 having a head 85. Mounted on each stud are two washers 86 and 88 and a spacer sleeve 87 that keeps those washers spaced apart by a distance that preferably is about two to three times greater than the thickness of the arms 22A and 22b of brackets 12 and the thickness of slides 40A and 40B of brackets 14. The studs 84 are mounted in holes in frame 76 and are secured in place by nuts as shown at 90, preferably with addition of another washer 92. Each stud is locked against axial movement relative to the frame by tight engagement of opposite sides of standoff portion 82 by washers 88 and 92. Each module is provided with four mounting pin assemblies, each adjacent a different corner of the PV module. Mounting a plurality of PV panels 6 on a roof by means of the present invention involves first placing a plurality of stands 2 on a roof in a grid pattern of rows and columns as shown, with the stands all oriented in the same direction so that the brackets 14 of the stands in one row face the brackets 12 of the stands in the next immediate row. The stands are set with each bracket 14 loosely attached to its base 10 so that it can be moved over a short range determined by the length of the elongate holes 45 in the base of its anchor member 38. Then individual modules 8, each with mounting pins 84 at their four corners, are attached to the brackets. Each module in turn is positioned so that two of its mounting pins 84 are inserted into slots 26 of one of the arms 22A or 22B of brackets 12 of adjacent stands 2 in one row and the other two of its mounting pins are inserted into the slots 52 of one of the slides 40A or 40B of the brackets 14 of two adjacent stands 2 in the next row of stands. With the mounting pins 84 of each module so engaged with brackets 12 and 14 of four different stands 2, the brackets 14 supporting each module are moved away from the brackets 12 supporting the same modules, whereby locking pins 84 of the modules are engaged with the ends of slots 26A and 52A that are remote from their entry portions 26B and 52B respectively. Then the nuts (not shown) coupling the brackets 14 to studs on the base plate are secured, so as to lock those brackets to the base plate. Essentially the brackets are positioned so as to capture mounting pins 84 in slots 26 and 52, thereby preventing the PV modules from being lifted out of engagement with the brackets without first loosening the fasteners that hold brackets 14 to the base plates, and then moving brackets 14 in a direction and for a sufficient distance permitted by holes 45 to allow the locking pins 84 to be lifted out of slots 26 and 52. To summarize, each of the arms 22A and 22B of brackets 12 is engaged by a locking pin assembly of a different solar module, and the same is true of the sliding members or slides 40A and 40B of the other brackets 14, i.e., each bracket 12 and 14 is connected to and supports two different modules. Referring to FIG. 2, brackets 14 are arranged so that when the slides 40A and 40B are in their lowermost position, the modules 6 are at a selected angle of tilt, e.g., 5°, determined by the fixed height of brackets 12 and the effective minimum height of the brackets 14. The length of elongate holes 50 in the anchor members of brackets 14 is such that when the studs 58 engage the upper ends of those holes, slides 40A and 40B coact with brackets 12 to support the PV modules in a substantially horizontal position (FIG. 3). Having the slides 40A and 40B free to move upwardly instead of locking them to anchor members 38 is advantageous—when extreme winds occur, brackets 14 will respond to pressure differentials on the PV modules the shifting upward of slides 40A and 40B, thereby releasing wind pressure and reducing or substantially eliminating excessive wind uplift forces on the modules and the stands 2. With this dynamic feature, every PV module (or PV assembly where two or more PV modules are ganged together) can independently adjust its tilt angle to eliminate uplift forces from high velocity winds. In this connection it should be noted that an important aspect of the invention is that all of the PV modules are mechanically linked together by the mounting stands, thereby aiding in resisting movement under the force of winds. If desired, ballast can be added around the perimeter of the array of Installed modules to aid in resisting movement under unusual wind forces. Thus, for example, as shown in FIGS. 1 and 2, paver blocks 94 may be placed on the base plates to add stability against uplifting wind forces. A further aspect of the invention is that the invention may include provision of junction boxes as shown at 96 in FIGS. 1, 2, 14 and 15. The junction boxes are formed with two arms 98A and 98B projecting forwardly or from opposite sides. Arms 98A and 98B are attached to the upstanding arms 22A and 22B respectively of a bracket 12 by means of screws (not shown) that pass through holes 102 in bracket arms 22A and 22B, and screw into nuts 104 welded to arms 98A and 98B in coaxial relation to the holes in those arms. The junction boxes may be interconnected by wiring as indicated by the dotted line 106 in FIG. 1 and serve to interconnect rows of modules while the nipples 32 serve as pass-throughs for wiring that interconnects the several modules in a row. A feature of the invention is that at the perimeter of an array of modules on a roof, the orientation of the base plates may be reversed as demonstrated by the position of the base plate 10A in FIG. 1, so as to minimize the extent to which it protrudes from the mounted array of PV modules. This feature is significant when the outermost PV modules are close to the perimeter of the supporting roof structure. The foregoing invention offers a number of advantages. First of all, no penetrations of the building roof are required, except as may be required to route wiring from the PV array into the supporting building. In this connection, actual tests have demonstrated that an array of PV modules supported by free-standing stands 2 as herein described, i.e., without the stands being secured to a roof or other supporting structure by any mechanical or adhesive fastening means, is capable of withstanding winds of a velocity in excess of 110 miles per hour without undergoing any movement due to the wind forces. Secondly, the entire weight of the distributed mounting stands and the modules carried thereby can be kept at below 3 pounds per square foot, so that the added loading on the building is well within the limits of typical building code requirements. A third advantage is that the mounting system is adaptable for use with individual large area PV modules and also with PV module assemblies. In the case of PV module assemblies, the several modules may be held fixed in side-by-side relation by pair of elongate rods, typically of C-shaped cross-section, that span across and are secured to the several PV modules. In such case, the locking pin assemblies are attached to those rods that span the several modules, with each PV module assembly having two locking pin assemblies attached to each support rod, with the four locking pin assemblies being located at points that define a square or rectangle, so that each PV module assembly can be supported in the same manner as a single module as described above. Still other advantages are as follows: (1) the angle of tilt can be adjusted to benefit annual energy production; (2) the mounting system assures that the PV modules are open on all sides and provides space between the PV modules and the supporting roof structure, whereby to provide ambient air circulation and passive cooling, to the benefit of module efficiency, energy production and life expectancy; (3) the mounting system can be deployed on a flat roof of any type construction, including those having a spray-on foam insulation (the foam insulation may be applied after the stands 2 have been placed on the underlying roof structure); (4) the provision of protective conduits as shown at 32 and junctions boxes as shown at 96 simplifies PV array wiring and expedites field labor; (5) the modules may be mounted so as to provide adequate space between rows of modules for easy access for service; (6) the mounting system permits easy replacement of modules and removal of modules for roof inspection or repair; (7) the dynamic feature provided by having extendible brackets 14 is beneficial in that the mounting system automatically responds to high velocity wind, allowing the modules to reduce horizontal blockage by traveling to a shallower tilt angle and thereby reducing or eliminating uplift forces; and (8) the invention may be used with different forms of modules. Other advantages will be obvious to persons skilled in the art. The invention is susceptible of modifications. For example, the sizes of the base plates and the brackets 12 and 14 may be varied. Additionally, the brackets 14 may be of fixed height rather than extendible as shown, with brackets 12 and 14 being made to support PV modules at a selected angle of tilt. Also, the brackets 14 could be modified to permit locking the slides against telescoping movement. By way of example, such locking action may be achieved by providing a screw thread on the outer end of studs 58 and mounting a washer and nut on each stud so that the washer engages the outer surface of arm 44A or 44B. Tightening the nut to force the washer to grip the outer surface of arm 44A or 44B will lock the associated slide 40A or 40B against up or down movement. It is to be appreciated also that the mounting pin assemblies may be modified and that a different mode of interlocking the modules to the brackets may be used. For example, the locking pin assemblies may be replaced L-shaped brackets, with each such bracket having one leg attached to the PV module and the other leg attached to a bracket 10 or 12 by a screw-and-nut connection. Still other modifications will be obvious to persons skilled in the art.

<SOH> BACKGROUND OF THE INVENTION <EOH>As used herein the term “PV module” identifies a photovoltaic power generating unit in the form of an integrated structure comprising a plurality of electrically interconnected photovoltaic cells and means for supporting and protecting the cells, and the term “PV module assembly” identifies a structure comprising two or more PV modules that are mechanically ganged together and electrically interconnected to form a unitary power source. A variety of systems and methods have been devised for mounting PV modules and associated components of solar electric (PV) power generating systems on buildings. The market for solar electric power generating systems that operate in parallel with existing grid electricity supply and that can be safely and simply installed on the rooftops of businesses, factories, schools, hospitals, commercial establishments and the like, is growing rapidly in the United States and elsewhere. As the cost per watt has dropped in recent years for photovoltaic units, the need for improving methods of mounting photovoltaic modules to building roofs has become more critical. More precisely, as the cost of solar cells per se has declined, the non-solar cell components required for installing a functioning photovoltaic system become more critical with respect to overall system costs. However, care must be taken to insure that photovoltaic systems are installed with due respect to environmental factors such as wind-loading and environmental stresses, and preserving building integrity, notably, avoiding the use of mechanical fasteners that penetrate the roof. A number of different approaches have been taken with respect to providing means for supporting photovoltaic panels on a roof. These prior methods are exemplified by the inventions described in U.S. Pat. No. 4,886,554, issued Dec. 12, 1989 to Woodring et al for “Solar Roofing Assembly”; U.S. Pat. No. 5,746,839, issued May 5, 1998 to Thomas L. Dinwoodie for “Lightweight, Self-Ballastng Photovoltaic Roofing Assembly”; and U.S. Pat. No. 6,148,570, issued Nov. 21, 2000 to Thomas L. Dinwoodie et al for “Photovoltaic Building Assembly With Continuous Insulation Layer”. U.S. Pat. No. 6,148,570 discloses a photovoltaic building assembly comprising the use of a plurality of PV module support assemblies to support photovoltaic modules in close proximity to one another on a roof or other building support surface on which the photovoltaic building assembly is installed. Each of the PV module support assemblies comprises a base located on the building support surface, and an outwardly extending portion that projects through a continuous insulation layer, preferably in the form of a sprayed-on foam insulation layer, that covers the building support surface and the base of the PV module support assembly. The PV modules are mounted to and supported by the outwardly extending portions of the module support assemblies above the insulation layer. The base of the PV module support assembly may be made of concrete pavers or other heavy material to help counteract wind-induced uplift and sliding forces by their weight alone. U.S. Pat. No. 6,148,570 also teaches that by having their bases embedded within the insulation layer, and also by being fastened to the building support surfaces by adhesive or through the use of mechanical fasteners which may, or may not penetrate the building support surface, additional stability and mounting strength is achieved. The patent also suggests that the base portions may be sized so that embedding them within the insulation layer may be all that is needed to secure the PV module support assemblies to the building support surface. A characterizing aspect of the photovoltaic building assembly disclosed in U.S. Pat. No. 6,148,570 is that each PV module support assembly extends horizontally parallel to and in supporting relation to the mutually confronting edges of two adjacent modules, with each side of each module being supported by a different PV module assembly and adjacent modules being close to one another so as to form a covering for the supporting roof structure.

<SOH> OBJECTS AND SUMMARY OF THE INVENTION <EOH>A primary object of the invention is to provide a new and improved method and apparatus for mounting PV modules to a building roof. A more specific object is to provide an improved system for mounting PV modules to flat roofs typical of commercial buildings that is economical, requires no special tools for installation and can be used with a variety of roofing surfaces. Another specific object of the invention is to provide a system for mounting solar modules on a building roof that eliminates the need for mechanically or adhesively attaching the module-mounting structure to the building roof, whereby to preserve the integrity and waterproof characteristics of the supporting roof structure. A further object of the invention is to provide a new and improved system for mounting solar modules on roofs that provides for walkways between rows of solar modules for easy access for servicing and repair. Still another object is to provide a photovoltaic module mounting system that is adapted to mount PV modules at a selected tilt angle, e.g., in the range of 0°-15°, to benefit annual energy production. A further object is to provide improved means for mounting a plurality of PV modules on a roof that allows the PV modules to shift from a tilt position to a near horizontal position in response to pressure differentials caused by extreme winds, whereby to release wind pressure and reduce or substantially eliminate wind uplift forces. These and other objects are achieved by providing a mounting system for PV modules and PV module assemblies in the form of a plurality of mounting stands that are intended to rest on a supporting roof, with each mounting stand consisting of a base plate, and first and second brackets attached to the base plate. The base plate rests on the supporting roof and is sized to introduce a defined separation distance between rows of PV modules to minimize row-to-row shading. The base plate also is sized also to distribute the dead load and to reduce the downward pressure on the supporting roof structure. The first and second brackets are secured at opposite ends of the base plate. These mounting stands are distributed in spaced relation to one another on a supporting roof in a row and column arrangement. The first and second brackets may be of fixed height, with one bracket being taller than the other. Preferably, however, one bracket has a fixed height and the second bracket is constructed to permit its effective height to vary from a first minimum value that is less than that of the first bracket to a second maximum value that is substantially the same as that of the first bracket. In the preferred embodiment, each bracket has dual members for supporting two different PV modules or PV module assemblies. The PV modules are rectangular or square and are supported by the mounting stands by attaching a corner of each module to a different mounting bracket. More specifically, two corners of each module are mounted to different first brackets and the other two corners of each module are attached to different second brackets. The first and second brackets of each mounting stand introduce a controlled gap between adjacent PV modules in a row. The distributed mounting stands and the supported PV modules provide sufficient weight to resist movement by wind uplift forces resulting from wind velocities of up to about 70 miles per hour. Under higher velocity winds, e.g., winds up to about 110 miles per hour, the ability of the mounting stands and the supported PV modules to withstand movement is enhanced and preserved by the ability of the second brackets to extend their heights so as to shift the modules to a near horizontal position, thereby releasing wind pressure on the modules and reducing wind uplift forces. Depending on the size of the modules, several modules may be ganged together to form a discrete PV module assembly, with each PV module assembly being supported at two spaced apart points by separate first brackets and at two other points by separate second brackets. Other features and advantages of the invention are disclosed or rendered obvious by the following detailed description which is to be considered together with the accompanying drawings.

20040831

20081014

20050602

60361.0

NGUYEN, CHI Q

APPARATUS AND METHOD FOR MOUNTING PHOTOVOLTAIC POWER GENERATING SYSTEMS ON BUILDINGS

UNDISCOUNTED

ACCEPTED

ACCEPTED

Apparatus for cleaning a local area of a fabric

An apparatus for cleaning a fabric or other sheet-like porous material. The apparatus comprises a manually driven pump for pumping a cleaning substance through a local area of the material. The pump further comprises an elastic member with a force acting oppositely to the direction of the manual pumping action.

1. Apparatus for cleaning a material, said material being a fabric or other sheet-like porous material, said apparatus comprising a manually driven pump for pumping a cleaning substance through a local area of said material, the pump comprising a first reservoir with an opening for communication with a local area of a first side of said material, said reservoir having a first volume in a deactivated state of said pump, said first reservoir being constructed with a variable volume for pumping of said cleaning substance through said local area of said material upon manual activation of said pump, wherein said pump comprises an elastic member with a force acting on the first reservoir to attain said first volume in said first reservoir. 2. Apparatus according to claim 1, wherein said first reservoir has a boundary in a first reservoir-chamber, said boundary comprising a cylindrical or substantially cylindrical inner wall of said first reservoir-chamber and a piston closely fitting to said inner wall, where a displacement of said piston varies the volume of said first reservoir. 3. Apparatus according to claim 2, wherein said inner wall is slightly conical. 4. Apparatus according to claim 2, wherein said piston is equipped with a resilient sealing for fitting closely to said inner wall, said sealing comprising a an inert, low friction sealing ring having a smooth outer side abutting said inner wall and an alternating thickness variation in its longitudinal direction for easing the elastic change of length of said inert, low friction sealing ring. 5. Apparatus according to claim 4, wherein said inert, low friction sealing ring is a PTFE(POM)-ring. 6. Apparatus according to claim 4, wherein said sealing comprises a resilient o-ring exerting force on said inert, low friction sealing ring in a direction towards said inner wall. 7. Apparatus according to claim 6, wherein said inert, low friction sealing ring has a sealing lip following the inner side of sealing ring along its longitudinal direction and abutting said o-ring. 8. Apparatus according to claim 2, wherein said elastic member is arranged between said piston and said first reservoir-chamber for actuating said piston towards said deactivated state. 9. Apparatus according to claim 8, wherein said piston is connected to an outer housing, configured to be able to enclose said first reservoir-chamber under storage conditions. 10. Apparatus according to claim 9, wherein said outer housing comprises a cavity accessible from the outside of said housing. 11. Apparatus according to claim 10, wherein said cavity contains a releasable container for cleaning fluid. 12. Apparatus according to claim 1, wherein said apparatus comprises a cover unit configured to sealingly cover said opening of said first reservoir, said cover unit having apertures for communication between said first reservoir and said local area of said material, said apertures having a width that increases with distance from the centre of said cover unit. 13. Apparatus according to claim 1, wherein said apparatus comprises a second reservoir-chamber with an opening for communication with said local area at the opposite side of said material, said second reservoir-chamber having apertures for allowing escape of air from said second reservoir chamber, wherein the rims of the openings of said first and said second reservoir-chambers are configured to mutually correspond for creating a substantially fluid tight connection between the first and the second reservoir chamber when said material is placed between said rim of said first reservoir-chamber and said corresponding rim of said second reservoir-chamber. 14. Apparatus according to claim 13, wherein said rim of said first reservoir-chamber or said rim of said second reservoir-chamber or both of them are provided with a resilient collar. 15. Apparatus according to claim 13, wherein said second reservoir-chamber is configured for storage conditions to receive said outer housing enclosing said first reservoir-chamber. 16. Apparatus according to claim 15, wherein said second reservoir-chamber is provided with a detachable lid for in detached configuration to allow receipt of said outer housing and under storage conditions in attached configuration covering said received housing. 17. Apparatus according to claim 1, wherein said pump comprises a first resilient bellow closed in one end and open at the other end for communication with said material, said internal volume of said first bellow comprising said first reservoir. 18. Apparatus according to claim 17, wherein said apparatus comprises a second bellow with a second reservoir-chamber with an opening for communication with said local area at the opposite side of said material, said second reservoir-chamber having an aperture for allowing escape of air from said second reservoir chamber, wherein the rims of the openings of said first and said second reservoir-chambers are configured to mutually correspond for creating a substantially fluid tight connection between the first and the second reservoir chamber when said material is placed between said rim of said first reservoir-chamber and said corresponding rim of said second reservoir-chamber. 19. Apparatus according to claim 1, wherein said pump comprises a resilient polymer container having an opening for communication with said fabric or other sheet-like porous material, said internal volume of said polymer container comprising said first reservoir.

FIELD OF THE INVENTION The invention concerns an apparatus for cleaning a fabric or other sheet-like porous material. The apparatus comprises a manually driven pump for pumping a cleaning substance through a local area of the material. BACKGROUND OF THE INVENTION In order to remove stains on clothes or other fabrics, it is common practice to apply efficient cleaning agents with a certain risk for discolorations of the fabric. Usually, the treatment implies that a region on the fabric is treated that is much larger than the size of the stain, which is unwanted. From U.S. Pat. No. 656,802 by Batz, a grease spot remover is disclosed comprising a pump having a reservoir chamber communicating with the pump-chamber and means for clamping the two chambers together. A cleaning agent may be pumped back and forth between the two chambers in order to clean the area of interest. The disclosed clamping means are wires that are needle pointed through the fabric and connected to the two chambers. This results in holes through the fabric, which in many cases are unwanted, especially in clothes of fine quality. The grease spot remover also is generally not very handy as the manual pumping action has to be performed under the fabric to be cleaned such that a simple resting against an underlying surface is not possible. Also, the pumping needs a pulling action and a pushing action, which makes the use of it tedious as at the same time the upper chamber has to be held vertically in order not to spill the liquid. Furthermore, the drawn embodiments are of a format, which does not make them suitable to transport in a hand bag or during travel. Therefore, needs exist for improvements. SUMMARY OF THE INVENTION An improved apparatus for cleaning a material, the material being a fabric or other porous material, is provided as set forth in the claims. The apparatus comprises a manually driven pump for pumping a cleaning substance through a local area of the material. The pump comprises a first reservoir with an opening for communication with a local area of a first side of the porous material. The reservoir has a first volume in a deactivated state of the pump and is constructed with a variable volume for pumping of the cleaning substance through the local area of the material upon manual activation of the pump. Furthermore, the pump comprises an elastic member with force acting on the first reservoir to attain the first volume in the first reservoir. The apparatus may be configured for a manual pushing pump action or a pulling pump action. Whether the former or latter is employed, depends on the desired properties. However, in many cases, a push action may be preferred, where the elastic member counteracts the pushing action with the change of the volume of the first reservoir, such that the first volume of the deactivated state is attained again after the force of the pushing action is relieved. In the following, the invention will be explained with a manual pushing pump action, though it will be apparent to the skilled in the art, how a modification has to be performed to employ the invention with a manual pulling pump action. Having an elastic member as described and the pump configured for a push action to achieve the pumping, the apparatus according to the invention has the advantage that it may be used with only one hand and by performing a very simple movement of the hand during the push action. Due to its very simple use, the apparatus according to the invention is extraordinarily user friendly. The apparatus according to the invention may be used for cleaning in the following way assuming that the apparatus requires a pushing pumping action in order to change the volume of the first reservoir from the deactivated state. Once a stain or spot has been observed, for example on the fabric of an arm chair, a cleaning fluid is put on the spot, and the apparatus according to the invention is arranged to cover the spot by resting the rim of the opening of the first reservoir against the fabric. By performing a manual pushing pump action, air is pressed out of the first reservoir and into the fabric. Thereby, the cleaning fluid is pumped through the fabric. When the pressure for the pushing action is relieved, the elastic member causes a pull back of air into the first reservoir by which the cleaning fluid is pulled through the fabric. By pressing the cleaning fluid back and forth through the fabric, the spot is removed. Especially, a foam may be produced by this action, which may improve the cleaning process. In a most simple embodiment, the pump comprises a resilient bellow closed in one end and open at the other end with a rim for communication with the material, In this case, the internal volume of the bellow comprises the first reservoir. Another simple embodiment is achieved in that the pump comprises a resilient polymer container having an opening for communication with the fabric or other sheet-like porous material, the internal volume of the polymer container comprising the first reservoir. However, preferred is a certain embodiment, wherein the first reservoir has a boundary in a first reservoir-chamber, the boundary comprising a cylindrical or substantially cylindrical inner wall of the first reservoir-chamber and a piston closely fitting to the inner wall, where a displacement of the piston varies the volume of the first reservoir. The inner wall may be truly cylindrical, where the term cylindrical does not necessarily imply that the inner wall is circular in cross section. However, the piston may be provided with an elastically fitting sealing such that a perfect cylindrical wall is not necessary. Substantially cylindrical, in this case, means a shape that for practical purposes in connection with the piston and an eventual sealing appears cylindrical. However, as the reservoir-chamber may be produced by injection moulding with polymers, it is of advantage that the inner wall of the reservoir-chamber is slightly conical such that the chamber easily can be released from the mould form. In case that the inner wall is not perfectly cylindrical but only substantially cylindrical, for example slightly conical due to the reasons mentioned above, the piston may be equipped with a resilient sealing for fitting closely to the inner wall. Such sealing rings may be made of rubber. However, it has turned out that this is not an optimum choise, as rubber shows a high friction with the typical materials, for example polymer or metal, used for the inner wall. Furthermore, it is not inert to a degree as high as desired when certain cleaning agents are used. Even further, such material is not long lasting for the purpose of concern and may already after relatively short time stop working properly as a sealing. Therefore, it is preferred that the sealing comprises a low friction, inert sealing ring having a smooth outer side abutting the inner wall and an alternating thickness variation in its longitudinal direction for easing the elastic change of length of the inert sealing ring. In this embodiment, it is possible to use inert, low friction materials as PTFE also known as Teflon®. Even more preferred is a blend of polytetrafluorethylen with polyoxymethylene-acetal-polymer (POM) which can be used for moulding being a cheap and production friendly solution. In the following the term PTFE-ring is used for a ring made of polytetrafluorethylen—PTFE—or alternatively of polytetrafluorethylen with polyoxymethylene-acetal-polymer—PTFE(POM) Inert materials as PTFE and PTFE(POM) are normally not very elastic as compared to rubber rings, but may be preferred due to the low friction with the inner wall and due to its inert properties in connection with cleaning fluids and due to its long lasting performance even after long time of dry storage. In order to achieve sufficiently elastic properties, parts of the inert, low friction sealing ring are thin such that a certain stretching and compression of it is possible. By having an alternating thickness such that the inert, low friction sealing ring is thicker between the thin sections, it is in addition assured that it does remain in a groove of the piston without the risk of sliding out of the groove under even intensive pumping action. Furthermore, the inert, low friction sealing ring may be supported in a groove of the piston by a resilient o-ring exerting force on the sealing ring in a direction towards the inner wall. As the sealing ring is not as elastic as rubber or, for example, silicone, an o-ring support of the sealing ring combines the low friction, inert and tightening capabilities with the resilient properties of a rubber o-ring. The alternating thickness variation of the inert, low friction sealing ring allows the o-ring to be more elastically deformed, because material may be displaced from the elastic o-ring into the grooves of the thin sections of the sealing ring during the deformation of the o-ring under compression. Therefore, the alternating thickness of the inert, low friction sealing ring serves a number of purposes. As the inert, low friction sealing ring has an alternating thickness, it may occur that the sealing is not completely tight between the sealing ring and the o-ring in the groove. An improvement may thus be achieved by providing the sealing ring with a sealing lip following the inner side of the sealing ring along its longitudinal direction and abutting the o-ring. In a practical embodiment, the elastic member, for example a spring, is arranged between the piston and the first reservoir-chamber for actuating the piston towards the deactivated state. In a further embodiment, the piston is connected to an outer housing, configured to be able to enclose the first reservoir-chamber under storage conditions. In addition, the outer housing may comprise a cavity accessible from the outside of the housing. Such a cavity may be used for containing a releasable container for cleaning fluid, such that the apparatus according to the invention constitutes a kit with the cleaning device and the necessary cleaning fluid, for example a fluid with enhanced foaming properties. When foam is pressed through a porous material, the flow of air and foam through the material at the centre of the volume changing reservoir resting against the material is usually not the same as the flow at the rim of the reservoir. In this case, the following embodiment of the invention is useful, where the apparatus comprises a cover unit configured to sealingly cover the opening of the first reservoir, the cover unit having apertures for communication between the first reservoir and the local area of the material. The apertures may be constructed in accordance with desired flow properties. For example, the apertures may have a width that increases with distance from the centre of the cover unit. In this case, a flow is achieved through the material, where the central flow and the flow at the rim are of the same order. However, it may be desirable that not only air and foam may be pressed through the material, for example a fabric, but it may as well be desirable to press water through the fabric in order to flush the cleaning fluid out of the material. Eventually, it may be desirable to press a larger amount of cleaning fluid, for example water with a grease dissolving agent, through the material. In these cases, it is of advantage that the apparatus comprises a second reservoir-chamber with an opening for communication with the local area at the opposite side of the material, the second reservoir-chamber having apertures for allowing escape of air from the second reservoir chamber, wherein the rims of the openings of the first and the second reservoir-chambers are configured to mutually correspond for creating a substantially fluid tight connection between the first and the second reservoir chamber when the material is placed between the rim of the first reservoir-chamber and the corresponding rim of the second reservoir-chamber. This embodiment may be used in the following way. Water, eventually with a cleaning agent, is filled into the first reservoir having the opening directed upwards. The housing with the filled first reservoir is placed on a platform, for example a table, and fabric or other porous material is placed on the rim of the opening of the first reservoir with the corresponding stain on the material within the periphery of the rim. Then, the second reservoir chamber is placed on the upper side of the porous material with its rim fittingly arranged in the rim of the first reservoir-chamber. By now pushing the second reservoir chamber downwards, the liquid from the first reservoir is pressed through the porous material and into the second reservoir. When the pushing force is released, the elastic member presses the chambers back into the deactivated state, such that the fluid is sucked back into the first reservoir. Due to the elastic member, for example a spring, a tight connection between the two chambers is retained. As the rims of the first and the second reservoir correspond, a liquid tight connection is achieved in combination with the porous material. The embodiment is therefore an easy-to-use cleaning apparatus. In order to achieve an optimum tight connection on both sides of the porous material, it may be of advantage—especially if the porous material is not very flexible—if the rim of the first reservoir-chamber or the rim of the second reservoir-chamber or both of them are provided with a resilient collar. In a further embodiment, the second reservoir-chamber is configured for storage conditions to receive the outer housing enclosing the first reservoir-chamber. This embodiment is suited as a first-aid in cleaning under travel conditions, because the apparatus according to this embodiment of the invention can be stored in a very compact way. In order to secure that the stored housing does not fall out of the second reservoir chamber under storage conditions, the second reservoir-chamber may be provided with a detachable lid for in detached configuration to allow receipt of the outer housing and under storage conditions with attached lid to cover the received housing. SHORT DESCRIPTION OF THE DRAWING The invention will be explained in more detail with reference to the drawing, where FIG. 1 is a drawing of a first embodiment of the apparatus according to the invention, FIG. 2 is a drawing of the PTFE-ring in a detailed view, FIG. 3 is a more detailed sketch of the first embodiment, FIG. 4 is a drawing of a second embodiment of the apparatus, FIG. 5 is an exploded view of the second embodiment, FIG. 6 is a drawing of the apparatus in a compact state, FIG. 7 is a drawing of an alternative simple embodiment of the invention. DETAILED DESCRIPTION OF THE INVENTION FIG. 1 illustrates an apparatus 100 according to a first embodiment of the invention, where FIG. 1a is a side view of the apparatus 100, FIG. 1b is a vertical cross section of the shown apparatus 100 in a deactivated state, and FIG. 1c is a vertical cross section of the apparatus 100 in a compressed state. The apparatus 100 comprises a manually driven pump 101 for pumping a cleaning substance 102 through a local area 103 of the material porous 104 to be cleaned. The pump 101 comprises a first reservoir 105 with an opening 106 for communication with the local area 103 of a first side 107 of the material 104. The reservoir 105 has a first volume in a deactivated state of the pump 101 as shown in FIG. 1b. The reservoir 105 is constructed with a variable volume for pumping of the cleaning substance 102 through the local area 103 of the material 104 upon manual activation of the pump in order to clean stains 108 from the material 104. The first reservoir 105 has a boundary in a first reservoir-chamber 112, the boundary comprising a cylindrical or substantially cylindrical inner wall 111 of the first reservoir-chamber 112 and a piston 113 closely fitting to the inner wall 111, where a displacement of the piston 113 in the reservoir-chamber 112 varies the volume of the first reservoir 105. The piston 113 is connected with a snap lock 114 to an extension 115 of the piston and connected to an outer housing 116. When the outer housing 116 is depressed towards the material 104, an elastic member in the form of a spring 109 arranged between the piston 113, 115 and the first reservoir-chamber 112 will be compressed and the outer housing 116 will move together with the piston 113, 115 towards the material 104. The compressed state after maximum compression is shown in FIG. 1c. As the first reservoir-chamber 112 is stationary with respect to the material 104, the volume of the first reservoir 105 will be decreased and air will be pressed out of the opening 106. The apparatus 100 as illustrated may be used for cleaning in the following way. Once a stain 108 or spot has been observed in the porous material 104, for example on the fabric of an arm chair or a carpet, a cleaning fluid 102 is put on the spot 108 as illustrated in FIG. 1b, and the apparatus 100 according to the invention is arranged to cover the stain 108 by resting the rim 110 of the opening 106 against the fabric 104, for example a carpet lying on the floor. A pumping action may now be performed by pressing the outer housing 116 towards the porous material 104 such air is pumped out of the first reservoir 105 and together with the cleaning fluid 102 into and through the porous material 104 as illustrated in FIG. 1c. During compression, the spring 109, as illustrated in FIG. 1c, is compressed and the outer housing 116 receives the reservoir-chamber 112. When the manual pressure on the outer housing 116 is released, the spring 109 will expand again and the apparatus 100 will attain its original deactivated state. The expansion causes a pull back of air into the first reservoir 105 by which the cleaning fluid 102 is pulled back through the fabric 104. By pressing the cleaning 102 fluid back and forth through the fabric 104, the spot 108 is dissolved in the cleaning fluid 102 and removed together with the remains of the fluid 102. Especially, foam from the cleaning fluid may be produced by this action, which may improve the cleaning process. In order to achieve a tight connection between the rim 110 of the first reservoir-chamber 112 and the porous material 104, the rim 110 may be constituted by a resilient collar fastened to the first reservoir-chamber 112. The inner wall 111 of the first reservoir chamber 112 may be truly cylindrical. However, the piston 113 may be provided with an elastically fitting sealing 117 such that a perfect cylindrical wall is not necessary. Substantially cylindrical, in this case, means a shape which for practical purposes in connection with the piston 113 and an eventual sealing 117 appears cylindrical. As the reservoir-chamber 112 may be produced by injection moulding with polymers, it is of advantage that the inner wall 111 of the reservoir-chamber 112 is slightly conical, for example with a slope of 0.25 degrees, such that the chamber 112 easily can be released from the mould form. In case that the inner wall 111 is not perfectly cylindrical but only substantially cylindrical, for example slightly conical due to the reasons mentioned above, the piston 117 may be equipped with a resilient sealing 117 for fitting closely to the inner wall 111 as illustrated in FIG. 1d. The sealing comprises an inert, low friction sealing ring, which in the following will be called a PTFE-ring, though this is no limitation of the invention in any way and also covers other comparable materials including the preferred embodiment, being a blend of polytetrafluorethylen and polyoxymethylene-acetal-polymer—PTFE(POM). The PTFE-ring is illustrated in greater detail in FIG. 2. The ring 200 has a smooth outer side 201 for abutting the inner wall 111 and an alternating thickness variation 202 in its longitudinal direction for easing the elastic change of length of the PTFE-ring. PTFE, is normally not very elastic as compared to rubber rings but may be preferred due to its low friction with the inner wall 111, its inert properties in connection with cleaning fluids 102 and due to its long lasting performance even after long time of dry storage. In order to achieve sufficiently elastic properties, parts 203 of the PTPE-ring are thin such that a certain stretching and compression of the PTFE-ring is possible. By having an alternating thickness such that the PTFE-ring has thicker parts 204 between the thin sections 203, it is assured that the PTFE-ring does remain in a groove 118 of the piston 113, as illustrated in FIG. 1d, without the risk of sliding out of the groove 118 under even intensive pumping action. A sealing 117 arrangement of the described embodiment is able to provide a fluid tight sealing at the bottom as well at the top of the first reservoir-chamber 112 even though the inner wall 111 has a slope of the order of 0.25 degrees. Providing a sealing ring 200 with an alternating thickness has a further advantage. During production of such rings, which typically is injection moulding, the rings contract during cooling. By providing a ring with alternating thickness, the moulding material during cooling will rearrange evenly in the mould along the periphery such that the sealing ring 200 with alternating thickness can be produced with small tolerances. This is in contrast to the conditions of rings with non-alternating thickness that are injection moulded, where the material during cooling may flow more to that side of the mould where the hardening starts, resulting in a ring having large thickness differences between diametrically opposite locations. The PTFE-ring 200 may in addition be supported in a groove 118 of the piston 113 by a resilient o-ring 119 exerting force on the PTFE-ring 200 in a direction towards the inner wall 111. As the PTFE-ring 200 is not as elastic as rubber or, for example, silicone, an o-ring 119 support of the PTFE-ring 200 combines the low friction, inert and tightening capabilities of the PTFE ring 200 with the resilient properties of a rubber o-ring 119. As the PTFE-ring 200 has an alternating thickness, it may under some conditions occur that the sealing 117 is not completely tight between the PTFE-ring 200 and the o-ring 119 in the groove 117. An improvement may thus be achieved by providing a sealing ring 200 with a sealing lip 205 following the inner side of the sealing ring 200 along its longitudinal direction and abutting the o-ring 119. In order not to damage the o-ring 119, the lip 205 may be rounded at its edge 206 facing the o-ring 119. The outer housing 116 as shown in FIG. 1b and in FIG. 3 in an exploded view may comprise a cavity 120 accessible from the outside of the housing 116. Such a cavity 120 may be used for containing a releasable container 121 for cleaning fluid, such that the apparatus 100 according to the invention constitutes a kit with the cleaning device and the necessary cleaning fluid, for example a fluid with enhanced foaming properties. The releasable container may be provided with a valve for release of cleaning fluid, the valve being activated by pressure, for example with a finger. When foam is pressed through a porous material 104 during pump action, the flow of air and foam through the material 104 at the centre of the opening 106 may not be the same as the flow at the rim of the reservoir-chamber 112. In this case, it is useful to provide the opening 116 with a cover unit 300 as shown in FIG. 3a configured to sealingly cover the opening 116 of the first reservoir 105. The cover unit 300 is provided with apertures 301 for communication between the first reservoir 105 and the local area 103 of the material 104. The apertures 301 have a width that increases with distance from the centre of the cover unit 300. In this case, a flow is achieved through the material 104, where the central flow and the flow at the rim are of the same order. The shape and arrangement of the apertures 301 may be differently as shown in dependence on the desired flow characteristics. A drawing of the apparatus 100 with the cover unit 300 is further shown in FIG. 3b in in cross-sectional view and in a perspective view illustrating that a vertical orientation of the apparatus 100 is not necessary. It may be desirable that not only air and foam may be pressed through the material, for example a fabric, but it may as well be desirable to press water through the fabric in order to flush the cleaning fluid out of the material. Also, it may be desirable to press a larger amount of cleaning fluid, for example water with a grease dissolving agent, through the material. In these cases with reference to FIGS. 4a and 4d, it is of advantage that the apparatus 100 comprises a second reservoir-chamber 400 to be arranged on the opposite side 402 of the porous material 104′, sketched by a dashed line in FIG. 4c. The second reservoir-chamber 400 has an opening 401 for communication with the local area 103 at the opposite side 402 of the material 104′ such that under compression of the pump 101, fluid 403 provided in the first reservoir 105 is pressed from the first reservoir 105 through the porous material 104′ and into the second reservoir 404. The second reservoir-chamber 400 has apertures 405 for allowing escape of air from the second reservoir 404. The rims 110, 406 of the openings 106, 401 of the first 112 and the second 400 reservoir-chambers are configured to mutually correspond for creating a fluid tight—or at least substantially fluid tight—connection between the first 400 and the second 112 reservoir chamber when the material 104′ is placed between the rim 110 of the first reservoir-chamber 112 and the corresponding rim 406 of the second reservoir-chamber 400. This embodiment may be used in the following way. Water 403 or a cleaning fluid containing a cleaning agent is filled into the first reservoir 105 having the opening 106 directed upwards as illustrated in FIG. 4d. The housing 112 with the filled first reservoir 105 may be placed on a platform, for example a table, preferably after removal of the container 121. A fabric or other porous material 104′ is placed on the rim 110 of the opening 106 of the first reservoir 105 with the corresponding stain on the material 104′ within the periphery of the rim 110. Then, the second reservoir-chamber 400 is placed on the upper side 402 of the porous material 104′ with its rim 406 fittingly arranged on the rim 110 of the first reservoir-chamber 112. By now pushing the second reservoir-chamber 400 downwards, the liquid 403 from the first reservoir 105 is pressed through the porous material 104′ and into the second reservoir 404. As the rims 110, 406 of the first 105 and the second reservoir 404 mutually correspond, a liquid tight connection is achieved in combination with the porous material 104′. The invention is therefore an easy-to-use cleaning apparatus. The shown embodiment is further illustrated in the exploded sketch of FIG. 5. However, the cover unit 300 as shown in FIG. 5 is normally not placed between the first reservoir-chamber 112 and the second reservoir-chamber 400 in the embodiment and use as shown in FIG. 4d. In order to achieve an optimum tight connection on both sides of the porous material, it may be of advantage—especially if the porous material is not very flexible—if the rim 110 of the first reservoir-chamber or the rim 406 of the second reservoir-chamber or both of them are provided with a resilient collar 122, as for example illustrated for the first reservoir-chamber 112 in FIG. 1b. In FIG. 4b and FIG. 4c, the apparatus is shown as seen from above and from below relative to the orientation of FIG. 1b. In a further embodiment, as illustrated in FIG. 5, the second reservoir-chamber 400 having a detachable lid 408 is configured for storage conditions to receive the outer housing 116 enclosing the first reservoir-chamber 112. After receipt of the outer housing 116, the lid is attached to the second reservoir-chamber 400 again, for example using screwing means 409, 410 as also illustrated in FIG. 5. The detachable lid may be constructed such as to comprise an additional chamber for containment of sewing equipment, for examples needles and threads or other convenient travel accessories, such as an cleaning agent, for example stored in small paper bags, in case that the releasable container 121 is not provided. This may be convenient for a travel-aid kit. In a most simple embodiment, the pump 101 in an apparatus 100 according to the invention comprises a resilient bellow 700 closed in one end 701 and open at the other 702 end with a rim 704 for communication with the material 104′. In this case, the internal volume of the bellow 700 comprises a first reservoir chamber 112′ containing a first reservoir 105′. The bellow 700 is resilient such that the volume of the first reservoir 105′ of the bellow 700 is decreases when the bellow 700 is compressed. In addition, a second reservoir-chamber 400′ with a rim 705 configured to correspond with the rim 704 of the first reservoir-chamber 112′ in order to achieve a fluid tight arrangement between the two reservoir-chambers 112′, 400′ and the porous material 104′ placed between them. The second reservoir chamber 400′ need not be a bellow, however, an embodiment where also the second reservoir-chamber 400′ is a bellow has the advantage that the first 112′ and the second 400′ reservoir-chamber may be compressed to a flat compressed state, well suited for travel conditions. Especially, the second reservoir-chamber 400′ may have dimensions that it can be placed inside the first reservoir-chamber 112′—however turned 180 degrees as compared to the shown orientation in FIG. 7. In the case that the second reservoir-chamber 400′ is a bellow, it may be preferred to perform the pumping action by manually pressing on the upper side of the rim 705. If it is desired to perform the pumping action by pressing on the second reservoir-chamber 400′, the stiffness of this bellow preferably is larger than the stiffness of the bellow 700 constituting the first reservoir-chamber 112′ in order not to compress the upper bellow too much when performing the manual pumping action. Another simple embodiment is achieved in that the pump comprises a resilient polymer container having an opening for communication with the fabric or other sheet-like porous material. For example, such a polymer container may be constructed like rubber bellows from old acoustic horns.

<SOH> BACKGROUND OF THE INVENTION <EOH>In order to remove stains on clothes or other fabrics, it is common practice to apply efficient cleaning agents with a certain risk for discolorations of the fabric. Usually, the treatment implies that a region on the fabric is treated that is much larger than the size of the stain, which is unwanted. From U.S. Pat. No. 656,802 by Batz, a grease spot remover is disclosed comprising a pump having a reservoir chamber communicating with the pump-chamber and means for clamping the two chambers together. A cleaning agent may be pumped back and forth between the two chambers in order to clean the area of interest. The disclosed clamping means are wires that are needle pointed through the fabric and connected to the two chambers. This results in holes through the fabric, which in many cases are unwanted, especially in clothes of fine quality. The grease spot remover also is generally not very handy as the manual pumping action has to be performed under the fabric to be cleaned such that a simple resting against an underlying surface is not possible. Also, the pumping needs a pulling action and a pushing action, which makes the use of it tedious as at the same time the upper chamber has to be held vertically in order not to spill the liquid. Furthermore, the drawn embodiments are of a format, which does not make them suitable to transport in a hand bag or during travel. Therefore, needs exist for improvements.

<SOH> SUMMARY OF THE INVENTION <EOH>An improved apparatus for cleaning a material, the material being a fabric or other porous material, is provided as set forth in the claims. The apparatus comprises a manually driven pump for pumping a cleaning substance through a local area of the material. The pump comprises a first reservoir with an opening for communication with a local area of a first side of the porous material. The reservoir has a first volume in a deactivated state of the pump and is constructed with a variable volume for pumping of the cleaning substance through the local area of the material upon manual activation of the pump. Furthermore, the pump comprises an elastic member with force acting on the first reservoir to attain the first volume in the first reservoir. The apparatus may be configured for a manual pushing pump action or a pulling pump action. Whether the former or latter is employed, depends on the desired properties. However, in many cases, a push action may be preferred, where the elastic member counteracts the pushing action with the change of the volume of the first reservoir, such that the first volume of the deactivated state is attained again after the force of the pushing action is relieved. In the following, the invention will be explained with a manual pushing pump action, though it will be apparent to the skilled in the art, how a modification has to be performed to employ the invention with a manual pulling pump action. Having an elastic member as described and the pump configured for a push action to achieve the pumping, the apparatus according to the invention has the advantage that it may be used with only one hand and by performing a very simple movement of the hand during the push action. Due to its very simple use, the apparatus according to the invention is extraordinarily user friendly. The apparatus according to the invention may be used for cleaning in the following way assuming that the apparatus requires a pushing pumping action in order to change the volume of the first reservoir from the deactivated state. Once a stain or spot has been observed, for example on the fabric of an arm chair, a cleaning fluid is put on the spot, and the apparatus according to the invention is arranged to cover the spot by resting the rim of the opening of the first reservoir against the fabric. By performing a manual pushing pump action, air is pressed out of the first reservoir and into the fabric. Thereby, the cleaning fluid is pumped through the fabric. When the pressure for the pushing action is relieved, the elastic member causes a pull back of air into the first reservoir by which the cleaning fluid is pulled through the fabric. By pressing the cleaning fluid back and forth through the fabric, the spot is removed. Especially, a foam may be produced by this action, which may improve the cleaning process. In a most simple embodiment, the pump comprises a resilient bellow closed in one end and open at the other end with a rim for communication with the material, In this case, the internal volume of the bellow comprises the first reservoir. Another simple embodiment is achieved in that the pump comprises a resilient polymer container having an opening for communication with the fabric or other sheet-like porous material, the internal volume of the polymer container comprising the first reservoir. However, preferred is a certain embodiment, wherein the first reservoir has a boundary in a first reservoir-chamber, the boundary comprising a cylindrical or substantially cylindrical inner wall of the first reservoir-chamber and a piston closely fitting to the inner wall, where a displacement of the piston varies the volume of the first reservoir. The inner wall may be truly cylindrical, where the term cylindrical does not necessarily imply that the inner wall is circular in cross section. However, the piston may be provided with an elastically fitting sealing such that a perfect cylindrical wall is not necessary. Substantially cylindrical, in this case, means a shape that for practical purposes in connection with the piston and an eventual sealing appears cylindrical. However, as the reservoir-chamber may be produced by injection moulding with polymers, it is of advantage that the inner wall of the reservoir-chamber is slightly conical such that the chamber easily can be released from the mould form. In case that the inner wall is not perfectly cylindrical but only substantially cylindrical, for example slightly conical due to the reasons mentioned above, the piston may be equipped with a resilient sealing for fitting closely to the inner wall. Such sealing rings may be made of rubber. However, it has turned out that this is not an optimum choise, as rubber shows a high friction with the typical materials, for example polymer or metal, used for the inner wall. Furthermore, it is not inert to a degree as high as desired when certain cleaning agents are used. Even further, such material is not long lasting for the purpose of concern and may already after relatively short time stop working properly as a sealing. Therefore, it is preferred that the sealing comprises a low friction, inert sealing ring having a smooth outer side abutting the inner wall and an alternating thickness variation in its longitudinal direction for easing the elastic change of length of the inert sealing ring. In this embodiment, it is possible to use inert, low friction materials as PTFE also known as Teflon®. Even more preferred is a blend of polytetrafluorethylen with polyoxymethylene-acetal-polymer (POM) which can be used for moulding being a cheap and production friendly solution. In the following the term PTFE-ring is used for a ring made of polytetrafluorethylen—PTFE—or alternatively of polytetrafluorethylen with polyoxymethylene-acetal-polymer—PTFE(POM) Inert materials as PTFE and PTFE(POM) are normally not very elastic as compared to rubber rings, but may be preferred due to the low friction with the inner wall and due to its inert properties in connection with cleaning fluids and due to its long lasting performance even after long time of dry storage. In order to achieve sufficiently elastic properties, parts of the inert, low friction sealing ring are thin such that a certain stretching and compression of it is possible. By having an alternating thickness such that the inert, low friction sealing ring is thicker between the thin sections, it is in addition assured that it does remain in a groove of the piston without the risk of sliding out of the groove under even intensive pumping action. Furthermore, the inert, low friction sealing ring may be supported in a groove of the piston by a resilient o-ring exerting force on the sealing ring in a direction towards the inner wall. As the sealing ring is not as elastic as rubber or, for example, silicone, an o-ring support of the sealing ring combines the low friction, inert and tightening capabilities with the resilient properties of a rubber o-ring. The alternating thickness variation of the inert, low friction sealing ring allows the o-ring to be more elastically deformed, because material may be displaced from the elastic o-ring into the grooves of the thin sections of the sealing ring during the deformation of the o-ring under compression. Therefore, the alternating thickness of the inert, low friction sealing ring serves a number of purposes. As the inert, low friction sealing ring has an alternating thickness, it may occur that the sealing is not completely tight between the sealing ring and the o-ring in the groove. An improvement may thus be achieved by providing the sealing ring with a sealing lip following the inner side of the sealing ring along its longitudinal direction and abutting the o-ring. In a practical embodiment, the elastic member, for example a spring, is arranged between the piston and the first reservoir-chamber for actuating the piston towards the deactivated state. In a further embodiment, the piston is connected to an outer housing, configured to be able to enclose the first reservoir-chamber under storage conditions. In addition, the outer housing may comprise a cavity accessible from the outside of the housing. Such a cavity may be used for containing a releasable container for cleaning fluid, such that the apparatus according to the invention constitutes a kit with the cleaning device and the necessary cleaning fluid, for example a fluid with enhanced foaming properties. When foam is pressed through a porous material, the flow of air and foam through the material at the centre of the volume changing reservoir resting against the material is usually not the same as the flow at the rim of the reservoir. In this case, the following embodiment of the invention is useful, where the apparatus comprises a cover unit configured to sealingly cover the opening of the first reservoir, the cover unit having apertures for communication between the first reservoir and the local area of the material. The apertures may be constructed in accordance with desired flow properties. For example, the apertures may have a width that increases with distance from the centre of the cover unit. In this case, a flow is achieved through the material, where the central flow and the flow at the rim are of the same order. However, it may be desirable that not only air and foam may be pressed through the material, for example a fabric, but it may as well be desirable to press water through the fabric in order to flush the cleaning fluid out of the material. Eventually, it may be desirable to press a larger amount of cleaning fluid, for example water with a grease dissolving agent, through the material. In these cases, it is of advantage that the apparatus comprises a second reservoir-chamber with an opening for communication with the local area at the opposite side of the material, the second reservoir-chamber having apertures for allowing escape of air from the second reservoir chamber, wherein the rims of the openings of the first and the second reservoir-chambers are configured to mutually correspond for creating a substantially fluid tight connection between the first and the second reservoir chamber when the material is placed between the rim of the first reservoir-chamber and the corresponding rim of the second reservoir-chamber. This embodiment may be used in the following way. Water, eventually with a cleaning agent, is filled into the first reservoir having the opening directed upwards. The housing with the filled first reservoir is placed on a platform, for example a table, and fabric or other porous material is placed on the rim of the opening of the first reservoir with the corresponding stain on the material within the periphery of the rim. Then, the second reservoir chamber is placed on the upper side of the porous material with its rim fittingly arranged in the rim of the first reservoir-chamber. By now pushing the second reservoir chamber downwards, the liquid from the first reservoir is pressed through the porous material and into the second reservoir. When the pushing force is released, the elastic member presses the chambers back into the deactivated state, such that the fluid is sucked back into the first reservoir. Due to the elastic member, for example a spring, a tight connection between the two chambers is retained. As the rims of the first and the second reservoir correspond, a liquid tight connection is achieved in combination with the porous material. The embodiment is therefore an easy-to-use cleaning apparatus. In order to achieve an optimum tight connection on both sides of the porous material, it may be of advantage—especially if the porous material is not very flexible—if the rim of the first reservoir-chamber or the rim of the second reservoir-chamber or both of them are provided with a resilient collar. In a further embodiment, the second reservoir-chamber is configured for storage conditions to receive the outer housing enclosing the first reservoir-chamber. This embodiment is suited as a first-aid in cleaning under travel conditions, because the apparatus according to this embodiment of the invention can be stored in a very compact way. In order to secure that the stored housing does not fall out of the second reservoir chamber under storage conditions, the second reservoir-chamber may be provided with a detachable lid for in detached configuration to allow receipt of the outer housing and under storage conditions with attached lid to cover the received housing.

20040901

20080624

20050804

98153.0

PERRIN, JOSEPH L

APPARATUS FOR CLEANING A LOCAL AREA OF A FABRIC

SMALL

ACCEPTED

ACCEPTED

Glass fixture-joined glass article and joint structure using this

The present invention is intended to provide a glass article with a metal member joined thereto in which an electroconductive coating film is formed on at least a part of the surface of the glass article by baking a silver paste that includes Ag particles and a glass frit, a joining plane of the metal member is fixed onto the electroconductive coating film with a lead-free solder alloy containing Sn as a main component, and the lead-free solder alloy contains at least 1.5 mass % of Ag, which prevents the appearance of the electroconductive coating film and the bonding strength from degrading. Furthermore, in the present invention, when using a metal member having at least two joining planes, the total area of the joining planes is set within a range of 37 mm2 to 50 mm2, which allows high bonding strength between the glass article and metal member to be maintained while using the lead-free solder alloy. Moreover, in the present invention, the volume of the lead-free solder alloy to be provided on each joining plane is set to be 1.0 to 2.0 times the product of the area of the joining plane concerned and the thickness of the lead-free solder alloy, which prevents cracks from occurring in the glass article.

