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<SOH> BRIEF DESCRIPTION OF THE INVENTION <EOH>According to the present invention, this object is achieved by polyolefin coated steel pipes with dynamic fracture toughness of the coating of the steel pipes during installation handling and in service, consisting of a steel pipe core, optionally an intermediate foamed plastic material, and a polyolefin coating, wherein the polyolefin coating consists of β-nucleated propylene copolymers from 90.0 to 99.9 wt % of propylene and 0.1 to 10.0 wt % of α-olefins with 2 or 4 to 18 carbon atoms with melt indices of 0.1 to 8 g/10 min at 230° C./2.16 kg, whereby a test polyolefin pipe fabricated from the β-nucleated propylene copolymer has a critical pressure of >25 bars and a dynamic fracture toughness of >3.5 MNm −3/2 in the hydrostatic small scale steady state (hydrostatic S 4 ) test at 3° C. |
Yin yang-1 |
The present invention provides a method of preventing or reducing cellular proliferation. The method involves administering to cells a composition which increases the level of YY1 protein, in particular YY1 mRNA, in the cells. |
1. A method of preventing or reducing cellular proliferation, the method comprising administering to cells a composition which increases the level of YY1 protein in the cells. 2. A method according to claim 1 wherein the composition increases the level of YY1 mRNA in the cells. 3. A method according to claim 1 or claim 2 wherein the composition comprises nucleic acid encoding YY1 and a pharmaceutically acceptable carrier. 4. A method according to claim 3 wherein the nucleic acid is DNA encoding YY1. 5. A method according to claim 4 wherein the DNA encoding YY1 is operatively linked to control sequences which promote expression of the DNA encoding YY1 in the cells. 6. A method according to claim 1 wherein the composition comprises a vector which comprises nucleic acid encoding YY1. 7. A method according to claim 6 wherein the vector is an adenovirus. 8. A method according to claim 7 wherein the vector is Ad2 or Ad5 adenovirus. 9. A method according to claim 1 wherein the composition comprises YY1 protein. 10. A method according to claim 1 wherein the cellular proliferation to be prevented or reduced is in cells other than HMEC-1, bovine aortic endothelial cells or microvascular endothelial cells. 11. A method of identifying compounds which inhibit the proliferation of cells, the method comprising determining the ability of a putative compound to increase induction of YY1, increase expression of YY1 or increase the nuclear accumulation or activity of the YY1 gene product thereby identifying compounds which inhibit the proliferation of cells. 12. A method of treating or preventing a cellular proliferation disorder in an individual, the method comprising administering to the individual a composition which increases the level of YY1 protein in the cells. 13. A method according to claim 12 wherein the composition increases the level of YY1 mRNA in the cells. 14. A method according to claim 12 or claim 13 wherein the cellular proliferation disorder is restenosis, atherosclerois or cancer. 15. A method according to claim 14 wherein the restenosis follows balloon angioplasty. 16. A method according to claim 14 wherein the cancer is prostate or breast cancer. 17. An angioplastic stent for inhibiting onset of restenosis comprising an angioplastic stent operably coated with a prophylactically effective dose of a composition which increases the level of YY1 protein in cells. 18. An angioplastic stent according to claim 17 wherein the composition increases the level of YY1 mRNA in the cells. 19. An angioplastic stent according to claim 17 or claim 18 wherein the composition comprises nucleic acid encoding YY1 and a pharmaceutically acceptable carrier. 20. An angioplastic stent according to claim 19 wherein the nucleic acid is DNA encoding YY1. 21. An angioplastic stent according to claim 20 wherein the DNA encoding YY1 is operatively linked to control sequences which promote expression of the DNA encoding YY1 in the cells. 22. An angioplastic stent according to claim 17 wherein the composition comprises a vector which comprises nucleic acid encoding YY1. 23. An angioplastic stent according to claim 22 wherein the vector in an adenovirus. 24. An angioplastic stent according to claim 23 wherein the vector is Ad2 or Ad5 adenovirus. 25. A method for inhibiting the onset of restenosis in a subject undergoing angioplasty comprising topically administering a stent according to claim 17 to the subject at around the time of angioplasty. |
<SOH> BACKGROUND OF THE INVENTION <EOH>YY1 (yin-yang 1, also called NF-E1, delta, or UCRBP) is a GLI-Kruppel-type zinc finger nuclear factor that is able to repress, activate and initiate transcription depending on promoter architecture and the cellular environment (1). YY1 can activate or repress the c-fos promoter depending on the orientation of a YY1 recognition element in the promoter. YY1 can switch between an activator or repressor of the human papillomavirus type 18 promoter depending on the integrity of a distinct element upstream in the promoter (2). YY1 competes with NF-kappaB for overlapping binding sites in the serum amyloid A1 promoter and inhibits promoter activity by passive means. Similarly YY1 can antagonize the interaction of SRF to overlapping binding sites in the actin promoter. The four GLI-Kruppel-related zinc fingers at the carboxyl terminus of YY1 constitute a strong repression domain (3). YY1 functionally interacts with a large number of other key transcriptional regulators, such as Sp1, c-Myc, adenovirus E1A, the cAMP response element-binding protein-related factor, p300, and components of the general transcriptional apparatus including the large subunit of RNA polymerase II and transcription factor IIB (TFIIB) (4,5). The capacity of YY1 to bend DNA when it binds the promoter facilitates direct contact between regulatory proteins. YY1 can