1. A glass article with a metal member joined thereto, comprising: an electroconductive coating film formed on at least a part of a surface of the glass article by baking a silver paste that includes Ag particles and a glass frit, wherein a joining plane of the metal member is fixed onto the electroconductive coating film with a lead-free solder alloy containing Sn as a main component, and the lead-free solder alloy contains at least 1.5 mass % of Ag. 2. The glass article according to claim 1, wherein the lead-free solder alloy contains 2 to 4 mass % of Ag. 3. The glass article according to claim 1, wherein the electroconductive coating film is at least one selected from an antenna and a defogger. 4. The glass article according to claim 1, wherein the metal member is a metal terminal comprising a leg part having at least two joining planes and a connection part that projects upward from the leg part and is to be connected to a cable. 5. A glass article with a metal member joined thereto, comprising: an electroconductive coating film containing Ag, wherein the electroconductive coating film is formed on at least a part of a surface of the glass article, at least two joining planes of the metal member are fixed onto the electroconductive coating film with a lead-free solder alloy containing Sn as a main component, and a total area of the at least two joining planes is in a range of 37 mm2 to 50 mm2. 6. The glass article according to claim 5, wherein the total area is in a range of 40 mm2 to 45 mm2. 7. The glass article according to claim 5, wherein the lead-free solder alloy contains 1.5 to 5 mass % of Ag. 8. The glass article according to claim 5, wherein the electroconductive coating film is at least one selected from an antenna and a defogger. 9. The glass article according to claim 5, wherein the electroconductive coating film is formed by baking a silver paste that includes Ag particles and a glass frit. 10. The glass article according to claim 5, wherein the metal member is a metal terminal comprising a leg part having the at least two joining planes and a connection part that projects upward from the leg part and is to be connected to a cable. 11. A glass article according to claim 5, wherein with respect to each of the at least two joining planes, a volume of the lead-free solder alloy is 1.0 to 2.0 times the product of an area of the joining plane concerned and a thickness of the lead-free solder alloy. 12. (canceled) 13. (canceled) 14. (canceled) 15. (canceled) 16. (canceled) 17. A junction structure, comprising a glass article according to claim 1, wherein a cable is connected to a connection part of the metal member, and the cable and the electroconductive coating film are connected electrically to each other. 18. A junction structure, comprising a glass article according to claim 5, wherein a cable is connected to a connection part of the metal member, and the cable and the electroconductive coating film are connected electrically to each other. 19. (canceled)

TECHNICAL FIELD The present invention relates to a glass article with a metal member joined thereto, and a structure of joining a glass article and a metal member together. Particularly, the present invention relates to an adequate junction made between a glass article and a metal member using a lead-free solder alloy. BACKGROUND ART In order to ensure the driver's view, electroconductive lines (heating wires) are formed as a defogger on the surface of a glass sheet to be used for a rear window of a car in some cases. The defogger is supplied with an electric current through a feeding metal terminal. This metal terminal is provided on a bus bar connected to the defogger. In some cases, a glass antenna may be used for the rear and side windows of a car. In the case of using the glass antenna, electroconductive lines are formed, on the surface of a glass sheet, in a pattern (an antenna pattern) corresponding to the wavelength to be received. A metal terminal also is provided for the feeding point of this antenna pattern. Generally, the electroconductive line and bus bar are formed by baking a silver (Ag) paste printed onto the surface of the glass sheet. The Ag paste normally contains Ag particles, a glass frit, and a solvent. A metal terminal is fixed onto the electroconductive coating film formed by baking this Ag paste. Conventionally, a metal terminal is soldered using a tin-lead (Sn—Pb-based) solder alloy. Recently, from the viewpoint of environmental protection, it has been demanded to use a lead-free solder in producing car window glass. However, when a metal terminal is joined to a glass sheet using a lead-free solder alloy, particularly, a Sn-based lead-free alloy, the following problems occur. First, the electroconductive coating film may melt and flow into the soldered junction, which may impair the appearance of the electroconductive coating film. The bond strength also degrades together with the degradation in appearance. Second, it tends to be more difficult to ensure the bond strength of the metal terminal as compared to the case of using the Sn—Pb-based alloy. This tendency becomes conspicuous when using a metal terminal having a plurality of joining planes. Third, cracks may occur at the surface of the glass sheet in the vicinity of the soldered junction due to a rapid temperature change. Even if the cracks caused in the glass sheet are minute, they should be avoided when consideration is given to the long term strength of the glass sheet. This phenomenon also becomes conspicuous when using a metal terminal having a plurality of joining planes. In conjunction with the second problem, for example, JP-U-61(1986)-37182 discloses that the bond strength increased with an increase in soldered joining area. DISCLOSURE OF THE INVENTION The first problems can be solved by an addition of Ag to a Sn-based lead-free solder alloy. The addition of Ag improves not only the appearance but also the bond strength. From a first aspect, the present invention provides a glass article with a metal member joined thereto in which an electroconductive coating film is formed on at least a part of the surface of the glass article by baking a silver paste that includes Ag particles and a glass frit. A joining plane of the metal member is fixed onto the electroconductive coating film with a lead-free solder alloy containing Sn as a main component, and the lead-free solder alloy contains at least 1.5 mass % of Ag, for example, 1.5 to 5 mass % of Ag. In order to solve the second problem, a metal terminal was used that had an enlarged joining plane, but thereby the bond strength rather decreased. Surprisingly, the bond strength was improved by using a metal terminal with a smaller joining plane than conventional one. From the second aspect, the present invention provides a glass article with a metal member joined thereto in which an electroconductive coating film containing Ag is formed on at least a part of the surface of the glass article. At least two joining planes of the metal member are fixed onto the electroconductive coating film with a lead-free solder alloy containing Sn as a main component, and a total area of the at least two joining planes is in the range of 37 mm2 to 50 mm2. The third problem can be relieved not by the increase but the decrease in amount of the solder to be used. When the solder was prevented from spreading outside the joining plane, less cracks occurred in the glass sheet. From the third aspect, the present invention provides a glass article with a metal member joined thereto in which an electroconductive coating film containing Ag is formed on at least a part of the surface of the glass article, at least two joining planes of the metal member are fixed onto the electroconductive coating film with a lead-free solder alloy containing Sn as a main component, and with respect to each of the at least two joining planes, a volume of the lead-free solder alloy is 1.0 to 2.0 times the product of the area of the joining plane concerned and the thickness of the lead-free solder alloy. In the present specification, the “main component” denotes a component that accounts for at least 50 mass % according to its common use. BRIEF DESCRIPTION OF DRAWINGS FIG. 1 is a sectional view showing an example of a glass article according to the present invention. FIG. 2A is a sectional view showing another example of a glass article according to the present invention; FIG. 2B shows a metal terminal of the glass article seen from its back side; and FIG. 2C is a plan view showing an example of a joining plane with another shape of the metal terminal. FIG. 3 is a sectional view showing still another example of a glass article according to the present invention. FIG. 4 is a graph showing measurement results obtained in Example 1. FIG. 5 is a graph showing measurement results obtained in Example 2. BEST MODE FOR CARRYING OUT THE INVENTION Since the Sn-based lead-free alloy lacks flexibility as compared to the Sn—Pb-based alloy, the junction soldered using this lead-free alloy is inferior in the stress relaxation characteristic. Particularly, when there are a plurality of joining planes, thermal stress is developed in the in-plane direction in the glass sheet by the temperature change caused by soldering due to the difference in thermal expansion coefficient between glass and the portion of a metal member that connects the joining planes to each other. Accordingly, the strength of the glass sheet decreases, and in some cases, cracks may occur at the surface of the glass that is a brittle material. Actually, it was confirmed by a tension test of a metal member (a metal terminal) that the terminal and the glass sheet were ruptured due to the breakage not of the junction soldered using the Sn-based lead-free alloy but rather the inner portion of the glass in the vicinity of the soldered junction. Thus, it is considered that the thermal stress has some part in both the decrease in bond strength and the occurrence of cracks. The former can be prevented by controlling the joining area within a predetermined range, and the latter can be prevented by controlling the amount of the solder to be used to a degree that does not allow the bond strength to decrease considerably. Specifically, it is preferable that the joining area is controlled within the range of 37 mm2 to 50 mm2, particularly 40 mm2 to 45 mm2. In order to prevent the solder from considerably spreading outside the joining plane, it is preferable to control the volume V of the solder alloy to be 1.0 to 2.0 times the product of the area S of the joining plane and the thickness T of the lead-free solder alloy. In other words, it is preferable to control the volume V so that the following relative equation holds: 1.0ST≦V≦2.0ST When the Sn-based lead-free solder alloy containing no Ag is used on an electroconductive coating film containing Ag that has been formed by baking a Ag paste, Sn contained in the solder alloy and Ag contained in the electroconductive coating film form a compound. As a result, the electroconductive coating film is corroded. In order to prevent the appearance of the glass article from degrading due to this corrosion, a Sn—Ag lead-free alloy may be used that contains at least 1.5 mass % of Ag. Another advantage in adding Ag is that the bond strength increases. The strength of the junction soldered using the Sn—Ag alloy increases with an increase in rate of Ag content, but becomes almost constant when the rate of Ag content exceeds about 2 wt. %. On the other hand, an excessively high rate of Ag content causes a considerable rise in material cost and also raises the liquidus temperature of the alloy. The increase in liquidus temperature causes an increase in soldering temperature. Hence, the thermal stress increases and thereby the workability in soldering also deteriorates. When consideration is given to this, it is preferable that the rate of Ag content in the Sn—Ag solder alloy is 5 mass % or less, further preferably 4 mass % or less. With respect to the Sn—Ag alloy, when it has an eutectic composition of Sn-3.5Ag (an alloy made of 3.5 mass % of Ag and Sn that accounts for the rest), it has the lowest liquidus temperature (221° C.). In this case, the tip of the soldering iron has a temperature of 310° C. to 320° C. A low temperature of the tip has an effect of relieving of thermal stress caused by the difference in thermal expansion coefficient between members to be joined together. In the Sn-3.5Ag alloy, all the Ag is present as an intermetallic compound of Ag3Sn. In the Sn-3.5Ag alloy, the precipitating grains do not become large as compared to the Sn—Pb alloy. This is because Ag atoms do not disperse easily in the solid phase Sn. As described above, a preferable rate of Ag content in the Sn—Ag alloy is 1.5 to 5 mass %, further preferably 2 to 4 mass %, and particularly 2 to 3 mass %. This Sn-based lead-free solder alloy having this rate of Ag content is particularly suitable for the purpose of joining a metal member onto the electroconductive coating film formed by baking an Ag paste onto the surface of a glass article. This alloy composition brings preferable results regardless of whether the number of the joining plane is one or more. The Sn—Ag alloy may contain other minor components. In this case, it is preferable that the content of the minor components is 0.5 mass % or less. The metal member having at least two joining planes is not particularly limited. For example, however, the metal member may be a metal terminal including a leg part having the at least two joining planes and a connection part that projects upward from the leg part and is to be connected to a cable. Through this metal terminal, electricity can be fed to the electroconductive coating film formed on the surface of the glass sheet. The glass article also is not particularly limited, and for example, a glass sheet may be used that is formed of a soda-lime silica composition, as in the conventional case. When it is used for car window glass, the glass sheet suitably is subjected to tempering, bending, or the like. The electroconductive coating film may be at least one selected from an antenna and a defogger. The electroconductive coating film may be formed by printing and baking a silver paste in a predetermined pattern that is suitable for functioning as an antenna and/or a defogger. For the silver paste, a composition may be used that includes silver particles, a glass frit, and a solvent, as is conventionally used for glass articles. Its composition is not particularly limited, but as an example, it contains 70 to 85 mass % of silver particles, 1 to 20 mass % of a glass frit, and 5 to 25 mass % of a solvent. Hereinafter, embodiments of the present invention are described with reference to the drawings. In a glass article 1 shown in FIG. 1, an electroconductive coating film 3 is formed in a predetermined pattern on the surface of a glass sheet 2. A metal terminal 5 is joined onto the electroconductive coating film 3 with a lead-free solder alloy 4. This terminal 5 has two joining planes 5a and 5b, a leg part 5c for bridging these joining planes, and a connection part 5d that projects upward from the leg part. In FIG. 1, the lead-free solder alloy 4 spreads slightly toward the electroconductive coating film 3. The solder alloy 4, however, does not spread out considerably from the joining planes 5a and 5b but substantially stays between the coating film 3 and the joining planes 5a and 5b. In order to diminish the spread of the solder alloy 4, for example, the amount of the solder alloy 4, which is supplied in a state of being applied onto the joining planes 5a and 5b of the terminal, may be limited within an adequate range. FIG. 1 shows the terminal 5 formed with a metal portion that forms the connection part 5d being disposed above a metal portion that forms the leg part 5c. The shape of the terminal, however, is not limited thereto. For instance, as shown in FIG. 2A, a terminal 5 may be employed in which a metal portion that forms parts of the connection part 5d and the leg part 5c is combined with a metal portion that forms the rest of the connection part 5d and the leg part 5c. Such a terminal can be formed with one metal plate being bent. To the connection part 5d of this terminal 5 is connected a wire 6 having a connector 7 on its end. Through this wire, the electroconductive coating film 3 is connected electrically to a power source, an amplifier, etc., which are omitted in the drawing. As described above, the glass article according to the present invention is suitable for a junction structure in which a cable is connected to the connection part of the metal fitting and this cable and the electroconductive coating film are electrically connected to each other, that is, a structure for supplying electricity to the electroconductive coating film provided on the glass surface. The shape of the joining planes of the metal terminal is not limited to a rectangle (FIG. 2B) but may be a circle, an ellipse, a semicircle (FIG. 2C), a triangle, a polygon with five vertices or more, or the like. As described above, the Sn—Ag alloy of the present invention also can be used for the junction structure with only one joining plane. In this case, for example, a planar terminal 9 can be used that has one joining plane 9a and a connection part 9d as shown in FIG. 3. EXAMPLES Example 1 The same junction structures as that shown in FIG. 1 were produced. In each of them, soda-lime silica glass having a thickness of 3.1 mm was used for the glass sheet 2, a Sn—Ag alloy whose Ag content is shown in Table 1 was used as the lead-free solder alloy 4, and a terminal formed of a Cu metal sheet was used as the metal terminal 5. The areas of the two joining planes of the metal terminal 5 are set to be equal (a ratio of 1:1) to each other and to sum up to 56 mm2. The electroconductive coating film 3 was formed by screen-printing an Ag paste containing about 80 mass % of Ag particles, about 5 mass % of a glass frit, and about 15 mass % of an organic solvent, drying it, and further baking it at about 700° C. The lead-free solder alloy was applied to the joining planes of the metal terminal beforehand. The soldering was carried out by applying a flux to the solder alloy, pressing the joining planes of the metal terminal onto the electroconductive coating film, and pressing a soldering iron (with its tip having a temperature of about 310° C.) against the terminal. After the completion of the process, it was left at room temperature for 24 hours. With respect to each sample thus obtained, its bond strength was measured. The stress caused when the terminal was pulled upward (FIG. 1) and thereby the terminal and the glass sheet were ruptured, was employed to indicate the bond strength. In addition, the state of a portion of the electroconductive coating film located in the vicinity of the junction was checked visually. The appearance of each sample was evaluated by comparison with the case of using a Sn—Pb-based solder alloy. The results are shown in Table 1. TABLE 1 Components Melting Bond (mass %) Temperature Strength Sn Ag (° C.) Appearance (N) Sample 1A The rest 0.5 220-235 D 245 Sample 1B The rest 1.0 220-234 C 333 Sample 1C The rest 1.5 218-231 B 471 Sample 1D The rest 2.0 219-229 B 529 Sample 1E The rest 2.5 219-228 B 476 Sample 1F The rest 3.0 220-225 B 515 Sample 1G The rest 3.5 220-222 B 494 Sample 1H The rest 4.0 220-228 B 478 Sample 1I The rest 5.0 220-244 B 503 Sample 1J The rest 6.0 220-257 B 457 Sample 1K The rest 7.0 220-268 B 482 In each column of the melting temperature, the numbers on the left and right sides indicate a solidus temperature and a liquidus temperature, respectively. The appearance was evaluated with A standing for “superior”, B “equivalent”, C “slightly inferior”, and D “considerably inferior”. In the test of the bond strength, rupture took place inside the glass in all the samples. In the electroconductive coating films of Samples 1A and 1B, which contain less than 1.5 wt. % of Ag, their appearances degraded due to the “silver corrosion phenomenon”. The relationship between the rate of Ag content and bond strength is summarized and shown in FIG. 4. The bond strength increases until the rate of Ag content increases up to around 1.5 to 2 wt. % but becomes almost constant when it exceeds 2 wt. %. Except for Samples 1J and 1K, which contain more than 5 wt. % of Ag, the solder alloys had a liquidus temperature of 250° C. or lower. In addition, the respective samples had a solidus temperature of 220° C. or slightly lower. The temperature characteristics (the liquidus temperature: 230° C. or lower, and the difference between the liquidus temperature and the solidus temperature: 10° C. or less) of the samples 1D to 1H are advantageous in reducing the thermal stress and shortening the cooling time after soldering. Example 2 Samples were obtained in the same manner as in Example 1 except that a Sn—Ag alloy was used that contains 98 mass % of Sn and 2 mass % of Ag, and the total area of the joining planes was set at the values shown in Table 2. With respect to each sample thus obtained, its bond strength was measured in the same manner as in Example 1. The results are shown in Table 2. In all the samples, rupture of the junction took place not at the soldered junction but inside the glass. TABLE 2 Total Area of Joining Planes Bond Strength Samples (mm2) (N) 2A 28 522.3 2B 35 519.5 2C 42 727.9 2D 49 591.8 2E 56 503.1 As is apparent from FIG. 5 showing the relationship between the total area of joining planes (joining area) and the bond strength, the bond strength degrades both in the case where the joining area is too large and where it is too small. Thus, in order to improve the bond strength in the junction structure in which the terminal having a plurality of joining planes is fixed with a “hard” lead-free solder alloy, the joining area needs to be designed properly. This proper design also brings preferable results from the viewpoint of the reduction in amount of the solder to be used. Example 3 Samples were obtained in the same manner as in Example 1 except that the amount of the lead-free solder alloy 4 provided on the respective joining planes and the total area of the joining planes were set at values shown in Table 3. With respect to each of n pieces of samples thus obtained, a thermal test was carried out through predetermined temperature cycling, and the state of the glass surface was checked visually every 100 cycles after 200 cycles. The temperature cycling was set to include a period of retention for 30 minutes at −30° C., a period of raising temperature to 80° C. in three minutes, a period of retention in this state for 30 minutes, and a period of decreasing temperature to −30° C. in three minutes, and thus the thermal cycle test was carried out. The results are shown in Table 3. In Samples 3A to 3D and 3F to 3G, no cracks occurred in the glass even when the above-mentioned thermal cycle was repeated 500 times. In Sample 3A, the bond strength determined by the tension test carried out in the same manner as in Example 1, however, was lower than that of Sample 3C by about 25%. On the other hand, since Sample 3G had a reduced joining area, its bond strength was higher than that of Sample 3C by about 18%. The volumes shown in the table were calculated from the mass of the solder alloy and its specific gravity. TABLE 3 Solder Alloy The number of cracks Amount Volume Joining Thickness V/ caused by thermal test Samples (g) (mm3) Area (mm) ST n 200 300 400 500 3A 0.1 13.6 Normal 0.5 0.5 2 0 0 0 0 3B 0.2 27.2 Normal 0.5 1.0 6 0 0 0 0 3C 0.3 40.8 Normal 0.5 1.5 10 0 0 0 0 3D 0.4 54.3 Normal 0.5 1.9 6 0 0 0 0 3E 0.5 67.9 Normal 0.5 2.4 6 3 1 0 1 3F 0.2 27.2 Reduced 0.5 1.3 6 0 0 0 0 3G 0.3 40.8 Reduced 0.5 1.9 6 0 0 0 0 3H 0.4 54.3 Reduced 0.5 2.6 6 0 0 2 1 “Normal” indicates 56 mm2, and “Reduced” denotes 42 mm2. INDUSTRIAL APPLICABILITY As described above, the present invention can provide a glass article including a junction with a metal member that is excellent in strength while using a lead-free solder alloy.

<SOH> BACKGROUND ART <EOH>In order to ensure the driver's view, electroconductive lines (heating wires) are formed as a defogger on the surface of a glass sheet to be used for a rear window of a car in some cases. The defogger is supplied with an electric current through a feeding metal terminal. This metal terminal is provided on a bus bar connected to the defogger. In some cases, a glass antenna may be used for the rear and side windows of a car. In the case of using the glass antenna, electroconductive lines are formed, on the surface of a glass sheet, in a pattern (an antenna pattern) corresponding to the wavelength to be received. A metal terminal also is provided for the feeding point of this antenna pattern. Generally, the electroconductive line and bus bar are formed by baking a silver (Ag) paste printed onto the surface of the glass sheet. The Ag paste normally contains Ag particles, a glass frit, and a solvent. A metal terminal is fixed onto the electroconductive coating film formed by baking this Ag paste. Conventionally, a metal terminal is soldered using a tin-lead (Sn—Pb-based) solder alloy. Recently, from the viewpoint of environmental protection, it has been demanded to use a lead-free solder in producing car window glass. However, when a metal terminal is joined to a glass sheet using a lead-free solder alloy, particularly, a Sn-based lead-free alloy, the following problems occur. First, the electroconductive coating film may melt and flow into the soldered junction, which may impair the appearance of the electroconductive coating film. The bond strength also degrades together with the degradation in appearance. Second, it tends to be more difficult to ensure the bond strength of the metal terminal as compared to the case of using the Sn—Pb-based alloy. This tendency becomes conspicuous when using a metal terminal having a plurality of joining planes. Third, cracks may occur at the surface of the glass sheet in the vicinity of the soldered junction due to a rapid temperature change. Even if the cracks caused in the glass sheet are minute, they should be avoided when consideration is given to the long term strength of the glass sheet. This phenomenon also becomes conspicuous when using a metal terminal having a plurality of joining planes. In conjunction with the second problem, for example, JP-U-61(1986)-37182 discloses that the bond strength increased with an increase in soldered joining area.

<SOH> BRIEF DESCRIPTION OF DRAWINGS <EOH>FIG. 1 is a sectional view showing an example of a glass article according to the present invention. FIG. 2A is a sectional view showing another example of a glass article according to the present invention; FIG. 2B shows a metal terminal of the glass article seen from its back side; and FIG. 2C is a plan view showing an example of a joining plane with another shape of the metal terminal. FIG. 3 is a sectional view showing still another example of a glass article according to the present invention. FIG. 4 is a graph showing measurement results obtained in Example 1. FIG. 5 is a graph showing measurement results obtained in Example 2. detailed-description description="Detailed Description" end="lead"?

20040902

20090407

20050526

93328.0

FUQUA, SHAWNTINA T

GLASS ARTICLE WITH METAL MEMBER JOINED THERETO,AND JUNCTION STRUCTURE USING THE SAME

UNDISCOUNTED

ACCEPTED

ACCEPTED

Cosmetic use of phytosphingosine as slimming agent and cosmetic compositions comprising phytosphingosine

The invention relates to novel cosmetic uses of phytosphingosine or of one of its cosmetically acceptable salts, particularly its hydrochloride, as a slimming agent and/or as an active agent which stimulates the synthesis of leptin by adipocytes, for preparing a cosmetic composition intended for reducing subcutaneous excess fat. The invention also relates to a method of cosmetic treatment intended for obtaining a slimming effect on the human body according to which a cosmetic composition containing phytosphingosine or one of its cosmetically acceptable salts, particularly its hydrochloride, is applied on the parts of the body to be treated. The invention also relates to novel cosmetic compositions containing phytosphingosine or one of its cosmetically acceptable salts, particularly its hydrochloride, in combination with a lipolytic agent selected from the group consisting of CAMP and its derivatives, adenylate cyclase enzyme activating agents and phosphodiesterase enzyme inhibiting agents.

1-30. (canceled) 31. A method of cosmetic treatment for obtaining a slimming effect on the human body, comprising the application on the parts of the body in need thereof of an effective amount of a cosmetic composition containing an active agent selected from the group consisting of phytosphingosine and its cosmetically acceptable salts. 32. The method according to claim 31, wherein said method is intended for reducing subcutaneous excess fat. 33. The method according to claim 31, wherein said active agent is phytosphingosine hydrochloride. 34. The method according to claim 31, wherein the concentration of said active agent is comprised between 0.001% and 1%, by weight with respect to the total weight of said composition. 35. The method according to claim 31, wherein said composition further comprises at least one cosmetically acceptable lipolytic agent. 36. The method according to claim 35, wherein said lipolytic agent is selected from the group consisting of adenosine-3′,5′-cyclic monophosphate (CAMP) and its cosmetically acceptable derivatives. 37. The method according to claim 36, wherein said cosmetically acceptable derivatives are selected from the group consisting of the salts and acylated derivatives of CAMP. 38. The method according to claim 37, wherein said derivative is selected from the group consisting of mono- and dibutyril derivatives of CAMP. 39. The method according to claim 36, wherein said CAMP or said lipolytic agent is at a concentration of between 0.001% and 5%, by weight with respect to the total weight of said composition. 40. The method according to claim 35, wherein said lipolytic agent is an adenylate cyclase enzyme activating agent. 41. The use according to claim 40, wherein said adenylate cyclase enzyme activating agent is selected from the group consisting of forskolin and plant extracts containing the same. 42. The method according to claim 41, wherein said adenylate cyclase enzyme activating agent is at a concentration of between 0.001% and 1%, by weight with respect to the total weight of said composition. 43. The method according to claim 41, wherein said adenylate cyclase enzyme activating agent is selected from the group consisting of extracts of Coleus forskohlii and Plectranthus barbatus. 44. The method according to claim 41, wherein said adenylate cyclase activating agent is an extract of the plant Tephrosia purpurea, at a concentration of between 0.001% and 5% by weight, with respect to the total weight of said composition. 45. The method according to claim 35, wherein said lipolytic agent is a phosphodiesterase enzyme inhibiting agent. 46. The method according to claim 45, wherein said phosphodiesterase enzyme inhibiting agent is selected from the group consisting of xanthines, IBMX, caffeine and theophylline. 47. The method according to claim 46, wherein said phosphodiesterase enzyme inhibiting agent is 3-isobutyl-1-methyl-xanthine. 48. The method according to claim 46, wherein said phosphodiesterase enzyme inhibiting agent is at a concentration of between 0.001% and 10% by weight, with respect to the weight of said composition. 49. A method of cosmetic treatment for stimulating the synthesis of leptin by adipocytes, comprising the application on the parts of the body in need thereof of an effective amount of a cosmetic composition containing an active agent selected from the group consisting of phytosphingosine and its cosmetically acceptable salts. 50. The method according to claim 49, wherein said method is intended for reducing subcutaneous excess fat. 51. The method according to claim 49, wherein said active agent is phytosphingosine hydrochloride. 52. The method according to claim 49, wherein the concentration of said active agent is comprised between 0.001% and 1%, by weight with respect to the total weight of said composition. 53. The method according to claim 49, wherein said composition further comprises at least one cosmetically acceptable lipolytic agent. 54. The method according to claim 53, wherein said lipolytic agent is selected from the group consisting of adenosine-3′,5′-cyclic monophosphate (CAMP) and its cosmetically acceptable derivatives. 55. The method according to claim 54, wherein said cosmetically acceptable derivatives are selected from the group consisting of the salts and acylated derivatives of CAMP. 56. The method according to claim 55, wherein said derivative is selected from the group consisting of mono- and dibutyril derivatives of CAMP. 57. The method according to claim 56, wherein said CAMP or said lipolytic agent is at a concentration of between 0.001% and 5%, by weight with respect to the total weight of said composition. 58. The method according to claim 53, wherein said lipolytic agent is an adenylate cyclase enzyme activating agent. 59. The use according to claim 58, wherein said adenylate cyclase enzyme activating agent is selected from the group consisting of forskolin and plant extracts containing the same. 60. The method according to claim 59, wherein said adenylate cyclase enzyme activating agent is at a concentration of between 0.001% and 1%, by weight with respect to the total weight of said composition. 61. The method according to claim 59, wherein said adenylate cyclase enzyme activating agent is selected from the group consisting of extracts of Coleus forskohlii and Plectranthus barbatus. 62. The method according to claim 59, wherein said adenylate cyclase activating agent is an extract of the plant Tephrosia purpurea, at a concentration of between 0.001% and 5% by weight, with respect to the total weight of said composition. 63. The method according to claim 53, wherein said lipolytic agent is a phosphodiesterase enzyme inhibiting agent. 64. The method according to claim 63, wherein said phosphodiesterase enzyme inhibiting agent is selected from the group consisting of xanthines, IBMX, caffeine and theophylline. 65. The method according to claim 64, wherein said phosphodiesterase enzyme inhibiting agent is 3-isobutyl-1-methyl-xanthine. 66. The method according to claim 64, wherein said phosphodiesterase enzyme inhibiting agent is at a concentration of between 0.001% and 10% by weight, with respect to the weight of said composition. 67. A cosmetic composition, notably intended for reducing subcutaneous excess fat, containing, as active agents: phytosphingosine or one of its cosmetically acceptable salts, and at least one lipolytic agent selected from the group consisting of CAMP and its cosmetically acceptable lipolytic derivatives, adenylate cyclase enzyme activating agents and phosphodiesterase enzyme inhibiting agents, in a cosmetically acceptable vehicle. 68. The composition according to claim 67, wherein said cosmetically acceptable salt is phytosphingosine hydrochloride. 69. The cosmetic composition according to claim 67, containing from 0.001 to 1%, by weight of phytosphingosine or of one of its cosmetically acceptable salts. 70. The cosmetic composition according to claim 67, wherein said lipolytic agent is selected from the group consisting of CAMP and its cosmetically acceptable derivatives. 71. The cosmetic composition according to claim 70, wherein said cosmetically acceptable derivative of CAMP is selected from the group consisting of the salts and acylated derivatives of CAMP. 72. The cosmetic composition according to claim 71, wherein said cosmetically acceptable derivative of CAMP is selected from the group consisting of mono- and dibutyryl derivatives of CAMP. 73. The cosmetic composition according to claim 70, wherein said lipolytic agent is at a concentration of between 0.001% and 5% by weight with respect to the total weight of said composition. 74. The cosmetic composition according to claim 67, wherein said the lipolytic agent is an adenylate cyclase enzyme activating agent. 75. The cosmetic composition according to claim 74, wherein said adenylate cyclase enzyme activating agent is selected from the group consisting of forskolin and plant extracts containing the same. 76. The cosmetic composition according to claim 75, wherein said adenylate cyclase enzyme activating agent is at a concentration of between 0.001% and 1%, by weight with respect to the total weight of said composition. 77. The cosmetic composition according to claim 75, wherein said adenylate cyclase enzyme activating agent is an extract of Coleus forskohlii or of Plectranthus barbatus. 78. The cosmetic composition according to claim 74, wherein said adenylate cyclase activating agent is an extract of the plant Tephrosia purpurea. 79. The cosmetic composition according to claim 78, wherein the extract of Tephrosia purpurea is at a concentration of between 0.001% and 5% by weight, with respect to the total weight of the composition. 80. The cosmetic composition according to claim 67, wherein said lipolytic agent is a phosphodiesterase enzyme inhibiting agent. 81. The cosmetic composition according to claim 80, wherein said phosphodiesterase inhibiting enzyme agent is selected from the group consisting of xanthines, caffeine and theophylline. 82. The cosmetic composition according to claim 81, wherein said phosphodiesterase inhibiting enzyme agent is selected from the group consisting of 3-isobutyl-1-methyl-xanthine and IBMX. 83. The cosmetic composition according to claim 81, wherein said phosphodiesterase inhibiting enzyme agent is at a concentration of between 0.001% and 10%, by weight with respect to the total weight of the composition.

The present invention relates to a novel cosmetic use of phytosphingosine, as a slimming agent, as well as to cosmetic compositions containing phytosphingosine. Phytosphingosine is of the following formula: Its molecular formula is C18H39NO3 and its CAS number is as follows: RN 100 000 403-19-8. This product is also known under the designation (2S,3S,4R)-2-amino-1,3,4-octadecanetriol. Phytosphingosine is a commercial product which corresponds to one of the three sphingoid bases which are present naturally in the skin, phytosphingosine being present in the stratum corneum. Applications of phytosphingosine and of its salts, and, more particularly, of its hydrochloride, are already known in the field of dermatology. Phytosphingosine is in fact known essentially for its anti-microbial activity, as well as for its activity as a <<second messenger>>, which is an application which results in a reduction of the sensitivity of the skin. More specifically, phytosphingosine is known for its activity in the treatment of acne, for its activity of inhibiting the growth of microorganisms on the skin, and for reducing various inflammatory phenomena observed on the skin. The inventors of the present invention have, in an entirely surprising way, now discovered a novel use of phytosphingosine, as well as of its cosmetically acceptable salts, particularly of its hydrochloride, as a slimming agent. They have furthermore demonstrated that this novel use is linked, at least partially, to the perfectly unexpected property of phytosphingosine, and of its salts, of promoting the synthesis of leptin by adipocytes of the skin. Furthermore, in pursuing their studies in this field, the inventors of the present invention have also demonstrated that a certain number of combinations of phytosphingosine or of its cosmetically acceptable salts turned out to be particularly interesting in these novel uses. Leptin from the mouse has recently been identified in 1994 as being the product of the “ob gene” (Zhang, y et al., Nature, 1994, 372:425 and Tartaglia L. A., 1997, J. Biol. Chem. 272:6093). The structure of human leptin (or human OB protein) and its use in the modulation of weight in animals are described in British patent application GB 2,292,382. Leptin is a protein which is secreted by the adipocyte which informs the brain of the state of the adipose reserves. It acts through membrane receptors which are situated in particular in the hypothalamus. Leptin was first studied in the rodent and then in man, and plays a key role in the regulation of body weight. In ob/ob mice, the absence of leptin in the serum, due to mutations of the ob gene (that which encodes leptin), leads to a massive obesity. In man, the first pieces of work in relation to leptin were directed towards obese and/or diabetic patients. In fact, the more an adipocyte possesses a higher content of triglycerides, the more it produces leptin, and vice versa (Medecine/Sciences, 1998, no8-9, 14, 858-864, G. Ailhaud: L'adipocyte, cellule secrétrice and endocrine (<<The adipocyte, a secretory and endocrine cell>>)). Thus, in the obese person, two situations can arise. Either a mutation of the leptin gene exists, this mutation is then non-functional, particularly on the receptors in the brain, or, a lack of transfer of leptin exists about the blood-brain barrier. One study, during which a daily injection of synthetic leptin was made in patients suffering from obesity or from excess weight, has shown conclusive results: a significant weight loss appeared in patients suffering from a certain form of obesity (work carried out at Tufts University in the USA, presented on the occasion of the conference: American Diabetes Association: Jean Mayer, USA Human Nutrition Research Center on Aging). Leptin does in fact trigger off a phenomenon of satiety which causes a reduction in food ingestion and which reduces the frequency of food ingestion. When the adipose mass increases, the leptin produced by the adipose tissue will inhibit the food ingestion and will stimulate energy expenditure. Leptin will thus act against an excessive weight gain. Hence, it may be considered that this protein is a regulator of the adipose mass, the prime role of which is to inhibit the deposit of excess adiposity. The role of local regulation which is played by leptin is well-known (see Systemically and Topically Administered Leptin Both Accelerate Wound Healing in Diabetic ob/ob Mice. B. D. Ring, S. Scully, C. R. Davis, M. B Baker, M. J. Cullen, M. A. Pelleymounter, D. Danilenko. Endocrinology, 2000 vol. 141, no1, p. 446-449). Furthermore, the role of leptin in the expression of certain genes leading to the accumulation of lipids (differentiation genes) is also well-known within the context of regulation of lipolysis. Leptin on the one hand supresses the expression of certain genes leading to an accumulation of lipids (differentiation genes), and this takes place without the participation of the brain. On the other hand, leptin induces a lipolysis directly on the adipocytes. This has been observed on mouse adipocytes in vitro (see In vitro Lipolytic Effect of Leptin on Mouse Adipocytes: Evidence for a possible Autocrine/Paracrine Role of Leptin, G. Frühbeck, M. Aguado, J. A. Martinez, Biochemical and Biophysical Research communications 1997: 240, p. 590-594). The effect of leptin on the lipolysis of the adipocytes is specific and operates via receptors which are present in the white adipose tissue. Leptin converts oestrone of the blood circulation (a hormone which increases lipid deposits) into oleyl-oestrone which is considered to be a “slimming” factor. The appearance of this factor causes a generalised lipolysis and a thermogenesis (see Leptin enhances the synthesis of oleyl-estrone from estrone in white adipose tissue, M. Esteve, J. Virgili, H. Aguilar, F. Balada, J. A. Fernandez-Lopez, W. Remesar, M. Alemany, Eur J. Nutr. 1999, 38, p. 99-104). When oleyl-oestrone is administered to obese or normal rats, it causes a loss in fatty mass. All the interest that there is is thus seen in having a means available to act upon the synthesis of leptin, which will notably act directly on the skin via receptors present therein, on the adipose tissue in causing lipolysis, on a factor acting as a weight regulator, namely, oleyl-oestrone. Tests carried out within the context of the present invention, on cultures of murine adipocytes as well as on cultures of human adipocytes, have enabled demonstrating that it was possible, by treating these cultures with phytosphingosine or one of its salts, particularly its hydrochloride, to stimulate the synthesis of leptin by these adipocytes, and this left predicting the possibility of using phytosphingosine or its salts as a slimming agent. It has been possible to confirm this effect. Hence, according to a first aspect, the present invention relates to a novel cosmetic use of phytosphingosine or of one of its cosmetically acceptable salts, particularly its hydrochloride, as a slimming agent for preparing a cosmetic composition intended for reducing subcutaneous excess fat. According to a second aspect, the invention relates to a novel cosmetic use of phytosphingosine or of one of its cosmetically acceptable salts, particularly of its hydrochloride, as an active agent which stimulates the synthesis of leptin by adipocytes, for preparing a cosmetic composition intended for reducing subcutaneous excess fat. According to a third aspect, the invention relates to a method of cosmetic treatment intended for obtaining a slimming effect on the human body, according to which an effective amount of a cosmetic composition containing phytosphingosine or one of its cosmetically acceptable salts, particularly its hydrochloride, is applied on the parts of the body where said effect is sought. Furthermore, according to the three aspects of the invention, as defined supra, it has appeared that certain combinations of phytosphingosine or of one of its cosmetically acceptable salts, particularly of its hydrochloride, turned out to be particularly interesting for improving the slimming effect obtained by the application of any one of the compositions containing these particular combinations. More specifically, it has appeared that the combination of phytosphingosine or of one of its cosmetically acceptable salts, with one or more agents, hereinafter designated as lipolytic agents, which induce a lipolysis, in the adipocytes, turned out to be particularly interesting within the context of the present invention, as will be explained further on. In particular, at least one cosmetically acceptable lipolytic agent will be selected from the group consisting of adenosine 3′,5′-cyclic monophosphate (CAMP) and its derivatives, adenylate cyclase enzyme activating agents and phosphodiesterase enzyme inhibiting agents, for making this combination. Forskolin, or a plant extract containing it, such as an extract of Coleus forskohlii or Plectranthus barbatus, or even an extract of the plant Tephrosia purpurea, will advantageously be selected as adenylate cyclase activating agent. It will be possible to use a xanthine, such as 3-isobutyl-1-methyl-xanthine or IBMX, caffeine or theophilline, as phosphodiesterase inhibiting agent. The cosmetic compositions containing such combinations, which are novel per se, constitute the fourth aspect of the invention. It is these compositions as they are defined infra which will preferably be made use of in all the cosmetic applications covered by the present invention. Hence, according to this fourth aspect, the present invention relates to a cosmetic composition, notably intended for reducing subcutaneous excess fat, characterised in that it contains, as active agent, phytosphingosine, or one of its cosmetically acceptable salts, particularly its hydrochloride, and at least one cosmetically acceptable lipolytic agent selected from the group consisting of CAMP and its cosmetically acceptable derivatives, adenylate cyclase enzyme activating agents and phosphodiesterase enzyme inhibiting agents, in a cosmetically acceptable vehicle. In the novel compositions of the invention, which are also the compositions which are preferred for the implementation of the various applications covered by the present invention, phytosphingosine, or one of its cosmetically acceptable salts, particularly its hydrochloride, is contained in the cosmetic composition at a concentration of between 0.001% and 1% and, preferably, between 0.05% and 0.5% by weight with respect to the total weight of said composition. The cosmetic composition further contains at least one lipolytic active agent selected from the group consisting of CAMP and its lipolytic derivatives, adenylate cyclase enzyme activating agents and phosphodiesterase enzyme inhibiting agents. In these cosmetic compositions, CAMP or its derivative will advantageously be used at a concentration of between 0.001% and 5% by weight with respect to the total weight of the composition. It will be possible to select any cosmetically acceptable derivative of CAMP, and particularly a salt or an acylated derivative, notably a mono- or dibutyryl derivative, as a derivative of CAMP. Forskolin, or a plant extract containing it, preferably at a concentration of between 0.001% and 1% and, preferably between 0.05% and 0.25%, by weight with respect to the total weight of the composition, is advantageously selected as an adenylate cyclase enzyme activating agent. An extract of Coleus forskohlii or Plectranthus barbatus will be preferably be selected as an extract containing forskolin. Such an extract can be obtained by an extraction method, such as the one described in the International application WO 91/02516. It will also be possible to use an extract of the plant Tephrosia purpurea, at a concentration of between 0.001% and 5%, preferably between 0.01% and 5%, by weight with respect to the total weight of the composition, as an adenylate cyclase activating agent. Such an extract can be obtained by an extraction method such as the one described in the International application WO 95/03780. Finally, as set forth supra, according to another variant, the preferred compositions according to the invention contain a phosphodiesterase inhibiting agent, particularly a xanthine, and, more particularly, 3-isobutyl-1-methyl-xanthine (IBMX), caffeine or theophilline, preferably at a concentration of between 0.001% and 10%, preferably between 0.01 and 1%, by weight with respect to the weight of the composition. The preferred compositions which are used in accordance with the present invention and which contain a combination of phytosphingosine or of one of its salts with a lipolytic agent such as CAMP and its lipolytic derivatives, adenylate cyclase activating agents and phosphodiesterase inhibiting agents, turn out to be particularly interesting by virtue of the synergistic action of the two types of constituents. Without the inventors considering to be totally bound by this explanation, a plausible interpretation of the synergy effect observed is given infra. It has in fact already been observed that the agents which promote a lipolysis in the adipocytes, such as the extracts of Coleus for example, possess a remarkable biological effectiveness which in general combines a significant lipolytic power with an inhibitory activity of adipocyte maturation. The significant reduction in volume and in quantity of the lipid vacuoles after a treatment with the lipolytic agent leads to a reduction in the production of leptin. It is thus probable that this local loss of leptin in the environment close to the adipocytes resulting from the treatment by the lipolytic agent might be compensated by the effect of a product which stimulates leptin synthesis, in the present case by phytosphingosine or its salt. The maintenance of a sufficient leptin concentration in the environment close to the adipocytes thus exerts a role with acts against the increase in the adipose mass. It thus seems that all takes place as though the message were emitted by fatty cells which inform, by a retro-control operation, of the necessity to reduce the storage in the form of triglycerides. Thus, by virtue of the combined action of phytosphingosine or of one of its salts, and of at least one other lipolytic agent, an increased and a longer-acting slimming effect is obtained. This hypothesis does seem to be confirmed entirely by the results obtained within the context of Examples 2 and 4 of the present invention which concern the combination of phytosphingosine with an extract of Coleus forskohlii. The following Examples are given purely as an illustration of the present invention. They are accompanied by FIGS. 1 to 6, which represent, respectively: FIG. 1: the effect upon the lipogenesis of various treatments carried out in Example 2; FIGS. 2 to 4: the morphology of the murine adipocytes at different stages of the treatment according to Example 2; FIG. 5: the morphology of the human adipocytes at D18 for a control solution (according to Example 3); and FIG. 6: the morphology of the human adipocytes at D18 for a treatment with a combination according to the invention (according to Example 3). EXAMPLES In the following Examples, and, unless indicated otherwise, the proportions are indicated in percentage by weight. Example 1 Demonstration of the Stimulating Activity of Phytosphingosine on the Production of Leptin by Murine Adipocytes in Culture. 1. Principle of the Test The concept according to which the adipose mass may be regulated via secreted circulating factors is very interesting. The principle of the test is to control the secretion of leptin by the adipocytes. 2. Material and Methods Culture of 3T3 F442A Cells A clone, which has the capacity to accumulate larges amounts of triglycerides, was isolated from an established cell-line of mouse 3T3 preadipocytes. The lipolytic agents reduce this accumulation. It thus appeared important to test potential lipolytic agents on this 3T3 F442A murine peradipocytes cell-line. These preadipocytes (GREEN H. and KEHINDE O.—Spontaneous Heritable Changes Leading to Increased Adipose Conversion in 3T3 Cells, Cell Vol. 7, 105-113, 1976) can multiply and differentiate by possessing the morphological and biochemical phenotype which is characteristic of the differentiated function of the mature adipocyte. When they are in exponential growth phase, they are of fibroblastic appearance, having an elongated shape and are very adherent to the support. At the confluence, when the conditions so permit, a very premature morphological transition gives them a rounded shape. The cells thus undergo a clonal amplification process. Increases in the activity of lipogenetic enzymes are added to these morphological changes, as well as increases in responses by the cells to hormones/factors which affect the lipogenesis and the lipolysis. The 3T3 F442A preadipoytes thus constitute an excellent model for study of lipolysis, by virtue of the morphological and metabolic transformations acquired by the cells during their development programme. (Pairault J and Lasnier F: Control of adipogenetic differenciation of 3T3 F442A cells by retinoic acid, dexamethasone and insulin: a topographic analysis J. cell Physiol. 1987, 132, 279-86). According to the literature, leptin is secreted in the culture medium since it is stored in the adipocytes. (Wabitsch M et al, Diabetes, 1996, vol 45, Bornstein S. et al, Diabetes, 2000, vol 49, Friedman J M, Nutrition Reviews, 1998, vol 56 no2). In 3T3 F442A cells, the expression of the ob gene has been studied in particular (Leroy P et al, J. of Biol. Chem, 1996, vol 271 no5, pp. 2365-2368, Considine R V et al—Horm. Res. 1996, 46: 249-256). The 3T3 F442A preadipocytes are sown at DO in 35 mm Petri dishes (Corning) and placed in an oven at 37° C. under an air-CO2 atmosphere (95-5). The cells are cultivated in an Eagle minimum essential medium modified according to Dulbecco (glucose 4.50 g/l) (DMEM-GIBCO BRL) supplemented with 5% of calf serum (CS) (BIOMEDIA®) and 5% of foetal calf serum (GIBCO) during the growth phase. The medium is changed at D2 and D4. At the cell confluence (at D7), the medium is changed: The basic medium remains the same (DMEM) but is supplemented with 10% of foetal calf serum (FCS) and insulin (5 μg/mL) (SIGMA). The medium is then changed at D9 and D11. At D14, D16 and D18, a treatment is made with the composition the effectiveness of which on the leptin synthesis it is sought to verify. The protocol is summarised in the Table below: D0 Sowing of the 3T3 F442A in DMEM, 5% CS, 5% FCS - cell density 2 × 104 cells/35 mm Petri dish D2 Change of medium D4 Change of medium D7 Confluence - Culture medium DMEM, 10% FCS, 1% insulin (mother solution at 500 μg/mL) D9 and Change of medium D11 D14 Treatment with the composition to be tested D16 and Treatment with the composition to be tested D18 D21 Collection of the cell supernatants 3. Leptin Determination The leptin secreted is determined by means of a sandwich-type Elisa technique re-running with a Quantikine M Mouse Leptin Immunoassay kit. This ELISA determination uses recombined mouse leptin, expressed in E. coli and antibodies directed against recombinant mouse leptin. The test uses a “sandwich” immunoenzymatic technique. The microplate wells are lined with a mouse leptin polyclonal antibody. The standards, controls and samples are deposited in the wells and, at the same moment, all the leptin present binds to the immobilised antibody. The bound leptin is then detected by a mouse anti-leptin antibody which is coupled to an enzyme peroxidase. A substrate solution is then added into the wells. The enzymatic reaction leads to a blue solution which turns yellow after addition of a quenching solution. The intensity of the colour measured is proportional to the amount of leptin present. The reading of the optical density is done at 450 nm on the spectrophotometer. The determination is obtained afterwards of the dose-response curves in relation to the measurement of natural leptin, parallel to the standard curves obtained with “recombinant” Quantikine M standards. The Quantikine M kit thus enables the relative mass values for the natural mouse leptin to be determined. The optical density measured at 450 nm is proportional to the amount of antibody fixed, which is itself proportional to the amount of leptin present initially. The results are expressed in pg/mL of leptin present in the cell supernatants. The samples were tested in triplicate. 4. Results Three compositions containing 0.25, 1 and 2 μg/mL, respectively, of phytosphingosine or of its hydrochloride, were tested. For the 3T3-F442A adipocytes which are maintained in culture without any treatment, the amount of leptin present in the culture supernatants increases strongly with time (16.4 pg/mL at D4, 802 pg/mL at D11 and 2,623 pg/mL at D20). This result is in conformity with the biological data (Leroy P. 1996, Considine R V. 1996): under basal conditions, the murine adipocytes secrete increasing amounts of leptin all throughout their maturation. We thus confirm that a mature adipocyte secretes amounts of leptin which are greater than those of a preadipocyte. The amounts of leptin present in the supernatants are reported in Table 1 below. The abbreviation PS designates phytosphingosine. TABLE 1 Amount of leptin, expressed in pg/mL, which is present in the culture supernatants of mature 3T3-F442A adipocytes treated with phytosphingosine at day D21 leptin (pg/mL) Standard phytosphingosine (μg/mL) Average deviation O (control) 1510 23.43 0.25 1789 11.27 1 1563.6 14.33 2 1428.8 200 After 7 days of treatment, i.e. at day D21, phytosphingosine induces an increase in the secretion of leptin by treated adipocytes, an effect which is maximum at the concentration of 0.25 μg/mL. The increase is of a little more than 18% at this concentration. Phytosphingosine hydrochloride, when tested under the same conditions, is also responsible for a stimulation of the leptin secretion: +52% at 1 μg/mL and +26% at 2 μg/mL and +18% at 0.25 μg/mL. The results for the hydrochloride are reported in Table 2 below. TABLE 2 Amount of leptin, expressed in pg/mL, which is present in the culture supernatants of mature 3T3-F442A adipocytes treated with phytosphingosine hydrochloride at day D21 leptin (pg/mL) phytosphingosine-HCl Standard (μg/mL) Average deviation 0 (control) 1510 23.43 0.25 1789 201.79 1 2301.3 49.821 2 1907.9 31.93 Thus, phytosphingosine is capable of inducing an increase in the basal adipocyte secretion of leptin in the 3T3-F442A adipose cell, a model which is very close to the human adipocyte. Phytosphingosine is thus capable of playing an important role in the control of the stability of the fatty mass. Example 2 Demonstration of the Interest in the Combination of Phytosphingosine with an Adenylate Cyclase Activator, Such as an Extract of Coleus forskohlii, for Promoting the Decrease of Lipogenesis in Murine Adipocytes in Culture. 1. Principle of the Study This study relates to the effects of the combination of the two actives, Coleus forskohlii (also named Plectranthus barbatus) (PB) and phytosphingosine (PS) on the recruiting of new adipocytes. It is known that the development of white adipose tissue represents a process which is continuous throughout the whole life (AILHAUD G., GRIMALDI P., NEGREL R., Trends in Endocrinology and Metabolism, (1994) 5 (3) 132-6). The adipocyte is associated, within the adipose tissue, with an abundant extracellular matrix which also includes endothelial cells, capillaries, nerve fibres and fibroadipoblast precursors. The mature adipocyte represents the phenotype of a cell originating from the differentiation of an adipocyte precursor. The preadipocytes are present within the same adipose tissue and can be recruited at any stage of life in order to generate new adipocytes: in the case of a weight gain, an initial phase exists of increase in the adipocyte volume until a critical point is attained, which then leads to the recruitment of new cells (Bjorntorp P., Int. J. Obesity, (1991) 15 67-81). The intrinsic capacity of the preadipocytes to multiply and to differentiate into adipocytes plays a determinant role in the development of fatty masses. A hyperplasia of these cells related to the fibroblasts leads to an increase of the adipose tissue. Thus, the mature adipocytes are firstly treated with PB+PS. Secondly, the culture medium which is conditioned with these adipocytes is placed in contact with preadipocytes the maturation of which into adipoctyes will be followed. The control cells at the start of the treatment commence to differentiate and undergo a certain number of changes: increase in volume, increase in number and of the size of the lipid droplets, increase in the activity of lipogenetic enzymes, etc. A key enzyme in the process of synthesis of triglycerides is glycerol-3-phosphate dehydrogenase (G3PDH): its specific activity increases considerably during maturation and can thus be used as a precise and sensitive measurement of adipocyte conversion (Pairault J., Green H., Proc. Nat. Acad. Sci. USA, (1979) 76, 5138-42; Koekemoer T. C. et al, Int. J. Biochem. Cell Biol. (1995) 27, 625-32). It was chosen to follow the evolution of the activity of this enzyme in order to measure the state of differentiation of the adipocytes. Since G3PDH is a hydrosoluble enzyme, its activity is measured in the supernatant of the cell grindings, in the presence of appropriate substrates (NADH, TEA (triethanolamine)—EDTA, 50 mM, 1 mM). The specific activity is calculated from these determinations. The treated cells are compared with the control cells. Since G3PDH is a reflection of the state of differentiation of the cells, the higher its specific activity, the more the cells are differentiated, and vice versa: the more limited the fat reserve will be by the agent tested, more the activity of the G3PDH will be lower. The average over three measurements with respect to a standard deviation gives an average specific activity. Then, the percentage inhibition is calculated of the inhibition of the activity of the G3PDH produced by the substances compared to the controls. The criteria which enable ensuring the quality of good anti-lipogenetic agents are on the one hand a percentage inhibition of the enzyme which is greater than 50%, and on the other hand crude data which are significantly different with respect to the controls. 2. Material and Methods a) Culture and Treatments The adipocytes undergoing differentiation, not very mature adipocytes, also named preadipocytes, obtained at D7 of the protocol given in Example 1 are treated with the medium which is conditioned with mature differentiated adipocytes which are not treated or treated with PB or PS and with the combination PB+PS for 8 days with a change of medium at days D9 and D11, as is indicated in the protocol below. The phytosphingosine was tested at the final concentrations of 0.25, 0.50 and 1 μg/mL. The extract de Plectranthus barbatus (PB) (batch No. 0B2, INDENA) is titrated at 80% of forskolin, a molecule which is recognised for being an effector of adenylate cyclase (Seamon K. et al., P.N.A.S. USA, (1981) 78 3363-67). The PB concentration used in the study is 25 μg/mL from a mother solution at 20 mg/mL in ethanol. b) Preparation of the Cell Extracts The cell plug is washed twice with PBS buffer and the cells are recovered by scratching in a 25 mM TRIS—HCl buffer, pH 7.5, containing 1 mM of EDTA at 4° C. The cells are homogenised by grinding and centrifugation at 10,000 g for 10 minutes at 4° C. The protocol followed is summarised in the Table below. D0 Sowing of the 3T3F442A - cell density 2 × 104 cells/35 mm Petri dish. Culture medium DMEM, 5% FCS/5% CS. D2 Change of medium D4 Change of medium D7 Confluence - culture medium DMEM, 10% FCS, 1% insulin (SM 500 μg/mL) Treatment with conditioned media: PB: 0.25 μg/mL PS: 0.5 and 1 μg/mL D9-D11 Change of medium, same medium + treatment D14 Treatment, same culture medium D16 Collection of the supernatants and G3PDH determination c) Determination of the glycero-3-phosphate Dehydrogenase (G3PDH) Activity. The determination of the G3PDH activity is made according to the method of Kozak and Jensen: Kozak and Jensen, 1974, J. Biol. Chem., 249, 7775-7781. G3PDH catalyses the following reaction The consumption of NADH as a function of time is measured by spectrophotometry (KONTRON) at 340 nm. An absorbance variation/minute (Δ Abs/minute) can thus be calculated which corresponds to the initial rate of the enzymatic reaction. The results are expressed in specific activity (SA), i.e. in nmoles of NADH transformed/min/mg of proteins. The total protein content is evaluated by the BCA method (Protein Assay Reagent-PIERCE LTD) SA = 81.25 × Δ ⁢ ⁢ Abs / min × 1 mg ⁢ ⁢ of ⁢ ⁢ proteins 3. Results Measurement of the glycero-3-phosphate dehydrogenase (G3PDH) activity. The amounts of NAD+ after 8 days as a function of the treatments of the cultures are reported in Table 3 below. TABLE 3 Appreciation of the lipogenesis by measurement of the OD, expressed in nmoles NAD+, for the PB extract and for the phytosphingosine PS PB PS O.D. (nmoles NAD+) (μg/mL) (μg/mL) average Standard deviation 0 (control) 0 (control) 0.0016 0.000195 25 0 0.0004 0.000015 0 0.5 0.0014 0.00009 0 1 0.00165 0.00006 25 1 0.00036 0.00002 25 0.5 0.00043 0.000048 The results of Table 3 above are also represented in FIG. 1. After 8 days' contact with the media which are conditioned with mature adipocytes, a slowing down of the maturation of the peradipocytes with the media containing PB (inhibition of the G3PDH activity) is observed, and this corresponds to an inhibition of the recruitment of the preadipocytes, the activity of which of the maturation marker enzyme is inhibited by 75%. Phytosphingosine does not modify this anti-lipogenetic profile the PS+PB combination causes between 74 and 79% of inhibition of the G3PDH activity, the 1 μg/mL PS+25 μg/mL PB combination even leads to a slowing down of the lipogenesis of these preadipocytes during maturation which is slightly greater than with PB alone. b) Analysis of the Morphology of the Adipocytes In parallel, the morphology of the adipocytes was analysed by direct observation of the cells in the Petri dishes, under reverse phase microscope (Olympus BH2). The cells are considered to be differentiated by morphological analysis when they acquire a round surround and that their cytoplasm is filled with lipid droplets. Inversely, a decrease in the amount of lipid vacuoles which is associated with a more elongated form gives evidence of a slowing down of this maturation. In the presence of the PS+PB combination, the cells are characterised by a very marked delipidation of the adipocytes, which is in agreement with the lowering of the activity of the G3PDH enzyme measured before. FIGS. 2, 3 and 4 show, respectively: FIG. 2: the cells of a control culture at D7. In this culture, the cells are not very differentiated, there are not many lipid vacuoles. This is the start of the treatment. FIG. 3: the cells of a control culture at D21. The cells are loaded with lipid vacuoles. FIG. 4: the cells of a culture treated with the 25 μg/mL PB+1 μg/mL PS combination. c) CONCLUSION This study shows that the treatment with the PB+PS combination of mature adipocytes gives information which is capable of all in all slowing down the accumulation of triglycerides in peradipocytes. The lowering of the activity of the lipogenetic enzyme G3PDH leads to a depletion in significant intracellular lipid droplets. The addition of phytosphingosine capable of stimulating the secretion of leptin did not inhibit the massive action of the PB on the decrease in lipids. The maintenance of leptin in the environment close to the adipocytes could thus exert its role of signal molecule acting against the increase in the adipose mass. One is tempted to believe that a collection of cells containing cells which are emptied of a part of their content of triglycerides by lipolysis in continuing to emit a retrocontrol leptin message should contribute to the reduction of the storage of fat by the panniculus adiposus. Example 3 Demonstration on Human Adipocytes in Culture of the Activity of Phytosphingosine and of the Combination of Phytosphingosine with an Extract of Coleus forskohlii, on the Production of Leptin and on Lipolysis. Human adipocytes originating from a plasty of a 41 year old woman, which are marketed by ZEN-BIO (USA), were used at an advanced stage of the adipocyte maturation. The reception of these cells in culture took place 16 days after sowing. They are cultivated in a specific medium ensuring their differentiation throughout the whole treatment. D-16: sowing D0: start of the treatment with the extract of Coleus (PB) and/or phytosphingosine (PS) D6 to D18: determination of the various parameters. The properties of Coleus described above for the 3T3F442A murine adipocytes were first of all verified on these human cells: lipolytic activity by measurement of the release of glycerol and non-esterified fatty acids. Table 4 below indicates the values of glycerol release in the control cultures and cultures treated with PS. TABLE 4 Release of glycerol, expressed in μg/mL, by human adipocytes in culture, which are non-treated or treated with 25 μg/mL of phytosphingosine, as a function of the duration of the culture glycerol (pg/mL) Days Control (PS = 0 μg/mL) PS = 25 μg/mL 3 73.78 174.4 6 120.8 196.2 9 147.2 302.9 12 198.4 416.4 15 196.3 460.6 18 230.9 659.8 21 276.6 777.1 23 238.9 687 It appears very clearly that the Coleus very strongly stimulates the adipocyte lipolysis (+128% increase in release of glycerol at 18 days with respect to the control). It is further observed, by a measurement of release of non-esterified fatty acids, that the Coleus causes a strong hydrolysis of the adipocyte triglycerides in releasing, in parallel to the glycerol, a large amount of non-esterified fatty acids, at a dose of 25 μg/mL. Other tests show that the phytosphingosine induces an increase of leptin secretion in human adipocytes as in murine adipocytes, the most effective doses being lower for the human adipocyte. In parallel to the leptin release, phytosphingosine, at the dose of 6 ng/mL is responsible for a release of glycerol with time, without concomitant release of non-esterified fatty acids. This observation could correspond to a new form of lipolysis which is proper to leptin, and which is already described in publications. FIGS. 5 and 6 present the evolution of the morphology of the cells under the conditions which have just been set forth. FIG. 5 presents a control culture of human adipocytes at day D18. A significant amount of fat vacuoles is clearly seen. FIG. 6 presents a culture of human adipocytes at day D18, after treatment by the combination of Coleus (25 μg/mL) with phytosphingosine (6 ng/mL). It appears clearly that the phytosphingosine-Coleus combination leads to a massive and visible decrease, with lipid droplets which are less numerous and of smaller size. In parallel, a higher number of cells take up an appearance of not very mature cells (elongated form and absence of lipid vacuoles). Thus, the combination of these two actives leads to a powerful reduction in the fat store, the modulation of leptin in the environment close to the human adipocyte being a key step in this action. Example 4 Slimming hydro/alcoholic formulation. Water qsp 100% Denatured alcohol 42% PPG-3 myristyl ether 10% Perfume 0.20% Phytosphingosine 0.10% Example 5 Slimming fluid emulsion. PPG-2 isoceteth-20 acetate 2% Poloxamer 407 0.50% Propylene glycol isoceteth-3 acetate 15% Pentacyclomethicone 15% Water qsp.100% Butylene glycol 3% Preservatives q.s. Extract of Coleus forskohlii (at 80% of forskolin) 0.1% Xanthan gum 0.05% Acrylates/c10-30 alkyl acrylate cross-polymer 0.04% Neutraliser q.s. Polyacrylamide c13-14 isoparaffin laureth-7 0.50% Perfume 0.20% Phytosphingosine 0.05% Example 6 Slimming cream. Steareth-2 0.50% Steareth-21 1.75% Cetyl alcohol 0.30% Stearyl alcohol 0.30% Stearic acid 0.50% 2-ethylhexyl stearate 4.00% Cetearyl isononanoate 3.00% Squalane 4.00% IBMX 1.00% Dimethicone 0.40% Water qsp.100.00% Glycerine 2.00% Butylene glycol 3.00% Preservatives q.s. Acrylates/c10-30 alkyl acrylate cross-polymer 0.35% Xanthan gum 0.10% Sodium hyaluronate 0.02% Neutraliser q.s. Polyacrylamide c13-14 isoparaffin laureth 7 0.50% Denatured alcohol 5.00% Perfume 0.20% Phytosphingosine 0.002%

20040901

20100615

20050519

97432.0

CARTER, KENDRA D

COSMETIC USE OF PHYTOSPHINGOSINE AS SLIMMING AGENT AND COSMETIC COMPOSITIONS COMPRISING PHYTOSPHINGOSINE

UNDISCOUNTED

ACCEPTED

ACCEPTED

Heterocycle-bearing onium salts

The present invention relates to a heterocycle-containing onium salt useful as, for example, a cationic photopolymerization initiator and an acid generator for a chemically amplified resist, and provides “a heterocycle-containing onium salt shown by the general formula [1]: [wherein R is a group shown by the general formula [2]: (wherein R3 and R4 are each independently a halogen atom, an alkyl group which may have a halogen atom or an aryl group as a substituent, or an aryl group which may have a halogen atom or a lower alkyl group as a substituent; X2 is an oxygen atom or a sulfur atom; i is an integer of 0 to 4; and j is an integer of 0 to 3), or a group shown by the general formula [3]: (wherein R5 and R6 are each independently a halogen atom, an alkyl group which may have a halogen atom or an aryl group as a substituent, or an aryl group which may have a halogen atom or a lower alkyl group as a substituent; X3 and X4 are each independently an oxygen atom or a sulfur atom; p is an integer of 0 to 2; and q is an integer of 0 to 3); R1 and R2 are each independently a halogen atom, an alkyl group which may have a halogen atom or an aryl group as a substituent, or an aryl group which may have a halogen atom or a lower alkyl group as a substituent; m and n are each independently an integer of 0 to 5; and A is a halogen atom or an anion derived from an inorganic strong acid, an organic acid or a compound shown by the general formula [4]: HM1(R7)4 [4] (wherein M1 is a boron atom or a gallium atom; and R7 is an aryl group which may have a substituent selected from a lower haloalkyl group, a halogen atom, a nitro group and a cyano group)]” or “a heterocycle-containing onium salt shown by the general formula [35]: [wherein R26 and R27 are each independently an aryl group which may have a halogen atom or a lower alkyl group as a substituent, a group shown by the above-mentioned general formula [2], or a group shown by the above-mentioned general formula [3]; and A3 is a halogen atom or an anion derived from an inorganic strong acid, an organic acid or a compound shown by the general formula [4]; and provided that at least one of R26 and R27 is a group shown by the above-mentioned general formula [2] or [3], and when only one of R26 and R27 is a group shown by the above-mentioned general formula [2] or [3], A3 is an anion derived from an inorganic strong acid shown by the general formula [36]; HM3F6 [36] (wherein M3 is a phosphorus atom, an arsenic atom or an antimony atom), an organic acid or a compound shown by the general formula [4]]”.

1. A heterocycle-containing onium salt shown by the general formula [1] or [35]: [wherein R is a group shown by the general formula [2]: (wherein R3 and R4 are each independently a halogen atom, an alkyl group which may have a halogen atom or an aryl group as a substituent, or an aryl group which may have a halogen atom or an alkyl group having 1 to 6 carbon atoms as a substituent; X2 is an oxygen atom or a sulfur atom; i is an integer of 0 to 4; and j is an integer of 0 to 3), or a group shown by the general formula [3]: (wherein R5 and R6 are each independently a halogen atom, an alkyl group which may have a halogen atom or an aryl group as a substituent, or an aryl group which may have a halogen atom or an alkyl group having 1 to 6 carbon atoms as a substituent; X3 and X4 are each independently an oxygen atom or a sulfur atom; p is an integer of 0 to 2; and q is an integer of 0 to 3); R1 and R2 are each independently a halogen atom, an alkyl group which may have a halogen atom or an aryl group as a substituent, or an aryl group which may have a halogen atom or an alkyl group having 1 to 6 carbon atoms as a substituent; m and n are each independently an integer of 0 to 5; and A is a halogen atom or an anion derived from an inorganic strong acid, an organic acid or a compound shown by the general formula [4]: HM1(R7)4 [4] (wherein M1 is a boron atom or a gallium atom; and R7 is an aryl group which may have a substituent selected from a haloalkyl group having 1 to 6 carbon atoms, a halogen atom, a nitro group and a cyano group)], R26—I⊕—R27A3 [35] [wherein R26 and R27 are each independently an aryl group which may have a halogen atom or an alkyl group having 1 to 6 carbon atoms as a substituent, a group shown by the above-mentioned general formula [2], or a group shown by the above-mentioned general formula [3]; A3 is a halogen atom or an anion derived from an inorganic strong acid, an organic acid or a compound shown by the general formula [4]; and provided that at least one of R26 and R27 is a group shown by the above-mentioned general formula [2] or [3], and when only one of R26 and R27 is a group shown by the above-mentioned general formula [2] or [3], A3 is an anion derived from an inorganic strong acid shown by the general formula [36]; HM3F6 [36] (wherein M3 is a phosphorus atom, an arsenic atom or an antimony atom), an organic acid or a compound shown by the general formula [4]]. 2. An onium salt according to claim 1, wherein the heterocycle-containing onium salt is one shown by the general formula [1]: [wherein R is a group shown by the general formula [2]: (wherein R and R4 are each independently a halogen atom, an alkyl group which may have a halogen atom or an aryl group as a substituent, or an aryl group which may have a halogen atom or an alkyl group having 1 to 6 carbon atoms as a substituent; X2 is an oxygen atom or a sulfur atom; i is an integer of 0 to 4; and j is an integer of 0 to 3), or a group shown by the general formula [3]: (wherein R and R6 are each independently a halogen atom, an alkyl group which may have a halogen atom or an aryl group as a substituent, or an aryl group which may have a halogen atom or an alkyl group having 1 to 6 carbon atoms as a substituent; X3 and X4 are each independently an oxygen atom or a sulfur atom; p is an integer of 0 to 2; and q is an integer of 0 to 3); R1 and R2 are each independently a halogen atom, an alkyl group which may have a halogen atom or an aryl group as a substituent, or an aryl group which may have a halogen atom or an alkyl group having 1 to 6 carbon atoms as a substituent; m and n are each independently an integer of 0 to 5; and A is a halogen atom or an anion derived from an inorganic strong acid, an organic acid or a compound shown by the general formula [4]: HM1(R7)4 [4] (wherein M1 is a boron atom or a gallium atom; and R7 is an aryl group which may have a substituent selected from a haloalkyl group having 1 to 6 carbon atoms, a halogen atom, a nitro group and a cyano group)]. 3. An onium salt according to claim 1, wherein the heterocycle-containing onium salt is one shown by the general formula [35]: R26—I⊕—R27A3 [35] [wherein R26 and R27 are each independently an aryl group which may have a halogen atom or an alkyl group having 1 to 6 carbon atoms as a substituent, a group shown by the general formula [2]; (wherein R3 and R4 are each independently a halogen atom, an alkyl group which may have a halogen atom or an aryl group as a substituent, or an aryl group which may have a halogen atom or an alkyl group having 1 to 6 carbon atoms as a substituent; X2 is an oxygen atom or a sulfur atom; i is an integer of 0 to 4; and j is an integer of 0 to 3), or a group shown by the general formula [3]: (wherein R5 and R6 are each independently a halogen atom, an alkyl group which may have a halogen atom or an aryl group as a substituent, or an aryl group which may have a halogen atom or an alkyl group having 1 to 6 carbon atoms as a substituent; X3 and X4 are each independently an oxygen atom or a sulfur atom; p is an integer of 0 to 2; and q is an integer of 0 to 3); A3 is a halogen atom, or an anion derived from an inorganic strong acid, an organic acid or a compound shown by the general formula [4]: HM1(R7)4 [4] (wherein M1 is a boron atom or a gallium atom; and R7 is an aryl group which may have a substituent selected from a haloalkyl group having 1 to 6 carbon atoms, a halogen atom, a nitro group and a cyano group); and provided that at least one of R26 and R27 is a group shown by the above-mentioned general formula [2] or [3], and when only one of R26 and R27 is a group shown by the above-mentioned general formula [2] or [3], A3 is an anion derived from an inorganic strong acid shown by the general formula [36]: HM3F6 [36] (wherein M3 is a phosphorous atom, an arsenic atom or an antimony atom), an organic acid, or a compound shown by the general formula [4])]. 4. A salt according to claim 2, wherein the anion derived from an inorganic strong acid, shown by A is one derived from nitric acid, sulfuric acid, halosulfuric acid, perhalogenic acid or a compound shown by the general formula [5]: HM2Fk [5] (wherein M2 is a metalloid atom or a metal atom; and k is an integer of 4 or 6). 5. A salt according to claim 4, wherein the metalloid atom shown by M2 is a boron atom, a silicon atom, a phosphorus atom, an arsenic atom or an antimony atom; and the metal atom shown by M2 is an aluminum atom, a titanium atom, an iron atom, a nickel atom, a zirconium atom or a gallium atom. 6. A salt according to claim 2, wherein the anion derived from the organic acid shown by A is one derived from a sulfonic acid shown by the general formula [6]: R8—SO3H [6] (wherein R8 is an alkyl group, an aryl group or an aralkyl group, which may have a halogen atom), or a carboxylic acid shown by the general formula [7]: R9—COOH [7] (wherein R9 is an alkyl group, an aryl group or an aralkyl group, which may have a halogen atom). 7. A salt according to claim 2, wherein R is a group shown by the general formula [2]. 8. A salt according to claim 7, wherein X2 in the general formula [2] is an oxygen atom. 9. A salt according to claim 7, wherein the group shown by the general formula [2] is a xanthonyl group. 10. A salt according to claim 2, wherein R is a group shown by the general formula [3]. 11. A salt according to claim 10, wherein each X3 and X4 in the general formula [3] is an oxygen atom. 12. A salt according to claim 10, wherein the group shown by the general formula [3] is a coumarinyl group. 13. A salt according to claim 2, wherein the sulfonium salt shown by the general formula [1] is diphenyl(xanthene-9-one-2-yl)sulfonium hexafluorophosphate or (coumarin-7-yl)diphenylsulfonium hexafluorophosphate. 14. A salt according to claim 3, wherein the anion derived from the inorganic strong acid shown by A3 is one derived from nitric acid, sulfuric acid, halosulfuric acid, perhalogenic acid or an inorganic strong acid shown by the general formula [5]: HM2Fk [5] (wherein M2 is a metalloid atom or a metal atom; and k is an integer of 4 or 6). 15. A salt according to claim 14, wherein the metalloid atom shown by M2 is a boron atom, a silicon atom, a phosphorus atom, an arsenic atom or an antimony atom; and the metal atom shown by M2 is an aluminum atom, a titanium atom, an iron atom, a nickel atom, a zirconium atom or a gallium atom. 16. A salt according to claim 3, wherein the anion derived from the organic acid shown by A3 is one derived from a sulfonic acid shown by the general formula [6]: R8—SO3H [6] (wherein R8 is an alkyl group, an aryl group or an aralkyl group, which may have a halogen atom), or a carboxylic acid shown by the general formula [7]: R9—COOH [7] (wherein R9 is an alkyl group, an aryl group or an aralkyl group, which may have a halogen atom). 17. A salt according to claim 3, wherein each R26 and R27 is a group shown by the general formula [2]. 18. A salt according to claim 17, wherein X2 in the general formula [2] is an oxygen atom. 19. A salt according to claim 17, wherein the group shown by the general formula [2] is a xanthonyl group. 20. A salt according to claim 3, wherein each R26 and R27 is a group shown by the general formula [3]. 21. A salt according to claim 20, wherein each X3 and X4 in the general formula [3] is an oxygen atom. 22. A salt according to claim 20, wherein the group shown by the general formula [3] is a coumarinyl group. 23. A salt according to claim 3, wherein the iodonium salt shown by the general formula [35] is bis(xanthene-9-one-2-yl)iodonium hexafluorophosphate or bis(coumarin-7-yl)iodonium hexafluorophosphate. 24. A cationic photopolymerization initiator comprising a heterocycle-containing onium salt shown by the general formula [8]: [wherein R is a group shown by the general formula [2]: (wherein R3 and R4 are each independently a halogen atom, an alkyl group which may have a halogen atom or an aryl group as a substituent, or an aryl group which may have a halogen atom or an alkyl group having 1 to 6 carbon atoms as a substituent; X2 is an oxygen atom or a sulfur atom; i is an integer of 0 to 4; and j is an integer of 0 to 3), or a group shown by the general formula [3]: (wherein R5 and R6 are each independently a halogen atom, an alkyl group which may have a halogen atom or an aryl group as a substituent, or an aryl group which may have a halogen atom or an alkyl group having 1 to 6 carbon atoms as a substituent; X3 and X4 are each independently an oxygen atom or a sulfur atom; p is an integer of 0 to 2; and q is an integer of 0 to 3); R1 and R2 are each independently a halogen atom, an alkyl group which may have a halogen atom or an aryl group as a substituent, or an aryl group which may have a halogen atom or an alkyl group having 1 to 6 carbon atoms as a substituent; m and n are each independently an integer of 0 to 5; and A1 is an anion derived from an inorganic strong acid, a sulfonic acid or a compound shown by the general formula [4]: HM1(R7)4 [4] (wherein M1 is a boron atom or a gallium atom; R7 is an aryl group which may have a substituent selected from a haloalkyl group having 1 to 6 carbon atoms, a halogen atom, a nitro group and a cyano group)]. 25. A polymerization initiator according to claim 24, wherein A1 is an anion derived from the compound shown by the general formula [4] or an inorganic strong acid shown by the general formula [5]: HM2Fk [5] (wherein M2 is a metalloid atom or a metal atom; and k is an integer of 4 or 6). 26. A polymerization initiator according to claim 24, wherein the sulfonium salt shown by the general formula [8] is diphenyl(xanthene-9-one-2-yl)sulfonium hexafluorophosphate or (coumarin-7-yl)diphenylsulfonium hexafluorophosphate. 27. A cationic photopolymerization initiator comprising a heterocycle-containing iodonium salt shown by the general formula [37]: R26—I⊕—R27A4 [37] [wherein R26 and R27 are each independently an aryl group which may have a halogen atom or an alkyl group having 1 to 6 carbon atoms as a substituent, a group shown by the general formula [2]: (wherein R3 and R4 are each independently a halogen atom, an alkyl group which may have a halogen atom or an aryl group as a substituent, or an aryl group which may have a halogen atom or an alkyl group having 1 to 6 carbon atoms as a substituent; X2 is an oxygen atom or a sulfur atom; i is an integer of 0 to 4; and j is an integer of 0 to 3), or a group shown by the general formula [3]: (wherein R5 and R6 are each independently a halogen atom, an alkyl group which may have a halogen atom or an aryl group as a substituent, or an aryl group which may have a halogen atom or an alkyl group having 1 to 6 carbon atoms as a substituent; X3 and X4 are each independently an oxygen atom or a sulfur atom; p is an integer of 0 to 2; and q is an integer of 0 to 3); and A4 is an anion derived from an inorganic strong acid, a sulfonic acid or a compound shown by the general formula [4]: HM1(R7)4 [4] (wherein M1 is a boron atom or a gallium atom; R7 is an aryl group which may have a substituent selected from a haloalkyl group having 1 to 6 carbon atoms, a halogen atom, a nitro group and a cyano group); and provided that at least one of R26 and R27 is a group shown by the above-mentioned general formula [2] or [3], and when only one of R26 and R27 is a group shown by the above-mentioned general formula [2] or [3], an inorganic strong acid is one shown by the general formula [36]: HM3F6 [36] (wherein M3 is a phosphorus atom, an arsenic atom or an antimony atom)]. 28. A polymerization initiator according to claim 27, wherein A4 is an anion derived from the compound shown by the general formula [4] or an inorganic strong acid shown by the general formula [5]: HM2Fk [5] (wherein M2 is a metalloid atom or a metal atom; and k is an integer of 4 or 6). 29. A polymerization initiator according to claim 27, wherein the iodonium salt shown by the general formula [37] is bis(xanthene-9-one-2-yl)iodonium hexafluorophosphate or bis(coumarin-7-yl)iodonium hexafluorophosphate. 30. A method for polymerization of an epoxy monomer, which comprises using the polymerization initiator in claim 24. 31. A method for polymerization of a vinyl ether monomer, which comprises using the polymerization initiator in claim 24. 32. A method for polymerization of an epoxy monomer, which comprisesd using the polymerization initiator in claim 27. 33. A method for polymerization of a vinyl ether monomer, which comprises using the polymerization initiator in claim 27. 34. An acid generator for a resist, comprising a sulfonium salt shown by the general formula [9]: [wherein R is a group shown by the general formula [2]: (wherein R and R4 are each independently a halogen atom, an alkyl group which may have a halogen atom or an aryl group as a substituent, or an aryl group which may have a halogen atom or an alkyl group having 1 to 6 carbon atoms as a substituent; X2 is an oxygen atom or a sulfur atom; i is an integer of 0 to 4; and j is an integer of 0 to 3), or a group shown by the general formula [3]: (wherein R5 and R6 are each independently a halogen atom, an alkyl group which may have a halogen atom or an aryl group as a substituent, or an aryl group which may have a halogen atom or an alkyl group having 1 to 6 carbon atoms as a substituent; X3 and X4 are each independently an oxygen atom or a sulfur atom; p is an integer of 0 to 2; and q is an integer of 0 to 3); R1 and R2 are each independently a halogen atom, an alkyl group which may have a halogen atom or an aryl group as a substituent, or an aryl group which may have a halogen atom or an alkyl group having 1 to 6 carbon atoms as a substituent; m and n are each independently an integer of 0 to 5; and A2 is an anion derived from an inorganic strong acid, an organic acid or a compound shown by the general formula [4]: HM1(R7)4 [4] (wherein M1 is a boron atom or a gallium atom; and R7 is an aryl group which may have a substituent selected from a haloalkyl group having 1 to 6 carbon atoms, a halogen atom, a nitro group and a cyano group)]. 35. An acid generator according to claim 34, wherein the sulfonium salt shown by the general formula [9] is diphenyl(xanthene-9-one-2-yl)sulfonium hexafluorophosphate or (coumarin-7-yl)diphenylsulfonium hexafluorophosphate. 36. An acid generator for a resist, comprising an iodonium salt shown by the general formula [38]: R26—I⊕—R27A5 [38] [wherein R26 and R27 are each independently an aryl group which may have a halogen atom or an alkyl group having 1 to 6 carbon atoms as a substituent, a group shown by the general formula [2]: (wherein R3 and R4 are each independently a halogen atom, an alkyl group which may have a halogen atom or an aryl group as a substituent, or an aryl group which may have a halogen atom or an alkyl group having 1 to 6 carbon atoms as a substituent; X2 is an oxygen atom or a sulfur atom; i is an integer of 0 to 4; and j is an integer of 0 to 3), or a group shown by the general formula [3]: (wherein R5 and R6 are each independently a halogen atom, an alkyl group which may have a halogen atom or an aryl group as a substituent, or an aryl group which may have a halogen atom or an alkyl group having 1 to 6 carbon atoms as a substituent; X3 and X4 are each independently an oxygen atom or a sulfur atom; p is an integer of 0 to 2; and q is an integer of 0 to 3); and A5 is an anion derived from an inorganic strong acid, an organic acid or a compound shown by the general formula [4]: HM1(R7)4 [4] (wherein M1 is a boron atom or a gallium atom; and R is an aryl group which may have a substituent selected from a haloalkyl group having 1 to 6 carbon atoms, a halogen atom, a nitro group and a cyano group); and provided that at least one of R26 and R27 is a group shown by the above-mentioned general formula [2] or [3], and when only one of R26 and R27 is a group shown by the above-mentioned general formula [2] or [3], an inorganic strong acid is one shown by the general formula [36]: HM3F6 [36] (wherein M3 is a phosphorus atom, an arsenic atom or an antimony atom)]. 37. An acid generator according to claim 36, wherein the iodonium salt shown by the general formula [38] is bis(xanthene-9-one-2-yl)iodonium hexafluorophosphate or bis(coumarin-7-yl)iodonium hexafluorophosphate.

TECHNICAL FIELD The present invention relates to a heterocycle-containing onium salt useful as, for example, a cationic photopolymerization initiator and an acid generator for a chemically amplified resist. BACKGROUND OF THE INVENTION Recently, in the field of photopolymerization, a research on a cationic polymerization, instead of a radical polymerization, has been promoted to make polymerization easy even in the air without the effect of oxygen. A cationic polymerization mainly uses as light source a high pressure mercury lamp or a metal halide lamp, including, for example, g-line (436 nm) and i-line (365 nm), and is widely known as a polymerization method for such as an epoxy compound and a vinyl ether compound, rather than a vinyl monomer. As a cationic photopolymerization initiator, for example, sulfonium salt such as triarylsulfonium hexafluoroantimonate (see U.S. Pat. No. 4,058,401) and a 4-(phenylthio)phenyldiphenylsulfonium salt compound (see U.S. Pat. No. 4,173,476), and an iodonium salt such as diphenyliodonium hexafluorophosphate and diphenyliodonium hexafluoroantimonate (see JP-A-50-151996, JP-A-60-47029, etc.) have been known. These compounds, however, have such problems of difficulty in preparing a polymer with high hardness when the said compounds are used as a cationic polymerization initiators, because use of a high pressure mercury lamp or a metal halide lamp as light source causes low acid generation efficiency. Further, these sulfonium salts and onium salts are known to significantly reduce photocuring, when an inorganic strong acid such as hexafluorophosphate (PF6−) is used as a counter anion, compared with hexafluoroantimonate (SbF6−). However, use of SbF6− may be inhibited in the future due to having strong toxicity. Furthermore, Polish J. Chem., 71, p. 1236-1245 (1997) discloses 2-(phenyliodonio)xanthene-9-one tetrafluoroborate (BF4—) having a xanthonyl group at the cation moiety of the iodonium salt, and a synthesis example thereof. However, there is no disclosure that this compound can be used as a cationic polymerization initiator or not, and use of said compound as a cationic polymerization initiator could not obtain a polymer with sufficient hardness. On the other hand, a high pressure mercury lamp or a metal halide lamp is widely used as exposure light source for such as a semiconductor resist, a liquid crystal resist, a solder resist for circuit board, PS (Pre-sensitized) plate and CTP (Computer To Plate) plate, and a sulfonium salt and an iodonium salt are also used as an acid generator for those applications. However, these compounds have such problems that a resist with sufficiently high sensitivity cannot be provided due to low acid generation efficiency, when such as a high pressure mercury lamp or a metal halide lamp is used as light source. Therefore, sulfonium salts with thioxanthone structure have been developed to provide high acid generation efficiency (see, for example, JP-A-8-165290, JP-A-9-12614, JP-A-9-12615, JP-A-10-60098, JP-A-10-67812, JP-A-10-101718, JP-A-10-120766, JP-A-10-130363, JP-A-10-152554, JP-A-10-168160, JP-A-10-182634, JP-A-10-182711, JP-A-10-279616, JP-A-11-269169 and JP-A-11-322944). However, because these sulfonium salts have absorption in the visible light region not shorter than 400 nm, and therefore show yellowish color. Thus use of these sulfonium salts as a polymerization initiator has such drawbacks that an obtained polymer has color under the influence of hue of said polymerization initiator itself, and therefore use of the said polymerization initiator as coating agents, adhesives or paints causes an obtained polymer with poor transparency and with hue which is different from desired hue. Under the circumstance, development of an onium salt, providing sufficient hardening function even though PF6− is used as a counter anion, and providing little effect on transparency of an obtained polymer, is required by research on a cation moiety with new structure providing high acid generation efficiency, even when such as a high pressure mercury lamp or a metal halide lamp is used as light source. SUMMARY OF THE INVENTION The present invention has been completed for the purpose of solving the above-mentioned problems and provides the following: (1) A heterocycle-containing sulfonium salt shown by the general formula [1]: [wherein R is a group shown by the general formula [2]: (wherein R3 and R4 are each independently a halogen atom, an alkyl group which may have a halogen atom or an aryl group as a substituent, or an aryl group which may have a halogen atom or a lower alkyl group as a substituent; X2 is an oxygen atom or a sulfur atom; i is an integer of 0 to 4; and j is an integer of 0 to 3) or a group shown by the general formula [3]: (wherein R5 and R6 are each independently a halogen atom, an alkyl group which may have a halogen atom or an aryl group as a substituent, or an aryl group which may have a halogen atom or a lower alkyl group as a substituent; X3 and X4 are each independently an oxygen atom or a sulfur atom; p is an integer of 0 to 2; and q is an integer of 0 to 3); R1 and R2 are each independently a halogen atom, an alkyl group which may have a halogen atom or an aryl group as a substituent, or an aryl group which may have a halogen atom or a lower alkyl group as a substituent; m and n are each independently an integer of 0 to 5; and A is a halogen atom or an anion derived from an inorganic strong acid, an organic acid or a compound shown by the general formula [4]: HM1(R7)4 [4] (wherein M1 is a boron atom or a gallium atom; and R7 is an aryl group which may have a substituent selected from a lower haloalkyl group, a halogen atom, a nitro group and a cyano group)], (2) An iodonium salt shown by the general formula [35]: [wherein R26 and R27 are each independently an aryl group which may have a halogen atom or a lower alkyl group as a substituent, a group shown by the above-mentioned general formula [2] or a group shown by the above-mentioned general formula [3]; A3 is a halogen atom or an anion derived from an inorganic strong acid, an organic acid or a compound shown by the general formula [4]; and provided that at least one of R26 and R27 is a group shown by the above-mentioned general formula [2] or [3] and when only one of R26 and R27 is a group shown by the above-mentioned general formula [2] or [3], A3 is an anion derived from an inorganic strong acid shown by the general formula [36]; HM3F6 [36] (wherein M3 is a phosphorus atom, an arsenic atom or an antimony atom), an organic acid or a compound shown by the general formula [4]], (3) A cationic photopolymerization initiator, comprising a sulfonium salt shown by the general formula [8]: (wherein A1 is an anion derived from an inorganic strong acid, a sulfonic acid or a compound shown by the general formula [41; and R, R1, R2, m and n have the same meaning as above), (4) A cationic photopolymerization initiator, comprising an iodonium salt shown by the general formula [37]: (wherein A4 is an anion derived from an inorganic strong acid, a sulfonic acid or a compound shown by the general formula [4]; R26 and R27 have the same meaning as above; and provided that at least one of R26 and R27 is a group shown by the above-mentioned general formula [2] or [3] and when only one of R26 and R27 is a group shown by the above-mentioned general formula [2] or [3], an inorganic strong acid is one shown by the general formula [36]), (5) A method for polymerization of an epoxy monomer, which comprises using the polymerization initiator in the above-mentioned (3) and (4), (6) A method for polymerization of a vinyl ether monomer, which comprises using the polymerization initiator in the above-mentioned (3) and (4), (7) An acid generator for a resist, comprising a sulfonium salt shown by the general formula [9]: (wherein A2 is an anion derived from an inorganic strong acid, an organic acid or a compound shown by the general formula [4]; and R, R1, R2, m and n have the same meaning as above), and (8) An acid generator for a resist, comprising an iodonium salt shown by the general formula [38]: (wherein A5 is an anion derived from an inorganic strong acid, an organic acid or a compound shown by the general formula [4]; R26 and R27 have the same meaning as above; and provided that at least one of R26 and R27 is a group shown by the above-mentioned general formula [2] or [3] and when only one of R26 and R27 is a group shown by the above-mentioned general formula [2] or [3], an inorganic strong acid is one shown by the general formula [36]). The present inventors have conducted extensive study in order to realize the above-mentioned object and to arrive at the finding that a heterocycle-containing onium salt shown by the above-mentioned general formulae [1], [8], [9], [35], [37] and [38] has superior acid generation efficiency in wavelength region of a high pressure mercury lamp and a metal halide lamp, and good transparency in the visible light region (not shorter than 400 nm) (that is, little absorption in the visible light region), and thus they can be used as cationic photopolymerization initiators or acid generators not having the above-mentioned problems, or synthesis raw materials thereof, and finally the present invention has been completed on the basis of these findings. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 shows UV-visible ray absorption spectra curves data on Examples 1 to 4. Each curve code corresponds to result of each Example as follows: curve to Example 1 curve to Example 2 curve to Example 3 curve to Example 4 FIG. 2 shows UV-visible ray absorption spectra curves data on Comparative Examples 1 to 5 and Reference Example 1. Each curve code corresponds to result of each Example as follows: curve to Comparative Example 1 curve to Comparative Example 2 curve to Comparative Example 3 curve to Comparative Example 4 curve to Comparative Example 5 curve to Reference Example 1 FIG. 3 shows UV-visible ray absorption spectra curves data on Examples 5 to 8, Comparative Example 6 and Reference Example 2. Each curve code corresponds to result of each Example as follows: curve to Example 5 curve to Example 6 curve to Example 7 curve to Example 8 curve to Comparative Example 6 curve to Reference Example 2 FIG. 4 shows UV-visible ray absorption spectra curves data on Examples 4 to 6 and 8 and Comparative Examples 2 and 3. Each curve code corresponds to result of each Example as follows: curve to Example 4 curve to Example 5 curve to Example 6 curve to Example 8 ••+•• curve to Comparative Example 2 ••Δ•• curve to Comparative Example 3 BEST MODE FOR CARRYING OUT OF THE INVENTION In the general formulae [1] to [3], [8] and [9], the halogen atom shown by R1 to R6 includes, for example, a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, and among others, a chlorine atom is preferable. The alkyl group of an alkyl group which may have a halogen atom or an aryl group as a substituent, shown by R1 to R6, may be straight chained, branched or cyclic, and includes one having generally 1 to 18, preferably 1 to 12 and more preferably 1 to 4 carbon atoms, which is specifically exemplified by, for example, a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a n-pentyl group, an isopentyl group, a sec-pentyl group, a tert-pentyl group, a neopentyl group, a n-hexyl group, an isohexyl group, a sec-hexyl group, a tert-hexyl group, a neohexyl group, a n-heptyl group, an isoheptyl group, a sec-heptyl group, a tert-heptyl group, a neoheptyl group, a n-octyl group, an isooctyl group, a sec-octyl group, a tert-octyl group, a neooctyl group, a n-nonyl group, an isononyl group, a sec-nonyl group, a tert-nonyl group, a neononyl group, a n-decyl group, an isodecyl group, a sec-decyl group, a tert-decyl group, a neodecyl group, a n-undecyl group, an isoundecyl group, a sec-undecyl group, a tert-undecyl group, a neoundecyl group, a n-dodecyl group, an isododecyl group, a sec-dodecyl group, a tert-dodecyl group, a neododecyl group, a n-tridecyl group, an isotridecyl group, a sec-tridecyl group, a tert-tridecyl group, a neotridecyl group, a n-tetradecyl group, an isotetradecyl group, a sec-tetradecyl group, a tert-tetradecyl group, a neotetradecyl group, a n-pentadecyl group, an isopentadecyl group, a sec-pentadecyl group, a tert-pentadecyl group, a neopentadecyl group, a n-hexadecyl group, an isohexadecyl group, a sec-hexadecyl group, a tert-hexadecyl group, a neohexadecyl group, a n-heptadecyl group, an isoheptadecyl group, a sec-heptadecyl group, a tert-heptadecyl group, a neoheptadecyl group, a n-octadecyl group, an isooctadecyl group, a sec-octadecyl group, a tert-octadecyl group, a neooctadecyl group, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, a cyclooctyl group, a cyclononyl group, a cyclodecyl group, a cycloundecyl group, a cyclododecyl group, a cyclotridecyl group, a cyclotetradecyl group, a cyclopentadecyl group, a cyclohexadecyl group, a cycloheptadecyl group and a cyclooctadecyl group, and among others, a preferable one includes, for example, a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group and a tert-butyl group, and a more preferable one includes, for example, a methyl group and an ethyl group. The halogen atom as the substituent of the above-mentioned alkyl group includes, for example, a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, and among others, a chlorine atom is preferable. The aryl group as the substituent of the above-mentioned alkyl group includes one having generally 6 to 16, preferably 6 to 14 carbon atoms, which is specifically exemplified by, for example, a phenyl group, a naphthyl group, an anthryl group, a phenanthrenyl group and a pyrenyl group, and among others, for example, a phenyl group, a naphthyl group, an anthryl group and a phenanthrenyl group are preferable. In the general formulae [1] to [3], [8], [9], [35], [37] and [38], the aryl group of the aryl group which may have a halogen atom or a lower alkyl group as a substituent, shown by R1 to R6, R26 and R27 includes one having generally 6 to 16, preferably 6 to 14 carbon atoms, which is specifically exemplified by, for example, a phenyl group, a naphthyl group, an anthryl group, a phenanthrenyl group and a pyrenyl group, and among others, for example, a phenyl group, a naphthyl group, an anthryl group and a phenanthrenyl group are preferable. The halogen atom as the substituent of the above-mentioned aryl group includes, for example, a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, and among others, a chlorine atom is preferable. The lower alkyl group as the substituent of the above-mentioned aryl group may be straight chained, branched or cyclic, and includes one having generally 1 to 6, preferably 1 to 4 carbon atoms, which is specifically exemplified by the same as examples of the alkyl group having 1 to 6 carbon atoms among the alkyl groups which may have a halogen atom or an aryl group as a substituent, shown by the above-mentioned R1 to R6, and among others, a preferable one includes, for example, a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group and a tert-butyl group, a more preferable one includes a methyl group and an ethyl group. In the general formulae [2] and [3], X2 to X4 are each independently an oxygen atom and a sulfur atom, and among them, an oxygen atom is preferable. In the general formulae [1], [8] and [9], m and n are each independently an integer of generally 0 to 5, preferably 0 to 2. In the general formula [2], i is an integer of generally 0 to 4, preferably 0 to 2 and j is an integer of generally 0 to 3, preferably 0 to 2. In the general formula [3], p is an integer of generally 0 to 2, preferably 0 to 1 and q is an integer of generally 0 to 3, preferably 0 to 2. In the general formula [4], the aryl group of the aryl group which may have a substituent selected from a lower haloalkyl group, a halogen atom, a nitro group and a cyano group, shown by R7 includes one having generally 6 to 16, preferably 6 to 14 carbon atoms, which is specifically exemplified by, for example, a phenyl group, a naphthyl group, an anthryl group, a phenanthrenyl group and a pyrenyl group, and among others, a phenyl group is preferable. The lower haloalkyl group as the substituent of the aryl group shown by the above-mentioned R7 may be straight chained, branched or cyclic, and includes one, wherein a part of or all of hydrogen atoms of the lower haloalkyl group having generally 1 to 6, preferably 1 to 4 carbon atoms are substituted by a halogen atom (e.g. a fluorine atom, a chlorine atom, a bromine atom and an iodine atom), which is specifically exemplified by, for example, a fluoromethyl group, a chloromethyl group, a bromomethyl group, an iodomethyl group, a difluoromethyl group, a dichloromethyl group, a dibromomethyl group, a diiodomethyl group, a trifluoromethyl group, a trichloromethyl group, a tribromomethyl group, a triiodomethyl group, a trifluoroethyl group, a trichloroethyl group, a tribromoethyl group, a triiodoethyl group, a pentafluoroethyl group, a pentachloroethyl group, a pentabromoethyl group, a pentaiodoethyl group, a heptafluoropropyl group, a heptachloropropyl group, a heptabromopropyl group, a heptaiodopropyl group, a nonafluorobutyl group, a nonachlorobutyl group, a nonabromobutyl group, a nonaiodobutyl group, a perfluoropentyl group, a perchloropentyl group, a perbromopentyl group, a periodopentyl group, a perfluorohexyl group, a perchlorohexyl group, a perbromohexyl group, a periodohexyl group, a trifluorocyclobutyl group, a trichlorocyclobutyl group, a tribromocyclobutyl group, a triiodocyclobutyl group, a tetrafluorocyclopentyl group, a tetrachlorocyclopentyl group, a tetrabromocyclopentyl group, a tetraiodocyclopentyl group, a pentafluorocyclohexyl group, a pentachlorocyclohexyl group, a pentabromocyclohexyl group and a pentaiodocyclohexyl group, and among others, a preferable one includes, for example, a trifluoromethyl group, a trichloromethyl group, a tribromomethyl group and a triiodomethyl group, and a more preferable one includes a trifluoromethyl group. The halogen atom as the substituent of the aryl group shown by the above-mentioned R7 includes, for example, a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, and among others, a fluorine atom is preferable. In the general formulae [1] and [35], the halogen atom shown by A and A3 includes, for example, a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, and among others, a chlorine atom and a bromine atom are preferable. In the general formulae (1], [8], [9], [35], [37] and [38], the anion derived from the inorganic strong acid shown by A and A1 to A5 includes one derived from inorganic strong acids such as nitric acid, sulfuric acid, halosulfuric acid, perhalogenic acid and one shown by the general formula [5]: HM2Fk [5] (wherein M2 is a metalloid atom or a metal atom; and k is an integer of 4 or 6). In the general formulae [35], [37] and [38], when only one of R26 and R27 is a group shown by the above-mentioned general formula [2] or [3], the ainion derived from the inorganic strong acid shown by A3 to A5 includes one derived from an inorganic strong acid shown by the general formula [36]: HM3F6 [36] (wherein M3 is a phosphorus atom, an arsenic atom or an antimony atom). In the general formula [5], the metalloid atom shown by M2 includes, for example, a boron atom, a silicon atom, a phosphorus atom, an arsenic atom and an antimony atom, and among others, for example, a phosphorus atom, an arsenic atom and an antimony atom are preferable. The metal atom shown by M2 includes, for example, a titanium atom, a zirconium atom, an iron atom, a nickel atom, an aluminum atom and a gallium atom, and among others, a gallium atom is preferable. In the general formulae [1], [9], [35] and [38], the anion derived from the organic acid and shown by A, A2, A3 and A5 includes, for example, one derived from a sulfonic acid shown by the general formula [6]: R8—SO3H [6] (wherein —R8 is an alkyl group, an aryl group or an aralkyl group, which may have a halogen atom) or a carboxylic acid shown by the general formula [7]: R9—COOH [7] (wherein R9 is an alkyl group, an aryl group or an aralkyl group, which may have a halogen atom). In the general formulae [8] and [37], the anion derived from the sulfonic acid shown by A1 and A4 includes, for example, one derived from the sulfonic acid shown by the above-mentioned general formula [6]. In the general formula [6], the alkyl group of the alkyl group which may have a halogen atom, shown by R8 may be straight chained, branched or cyclic, and includes one having generally 1 to 29, preferably 1 to 18 and more preferably 1 to 8 carbon atoms, which is specifically exemplified by, for example, a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a n-pentyl group, an isopentyl group, a sec-pentyl group, a tert-pentyl group, a neopentyl group, a n-hexyl group, an isohexyl group, a sec-hexyl group, a tert-hexyl group, a neohexyl group, a n-heptyl group, an isoheptyl group, a sec-heptyl group, a tert-heptyl group, a neoheptyl group, a n-octyl group, an isooctyl group, a sec-octyl group, a tert-octyl group, a neooctyl group, a n-nonyl group, an isononyl group, a sec-nonyl group, a tert-nonyl group, a neononyl group, a n-decyl group, an isodecyl group, a sec-decyl group, a tert-decyl group, a neodecyl group, a n-undecyl group, an isoundecyl group, a sec-undecyl group, a tert-undecyl group, a neoundecyl group, a n-dodecyl group, an isododecyl group, a sec-dodecyl group, a tert-dodecyl group, a neododecyl group, a n-tridecyl group, an isotridecyl group, a sec-tridecyl group, a tert-tridecyl group, a neotridecyl group, a n-tetradecyl group, an isotetradecyl group, a sec-tetradecyl group, a tert-tetradecyl group, a neotetradecyl group, a n-pentadecyl group, an isopentadecyl group, a sec-pentadecyl group, a tert-pentadecyl group, a neopentadecyl group, a n-hexadecyl group, an isohexadecyl group, a sec-hexadecyl group, a tert-hexadecyl group, a neohexadecyl group, a n-heptadecyl group, an isoheptadecyl group, a sec-heptadecyl group, a tert-heptadecyl group, a neoheptadecyl group, a n-octadecyl group, an isooctadecyl group, a sec-octadecyl group, a tert-octadecyl group, a neooctadecyl group, a n-nonadecyl group, an isononadecyl group, a sec-nonadecyl group, a tert-nonadecyl group, a neononadecyl group, a n-icosyl group, an isoicosyl group, a sec-icosyl group, a tert-icosyl group, a neoicosyl group, a n-henicosyl group, an isohenicosyl group, a sec-henicosyl group, a tert-henicosyl group, a neohenicosyl group, a n-docosyl group, an isodocosyl group, a sec-docosyl group, a tert-docosyl group, a neodocosyl group, a n-tricosyl group, an isotricosyl group, a sec-tricosyl group, a tert-tricosyl group, a neotricosyl group, a n-tetracosyl group, an isotetracosyl group, a sec-tetracosyl group, a tert-tetracosyl group, a neotetracosyl group, a n-pentacosyl group, an isopentacosyl group, a sec-pentacosyl group, a tert-pentacosyl group, a neopentacosyl group, a n-hexacosyl group, an isohexacosyl group, a sec-hexacosyl group, a tert-hexacosyl group, a neohexacosyl group, a n-heptacosyl group, an isoheptacosyl group, a sec-heptacosyl group, a tert-heptacosyl group, a neoheptacosyl group, a n-octacosyl group, an isooctacosyl group, a sec-octacosyl group, a tert-octacosyl group, a neooctacosyl group, a n-nonacosyl group, an isononacosyl group, a sec-nonacosyl group, a tert-nonacosyl group, a neononacosyl group, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cyclooctyl group, a cyclononyl group, a cyclodecyl group, a cycloundecyl group, a cyclododecyl group, a cyclotridecyl group, a cyclotetradecyl group, a cyclopentadecyl group, a cyclohexadecyl group, a cycloheptadecyl group, a cyclooctadecyl group, a cyclononadecyl group, a cycloicosyl group, a cyclohenicosyl group, a cyclodocosyl group, a cyclotricosyl group, a cyclotetracosyl group, a cyclopentacosyl group, a cyclohexacosyl group, a cycloheptacosyl group, a cyclooctacosyl group and a cyclononacosyl group, and among others, for example, a methyl group, a butyl group and an octyl group are preferable. In the general formula [7], then alkyl group of the alkyl group which may have a halogen atom, shown by R9 may be straight chained, branched or cyclic, and includes one having generally 1 to 29, preferably 1 to 18 and more preferably 1 to 11 carbon atoms, which is specifically exemplified by, for example, the same as examples of the alkyl group of the alkyl group which may have a halogen atom, shown by the above-mentioned R8, and among others, a methyl group, a propyl group, a heptyl group and an undecyl group are preferable. An aryl group of an aryl group shown by R8 and R9 in the general formulae [6] and [7], which may have a halogen atom, includes one having generally 6 to 16 carbon atoms, preferably 6 to 14 carbon atoms, which is specifically exemplified by, for example, a phenyl group, a naphthyl group, an anthryl group, a phenanthrenyl group and a pyrenyl group, and among others, a phenyl group is preferable. The aralkyl group of the aralkyl group which may have a halogen atom, shown by R8 and R9 includes one having generally 7 to 15, preferably 7 to 10 carbon atoms, which is specifically exemplified by, for example, a benzyl group, a phenethyl group, a phenylpropyl group, a phenylbutyl group, a 1-methyl-3-phenylpropyl group, a phenylpentyl group, a phenylhexyl group, a phenylheptyl group, a phenyloctyl group and a phenylnonyl group, and among others, a benzyl group and a phenethyl group are preferable. An alkyl group, an aryl group and an aralkyl group which have a halogen atom, shown by R8 and R9 are one, wherein a part of or all of hydrogen atoms of the above-mentioned alkyl group, aryl group and aralkyl group are substituted by a halogen atom (e.g. a fluorine atom, a chlorine atom, a bromine atom and an iodine atom). Specifically, in the alkyl group, it is preferable that one, wherein all hydrogen atoms, or generally 1 to 30 hydrogen atoms, preferably 1 to 16 hydrogen atoms thereof are substituted by a halogen atom, and among others, one wherein all hydrogen atoms are substituted by a halogen atom is preferable. Specifically, in the aryl group, it is preferable that one, wherein 1 to 5 hydrogen atoms, preferably 3 to 5 hydrogen atoms in the ring thereof are substituted by a halogen atom, and among others, one wherein all hydrogen atoms in the ring thereof are substituted by a halogen atom is preferable. Specifically, in the aralkyl group, it is preferable that one, wherein hydrogen atoms in the alkyl group moiety and/or aryl group moiety are substituted by a halogen atom, and includes one wherein all or a part of hydrogen atoms in the alkyl group moiety thereof are substituted by a halogen atom, and 1 to 5 hydrogen atoms, preferably 5 hydrogen atoms in the aryl ring thereof are substituted by a halogen atom. An alkyl group, an aryl group or an aralkyl group which may have a halogen atom, shown by R8 and R9, may further have a substituent other than said halogen atom and said substituent includes, for example, a lower alkyl group having 1 to 4 carbon atoms such as a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group and a tert-butyl group; a lower haloalkyl group having 1 to 4 carbon atoms such as a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a chloromethyl group, a dichloromethyl group, a trichloromethyl group, a bromomethyl group, a dibromomethyl group, a tribromomethyl group, an iodomethyl group, a diiodomethyl group, a triiodomethyl group, a trifluoroethyl group, a trichloroethyl group, a tribromoethyl group, a pentafluoroethyl group, a pentachloroethyl group, a pentabromoethyl group, a heptafluoropropyl group, a heptachloropropyl group, a nonafluorobutyl group, a nonachlorobutyl group, a nonabromobutyl group and a nonaiodobutyl group; and a lower alkoxy group having 1 to 4 carbon atoms such as a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, a n-butoxy group, an isobutoxy group, a sec-butoxy group and a tert-butoxy group. The specific example of the compound shown by the general formula [4] includes, for example, tetraphenyl borate, tetrakis[4-(trifluoromethyl)phenyl]borate, tetrakis[4-(trichloromethyl)phenyl]borate, tetrakis[4-(tribromomethyl)phenyl]borate, tetrakis[4-(triiodomethyl)phenyl]borate, tetrakis[3,5-bis(trifluoromethyl)phenyl]borate, tetrakis[3,5-bis(trichloromethyl)phenyl]borate, tetrakis[3,5-bis(tribromomethyl)phenyl]borate, tetrakis[3,5-bis(triiodomethyl)phenyl]borate, tetrakis(pentafluorophenyl) borate, tetrakis(pentachlorophenyl)borate, tetrakis(pentabromophenyl)borate, tetrakis(pentaiodophenyl) borate, tetraphenyl gallate, tetrakis[4-(trifluoromethyl)phenyl]gallate, tetrakis[4-(trichloromethyl)phenyl]gallate, tetrakis[4-(tribromomethyl)phenyl]gallate, tetrakis[4-(triiodomethyl)phenyl]gallate, tetrakis[3,5-bis(trifluoromethyl)phenyl]gallate, tetrakis[3,5-bis(trichloromethyl)phenyl]gallate, tetrakis[3,5-bis(tribromomethyl)phenyl]gallate, tetrakis[3,5-bis(triiodomethyl)phenyl]gallate, tetrakis(pentafluorophenyl) gallate, tetrakis(pentachlorophenyl) gallate, tetrakis(pentabromophenyl) gallate and tetrakis(pentaiodophenyl) gallate, and among others, tetraphenyl borate, tetrakis[4-(trifluoromethyl)phenyl]borate, tetrakis[3,5-bis(trifluoromethyl)phenyl]borate, tetrakis(pentafluorophenyl) borate, tetraphenyl gallate, tetrakis[4-(trifluoromethyl)phenyl]gallate, tetrakis[3,5-bis(trifluoromethyl)phenyl]gallate and tetrakis(pentafluorophenyl) gallate are preferable. The specific example of the halosulfuric acid as the inorganic strong acid includes, for example, fluorosulfuric acid, chlorosulfuric acid, bromosulfuric acid and iodosulfuric acid, and among others, chlorosulfuric acid and bromosulfuric acid are preferable. The specific example of the perhalogenic acid as the inorganic strong acid includes, for example, perfluoric acid, perchloric acid, perbromic acid and periodic acid, and among others, a preferable one includes perchloric acid, perbromic acid and periodic acid, and a more preferable one includes perchloric acid. The specific example of the inorganic strong acid shown by the general formula [5] includes, for example, tetrafluoroborate, tetrafluoroaluminate, tetrafluoroferrate, tetrafluorogallate, hexafluorophosphate, hexafluoroarsenate, hexafluoroantimonate, hexafluorosilicate, hexafluoronickelate, hexafluorotitanate and hexafluorozirconate, and among others, hexafluorophosphate, hexafluoroarsenate and hexafluoroantimonate are preferable. The specific example of the inorganic strong acid shown by the general formula [36] includes, for example, hexafluorophosphate, hexafluoroarsenate and hexafluoroantimonate. The specific example of the sulfonic acid shown by the general formula [6] includes, for example, an alkylsulfonic acid such as methanesulfonic acid, ethanesulfonic acid, propanesulfonic acid, butanesulfonic acid, pentanesulfonic acid, hexanesulfonic acid, heptanesulfonic acid, octanesulfonic acid, nonanesulfonic acid, decanesulfonic acid, undecanesulfonic acid, dodecanesulfonic acid, tridecanesulfonic acid, tetradecanesulfonic acid, pentadecanesulfonic acid, hexadecanesulfonic acid, heptadecanesulfonic acid, octadecanesulfonic acid, nonadecanesulfonic acid, icosanesulfonic acid, henicosanesulfonic acid, docosanesulfonic acid, tricosanesulfonic acid and tetracosanesulfonic acid; a haloalkylsulfonic acid such as fluoromethanesulfonic acid, difluoromethanesulfonic acid, trifluoromethanesulfonic acid, chloromethanesulfonic acid, dichloromethanesulfonic acid, trichloromethanesulfonic acid, bromomethanesulfonic acid, dibromomethanesulfonic acid, tribromomethanesulfonic acid, iodomethanesulfonic acid, diiodomethanesulfonic acid, triiodomethanesulfonic acid, fluoroethanesulfonic acid, difluoroethanesulfonic acid, trifluoroethanesulfonic acid, pentafluoroethanesulfonic acid, chloroethanesulfonic acid, dichloroethanesulfonic acid, trichloroethanesulfonic acid, pentachloroethanesulfonic acid, tribromoethanesulfonic acid, pentabromoethanesulfonic acid, triiodoethanesulfonic acid, pentaiodoethanesulfonic acid, fluoropropanesulfonic acid, trifluoropropanesulfonic acid, heptafluoropropanesulfonic acid, chloropropanesulfonic acid, trichloropropanesulfonic acid, heptachloropropanesulfonic acid, bromopropanesulfonic acid, tribromopropanesulfonic acid, heptabromopropanesulfonic acid, triiodopropanesulfonic acid, heptaiodopropanesulfonic acid, trifluorobutanesulfonic acid, nonafluorobutanesulfonic acid, trichlorobutanesulfonic acid, nonachlorobutanesulfonic acid, tribromobutanesulfonic acid, nonabromobutanesulfonic acid, triiodobutanesulfonic acid, nonaiodobutanesulfonic acid, trifluoropentanesulfonic acid, perfluoropentanesulfonic acid, trichloropentanesulfonic acid, perchloropentanesulfonic acid, tribromopentanesulfonic acid, perbromopentanesulfonic acid, triiodopentanesulfonic acid, periodopentanesulfonic acid, trifluorohexanesulfonic acid, perfluorohexanesulfonic acid, trichlorohexanesulfonic acid, perchlorohexanesulfonic acid, perbromohexanesulfonic acid, periodohexanesulfonic acid, trifluoroheptanesulfonic acid, perfluoroheptanesulfonic acid, trichloroheptanesulfonic acid, perchloroheptanesulfonic acid, perbromoheptanesulfonic acid, periodoheptanesulfonic acid, trifluorooctanesulfonic acid, perfluorooctanesulfonic acid, trichlorooctanesulfonic acid, perchlorooctanesulfonic acid, perbromooctanesulfonic acid, periodooctanesulfonic acid, trifluorononanesulfonic acid, perfluorononanesulfonic acid, trichlorononanesulfonic acid, perchlorononanesulfonic acid, perbromononanesulfonic acid, periodononanesulfonic acid, trifluorodecanesulfonic acid, perfluorodecanesulfonic acid, trichlorodecanesulfonic acid, perchlorodecanesulfonic acid, perbromodecanesulfonic acid, periododecanesulfonic acid, trifluoroundecanesulfonic acid, perfluoroundecanesulfonic acid, trichloroundecanesulfonic acid, perchloroundecanesulfonic acid, perbromoundecanesulfonic acid, periodoundecanesulfonic acid, trifluorododecanesulfonic acid, perfluorododecanesulfonic acid, trichlorododecanesulfonic acid, perchlorododecanesulfonic acid, perbromododecanesulfonic acid, periodododecanesulfonic acid, trifluorotridecanesulfonic acid, perfluorotridecanesulfonic acid, trichlorotridecanesulfonic acid, perchlorotridecanesulfonic acid, perbromotridecanesulfonic acid, periodotridecanesulfonic acid, trifluorotetradecanesulfonic acid, perfluorotetradecanesulfonic acid, trichlorotetradecanesulfonic acid, perchlorotetradecanesulfonic acid, perbromotetradecanesulfonic acid, periodotetradecanesulfonic acid, trifluoropentadecanesulfonic acid, perfluoropentadecanesulfonic acid, trichloropentadecanesulfonic acid, perchloropentadecanesulfonic acid, perbromopentadecanesulfonic acid, periodopentadecanesulfonic acid, perfluorohexadecanesulfonic acid, perchlorohexadecanesulfonic acid, perbromohexadecanesulfonic acid, periodohexadecanesulfonic acid, perfluoroheptadecanesulfonic acid, perchloroheptadecanesulfonic acid, perbromoheptadecanesulfonic acid, periodoheptadecanesulfonic acid, perfluorooctadecanesulfonic acid, perchlorooctadecanesulfonic acid, perbromooctadecanesulfonic acid, periodooctadecanesulfonic acid, perfluorononadecanesulfonic acid, perchlorononadecanesulfonic acid, perbromononadecanesulfonic acid, periodononadecanesulfonic acid, perfluoroicosanesulfonic acid, perchloroicosanesulfonic acid, perbromoicosanesulfonic acid, periodoicosanesulfonic acid, perfluorohenicosanesulfonic acid, perchlorohenicosanesulfonic acid, perbromohenicosanesulfonic acid, periodohenicosanesulfonic acid, perfluorodocosanesulfonic acid, perchlorodocosanesulfonic acid, perbromodocosanesulfonic acid, periododocosanesulfonic acid, perfluorotricosanesulfonic acid, perchlorotricosanesulfonic acid, perbromotricosanesulfonic acid, periodotricosanesulfonic acid, perfluorotetracosanesulfonic acid, perchlorotetracosanesulfonic acid, perbromotetracosanesulfonic acid and periodotetracosanesulfonic acid; a cycloalkylsulfonic acid such as cyclopentanesulfonic acid and cyclohexanesulfonic acid; a halocycloalkylsulfonic acid such as 2-fluorocyclopentanesulfonic acid, 2-chlorocyclopentanesulfonic acid, 2-bromocyclopentanesulfonic acid, 2-iodocyclopentanesulfonic acid, 3-fluorocyclopentanesulfonic acid, 3-chlorocyclopentanesulfonic acid, 3-bromocyclopentanesulfonic acid, 3-iodocyclopentanesulfonic acid, 3,4-difluorocyclopentanesulfonic acid, 3,4-dichlorocyclopentanesulfonic acid, 3,4-dibromocyclopentanesulfonic acid, 3,4-diiodocyclopentanesulfonic acid, 4-fluorocyclohexanesulfonic acid, 4-chlorocyclohexanesulfonic acid, 4-bromocyclohexanesulfonic acid, 4-iodocyclohexanesulfonic acid, 2,4-difluorocyclohexanesulfonic acid, 2,4-dichlorocyclohexanesulfonic acid, 2,4-dibromocyclohexanesulfonic acid, 2,4-diiodocyclohexanesulfonic acid, 2,4,6-trifluorocyclohexanesulfonic acid, 2,4,6-trichlorocyclohexanesulfonic acid, 2,4,6-tribromocyclohexanesulfonic acid, 2,4,6-triiodocyclohexanesulfonic acid, tetrafluorocyclohexanesulfonic acid, tetrachlorocyclohexanesulfonic acid, tetrabromocyclohexanesulfonic acid and tetraiodocyclohexanesulfonic acid; an aromatic sulfonic acid such as benzenesulfonic acid, naphthalenesulfonic acid, anthracenesulfonic acid, phenanthrenesulfonic acid and pyrenesulfonic acid; a haloaromatic sulfonic acid such as 2-fluorobenzenesulfonic acid, 3-fluorobenzenesulfonic acid, 4-fluorobenzenesulfonic acid, 2-chlorobenzenesulfonic acid, 3-chlorobenzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-bromobenzenesulfonic acid, 3-bromobenzenesulfonic acid, 4-bromobenzenesulfonic acid, 2-iodobenzenesulfonic acid, 3-iodobenzenesulfonic acid, 4-iodobenzenesulfonic acid, 2,4-difluorobenzenesulfonic acid, 2,6-difluorobenzenesulfonic acid, 2,4-dichlorobenzenesulfonic acid, 2,6-dichlorobenzenesulfonic acid, 2,4-dibromobenzenesulfonic acid, 2,6-dibromobenzenesulfonic acid, 2,4-diiodobenzenesulfonic acid, 2,6-diiodobenzenesulfonic acid, 2,4,6-trifluorobenzenesulfonic acid, 3,4,5-trifluorobenzenesulfonic acid, 2,4,6-trichlorobenzenesulfonic acid, 3,4,5-trichlorobenzenesulfonic acid, 2,4,6-tribromobenzenesulfonic acid, 3,4,5-tribromobenzenesulfonic acid, 2,4,6-triiodobenzenesulfonic acid, 3,4,5-triiodobenzenesulfonic acid, pentafluorobenzenesulfonic acid, pentachlorobenzenesulfonic acid, pentabromobenzenesulfonic acid, pentaiodobenzenesulfonic acid, fluoronaphthalenesulfonic acid, chloronaphthalenesulfonic acid, bromonaphthalenesulfonic acid, iodonaphthalenesulfonic acid, fluoroanthracenesulfonic acid, chloroanthracenesulfonic acid, bromoanthracenesulfonic acid and iodoanthracenesulfonic acid; an alkylaromatic sulfonic acid such as p-toluenesulfonic acid, 4-isopropylbenzenesulfonic acid, 3,5-bis(trimethyl)benzenesulfonic acid, 3,5-bis(isopropyl)benzenesulfonic acid, 2,4,6-tris(trimethyl)benzenesulfonic acid and 2,4,6-tris(isopropyl)benzenesulfonic acid; a haloalkylaromatic sulfonic acid such as 2-trifluoromethylbenzenesulfonic acid, 2-trichloromethylbenzenesulfonic acid, 2-tribromomethylbenzenesulfonic acid, 2-triiodomethylbenzenesulfonic acid, 3-trifluoromethylbenzenesulfonic acid, 3-trichloromethylbenzenesulfonic acid, 3-tribromomethylbenzenesulfonic acid, 3-triiodomethylbenzenesulfonic acid, 4-trifluoromethylbenzenesulfonic acid, 4-trichloromethylbenzenesulfonic acid, 4-tribromomethylbenzenesulfonic acid, 4-triiodomethylbenzenesulfonic acid, 2,6-bis(trifluoromethyl)benzenesulfonic acid, 2,6-bis(trichloromethyl)benzenesulfonic acid, 2,6-bis(tribromomethyl)benzenesulfonic acid, 2,6-bis(triiodomethyl)benzenesulfonic acid, 3,5-bis(trifluoromethyl)benzenesulfonic acid, 3,5-bis(trichloromethyl)benzenesulfonic acid, 3,5-bis(tribromomethyl)benzenesulfonic acid and 3,5-bis(triiodomethyl)benzenesulfonic acid; an aromatic aliphatic sulfonic acid such as benzylsulfonic acid, phenethylsulfonic acid, phenylpropylsulfonic acid, phenylbutylsulfonic acid, phenylpentylsulfonic acid, phenylhexylsulfonic acid, phenylheptylsulfonic acid, phenyloctylsulfonic acid and phenylnonylsulfonic acid; a haloaromatic aliphatic sulfonic acid such as 4-fluorophenylmethylsulfonic acid, 4-chlorophenylmethylsulfonic acid, 4-bromophenylmethylsulfonic acid, 4-iodophenylmethylsulfonic acid, tetrafluorophenylmethylsulfonic acid, tetrachlorophenylmethylsulfonic acid, tetrabromophenylmethylsulfonic acid, tetraiodophenylmethylsulfonic acid, 4-fluorophenylethylsulfonic acid, 4-chlorophenylethylsulfonic acid, 4-bromophenylethylsulfonic acid, 4-iodophenylethylsulfonic acid, 4-fluorophenylpropylsulfonic acid, 4-chlorophenylpropylsulfonic acid, 4-bromophenylpropylsulfonic acid, 4-iodophenylpropylsulfonic acid, 4-fluorophenylbutylsulfonic acid, 4-chlorophenylbutylsulfonic acid, 4-bromophenylbutylsulfonic acid and 4-iodophenylbutylsulfonic acid; and an alicyclic sulfonic acid such as camphorsulfonic acid and adamantanesulfonic acid. The specific example of the carboxylic acid shown by the general formula [7] includes, for example, a saturated aliphatic carboxylic acid such as formic acid, acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, isovaleric acid, pivalic acid, hexanoic acid, peptanoic acid, octanoic acid, nonanoic acid, decanoic acid, undecanoic acid, lauric acid, tridecanoic acid, myristic acid, pentadecanoic acid, palmitic acid, heptadecanoic acid, stearic acid, nonadecanoic acid, icosanoic acid, henicosanoic acid, docosanoic acid and tricosanoic acid; a saturated haloaliphatic carboxylic acid such as fluoroacetic acid, chloroacetic acid, bromoacetic acid, iodoacetic acid, difluoroacetic acid, dichloroacetic acid, dibromoacetic acid, diiodoacetic acid, trifluroacetic acid, trichloroacetic acid, tribromoacetic acid, triiodmoacetic acid, 2-fluoropropionic acid, 2-chloropropionic acid, 2-bromopropionic acid, 2-iodopropionic acid, trifluoropropionic acid, trichloropropionic acid, pentafluoropropionic acid, pentachloropropionic acid, pentabromopropionic acid, pentaiodopropionic acid, 2,2-bis(trifluoromethyl)propionic acid, 2,2-bis(trichloromethyl)propionic acid, 2,2-bis(tribromomethyl)propionic acid, 2,2-bis(triiodomethyl)propionic acid, trifluorobutyric acid, trichlorobutyric acid, pentafluorobutyric acid, heptachlorobutyric acid, heptafluorobutyric acid, heptabromobutyric acid, heptaiodobutyric acid, heptafluoroisobutyric acid, heptachloroisobutyric acid, heptabromoisobutyric acid, heptaiodoisobutyric acid, trifluorovaleric acid, 5H-perfluorovaleric acid, 5H-perchlorovaleric acid, 5H-perbromovaleric acid, 5H-periodovaleric acid, nonafluorovaleric acid, nonachlorovaleric acid, nonabromovaleric acid, nonaiodovaleric acid, trifluorohexanoic acid, trichlorohexanoic acid, perfluorohexanoic acid, perchlorohexanoic acid, perbromohexanoic acid, periodohexanoic acid, 7-chlorododecafluoroheptanoic acid, 7-chlorododecachloroheptanoic acid, 7-chlorododecabromoheptanoic acid, 7-chlorododecaiodoheptanoic acid, trifluoroheptanoic acid, trichloroheptanoic acid, 7H-perfluoroheptanoic acid, 7H-perchloroheptanoic acid, 7H-perbromoheptanoic acid, 7H-periodoheptanoic acid, trifluorooctanoic acid, trichlorooctanoic acid, pentadecafluorooctanoic acid, pentadecachlorooctanoic acid, pentadecabromooctanoic acid, pentadecaiodoctanoic acid, trifluorononanoic acid, trichlorononanoic acid, 9H-hexadecafluorononanoic acid, 9H-hexadecachlorononanoic acid, 9H-hexadecabromononanoic acid, 9H-hexadecaiodononanoic acid, perfluorononanoic acid, perchlorononanoic acid, perbromononanoic acid, periodononanoic acid, trifluorodecanoic acid, trichlorodecanoic acid, nonadecafluorodecanoic acid, nonadecachlorodecanoic acid, nonadecabromodecanoic acid, nonadecaiododecanoic acid, trifluoroundecanoic acid, trichloroundecanoic acid, perfluoroundecanoic acid, perchloroundecanoic acid, perbromoundecanoic acid, periodoundecanoic acid, trifluorododecanoic acid, trichlorododecanoic acid, perfluorododecanoic acid, perchlorododecanoic acid, perbromododecanoic acid, periodododecanoic acid, trifluorotridecanoic acid, trichlorotridecanoic acid, perfluorotridecanoic acid, perchlorotridecanoic acid, perbromotridecanoic acid, periodotridecanoic acid, trifluorotetradecanoic acid, trichlorotetradecanoic acid, perfluorotetradecanoic acid, perchlorotetradecanoic acid, perbromotetradecanoic acid, periodotetradecanoic acid, trifluoropentadecanoic acid, trichloropentadecanoic acid, perfluoropentadecanoic acid, perchloropentadecanoic acid, perbromopentadecanoic acid, periodopentadecanoic acid, perfluorohexadecanoic acid, perchlorohexadecanoic acid, perbromohexadecanoic acid, periodohexadecanoic acid, perfluoroheptadecanoic acid, perchloroheptadecanoic acid, perbromoheptadecanoic acid, periodoheptadecanoic acid, perfluorooctadecanoic acid, perchlorooctadecanoic acid, perbromooctadecanoic acid, periodooctadecanoic acid, perfluorononadecanoic acid, perchlorononadecanoic acid, perbromononadecanoic acid, periodononadecanoic acid, perfluoroicosanoic acid, perchloroicosanoic acid, perbromoicosanoic acid, periodoicosanoic acid, perfluorohenicosanoic acid, perchlorohenicosanoic acid, perbromohenicosanoic acid, periodohenicosanoic acid, perfluorodocosanoic acid, perchlorodocosanoic acid, perbromodocosanoic acid, periododocosanoic acid, perfluorotricosanoic acid, perchlorotricosanoic acid, perbromotriocosanoic acid and periodotricosanoic acid; a hydroxyaliphatic carboxylic acid such as glycolic acid, lactic acid, glyceric acid and 3-hydroxy-2-methylpropionic acid; a hydroxyhaloaliphatic carboxylic acid such as 3-hydroxy-2-(trifluoromethyl)propionic acid, 3-hydroxy-2-(trichloromethyl)propionic acid, 3-hydroxy-2-(tribromomethyl)propionic acid, 3-hydroxy-2-(triiodomethyl)propionic acid, 2-hydroxy-2-(trifluoromethyl)butyric acid, 2-hydroxy-2-(trichloromethyl)butyric acid, 2-hydroxy-2-(tribromomethyl)butyric acid and 2-hydroxy-2-(triiodomethyl)butyric acid; an alicyclic carboxylic acid such as cyclohexanecarboxylic acid, camphoric acid and adamantane carboxylic acid; a haloalicyclic carboxylic acid such as 4-fluorocyclohexanecarboxylic acid, 4-chlorocyclohexanecarboxylic acid, 4-bromocyclohexanecarboxylic acid, 4-iodocyclohexanecarboxylic acid, pentafluorocyclohexanecarboxylic acid, pentachlorocyclohexanecarboxylic acid, pentabromocyclohexanecarboxylic acid, pentaiodocyclohexanecarboxylic acid, 4-(trifluoromethyl)cyclohexanecarboxylic acid, 4-(trichloromethyl)cyclohexanecarboxylic acid, 4-(tribromomethyl)cyclohexanecarboxylic acid and 4-(triiodomethyl)cyclohexanecarboxylic acid; an aromatic carboxylic acid such as benzoic acid, naphthoic acid, anthracene carboxylic acid, pyrene carboxylic acid, perylene carboxylic acid and pentaphene carboxylic acid; a haloaromatic carboxylic acid such as fluorobenzoic acid, chlorobenzoic acid, bromobenzoic acid, iodobenzoic acid, difluorobenzoic acid, dichlorobenzoic acid, dibromobenzoic acid, diiodobenzoic acid, trifluorobenzoic acid, trichlorobenzoic acid, tribromobenzoic acid, triiodobenzoic acid, tetrafluorobenzoic acid, tetrachlorobenzoic acid, tetrabromobenzoic acid, tetraiodobenzoic acid, pentafluorobenzoic acid, pentachlorobenzoic acid, pentabromobenzoic acid, pentaiodobenzoic acid, fluoronaphthoic acid, chloronaphthoic acid, bromonaphthoic acid, iodonaphthoic acid, perfluoronaphthoic acid, perchloronaphthoic acid, perbromonaphthoic acid, periodonaphthoic acid, fluoroanthracene carboxylic acid, chloroanthracene carboxylic acid, bromoanthracene carboxylic acid, iodoanthracene carboxylic acid, perfluoroanthracene carboxylic acid, perchloroanthracene carboxylic acid, perbromoanthracene carboxylic acid and periodoanthracene carboxylic acid; an alkylaromatic carboxylic acid such as toluic acid and 2,4,6-tri(isopropyl)benzoic acid; a haloalkylaromatic carboxylic acid such as 2-trifluoromethylbenzoic acid, 2-trichloromethylbenzoic acid, 2-tribromomethylbenzoic acid, 2-triiodomethylbenzoic acid, 3-trifluoromethylbenzoic acid, 3-trichloromethylbenzoic acid, 3-tribromomethylbenzoic acid, 3-triiodomethylbenzoic acid, 4-trifluoromethylbenzoic acid, 4-trichloromethylbenzoic acid, 4-tribromomethylbenzoic acid, 4-triiodomethylbenzoic acid, 2-fluoro-4-(trifluoromethyl)benzoic acid, 2-chloro-4-(trichloromethyl)benzoic acid, 2-bromo-4-(tribromomethyl)benzoic acid, 2,3,4-trifluoro-6-(trifluoromethyl)benzoic acid, 2,3,4-trichloro-6-(trichloromethyl)benzoic acid, 2,3,4-tribromo-6-(tribromomethyl)benzoic acid, 2,3,4-triiodo-6-(triiodomethyl)benzoic acid, 2-iodo-4-(triiodomethyl)benzoic acid, 2,4-bis(trifluoromethyl)benzoic acid, 2,4-bis(trichloromethyl)benzoic acid, 2,4-bis(tribromomethyl)benzoic acid, 2,4-bis(triiodomethyl)benzoic acid, 2,6-bis(trifluoromethyl)benzoic acid, 2,6-bis(trichloromethyl)benzoic acid, 2,6-bis(tribromomethyl)benzoic acid, 2,6-bis(triiodomethyl)benzoic acid, 3,5-bis(trifluoromethyl)benzoic acid, 3,5-bis(trichloromethyl)benzoic acid, 3,5-bis(tribromomethyl)benzoic acid, 3,5-bis(triiodomethyl)benzoic acid, 2,4,6-tris(trifluoromethyl)benzoic acid, 2,4,6-tris(trichloromethyl)benzoic acid, 2,4,6-tris(tribromomethyl)benzoic acid, 2,4,6-tris(triiodomethyl)benzoic acid, 2-chloro-6-fluoro-3-methylbenzoic acid, trifluoromethylnaphthoic acid, trichloromethylnaphthoic acid, tribromomethylnaphthoic acid, triiodomethylnaphthoic acid, bis(trifluoromethyl)naphthoic acid, bis(trichloromethyl)naphthoic acid, bis(tribromomethyl)naphthoic acid, bis(triiodomethyl)naphthoic acid, tris(trifluoromethyl)naphthoic acid, tris(trichloromethyl)naphthoic acid, tris(tribromomethyl)naphthoic acid, tris(triiodomethyl)naphthoic acid, trifluoromethylanthracene carboxylic acid, trichloromethylanthracene carboxylic acid, tribromomethylanthracene carboxylic acid and triiodomethylanthracene carboxylic acid; an alkoxyaromatic carboxylic acid such as anisic acid, veratric acid and o-veratric acid; a haloalkoxyaromatic carboxylic acid such as 4-trifluoromethoxybenzoic acid, 4-trichloromethoxybenzoic acid, 4-tribromomethoxybenzoic acid, 4-triiodomethoxybenzoic acid, 4-pentafluoroethoxybenzoic acid, 4-pentachloroethoxybenzoic acid, 4-pentabromoethoxybenzoic acid, 4-pentaiodoethoxybenzoic acid, 3,4-bis(trifluoromethoxy)benzoic acid, 3,4-bis(trichloromethoxy)benzoic acid, 3,4-bis(tribromomethoxy)benzoic acid, 3,4-bis(triiodomethoxy)benzoic acid, 2,5-bis(2,2,2-trifluoroethoxy)benzoic acid, 2,5-bis(2,2,2-trichloroethoxy)benzoic acid, 2,5-bis(2,2,2-tribromoethoxy)benzoic acid and 2,5-bis(2,2,2-triiodoethoxy)benzoic acid; a hydroxyaromatic carboxylic acid such as salicylic acid, o-pyrocatechuic acid, β-resorcylic acid, gentisic acid, γ-resorcylic acid, protocatechuic acid, α-resorcylic acid and gallic acid; a hydroxyalkoxyaromatic carboxylic acid such as vanillic acid and isovanillic acid; a nitroaromatic carboxylic acid such as trinitrobenzoic acid; an amino aromatic carboxylic acid such as anthranilic acid; an aromaticaliphatic carboxylic acid such as α-toluic acid, hydrocinnamic acid, hydroatropic acid, 3-phenylpropionic acid, 4-phenylbutyric acid, 5-phenylpentanoic acid, 6-phenylhexanoic acid, 7-phenylheptanoic acid and 6-(2-naphthyl)hexanoic acid; a hydroxyaromaticaliphatic carboxylic acid such as homogentisic acid; an aromatic hydroxyalkyl carboxylic acid such as mandelic acid, benzylic acid, atrolactinic acid, tropic acid and atroglyceric acid; an oxocarboxylic acid such as 2-formylacetic acid, acetoacetic acid, 3-benzoylpropionic acid, 4-formylacetic acid, 3-oxovaleric acid, 3,5-dioxovaleric acid, 6-formylhexanecarboxylic acid, 2-oxo-1-cyclohexanecarboxylic acid, 4-(2-oxobutyl)benzoic acid, p-(3-formylpropyl)benzoic acid, 4-formylphenylacetic acid, β-oxocyclohexanepropionic acid and pyruvic acid. The group shown by the general formula [2] includes, for example, a group shown by the following general formula [10] and [12]: (wherein R3, R4, i and j have the same meaning as above), and among others, a group shown by the general formula [10] is preferable. The group shown by the general formula [10] includes, for example, a xanthene-9-one-2-yl group and a xanthene-9-one-4-yl group, and among others, a xanthene-9-one-2-yl group is preferable. The group shown by the general formula [3] includes, for example, a group shown by the following general formula [14] and [15]: (wherein R5, R6, p and q have the same meaning as above), and among others, a group shown by the general formula [14] is preferable. The group shown by the general formula [14] includes, for example, a coumarin-7-yl group, a coumarin-5-yl group, a 4-methoxycoumarin-7-yl group, a 4-methoxycoumarin-5-yl group, 6-methylcoumarin-7-yl group and a 6-methylcoumarin-5-yl group, and among others, a coumarin-7-yl group is preferable. The group shown by the general formula [15]-includes, for example, a coumarin-2-thione-7-yl group, a coumarin-2-thione-5-yl group, a 4-methoxycoumarin-2-thione-7-yl group, a 4-methoxycoumarin-2-thione-5-yl group, 6-methylcoumarin-2-thione-7-yl group and a 6-methylcoumarin-2-thione-5-yl group. The sulfonium salt shown by the general formula [1] includes, for example, a group shown by the following general formulae [16], [18], [20] and [21]: (wherein R1 to R6, A, i, j, m, n, p and q have the same meaning as above), and among others, groups shown by the general formulae [16] and [20] are preferable. The iodonium salt shown by the general formula [35] includes, for example, one shown by the following general formulae [39] to [43]: (wherein R28 is a halogen atom or a lower alkyl group; u is an integer of 0 to 5; and R1 to R6, X2 to X4, A3, i, j, m, n, p and q have the same meaning as above), and among others, groups shown by the general formulae [39] to [41] are preferable, and groups shown by the general formulae [39] and [40] are more preferable. In the general formulae [42] and [43], the halogen atom shown by R28 includes, for example, a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. The lower alkyl group shown by R28 may be straight chained, branched or cyclic, and includes one having generally 1 to 6, preferably 1 to 4 carbon atoms, which is specifically exemplified by, for example, the lower alkyl group examples as the substituent of an aryl group which may have a halogen atom or a lower alkyl group as a substituent, shown by the above R1 to R6 and among others, a preferable one includes, for example, a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group and a tert-butyl group, and a more preferable one includes a methyl group and an ethyl group. U is an integer of generally 0 to 5, preferably 0 to 1. The preferable specific example shown by the general formula [16] includes, for example, diphenyl(xanthene-9-one-2-yl)sulfonium chloride, diphenyl(xanthene-9-one-2-yl)sulfonium bromide, diphenyl(xanthene-9-one-2-yl)sulfonium perchlorate, diphenyl(xanthene-9-one-2-yl)sulfonium tetrafluoroborate, diphenyl(xanthene-9-one-2-yl)sulfonium hexafluorophosphate, diphenyl(xanthene-9-one-2-yl)sulfonium hexafluoroarsenate, diphenyl(xanthene-9-one-2-yl)sulfonium hexafluoroantimonate, diphenyl(xanthene-9-one-2-yl)sulfonium tetraphenylborate, diphenyl(xanthene-9-one-2-yl)sulfonium tetrakis{3,5-bis(trifluoromethyl)phenyl}borate, diphenyl(xanthene-9-one-2-yl)sulfonium tetrakis(pentafluorophenyl)borate, diphenyl(xanthene-9-one-2-yl)sulfonium tetraphenylgallate, diphenyl(xanthene-9-one-2-yl)sulfonium tetrakis(pentafluorophenyl)gallate, diphenyl(xanthene-9-one-2-yl)sulfonium trifluoromethanesulfonate, diphenyl(xanthene-9-one-2-yl)sulfonium nonafluorobutanesulfonate, diphenyl(xanthene-9-one-2-yl)sulfonium perfluorooctanesulfonate, diphenyl(xanthene-9-one-2-yl)sulfonium benzenesulfonate, diphenyl(xanthene-9-one-2-yl)sulfonium p-toluenesulfonate, diphenyl(xanthene-9-one-2-yl)sulfonium 4-dodecylbenzenesulfonate, diphenyl(xanthene-9-one-2-yl)sulfonium 4-fluorobenzenesulfonate, diphenyl(xanthene-9-one-2-yl)sulfonium, 2,4-difluorobenzenesulfonate, diphenyl(xanthene-9-one-2-yl)sulfonium pentafluorobenzenesulfonate, diphenyl(xanthene-9-one-2-yl)sulfonium 4-trifluoromethylbenzenesulfonate, diphenyl(xanthene-9-one-2-yl)sulfonium 3,5-bis(trifluoromethyl)benzenesulfonate, diphenyl(xanthene-9-one-2-yl)sulfonium acetate, diphenyl(xanthene-9-one-2-yl)sulfonium heptafluorobutanoate, diphenyl(xanthene-9-one-2-yl)sulfonium perfluorooctanoate, diphenyl(xanthene-9-one-2-yl)sulfonium perfluorododecanoate, bis(4-methylphenyl)(xanthene-9-one-2-yl)sulfonium hexafluorophosphate, bis(4-methylphenyl)(xanthene-9-one-2-yl)sulfonium tetraphenylborate, bis(4-methylphenyl)(xanthene-9-one-2-yl)sulfonium trifluoromethanesulfonate, bis(4-methylphenyl)(xanthene-9-one-2-yl)sulfonium nonafluorobutanesulfonate, bis(4-methylphenyl)(xanthene-9-one-2-yl)sulfonium p-toluenesulfonate, diphenyl(xanthene-9-one-4-yl)sulfonium hexafluorophosphate, diphenyl(xanthene-9-one-4-yl)sulfonium tetraphenylborate, diphenyl(xanthene-9-one-4-yl)sulfonium trifluoromethanesulfonate, diphenyl(xanthene-9-one-4-yl)sulfonium nonafluorobutanesulfonate and diphenyl(xanthene-9-one-4-yl)sulfonium p-toluenesulfonate, and among others, a preferable one includes, for example, diphenyl(xanthene-9-one-2-yl)sulfonium hexafluorophosphate, diphenyl(xanthene-9-one-2-yl)sulfonium tetrafluoroborate, diphenyl(xanthene-9-one-2-yl)sulfonium trifluoromethanesulfonate, diphenyl(xanthene-9-one-2-yl)sulfonium nonafluorobutanesulfonate and diphenyl(xanthene-9-one-2-yl)sulfonium p-toluenesulfonate, among others, a more preferable includes diphenyl(xanthene-9-one-2-yl)sulfonium trifluoromethanesulfonate and diphenyl(xanthene-9-one-2-yl)sulfonium hexafluorophosphate. The preferable specific example shown by the general formula [18] includes, for example, diphenyl(xanthene-9-thione-2-yl)sulfonium chloride, diphenyl(xanthene-9-thione-2-yl)sulfonium bromide, diphenyl(xanthene-9-thione-2-yl)sulfonium perchlorate, diphenyl(xanthene-9-thione-2-yl)sulfonium tetrafluoroborate, diphenyl(xanthene-9-thione-2-yl)sulfonium hexafluorophosphate, diphenyl(xanthene-9-thione-2-yl)sulfonium hexafluoroarsenate, diphenyl(xanthene-9-thione-2-yl)sulfonium hexafluoroantimonate, diphenyl(xanthene-9-thione-2-yl)sulfonium tetraphenylborate, diphenyl(xanthene-9-thione-2-yl)sulfonium tetrakis{3,5-bis(trifluoromethyl)phenyl}borate, diphenyl(xanthene-9-thione-2-yl)sulfonium, tetrakis(pentafluorophenyl)borate, diphenyl(xanthene-9-thione-2-yl)sulfonium tetraphenylgallate, diphenyl(xanthene-9-thione-2-yl)sulfonium trifluoromethanesulfonate, diphenyl(xanthene-9-thione-2-yl)sulfonium nonafluorobutanesulfonate, diphenyl(xanthene-9-thione-2-yl)sulfonium perfluorooctanesulfonate, diphenyl(xanthene-9-thione-2-yl)sulfonium benzenesulfonate, diphenyl(xanthene-9-thione-2-yl)sulfonium p-toluenesulfonate, diphenyl(xanthene-9-thione-2-yl)sulfonium acetate, diphenyl(xanthene-9-thione-2-yl)sulfonium heptafluorobutanoate, diphenyl(xanthene-9-thione-2-yl)sulfonium perfluorooctanoate, bis(4-methylphenyl)(xanthene-9-thione-2-yl)sulfonium hexafluorophosphate, bis(4-methylphenyl)(xanthene-9-thione-2-yl)sulfonium tetraphenylborate, bis(4-methylphenyl) (xanthene-9-thione-2-yl)sulfonium trifluoromethanesulfonate, bis(4-methylphenyl)(xanthene-9-thione-2-yl)sulfonium nonafluorobutanesulfonate, bis(4-methylphenyl)(xanthene-9-thione-2-yl)sulfonium p-toluenesulfonate, diphenyl(xanthene-9-thione-4-yl)sulfonium hexafluorophosphate, diphenyl(xanthene-9-thione-4-yl)sulfonium tetraphenylborate, diphenyl(xanthene-9-thione-4-yl)sulfonium trifluoromethanesulfonate, diphenyl(xanthene-9-thione-4-yl)sulfonium nonafluorobutanesulfonate and diphenyl(xanthene-9-thione-4-yl)sulfonium p-toluenesulfonate, and among others, a preferable one includes, for example, diphenyl(xanthene-9-thione-2-yl)sulfonium hexafluorophosphate, diphenyl(xanthene-9-thione-2-yl)sulfonium tetraphenylborate, diphenyl(xanthene-9-thione-2-yl)sulfonium trifluoromethanesulfonate, diphenyl(xanthene-9-thione-2-yl)sulfonium nonafluorobutanesulfonate and diphenyl(xanthene-9-thione-2-yl)sulfonium p-toluenesulfonate. The preferable specific example shown by the general formula [20] includes, for example, diphenyl(coumarin-7-yl)sulfonium chloride, diphenyl(coumarin-7-yl)sulfonium bromide, diphenyl(coumarin-7-yl)sulfonium perchlorate, diphenyl(coumarin-7-yl)sulfonium tetrafluoroborate, diphenyl(coumarin-7-yl)sulfonium hexafluorophosphate, diphenyl(coumarin-7-yl)sulfonium hexafluoroarsenate, diphenyl(coumarin-7-yl)sulfonium hexafluoroantimonate, diphenyl(coumarin-7-yl)sulfonium tetraphenylborate, diphenyl(coumarin-7-yl)sulfonium tetrakis{3,5-bis(trifluoromethyl)phenyl}borate, diphenyl(coumarin-7-yl)sulfonium tetrakis(pentafluorophenyl)borate, diphenyl(coumarin-7-yl)sulfonium tetrafluorogallate, diphenyl(coumarin-7-yl)sulfonium tetraphenylgallate, diphenyl(coumarin-7-yl)sulfonium tetrakis(pentafluorophenyl)gallate, diphenyl(coumarin-7-yl)sulfonium trifluoromethanesulfonate, diphenyl(coumarin-7-yl)sulfonium nonafluorobutanesulfonate, diphenyl(coumarin-7-yl)sulfonium perfluorooctanesulfonate, diphenyl(coumarin-7-yl)sulfonium benzenesulfonate, diphenyl(coumarin-7-yl)sulfonium p-toluenesulfonate, diphenyl(coumarin-7-yl)sulfonium 4-dodecylbenzenesulfonate, diphenyl(coumarin-7-yl)sulfonium 4-fluorobenzenesulfonate, diphenyl(coumarin-7-yl)sulfonium 2,4-difluorobenzenesulfonate, diphenyl(coumarin-7-yl)sulfonium pentafluorobenzenesulfonate, diphenyl(coumarin-7-yl)sulfonium 4-trifluoromethylbenzenesulfonate, diphenyl(coumarin-7-yl)sulfonium 3,5-bis(trifluoromethyl)benzenesulfonate, diphenyl(coumarin-7-yl)sulfonium acetate, diphenyl(coumarin-7-yl)sulfonium heptafluorobutanoate, diphenyl(coumarin-7-yl)sulfonium perfluorooctanoate, diphenyl(coumarin-7-yl)sulfonium perfluorododecanoate, bis(4-methylphenyl)(coumarin-7-yl)sulfonium hexafluorophosphate, bis(4-methylphenyl) (coumarin-7-yl)sulfonium tetraphenylborate, bis(4-methylphenyl) (coumarin-7-yl)sulfonium trifluoromethanesulfonate, bis(4-methylphenyl)(coumarin-7-yl)sulfonium nonafluorobutanesulfonate, bis(4-methylphenyl)(coumarin-7-yl)sulfonium p-toluenesulfonate, diphenyl(4-methoxycoumarin-7-yl)sulfonium hexafluorophosphate, diphenyl(4-methoxycoumarin-7-yl)sulfonium tetraphenylborate, diphenyl(4-methoxycoumarin-7-yl)sulfonium trifluoromethanesulfonate, diphenyl(4-methoxycoumarin-7-yl)sulfonium nonafluorobutanesulfonate, diphenyl(4-methoxycoumarin-7-yl)sulfonium p-toluenesulfonate, diphenyl(6-methylcoumarin-7-yl)sulfonium hexafluorophosphate, diphenyl(6-methylcoumarin-7-yl)sulfonium tetraphenylborate, diphenyl(6-methylcoumarin-7-yl)sulfonium trifluoromethanesulfonate, diphenyl(6-methylcoumarin-7-yl)sulfonium nonafluorobutanesulfonate, diphenyl(6-methylcoumarin-7-yl)sulfonium p-toluenesulfonate, diphenyl(coumarin-5-yl)sulfonium hexafluorophosphate, diphenyl(coumarin-5-yl)sulfonium tetraphenylborate, diphenyl(coumarin-5-yl)sulfonium trifluoromethanesulfonate, diphenyl(coumarin-5-yl)sulfonium nonafluorobutanesulfonate and diphenyl(coumarin-5-yl)sulfonium p-toluenesulfonate, and among others, a preferable one incdlues diphenyl(coumarin-7-yl)sulfonium hexafluorophosphate, diphenyl(coumarin-7-yl)sulfonium tetraphenylborate, diphenyl(coumarin-7-yl)sulfonium trifluoromethanesulfonate, diphenyl(coumarin-7-yl)sulfonium nonafluorobutanesulfonate and diphenyl(coumarin-7-yl)sulfonium p-toluenesulfonate, a more preferable includes diphenyl(coumarin-7-yl)sulfonium trifluoromethanesulfonate and diphenyl(coumarin-7-yl)sulfonium hexafluorophosphate. The preferable specific example shown by the general formula [21] includes, for example, diphenyl(coumarin-2-thione-7-yl)sulfonium chloride, diphenyl(coumarin-2-thione-7-yl)sulfonium bromide, diphenyl(coumarin-2-thione-7-yl)sulfonium perchlorate, diphenyl(coumarin-2-thione-7-yl)sulfonium tetrafluoroborate, diphenyl(coumarin-2-thione-7-yl)sulfonium hexafluorophosphate, diphenyl(coumarin-2-thione-7-yl)sulfonium hexafluoroarsenate, diphenyl(coumarin-2-thione-7-yl)sulfonium hexafluoroantimonate, diphenyl(coumarin-2-thione-7-yl)sulfonium tetraphenylborate, diphenyl(coumarin-2-thione-7-yl)sulfonium tetrakis{3,5-bis(trifluoromethyl)phenyl}borate, diphenyl(coumarin-2-thione-7-yl)sulfonium tetrakis(pentafluorophenyl)borate, diphenyl(coumarin-2-thione-7-yl)sulfonium tetrafluorogallate, diphenyl(coumarin-2-thione-7-yl)sulfonium trifluoromethanesulfonate, diphenyl(coumarin-2-thione-7-yl)sulfonium nonafluorobutanesulfonate, diphenyl(coumarin-2-thione-7-yl)sulfonium perfluorooctanesulfonate, diphenyl(coumarin-2-thione-7-yl)sulfonium benzenesulfonate, diphenyl(coumarin-2-thione-7-yl)sulfonium p-toluenesulfonate, diphenyl(coumarin-2-thione-7-yl)sulfonium acetate, diphenyl(coumarin-2-thione-7-yl)sulfonium heptafluorobutanoate, diphenyl(coumarin-2-thione-7-yl)sulfonium perfluorooctanoate, bis(4-methylphenyl)(coumarin-2-thione-7-yl)sulfonium hexafluorophosphate, bis(4-methylphenyl)(coumarin-2-thione-7-yl)sulfonium tetraphenylborate, bis(4-methylphenyl)(coumarin-2-thione-7-yl)sulfonium trifluoromethanesulfonate, bis(4-methylphenyl)(coumarin-2-thione-7-yl)sulfonium nonafluorobutanesulfonate, bis(4-methylphenyl)(coumarin-2-thione-7-yl)sulfonium p-toluenesulfonate, diphenyl(coumarin-2-thione-5-yl)sulfonium hexafluorophosphate, diphenyl(coumarin-2-thione-5-yl)sulfonium tetraphenylborate, diphenyl(coumarin-2-thione-5-yl)sulfonium trifluoromethanesulfonate, diphenyl(coumarin-2-thione-5-yl)sulfonium nonafluorobutanesulfonate and diphenyl(coumarin-2-thione-5-yl)sulfonium p-toluenesulfonate, and among others, a preferable one includes, for example, diphenyl(coumarin-2-thione-7-yl)sulfonium hexafluorophosphate, diphenyl coumarin-2-thione-7-yl)sulfonium tetraphenylborate, diphenyl(coumarin-2-thione-7-yl)sulfonium trifluoromethanesulfonate, diphenyl(coumarin-2-thione-7-yl)sulfonium nonafluorobutanesulfonate and diphenyl(coumarin-2-thione-7-yl)sulfonium p-toluenesulfonate. The preferable specific example shown by the general formula [39] includes, for example, bis(xanthene-9-one-2-yl)iodonium chloride, bis(xanthene-9-one-2-yl)iodonium bromide, bis(xanthene-9-one-2-yl)iodonium perchlorate, bis(xanthene-9-one-2-yl)iodonium tetrafluoroborate, bis(xanthene-9-one-2-yl)iodonium hexafluorophosphate, bis(xanthene-9-one-2-yl)iodonium hexafluoroarsenate, bis(xanthene-9-one-2-yl)iodonium hexafluoroantimonate, bis(xanthene-9-one-2-yl)iodonium tetraphenylborate, bis(xanthene-9-one-2-yl)iodonium tetrakis{3,5-bis(trifluoromethyl)phenyl)borate, bis(xanthene-9-one-2-yl)iodonium tetrakis(pentafluorophenyl)borate, bis(xanthene-9-one-2-yl)iodonium tetraphenylgallate, bis(xanthene-9-one-2-yl)iodonium tetrakis(pentafluorophenyl)gallate, bis(xanthene-9-one-2-yl)iodonium trifluoromethanesulfonate, bis(xanthene-9-one-2-yl)iodonium nonafluorobutanesulfonate, bis(xanthene-9-one-2-yl)iodonium perfluorooctanesulfonate, bis(xanthene-9-one-2-yl)iodonium benzenesulfonate, bis(xanthene-9-one-2-yl)iodonium p-toluenesulfonate, bis(xanthene-9-one-2-yl)iodonium 4-dodecylbenzenesulfonate, bis(xanthene-9-one-2-yl)iodonium 4-fluorobenzenesulfonate, bis(xanthene-9-one-2-yl)iodonium 2,4-difluorobenzenesulfonate, bis(xanthene-9-one-2-yl)iodonium pentafluorobenzenesulfonate, bis(xanthene-9-one-2-yl)iodonium 4-trifluoromethylbenzenesulfonate, bis(xanthene-9-one-2-yl)iodonium 3,5-bis(trifluoromethyl)benzenesulfonate, bis(xanthene-9-one-2-yl)iodonium acetate, bis(xanthene-9-one-2-yl)iodonium pentafluorobutanoate, bis(xanthene-9-one-2-yl)iodonium perfluorooctanoate and bis(xanthene-9-one-2-yl)iodonium perfluorododecanoate, and among others, a preferable one includes, for example, bis(xanthene-9-one-2-yl)iodonium hexafluorophosphate, bis(xanthene-9-one-2-yl)iodonium tetraphenylborate, bis(xanthene-9-one-2-yl)iodonium trifluoromethanesulfonate, bis(xanthene-9-one-2-yl)iodonium nonafluorobutanesulfonate and bis(xanthene-9-one-2-yl)iodonium p-toluenesulfonate, a more preferable one includes bis(xanthene-9-one-2-yl)iodonium hexafluorophosphate. The preferable specific example shown by the general formula [40] includes, for example, bis(coumarin-7-yl)iodonium chloride, bis(coumarin-7-yl)iodonium bromide, bis(coumarin-7-yl)iodonium perchlorate, bis(coumarin-7-yl)iodonium tetrafluoroborate, bis(coumarin-7-yl)iodonium hexafluorophosphate, bis(coumarin-7-yl)iodonium hexafluoroarsenate, bis(coumarin-7-yl)iodonium hexafluoroantimonate, bis(coumarin-7-yl)iodonium tetraphenylborate, bis(coumarin-7-yl)iodonium tetrakis(3,5-bis(trifluoromethyl)phenyl}borate, bis(coumarin-7-yl)iodonium tetrakis(pentafluorophenyl)borate, bis(coumarin-7-yl)iodonium tetraphenylgallate, bis(coumarin-7-yl)iodonium tetrakis(pentafluorophenyl)gallate, bis(coumarin-7-yl)iodonium trifluoromethanesulfonate, bis(coumarin-7-yl)iodonium nonafluorobutanesulfonate, bis(coumarin-7-yl)iodonium perfluorooctanesulfonate, bis(coumarin-7-yl)iodonium benzenesulfonate, bis(coumarin-7-yl)iodonium p-toluenesulfonate, bis(coumarin-7-yl)iodonium 4-dodecylbenzenesulfonate, bis(coumarin-7-yl)iodonium 4-fluorobenzenesulfonate, bis(coumarin-7-yl)iodonium 2,4-difluorobenzenesulfonate, bis(coumarin-7-yl)iodonium pentafluorobenzenesulfonate, bis(coumarin-7-yl)iodonium 4-trifluoromethylbenzenesulfonate, bis(coumarin-7-yl)iodonium 3,5-bis(trifluoromethyl)benzenesulfonate, bis(coumarin-7-yl)iodonium acetate, bis(coumarin-7-yl)iodonium pentafluorobutanoate, bis(coumarin-7-yl)iodonium perfluorooctanoate and bis(coumarin-7-yl)iodonium perfluorododecanate, and among others, a preferable one includes, for example, bis(coumarin-7-yl)iodonium hexafluorophosphate, bis(coumarin-7-yl)iodonium tetraphenylborate, bis(coumarin-7-yl)iodonium trifluoromethanesulfonate, bis(coumarin-7-yl)iodonium nonafluorobutanesulfonate and bis(coumarin-7-yl)iodonium p-toluenesulfonate. The preferable specific example shown by the general formula [41] includes, for example, (coumarin-7-yl)(xanthene-9-one-2-yl)iodonium chloride, (coumarin-7-yl)(xanthene-9-one-2-yl)iodonium bromide, (coumarin-7-yl) (xanthene-9-one-2-yl)iodonium tetrafluoroborate, (coumarin-7-yl)(xanthene-9-one-2-yl)iodonium hexafluorophosphate, (coumarin-7-yl)(xanthene-9-one-2-yl)iodonium hexafluoroarsenate, (coumarin-7-yl)(xanthene-9-one-2-yl)iodonium hexafluoroantimonate, (coumarin-7-yl) (xanthene-9-one-2-yl)iodonium tetraphenylgallate, (coumarin-7-yl)(xanthene-9-one-2-yl)iodonium tetraphenylborate, (coumarin-7-yl)(xanthene-9-one-2-yl)iodonium tetrakis{3,5-bis(trifluoromethyl)phenyl}borate, (coumarin-7-yl)(xanthene-9-one-2-yl)iodonium tetrakis(pentafluorophenyl)borate, (coumarin-7-yl)(xanthene-9-one-2-yl)iodonium tetraphenylgallate, (coumarin-7-yl)(xanthene-9-one-2-yl)iodonium tetrakis(pentafluorophenyl)gallate, (coumarin-7-yl)(xanthene-9-one-2-yl)iodonium, trifluoromethanesulfonate, (coumarin-7-yl)(xanthene-9-one-2-yl)iodonium nonafluorobutanesulfonate, (coumarin-7-yl)(xanthene-9-one-2-yl)iodonium perfluorooctanesulfonate, (coumarin-7-yl)(xanthene-9-one-2-yl)iodonium benzenesulfonate, (coumarin-7-yl) (xanthene-9-one-2-yl)iodonium p-toluenesulfonate, (coumarin-7-yl) (xanthene-9-one-2-yl)iodonium 4-dodecylbenzenesulfonate, (coumarin-7-yl)(xanthene-9-one-2-yl)iodonium 4-fluorobenzenesulfonate, (coumarin-7-yl)(xanthene-9-one-2-yl)iodonium 2,4-difluorobenzenesulfonate, (coumarin-7-yl)(xanthene-9-one-2-yl)iodonium pentafluorobenzenesulfonate, (coumarin-7-yl)(xanthene-9-one-2-yl)iodonium 4-trifluoromethylbenzenesulfonate, (coumarin-7-yl)(xanthene-9-one-2-yl)iodonium 3,5-bis(trifluoromethyl)benzenesulfonate, (coumarin-7-yl)(xanthene-9-one-2-yl)iodonium acetate, (coumarin-7-yl)(xanthene-9-one-2-yl)iodonium pentafluorobutanoate, (coumarin-7-yl)(xanthene-9-one-2-yl)iodonium perfluorooctanoate and (coumarin-7-yl) (xanthene-9-one-2-yl)iodonium perfluorododecanoate, and among others, a preferable one includes, for example, (coumarin-7-yl) (xanthene-9-one-2-yl)iodonium hexafluorophosphate, (coumarin-7-yl)(xanthene-9-one-2-yl)iodonium tetraphenylborate, (coumarin-7-yl)(xanthene-9-one-2-yl)iodonium trifluoromethanesulfonate, (coumarin-7-yl)(xanthene-9-one-2-yl)iodonium nonafluorobutanesulfonate, (coumarin-7-yl)(xanthene-9-one-2-yl)iodonium p-toluenesulfonate, and a more preferable one includes (coumarin-7-yl)(xanthene-9-one-2-yl)iodonium hexafluorophosphate. The preferable specific example shown by the general formula [42] includes, for example, 2-(phenyliodonio)xanthene-9-one hexafluorophosphate, 2-(phenyliodonio)xanthene-9-one hexafluoroarsenate, 2-(phenyliodonio)xanthene-9-one hexafluoroantimonate, 2-(phenyliodonio)xanthene-9-one tetrafluoroborate, 2-(phenyliodonio)xanthene-9-one tetrakis{3,5-bis(trimethyl)phenyl}borate, 2-(phenyliodonio)xanthene-9-one tetrakis(pentafluorophenyl)borate, 2-(phenyliodonio)xanthene-9-one tetraphenylgallate, 2-(phenyliodonio)xanthene-9-one trifluoromethanesulfonate, 2-(phenyliodonio)xanthene-9-one nonafluorobutanesulfonate, 2-(phenyliodonio)xanthene-9-one perfluorooctanesulfonate, 2-(phenyliodonio)xanthene-9-one benzenesulfonate, 2-(phenyliodonio)xanthene-9-one p-toluenesulfonate, 2-(phenyliodonio)xanthene-9-one p-dodecylbenzenesulfonate, 2-(phenyliodonio)xanthene-9-one 4-fluorobenzenesulfonate, 2-(phenyliodonio)xanthene-9-one 2,4-difluorobenzenesulfonate, 2-(phenyliodonio)xanthene-9-one pentafluorobenzenesulfonate, 2-(phenyliodonio)xanthene-9-one acetate, 2-(phenyliodonio)xanthene-9-one pentafluorobutanoate, 2-(phenyliodonio)xanthene-9-one perfluorooctanoate and 2-(phenyliodonio)xanthene-9-one perfluorodecanoate, and among others a preferable one includes, for example, 2-(phenyliodonio)xanthene-9-one hexafluorophosphate, 2-(phenyliodonio)xanthene-9-one tetraphenylborate, 2-(phenyliodonio)xanthene-9-one trifluoromethanesulfonate, 2-(phenyliodonio)xanthene-9-one nonafluorobutanesulfonate and 2-(phenyliodonio)xanthene-9-one p-toluenesulfonate, and a more preferable one includes 2-(phenyliodonio)xanthene-9-one hexafluorophosphate. The preferable specific example shown by the general formula [43] includes, for example, 7-(phenyliodonio)coumarin hexafluorophosphate, 7-(phenyliodonio) coumarin hexafluoroarsenate, 7-(phenyliodonio)coumarin hexafluoroantimonate, 7-(phenyliodonio)coumarin tetraphenylborate, 7-(phenyliodonio)coumarin trifluoromethanesulfonate, 7-(phenyliodonio)coumarin nonafluorobutanesulfonate, 7-(phenyliodonio)coumarin p-toluenesulfonate, 7-(p-methylphenyliodonio)coumarin hexafluorophosphate, 7-(p-methylphenyliodonio)coumarin hexafluoroarsenate, 7-(p-methylphenyliodonio)coumarin hexafluoroantimonate, 7-(p-methylphenyliodonio)coumarin tetraphenylborate, 7-(p-methylphenyliodonio)coumarin trifluoromethanesulfonate, 7-(phenyliodonio)coumarin nonafluorobutanesulfonate and 7-(p-methylphenyliodonio)coumarin p-toluenesulfonate and among others, for example, 7-(phenyliodonio)coumarin hexafluorophosphate is preferable. The sulfonium salt shown by the general formula [1] can be synthesized by, for example, the following [A], [B] and [C] methods. (wherein M is a metal atom; X and X′ is a halogen atom; and R, R1, R2, A, m and n have the same meaning as above). The iodonium salt shown by the general formula [35] can be synthesized by, for example, the following [D], [E] and [F] methods. (wherein one of R29 and R30 is a group shown by the general formula [2] and the other is a group shown by the general formula [3]; R31 is a lower alkyl group or a lower haloalkyl group; R32 is a lower alkyl group or a lower haloalkyl group; M′ is an alkali metal atom; A6 is a halogen atom, a hydrogen sulfate ion or an anion derived from a perfluoroalkylcarboxylic acid; A3′ is an objective anion; and R28, M and u have the same meaning as above.) The metal atom shown by M includes, for example, a silver atom, a lithium atom, a sodium atom, a potassium atom, a rubidium atom and a cesium atom, and among others, a silver atom is preferable. The halogen atom shown by X and X′ includes, for example, a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. The alkali metal atom shown by M′ includes, for example, a lithium atom, a sodium atom, a potassium atom, a rubidium atom and a cesium atom, and among others, a lithium atom, a sodium atom and a potassium atom are preferable. The lower alkyl group shown by R31 and R32 may be straight chained, branched or cyclic and includes one having generally 1 to 6, preferably 1 to 4 carbon atoms, which is specifically exemplified by the same as examples of the alkyl group having 1 to 6 carbon atoms among the alkyl group which may have a halogen atom or an aryl group as a substituent, shown by the above-mentioned R1 to R6 and among others, a preferable one includes, for example, a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group and a tert-butyl group and a more preferable one includes a methyl group and an ethyl group. The lower haloalkyl group shown by R31 and R32 may be straight chained, branched or cyclic, and includes one, wherein a part of or all of hydrogen atoms of the lower alkyl group having generally 1 to 6, preferably 1 to 4 carbon atoms, shown by the above-mentioned R3 are substituted by a halogen atom (e.g. a fluorine atom, a chlorine atom, a bromine atom and an iodine atom), which is specifically exemplified by the same as examples of the lower haloalkyl group as the substituent of the aryl group which may have a substituent selected from a lower haloalkyl group, a halogen atom, a nitro group and a cyano group, shown by the above-mentioned R7, and among others, a trifluoromethyl group and a pentafluoroethyl group are preferable. The halogen atom shown by A6 includes, for example, a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, and among others, a chlorine atom and a bromine atom are preferable. The anion derived from the perfluoroalkylcarboxylic acid shown by A6 includes, for example, one derived from a trifluoroacetic acid and a pentafluoropropionic acid. The peracid shown by the general formula [46] includes, for example, peracetic acid, perpropionic acid and trifluoroperacetic acid. Those peracid may be a commercial product or suitably be synthesized according to common methods such as a reaction of carboxylic anhydrides such as acetic anhydride, propionic anhydride and trifluoroacetic anhydride with hydrogen peroxide. The compound shown by the general formulae [23], [25], [44], [48], [50] and [52] may be a commercial product or may suitably be synthesized according to common methods. Namely, a synthesis method for a sulfonium salt of the present invention is explained in detail. In a method [A], a sulfoxide shown by the general formula [22], synthesized by a common method (see Ber., 23, 1844 (1890), J. Chem. Soc. (C), 2424 (1969)) is dissolved in a solvent such as ethers including ethyl ether, isopropyl ether, tetrahydrofuran and 1,2-dimethoxyethane; hydrocarbons including hexane and heptane; and aromatic hydrocarbons including benzene and nitrobenzene, or a mixed solvent consisting of the above solvent and halogenated hydrocarbons such as methylene chloride, methylene bromide, 1,2-dichloroethane and chloroform, and a compound shown by the general formula [23] in an amount of 1 to 10 mole parts, (hereinafter in the description on methods [A], [B] and [C], “mole parts”, means how many mole parts relative to 1 mole part of a raw compound such as a sulfoxide shown by the general formula [22]), trifluoromethanesulfonic anhydride in an amount of 1 to 3 mole parts of, or trifluoromethane sulfonic acid in an amount of 1 to 3 mole parts, and trifluoroacetic anhydride in an amount of 1 to 3 mole parts, relative to the sulfoxide shown by the general formula [22], are added thereto at −80 to 30° C., followed by allowing a reaction to take place at −80 to 30° C. for 0.5 to 10 hours with stirring to obtain a compound shown by the general formula [24]. Then, the obtained compound shown by the general formula [24] is dissolved in an aqueous solution of an alcohol such as methanol, ethanol and isopropanol, and treated with an anion exchange resin, and then an acid (HA) in an amount of 0.9 to 1.5 mole parts is added thereto. After removing the alcohol, the resultant is redissolved in an organic solvent such as methylene chloride, 1,2-dichloroethane, ethyl acetate, butyl acetate, propylene glycol monomethyl ether acetate, methyl isobutyl ketone and methyl ethyl ketone, followed by washing with water and concentrating under reduced pressure to obtain the compound of the present invention, shown by the general formula [1]. In another method, the obtained compound shown by the general formula [24] is dissolved in an organic solvent such as methylene chloride, 1,2-dichloroethane, ethyl acetate, butyl acetate, propylene glycol monomethyl ether acetate, methyl isobutyl ketone and methyl ethyl ketone, and an acid salt (MA) in an amount of 0.9 to 1.5 mole parts is added thereto, followed by allowing a reaction to take place at 5 to 30° C. for 0.5 to 10 hours with stirring, removing a water layer, washing with water and concentrating under reduced pressure to obtain the compound shown by the general formula [1]. In a method [B], a sulfoxide shown by the general formula [22] is dissolved in ethers such as ethyl ether, isopropyl ether, tetrahydrofuran and 1,2-dimethyl ether or a mixed solvent consisting of the ethers and halogenated hydrocarbons such as methylene chloride, methylene bromide, 1,2-dichloroethane and chloroform or aromatic hydrocarbons such as benzene, toluene and xylene, and Grignard reagent (RMgX) in an amount of 0.5 to 3 mole parts, shown by the general formula [25] is added thereto, if necessary, in the presence of a catalyst such as trimethylsilyl triflate and trimethylsilyl chloride at −70 to 50° C., followed by allowing a reaction to take place at −70 to 50° C. for 0.5 to 10 hours with stirring. After completion of the reaction, the reaction solution is treated with an aqueous solution of hydrohalic acid (HX′) such as an aqueous solution of hydrobromic acid, hydrochloric acid and hydroiodic acid to obtain a compound shown by the general formula [26]. Then, the obtained compound is dissolved in alcohols such as methanol, ethanol and isopropanol, followed by treatment with silver oxide, an acid (HA) in an amount of 0.9 to 1.5 mole parts is added thereto. After removing the alcohol, the resultant is redissolved in an organic solvent such as methylene chloride, 1,2-dichloroethane, ethyl acetate, butyl acetate, propylene glycol monomethyl ether acetate, methyl isobutyl ketone and methyl ethyl ketone, followed by washing with water and concentrating under reduced pressure to obtain a compound of the present invention, shown by the general formula [1]. In another method, the obtained compound shown by the general formula [26] is dissolved in an organic solvent such as methylene chloride, 1,2-dichloroethane, ethyl acetate, butyl acetate, propylene glycol monomethyl ether acetate, methyl isobutyl ketone and methyl ethyl ketone, and an aqueous solution of an acid salt (MA) in an amount of 0.9 to 1.5 mole parts is added thereto, followed by allowing a reaction to take place at 5 to 30° C. for 0.5 to 10 hours with stirring, removing a water layer, washing with water and concentrating under reduced pressure to obtain the compound of the present invention, shown by the general formula [1]. In a method [C], a compound shown by the general formula [22] is reacted with a compound shown by the general formula [23] in an amount of 1 to 50 mole parts and Lewis acid such as a halogenated aluminum (e.g. aluminum chloride, aluminum bromide and aluminum iodide), a halogenated boron (e.g. boron trifluoride and boron tribromide) and a trihalogenated metal (e.g. iron trichloride, iron tribromide, titanium tribromide, titanium trichloride and titanium tribromide) in an amount of 1 to 10 mole parts at −20 to 180° C. for 0.5 to 24 hours with stirring, followed by treating with an aqueous solution of hydrohalic acid (HX) such as an aqueous solution of hydrobromic acid, hydrochloric acid and hydroiodic acid to obtain the compound shown by the general formula [26]. Then, the obtained compound is dissolved in alcohols such as methanol, ethanol and isopropanol, and treated with silver oxide, and then an acid (HA) in an amount of 0.9 to 1.5 mole parts is added thereto. After removing the alcohol, redissolving in an organic solvent such as methylene chloride, 1,2-dichloroethane, ethyl acetate, butyl acetate, propylene glycol monomethyl ether acetate, methyl isobutyl ketone and methyl ethyl ketone, washing with water and concentrating under reduced pressure to obtain the compound of the present invention, shown by the general formula [1]. In another method, the obtained compound shown by the general formula [26] is dissolved in an organic solvent such as methylene chloride, 1,2-dichloroethane, ethyl acetate, butyl acetate, propylene glycol monomethyl ether acetate, methyl isobutyl ketone and methyl ethyl ketone, and an aqueous solution of an acid salt (MA) in an amount of 0.9 to 1.5 mole parts is added thereto, followed by allowing a reaction to take place at 5 to 30° C. for 0.5 to 10 hours with stirring, removing a water layer, washing with water and concentrating under reduced pressure to obtain the compound of the present invention, shown by the general formula [1]. Compounds shown by the general formulae [24] and [26], obtained by the above-mentioned methods [A], [B] and [C] are also included in sulfonium salts of the present invention, shown by the general formula [1]. Further, a synthesis method for an iodonium salt of the present invention is explained described bellow in detail. In a method [D], a heterocycle-containing aromatic compound shown by the general formula [44] is dissolved in carboxylic anhydrides such as acetic anhydride and propionic anhydride or a mixed solvent consisting of the carboxylic anhydrides and halogenated hydrocarbons such as methylene chloride, methylene bromide, 1,2-dichloroethane and chloroform, and an iodate salt (M′IO3) in an amount of 0.4 to 0.6 mole parts, relative to the compound shown by the general formula [44] (hereinafter in the description on methods [D], [E] and [F], “mole parts” means how many mole parts relative to 1 mole part of the raw compound shown by the general formula [44]) at −70 to 30° C., and then a compound (HA6) such as concentrated sulfuric acid in an amount of 1 to 10 times moles of or a mixed acid consisting of the HA6 and a carboxylic anhydride such as acetic anhydride, propionic anhydride, trifluoroacetic anhydride is added dropwise thereto at −70 to 30° C. for 0.5 to 10 hours, followed by allowing a reaction to take place at −70 to 30° C. for 0.5 to 10 hours with stirring. After completion of the reaction, the reaction solution is poured at 0 to 30° C. into ice water, followed by extracting with halogenated hydrocarbons such as methylene chloride, methylene bromide, 1,2-dichloroethane and chloroform, and concentrating to obtain a compound shown by the general formula [45]. Then the obtained compound shown by the general formula [45] is dissolved in halogenated hydrocarbons such as methylene chloride, methylene bromide, 1,2-dichloroethane and chloroform, and an aqueous solution of a compound (MA3′) in an amount of 1 to 10 mole parts is poured thereto, followed by allowing a reaction to take place at 0 to 30° C. for 0.5 to 10 hours with stirring to obtain an iodonium salt having a desired counter anion A3′, shown by the general formula [35-1]. In a method [E], an iodized heterocycle-containing aromatic compound shown by the general formula [52] is reacted with a peracid shown by the general formula [46] to synthesize a compound shown by the general formula [47]. Then the obtained compound shown by the general formula [47] is dissolved in carboxylic anhydrides such as acetic anhydride and propionic anhydride, or a mixed solvent consisting of the carboxylic anhydrides and halogenated hydrocarbons such as methylene chloride, methylene bromide, 1,2-dichloroethane and chloroform, and a heterocycle-containing aromatic compound shown by the general formula [48], in an amount of 1 to 10 mole parts is added thereto at −80 to 30° C., and then a compound (HA6) in an amount of 1 to 10 mole parts is added dropwise thereto at −80 to 30° C. for 0.5 to 10 hours, followed by allowing a reaction to take place at −80 to 30° C. for 0.5 to 10 hours with stirring to obtain a compound shown by the general formula [49]. Then the obtained compound shown by the general formula [49] is dissolved in halogenated hydrocarbons such as methylene chloride, methylene bromide, 1,2-dichloroethane and chloroform, and a solution of a compound (MA3′) in an amount of 1 to 10 mole parts is poured thereto, followed by allowing a reaction to take place at 0 to 30° C. for 0.5 to 10 hours with stirring to obtain an iodonium salt having a desired counter anion A3′, shown by the general formula [35-2]. In a method [F], an iodoaryl compound shown by the general formula [50] is reacted with a peracid shown by the general formula [46] to synthesize a compound shown by the general formula [51]. Then a heterocycle-containing aromatic compound shown by the general formula [44] is dissolved in carboxylic anhydrides such as acetic anhydride and propionic anhydride or a mixed solvent consisting of the carboxylic anhydrides and halogenated hydrocarbons such as methylene chloride, methylene bromide, 1,2-dichloroethane and chloroform, and a compound shown by the general formula [51] in an amount of 1 to 10 mole parts is added thereto at −80 to 30° C., and then a compound (HA6) in an amount of 1 to 10 mole parts is added dropwise thereto at −80 to 30° C. for 0.5 to 10 hours, followed by allowing a reaction to take place at −80 to 30° C. for 0.5 to 10 hours with stirring to obtain a compound shown by the general formula [53]. Then the obtained compound shown by the general formula [53] is dissolved in halogenated hydrocarbons such as methylene chloride, methylene bromide, 1,2-dichloroethane and chloroform, and then a solution of a compound (MA3′) in an amount of 1 to 10 mole parts is poured thereto, followed by allowing a reaction to take place at 0 to 30° C. for 0.5 to 10 hours with stirring to obtain an iodonium salt having a desired counter anion A3′, shown by the general formula [35-3]. Compounds shown by the general formulae [45], [49] and [53], obtained by the above-mentioned methods [D], [E] and [F] and are also included in iodonium salts of the present invention, shown by the general formula [35]. Among sulfonium salts of the present invention, shown by the general formula [1] and iodnium salts of the present invention, shown by the general formula [35], those with a halogen atom as an anion, shown by A and A are useful as raw materials for various onium salts of the present invention, on the other hand, those with an anion derived from an inorganic strong acid, a sulfonic acid and a compound shown by the above-mentioned general formula [4] are useful as cationic photopolymerization initiators and those with an anion derived from an inorganic strong acid, an organic acid and a compound shown by the above-mentioned general formula [4] have superior effects as acid generators composing a resist composition used for manufacturing liquid crystal panel, various semiconductor elements and printed circuit boards, and printing materials such as PS boards and CTP boards. <1> First, use of a sulfonium salt and an iodnium salt of the present invention as a cationic photopolymerization initiator will be explained. The preferable sulfonium salt of the present invention useful as a cationic photopolymerization initiator includes, for example, one shown by the general formula [8]: (wherein A1 is an anion derived from an inorganic strong acid, a sulfonic acid or a compound shown by the above-mentioned general formula [4]; and R, R, R2, m and n have the same meaning as above.), and among others, sulfonium salts wherein A1 is an anion derived from a compound shown by the general formulae [4] and [5] are preferable. The preferable iodonium salt of the present invention useful as a cationic photopolymerization initiator includes, for example, one shown by the general formula [37]: (wherein A4 is an anion derived from an inorganic strong acid, a sulfonic acid or a compound shown by the general formula [4]; and R26, R27 and others are the same as described above), and among others, iodonium salts wherein A4 is an anion derived from a compound-shown by the general formulae [4] and [5] are preferable. The sulfonium salt and the iodonium salt of the present invention (hereinafter collectively abbreviated as onium salts) generate an acid by irradiation with light, whereby polymerization rapidly proceeds if a various kind of epoxy monomers or vinyl ether monomers exist in the reaction system. Polymerization or copolymerization of an epoxy monomer or a vinyl ether monomer by using the onium salt of the present invention, shown by the general formula [8] or [37], as a polymerization initiator can be performed by a common polymerization reaction of the onium salt of the present invention, shown by the general formula [8] or [37], and these various monomers in a suitable solvent or without using a solvent under inert gas atmosphere, if necessary. The epoxy monomer includes, for example, one shown by the general formula [27]: [wherein R10 and R11 are each independently a hydrogen atom, a lower alkyl group, an aryl group or a carboxyl group; R12 is a hydrogen atom, an alkyl group, a lower haloalkyl group, a lower hydroxyalkyl group, an aryl group, a lower alkoxycarbonyl group, a carboxyl group, a group shown by the general formula [28]: —CH2-E-R13 [28] (wherein E is an oxygen atom or a —OCO— group; and R13 is an alkyl group, a lower alkenyl group or an aryl group), an epoxyethyl group or an epoxycyclohexyl group; and R10 and R12 may form an aliphatic ring together with the adjacent carbon atoms] and one shown by the general formula [29]: (wherein R14 to R16 are each independently a lower alkylene chain; and s is an integer of 0 or 1). In the general formula [27], the lower alkyl group shown by R10 and R11 may be straight chained, branched or cyclic, and includes one having generally 1 to 6, preferably 1 to 3 carbon atoms, which is specifically exemplified by a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a n-pentyl group, an isopentyl group, a sec-pentyl group, a tert-pentyl group, a neopentyl group, a n-hexyl group, an isohexyl group, a sec-hexyl group, a tert-hexyl group, a neohexyl group, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group and a cyclohexyl group. In the general formulae [27] and [28], the aryl group shown by R10 to R13 includes one having generally 6 to 15, preferably 6 to 10 carbon atoms, which is specifically exemplified by a phenyl group, a naphtyl group, an anthryl group and a phenanthryl group. The alkyl group shown by R12 and R13 may be straight chained, branched or cyclic, and includes one having generally 1 to 18, preferably 1 to 16 carbon atoms, which is specifically exemplified by the same as ecamples of the lower alkyl group shown by R10 and R11, a n-heptyl group, an isoheptyl group, a sec-heptyl group, a tert-heptyl group, a neoheptyl group, a n-octyl group, an isooctyl group, a sec-octyl group, a tert-octyl group, a neooctyl group, a n-nonyl group, an isononyl group, a sec-nonyl group, a tert-nonyl group, a neononyl group, a n-decyl group, an isodecyl group, a sec-decyl group, a tert-decyl group, a neodecyl group, a n-undecyl group, an isoundecyl group, a sec-undecyl group, a tert-undecyl group, a neoundecyl group, a n-dodecyl group, an isododecyl group, a sec-dodecyl group, a tert-dodecyl group, a neododecyl group, a n-tridecyl group, an isotridecyl group, a sec-tridecyl group, a tert-tridecyl group, a neotridecyl group, a n-tetradecyl group, an isotetradecyl group, a sec-tetradecyl group, a tert-tetradecyl group, a neotetradecyl group, a n-pentadecyl group, an isopentadecyl group, a sec-pentadecyl group, a tert-pentadecyl group, a neopentadecyl group, a n-hexadecyl group, an isohexadecyl group, a sec-hexadecyl group, a tert-hexadecyl group, a neohexadecyl group, a n-heptadecyl group, an isoheptadecyl group, a sec-heptadecyl group, a tert-heptadecyl group, a neoheptadecyl group, a n-octadecyl group, an isooctadecyl group, a sec-octadecyl group, a tert-octadecyl group, a neooctadecyl group, a cycloheptyl group, a cyclooctyl group, a cyclononyl-group and a cyclodecyl group. In the general formula [27], the lower haloalkyl group shown by R12 includes one, wherein a part of or all of the hydrogen atoms of the lower alkyl group having 1 to 6, preferably 1 to 3 carbon atoms, shown by the above-mentioned R10 and R11, are substituted by a halogen atom (e.g. a fluorine atom, a chlorine atom, a bromine atom and an iodine atom), which is specifically exemplified by a fluoromethyl group, a chloromethyl group, a bromomethyl group, an iodomethyl group, a difluoromethyl group, a dichloromethyl group, a trifluoromethyl group, a trichloromethyl group, a tribromomethyl group, a triiodomethyl group, a pentafluoroethyl group, a pentachloroethyl group, a pentabromoethyl group, a pentaiodoethyl group, a heptafluoropropyl group, a heptachloropropyl group, a heptabromopropyl group, a heptaiodopropyl group, a nonafluorobutyl group, a nonachlorobutyl group, a nonabromobutyl group, a nonaiodobutyl group, a perfluoropentyl group, a perchloropentyl group, a perfluorohexyl group and a perchlorohexyl group. The lower hydroxyalkyl group shown by R12 includes one, wherein the terminal hydrogen atom of the lower alkyl group shown by the above-mentioned R10 and R11, is substituted by a hydroxyl group. The lower alkoxycarbonyl group shown by R12 may be straight chained, branched or cyclic, and includes one having generally 2 to 7, preferably 2 to 4 carbon atoms, which is specifically exemplified by a methoxycarbonyl group, an ethoxycarbonyl group, a n-propoxycarbonyl group, an isopropoxycarbonyl group, a n-butoxycarbonyl group, an isobutoxycarbonyl group, a sec-butoxycarbonyl group, a tert-butoxycarbonyl group, a n-pentyloxycarbonyl group, an isopentyloxycarbonyl group, a sec-pentyloxycarbonyl group, a tert-pentyloxycarbonyl group, a neopentyloxycarbonyl group, a n-hexyloxycarbonyl group, an isohexyloxycarbonyl group, a sec-hexyloxycarbonyl group, a tert-hexyloxycarbonyl group, a neohexyloxycarbonyl group, a cyclopropyloxycarbonyl group, a cyclobutyloxycarbonyl group, a cyclopentyloxycarbonyl group and a cyclohexyloxycarbonyl group. In the general formula [28], the lower alkenyl group shown by R13 may be straight chained, branched or cyclic, and includes one having generally 2 to 6, preferably 2 to 3 carbon atoms, which is specifically exemplified by a vinyl group, an allyl group, a 1-propenyl group, an isopropenyl group, a 1-butenyl group, a 2-butenyl group, a 3-butenyl group, a 2-methylallyl group, a 1-pentenyl group, a 2-pentenyl group, a 3-pentenyl group, a 4-pentenyl group, a 2-methy-2-butenyl group, a 1-hexenyl group, a 2-hexenyl group, a 3-hexenyl group, a 5-hexenyl group, a 2-methyl-2-pentenyl group, a 1-cyclobutenyl group, a 1-cyclopentenyl group and a 1-cyclohexenyl group. The case where R10 and R12 form an aliphatic ring together with the adjacent carbon atoms includes a case where a saturated aliphatic ring having 5 to 10 carbon atoms is formed. The specific example s of these rings are a cyclopentane ring, a cyclohexane ring, a cycloheptane ring, a cyclooctane ring, a cyclononane ring and a cyclodecane ring. These aliphatic rings may further be condensed with an aromatic ring such as a benzene ring or a naphthalene ring. In the general formula [29], the lower alkelene chain shown by R14 to R16 includes one having generally 1 to 6, preferably 1 to 4 carbon atoms, which is specifically exemplified by a methylene group, an ethylene group, a trimethylene group, a tetramethylene group, a pentamethylene group and a hexamethylene group. The vinyl ether group includes one shown by the general formula [31]: [wherein R19 is a hydrogen atom or a lower alkyl group; and R20 is an alkyl group, a group shown by the formula [32]: or a group shown by the general formula [33]: —(R21—O)t-R22 [33] (where R21 is an alkylenen group; R22 is a hydrogen atom or a vinyl group; and t is an integer of 1 to 3.) In the general formula [31], the lower alkyl group shown by R19 may be straight chained, branched or cyclic and includes one having generally 1 to 6 carbon atoms, which is specifically exemplified by a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a n-pentyl group, an isopentyl group, a sec-pentyl group, a tert-pentyl group, a neopentyl group, a 2-methylbutyl group, a 1-ethylpropyl group, a n-hexyl group, an isohexyl group, a sec-hexyl group, a tert-hexyl group, a neohexyl group, a 2-methylpentyl group, a 3-methylpentyl group, a 1,2-dimethylbutyl group, a 2,2-dimethylbutyl group, a 1-ethylbutyl group, a 2-ethylbutyl group, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group and a cyclohexyl group. The alkyl group shown by R20 may be straight chained, branched or cyclic, and includes one having generally 1 to 15, preferably 1 to 12 carbon atoms, which is specifically exemplified by a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a n-pentyl group, an isopentyl group, a sec-pentyl group, a tert-pentyl group, a neopentyl group, a n-hexyl group, an isohexyl group, a sec-hexyl group, a tert-hexyl group, a neohexyl group, a n-heptyl group, an isoheptyl group, a sec-heptyl group, a tert-heptyl group, a neoheptyl group, a n-octyl group, an isooctyl group, a sec-octyl group, a tert-octyl group, a neooctyl group, a n-nonyl group, an isononyl group, a sec-nonyl group, a tert-nonyl group, a neononyl group, a n-decyl group, an isodecyl group, a sec-decyl group, a tert-decyl group, a neodecyl group, a n-undecyl group, an isoundecyl group, a sec-undecyl group, a tert-undecyl group, a neoundecyl group, a n-dodecyl group, an isododecyl group, a sec-dodecyl group, a tert-dodecyl group, a neododecyl group, a n-tridecyl group, an isotridecyl group, a sec-tridecyl group, a tert-tridecyl group, a neotridecyl group, a n-tetradecyl group, an isotetradecyl group, a sec-tetradecyl group, a tert-tetradecyl group, a neotetradecyl group, a n-pentadecyl group, an isopentadecyl group, a sec-pentadecyl group, a tert-pentadecyl group, a neopentadecyl group, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, a cyclooctyl group, a cyclononyl group and a cyclodecyl group. In the general formula [33], the alkylene group shown by R21 may be straight chained, branched or cyclic, and includes one having generally 2 to 10, preferably 2 to 8 carbon atoms, which is specifically exemplified by linear alkylene groups such as a methylene group, an ethylene group, a trimethylene group, a tetramethylene group, a pentamethylene group, a hexamethylene group, a heptamethylene group, an octamethylene group, a nonamethylene group and a decamethylene group; branched alkylene groups such as an ethylidene group, a propylene group, an isopropylidene group, a 1-methyltrimethylene group, a 2-methyltrimethylene group, a 1,1-dimethylethylene group, a 1,2-dimethylethylene group, an ethylethylene group, a 1-methyltetramethylene group, a 1,1-dimethyltrimethylene group, a 2,2-dimethyltrimethylene group, a 2-ethyltrimethylene group, a 1-methylpentamethylene group, a 2-methylpentamethylene group, a 1,3-dimethyltetramethylene group, a 3-ethyltetramethylene group, a 1-methylhexamethylene group, a 1-methylheptamethylene group, a 1,4-diethyltetramethylene group, a 2,4-dimethylheptamethylene group, a 1-methyloctamethylene group and a 1-methylnonamethylene group; and cyclic alkylene groups such as a cyclopropylene group, a 1,3-cyclobutylene group, a 1,3-cyclopentylene group, a 1,4-cyclohexylene group, a 1,5-cycloheptylene group, a 1,5-cyclooctylene group, a 1,5-cyclononylene group and a 1,6-cyclodecylene group. The specific examples of an epoxy monomer shown by the general formula [27] are, for example, epoxyalkanes such as ethylene oxide, 1,2-epoxypropane, 1,2-epoxybutane, 0,2,3-epoxybutane, 1,2-epoxypentane, 2,3-epoxypentane, 1,2-epoxyhexane, 1,2-epoxyheptane, 1,2-epoxyoctane, 1,2-epoxynonane, 1,2-epoxydecane, 1,2-epoxyundecane, 1,2-epoxydodecane, 1,2-epoxytridecane, 1,2-epoxytetradecane, 1,2-epoxyhexadecane, 1,2-epoxyheptadecane and 1,2-epoxyoctadecane; epoxyhaloalkanes such as 2,3-epoxy-1,1,1-trifluoropropane and 2,3-epoxy-1-chloropropane; epoxyalcohols such as 2,3-epoxypropanol; alkyl glycidyl ethers such as methyl glycidyl ether, ethyl glycidyl ether, propyl glycidyl ether, buthyl glycidyl ether, pentyl glycidyl ether, hexyl glycidyl ether, heptyl glycidyl ether, octyl glycidyl ether, nonyl glycidyl ether, decyl glycidyl ether, undecyl glycidyl ether and dodecyl glycidyl ether; aryl glycidyl ethers such as phenyl glycidyl ether and naphthyl glycidyl ether; alkenyl glycidyl ethers such as allyl glycidyl ether; glycidyl esters such as glycidyl methacrylate; 2,3-epoxyethylbenzene, α,α′-epoxybibenzyl, 2,3-epoxy-2,3-dihydro-1,4-naphthoquinone, epoxysuccinic acid, ethyl 2,3-epoxy-3-phenylbutyrate, 1,2,3,4-diepoxybutane and 1,2-epoxy-5-(epoxyethyl)cyclohexane. The specific examples of the epoxy monomer shown by the general formula [29] are, for example, bis(3,4-epoxycyclohexyl) adipate and 3,4-epoxycyclohexyl-3,4-epoxycyclohexane carboxylic acid. The specific examples of the vinyl ether monomer shown by the general formula [31] are, for example, alkyl vinyl ethers such as methyl vinyl ether, ethyl vinyl ether, propyl vinyl ether, isobutyl vinyl ether, 2-ethylhexyl vinyl ether, octadecyl vinyl ether, dodecyl vinyl ether and cyclohexyl vinyl ether; hydroxyalkyl vinyl ethers such as hydroxyethyl vinyl ether, hydroxybutyl vinyl ether, di(ethyleneglycol)monovinyl ether and 1,4-cyclohexanedimethanol monovinyl ether; divinyl ethers such as 1,4-butanediol divinyl ether, 1,6-hexanediol divinyl ether, 1,4-cyclohexanedimethanol divinyl ether, di(ethyleneglycol)divinyl ether, tri(ethyleneglycol)divinyl ether, di(proyleneglycol)divinyl ether and tri(proyleneglycol)divinyl ether; and propylene carbonate propenyl ether. These may be used alone or in a suitable combination of two or more kinds thereof. The above-mentioned polymerization method includes, for example, a solution polymerization, a bulk polymerization, a suspension polymerization and an emulsion polymerization. The solvent for polymerization includes, for example, halogenated hydrocarbons such as chloroform, methylene chloride and 1,2-dichloroethane, hydrocarbons such as toluene, benzene and xylene; N,N-dimethylformamide and dimethylsulfoxide. These solvents may be used alone or in a suitable combination of two or more kinds thereof. The polymerization is preferably carried out under an inert gas atmosphere. The inert gas includes, for example, nitrogen gas and argon gas. As amount of the onium salt of the present invention to be used, shown by the general formula [81 or [37] depends on kinds of monomer to be used and generally 0.1 to 200 wt %, preferably 1 to 50 wt % relative to various monomers. A concentration of the monomer in the polymerization depends on kindes of monomer to be used and generally 1 to 100 wt % (no solvent), preferably 10 to 80 wt %. A polymerization temperature is generally −78 to 120° C., preferably −20 to 50° C. A polymerization time depends reaction conditions such as a reaction temperature, kinds of an onium salt of the present invention and various monomers to be reacted or concentrations thereof, and generally 1 to 50 hours. Post-treatment after the reaction may be performed in accordance with common methods generally performed in this field. <2> Secondly, use of the onium salt of the present invention as an acid generator for a chemically amplified resist composition will be explained. The preferable sulfonium salt of the present invention used as an acid generator includes is, for example, one shown by the general formula [9]: (wherein A2 is an anion derived from an inorganic strong acid, an organic acid or a compound shown by the above-mentioned general formula [4]; and R, R1, R2, m and n have the same meaning as above), (among sulfonium salts shown by the general formula [1], corresponding to one wherein an anion shown by A is derived from an inorganic strong acid, an organic acid or a compound shown by the above-mentioned general formula [4]). The iodonium salt of the present invention used as an acid generator includes such one as shown by the general formula [38]: (wherein A5 is an anion derived from an inorganic strong acid, an organic acid or a compound shown by the above-mentioned general formula [4]; and R26, R27 and others meanings have the same as described above.) The onium salts of the present invention, shown by the general formulae [9] and [38] can be used alone as an acid generator, and more exellent effect can be expected by use of the salt in a combination with other acid generators. In particular, the onium salt of the present invention provides very superior effect as an acid generator when the salt is used in combination with an acid generator generating a weak acid such as a diazodisulfone compound having an alkyl group as a pending group. The diazodisulfone compound to be used in combination includes, for example, one shown by the general formula [30]: (wherein R17 and R18 are each independently an alkyl group.) In the general formula [30], the alkyl group shown by R17 may be straight chained, branched or cyclic, and includes one having generally 1 to 8, preferably 3 to 8 carbon atoms, and among others, preferably a branched or cyclic one, which is specifically exemplified by a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a n-pentyl group, an isopentyl group, a sec-pentyl group, a tert-pentyl group, a neopentyl group, a n-hexyl group, an isohexyl group, a sec-hexyl group, a tert-hexyl group, a neohexyl group, a 3-methylpentyl group, a 2-methylpentyl group, a 1,2-dimethylbutyl group, a n-heptyl group, an isoheptyl group, a sec-heptyl group, a tert-heptyl group, a neoheptyl group, a n-octyl group, an isooctyl group, a sec-octyl group, a tert-octyl group, a neooctyl group, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group and a cyclooctyl group. The alkyl group shown by R18 may be straight chained, branched or cyclic, and includes one having generally 3 to 8 carbon atoms, and among others, preferably a branched or cyclic one, which is specifically exemplified by an isopropyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, an isopentyl group, a sec-pentyl group, a tert-pentyl group, a neopentyl group, an isohexyl group, a sec-hexyl group, a tert-hexyl group, a neohexyl group, a 3-methylpentyl group, a 2-methylpentyl group, a 1,2-dimethylbutyl group, an isoheptyl group, a sec-heptyl group, a tert-heptyl group, a neoheptyl group, an isooctyl group, a sec-octyl group, a tert-octyl group, a neooctyl group, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group and a cyclooctyl group. The specific examples of the diazodisulfone compound shown by the general formula [30] are, for example, bis(1-methylethylsulfonyl)diazomethane, bis(1,1-dimethylethylsulfonyl)diazomethane, bis(cyclohexylsulfonyl)diazomethane, methylsulfonyl-1-methylethylsulfonyldiazomethane, methylsulfonyl-1,1-dimethylethylsulfonyldiazomethane, methylsulfonylcyclohexylsulfonyldiazomethane, ethylsulfonyl-1-methylethylsulfonyldiazomethane, ethylsulfonyl-1,1-dimethylethylsulfonyldiazomethane, ethylsulfonylcyclohexylsulfonyldiazomethane, bis(octanesulfonyl)diazomethane, methylethylsulfonyl-1,1-dimethylethylsulfonyldiazomethane, 1-methylethylsulfonyl]cyclohexylsulfonyldiazomethane and 1,1-dimethylethylsulfonylcyclohexylsulfonyldiazomethane. An amount of the onium salt of the present invention to be used, shown by the general formulae [9] and [38] is, when used alone, generally 0.1 to 10 wt %, preferably 0.5 to 5 wt %, relative to the resin amount of a chemically amplified resist composition, and when used together with other kind of acid generators, 0.05 to 5 wt %, preferably 0.1 to 3 wt % relative to the resin amount, while an amount of other kind of acid generators is generally 1 to 10 wt %, preferably 3 to 7 wt % relative to the resin amount. The onium salt of the present invention, shown by the general formulae [9] and [38], can generate an acid by irradiation with light from a high pressure mercury lamp and a metal halide lamp, deep UV rays, KrF excimer laser, ArF excimer laser, F2 excimer laser (157 nm), electron beams (EB) and soft X-rays. Therefore, the onium salt of the present invention, shown by the general formulae [9] and [38] is useful as an acid generator for a resist by irradiation with light from high pressure mercury lamp and metal halide lamp, deep UV rays, KrF excimer laser, ArF excimer laser, F2 excimer laser (157 nm), electron beams and soft X-rays, in particular, light from a high pressure mercury lamp and a metal halide lamp. Since the onium salt of the present invention, shown by the general formulae [8], [9], [37] and [38] has a heterocycle in the cation moiety, it provides higher absorption wavelength region than conventional onium salts and provides an improved acid generation efficiency by irradiation with, for example, light from a high pressure mercury lamp or a metal halide lamp, UV rays, far ultraviolet ray, KrF excimer laser, ArF excimer laser, F2 excimer laser, electron beams, X-rays and radiactive rays. In particular, since these compounds have absorption wavelength, at wavelength region of light, for example, from a high pressure mercury lamp and a metal halide lamp, use of these as light source can generate an acid effectively without the addition of a conventional sensitizer. The onium salt of the present invention has little absorption in wavelength region not shorter than 400 nm, which provides good transparency in the visible light region. Therefore, use of these as a cationic photopolymerization initiator for such as coating materials, adhesives and paints provides good effect of remaining nearly uneffected by transparency of a obtained polymer. Further, among iodonium salts of the present invention, shown by the general formulae [37] and [38], one having two heterocycles in the cation moiety has improved light absorption efficiency, when a high pressure mercury lamp or a metal halide lamp is used as light source, therefore use of these as light source can provide higher acid generation efficiency. The onium salt of the present invention, shown by the general formulae [8], [9], [37] and [38] can form a polymer with high hardness even when PF6− is used as a counter anion without having such a problem that conventional sulfonium salts and iodonium salts, wherein a counter anion thereof is PF6−, photocuring is significantly lowered. On the other hand, 2-(phenyliodonium)xanthene-9-one tetrafluoroborate (BF4−), as an analogous compound of the present invention, is an iodonium salt having one heterocycle at the cation moiety, however, one having as an anion BF4−, which is derived from a weak acid among an inorganic strong acid, therefore, is has drawbacks that acid generation efficiency is low and use of a sensitizer is required, when a high pressure mercury lamp or a metal halide lamp is used as light source. Therefore, use of an onium salt shown by the above-mentioned general formulae [8] and [37] as a cationic photopolymerization initiator can form a polymer with good transparency and high hardness, on the other hand, use of an onium salt shown by the above-mentioned general formulae [9] and [38] as an acid generator for a resist can provide a resist composition with high sensitivity. In the following, the present invention is explained in further detail referring to examples, but the present invention is not limited thereto by any means. EXAMPLE Example 1 Synthesis of diphenyl(coumarin-7-yl)sulfonium trifluoromethanesulfonate To 160 ml of dichloromethane were dissolved 20.2 g (0.1 mol) of diphenylsulfoxide and 17.5 g (0.12 mol) of coumarin, and 28.2 g (0.1 mol) of trifluoromethanesulfonic anhydride was added dropwise thereto at −70 to −60° C., followed by gradually warming to room temperature and reacting with stirring for 2 hours. After completion of the reaction, the obtained reaction solution was washed with water (160 ml×5 times) and concentrated under reduced pressure, followed by purifying the resulting crude product by a column chromatography to obtain 32.1 g of objective substance as pale yellow glassy substance (yield: 67%). 1H NMR(CDCl3) δppm: 6.53(1H, d, Ar—H), 7.55(1H, d, Ar—H), 7.71-7.79(11H, m, Ar—H), 8.02(1H, d, Ar—H), 8.49(1H, s, Ar—H) Example 2 Synthesis of diphenyl(coumarin-7-yl)sulfonium hexafluorophosphate To 200 ml of dichloromethane was dissolved 24.0 g (0.05 mol) of (coumarin-7-yl)diphenylsulfonium trifluoromethanesulfonate obtained in Example 1, and 18.4 g (0.1 mol) of potassium hexafluorophosphate and 200 ml of water was added thereto, followed by stirring at room temperature for 2 hours. Then, the solution was fractionated and 9.2 g (0.05 mol) of potassium hexafluorophosphate and 100 ml of water were further added to the obtained dichloromethane layer, followed by stirring at room temperature for 2 hours, and then fractionating the solution. The obtained dichloromethane layer was washed with 200 ml of water and concentrated to dryness under reduced pressure to obtain 23.8 g of objective substance as pale yellow glassy substance (yield: 98%). 1H NMR(CDCl3) δppm: 6.63(1H, d, Ar—H), 7.55(1H, d, Ar—H), 7.69-7.82(11H, m, Ar—H), 7.92(1H, d, Ar—H), 8.19(1H, s, Ar—H) Example 3 Synthesis of diphenyl(xanthene-9-one-2-yl)sulfonium trifluoromethanesulfonate To 320 ml of dichloromethane were dissolved 20.2 g (0.1 mol) of diphenylsulfoxide and 19.6 g (0.1 mol) of xanthene-9-one, and 28.2 g (0.1 mol) of trifluoromethanesulfonic anhydride was added dropwise thereto at −70 to −60° C., followed by gradually warming to room temperature and reacting with stirring for 4 hours. After completion of the reaction, the obtained reaction solution was washed with water (160 ml×4 times) and concentrated under reduced pressure, followed by purifying the obtained crude product with column chromatography to obtain 30.7 g of objective substance as pale brown glassy substance (yield: 58%). 1H NMR(CDCl3) δppm: 7.49(1H, t, Ar—H), 7.60(1H, d, Ar—H), 7.72-7.86(11H, m, Ar—H), 7.94(1H, d, Ar—H), 8.25(1H, t, Ar—H), 8.48(1H, d, Ar—H) Example 4 Synthesis of diphenyl(xanthene-9-one-2-yl)sulfonium hexafluorophosphate The same procedure as in Example 2 was conducted, except for using 26.5 g (0.05 mol) of diphenyl(xanthene-9-one-2-yl)sulfonium trifluoromethanesulfonate instead of diphenyl(coumarin-6-yl)sulfonium trifluoromethanesulfonate used in Example 2 to obtain 24.6 g objective substance as pale brown glassy substance (yield: 94%). 1H NMR(CDCl3) δppm: 7.27(1H, t, Ar—H), 7.59(1H, d, Ar—H), 7.72-7.89(11H, m, Ar—H), 7.94(1H, d, Ar—H), 8.25(1H, t, Ar—H), 8.48(1H, d, Ar—H) Example 5 Synthesis of bis(coumarin-7-yl)iodonium hexafluorophosphate To 50 ml of acetic anhydride was dissolved 14.6 g (0.1 mol) of coumarin, and 10.7 g (0.05 mol) of potassium iodate was added thereto at 0° C., and then mixed acid consisting of 25 g (0.25 mol) of concentrated sulfuric acid and 30 g of acetic anhydride was added dropwise thereto at 0 to 7° C. for 2 hours, followed by gradually warming to room temperature and reacting with stirring for 5 hours. After completion of the reaction, the reaction solution was poured in 200 ml of ice water, and 18.4 g (0.1 mol) of potassium hexafluorophosphate was added thereto and 100 ml of dichloromethane was poured thereinto, followed by stirring at room temperature for 2 hours. The precipitated crude crystal was filtered off to obtain 8.0 g of pale yellow crystal. The obtained crystal was dissolved in 60 ml of acetone and then 100 ml of ethyl acetate was gradually poured thereto, followed by filtering the precipitated crystal and drying under vacuum at 50° C. for 2 hours to obtain 6.5 g of objective substance as pale yellow crystal (yield: 23%). m.p.: 227-228° C. (decomposition) 1H NMR(CDCl3) δppm: 6.64 (2H, d, Ar—H), 7.56 (2H, d, Ar—H), 8.06 (2H, d, Ar—H), 8.42(2H, d, Ar—H), 8.61(2H, s, Ar—H) Example 6 Synthesis of bis(xanthene-9-one-2-yl)iodonium hexafluorophosphate To 100 ml of acetic anhydride was suspended 19.6 g (0.1 mol) of xanthene-9-one, and 10.7 g (0.05 mol) of potassium iodate was added thereto at 0° C., and then mixed acid consisting of 25 g (0.25 mol) of concentrated sulfuric acid and 30 g of acetic anhydride was added dropwise thereto at 0 to 7° C. over 2 hours, followed by gradually warming to room temperature and reacting with stirring for 6 hours. After completion of the reaction, the reaction solution was poured in 200 ml of ice water, and 100 ml of dichloromethane was added thereto to dissolve insolble substance. Then 18.4 g (0.1 mol) of potassium hexafluorophosphate was added and stirred thereto at room temperature for 2 hours, followed by filtering precipitated crystal off to obtain 8.0 g of yellowish pale brown crystal. The obtained crystal was dissolved in 100 ml of acetone and then 100 ml of ethyl acetate was gradually poured thereto to precipitate crystal, followed by filtering precipitated crystal off and drying under vacuum at 50° C. for 2 hours to obtain 6.6 g of objective substance as yellowish pale brown crystal (yield: 20%). m.p.: 223° C. (decomposition) 1HNMR(CDCl3) δppm: 7.53(2H, t, Ar—H), 7.69(2H, d, Ar—H), 7.85-7.94(4H, m, Ar—H), 8.20(2H, d, Ar—H), 8.75(2H, d, Ar—H), 9.23(2H, s, Ar—H) Example 7 Synthesis of 7-(phenyliodonio)coumarin hexafluorophosphate To 80 ml of acetic anhydride was suspended 7.3 g (0.05 mol) of coumarin and 16.1 g (0.05 mol) of iodobenzene diacetate, and 10 g (0.1 mol) of concentrated sulfuric acid was added dropwise thereto at 0 to 7° C. for 1 hour, followed by gradually warming to room temperature and reacting with stirring for 8 hours. After completion of the reaction, the reaction solution was poured in 200 ml of ice water, and 150 ml of dichloromethane was added thereto to dissolve insolble substance. Then 18.4 g (0.1 mol) of potassium hexafluorophosphate was added to the obtained solution, followed by stirring at room temperature for 2 hours. The dichloromethane layer obtained by fractionation was washed with 100 ml of water twice. The obtained dichloromethane layer was semi concentrated under reduced pressure and the precipitated crystal was filtered off, followed by drying under vacuum at 50° C. for 2 hours to obtain 2.4 g of objective substance as pale yellow crystal (yield: 10%). m.p.: 211° C. (decomposition) 1H NMR(CDCl3) δppm: 6.64(1H, d, Ar—H), 7.57(3H, t, Ar—H), 7.68(1H, t, Ar—H), 8.05(1H, d, Ar—H), 8.25(2H, d, Ar—H), 8.41(1H, d, Ar—H), 8.63(1H, s, Ar—H) Example 8 Synthesis of 2-(phenyliodonio)xanthene-2-one hexafluorophosphate To 80 ml of acetic anhydride were suspended 9.8 g (0.05 mol) of xanthene-9-one and 16.1 g (0.05 mol) of iodobenzene diacetate, and 10 g (0.1 mol) of concentrated sulfuric acid was added dropwise thereto at 0 to 7° C. for 1 hour, followed by gradually warming to room temperature and reacting with stirring for 8 hours. After completion of the reaction, the reaction solution was poured in 200 ml of ice water, and 150 ml of toluene was added thereto to dissolve insoluble substance and fractionation. Then 18.4 g (0.1 mol) of potassium hexafluorophosphate was added to water layer and stirred at room temperature for 2 hours. The precipitated crystal was filtered off, followed by drying under vacuum at 50° C. for 2 hours to obtain 16.1 g of objective substance as pale yellow crystal (yield: 59%). m.p.: 222° C. (decomposition) 1HNMR(CDCl3) δppm: 7.51-7.58(3H, m, Ar—H), 7.69(2H, t, Ar—H), 7.83(1H, d, Ar—H), 7.93(1H, t, Ar—H), 8.20(1H, d, Ar—H), 8.36(2H, d, Ar—H), 8.62(1H, d, Ar—H), 9.05(1H, s, Ar—H) Comparative Example 1 Synthesis of diphenyl(thioxanthene-9-one-2-yl)sulfonium trifluoromethanesulfonate To 320 ml of dichloromethane were suspended 20.2 g (0.1 mol) of diphenylsulfoxide and 21.2 g (0.1 mol) of thioxanthene-9-one, and 28.2 g (0.1 mol) of trifluoromethanesulfonic anhydride was added dropwise thereto at −70 to −60° C., followed by gradually warming to room-temperature and reacting with stirring for 3 hours. After completion of the reaction, the obtained reaction solution was washed with water (320 ml×5 times) and the obtained dichloromethane layer was concentrated to dryness under reduced pressure. The obtained crude product was purified by column chromatography to obtain 18.6 g of objective substance as yellow glassy substance (yield: 34%). 1H NMR(CDCl3) δ ppm: 7.40-7.83(11H, m, Ar—H), 7.93(1H, q, Ar—H), 8.02(1H, d, Ar—H), 8.27(1H, q, Ar—H), 8.54(1H, d, Ar—H), 8.60(1H, d, Ar—H), 8.68(1H, s, Ar—H) Comparative Example 2 Synthesis of diphenyl(thioxanthene-9-one-2-yl)sulfonium hexafluorophosphate The same procedure as in Example 2 was conducted, except for using 13.7 g (0.025 mol) of diphenyl(thioxanthene-9-one-2-yl)sulfonium trifluoromethanesulfonate instead of diphenyl(coumarin-6-yl)sulfonium trifluoromethanesulfonate used in Example 2 to obtain 13.0 g of objective substance as yellow glassy substance (yield: 96%). 1H NMR(CDCl3) δppm: 7.45-7.85(11H, m, Ar—H), 7.96(1H, q, Ar—H), 7.98(1H, d, Ar—H), 8.08(1H, q, Ar—H), 8.52(1H, d, Ar—H), 8.60(1H, d, Ar—H), 8.73(1H, s, Ar—H) Comparative Example 3 Synthesis of diphenyl(7-chlorothioxanthene-9-one-2-yl)sulfonium hexafluorophosphate To 320 ml of dichloromethane were suspended 20.2 g (0.1 mol) of diphenylsulfoxide and 24.6 g (0.1 mol) of 2-chlorothioxanthene-9-one, and 28.2 g (0.1 mol) of trifluoromethanesulfonic anhydride was added dropwise thereto at −70 to −60° C., followed by gradually warming to room temperature and reacting with stirring for 3 hours. After completion of the reaction, the obtained reaction solution was washed with water (320 ml×5 times) and 18.4 g (0.1 mol) of potassium hexafluorophosphate and 200 ml of water were added to the obtained dichloromethane layer, followed by stirring at room temperature for 2 hours and fractionating the solution. Then, 9.2 g (0.05 mol) of potassium hexafluorophosphate and 100 ml of water were futher added to the obtained dichloromethane layer, followed by stirring at room temperature for 2 hours and fractionating the solution. Then the obtained dichloromethane layer was washed with 200 ml of water and concentrated to dryness under reduced pressure. The obtained crude product was purified by column chromatography to obtain 4.0 g of objective substance as pale yellow glassy substance (yield: 7%). 1H NMR (CDCl3) δppm: 7.79-7.95(11H, m, Ar—H), 8.05(1H, d, Ar—H), 8.14(1H, d, Ar—H), 8.31(1H, d, Ar—H), 8.37(1H, s, Ar—H), 8.73(1H, s, Ar—H) Comparative Example 4 Synthesis of diphenyl(5,7-diethylthioxanthene-9-one-2-yl)sulfonium trifluoromethanesulfonate To 320 ml of dichloromethane were dissolved 20.2 g (0.1 mol) of diphenylsulfoxide and 26.8 g (0.1 mol) of 2,4-diethylthioxanthene-9-one, and 28.2 g (0.1 mol) of trifluoromethanesulfonic anhydride was added dropwise thereto at −70 to −60° C., followed by gradually warming to room temperature and reacting with stirring for 4 hours. After completion of the reaction, the obtained reaction solution was washed with water (160 ml×4 times) and concentrated under reduced pressure. The obtained crude product was purified by column chromatography to obtain 38.6 g of objective substance as yellow glassy substance (yield: 64%). 1HNMR (CDCl3) δppm: 1.28(3H, t, CH3), 1.38(3H, t, CH3), 2.80(2H, q, CH2), 2.93(2H, q, CH2), 7.46(1H, s, Ar—H), 7.70-7.85(11H, m, Ar—H), 8.07(1H, w, Ar—H), 8.28(1H, s, Ar—H), 8.66(1H, s, Ar—H) Comparative Example 5 Synthesis of diphenyl(5,7-diethylthioxanthene-9-one-2-yl)sulfonium hexafluorophosphate The same procedure as in Example 2 was conducted, except for using 30.1 g (0.05 mol) of diphenyl(5,7-diethylthioxanthene-9-one-2-yl)sulfonium trifluoromethanesulfonate instead of diphenyl(coumarin-6-yl)sulfonium trifluoromethanesulfonate used in Example 2 to obtain 29.0 g of objective substance as yellow glassy substance (yield: 97%). 1H NMR (CDCl3) δppm: 1.32(3H, t, CH3), 1.36(3H, t, CH3), 2.77(2H, q, CH2), 2.91(2H, q, CH2), 7.46(1H, s, Ar—H), 7.72-7.85(11H, m, Ar—H), 8.05(1H, w, Ar—H), 8.28(1H, s, Ar—H), 8.71(1H, s, Ar—H) Comparative Example 6 Synthesis of 2-(phenyliodonio)xanthene-9-one tetrafluoroborate To 80 ml of acetic anhydride were suspended 9.8 g (0.05 mol) of xanthene-9-one and 16.1 g (0.05 mol) of iodobenzene diacetate, and 10 g (0.1 mol) of concentrated sulfuric acid was added dropwise thereto at 0 to 7° C. for 1 hour, followed by gradually warming to room temperature and reacting with stirring for 8 hours. After completion of the reaction, the obtained reaction solution was poured into 200 ml of ice water, and 150 ml of toluene was added thereto to dissolve insoluble substance. The solution was fractionated and 12.6 g (0.1 mol) of potassium tetrafluoroborate was added to the obtained water layer, followed by stirring at room temperature for 2 hours. The precipitated crystal was filtered off and dried at 50° C. under vacuum for 2 hours to obtain 11.4 g of 2-(phenyliodonio)xanthene-9-one tetrafluoroborate as pale orange crystal (yield: 47%). m.p.: 229-231° C. (decomposition) 1H NMR (CDCl3) δppm: 7.51-7.56(3H, Q, Ar—H), 7.66-7.73(2H, m, Ar—H), 7.83(1H, d, Ar—H), 7.93(1H, t, Ar—H), 8.20(1H, d, Ar—H), 8.36(2H, d, Ar—H), 8.62(1H, d, Ar—H), 9.06(1H, s, Ar—H) Example 9 Measurement of UV-Visible Ray Absorption Spectra 0.0016 (w/v) % acetonitrile solution of compounds obtained in Examples 1 to 8 and Comparative Examples 1 to 6 (about 3×10−5 mol/l) were prepared to measure ultraviolet-visible ray absorption spectra. As reference examples, absorption spectra of triphenylsulfonium hexafluorophosphate (Reference Example 1) and diphenyliodonium hexafluorophosphate (Reference Example 2) were also measured. Table 1 shows wavelength (nm) for maximum absorption, molecular extinction coefficient (ε) at said wavelength and molecular extinction coefficient (ε) at 300 nm, 350 nm and 400 nm. Absorption curve data on sulfonium salts are shown in FIGS. 1 and 2 and the data on iodonium salts are shown in FIG. 3, respectively. Each curve code in FIG. 1 shows the following compounds, respectively: curve: a sulfonium salt of the present invention (Example 1) curve: a sulfonium salt of the present invention (Example 2) curve: a sulfonium salt of the present invention (Example 3) curve: a sulfonium salt of the present invention (Example 4) Each curve code in FIG. 2 shows the following compound, respectively: curve: a compound of Comparative Example 1 curve: a compound of Comparative Example 2 curve: a compound of Comparative Example 3 curve: a compound of Comparative Example 4 curve: a compound of Comparative Example 5 curve: a compound of Reference Example 1 Each curve code in FIG. 3 shows the following compound, respectively: curve: an iodonium salt of the present invention (Example 5) curve: an iodonium salt of the present invention (Example 6) curve: an iodonium salt of the present invention (Example 7) curve: an iodonium salt of the present invention (Example 8) curve: a compound of Comparative Example 6 curve: a compound of Reference Example 2 TABLE 1 Maximum absorption wave length Cationic (nm) Molecular extinction photopolymerization (Molecular extinction coefficient initiator coefficient) 300 nm 350 nm 400 nm Compd. of Example 1 243 (39380) 310 (6593) 5634 174 0 Compd. of Example 2 243 (40130) 310 (6864) 6063 229 0 Compd. of Example 3 248 (44410) 335 (5260) 1646 32 0 Compd. of Example 4 248 (44290) 336 (5270) 2127 31 0 Compd. of Comparative 315 (16010) 371 (2773) 12210 2524 592 Example 1 Compd. of Comparative 315 (15820) 378 (2688) 12000 2444 519 Example 2 Compd. of Comparative 321 (19070) 387 (4464) 8689 3136 2251 Example 3 Compd. of Comparative 324 (16000) 379 (3731) 12750 4623 2564 Example 4 Compd. of Comparative 324 (15890) 379 (3731) 12680 4560 2522 Example 5 Compd. of Example 10 248 (42240) 310 (13420) 11730 382 32 Compd. of Example 11 252 (54540) 335 (9246) 6332 3302 39 Compd. of Example 12 241 (31370) 309 (6376) 5512 0 0 Compd. of Example 13 248 (41130) 337 (5347) 2198 1411 0 Compd. of Comparative 248 (41130) 337 (5347) 2890 1821 0 Example 6 triphenylsulfonium 197 (59090) 233 (18220) 175 50 0 hexafluorophosphate diphenyliodonium 194 (35600) 229 (14400) 207 0 0 hexafluorophosphate As is clear from the results in FIGS. 1 and 2, triphenylsulfonium hexafluorophosphate (Reference Example 1), as a conventional sulfonium salt, has little absorption in wavelength region not shorter than 300 nm and sulfonium salts having thioxantone skeleton, wherein the anion thereof is hexafluorophosphate (Comparative Examples 1 to 5) have absorption in wavelength region not shorter than 400 nm and thus provides yellow color. Therefore, when the polymerization of monomer is conducted by using them as cationic photopolymerization initiators for light source of a high pressure mercury lamp having effective wavelength not shorter than UV region (300 nm and longer), use of triphenylsulfonium hexafluorophosphate (Reference Example 1) provides a problem of poor acid generation efficiency, and further use of sulfonium salts having thioxantone skeleton (Comparative Examples 1 to 5) provides good acid generation efficiency, but a problem that because said sulfonium salts themselves shows yellow color in visible region, the obtained polymers give rellow color and therefore they have lower transparency. On the other hand, sulfonium salts of the present invention, have absorption at 300 to 360 nm region and no absorption at not shorter than 400 nm, and thus it was found that when they are used as cationic photopolymerization initiators for light source of a high pressure mercury lamp to polymerize a monomer, they provide good acid generation efficiency, and the obtained polymers have good transparency in the visible light region. As is clear from the results in FIG. 3, diphenyliodonium hexafluorophosphate, as a conventional iodonium salt, has little absorption in wavelength region not shorter than 300 nm, while iodonium salts of the present invention have absorption in wavelength region not shorter than 300 nm and little absorption in wavelength region not shorter than 400 nm, and there it was found that iodonium salts of the present invention, just like sulfonium salts of the present invention, have acid generation efficiency when they are used as cationic photopolymerization initiators for light source of a high pressure mercury lamp to polymerize a monomer, and the obtained polymers have high transparency in the visible light region. Example 10 Photocuring Test A mixture was prepared by mixing 7 g of 3,4-epoxycyclohexylmethyl-3,4-epoxycyclohexanecarboxylate, 3 g of cyclohexeneoxide and 0.20 g of a 50% (w/w) propylene carbonate solution of each compound obtained in Examples 2 to 4 as a cationic photopolymerization initiator. This solution was coated on a glass plate to obtain film with thickness of 40±10 μm, followed by irradiation with a 50 W/cm high pressure mercury lamp for 60 seconds. Pencil hardness was measured just after the irradiation and one day after the irradiation. As comparative examples, a photocuring test of triphenylsulfonium hexafluorophosphate was also performed at the same time. The results are shown in Table 2. TABLE 2 Cationic photopolymerization initiator Just after One day after Compound of Example 2 HB H Compound of Example 5 HB H Compound of Example 6 4H 4H Compound of Example 8 HB H Compound of Comparative Example 1 HB H Compound of Comparative Example 2 4H 4H Compound of Comparative Example 5 HB H Compound of Comparative Example 6 2B B triphenylsulfonium hexafluorophosphate HB HB diphenyliodonium hexafluorophosphate HB HB As is clear from the results of the comparison of a sulfonium salt in Example 2 with triphenylsulfonium hexafluorophosphate, and comparison of idonium salts in Examples 5, 6 and 8 with diphenyliodonium hexafluorophosphate, in Table 2, it was found that hardness, of sulfonium salts and iodonium salts of the present invention, just after curing provides equivalent to or higher than those of conventional sulfonium salts and iodonium salts, and higher hardness, of said salts of the present invention, one day after curing provides higher than those of conventional sulfonium salts and iodonium salts. Further, it is also clear from the results of the comparison of sulfonium salts having thioxantone skeleton in Comparative Examples 1, 2 and 5 with a sulfonium salt of the present invention (Example 2) that, as is also described in discussion on Table 1, sulfonium salts having thioxantone skeleton have yellow color and are not preferable due to providing poor transparency to the obtained polymers when used as coating materials, adhesives and paints, although a compound in Comparative Example 2 provides hardness higher than that of a compound of the present invention. Furthermore, as is clear from the results of the comparison between a compound (PF6−) in Example 8 and a compound (BF4−) in Comparative Example 6, is was found that iodonium salts of the present invention provide higher hardness than conventional iodonium salts from the viewpoint of the results of hardness just after and one day after curing. It was also clear from the comparison between the results in Examples 5 and 6 and Example 8, that among others, iodonium salts, one wherein both R26 and R27 in the general formula [35] are one shown by the general formula [2] or [3], can be used as a cationic initiator to obtain polymers with higher hardness. Example 11 Photopolymerization Test As cationic photo polymerization initiators, 20% (w/w) propylene carbonate solutions of compounds obtained in Examples 4 to 8 were prepared. They were each added and mixed to 50.00 g of cyclohexeneoxide to become the polymerization initiator concentration of 0.5% (w/w). To a test tube added 5 ml of this solution, followed by nitrogen bubbling and sealing the tube with parafilm (trade name). The reaction solution was kept to 17 to 22° C. in a water bath, followed by irradiation with a 100 W high pressure mercury lamp (HL-100 model: mfd. by Fuji Glass Co., Ltd.) from measurement distance of 7 cm for predetermined time to precipitate a polymer from excess of methanol solution. The obtained polymer was washed several times, followed by filtering with a glass filter and drying. Polymerization rate was calculated by dividing polymer weigh after drying by monomer weight at the time tube charged to the test tube. The polymerization rate to each irradiation time is measured. The results are shown in FIG. 4. Each curve code in FIG. 4 shows the following compound, respectively: curve: a compound of Example 4 curve: a compound of Example 5 curve: a compound of Example 6 curve: a compound of Example 8 curve: a compound of Comparative Example 2 curve: a compound of Comparative Example 3 As is clear from the results in FIG. 4, use of compounds in Examples 2, 4 to 6 as polymerization initiators provides polymerization rate quite similar to obtain by use of compounds in Comparative Examples 2 and 3 as polymerization initiators. INDUSTRIAL APPLICABILITY An onium salt of the present invention has a heterocycle in the cation moiety, and thus provides higher light absorption efficiency of light such as a high pressure mercury lamp, a metal halide lamp, UV rays, deep UV rays, KrF excimer laser, ArF excimer laser, F2 excimer laser, electron beams, X-rays and radioactive rays, in particular, light such as a high pressure mercury lamp and a metal halide lamp. Therefore, onium salts shown by the general formulae [8], [9], [37] and [38] have advantage such as providing improved acid generation efficiency compared with conventional onium salts, when a high pressure mercury lamp or a metal halide lamp is used as light source among various light sources. Furthermore, an onium salt of the present invention has little absorption at wavelength not shorter than 400 nm, and thus provides effect that a polymer obtained by using said onium salts as a cationic photopolymerization initiator maintains transparency in the visible light region. Such use of said onium salt as an acid generator for a chemically amplified resist can prepare a resist composition with high sensitivity to light source of a high pressure mercury lamp and a metal halide lamp.

<SOH> BACKGROUND OF THE INVENTION <EOH>Recently, in the field of photopolymerization, a research on a cationic polymerization, instead of a radical polymerization, has been promoted to make polymerization easy even in the air without the effect of oxygen. A cationic polymerization mainly uses as light source a high pressure mercury lamp or a metal halide lamp, including, for example, g-line (436 nm) and i-line (365 nm), and is widely known as a polymerization method for such as an epoxy compound and a vinyl ether compound, rather than a vinyl monomer. As a cationic photopolymerization initiator, for example, sulfonium salt such as triarylsulfonium hexafluoroantimonate (see U.S. Pat. No. 4,058,401) and a 4-(phenylthio)phenyldiphenylsulfonium salt compound (see U.S. Pat. No. 4,173,476), and an iodonium salt such as diphenyliodonium hexafluorophosphate and diphenyliodonium hexafluoroantimonate (see JP-A-50-151996, JP-A-60-47029, etc.) have been known. These compounds, however, have such problems of difficulty in preparing a polymer with high hardness when the said compounds are used as a cationic polymerization initiators, because use of a high pressure mercury lamp or a metal halide lamp as light source causes low acid generation efficiency. Further, these sulfonium salts and onium salts are known to significantly reduce photocuring, when an inorganic strong acid such as hexafluorophosphate (PF 6 − ) is used as a counter anion, compared with hexafluoroantimonate (SbF 6 − ). However, use of SbF 6 − may be inhibited in the future due to having strong toxicity. Furthermore, Polish J. Chem., 71, p. 1236-1245 (1997) discloses 2-(phenyliodonio)xanthene-9-one tetrafluoroborate (BF 4 —) having a xanthonyl group at the cation moiety of the iodonium salt, and a synthesis example thereof. However, there is no disclosure that this compound can be used as a cationic polymerization initiator or not, and use of said compound as a cationic polymerization initiator could not obtain a polymer with sufficient hardness. On the other hand, a high pressure mercury lamp or a metal halide lamp is widely used as exposure light source for such as a semiconductor resist, a liquid crystal resist, a solder resist for circuit board, PS (Pre-sensitized) plate and CTP (Computer To Plate) plate, and a sulfonium salt and an iodonium salt are also used as an acid generator for those applications. However, these compounds have such problems that a resist with sufficiently high sensitivity cannot be provided due to low acid generation efficiency, when such as a high pressure mercury lamp or a metal halide lamp is used as light source. Therefore, sulfonium salts with thioxanthone structure have been developed to provide high acid generation efficiency (see, for example, JP-A-8-165290, JP-A-9-12614, JP-A-9-12615, JP-A-10-60098, JP-A-10-67812, JP-A-10-101718, JP-A-10-120766, JP-A-10-130363, JP-A-10-152554, JP-A-10-168160, JP-A-10-182634, JP-A-10-182711, JP-A-10-279616, JP-A-11-269169 and JP-A-11-322944). However, because these sulfonium salts have absorption in the visible light region not shorter than 400 nm, and therefore show yellowish color. Thus use of these sulfonium salts as a polymerization initiator has such drawbacks that an obtained polymer has color under the influence of hue of said polymerization initiator itself, and therefore use of the said polymerization initiator as coating agents, adhesives or paints causes an obtained polymer with poor transparency and with hue which is different from desired hue. Under the circumstance, development of an onium salt, providing sufficient hardening function even though PF 6 − is used as a counter anion, and providing little effect on transparency of an obtained polymer, is required by research on a cation moiety with new structure providing high acid generation efficiency, even when such as a high pressure mercury lamp or a metal halide lamp is used as light source.

<SOH> SUMMARY OF THE INVENTION <EOH>The present invention has been completed for the purpose of solving the above-mentioned problems and provides the following: (1) A heterocycle-containing sulfonium salt shown by the general formula [1]: [wherein R is a group shown by the general formula [2]: (wherein R 3 and R 4 are each independently a halogen atom, an alkyl group which may have a halogen atom or an aryl group as a substituent, or an aryl group which may have a halogen atom or a lower alkyl group as a substituent; X 2 is an oxygen atom or a sulfur atom; i is an integer of 0 to 4; and j is an integer of 0 to 3) or a group shown by the general formula [3]: (wherein R 5 and R 6 are each independently a halogen atom, an alkyl group which may have a halogen atom or an aryl group as a substituent, or an aryl group which may have a halogen atom or a lower alkyl group as a substituent; X 3 and X 4 are each independently an oxygen atom or a sulfur atom; p is an integer of 0 to 2; and q is an integer of 0 to 3); R 1 and R 2 are each independently a halogen atom, an alkyl group which may have a halogen atom or an aryl group as a substituent, or an aryl group which may have a halogen atom or a lower alkyl group as a substituent; m and n are each independently an integer of 0 to 5; and A is a halogen atom or an anion derived from an inorganic strong acid, an organic acid or a compound shown by the general formula [4]: in-line-formulae description="In-line Formulae" end="lead"? HM 1 (R 7 ) 4 [4] in-line-formulae description="In-line Formulae" end="tail"? (wherein M 1 is a boron atom or a gallium atom; and R 7 is an aryl group which may have a substituent selected from a lower haloalkyl group, a halogen atom, a nitro group and a cyano group)], (2) An iodonium salt shown by the general formula [35]: [wherein R 26 and R 27 are each independently an aryl group which may have a halogen atom or a lower alkyl group as a substituent, a group shown by the above-mentioned general formula [2] or a group shown by the above-mentioned general formula [3]; A 3 is a halogen atom or an anion derived from an inorganic strong acid, an organic acid or a compound shown by the general formula [4]; and provided that at least one of R 26 and R 27 is a group shown by the above-mentioned general formula [2] or [3] and when only one of R 26 and R 27 is a group shown by the above-mentioned general formula [2] or [3], A 3 is an anion derived from an inorganic strong acid shown by the general formula [36]; in-line-formulae description="In-line Formulae" end="lead"? HM 3 F 6 [36] in-line-formulae description="In-line Formulae" end="tail"? (wherein M 3 is a phosphorus atom, an arsenic atom or an antimony atom), an organic acid or a compound shown by the general formula [4]], (3) A cationic photopolymerization initiator, comprising a sulfonium salt shown by the general formula [8]: (wherein A 1 is an anion derived from an inorganic strong acid, a sulfonic acid or a compound shown by the general formula [41; and R, R 1 , R 2 , m and n have the same meaning as above), (4) A cationic photopolymerization initiator, comprising an iodonium salt shown by the general formula [37]: (wherein A 4 is an anion derived from an inorganic strong acid, a sulfonic acid or a compound shown by the general formula [4]; R 26 and R 27 have the same meaning as above; and provided that at least one of R 26 and R 27 is a group shown by the above-mentioned general formula [2] or [3] and when only one of R 26 and R 27 is a group shown by the above-mentioned general formula [2] or [3], an inorganic strong acid is one shown by the general formula [36]), (5) A method for polymerization of an epoxy monomer, which comprises using the polymerization initiator in the above-mentioned (3) and (4), (6) A method for polymerization of a vinyl ether monomer, which comprises using the polymerization initiator in the above-mentioned (3) and (4), (7) An acid generator for a resist, comprising a sulfonium salt shown by the general formula [9]: (wherein A 2 is an anion derived from an inorganic strong acid, an organic acid or a compound shown by the general formula [4]; and R, R 1 , R 2 , m and n have the same meaning as above), and (8) An acid generator for a resist, comprising an iodonium salt shown by the general formula [38]: (wherein A 5 is an anion derived from an inorganic strong acid, an organic acid or a compound shown by the general formula [4]; R 26 and R 27 have the same meaning as above; and provided that at least one of R 26 and R 27 is a group shown by the above-mentioned general formula [2] or [3] and when only one of R 26 and R 27 is a group shown by the above-mentioned general formula [2] or [3], an inorganic strong acid is one shown by the general formula [36]). The present inventors have conducted extensive study in order to realize the above-mentioned object and to arrive at the finding that a heterocycle-containing onium salt shown by the above-mentioned general formulae [1], [8], [9], [35], [37] and [38] has superior acid generation efficiency in wavelength region of a high pressure mercury lamp and a metal halide lamp, and good transparency in the visible light region (not shorter than 400 nm) (that is, little absorption in the visible light region), and thus they can be used as cationic photopolymerization initiators or acid generators not having the above-mentioned problems, or synthesis raw materials thereof, and finally the present invention has been completed on the basis of these findings.

20040902

20080115

20051020

71496.0

DENTZ, BERNARD I

HETEROCYCLE-BEARING ONIUM SALTS

UNDISCOUNTED

ACCEPTED

ACCEPTED

Air purification filter and process for producing the same

It is intended to provide an air purification filter which has a high dry tensile strength, a high wet tensile strength in association with a high water resistance and a high water repellency and exhibits a bactericidal effect due to a gas phase reaction in a gas phase. Namely, an air purification filter having a high dry tensile strength, a high wet tensile strength (a high water resistance) and a high water repellency as well as a bactericidal effect which is obtained by blending a filter fiber having a functional group with a mixture of a modification enzyme which has an ionic polarity opposite to the ionic polarity of the whole filter fiber as described above and a bactericidal effect with an ionic synthetic resin binder having the opposite ionic polarity similar to the modification enzyme.

1. An air purifying filter media having a dry tensile strength, a wet tensile strength in association with water resistance and water repellency and exhibiting bactericidal/sterilizing or antimicrobial means properties using enzyme reaction, obtained by applying a mixture of the modified enzyme which has an ionic polarity opposite to the ionic polarity of the whole filter media fiber having a functional group and which has sterilizing properties, and an ionic synthetic resin binder having the opposite ionic polarity similar to the modified enzyme, to the whole filter media fiber as described above. 2. The air purifying filter media according to claim 1, wherein the filter media fiber having the functional group is at least one of a group consisting of inorganic fiber, nature fiber or derivative thereof, organic synthetic fiber having at least one of a group consisting of hydroxyl and carboxyl group having an anionic polarity, and an amino or an imino group having a cationic polarity. 3. The air purifying filter media according to claim 1, wherein the filter media fiber is at least one fiber having at least one of a group consisting of a hydroxyl and carboxyl group having an anionic polarity, and an amino or an imino group having a cationic polarity, and selecting from a group consisting the inorganic fiber from boron-silica glass fibers, alkyl amine glass fibers, silica-alumina fibers; the nature fiber or derivative thereof selected from non-wood fiber or wood fibers, namely, rayon fibers, cotton fibers, hemp fibers, wool fibers; the organic synthetic fibers selected from polyamide fibers, polyvinyl alcohol fibers, acetate fibers, polyacrylamide fibers or copolymer thereof. 4. The air purifying filter media according to claim 1, wherein the modified enzyme being immobilized on the functional group of the filter media fiber is at least one modified enzyme modified with at least one compound selected from a group consisting of N-substituted carbamate bromide, N-substituted imide carbonate bromide, acetyl bromide+triacetyl cellulose, dimethylaminoethyl, diethylaminoothyl, protanine, polyethylene imine, polyvinyl amine, polyallyl amine, polylysine, polyornitine, dextran, dextran sulfate, dextrin and chondroitin sulfate. 5. The air purifying filter media according to claim 1, wherein the to be modified enzyme is at least one selected from a group consisting of β-1,3-glucanase, chitinase, lysozyme, protease, glucosidase, β-galactosidase, endo-β-N-acetylglucosamidase and endolysin. 6. The air purifying filter media according to claim 1, wherein the ionic synthetic resin binder is at least one selected from a group consisting of acrylic resin, urethane resin, vinyl acetate resin, SBR resin, Epoxy resin, polyvinyl alcohol resin. 7. The air purifying filter media according to claim 1, wherein the used amount of the modified enzymes is 0.01% by weight or more, based on the weight of the filter media. 8. The air purifying filter media according to claim 1, wherein the used amount of the ionic synthetic resin binder is 0.1 to 10.0% by weight, based on the weight of the filter media. 9. The air purifying filter media according to claim 1, wherein the dry tensile strength of the filter media, measured according to MIL-F-51079 C, is 0.45 kN/m or more in a machine direction of the filter media and 0.35 kN/m or more in a cross direction of the filter media. 10. The air purifying filter media according to claim 1, wherein the wet tensile strength of the filter media, measured according to MIL-F-51079 C, is 0.176 kN/m or more in a cross direction of the filter media. 11. The air purifying filter media according to claim 1, wherein the water repellency of the filter media comprising the glass fiber as main component, measured according to M1282, is 150 mm or more (the height of the water column). 12. The air purifying filter media according to claim 1, wherein the main component of the filter media fiber is selected from the nature fiber or derivative thereof selected from non-wood fiber or wood fibers, namely, rayon fibers, cotton fibers, hemp fibers, wool fibers; the organic synthetic fibers selected from polyamide fibers, polyvinyl alcohol fibers, acetate fibers, polyacrylamide fibers or copolymer thereof, and the water repellency of the filter media, measured according to MIL-282, is 100 mm or more (the height of the water column). 13. The air purifying filter media according to claim 1, wherein the sterilization ratio is 99.9% or more. 14. The air purifying filter media according to claim 1, wherein other than the modified enzyme and the ionic synthetic resin binder, the water repellent agent is additionally applied. 15. The air purifying filter media according to claim 14, wherein the applied amount of the water repellent agent is 0.1% by weight or less, based on the filter media. 16. The air purifying filter media according to claim 1, wherein in addition to the ionic synthetic resin binder an internal fibrous binder is used. 17. A process for tile preparation of the air purifying filter media according to claim 1, wherein, after preparation of a slurry containing the filter media fiber having the functional group, to a wet paper web produced from the slurry under dehydration by using a wet-type paper machine or a dried paper thereof, the modified enzyme and an ionic synthetic resin binder and, if desired, the water repellent agent is applied. 18. The process according to claim 17, wherein the wet paper web applied the modified enzyme and the ionic synthetic resin binder and, if desired, the water repellent agent or the dry paper is dried at a temperature between 80° C. to 220° C. 19. The air purifying filter media according to claim 2, wherein the filter media fiber is at least one fiber having at least one of a group consisting of a hydroxyl and carboxyl group having an anionic polarity, and an amino or an imino group having a cationic polarity, and selecting from a group consisting the inorganic fiber from boron-silica glass fibers, alkyl amine glass fibers, silica-alumina fibers; the nature fiber or derivative thereof selected from non-wood fiber or wood fibers, namely, rayon fibers, cotton fibers, hemp fibers, wool fibers; the organic synthetic fibers selected from polyamide fibers, polyvinyl alcohol fibers, acetate fibers, polyacrylamide fibers or copolymer thereof. 20. The air purifying filter media according to claim 2, wherein the modified enzyme being immobilized on the functional group of the filter media fiber is at least one modified enzyme modified with at least one compound selected from a group consisting of N-substituted carbamate bromide, N-substituted imide carbonate bromide, acetyl bromide+triacetyl cellulose, dimethylaminoethyl, diethylaminoethyl, protamine, polyethylene imine, polyvinyl amine, polyallyl amine, polylysine, polyornitine, dextran, dextran sulfate, dextrin and chondroitin sulfate. 21. The air purifying filter media according to claim 2, wherein the to be modified enzyme is at least one selected from a group consisting of β-1,3-glucanase, chitinase, lysozymne, protease, glucosidase, β-galactosidase, endo-β-acetylglucosamidase and endolysin. 22. The air purifying filter media according to claim 4, wherein the to be modified enzyme is at least one selected from a group consisting of β-1,3-glucanase, chitinase, lysozyme, protease, glucosidase, β-galactosidase, endo-β-acetylglucosamidase and endolysin. 23. The air purifying filter media according to claim 2, wherein the ionic synthetic resin binder is at least one selected from a group consisting of acrylic resin, urethane resin, vinyl acetate resin, SBR resin, Epoxy resin, polyvinyl alcohol resin. 24. The air purifying filter media according to claim 3, wherein the ionic synthetic resin binder is at least one selected from a group consisting of acrylic resin, urethane resin, vinyl acetate resin, SBR resin, Epoxy resin, polyvinyl alcohol resin. 25. The air purifying filter media according to claim 4, wherein the ionic synthetic resin binder is at least one selected from a group consisting of acrylic resin, urethane resin, vinyl acetate resin, SBR resin, Epoxy resin, polyvinyl alcohol resin. 26. The air purifying filter media according to claim 5, wherein the ionic synthetic resin binder is at least one selected from a group consisting of acrylic resin, urethane resin, vinyl acetate resin, SBR resin, Epoxy resin, polyvinyl alcohol resin. 27. The air purifying filter media according to claim 2, wherein the used amount of the modified enzymes is 0.01% by weight or more, based on the weight of the filter media. 28. The air purifying filter media according to claim 4, wherein the used amount of the modified enzymes is 0.01% by weight or more, based on the weight of the filter media. 29. The air purifying filter media according to claim 5, wherein the used amount of the modified enzymes is 0.01% by weight or more, based on the weight of the filter media. 30. The air purifying filter media according to claim 2, wherein the used amount of the ionic synthetic resin binder is 0.1 to 10.0% by weight, based on the weight of the filter media. 31. The air purifying filter media according to claim 6, wherein the used amount of the ionic synthetic resin binder is 0.1 to 10.0% by weight, based on the weight of the filter media. 32. The air purifying filter media according to claim 7, wherein the used amount of the ionic synthetic resin binder is 0.1 to 10.0% by weight, based on the weight of the filter media. 33. The air purifying filter media according to claim 2, wherein the dry tensile strength of the filter media, measured according to MIL-F-51079 C, is 0.45 kN/m or more in a machine direction of the filter media and 0.35 kN/m or more in a cross direction of the filter media. 34. The air purifying filter media according to claim 8, wherein the dry tensile strength of the filter media, measured according to MIL-F-51079 C, is 0.45 kN/m or more in a machine direction of the filter media and 0.35 kN/m or more in a cross direction of the filter media. 35. The air purifying filter media according to claim 32, wherein the dry tensile strength of the filter media, measured according to MIL-F-51079 C, is 0.45 kN/m or more in a machine direction of the filter media and 0.35 kN/m or more in a cross direction of the filter media. 36. The air purifying filter media according to claim 2, wherein the wet tensile strength of the filter media, measured according to MIL-F-51079 C, is 0.176 kN/m or more in a cross direction of the filter media. 37. The air purifying filter media according to claim 6, wherein the wet tensile strength of the filter media, measured according to MIL-F-51079 C, is 0.176 kN/m or more in a cross direction of the filter media. 38. The air purifying filter media according to claim 8, wherein the wet tensile strength of the filter media, measured according to MIL-F-51079 C, is 0.176 kN/m or more in a cross direction of the filter media. 39. The air purifying filter media according to claim 32, wherein the wet tensile strength of the filter media, measured according to MIL-F-51079 C, is 0.176 kN/m or more in a cross direction of the filter media. 40. The air purifying filter media according to claim 2, wherein the water repellency of the filter media comprising the glass fiber as main component, measured according to MIL-282, is 150 mm or more (the height of the water column). 41. The air purifying filter media according to claim 4, wherein the water repellency of the filter media comprising the glass fiber as main component, measured according to MIL-282, is 150 mm or more (the height of the water column). 42. The air purifying filter media according to claim 5, wherein the water repellency of the filter media comprising the glass fiber as main component, measured according to MIL-282, is 150 mm or more (the height of the water column). 43. The air purifying filter media according to claim 8, wherein the water repellency of the filter media comprising the glass fiber as main component, measured according to MIL-282, is 150 mm or more (the height of the water column). 44. The air purifying filter media according to claim 32, wherein the water repellency of the filter media comprising the glass fiber as main component, measured according to MIL-282, is 150 mm or more (the height of the water column). 45. The air purifying filter media according to claim 2, wherein the main component of the filter media fiber is selected from the nature fiber or derivative thereof selected from non-wood fiber or wood fibers, namely, rayon fibers, cotton fibers, hemp fibers, wool fibers; the organic synthetic fibers selected from polyamide fibers, polyvinyl alcohol fibers, acetate fibers, polyacrylamide fibers or copolymer thereof, and the water repellency of the filter media, measured according to MIL-282, is 100 mm or more (the height of the water column). 46. The air purifying filter media according to claim 4, wherein the main component of the filter media fiber is selected from the nature fiber or derivative thereof selected from non-wood fiber or wood fibers, namely, rayon fibers, cotton fibers, hemp fibers, wool fibers; the organic synthetic fibers selected from polyamide fibers, polyvinyl alcohol fibers, acetate fibers, polyacrylamide fibers or copolymer thereof, and the water repellency of the filter media, measured according to MIL-282, is 100 mm or more (the height of the water column). 47. The air purifying filter media according to claim 5, wherein the main component of the filter media fiber is selected from the nature fiber or derivative thereof selected from non-wood fiber or wood fibers, namely, rayon fibers, cotton fibers, hemp fibers, wool fibers; the organic synthetic fibers selected from polyamide fibers, polyvinyl alcohol fibers, acetate fibers, polyacrylamide fibers or copolymer thereof, and the water repellency of the filter media, measured according to MIL-282, is 100 mm or more (the height of the water column). 48. The air purifying filter media according to claim 8, wherein the main component of the filter media fiber is selected from the nature fiber or derivative thereof selected from non-wood fiber or wood fibers, namely, rayon fibers, cotton fibers, hemp fibers, wool fibers; the organic synthetic fibers selected from polyamide fibers, polyvinyl alcohol fibers, acetate fibers, polyacrylamide fibers or copolymer thereof, and the water repellency of the filter media, measured according to MIL-282, is 100 mm or more (the height of the water column). 49. The air purifying filter media according to claim 32, wherein the main component of the filter media fiber is selected from the nature fiber or derivative thereof selected from non-wood fiber or wood fibers, namely, rayon fibers, cotton fibers, hemp fibers, wool fibers; the organic synthetic fibers selected from polyamide fibers, polyvinyl alcohol fibers, acetate fibers, polyacrylamide fibers or copolymer thereof, and the water repellency of the filter media, measured according to MIL-282, is 100 mm or more (the height of the water column). 50. The air purifying filter media according to claim 2, wherein the sterilization ratio is 99.9% or more. 51. The air purifying filter media according to claim 4, wherein the sterilization ratio is 99.9% or more. 52. The air purifying filter media according to claim 5, wherein the sterilization ratio is 99.9% or more. 53. The air purifying filter media according to claim 6, wherein the sterilization ratio is 99.9% or more. 54. The air purifying filter media according to claim 7, wherein the sterilization ratio is 99.9% or more. 55. The air purifying filter media according to claim 8, wherein the sterilization ratio is 99.9% or more. 56. The air purifying filter media according to claim 32, wherein the sterilization ratio is 99.9% or more. 57. The air purifying filter media according to claim 2, wherein other than the modified enzyme and the ionic synthetic resin binder, the water repellent agent is additionally applied. 58. The air purifying filter media according to claim 2, wherein the applied amount of the water repellent agent is 0.1% by weight or less, based on the filter media. 59. (canceled) 60. The air purifying filter media according to one from claim 2, wherein in addition to the ionic synthetic resin binder an internal fibrous binder is used. 61. The air purifying filter media according to one from claim 9, wherein in addition to the ionic synthetic resin binder an internal fibrous binder is used. 62. The air purifying filter media according to one from claim 10, wherein in addition to the ionic synthetic resin binder an internal fibrous binder is used. 63. A process for the preparation of the air purifying filter media according to claim 2, wherein, after preparation of a slurry containing the filter media fiber having the functional group, to a wet paper web produced from the slurry under dehydration by using a wet-type paper machine or a dried paper thereof, the modified enzyme and an ionic synthetic resin binder and, if desired, the water repellent agent is applied. 64. A process for the preparation of the air purifying filter media according to claim 3, wherein, after preparation of a slurry containing the filter media fiber having the functional group, to a wet paper web produced from the slurry under dehydration by using a wet-type paper machine or a dried paper thereof, the modified enzyme and an ionic synthetic resin binder and, if desired, the water repellent agent is applied. 65. A process for the preparation of the air purifying filter media according to claim 4, wherein, after preparation of a slurry containing the filter media fiber having the functional group, to a wet paper web produced from the slurry under dehydration by using a wet-type paper machine or a dried paper thereof, the modified enzyme and an ionic synthetic resin binder and, if desired, the water repellent agent is applied. 66. A process for the preparation of the air purifying filter media according to claim 5, wherein, after preparation of a slurry containing the filter media fiber having the functional group, to a wet paper web produced from the slurry under dehydration by using a wet-type paper machine or a dried paper thereof, the modified enzyme and an ionic synthetic resin binder and, if desired, the water repellent agent is applied. 67. A process for the preparation of the air purifying filter media according to claim 6, wherein, after preparation of a slurry containing the filter media fiber having the functional group, to a wet paper web produced from the slurry under dehydration by using a wet-type paper machine or a dried paper thereof, the modified enzyme and an ionic synthetic resin binder and, if desired, the water repellent agent is applied. 68. A process for the preparation of the air purifying filter media according to claim 14, wherein, after preparation of a slurry containing the filter media fiber having the functional group, to a wet paper web produced from the slurry under dehydration by using a wet-type paper machine or a dried paper thereof, the modified enzyme and an ionic synthetic resin binder and, if desired, the water repellent agent is applied. 69. A process for the preparation of the air purifying filter media according to claim 16, wherein, after preparation of a slurry containing the filter media fiber having the functional group, to a wet paper web produced from the slurry under dehydration by using a wet-type paper machine or a dried paper thereof, the modified enzyme and an ionic synthetic resin binder and, if desired, the water repellent agent is applied.

TECHNICAL FIELD This invention relates to an air purifying filter media having a high water resistance and a high repellency as well as exhibiting bactericidal/sterilizing or antimicrobial means properties using enzyme reaction in a gas phase. RELATED ART Air purifying filter media of the related art capture primarily suspended particles such as dust and fine particles on which microorganisms such as bacteria are deposited, in air. In the conventional air purifying filter media, the microorganisms captured on the filter media may grow and scatter based on the nutritional source existing in the dust. Today, this situation is regarded as a problematic matter. Namely, it may cause secondary contamination. Therefore, recently, a development of an air filter media that exhibits bactericidal/sterilizing or antimicrobial means properties using enzyme has been attempted. Among the prior art, filter media in which a silver complex ion as an antibacterial agent was fixed by a binder, has been provided (see, for example, Patent Literature 1). However, in this technique, as the binder deteriorates, silver itself falls off from the filter media in the form of a powder, and, after the silver complex ion performs an antimicrobial reaction, it will not achieve the expected result because the antimicrobial reaction cannot occur again. Therefore, new treatment of the surface is required, so that this process requires time and expense and, furthermore, an original function of the filter media is inhibited. Furthermore, another disadvantage of this process is that silver itself has a high price. An antimicrobial air filter prepared by impregnating it with a binder liquid containing a thiabendazole-based chemical and an inorganic powder containing silver as an antimicrobial agent to a wet paper web consisting of the air filter glass fiber is proposed (see, for example, Patent Literature 2). However, in this case, there is such a problem that, as time passes, the antimicrobial effect is lost due to high volatility of the thiabendazole-based chemical. Also, this process has a problematic matter that the silver-containing inorganic powder causes a falling in the form of a powder due to a deterioration of the binder applied to the filter media. Recently, a technique in which an enzyme is used as a sterilizing, bactericidal and antimicrobial mean is provided. Among related art techniques, it is provided that, as a carrier on which lytic enzyme having sterilizing properties is immobilized, a nonwoven fabric containing a natural fiber or chemical fiber, or a mixture thereof as a web-consisting fiber is employed (see, for example, Patent Literature 3). Furthermore, as a carrier on which an enzyme is immobilized, ceramic, glass or organic high molecular materials in the form of porous film, fiber, spun fiber as well as woven network prepared by knitting fiber or spun fiber, or particle is provided (see, for example, Patent Literature 4). However, both these related arts are based on a liquid phase reaction in which sterilizing properties are developed only in the presence of water, and are not based on a gas phase reaction attended with sterilizing properties. Furthermore, a filter media containing a glass fiber as main fiber, on which the enzyme is immobilized and which a repellent treatment is not performed, has a high antimicrobial effect. For example, immobilizing enzyme on silica glass fiber is possibly due to having hydroxyl group on its surface (see, for example, Patent Literature 5). In the filter media on which the enzyme is immobilized, the filter media tend to lower water resistance and the repellency effect because the enzyme is immobilized to a fiber without a repellency treatment. Recently, in a lot of fields such as in the filter media for a fan coil, which is used frequently in a high humidity atmosphere, or in prevention of soaking up a sealing agent during processing a filter media, etc., a high water resistance (a high wet tensile strength), and an improved repellency which can repel humidity and drops of water is demanded. Examples of the demand as a strength against wetness in the case of its use in humidity during a ventilation or in outdoors are a dry tensile strength of 0.45 kN/m or more in a machine direction and 0.35 kN/m or more in a cross direction and a wet tensile strength of 0.176 kN/m in a cross direction of the filter media, according to a method of measurement defined in MIL-F-51079 C respectively. Furthermore, the repellency of 508 mm or more (the height of the water column), defined in MIL-282, is desired simultaneously. It can be regarded that, in order to achieve it, a repellent is applied to the enzyme-immobilized filter media of the said Patent Literature 5. However, in this filter media, a repellent-untreated surface of the fiber is a precondition for the absolute immobilization of the enzyme on the surface of the fiber. Since the repellent treatment after the enzyme immobilization, in order to achieve the high repellency, lowers the activity of the enzyme, it was difficult to simultaneously achieve a high water resistance and a high water repellency. Furthermore, as a related art, a process for the preparation of a usual air filter media is provided (see, for example, Patent Literature 6). The herein provided process for the preparation of a usual air filter media comprised applying a solution containing an organic synthetic resin binder, polyisocyanate compound and repellent to glass fiber constituting an air filter media and drying so that a satisfactory strength of the filter media, such as a high dry tensile strength and a high wet tensile strength, is achieved. However, after dehydrating an air filter media fiber and forming, the solution containing the organic synthetic resin binder, polyisocyanate compound and repellent is mixed with the enzyme and the resulting mixture is applied only to a filter media fiber according to this preparation process, sufficient strength of the filter media, such as a dry tensile strength and a wet tensile strength is not achieved. If this related art is copied simply, the enzyme is taken into synthetic resin binder film, a part in which the enzyme was taken into is heterogeneous concerning a fixing between each filter media fiber so that a development of binding strength between each fiber is hindered. As a result, a deterioration of the dry tensile strength and the wet tensile strength occurs. Furthermore, since the synthetic resin binder hinders a binding between fiber and the enzymes by covering the enzyme with a film of the synthetic resin binder, the enzyme is in a heterogeneously fixing state on the filter media fiber so that its sterilizing properties are lost. Patent Literature 1: JP-A-2000-288323, page 3, left column, Patent Literature 2: JP-A-8-144199, page 2, left column to page 3, right column, Patent Literature 3: JP-A-60-49795, page from 1 to 2, Patent Literature 4: JP-A-2-4116, page from 1 to 2, FIGS. 1 to 3, Patent Literature 5: WO 98/04334, page 3, lower left column to page 4, upper right column, Patent Literature 6: JP-A-9-225226, page 2, right column to page 3, right column. OBJECT TO BE SOLVED BY THE INVENTION It is therefore an object of the invention to provide an air purifying filter media immobilized by the enzyme, which improves the bactericidal/sterilizing or antimicrobial means properties using enzyme, and also improves a high dry tensile strength and a high wet tensile strength in association with a high water resistance, and a high repellency. MEANS FOR SOLVING THE OBJECT This object was solved by an air purifying filter media having bactericidal/sterilizing or antimicrobial means properties using enzyme reaction, which is obtained by applying a mixture of the modified enzyme which has an ionic polarity opposite to the ionic polarity of the whole filter media fiber having a functional group, and which has sterilizing properties, with an ionic synthetic resin binder having the opposite ionic polarity similar to the modified enzyme, to the whole filter media fiber, as described above. This filter media also has an outstanding water resistance and an excellent repellency. The filter media fiber of the air purifying filter according to the invention is not limited in any particular way as long as it is capable of performing as an air purifying filter media and has a functional group. Preferably, it is at least one of a group consisting of boron-silica glass fibers, alkyl amine glass fibers, silica-alumina fibers, rayon fibers, cotton fibers, hemp fibers, wool fibers, polyamide fibers, polyvinyl alcohol fibers, acetate fibers, polyacrylamide fibers or a copolymer thereof. The functional group which the air purifying filter media fibers, used according to the invention, possess, is at least one of a group consisting of hydroxyl and carboxyl group having an anionic polarity, and an amino and an imino group having a cationic polarity. When the modified enzyme is used in a mixture with an ionic synthetic resin binder, in case they have the same polarity as each other, the mixture is in a stabile state without an occurrence of an interferential action. In case they have different polarities, the interferential action occurs with both materials so that a new compound is produced. As a result, they cannot coexist as a stabile mixture. Therefore both materials used must possess the same ionic polarity. Most of the modified enzyme immobilized to the functional group of the filter media fiber has plural groups selected from a group consisting of an amino and carboxyl group and others. The polar condition is largely variable depending on the external environment such as pH (hydrogen ion concentration). Concerning the optimum pH-width of the modified enzyme, there is a wide case or a narrow case, where each of the modified enzymes has a different optimum pH-width. The modified enzymes having the ionic polarity opposite to the ionic polarity of the filter media fiber become easily chemically binding, for example in a form of covalent bond or ionic bond to the filter media fiber optionally by controlling pH-value, so that the strength binding with the fiber is achieved. Such the modified enzyme is preferably at least one selected from a group consisting of N-substituted carbamate bromide, N-substituted imide carbonate bromide, acetyl bromide+triacetyl cellulose, dimethylaminoethyl, diethylaminoethyl, protamine, polyethylene imine, polyvinyl amine, polyallyl amine, polylysine, polyornitine, dextran, dextran sulfate, dextrin and chondroitin sulfate. The modified enzyme used according to the invention is not limited in any particular way, but preferably is at least one selected from a group consisting of β-1,3-glucanase, chitinase, lysozyme, protease, glucosirase, β-galactosidase, endo-β-N-acetylglucosamidase and endolysin. Binder is used mainly in order to bind fibers to each other and to finish the form of the filter media, and for this reason is necessary for the preparation of the filter media. The ionic synthetic resin binders having an ionic polarity opposite to the ionic polarity of the filter media fiber are a cationic synthetic resin binder or an anionic synthetic resin binder. The cationic synthetic resin binder has a weak to strong cationic property, while the anionic synthetic resin binder has a weak to strong anionic property. The cationic synthetic resin binder is acrylic resin, for example, Light-Epoch®BX-71 (maker: KYOUEISYA CHEMICAL Co., Ltd.), urethane resin, for example, Super-Flex® 600 (maker: DAI-ICHI KOGYO SEIYAKU CO., LTD.), vinyl acetate resin, for example, Movinyl® 350 (maker: Clariant polymer Cop., Ltd.), SBR resin, for example, Cementex® C220T (maker: Obanaya Cementex Co. Ltd.), Epoxy resin, for example, Santax® P-5500 (maker: Mitsui Chemicals Inc.), polyvinyl alcohol resin, for example, C-506 (maker: Kuraray Co., Ltd.). Among these cationic synthetic resins, at least one is used. The anionic synthetic resin binder is at least one selected from a group consisting of acrylic resin, Voncoat® AN-155 (maker: DAINIPPON INK AND CHEMICALS INC.), urethane resin, Super-flex® 700 (maker: DAI-ICHI KOGYO SEIYAKU CO., LTD.), vinyl acetate resin, for example, Movinyl® 303 (maker: Clariant polymer Cop. Ltd.), SBR resin, for example, Lacstar® 7300A(maker: DAINIPPON INK AND CHEMICALS INC.), Epoxy resin, for example, Dicfine® EN-0270 (maker: DAI NIPPON INK AND CHEMICALS INC.), polyvinyl alcohol resin, for example, KL-318 (maker: Kuraray Co., Ltd.). Among these anionic synthetic resins, at least one is used. It is shown that the effect concerning a high dry tensile strength, a high wet tensile strength developing a high water resistance, and a high repellency, which cannot be achieved by each of the said ionic synthetic resin binders and the modified enzymes, is developed by the combination of both. If the functional group of the filter media fibers to be used has an anionic polarity such as hydroxyl and carboxylic group, using the cationic synthetic resin binder is most suitable. While, if the functional group of the filter media fibers to be used has a cationic polarity such as an amino group, using the anionic synthetic resin binder is most suitable. This combination is an embodiment of the inventive process for the preparation of the filter media on which the modified enzyme is immobilized. When the ionic synthetic resin is selected, in case the functional group of the filter media fiber used is an anion group such as hydroxyl and carboxylic group, selecting a cationic synthetic resin is most suitable. If the functional group of the filter media fiber has a cationic polarity, as an amino group, selecting an anionic synthetic resin binder is most suitable. If the mixture consisting of the said fiber having an anionic polarity and the fiber having a cationic polarity is used, the modified enzyme and the ionic synthetic resin binder must be so selected that they are suited to the fiber accounting for a major mixing proportion. If using the said ionic synthetic resin binder and the modified enzyme is unsatisfactory for a desired repellency, a water repellent agent can be also used in order to supplement a repellency of the filter media. A fluorine compound repellent is very suitable to annex high water repellency and high oil repellency to the filter media, because it gives not only water repellency but also oil repellency to the filter media. However, in case a large amount of the repellent is applied to the filter media, the sterilizing properties of the modified enzyme are decreased. Therefore, in order to keep a sterilization ratio of 99.9% or more, it is desired that the applied amount of the repellent is limited to a minimum amount. The applied amount of the repellent is below 0.1% by weight, preferably below 0.08% by weight based on the weight of the filter media. In addition to the ionic synthetic resin binder used in the invention, an internal fibrous binder such as polyvinyl alcohol fiber, olefin fiber, etc., can be used without a problem, because they do not prevent the effect achieved by the invention. Viewed in the practical economy, an embodiment of the process for the preparation of the enzyme-immobilized filter media of the invention is shown as follows: The filter media fibers used are selected in a most suitable mean fiber-diameter thereof in consideration for desired physical properties such as a pressure drop, a filter media collection efficiency and basis weight of the filter media and are compounded with each other. In the case of one example of the high efficiency particulate air filter media (HEPA filter media), a compound consisting of 95% of an ultrafine glass fiber of 3 μm or less, a mean diameter, and 5% of a chopped strand glass fiber is used. In the case of one example of the middle efficiency air filter media, a compound consisting of 50% of an ultrafine glass fiber of 3 μm or less in mean diameter and 50% of a chopped strand glass fiber is used. The ionic synthetic resin binder having the same polarity as that of the modified enzyme has compatibility with the latter so that it possess an advantageous property that it is not easily interfered with. After preparation of a slurry containing both fibers having a different diameter by using this property for obtaining the desired filter media, to a wet paper web produced from the slurry under dehydration by using a wet-type paper machine or a dried paper thereof is applied a mixture (in a solution or dispersion) consisting of the modified enzyme and an ionic synthetic resin binder and, if desired, a repellent. This enables the uniform immobilization of the modified enzyme to the filter media fiber and uniform adherence of the ionic synthetic resin binder to the filter media fiber. Herein, a wet paper web is that which has a water content of from 10% to 90%, preferably from 20% to 80%, while a dry paper is that which has water content of 10% or less. An application of a mixture consisting of the modified enzyme and an ionic synthetic resin binder on a wet paper web or a dry paper is preferably carried out before following the paper-making step, for example dehydration and/or washing and/or drying step, but it can be effected by applying on the dry paper applied the mixture of the modified enzyme and an ionic synthetic resin binder, by washing and again drying. A method for applying the modified enzyme and an ionic synthetic resin binder is a dipping method, a spraying method, roll transcribing method, etc. Cylinder dryer, Yankee dryer, through dryer, rotary dryer or infrared dryer, etc., can be used for the drying method. Furthermore, 2 types of dryer may be also used for drying the inventive filter media, without prevention. An embodiment of the process of the invention is shown as follows: The slurry compounded a fiber having a diameter suitable for the desired filter media is prepared, thereafter the said slurry is dehydrated in a paper-making machine to form a wet paper web, and this wet paper web is impregnated in an aqueous solution containing the modified enzyme and an ionic synthetic resin binder, dehydrated and, if desired, washed with water and dried by the rotary dryer. In this drying step, in order to develop simultaneously high sterilizing properties, a high dry tensile strength and a high wet tensile strength, as well as a high water repellency, the preferable reaction time and the reaction temperature range, as well as the optimal amount of the modified enzyme and the ionic synthetic resin binder, have importance for optimally immobilizing the enzyme by the chemical binding between the functional group of the filter media fiber and the modified enzyme, such as a covalent bond or ionic bond, etc. As a result of our verification, when the temperature of the drying step is less than 80° C., the immobilization of the modified enzyme by the chemical bond between the filter media fiber and the modified enzyme is not progressed virtually, and the wet tensile strength and the repellency are not developed, because there is no development of the strength based on the solidification of the ionic synthetic resin binder. In case the drying temperature is more than 220° C., the high dry tensile strength and the high wet tensile strength are achieved, but the sterilizing properties of the modified enzyme decrease. Therefore, the temperature of the drying step is between 80° C. to 220° C., and preferably 100° C. to 200° C. If the amount of the ionic synthetic resin binder is less than 0.1% by weight, based on the filter media after drying, an effect required for a practical use is not achieved. If that amount is more than 10.0% by weight, the pressure drop of the filter media increase, physical properties such as dust particles collection efficiency as a filter media decrease, and at the same time, the sterilizing properties also decrease by coating a part of the modified enzyme with an ionic synthetic resin binder. Therefore, the suitable amount of the ionic synthetic resin binder is 0.1 to 10.0% by weight, and preferably 0.5 to 7.0% by weight. If the amount of the modified enzyme is also less than 0.01% by weight, based on the dried filter media, an effect required for a practical use is not achieved. The upper limit thereof is equivalent to the number of the functional group. For example, in case the fiber is boron silica fiber having many functional groups, it is 4.0% by weight. If more than this is used, only the number of the functional groups is immobilized on the filter media fiber. Therefore, the suitable amount is 0.01% by weight or more, and preferably 0.05% by weight or more. The invention enables the satisfactory, simultaneous effect of the high dry tensile strength and the high wet tensile strength, as well as the high water repellency of the filter media without decreasing the sterilizing properties and the dust collection efficiency. As a result, the use of the filter media in an environment of high humidity in which using a filter media was difficult until today is enabled. By using the inventive air purifying filter media having the sterilizing properties the microorganism floated in air, such as bacteria and fungi is collected by the filter media, even if in an environment which an absolute humidity of the air is 100 ppm or more, glycoside, amide, peptide, etc., which construct a cell wall, are cut by hydrolysis, the microorganism is ruptured at the cut part of its cell wall by osmotic pressure and dies out. As a result, this mechanism leads to a bactericidal, bacteria-removal, bacteriostatic effect, and then a growth and scatter of the microorganism is prevented and a secondary pollution is kept out. The air filter media by which the secondary pollution is kept out like this can be used in an industrial or domestic field that requires an air filter media. Preferably, it is most suitable for business in a food factory, a drink factory, a pharmaceutical factory, facilities for experiment on animals, facilities for a hospital, facilities for a semiconductor, facilities for bioscience, etc. The present invention will be described below in detail with reference to Examination, Comparative Examples and Tests. It should, however, be noted that the invention is in no way limited by those Examples. EXAMPLES Example 1 95% ultrafine glass fiber of 3 μm or less in mean diameter, which has hydroxyl group as a functional group having an anionic polarity, and the 5% chopped strand glass fiber of 9 μm in mean diameter were dispersed in 0.4% aq. solution in 1 m3 acid water (pH 3.5) in a pulper to prepare a slurry. A wet paper web was produced from this slurry under dehydration by using a wet-type paper machine. The wet paper web was impregnated with a mild acidic aq. solution of pH 4.5 so as to apply the modified enzyme contained 3% by weight β-1,3-glucanase modified with bromide N-substituted carbamate and 3% by weight cationic synthetic resin binder (Light-Epoch® BX-71, KYOUEISYA CHEMICAL Co., Ltd.) based on the weight of the dried filter media, respectively. After dehydration it was dried by rotary drier at 120° C. to obtain HEPA filter media 1A having a basis weight of 63 g/m2. Example 2 95% ultrafine glass fiber of 3 μm or less in mean diameter, which has hydroxyl group as a functional group having an anionic polarity, and the 5% chopped strand glass fiber of 9 μm in mean diameter were dispersed in 0.4% aq. solution in 1 m3 acid water (pH 3.5) in a pulper to prepare a slurry. A wet paper web was produced from this slurry under dehydration by using a wet-type paper machine. The wet paper web was dried by rotary drier to obtain a dry paper. The dry paper was impregnated with a mild acidic aq. solution of pH 4.5, so as to apply the modified enzyme contained 3% by weight β-1,3-glucanase modified with bromide N-substituted carbamate and 3% by weight cationic synthetic resin binder (Light-Epoch® BX-71, KYOUEISYA CHEMICAL Co., Ltd.) based on the weight of the dried filter media, respectively. Thereafter it was dehydrated, washed and dried by rotary drier at 120° C. to obtain filter media 2A having a basis weight of 63 g/m2. Example 3 The procedure of Example 1 was repeated, except that the 50% ultrafine glass fiber of 3 μm or less in mean diameter, which has hydroxyl group as a functional group having an anionic polarity, and the 50% chopped strand glass fiber of 9 μm in mean diameter, were dispersed in 0.4% aq. solution in 1 m3 acid water (pH 3.5) by a pulper to prepare a slurry to obtain ASHRAE filter media 3A having a basis weight of 63 g/m2. Example 4 The procedure of Example 1 was repeated, except that, in Example 1, 0.03% by weight of fluorine compound repellent (Light-guard® FRG-1, KYOUEISYA CHEMICAL Co., Ltd.) based on weight of the filter media was applied to the wet paper web simultaneous with the modified enzyme and the cationic synthetic resin binder. HEPA filter media 4A having a basis weight of 63 g/m2 was produced. Example 5 The procedure of Example 1 was repeated, except that 100% by weight of Rayons fiber of 17 μm in mean diameter (3.3 Detx×5 mm, Cut goods, Daiwabo Rayon Co., Ltd.), which has hydroxyl group as a functional group having an anionic polarity was dispersed in 0.4% aq. solution in Jm3 acid water (pH 3.5) by a pulper to prepare a slurry. ASHRAE filter media 5A having a basis weight of 63 g/m2 was obtained. Example 6 95% ultrafine glass fiber of 3 μm or less in mean diameter and having hydroxyl group as a functional group having an anionic polarity, and the 5% chopped strand glass fiber of 9 μm in mean diameter were dispersed in 0.4% aq. solution in 1 m3 acid water (pH 3.5) by a pulper to prepare a slurry. A wet paper web was produced from this slurry under dehydration by using a wet-type paper machine. The wet paper web was impregnated with a mild acidic aq. solution of pH 4.5 so as to apply the modified enzyme containing 1.5% by weight protease modified with polyallylamine and 1.5% by weight β-1,3-glucanase modified with polyallylamine as well as 3% by weight cationic synthetic resin binder (Light-Epoch® BX-71, KYOUEISYA CHEMICAL Co., Ltd.) based on the weight of the dried filter media, respectively. Thereafter it was dehydrated, dried by rotary drier at 120° C. to obtain HEPA filter media 6A having a basis weight of 63 g/m2. Example 7 95% ultrafine glass fiber of 3 μm or less in mean diameter and having hydroxyl group as a functional group having an anionic polarity, and 5% chopped strand glass fiber of 9 μm in mean diameter were dispersed in 0.4% aq. solution in 1 m3 acid water (pH 3.5) by a pulper to prepare a slurry. The wet paper web was produced from this slurry under dehydration by using a wet-type paper machine. The wet paper web was impregnated with a mild acidic aq. solution of pH 4.5 so as to apply the modified enzyme containing 1% by weight protease modified with polyornitine, 1% by weight β-1,3-glucanase modified with polyornitine and 1% by weight lysozyme modified with polyornitine as well as 3% by weight cationic synthetic resin binder (Light-Epoch® BX-71, KYOUEISYA CHEMICAL Co., Ltd.) based on the weight of the dried filter media, respectively. Thereafter it was dehydrated, dried by rotary drier at 120° C. to obtain HEPA filter media 7A having a basis weight of 63 g/m2. Example 8 100% ion-exchange resin fiber of 30 μm in mean diameter, which has an amino group as a functional group having a cationic polarity (IEF-WA, Nitivy Co., Ltd.) was dispersed in 0.4% aq. solution in 1 m3 mild alkali water (pH 8.5) by a pulper to prepare a slurry. A wet paper web was produced from this slurry under dehydration by using a wet-type paper machine. The wet paper web was impregnated with a mild alkaline aq. solution of pH 8.5 so as to apply the modified enzyme containing 3% by weight β-1,3-glucanase modified with polyornitine and 3% by weight anionic synthetic resin binder (Voncoat® AN-155, DAINIPPON INK AND CHEMICALS INC.) based on the weight of the dried filter media, respectively. By this pH-control the modified enzyme indicated an anionic polarity. Thereafter it was dehydrated, dried by rotary drier at 120° C. to obtain ASHRAE filter media 8A having a basis weight of 63 g/m2. Example 9 The procedure of Example 1 was repeated, except that, in Example 1, the amount of the modified enzyme was replaced by 0.02% by weight. HEPA filter media 9A having a basis weight of 63 g/m2 was produced. Example 10 The procedure of Example 1 was repeated, except that, in Example 1, the amount of the cationic synthetic resin binder was replaced by 6% by weight based on the weight of the dried filter media. HEPA filter media 10A having a basis weight of 63 g/m2 was produced. Example 11 The procedure of Example 1 was repeated, except that, in Example 1, 70% ultrafine glass fiber of 3 μm or less in mean diameter, which has hydroxyl group as a functional group having an anionic polarity, and 30% ion exchange resin fiber of 30 μm in mean diameter were mixed in a pulper. HEPA filter media 11A having a basis weight of 63 g/m2 was produced. Comparative Example 1 The procedure of Example 1 was repeated, except that, in Example 1, the to be applied, modified enzyme mixture was omitted. HEPA filter media 1X having a basis weight of 63 g/m2 was produced. Comparative Example 2 The procedure of Example 1 was repeated, except that, in Example 1, the to be applied cationic synthetic resin binder was omitted. HEPA filter media 2X having a basis weight of 63 g/m2 was produced. Comparative Example 3 The procedure of Example 1 was repeated, except that, in Example 1, the to be applied cationic synthetic resin binder was replaced by the nonionic synthetic resin binder (MD-61, NIPPON NSC LTD.). HEPA filter media 3X having a basis weight of 63 g/m2 was produced. Comparative Example 4 The procedure of Comparative Example 4 was repeated, except that, in Comparative Example 4, in the step in which 3% by weight of the modified enzyme, 3% by weight of the cationic synthetic resin binder and 3% by weight of the water- and oil-repellent agent (Light-guard FRG-1, KOUEISYA CHEMICAL Co., Ltd.) were added additionally. HEPA filter media 4Y having a basis weight of 63 g/m2 was produced. Comparative Example 5 The procedure of, Comparative Example 4 was repeated, except that, in Comparative Example 4, the to be applied cationic synthetic resin binder was replaced by the nonionic synthetic resin binder (MD-61, NIPPON NSC LTD.). HEPA filter media 5Y having a basis weight of 63 g/m2 was produced. Comparative Example 6 The procedure of Example 5 was repeated, except that, in Example 5, the to be applied modified enzyme was omitted. ASHRAE filter media 6X having a basis weight of 63 g/m2 was produced. Comparative Example 7 The procedure of Example 5 was repeated, except that, in Example 5, the to be applied cationic synthetic resin binder was omitted. ASHRAE filter media 7X having a basis weight of 63 g/m2 was produced. Comparative Example 8 The procedure of Example 5 was repeated, except that, in Example 5, the to be applied cationic synthetic resin binder was replaced by the nonionic synthetic resin binder (MD-61, NIPPON NSC LTD.). ASHRAE filter media 8X having a basis weight of 63 g/m2 was produced. Comparative Example 9 The procedure of Example 6 was repeated, except that, in Example 6, the to be applied cationic synthetic resin binder was replaced by the nonionic synthetic resin binder (MD-61, NIPPON NSC LTD.). HEPA filter media 9X having a basis weight of 63 g/m2 was produced. Comparative Example 10 The procedure of Example 6 was repeated, except that, in Example 6, the to be applied cationic synthetic resin binder was replaced by the anionic synthetic resin binder (Voncoat® AN-155, DAINIPPON INK AND CHEMICALS INC.). HEPA filter media 10X having a basis weight of 63 g/m2 was produced. Comparative Example 11 The procedure of Example 7 was repeated, except that, in Example 7, the rotary drier temperature of 120° C. was replaced by 50° C. HEPA filter media 11X having a basis weight of 63 g/m2 was produced. Comparative Example 12 The procedure of Example 7 was repeated, except that, in Example 7, the rotary drier temperature of 120° C. was replaced by 230° C. HEPA filter media 12X having a basis weight of 63 g/m2 was produced. Comparative Example 13 The procedure of Example 8 was repeated, except that, in Example 8, the to be applied cationic synthetic resin binder was replaced by the nonionic synthetic resin binder (MD-61, NIPPON NSC LTD.). ASHRAE filter media 13X having a basis weight of 63 g/m2 was produced. Test 1: Water repellency This test was carried out in accordance with MIL-282. Test 2: Dry tensile strength and wet tensile strength This test was carried out in accordance with MIL-F-51079. Test 3: Pressure drop When the face velocity of 5.3 cm/sec passed to the filter media having an effective area of 100 cm2, a difference of the pressure was measured by manometer. Test 4: 0.3 μm DOP collecting efficiency The DOP collecting efficiency was measured by the laser particle counter, when the air contained DOP particles which was generated by the Laskin nozzle was passed to the filter media having an effective area of 100 cm2, in the face velocity of 5.3 cm/sec, wherein the diameter of the objective particle is 0.3 μm. Test 5: PF-Value This value is a guidepost of filter media efficiency and was determined based on the pressure drop and the DOP collecting efficiency according to the following formula I. A larger value is judged to be a better filter media efficiency. PF-Value=[LOG 10 {(100−DOP collecting efficiency)/100}×(−100)]/(pressure drop/9.81) Formula 1 Test 6: Bactericidal/sterilizing evaluation The test piece having an area 25 cm2 (dimension: 5×5 cm) was prepared by cutting a cut sample. In Test A; Micrococcus luteus cells were atomized to the test piece. In Test B; Bacillus subtilis cells were atomized to the test piece. In Test C; Staphlococcus aureus cells were atomized to the test piece. A sterilization ratio of the atomized bacteria is calculated as a percentage. Summary of These Tests Will be Explained as Follows: (1) A aqueous solution (concentration: 1×107 CFU/filter media) of the to be tested bacteria which was cultured in the heart infusion media, centrifuged and washed, was atomized on all required filter media papers in order to evaluate it. (2) After the said filter media papers were dried in air in a bio-safety-cabinet for a prescribed period, a bacterium was extracted by using a phosphate buffer solution in the violating mixer (or Stomacher®). (3) The extracted undiluted solution and the diluted solution were transplanted into the natural agar medium. (4) After 48-hours of cultivation, the colony count was measured, and the living bacteria were calculated. Result 1: 1A 2A 3A 1X 2X 3X Fiber material Glass fiber Glass fiber Glass fiber Glass fiber Glass fiber Glass fiber having OH having OH having OH having OH having OH having OH group group group group group group Wet paper Dry paper Wet paper Wet paper Wet paper Wet paper web web web web web HEPA filter HEPA filter ASHRAE HEPA filter HEPA filter HEPA filter media media filter media media media media Binder Cationic Cationic Cationic Cationic None used Anionic Enzyme Modified Modified Modified None used Modified Modified enzyme enzyme enzyme enzyme enzyme Pressure drop 285 288 38 285 282 280 (Pa) 0.3 μm DOP 99.9914 99.9927 73.00 99.9914 99.9912 99.9911 collecting efficiency (%) PF-Value 14.0 14.1 14.2 14.0 14.1 14.2 Water repellency 550 560 520 50 220 80 (mm: height of water column) Dry tensile 1.27 1.26 1.45 0.64 0.01 or less 0.25 strength (kN/m) Wet tensile 0.42 0.43 0.41 0.10 0.01 or less 0.10 strength (kN/m) Sterilization ratio Test A 99.99 or more 99.99 or more 99.99 or more Without effect 99.99 or more 99 Test B 99.99 or more 99.99 or more 99.99 or more Without effect 99.99 or more 99 Test C 99.99 or more 99.99 or more 99.99 or more Without effect 99.99 or more 99 When the filter media of Examples 1, 2 or 3 in which the modified enzyme having cationic polarity and the cationic synthetic resin binder were opposite polarity of the glass fiber having hydroxyl group as the functional group having the anionic polarity, the sterilizing properties, the sterilization ratio, of 99.99% or more, and the wet tensile strength of 0.42, 0.43 and 0.41 kN/m were achieved. However, in case of Comparative Example 1X in which the modified enzyme was not used, there is no sterilizing properties, and also the water repellency and the wet tensile strength were extremely worse. In the case of Comparative Example 2X in which the ionic synthetic resin binder was not used, but in which the modified enzyme was used, the wet tensile strength was 0.01 or less. In the case of Comparative Example 3X in which the nonionic synthetic resin binder was used, the water repellency is worse, and the sterilization ratio was 99%, that is, insufficient. As above-mentioned result, the filter media of Example 1A shows that, in case of using the mixture of the modified enzyme having cationic polarity and the cationic synthetic resin binder were opposite polarity of the glass fiber having hydroxyl group as the functional group having the anionic polarity is used, all of the water repellency, the dry tensile strength and the wet tensile strength are achieved effectively. Result 2: 1A 4A 4Y 3X 5Y Fiber material Glass fiber Glass fiber Glass fiber Glass fiber Glass fiber having OH having OH having OH having OH having OH group group group group group Wet paper Wet paper Wet paper Wet paper Wet paper web web web web web HEPA filter HEPA filter HEPA filter HEPA filter HEPA filter media media media media media Binder Cationic Cationic Cationic Nonionic Nonionic Enzyme Modified Modified Modified Modified Modified enzyme enzyme enzyme enzyme enzyme Repellent No 0.03% by 3.0% by None used 3.0% by weight weight weight Pressure drop (Pa) 285 291 286 280 281 0.3 μm DOP 99.9914 99.9945 99.9900 99.9911 99.9890 collecting efficiency (%) PF-Value 14.0 14.5 13.7 14.2 13.8 Water repellency 550 1020 1020 80 550 (mm: height of water column) Dry tensile strength 1.27 1.35 1.27 0.25 0.25 (kN/m) Wet tensile strength 0.42 0.45 0.42 0.10 0.10 (kN/m) Sterilization ratio (%) Test A 99.99 or more 99.99 or more 99 99 Without effect Test B 99.99 or more 99.99 or more 99 99 Without effect Test C 99.99 or more 99.99 or more 99 99 Without effect The filter media 4A of Example 4 was also prepared by using the water and oil repellent, in comparison with the filter media 1A of Example 1. Since the amount of the water and oil repellent was 0.03% by weight, the sterilization ratio and the wet tensile strength did not decrease, and excellent repellency was achieved. In the case of Comparative Example 4 in which the large amount, or 3.0% by weight of the water and oil repellent was used, the sterilization ratio was decreased in the level of 1/100 times in comparison with the filter media of Example 4. The filter media 5Y of Comparative Example 5 in which, in Comparative Example 4, the cationic synthetic resin binder was replaced by nonionic synthetic resin binder, and did not exhibit any sterilizing properties at all. Also its wet tensile strength was decreased remarkably to 0.10 kN/m. It seems that the water repellent exhibits excellent repellency by extinction of the hydrophilic group (hydroxyl group) on the fiber. Result 3: 5A 6X 7Y 8X Fiber material Rayon fiber Rayon fiber Rayon fiber Rayon fiber having OH having OH having OH having OH group group group group Wet paper web Wet paper web Wet paper web Wet paper web ASHRAE ASHRAE ASHRAE ASHRAE filter media filter media filter media filter media Binder Cationic Cationic None used Nonionic Enzyme Modified None used Modified Modified enzyme enzyme enzyme Pressure drop (Pa) 2.3 2.9 2.6 2.2 0.3 μm DOP collecting 12.50 15.00 10.90 11.80 efficiency (%) PF-Value 24.7 23.8 24.5 24.3 Water repellency 300 50 160 60 (mm: height of water column) Dry tensile strength 1.90 0.88 0.01 or less 0.39 (kN/m) Wet tensile strength 0.22 0.06 0.01 or less 0.04 (kN/m) Sterilization ratio (%) Test A 99.99 or more Without effect 99.99 or more 99 Test B 99.99 or more Without effect 99.99 or more 99 Test C 99.99 or more Without effect 99.99 or more 99 In case of the Rayon fiber having hydroxyl group as the functional group having the anionic polarity, the combination of the modified enzyme having the cationic polarity and the cationic synthetic resin binder achieves effectively all of the water repellency, the dry tensile strength and the wet tensile strength while maintaining the excellent sterilizing properties in the same manner as the glass fiber. The filter media of Comparative Examples 6 to 8 differed from that of Example 5, namely the filter media do not contain the modified enzyme (Comparative Example 6X), do not contain the binder (Comparative Example 7X) and that do not contain the nonionic binder (Comparative Example 8X), so that they could not achieve the desired properties. In detail, the filter media 6X had neither the water repellency nor the sterilizing property, the filter media 7X had neither the dry tensile strength nor the wet tensile strength, and the filter media 8X had a sterilizing property which is lower than the level of 1/100 of Example 5A, in the level of 100 times. Also its repellency and the dry tensile strength is much lower. Result 4: 6A 9X 10X Fiber material Glass fiber Glass fiber Glass fiber having OH having OH having OH group group group Wet paper web Wet paper web Wet paper web HEPA filter HEPA filter HEPA filter media media media Binder Cationic Nonionic Anionic Enzyme Modified Modified Modified enzyme enzyme enzyme Pressure drop (Pa) 290 283 288 0.3 μm DOP 99.9945 99.9909 99.9937 collecting efficiency (%) PF-Value 14.4 14.0 14.3 Water repellency 570 100 60 (mm: height of water column) Dry tensile strength 1.27 0.29 0.22 (kN/m) Wet tensile strength 0.42 0.10 0.10 (kN/m) Sterilization ratio (%) Test A 99.99 or more 99 99 Test B 99.99 or more 99 99 Test C 99.99 or more 99 99 The filter media 6A of Example 6 is an example in which the modified enzyme having the cationic enzyme and the cationic synthetic resin binder were used for the filter media fiber having the anionic polarity, wherein the excellent sterilizing properties, wet tensile strength and water repellency were achieved. In case of the filter media 9X of Comparative Example 9 in which the nonionic synthetic resin binder was used and of the filter media 10X of Comparative Example 10 in which the filter media fiber having the anionic polarity, and the same anionic synthetic resin binder were used, the sterilizing property, the wet tensile strength and the water repellency were very bad. Result 5: 7A 11X 12X Fiber material Glass fiber Glass fiber Glass fiber having OH having OH having OH group group group Wet paper web Wet paper web Wet paper web HEPA filter HEPA filter HEPA filter media media media Binder Cationic Cationic Cationic Enzyme Modified Modified Modified enzyme enzyme enzyme Drying Temperature 120 50 230 of rotary dryer Pressure drop (Pa) 288 275 282 0.3 μm DOP collecting 99.9927 99.9987 99.9905 efficiency (%) PF-Value 14.1 13.9 14.0 Water repellency 530 120 700 (mm: height of water column) Dry tensile strength 1.33 1.03 1.90 (kN/m) Wet tensile strength 0.42 0.11 0.69 (kN/m) Sterilization ratio (%) Test A 99.99 or more 99.99 or more 99 Test B 99.99 or more 99.99 or more 99 Test C 99.99 or more 99.99 or more 99 Since, in case of Comparative Example 11 in which the temperature of the dry step was 50° C., the immobilization of the modified enzyme through covalent bonding, etc, and development of the strength by the cationic synthetic resin binder was not progressed completely, the wet tensile strength which means water resistance, and the water repellency were developed insufficiently (Filter media 11X). In Comparative Example 12 in which the temperature of the drying step was 230° C., the sterilizing properties of the modified enzyme decreased (Filter media 12X). Therefore, it has known that the temperature of the drying step is preferably from 80 to 220° C. Result 6: 8A 13X Fiber material Ion exchange resin Ion exchange resin fiber having amino fiber having amino group group Wet paper web Wet paper web ASHRAE ASHRAE filter media filter media Binder Anionic Nonionic Enzyme Modified enzyme Modified enzyme Pressure drop (Pa) 1.0 0.9 0.3 μm DOP collecting 5.70 5.20 efficiency (%) PF-Value 25.0 25.2 Water repellency 520 50 (mm: height of water column) Dry tensile strength 1.33 0.29 (kN/m) Wet tensile strength 0.37 0.04 (kN/m) Sterilization ratio (%) Test A 99.99 or more 99 Test B 99.99 or more 99 Test C 99.99 or more 99 When the filter media 8A of Example 8 compares with the filter media 13X of Comparative Example 13, it has known that, in the case where the functional group of the filter media fiber is the amino group having the cationic polarity, using the anionic modified enzyme and the anionic synthetic resin binder lead to the excellent sterilizing properties and the wet tensile strength. Result 7: 1A 9A 10A 11A 1X Fiber material Glass fiber Glass fiber Glass fiber 70% Glass fiber Glass fiber having OH having OH having OH having OH having OH group group group group, and group 30% Ion exchange resin fiber having amino group Wet paper Wet paper Wet paper Wet paper Wet paper web web web web web HEPA filter HEPA filter HEPA filter HEPA filter HEPA filter media media media media media Binder Cationic Cationic Cationic Cationic Cationic Enzyme Modified Modified Modified Modified None used enzyme enzyme enzyme enzyme Pressure drop 285 290 280 220 285 (Pa) 0.3 μm DOP 99.9914 99.9937 99.9917 99.9915 99.9914 collecting efficiency (%) PF-Value 14.0 14.2 14.3 14.3 14.0 Water repellency 550 540 1250 620 50 (mm: height of water column) Dry tensile 1.27 1.18 1.45 1.20 0.64 strength (kN/m) Wet tensile 0.42 0.38 0.55 0.40 0.10 strength (kN/m) Sterilization ratio (%) Test A 99.99 or more 99.99 99.99 99.99 or more Without effect Test B 99.99 or more 99.99 99.99 99.99 or more Without effect Test C 99.99 or more 99.99 99.99 99.99 or more Without effect The filter media 9A of Example 9 demonstrates that, when the applied amount of the modified enzyme was decreased, the sterilizing properties decrease, but a sterilization ratio of 99.99% or more is achieved. The filter media 10A of Example 10 demonstrates that, when the applied amount of the cationic synthetic resin binder was increased, the sterilizing properties decrease, but a sterilization ratio of 99.9% or more is achieved. The filter media 11A of Example 11 demonstrates that, even if the glass fiber having the hydroxyl group as the functional group having the anionic polarity was used in a mixture with the ion exchange resin fiber having an amino group as the functional group having the cationic polarity, in that case the ionic polarity of the whole glass fiber is the anionic polarity opposite to the ionic polarity of the cationic modified enzyme, and the cationic synthetic resin binder, the sufficient repellency, the sufficient wet tensile strength, and the sufficient sterilizing properties are achieved.

<SOH> TECHNICAL FIELD <EOH>This invention relates to an air purifying filter media having a high water resistance and a high repellency as well as exhibiting bactericidal/sterilizing or antimicrobial means properties using enzyme reaction in a gas phase.

20050131

20090421

20060608

68076.0

B01D4600

PHAM, MINH CHAU THI

AIR PURIFYING FILTER MEDIA AND PROCESS FOR PRODUCING THE SAME

UNDISCOUNTED

ACCEPTED

B01D

ACCEPTED

Polyethers and their use as carrier oils

The present invention relates to polyethers which are obtainable from 1-butene oxide and an alcohol using a double metal cyanide compound as a catalyst and have a content of unsaturated components of 6 mol % or more, to a process for preparing such a polyether and also to the use of a polyether according to the invention as a carrier oil or in a carrier oil formulation, in particular in additive packages for gasoline fuels, and furthermore also to carrier oil formulations and also to fuels comprising a polyether according to the invention.

1. A polyether obtained by reacting 1-butene oxide and an alcohol in the presence of a double metal cyanide compound as a catalyst, wherein the content of unsaturated components is 6 mol % or more. 2. The polyether as claimed in claim 1, wherein the content of unsaturated components is from 7 mol % to 50 mol %. 3. The polyether as claimed in claim 1, wherein the alcohol has from 2 to 24 carbon atoms. 4. The polyether as claimed in claim 1, wherein the alcohol is a monofunctional alcohol. 5. The polyether as claimed in claim 1, wherein (A) the polyether has a viscosity at 40° C. of from 20 to 330 mm2/s; or (B) the polyether has an oxygen content of at least 15.5%. 6. A process for preparing the polyether as claimed in claim 1, the process comprising: reacting 1-butene oxide and an alcohol in the presence of a double metal cyanide compound as a catalyst. 7. (canceled) 8. A carrier oil formulation comprising at least one polyether as claimed in claim 1. 9. A carrier oil formulation as claimed in claim 8, which is an additive package for gasoline fuels. 10. A fuel comprising at least one polyether as claimed in claim 1. 11. A carrier oil formulation comprising a polyether obtained by the process as claimed in claim 6. 12. A carrier oil formulation as claimed in claim 11, which is an additive package for gasoline fuels. 13. A fuel comprising a polyether obtained by the process as claimed in claim 6. 14. A fuel comprising a carrier oil formulation as claimed in claim 8. 15. A fuel comprising a carrier oil formulation as claimed in claim 11.

The present invention relates to polyethers which are obtainable from 1-butene oxide and an alcohol using a double metal cyanide compound as a catalyst and have a content of unsaturated components of 6 mol % or more, to a process for preparing such a polyether and also to the use of a polyether according to the invention as a carrier oil or in a carrier oil formulation, in particular in additive packages for gasoline fuels, and also to carrier oil formulations and to fuels comprising a polyether according to the invention. The prior art discloses various preparative processes for polyethers. Polyethers based on 1-butene oxide are reacted with long-chain fatty alcohols as the initiator to give monofunctional polyethers, conventionally by basic catalysis, for example using potassium hydroxide. These monofunctional polyethers may be used as carrier oils for petroleum additives. These polyethers prepared by means of basic catalysis have a certain level of unsaturated compounds, generally from 0.5 to less than 6 mol %. As described, for example, in WO 98/44022, it had been hitherto assumed that the by-products resulting from the basically catalyzed polymerization, in particular polyols and unsaturated components, have a negative influence on the performance of the products obtained. WO 98/44022 discloses that polyethers prepared by means of double metal cyanide catalysis and having a content of less than 6 mol % of unsaturated compounds have distinctly improved properties as petroleum additives. It is an object of the present invention to use this prior art as a starting point to provide further inexpensive, lipophilic polyethers based on 1-butene oxide which may be used, for example, as petroleum additives. We have found that this object is achieved by polyethers which are obtainable from 1-butene oxide and an alcohol using a double metal cyanide compound as a catalyst and have a content of unsaturated components of 6 mol % or more. Surprisingly, 1-butene oxide polyethers which have a relatively high content of unsaturated compounds and have been obtained by means of double metal cyanide catalysis in particular have very good properties as carrier oils. The utility of lipophilic 1-butene oxide polyethers which have an elevated content of unsaturated compounds as carrier oils for fuel additives was investigated. It was found that in contrast to the teaching of WO 98/44022, these lipophilic 1-butene oxide polyethers having an increased level of unsaturated components show no performance losses compared to classically prepared carrier oils based on 1-butene oxide having a lower proportion of unsaturated components. According to the invention, polyethers having a content of unsaturated components of from 7 mol % to 50 mol %, for example from 8 mol % to 30 mol %, in particular from 9 mol % to 15 mol %, are particularly advantageous. In preferred embodiments, the present invention therefore relates to polyethers having a content of unsaturated components of from 7 mol % to 50 mol %, to polyethers having a content of unsaturated components of from 8 mol % to 30 mol % or to polyethers having a content of unsaturated components of from 9 mol % to 15 mol %. To prepare the polyethers according to the invention, alcohols, for example, having from 2 to 24 carbon atoms may be used, in particular alcohols having from 5 to 15, or, for example, having from 8 to 13, carbon atoms. A further embodiment of the present invention therefore relates to polyethers which are prepared using an alcohol having from 2 to 24 carbon atoms. For the purposes of the invention, the alcohol used for the preparation is advantageously a monofunctional alcohol. A further embodiment of the invention therefore relates to polyethers which are prepared using a monofunctional alcohol. Examples of useful alcohols according to the invention include octanol, nonanol, decanol, undecanol, dodecanol, tridecanol, tetradecanol, pentadecanol, iso-octanol, iso-nonanol, iso-decanol, iso-undecanol, iso-dodecanol, iso-tridecanol, iso-tetradecanol, iso-pentadecanol, preferably iso-decanol, 2-propylheptanol, tridecanol, iso-tridecanol and mixtures of C13- to C15 alcohols. The polyethers according to the invention have a viscosity at 40° C. of, for example, from 20 to 330 mm2/sec, in particular from 30 to 300 mm2/sec. According to the invention, the oxygen content of the polyethers may vary, but is at least 15.5%, in particular 16.5%. A further embodiment of the invention therefore relates to polyethers which fulfill at least one of the following properties (A) or (B): (A) the polyether has a viscosity at 40° C. of from 20 to 330 mm2/s; (B) the polyether has an oxygen content of at least 15.5%. The present invention furthermore relates to a process for preparing a polyether having a content of unsaturated components of 6 mol % or more by reacting 1-butene oxide and an alcohol with each other in the presence of a double metal cyanide compound as a catalyst. The process according to the invention may be effected, for example, in a batch process, but according to the invention it is equally possible to perform the process semicontinuously or continuously. In the process according to the invention, 1-butene oxide and an alcohol are reacted with each other. According to the invention, a monofunctional alcohol having from 2 to 24 carbon atoms is used for the process. A further embodiment of the present invention therefore relates to a process in which the alcohol used is a monofunctional alcohol having from 2 to 24 carbon atoms. According to the invention, the alcohol and 1-butene oxide are reacted with each other in a molar ratio of from at least 1:3 to a maximum of 1:100, for example from 1:5 to 1:80, in particular from 1:1 to 1:50. The catalyst used in the process according to the invention is a double metal cyanide compound. DMC compounds suitable as catalysts are described, for example, in WO 99/16775 and DE 10117273.7. According to the invention, double metal cyanide compounds of the general formula I in particular are used as catalysts for the process according to the invention: M1a[M2(CN)b(A)c]d.fM1gXn.h(H2O).eL.kP (I) where M1 is at least one metal ion selected from the group consisting of Zn2+, Fe2+, Fe3+, Co3+, Ni2+, Mn2+, Co2+, Sn2+, Pb2+, Mo4+, Mo6+, Al3+, V4+, V5+, Sr2+, W4+, W6+, Cr2+, Cr3+, Cd2+, Hg2+, Pd2+, Pt2+, V2+, Mg2+, Ca2+, Ba2+, Cu2+, La3+, Ce3+, Ce4+, Eu3+, Ti3+, Ti4+, Ag+, Rh2+, Rh3+, Ru2+ and Ru3+, M2 is at least one metal ion selected from the group consisting of Fe2+, Fe3+, Co2+, Co3+, Mn2+, Mn3+, V4+, V5+, Cr2+, Cr3+, Rh3+, Ru2+ and Ir3+, A and X are each independently an anion selected from the group consisting of halide, hydroxide, sulfate, carbonate, cyanide, thiocyanate, isocyanate, cyanate, carboxylate, oxalate, nitrate, nitrosyl, hydrogensulfate, phosphate, dihydrogenphosphate, hydrogenphosphate and hydrogencarbonate, L is a water-miscible ligand selected from the group consisting of alcohols, aldehydes, ketones, ethers, polyethers, esters, polyesters, polycarbonate, ureas, amides, primary, secondary and tertiary amines, ligands having pyridine nitrogen, nitriles, sulfides, phosphides, phosphites, phosphines, phosphonates and phosphates, k is a fraction or an integer greater than or equal to zero, and P is an organic additive, a, b, c, d, g and n are selected in such a manner as to ensure the electronic neutrality of the compound (I) and c may be 0, e, the number of ligand molecules, is a fraction or integer greater than or equal to 0, f, k, h and m are each independently a fraction or an integer greater than or equal to 0. Organic additives P include: polyethers, polyesters, polycarbonates, polyalkylene glycol sorbitan esters, polyalkylene glycol glycidyl ethers, polyacrylamide, poly(acrylamide-co-acrylic acid), polyacrylic acid, poly(acrylamide-co-maleic acid), polyacrylonitrile, polyalkyl acrylates, polyalkyl methacrylates, polyvinyl methyl ethers, polyvinyl ethyl ethers, polyvinyl acetate, polyvinyl alcohol, poly-N-vinylpyrrolidone, poly(N-vinylpyrrolidone-co-acrylic acid), polyvinyl methyl ketone, poly(4-vinylphenol), poly(acrylic acid-co-styrene), oxazoline polymers, polyalkylenimines, maleic acid and maleic anhydride copolymers, hydroxyethylcellulose, polyacetates, ionic surface- and interface-active compounds, bile acid or salts, esters or amides thereof, carboxylic esters of polyhydric alcohols and glycosides. These catalysts may be crystalline or amorphous. When k is zero, preference is given to crystalline double metal cyanide compounds. When k is greater than zero, preference is given to crystalline, semicrystalline and also substantially amorphous catalysts. There are various preferred embodiments of the modified catalysts. One preferred embodiment is a catalyst of the formula (I) where k is greater than zero. The preferred catalyst then contains at least one double metal cyanide compound, at least one organic ligand and at least one organic additive P. In another preferred embodiment, k is zero, e is optionally also zero and X is exclusively a carboxylate, preferably formate, acetate or propionate. Such catalysts are described in WO 99/16775. In this embodiment, preference is given to crystalline double metal cyanide catalysts. Preference is further given to double metal cyanide catalysts as described in WO 00/74845 which are crystalline and platelet-shaped. The modified catalysts are prepared by combining a metal salt solution with a cyanometallate solution, each of which may optionally comprise both an organic ligand L and also an organic additive P. The organic ligand and optionally the organic additive are then added. In a preferred embodiment of the catalyst preparation, an inactive double metal cyanide phase is first prepared and then converted by recrystallization into an active double metal cyanide phase, as described in PCT/EP01/01893. In another preferred embodiment of the catalysts, f, e and k are not equal to zero. These are double metal cyanide catalysts which comprise a water-miscible organic ligand (generally in amounts of from 0.5 to 30% by weight) and an organic additive (generally in amounts of from 5 to 80% by weight), as described in WO 98/06312. The catalysts may be prepared either with vigorous stirring (24 000 rpm with Turrax) or with stirring (U.S. Pat. No. 5,158,922). Useful catalysts for the process according to the invention are in particular double metal cyanide compounds which comprise zinc, cobalt or iron or two thereof. A particularly suitable example is Prussian Blue. According to the invention, preference is given to using crystalline DMC compounds. In a preferred embodiment, a crystalline DMC compound of the Zn—Co type which comprises zinc acetate as a further metal salt component is used as the catalyst. Such compounds crystallize in monoclinic structure and have a platelet-shaped habit. Such compounds are described, for example, in WO 00/74845 and PCT/EP01/01893. DMC compounds suitable as catalysts for the process according to the invention may in principle be prepared in any of the ways known to those skilled in the art. The DMC compounds may be prepared, for example, by direct precipitation, the incipient wetness method, or by preparing a precursor phase and recrystallizing. The DMC compounds may be used in the process according to the invention as a powder, paste or suspension or may be shaped into a shaped body, incorporated in shaped bodies, foams or the like, or applied to shaped bodies, foams or the like. According to the invention, the double metal cyanide compound is used in an amount of from 5 ppm to 5000 ppm, for example from 100 ppm to 1000 ppm, in particular from 20 ppm to 500 ppm, based on the final amounts. A further embodiment of the present invention therefore relates to a process in which the double metal cyanide compound is used in an amount of from 5 ppm to 5000 ppm, based on the final amounts. According to the invention, it is possible, for example, to carry out the process in a batch method, in a semibatch method or continuously. For example, the initiator/DMC mixture may initially be dewatered by conventional vacuum means. The vacuum may then be broken using nitrogen and the epoxide metered in under elevated pressure of from about 1 bar to about 2 bar. According to the invention, it is also possible that the vacuum is not completely removed and the internal reactor pressure at the initiation of the epoxidation is less than 1 bar. The present invention furthermore relates to the use of a polyether according to the invention as a carrier oil or in a carrier oil formulation, in particular in an additive package for gasoline fuels. For the purposes of the present invention, a carrier oil formulation is a composition comprising at least one carrier oil according to the invention. For the purposes of the present invention, a carrier oil is a substance which is used, for example, in an additive package for gasoline fuels and has the purpose of suppressing the tendency of a further additive of the carrier oil formulation, for example a detergent, to cause a valve to stick and/or of improving the properties of an additive package with respect to keeping the inlet system and the inlet valve clean. For the purposes of the present invention, an additive package for gasoline fuels is a composition which can be added to gasoline fuels in order to achieve an improved property profile of the gasoline fuel. According to the invention, an additive package for gasoline fuels comprises at least one carrier oil according to the invention or a carrier oil formulation according to the invention. According to the invention, the carrier oil formulations, in particular the additive packages for gasoline fuels, comprise, in addition to a carrier oil, for example, the following additives: at least one detergent, at least one solvent, at least one corrosion inhibitor, at least one demulsifier, at least one lubricity improver, at least one conductivity improver, and at least one colorant or marker. For the purposes of the present invention, examples of detergents, in particular for additive packages for gasoline fuels, include in principle the following compounds: polyisobutenamine (PIBA) prepared by hydroformylation of polyisobutene and subsequent hydrogenating amination; PIBA prepared by nitration of polyisobutene and subsequent hydrogenating amination; PIBA prepared by epoxidation of polyisobutene and subsequent hydrogenating amination; PIBA prepared by alkylation of phenol (cresol) using polyisobutene and subsequent Mannich synthesis with mono- and/or polyamines; PIBA prepared by chlorination of polyisobutene and subsequent reaction with mono- and/or polyamines; or polyisobutenesuccinimide prepared by maleating polyisobutene and subequent imidation using mono- and/or polyamines. In a preferred embodiment, the present invention therefore relates to the use of a polyether according to the invention or of a polyether preparable by the process according to the invention as a carrier oil and also to the use of a polyether according to the invention or a polyether preparable according to the invention in a carrier oil formulation, in particular in an additive package for gasoline fuels. The carrier oils, carrier oil formulations and additive packages according to the invention for gasoline fuels have the advantage, for example, that they may be prepared particularly inexpensively using the DMC compounds used in preparing the polyethers according to the invention. According to the invention, the carrier oil formulations, in particular the additive packages for gasoline fuels, have a content of at least one detergent of at least 10%. Preferred detergents for the additive packages according to the invention for gasoline fuels are polyisobutenamine or Mannich PIBA. A further embodiment of the present invention accordingly relates to the use of a polyether according to the invention or a polyether preparable by a process according to the invention in a carrier oil formulation, in particular in an additive package for gasoline fuels, each of which has a content of at least one detergent, preferably polyisobutenamine or Mannich PIBA, of at least 10%. In principle, the carrier oil formulations according to the invention, in particular the additive packages according to the invention, may also comprise mixtures of one or more of the detergents mentioned. The present invention also relates to carrier oil formulations, in particular to additive packages for gasoline fuels themselves, which comprise a polyether according to the invention, and also to a fuel which comprises a polyether according to the invention or a carrier oil formulation according to the invention, in particular an additive package according to the invention for gasoline fuels. In a preferred embodiment, the present invention relates to a carrier oil formulation which is an additive package for gasoline fuels. A carrier oil formulation according to the invention or an additive package according to the invention for gasoline fuels may be added to a fuel, for example, in amounts of from 100 to 2000 mg/kg of fuel. The invention is illustrated hereinbelow with the aid of examples. EXAMPLES Catalyst Synthesis: In a stirred tank having a capacity of 30 l equipped with a pitched blade turbine, a submerged pipe for the metering-in, a pH electrode, a conductivity measuring cell and scattered light probe, 16 500 g of aqueous hexacyanocobaltic acid (cobalt content: 9 g/l cobalt) were initially charged and heated with stirring to 50° C. 9695.1 g of aqueous zinc acetate dihydrate solution (zinc content: 2.6% by weight) which had likewise been heated to 50° C. were then added within 45 minutes with stirring at a stirrer output of 0.5 W/l. 354 g of Pluronic PE 6200 (BASF AG) were then added. The batch was heated to 55° C. and stirring was continued at this temperature for 1.5 hours. 3370 g of aqueous zinc acetate dihydrate solution (zinc content: 2.6% by weight) were then metered in at 50° C. within 5 minutes. The stirring energy was increased to 1 W/l. The stirring of the suspension was continued at a temperature of 55° C. and a stirrer output of 1.0 W/l until the pH had fallen from 4.15 to 3.09 and remained constant. The resulting precipitate suspension was filtered off and washed with 10 l of water. The damp filter cake was dried at 50° C. under reduced pressure. A crystalline solid was obtained. The X-ray diffraction pattern of the solid obtained could be monoclinically indexed, and the particle habit was platelet-shaped. 1. Synthesis of Tridecanol N+22 1-butene Oxide (KOH-catalyzed, Comparative Example): In a 2 l stirred reactor, 150 g (0.75 mol) of tridecanol N and 2.7 g of KOH were initially charged. The reactor was purged three times with nitrogen and then a pressure test was carried out. The reactor was evacuated to from about 10 to 20 mbar. Under vacuum, the mixture was heated to 100° C. and dewatered at 100° C. for 2 hours. The vacuum was broken using nitrogen. The mixture was heated to from 135 to 140° C. and 50 g of 1-butene oxide were then metered in at this temperature. After the reaction commenced, 1-butene oxide was metered in up to a maximum pressure of 8 bar within about 13 hours, and the total amount of 1-butene oxide metered in was 1188 g. Stirring was then continued at 140° C. to constant pressure, and the mixture was cooled to 80° C., depressurized and degassed in a vacuum of from 10 to 20 mbar for 2 hours. The reactor was then emptied. The content of unsaturated components was less than 1 mol %. 2. Synthesis of Tridecanol N+22 1-butene Oxide (DMC-catalyzed): In a 2 l stirred reactor, 120 g (0.6 mol) of tridecanol N and 4.28 g of DMC catalyst were initially charged. The reactor was purged three times with nitrogen and then a pressure test was carried out. The reactor was evacuated (about 10 to 20 mbar). Under vacuum, the mixture was heated to 120° C. and dewatered at 120° C. for 1.5 hours. The vacuum was broken using nitrogen. The mixture was heated to 140° C. and 50 g of 1-butene oxide were initially metered in at this temperature at a starting pressure of 0.9 bar. Once the reaction had commenced, 1-butene oxide was added within 9.5 hours, and the total amount of 1-butene oxide was 952 g. Stirring was continued at 140° C. to constant pressure, then the mixture was cooled to 80° C. and degassed in a vacuum of from 10 to 20 mbar for 2 hours. The reactor was then emptied. The content of unsaturated components of the reaction product was 28.8 mol %, and the kinematic viscosity at 40° C. was 113.4 m2/s. Experiments 3 to 7 were carried out in a similar manner to experiment 2. The results of the experiments are compiled in Table 1. TABLE 1 Ini- Epoxide Cat. Experi- tiator quantity quantity Temp. Unsaturated Viscosity ment Initiator [g] Epoxide [g] Catalyst [ppm] [° C.] [mol %] [mm2/s] 1 Tridecanol 150 1-BO 1188 KOH 2000 140 <1 150.00 2 Tridecanol 120 1-BO 952 DMC 200 140 28.8 113.37 3 Tridecanol 120 1-BO 949 DMC 200 55 21 128.89 4 Tridecanol 120 1-BO 952 DMC 25 135 28.1 112.81 5 Tridecanol 120 1-BO 955 DMC 300 170 27.1 103.23 6 Tridecanol 100 1-BO 792 DMC 200 135 14.1 144.00 7 Tridecanol 200 PO 845 DMC 25 135 4.2 56.47 Application Examples A model additive package comprising a detergent (PIBA prepared via hydroformylation of polyisobutene and subsequent hydrogenating amination), a carrier oil (from experiment No. 1 or experiment No. 4) and a corrosion protector was tested by the following experiments: a) Emulsion test to DIN 51415 b) Corrosion test to DIN 51585 (method A and B) c) Storage stability at −20° C., 0°C. and +35° C. d) Performance relating to intake valve cleanliness (IVD: intake valve deposits) and tendency to form chamber deposits (TCD: total chamber deposits) in MB M 111 according to CEC F-20-A-98 (CEC: Coordinating European Council). The experiments were carried out according to the standards cited. The results of the experiments are presented in Tables 2 to 5. TABLE 2 Emulsion test to DIN 51415 (dose: 600 mg/kg in a gasoline fuel according to DIN EN 228) Additive package Additive package based on carrier based on carrier oil from oil from Time [min] experiment 1 experiment 4 pH 4 1 4 (4 ml of foam) 4 (4 ml of foam) 5 4 (1 ml of foam) 3 30 2 3 60 1 1b pH 7 1 3 3 5 2 2 30 1 1 60 1 1 pH 9 1 3 2 5 1b 1b 30 1b 1b 60 1 1 TABLE 3 Corrosion test to DIN 51585 (method A and B) (dose: 600 mg/kg in fuel according to DIN EN 228) Double-distilled Synthetic water salt water Blank value 0 3 Additive package 0 0 based on carrier oil from experiment 1 Additive package 0 0 based on carrier oil from experiment 4 TABLE 4 Storage stability at −20° C., 0° C. and +35° C. Additive package Additive package based on carrier based on carrier Temperature oil from oil from Time [° C.] experiment 1 experiment 4 Start −20 — — 0 — — room clear, monophasic clear, monophasic temperature (RT) 35 — — 1 day −20 clear, monophasic clear, monophasic 0 clear, monophasic clear, monophasic RT — — 35 clear, monophasic clear, monophasic 1 week −20 clear, monophasic clear, monophasic 0 clear, monophasic clear, monophasic RT — — 35 clear, monophasic clear, monophasic 2 weeks −20 clear, monophasic clear, monophasic 0 clear, monophasic clear, monophasic RT — — 35 clear, monophasic clear, monophasic 4 weeks −20 clear, monophasic clear, monophasic 0 clear, monophasic clear, monophasic RT — — 35 clear, monophasic clear, monophasic TABLE 5 Performance relating to intake valve cleanliness (IVD) and tendency to form chamber deposits (TCD) in MB M 111 according to CEC F-20-A-98 (dose: 275 mg/kg and 325 mg/kg of additive package in a gasoline fuel according to DIN EN 228) Active Dose rate Average IVD TCD ingredient [mg/kg] IVD [mg/V] [mg/V] [mg/cyl.] Basis value 0 329, 388, 273, 336 1479 237, 244, 298, 474, 441 Basis value 0 348, 389, 217, 341 1458 209, 236, 232, 537, 557 Package based 275 0, 0, 51, 20, 19 1530 on carrier oil 23, 44, 0, 13 from experiment 1 Package based 275 23, 0, 58, 42, 36 1417 on carrier oil 45, 101, 0, 17 from experiment 4 Package based 325 4, 0, 21, 0, 1, 8 1544 on carrier oil 34, 1, 4 from experiment 1 Package based 325 0, 0, 6, 0, 0, 7 1494 on carrier oil 40, 0, 11 from experiment 4

20040910

20081230

20050721

68418.0

KEYS, ROSALYND ANN

POLYETHERS AND THEIR USE AS CARRIER OILS

UNDISCOUNTED

ACCEPTED

ACCEPTED

Service provisioning in telecommunications system comprising call control service capability servers

This invention describes a method of service provisioning in a telecommunication system, which telecommunication system is comprised of configurations of service switching point (SSP), service capability server (SCS) and service provisioning equipment, which configurations are configured to provide services to users, wherein the provisioning of at least one of said services requires the involvement of more than one service capability server. To set up the service, a direct interaction between the service capability servers is provided.

1. A method of service provisioning in a telecommunications system comprising at least two service switching points (SSP), at least two service capability servers (SCS) for providing services to users and service provisioning equipment, wherein the method comprises: responsive to a request from a user for a user interaction sequence, via a call control service capability server (CCSCS), an application on an application server forwarding the request to a user interaction service capability server (UISCS) the UISCS reserving a port on the service provisioning equipment in order to perform the user interaction sequence; notifying the CCSCS of the service provisioning equipment location; and instructing the CCSCS to connect the user to the service provisioning equipment via the at least two service switching points. 2. The method according to claim 1, wherein said interaction sequence comprises exchanging of instructions. 3. The method according to claim 2, wherein said instructions trigger the establishing of a communication link between a user and the service provisioning equipment of said telecommunications system. 4. The method according to claim 3, wherein prior to said direct interaction between the at least two service capability servers involved, at least one of said service capability servers instructs said service provisioning equipment to reserve at least one communication port for establishing said communication link. 5. The method according to claim 3, wherein following upon said direct interaction between said service capability servers, one of said service capability servers instructs one of the at least two service switching point to establish a connection with said service provisioning equipment. 6. The method according to claim 3, wherein said establishing of a communication link is the establishing of a speech channel. 7. The method according to claim 3 further comprising: reporting the establishment of said communication link to one of the service capability servers involved in the provisioning of service. 8. The method according to claim 3, further comprising: one of said service capability servers instructing the service provisioning equipment to perform an interaction sequence with said user. 9. The method according to claim 8, wherein said service provisioning equipment reports the results of said user interaction sequence to one of said service capability servers. 10. The method according to claim 3 further comprising: upon receiving results of the user interaction, the application instructing the UISCS to close the connection between the user and the provisioning service equipment. 11. The method according to claim 1, wherein said service provisioning equipment comprises: a resource server, such as a media server, and wherein said interaction between said service capability servers triggers the setup and disconnection of the communication link between the user and said resource server. 12. (canceled) 13. An arrangement for the provisioning of services via a telecommunications network, comprising: at least two service switching points (SSP) for setting up communications connections between users and service provisioning equipment; at least two service capability servers (SCS) for providing services to the users comprising a call control service capability server (CCSCS) and a user interaction service capability server (UISCS), wherein the CCSCS, passes a request for a user interaction sequence to an application running on an application server, the application server managing the at least two service capability servers; and the UISCS being instructed to reserve a port on the service provisioning equipment to perform the user interaction sequence, inform the application of the port reservation, notify the CCSCS of the service provisioning equipment location and instruct the CCSCS to connect the user to the service provisioning equipment via the at least two service switching points. 14. The arrangement according to claim 13, wherein the telecommunication system is a universal mobile telecommunications system (UMTS). 15. The arrangement according to claim 13, wherein said instructions trigger the establishing of a communication link between a user and the service provisioning equipment of said telecommunications system. 16. The arrangement according to claim 14, wherein following upon said direct interaction between said service capability servers, one of said service capability servers instructs one of the at least two service switching point to establish a connection with said service provisioning equipment. 17. The arrangement according to 15 wherein the establishing of a communication link is the establishing of a speech channel.

FIELD OF THE INVENTION The present invention relates generally to service provisioning in a telecommunications system, and more specifically, to a method of service provisioning in a telecommunications system, which telecommunications system is comprised of configurations of service switching point (SSP), service capability server (SCS) and service provisioning equipment, which configurations are configured to provide services to users, wherein the provisioning of at least one of said services requires the involvement of more than one service capability server. BACKGROUND OF THE INVENTION A method as described above is disclosed in International Patent Application nr. WO 01/88739, describing a personal service environment manager (PSEM). The document describes an open service architecture (OSA) comprising service capabilities servers and service provisioning servers or application servers. The document further describes the underlying network technology consisting of service switching points, and the setting up of services through one or more service capability servers interacting with the service provisioning servers or application servers. The number of services that can be offered over telecommunications networks and the integration of the services within modern society has increased rapidly over the past decennia. Services are becoming more and more sophisticated, and can be accessed by any user from any location at any point in time. The introduction of the universal mobile telecommunications system (UMTS) has accelerated this development even more. In general, in a telecommunications system, services are offered over the network using service capability servers (SCS). These service capability servers are responsible for management of the service and the telecommunications infrastructure required to provide that service. In the hierarchy below the service capability servers, the telecommunications infrastructure is comprised of service switching points (SSP), which are interconnected with each other. Service provisioning equipment, such as media servers, and user equipment, like a telephone set or a mobile phone, also connects to the service switching points. In recent years, UMTS has triggered the development of the so-called open service architecture (OSA), in which service providers can easily incorporate the services offered by a third party into there own service without having to reveal this to their customers. The customer will only deal with one provider from which he receives support, and which provider sends him one bill for all the services used. The use of this principle is not limited to UMTS. Those skilled in the art will appreciate that similar methods can be used in any telecommunications system. According to the open service architecture principle the user calls, for instance, to an application server, and accesses an application that provides the user with a choice of services. These services could be voice mail service, fax service, IP services, multi media, etc. As explained above, the provisioning of services itself over the telecommunications infrastructure is managed by service capability servers, and this is also the case for applications on an application server, which is accessed by users. As more complicated services are made up of interactions on different levels of communications, call control, user interaction, etc, each service capability (level/type of communication) may be handled by a different service capability server. A number of these service capability servers may be operated from the same location on the network, e.g. being part of a framework, but in some cases in order to offer a service a plurality of service capability servers are used from different locations. It is best to consider an example to illustrate this principle. Take for example the user calling into an application. First, the connection between the user and the application will be set up by a call control service capability server. As soon as this connection has been established the application will, for example, start a security authentication procedure. This security authentication procedure may consist of a digitised voice message after which the user can enter his pin code via dual tone multi-frequencies (DTMF) on the keyboard of his telephone set. Suppose however that the authentication procedure will not be handled by the application itself, but by a remote media server. In order to perform this action, the application needs to contact a remote user interaction service capability server. This service capability server may be in a different location than the service capability server that has established the call between the application and the user. The application knows exactly which service capability server to contact in order to start the authentication procedure. Ideally the application only temporarily transfers the call to the media server, responsible for carrying out the security authentication procedure, and take back the call after the procedure has ended. The transfer of a call is handled, as mentioned, by the call control service capability server. The problem is that the user interaction service capability server knows where the media server is, and the call control server, handling all details of the user call, needs to transfer the call whilst maintaining contact to the application. In this case an extra speech channel needs to be set up between the service switching point and the media server. In an existing solution, the location details of the media server are offered by the user interaction service capability server to the application, and the application, on his turn, forwards this information to the call control service capability server. Upon receiving this information the call control service capability server instructs the service switching point to open a speech channel to the media server as it now knows where this media server is located. The major issue with this solution is that the application is involved in the management of the telecommunication services, while in principle, the underlaying telecommunications infrastructure needs to be transparent to the application, as well as to the user. SUMMARY OF THE INVENTION It is an object of the present invention to provide a solution to the management of a telecommunications infrastructure in case a service is offered by an application in an open service architecture, which service requires the involvement of more than one service capability server. In addition, the solution offered needs to be transparent to both the application offering the service, as well as the user requesting the service. According to the present invention management of the telecommunications infrastructure is controlled via direct interaction between the service capability servers involved in the provisioning of service. In particular this means that, for instance in the example described above, upon receiving instructions from the application, the user interaction service capability server forwards the location of the media server directly to the call control service capability server handling the call between the user and the application (and not to the application). In order to enable this a protocol and instructions need to be defined as the language between the service capability servers. Naturally, these instructions would comprise instructions for setting up a connection, as well as for terminating connections, and instructions for the exchange of specific information required to control the telecommunications infrastructure. A method for the provisioning of services in a telecommunications system according to the invention, comprised of an application server, service capability servers, service switching points and service provisioning equipment, such as a media server, is described below. It will be comprised of the steps of accessing the application, requesting a user interaction sequence, preparing of the telecommunications infrastructure, the user interaction itself, and closing all connections made except for the call between the user and the application. The procedure starts by an incoming call, from the service switching point to the call control service capability server, which call will be passed on by the service capability server to the application running on the application server. Here, a user interaction is required, for example the security authentication, and the application will contact the user interaction service capability server and forward the user interaction request. The user interaction service capability server, upon receiving the user interaction request, will instruct the media server to reserve a communications port over which the user interaction can be performed. It will then contact the call control service capability server, and inform the call control service capability server of the location of the media server, and instruct the call control service capability server to establish a connection between the service switching point and the media server. The call control service capability server will then instruct the service switching point to set up a, for instance, speech channel between the service switching point and the media server, informing the service switching point of the reserved communication ports on the media server that can be used to establish the connection. After this the speech channel will be set up and the media server will acknowledge to the user interaction service capability server that a connection has been established between the media server and the service switching point. The user interaction service capability server will now forward the user interaction request to the media server which, on his turn, carries out the user interaction sequence. This sequence could be the playing of a digitalised message or a sound, the input of a pin code or a choice by the user, or a simular interaction. The result of that user interaction sequence will be send by the media server to the user interaction service capability server, which user interaction service capability server can forward this information to the application. The procedure will end after the application instructs the user interaction service capability server that the required information has been received and that his services are no longer required. The user interaction service capability server will instruct the call control service capability server to terminate the connection between the service switching point and the media server. An instruction will be passed on from the call control service capability server to the service switching point to terminate the connection. In the mean time the connection between the user and the application via the call control service capability server will remain, so that after transferring the call back to the application the interaction between the user and the application can be continued. The above-mentioned and other features and advantages of the invention are illustrated in the following description of a preferred embodiment of the present invention in a UMTS environment, with reference to the enclosed drawings. The present invention, described hereinafter, will be likewise applicable to any telecommunications system which is comprised service switching points, service capability servers and service provisioning equipment, such as but not limited to 2G and 3G mobile telecommunications systems, like CDMA 2000. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 shows a configuration of telecommunications equipment to which a method according to the invention may be applied. FIG. 2 shows a process flow diagram, with reference to the elements of FIG. 1, according to the invention. DETAILED DESCRIPTION OF THE EMBODIMENTS FIG. 1 shows an arrangement 1 for the provisioning of telecommunications services which is comprised of a configuration of service switching points 4 and 5, service capability servers 6 and 7, an application server 8 running an application 9, a user 2 and a media server 10. The elements of the configuration are interconnected by communication links 11-18. The basis of this arrangement is a telecommunications network 3 which is comprised of service switching point A 4 and service switching point B 5 and a number of interconnections (amongst which interconnection 11, 12, 15, 16, 17). Note that interconnection 18, between call control service capability server 6 and user interaction service capability server 7, is not necessarily a physical direct connection but could be virtual direct, in case user interaction service capability server 7 is in a different location than call control service capability server 6. By virtual direct, it is meant here that the communication of instructions is direct between both service capability servers, rather than the presence of a direct physical connection, such as a cable. Interconnection 18, in this latter case, would be part of telecommunications network 3 as well. The same holds for interconnections 13 and 14. Note therefor, that the configuration as shown in FIG. 1 also illustrates the hierarchy of the configuration. The arrangement 1 in FIG. 1 is configured to provide services to a user 2, which user 2 can access these services through one single application 9. The arrangement 1 could, for instance, be used within an open service architecture (OSA) in a universal mobile telecommunication system (UMTS), wherein providers can offer services of third parties, while these third parties may be transparent to the user 2. This clarifies the hierarchy as shown in FIG. 1. The application 9, being in charge of all other services, is the upper most element of the configuration in the figure. Just below this the service capability servers 6 and 7, are in charge of management of the telecommunications network 3, each one individually for the provisioning of a single type of service capability. The call control service capability 6 determines where and how the call is routed in a network, whilst the user interaction service capability server 7 manages the operational steps carried out to provide a certain user interaction. The switching on the network, the actual work required to enable the data flow, is carried out by the service switching points 4 and 5. These service switching points are therefor in the hierarchy just below the service capability servers. Below the service switching points A and B (4, 5), are the end points of the data flow. On one end this is the user 2, and on the other end this is the media server 10 being the source of the service. In an ideal case, the application 9 and the application server 8 should not be aware of the telecommunications network 3. The application 9 and the application server 8 only need to know the locations of the call control service capability server 6 and the user interaction service capability server 7. The call control service capability server 6 should be aware of the telecommunications network 3 and as such the service switching point A 4 and B 5. The user interaction service capability server 7 only needs to know the source of the service or data which is in our case the media server 10. In general the user interaction service capability server is not even aware of the switching being done between himself and the media server 10, i.e. to the user interaction service capability server 7 there will be a virtual connection between the user interaction service capability server 7 and the media server 10. The user 2 should only be aware of the location of the application server 8, i.e. the user 2 will, for instance, call a telephone number, and is automatically connected to the application 9 running on the application server 8. Service switching points A 4 and B 5 are not aware of any other elements in the telecommunications system, as the service switching points (4, 5) will receive the necessary information from the elements that contact the service switching points (user 2, call control service capability server 6, etc). The media server 10 is a passive element from a telecommunications point of view. In this preferred embodiment the media server 10 only responds to requests by other elements, such as the user interaction service capability server 7, in the network. According to the present invention the interaction between the user interaction service capability server 7, and the call control service capability server 6, is a direct interaction that will be communicated over communication link 18. In prior art, the application 9 and the application server 8 were involved in this interaction, and thus the interaction was indirect. As a result, the telecommunications infrastructure was not transparent to the application 9 and the application server 8 as they were involved in the management of the telecommunications infrastructure. In FIG. 2 a process flow diagram is shown according to the present invention. The process flow diagram shows a method of providing, for instance, a security authentication procedure to the user, before the user can access any other services on the application server. In this case the security authentication procedure is performed by a media server which has access to the security information of said user. This media server is shown in FIG. 1 as media server 10, and is in a different location then the application server, shown in FIG. 1 as application server 8. The present invention relates to the provisioning of any service that requires more than one service capability server, which service capability servers are logically or physically separated. In this case the user interaction service capability server would be located near the media server, and a virtual connection exists between the user interaction service capability server 7 and the media server 10 of FIG. 1. The process starts by the user making a call to the application in step 19. The call comes into a service switching point A which connects 20 the call to a call control service capability server, and the call control service capability server will connect 21 the call to the application. The application will send a user interaction request 22 to the user interaction service capability server, in this case the user interaction request will be a request for security authentication. The user interaction service capability server will, on his turn, request a communication port to be reserved 23 on the media server. The media server will open the port 24 and inform the user interaction service capability server. Than the user interaction service capability server will request the connection 25 to be set up between the user and the media server. In step 25 it will inform the call control service capability server of the location details of the media server, so that the connection can be set up. The call control service capability server will establish the connection 26 by sending an instruction to service switching point A and service switching point B. Service switching point A will connect 27 to service switching point B, and service switching point B will connect 28 to the media server. The media server will receive an incoming call and report this 20 to the user interaction service capability server. The user interaction service capability server will send the user interaction request 30 that he has received from the application in step 22 to the media server. The user interaction will be performed between the media server and the user (31, 32) in this case the media server could for instance play a digitised voice message, and the user could key in his pin code via dual tone multi-frequency, or maybe just say his pin code which is analysed by a voice analysis system on the media server. The results of the user interaction will be send to the user interaction service capability server, which will forward 34 the result to the application. As soon as the application has received the results correctly, it will instruct the user interaction service capability server to close the connection 35. The user interaction service capability server will instruct the call control service capability server to close the connection 36, upon which the call control service capability server will take back the call 37 (so that the user is again connected to the application), and close the connection to the media server, in step 37. The service switching point upon receiving the instructions from the call control service capability server will switch back the call 38 to the call control service capability server and the user will continue his interaction with the application 39. For the arrangement and configuration shown in FIG. 1, the process flow diagram in FIG. 2 can be used in all cases where more than one service capability server is required to provide a service. The main principle behind the idea, is the direct interaction between both service capability servers. Due to this direct interaction, the telecommunications infrastructure will be transparent to elements outside the network, such as the application server, the user and the media server. It will be appreciated that numerous modifications and variations of the present invention are possible in the light of the above teachings. It is therefor understood that within the scope of the amended claims, the invention may be practised otherwise than as specifically described herein.

<SOH> BACKGROUND OF THE INVENTION <EOH>A method as described above is disclosed in International Patent Application nr. WO 01/88739, describing a personal service environment manager (PSEM). The document describes an open service architecture (OSA) comprising service capabilities servers and service provisioning servers or application servers. The document further describes the underlying network technology consisting of service switching points, and the setting up of services through one or more service capability servers interacting with the service provisioning servers or application servers. The number of services that can be offered over telecommunications networks and the integration of the services within modern society has increased rapidly over the past decennia. Services are becoming more and more sophisticated, and can be accessed by any user from any location at any point in time. The introduction of the universal mobile telecommunications system (UMTS) has accelerated this development even more. In general, in a telecommunications system, services are offered over the network using service capability servers (SCS). These service capability servers are responsible for management of the service and the telecommunications infrastructure required to provide that service. In the hierarchy below the service capability servers, the telecommunications infrastructure is comprised of service switching points (SSP), which are interconnected with each other. Service provisioning equipment, such as media servers, and user equipment, like a telephone set or a mobile phone, also connects to the service switching points. In recent years, UMTS has triggered the development of the so-called open service architecture (OSA), in which service providers can easily incorporate the services offered by a third party into there own service without having to reveal this to their customers. The customer will only deal with one provider from which he receives support, and which provider sends him one bill for all the services used. The use of this principle is not limited to UMTS. Those skilled in the art will appreciate that similar methods can be used in any telecommunications system. According to the open service architecture principle the user calls, for instance, to an application server, and accesses an application that provides the user with a choice of services. These services could be voice mail service, fax service, IP services, multi media, etc. As explained above, the provisioning of services itself over the telecommunications infrastructure is managed by service capability servers, and this is also the case for applications on an application server, which is accessed by users. As more complicated services are made up of interactions on different levels of communications, call control, user interaction, etc, each service capability (level/type of communication) may be handled by a different service capability server. A number of these service capability servers may be operated from the same location on the network, e.g. being part of a framework, but in some cases in order to offer a service a plurality of service capability servers are used from different locations. It is best to consider an example to illustrate this principle. Take for example the user calling into an application. First, the connection between the user and the application will be set up by a call control service capability server. As soon as this connection has been established the application will, for example, start a security authentication procedure. This security authentication procedure may consist of a digitised voice message after which the user can enter his pin code via dual tone multi-frequencies (DTMF) on the keyboard of his telephone set. Suppose however that the authentication procedure will not be handled by the application itself, but by a remote media server. In order to perform this action, the application needs to contact a remote user interaction service capability server. This service capability server may be in a different location than the service capability server that has established the call between the application and the user. The application knows exactly which service capability server to contact in order to start the authentication procedure. Ideally the application only temporarily transfers the call to the media server, responsible for carrying out the security authentication procedure, and take back the call after the procedure has ended. The transfer of a call is handled, as mentioned, by the call control service capability server. The problem is that the user interaction service capability server knows where the media server is, and the call control server, handling all details of the user call, needs to transfer the call whilst maintaining contact to the application. In this case an extra speech channel needs to be set up between the service switching point and the media server. In an existing solution, the location details of the media server are offered by the user interaction service capability server to the application, and the application, on his turn, forwards this information to the call control service capability server. Upon receiving this information the call control service capability server instructs the service switching point to open a speech channel to the media server as it now knows where this media server is located. The major issue with this solution is that the application is involved in the management of the telecommunication services, while in principle, the underlaying telecommunications infrastructure needs to be transparent to the application, as well as to the user.

<SOH> SUMMARY OF THE INVENTION <EOH>It is an object of the present invention to provide a solution to the management of a telecommunications infrastructure in case a service is offered by an application in an open service architecture, which service requires the involvement of more than one service capability server. In addition, the solution offered needs to be transparent to both the application offering the service, as well as the user requesting the service. According to the present invention management of the telecommunications infrastructure is controlled via direct interaction between the service capability servers involved in the provisioning of service. In particular this means that, for instance in the example described above, upon receiving instructions from the application, the user interaction service capability server forwards the location of the media server directly to the call control service capability server handling the call between the user and the application (and not to the application). In order to enable this a protocol and instructions need to be defined as the language between the service capability servers. Naturally, these instructions would comprise instructions for setting up a connection, as well as for terminating connections, and instructions for the exchange of specific information required to control the telecommunications infrastructure. A method for the provisioning of services in a telecommunications system according to the invention, comprised of an application server, service capability servers, service switching points and service provisioning equipment, such as a media server, is described below. It will be comprised of the steps of accessing the application, requesting a user interaction sequence, preparing of the telecommunications infrastructure, the user interaction itself, and closing all connections made except for the call between the user and the application. The procedure starts by an incoming call, from the service switching point to the call control service capability server, which call will be passed on by the service capability server to the application running on the application server. Here, a user interaction is required, for example the security authentication, and the application will contact the user interaction service capability server and forward the user interaction request. The user interaction service capability server, upon receiving the user interaction request, will instruct the media server to reserve a communications port over which the user interaction can be performed. It will then contact the call control service capability server, and inform the call control service capability server of the location of the media server, and instruct the call control service capability server to establish a connection between the service switching point and the media server. The call control service capability server will then instruct the service switching point to set up a, for instance, speech channel between the service switching point and the media server, informing the service switching point of the reserved communication ports on the media server that can be used to establish the connection. After this the speech channel will be set up and the media server will acknowledge to the user interaction service capability server that a connection has been established between the media server and the service switching point. The user interaction service capability server will now forward the user interaction request to the media server which, on his turn, carries out the user interaction sequence. This sequence could be the playing of a digitalised message or a sound, the input of a pin code or a choice by the user, or a simular interaction. The result of that user interaction sequence will be send by the media server to the user interaction service capability server, which user interaction service capability server can forward this information to the application. The procedure will end after the application instructs the user interaction service capability server that the required information has been received and that his services are no longer required. The user interaction service capability server will instruct the call control service capability server to terminate the connection between the service switching point and the media server. An instruction will be passed on from the call control service capability server to the service switching point to terminate the connection. In the mean time the connection between the user and the application via the call control service capability server will remain, so that after transferring the call back to the application the interaction between the user and the application can be continued. The above-mentioned and other features and advantages of the invention are illustrated in the following description of a preferred embodiment of the present invention in a UMTS environment, with reference to the enclosed drawings. The present invention, described hereinafter, will be likewise applicable to any telecommunications system which is comprised service switching points, service capability servers and service provisioning equipment, such as but not limited to 2G and 3G mobile telecommunications systems, like CDMA 2000.

20040903

20101228

20050519

98483.0

GAY, SONIA L

SERVICE PROVISIONING IN TELECOMMUNICATIONS SYSTEM COMPRISING CALL CONTROL SERVICE CAPABILITY SERVERS

UNDISCOUNTED

ACCEPTED

ACCEPTED

System for and method of displaying information

A system (100) for displaying information on a display device (104) comprises; receiving means (202) for receiving services; user interface means (220) for making a user selection of a type of information to be displayed on the display device (104); a filter (206) for selecting a data-element of a first one of the services on basis of the user selection; and rendering means (208) for calculating an output image to be displayed on the display device (104), on basis of output of the filter (206). The system (100) is designed to apply the filter (206) for selecting a second data-element of the second one of the services, on basis of the user selection, when being switched from the first one of the services to a second one of the services, with the data-element and the second data-element being mutually semantically related.

1. A system (100) for displaying information on a display device (104), comprising: receiving means (202) for receiving a transport stream comprising services, with the services having elementary streams of video and of data-elements; user interface means (220) for making a user selection of a type of information to be displayed on the display device (104); a filter (206) for selecting a first data-element of a first one of the services on basis of the user selection; rendering means (208) for calculating an output image to be displayed on the display device (104), on basis of the first data-element selected by the filter (206); and switching means (204) for switching from the first one of the services to a second one of the services, characterized in that the system (100) is designed to apply the filter (206) for selecting a second data-element of the second one of the services, on basis of the user selection, when being switched from the first one of the services to the second one of the services, with the first data-element and the second data-element being mutually semantically related and to apply the rendering means (208) for calculating the output image to be displayed on the display device (104), on basis of the second data-element selected by the filter (206). 2. A system (100) as claimed in claim 1, characterized in that the system (100) is designed to apply the filter (206) for selecting the second data-element, when being switched from the first one of the services to the second one of the services, with the data-element and the second data-element being mutually semantically equal. 3. A system (100) as claimed in claim 1, characterized in comprising a converter for controlling the filter (206) to select the second data-element on basis of the user selection and a third data-element of the second one of the services. 4. A system (100) as claimed in claim 1, characterized in that the rendering means (208) are arranged to calculate a mixed output image to be displayed on the display device (104), on basis of the selected data-element and a first image of a first elementary stream of video. 5. A system (100) as claimed in claim 1, characterized in comprising storage means for storage of a parameter which determines the filter (206). 6. A system (100) as claimed in claim 1, characterized in being arranged to run an application, which enables in making the user selection and of which software code is being exchanged by means of a first elementary stream of data-elements. 7. A system (100) as claimed in claim 1, characterized in comprising the display device (104). 8. A method of displaying information on a display device (104), comprising the steps of: receiving a transport stream comprising services, with the services having elementary streams of video and of data-elements; user actions of making a user selection of a type of information to be displayed on the display device (104); filtering to select a data-element of a first one of the services on basis of the user selection; rendering to calculate an output image to be displayed on the display device (104), on basis of the first data-element selected by the filter (206); and switching from the first one of the services to a second one of the services, characterized in comprising a second step of filtering to select a second data-element of the second one of the services, on basis of the user selection, when being switched from the first one of the services to the second one of the services, with the data-element and the second data-element being mutually semantically related and a second step of rendering to calculate the output image to be displayed on the display device (104), on basis of the second data-element selected by the filter (206).

The invention relates to a system for displaying information on a display device, comprising: receiving means for receiving a transport stream comprising services, with the services having elementary streams of video and of data-elements; user interface means for making a user selection of a type of information to be displayed on the display device; a filter for selecting a first data-element of a first one of the services on basis of the user selection; rendering means for calculating an output image to be displayed on the display device, on basis of the first data-element selected by the filter; and switching means for switching from the first one of the services to a second one of the services. The invention further relates a method of displaying information on a display device comprising the steps of: receiving a transport stream comprising services, with the services having elementary streams of video and of data-elements; user actions of making a user selection of a type of information to be displayed on the display device; filtering to select a first data-element of a first one of the services on basis of the user selection; rendering to calculate an output image to be displayed on the display device, on basis of the first data-element selected by the filter; and switching from the first one of the services to a second one of the services. An embodiment of the system of the kind described in the opening paragraph is known as set top box. A set top box is linked to a Digital Video Broadcast (DVB) server by means of a broadband network and optionally by means of a second network, primarily for data flow from the set top box. Typically the broadcast server and the set top box are in compliance with a standard, e.g. Multimedia Home Platform (MHP). The Broadcast server is responsible for generating a transport stream, e.g. an MPEG-2 transport stream comprising video, audio and data. The data comprises application data, i.e. software code representing an application to be run on the set top box, and data to be processed by such an application. A set top box provides its output to a television. Optionally the set top box is integrated into the television. The set top box is arranged to receive the transport stream and to select one of the services. Typically a service comprises mutually related elementary streams of video, audio and data. E.g. a video stream of a service represents a sequence of images being captured of a football match. Optionally there is a further video stream which represents another sequence of images being captured of the football match from another point of view. An audio stream corresponds to the sound being captured in the stadium of this football match and another audio stream corresponds to the voice of a reporter. The data is also related to football. The data of the data stream might correspond to the actual situation of the match, e.g. the score, who made the goals and when, the number of yellow and red cards, the current players of the teams, etcetera. The data might also correspond to other aspects of football, e.g. the tournament schedule, statistical information on teams and players, etcetera. The set top box comprises means to select a service from the transport stream. The set top box further comprises user interface means for making a user selection of the type of information to be displayed on the television. Typically this works by means of a graphical user interface which is the visible part of an application. The user is provided with menus of options corresponding to information which is available in the elementary data stream of the selected service. By browsing through the menus and by selecting an option the user defines which type of data, i.e. which data-elements, should be selected from this elementary data stream which has been partly received and is partly to be received, by the set top box. A visual representation of the selected data-elements is then displayed on the television. E.g. “Team A-Team B: 0-2”. The user can switch to another service for which he can also select information to be displayed, by means of browsing and selecting provided options. In the latter case the provided options relate to the most recently selected service. It is an object of the invention to provide a system of the kind described in the opening paragraph which is more user friendly. The object of the invention is achieved in that the system is designed to apply the filter for selecting a second data-element of the second one of the services, on basis of the user selection, when being switched from the first one of the services to the second one of the services, with the first data-element and the second data-element being mutually semantically related and to apply the rendering means for calculating the output image to be displayed on the display device, on basis of the second data-element selected by the filter. The user does not have to make a new selection after being switched from the first service to the second service. That means that the user does not have to browse again through the menus in order to define which type of information he is interested in. The user selection being made on basis of the provided options while the first service was selected, is used to select the appropriate data-elements of the stream of the second service. The invention is based on the insight that different services often have the same information model, i.e. data model. That also means that various content providers share one information model or make use of similar information models. An embodiment of the system according to the invention is designed to apply the filter for selecting the second data-element, when being switched from the first one of the services to the second one of the services, with the data-element and the second data-element being mutually semantically equal. Preferably the data-element and the second data-element are also syntactically equal. The working of this embodiment will be explained by means of an example. Suppose that the user has selected the option “show actual score” while watching a football match being provided by means of the first service. The result is that data-elements which are classified with label “Score” are filtered from the incoming data-elements belonging to the first service. The current score of the football match, which is broadcast via the first service, is displayed on the display device. After being switched to a second service, corresponding to another football match, data-elements which are classified with label “Score” are filtered from the incoming data-elements belonging to the second service. Now the current score of the other football match, which is broadcast via the second service, is displayed on the display device. Another embodiment of the system according to the invention comprises a converter for controlling the filter to select the second data-element on basis of the user selection and a third data-element of the second one of the services. The working of this embodiment will be explained by means of an extension of the example above. Suppose that the user has selected the option “show actual score” while watching a football match being provided by means of the first service. The result is that data-elements which are classified with label “Score” are filtered from the incoming data-elements belonging to the first service. Now the user switches to the second service, which comprises streams of video, audio and data of a tennis game. In this latter data stream there are no data-elements with label “Score”. However there are data-elements with label “tennis” and there are data-elements with labels “Scores”. The converter is able to map “Score” to “Scores” on basis of a data-element with label “tennis”. This embodiment of the system according to the invention is advantageous in the case that different services do not have the same information model but that it is possible to map a data type of a first information model into a data type of a second information model. In an embodiment of the system according to the invention, the rendering means are arranged to calculate a mixed output image to be displayed on the display device, on basis of the selected data-element and a first image of a first elementary stream of video. Preferably the graphical representation of the data-element is displayed as an overlay on the input images of the video stream. An embodiment of the system according to the invention comprises storage means for storage of a parameter which determines the filter. The advantage of this embodiment is that the properties of the filter are made persistent. After a restart of the system or application the same filtering operation can be performed. An embodiment of the system according to the invention is arranged to run an application, which enables in making the user selection and of which software code is being exchanged by means of a first elementary stream of data-elements. By exchanging the software code via the transport stream, it is possible to have up-to-date software at the client side of the network, i.e. in the system, e.g. set top box. This is especially important in the case of modifications of an information model and for the converter. An embodiment of the system according to the invention comprises the display device. The system might comprise a separate set top box and television. But preferably these two are integrated into one unit. It is a further object of the invention to provide a method of the kind described in the opening paragraph which is more user friendly. This object of the invention is achieved in that the method of displaying information on a display device is characterized in comprising a second step of filtering to select a second data-element of the second one of the services, on basis of the user selection, when being switched from the first one of the services to the second one of the services, with the first data-element and the second data-element being mutually semantically related and a second step of rendering to calculate the output image to be displayed on the display device, on basis of the second data-element selected by the filter. Modifications of the system and variations thereof may correspond to modifications and variations thereof of the method described. These and other aspects of the system and of the method according to the invention will become apparent from and will be elucidated with respect to the implementations and embodiments described hereinafter and with reference to the accompanying drawings, wherein: FIG. 1 schematically shows an embodiment of the system according to the invention in its context; and FIG. 2 schematically shows components of an embodiment of the system according to the invention. Corresponding reference numerals have same or like meaning in all of the Figures. FIG. 1 schematically shows an embodiment of the system 100 according to the invention in its context. The system 100 has a number of connections with other systems 102 and 110: The system 100 is connected to a broadcast server 110 by means of a broadband network 106. The broadcast server 110 is responsible for providing the transport streams to the broadband network 106. The system 100 is connected to a television 102 which comprises a display device 104. Video and audio content and data being exchanged via the system 100 are displayed on the television 102. The system 100 is optionally connected to a broadcast server 110 by means of a second network 108, e.g. Ethernet. This second network is primarily used for data exchange from the system 100 to e.g. the broadcast server 110. The broadcast server 110 comprises a first storage means 112 for storage of video and audio content being provided by means of input connector 120. The broadcast server 110 also comprises a second storage means 114 for storage of data. This data comprises application data, i.e. software code which is the base of an application to be run on the system 100, and of data to be processed by the application. The video and audio content are multiplexed with the data by means of multiplexer 116. The resulting transport stream is modulated by means of the modulator 118 which is designed to convert the transport stream to a higher frequency such that it can be transmitted on the broadband network 106 (e.g. terrestrial or satellite). FIG. 2 schematically shows components 202-208, 222-224 and interfaces 212216 of an embodiment of the system 100 according to the invention. The system 100 comprises: receiving means 202 for receiving transport streams being provided on the input connector 214. A transport stream comprises services. A service comprises elementary streams of video, audio and of data-elements; user interface means 220 for making a user selection of a type of information to be displayed on the display device 104. Preferably the user interface means comprise a remote control unit 220. The signals sent by the remote control 220 are received via input sensor 212. Another part of the user interface means is the display device 104 of the television 102. Use is made of the so-called On Screen Display feature (OSD). Via the display device 104 the user is provided with graphical representations 218 of the data-elements; switching means 204 for switching from a first one of the services to a second one of the services. Switching might mean that new application data is downloaded to be run. But it is also possible that one and the same application is handling multiple services. a filter 206 for selecting data-elements of the first one of the services on basis of the user selection made by the user. Note that multiple data-elements related to the same information are sent. E.g. assume that the information is the current score of a live football match. As long as the score equals “0-1” data-elements are exchanged, e.g. every second, containing this information. However, if a goal has been made the situation is changed and from that moment on data-elements will be exchanged reflecting the new situation, e.g. data-elements representing the score with value “0-2”. rendering means 208 for calculating graphical representations of data-elements to be displayed on the display device 104, on basis of output of the filter 206; an Ethernet connector 216 for exchange of information from the system 100 back to e.g. the broadcast server 110; a video processor 222 for processing the video stream. Eventually the graphical representations of data-elements are merged with the input images of the video stream resulting in a series of output images to be displayed on the display device 104. The rendering means 208 are arranged to merge these. The signal representing these output images is provided to the input connector 210 of the television 102. an audio processor 224 for processing the audio stream. The signal representing the processed audio stream is provided to the input connector 211 of the television 102. The working of the system 100 according to the invention will be explained by means of examples. It is assumed that the data-elements being exchanged from broadcast server 110 to the system 100 are conform a predefined information model. Table 1 comprises a part of such an information model. Each row of Table 1 belongs to a separate data type. The first column corresponds to a unique identification of each data type. The second column corresponds to the name of the data type. The third column corresponds to the type of the data type. In the fourth column a description of the data type is given and in the fifth column an example of the data type is given. TABLE 1 specification of data-elements: Identification Name Type Description Example 0000 Score Integer array Current score 2, 3 of sports game 0001 HalfScore Integer array Score of sports 0, 0 game after half playing time 0002 FinalScore Integer array Score of sports 3, 4 game after full playing time 0003 Goaltimes Integer array Moments of time 12, 34, 56 of the goals Suppose that a user has selected a first service of the transport stream. This service corresponds with a football match between teams A and B. The user is interested to be informed about the current score of the match. Via the remote control 220 of the system the user provides a command to show which type of score information is available in the first service. The result of this command is that the application running on the system 100 creates a graphical overlay, which is mixed with the input images of the video stream, by means of the rendering means 208. The final output images are displayed on the display device 104 of the television. These output images comprises the following text: “What do you want to be shown?” “Current score” “Score after half playing time” “When were the goals made” The user indicates that only the current score should be displayed. As a result, from now on the filter 204 will fetch all data-elements of the data stream with the right type, i.e. with identification 0000 and with name “Score” (See Table 1). Data-elements which do not have this type will be skipped by the filter. A graphical representation of the current score will be displayed on the display device 104. Note that the values of the series of incoming data-elements might be mutually different, e.g. “0-0”, “0-1”, “1-1”, etcetera. After a while the user switches to another service, e.g. corresponding to a movie. In the elementary streams corresponding to this service there are no data-elements with the type corresponding to “Score”. Hence there will be nothing displayed about football scores. Then the user zaps further to a third service which corresponds to a football match between team C and team D. In the elementary streams corresponding to this third service there are data-elements with the type corresponding to “Score”. The filter 204 will fetch these data-elements and a graphical representation of the current score of the match between team C and D will be displayed on the display device 104. Up till now the data-elements were considered as independent information entities. However in most cases data-elements are structured, e.g. in modules or objects. A common approach of modeling is based on objects being specified by their data-elements and the parents and child they have. In such a way a so-called object tree can be defined. For instance a tree with as root “sports”. The children of the root-object are “tennis” and “football”. The children of the “football”-object are “World championship”, “European championship” and “Dutch championship”. The children of the “Dutch championship”-object are “schedule”, “team” and “results”. The “team”-object comprises “player”-objects and “coach”-object. In Table 2 some data-elements of the “player”-object, having a “football”-object as ancestor, are specified. TABLE 2 specification of data-elements of “player” object for “football”: Identification Name Type Description Example 1000 FirstName String Family name Jansen 1001 NickName String Nick name Speedy 1002 Age Integer Age 25 1003 Interlands Integer Number of international 17 games played For tennis a similar object definition is made, but which is slightly different. See table 3. TABLE 3 specification of data-elements of “player” object for “tennis”: Identification Name Type Description Example 2000 FirstName String Family name Jansen 2001 NickName String Nick name Speedy 2002 Age Integer Age 25 2003 Tournaments Array of International Wimbledon Strings tournaments won Suppose that the user, watching the football match between team A and B had indicated to display the information of the players. Then the user switches to a service corresponding to a tennis game. The result will be that the information comprised by the “player”-objects of tennis will be displayed. Hence, the number of international games played will not be shown but instead the international tournaments won will be listed. This can be realized in several ways. A first approach is based on filtering on a data-element related to a “player”-object. Another approach is based on a mapping table in which is specified that data-elements with identification 1003 (Interlands) must be mapped to 2003 (Tournaments). This mapping can be realized by a so-called converter. Not only for sports but for every type of service an information model can be made. Even by switching from a sport service to a movie service, the filter defined while watching the first service, can be reused. By means of example the “actor”-object of a movie is given in Table 4. So switching from football to a movie might mean that a data-sheet of an actor currently visible is provided too. This is because the converter maps a “player”-object to an “actor”-object. TABLE 4 specification of data-elements of “actor” object for “movie” Identification Name Type Description Example 3000 FirstName String Family name Nickelson 3001 NickName String Nick name Speedy 3002 Age Integer Age 25 3003 Movies Array of Played in these movies Shining Strings It should be noted that the above-mentioned embodiments illustrate rather than limit the invention and that those skilled in the art will be able to design alternative embodiments without departing from the scope of the appended claims. In the claims, any reference signs placed between parentheses shall not be constructed as limiting the claim. The word ‘comprising’ does not exclude the presence of elements or steps not listed in a claim. The word “a” or “an” preceding an element does not exclude the presence of a plurality of such elements. The invention can be implemented by means of hardware comprising several distinct elements and by means of a suitable programmed computer. In the unit claims enumerating several means, several of these means can be embodied by one and the same item of hardware.

20040907

20090804

20050602

65380.0

RIAZ, SAHAR AQIL

SYSTEM FOR AND METHOD OF DISPLAYING INFORMATION

UNDISCOUNTED

ACCEPTED

ACCEPTED

Method and arrangement for automatic adjustment of devices having setting elements, and a corresponding computer program product and a corresponding computer-readable storage medium

In a method and an arrangement for automatic adjustment of devices having setting elements, and a corresponding computer program product and computer-readable storage medium, the adjustment includes carrying out a first measurement of a characteristic curve to be controlled by the adjustment at predefined measurement points, each setting element assuming a reference setting; testing a termination condition and terminating the method if this condition is satisfied; and, if the termination condition is not satisfied, modifying the reference setting of each setting element and measuring the characteristic curve again at predefined measurement points for this configuration of the setting elements; reproducing the initial reference setting of the modified setting element; when there is more than one setting element, calculating the gradient functions of the characteristic curve; calculating new settings of the setting elements by minimizing an error function by using the obtained measured values and the calculated gradient functions; and carrying out the method again, beginning with the new calculated settings serving as the new reference setting.

1-20. (canceled) 21. A method of automatic adjustment of devices having setting elements, comprising the steps of: a) carrying out a first measurement of a characteristic curve to be controlled by the adjustment at predefined measurement points, at least one setting element assuming a first reference setting; b) testing a termination condition, and terminating the method if the termination condition is satisfied; and c) executing the following steps if the termination condition is not satisfied: i) modifying the first reference setting of the at least one setting element, and measuring the characteristic curve again at predefined measurement points for a configuration of the at least one setting element, ii) reproducing the first reference setting of the at least one setting element modified in step i), iii) when there is more than one setting element, repeating the steps i) and ii) for each setting element, iv) calculating gradient functions of the characteristic curve, v) calculating new settings of the setting elements by minimizing an error function by using measured values obtained in steps a) and i) and the gradient functions calculated in step iv), and setting the setting elements to calculated values, and vi) carrying out the method again, beginning with step a) with the new settings calculated in step v) serving as a new reference setting. 22. The method according to claim 21, in that the first reference setting of the at least one setting element is assumed to be in a middle of a setting range of the at least one setting element, or is predefined by means of values from experience, or is determined by a preliminary adjustment method. 23. The method according to claim 21, in that after each measurement of the characteristic curve, a test of the termination condition is carried out, and the method is terminated if the termination condition is satisfied. 24. The method according to claim 21, in that the test of the termination condition comprises an automatic comparison between the measured values of the characteristic curve and predefinable desired values or desired ranges. 25. The method according to claim 21, in that the measurement of the characteristic curve is carried out as a scalar or vectorial measurement. 26. The method according to claim 21, in that, in order to minimize the error function in step v), a gradient method and/or a random method is used. 27. The method according to claim 21, in that the minimization of the error function in step v) is terminated if, at one of the measurement points, a difference between a last determined theoretical value of the characteristic curve and the measured value of the characteristic curve assumes or exceeds a first predefinable magnitude (deltaS11max) for a corresponding setting of the at least one setting element, or if, at one of the measurement points, a difference between a last determined theoretical setting and the corresponding setting of the at least one setting element assumes or exceeds a second predefinable magnitude (deltaEEmax), or if, in a set of predefinable measurement points, the last determined theoretical values of the characteristic curve have reached a predefinable desired value or desired range, or if, in a set of predefinable measurement points, the difference between theoretical values, determined in successive steps of the minimization method, of the predefinable measurement points assumes or falls below a third predefinable magnitude. 28. The method according to claim 27, in that the predefinable magnitudes and/or the predefinable measurement points for each device to be adjusted are determined individually by means of test measurements. 29. The method according to claim 28, in that the theoretical values of the characteristic curve are determined by calculating a linear approximation function of the characteristic curve. 30. The method according to claim 29, in that the gradient function of a characteristic curve (f) is determined in accordance with the following rules: f ⁢ ⁢ Gradient ⁡ ( a , i ) = df ⁡ ( a , i ) / dEE ⁡ ( i ) = ( f ⁡ ( a , i , 1 ) - f ⁡ ( a , i , 0 ) ) / ( EE ⁡ ( i , 1 ) - EE ⁡ ( i , 0 ) ) , where: i=number of the setting element, a=parameter, EE=setting element, EE (i, 0)=position of the setting element No. i before the modification of the reference setting, EE (i, 1)=position of the setting element No. i after the modification of the reference setting, f (a,i,0)=f before the modification of the reference setting of the setting element No. i, and f (a,i,1)=f after the modification of the reference setting of the setting element No. i. 31. The method according to claim 21, in that for a characteristic curve which, in addition to the setting of the setting elements, depends on further variable parameters, for each configuration of the setting elements, a measurement of the characteristic curve for a plurality of measurement points is carried out, each parameter assuming a plurality of different values. 32. The method according to claim 31, in that a number of the measurement points corresponds to a number of the setting elements. 33. The method according to claim 21, in that the device to be adjusted by means of adjustment is designed as a microwave filter. 34. The method according to claim 33, in that for each configuration of the adjusting elements of the microwave filter, a measurement of the characteristic curve is carried out for a plurality of measurement points, and in that a frequency parameter assumes a plurality of different values. 35. The method according to claim 34, in that the measurement points are distributed uniformly only over a forward pass range of the microwave filter. 36. The method according to claim 35, in that the characteristic curve to be controlled describes a reflection factor (S11) and/or an S12 parameter and/or an S21 parameter and/or an S22 parameter of the microwave filter. 37. The method according to claim 21, in that the calculation of new settings of the setting elements in step v) is carried out by a theoretical behavior of each individual measurement point in the event of a simultaneous change in all the setting elements being simulated by means of linear superposition. 38. An arrangement having a processor set up for automatic adjustment of devices having setting elements, comprising: a) means for carrying out a first measurement of a characteristic curve to be controlled by the adjustment at predefined measurement points, the setting elements assuming a first reference setting; b) means for testing a termination condition, and for terminating adjustment if the termination condition is satisfied, and for executing the adjustment if the termination condition is not satisfied; c) means for modifying the first reference setting of the setting elements, and for measuring the characteristic curve again at predefined measurement points for a configuration of the setting elements; d) means for reproducing the first reference setting of the setting elements modified by the modifying means; e) in the presence of a plurality of the setting elements, means for repeating operation of the modifying means and the reproducing means for each setting element; f) means for calculating gradient functions of the characteristic curve; g) means for calculating new settings of the setting elements by minimizing an error function by using measured values obtained by the carrying means and the modifying means and the gradient functions calculated by the calculating means, and means for setting the setting elements to the calculated values; and h) means for carrying out the adjustment again, with the new settings calculated by the calculating means. 39. A computer program product comprising a computer-readable storage medium on which a program is stored which, after the program has been loaded into a memory of a computer, makes it possible for the computer to carry out a method for automatic adjustment of devices having setting elements, the adjustment comprising the steps of: a) carrying out a first measurement of a characteristic curve to be controlled by the adjustment at predefined measurement points, the setting elements assuming a first reference setting; b) testing a termination condition, and terminating the adjustment if the termination condition is satisfied; and c) executing the following steps if the termination condition is not satisfied: i) modifying the first reference setting of the setting elements, and measuring the characteristic curve again at predefined measurement points for a configuration of the setting elements, ii) reproducing the first reference setting of the setting elements modified in step i), iii) in the presence of a plurality of the setting elements, repeating the steps i) and ii) for each setting element, iv) calculating gradient functions of the characteristic curve, v) calculating new settings of the setting elements by minimizing an error function by using measured values obtained in steps a) and i) and the gradient functions calculated in step iv), and setting the setting elements to the calculated values, and vi) carrying out the adjustment again, beginning with step a) with the new settings calculated in step v) serving as a new reference setting. 40. A computer-readable storage medium, on which a program is stored which, after the program has been loaded into a memory of a computer, makes it possible for the computer to carry out a method for automatic adjustment of devices having setting elements, the adjustment comprising the following steps: a) carrying out a first measurement of a characteristic curve to be controlled by the adjustment at predefined measurement points, the setting elements assuming a first reference setting; b) testing a termination condition, and terminating the adjustment if this condition is satisfied; and c) executing the following steps if the termination condition is not satisfied: i) modifying the first reference setting of the setting elements, and measuring the characteristic curve again at predefined measurement points for a configuration of the setting elements, ii) reproducing the first reference setting of the setting elements modified in step i), iii) in the presence of a plurality of the setting elements, repeating the steps i) and ii) for each setting element, iv) calculating gradient functions of the characteristic curve, v) calculating new settings of the setting elements by minimizing an error function by using the measured values obtained in steps a) and i) and the gradient functions calculated in step iv), and setting the setting elements to the calculated values, and vi) carrying out the adjustment again, beginning with step a) with the new settings calculated in step v) serving as a new reference setting.