interact with histone deacetylases to repress the activity of certain promoters, including the human immunodeficiency virus type 1 long terminal repeat (6), thereby modulating histone and chromatin structure. The pathogenesis of common vascular disorders such as atherosclerosis and restenosis after balloon angioplasty is believed to be mediated at least in part by phenotypic changes involving smooth muscle cells of the artery wall. These cells normally adopt a “contractile” phenotype (7) in the vessel wall, but upon activation (such as mechanical injury imparted by angioplasty balloons), these cells become “synthetic” (7) and contribute to developing lesions by migrating, proliferating, producing extracellular matrix, and elaborating and responding to a myriad of growth-regulatory molecules (8). YY1 can repress the promoters of a wide spectrum of pro-atherogenic genes, including cytokines, hormones and growth factors (9-14). As such, YY1 may play an atheroprotective role in the artery wall. However, whether YY1 is even expressed in the artery wall or is regulated in the adaptive response to injury is presently not known, nor is whether YY1 can influence the growth of smooth muscle cells or other cell types. |
<SOH> SUMMARY OF THE INVENTION <EOH>The present inventors have found that YY1 has an anti-proliferative activity. Accordingly, in a first aspect the present invention consists in a method of preventing or reducing cellular proliferation, the method comprising administering to cells a composition which increases the level of YY1 protein in the cells. In a preferred embodiment the composition increases the level of YY1 mRNA in the cells. In a further preferred embodiment of the present invention the composition comprises nucleic acid encoding YY1, preferably DNA encoding YY1. It is also preferred that the DNA encoding YY1 is operatively linked to control sequences which promote expression of the DNA encoding YY1 in the cells. In yet a further preferred embodiment the composition comprises a vector which comprises nucleic acid encoding YY1. It is preferred that the cellular proliferation to be prevented or reduced is in cells other than HMEC-1 or bovine aortic endothelial cells or microvascular endothelial cells. Clearly as the method of the present invention prevents or reduce cellular proliferation the method can be used in the treatment of disease states involving cellular proliferation. Such diseases include cancer, restenosis and atherosclerosis. Following the findings of the present inventors that YY1 is a negative regulator of cellular proliferation the present invention also provides a method of screening for agents which reduce or prevent cellular proliferation. Accordingly, in a second aspect the present invention consists in a method of screening for compounds which inhibit the proliferation of cells, the method comprising determining the ability of a putative compound to increase induction of YY1, increase expression of YY1 or increase the nuclear accumulation or activity of the YY1 gene product. |
Automatic and guided system for transporting people and method for controlling transport modules running in such a system |
A system for automatic and guided transport of people, the system including: at least one running track having guide members for guiding transport modules; an electric power supply system comprising a sequence of power supply blocks; electric self-propelled transport modules travelling individually along the running track and fitted with a collector for picking up electric power supplied by the power supply blocks; and an electric power supply distributor controlled by a central control unit managing the progress of the transport modules by powering or unpowering various power supply blocks. |
1. A system for automatic and guided transport of people, the system comprising: at least one running track having means for guiding transport modules, each transport module being constituted by a single self-propelled vehicle or a self-propelled vehicle associated with one or more other transport vehicles; an electric power supply system comprising a sequence of power supply blocks; electric self-propelled transport modules travelling individually along the running track and fitted with means for collecting electric power supplied by the power supply blocks; and electric power distribution means comprising switch means which supply said electric power to the various power supply blocks and which are controlled by a central control unit managing the progress of the transport modules by causing the various power supply blocks to be powered or unpowered, the presence of a transport module on a power supply block preventing power being applied to one or more blocks situated behind the block that is occupied so as to maintain a safety distance between the various transport modules travelling independently along the track, the system being characterized in that said transport modules are provided with fixed onboard functions controlling starting acceleration, cruising speed, and deceleration, both while slowing down and while braking, of the transport module, said fixed onboard functions being actuated as a function of the presence or absence of a voltage on one or more electric power supply conductors, said transport modules moving automatically along the track when the collector means are electrically powered, and including brake means that come into operation when the collector means are no longer powered with electricity. 2. A system according to claim 1, characterized in that the transport modules possess operating parameters that are fixed under nominal voltage and load, specifically: starting with determined acceleration when power is established; travelling at a controlled cruising speed using traction means and/or brake means as a function of the speed reached; slowing down with determined deceleration; and braking with predetermined deceleration when power is removed. 3. A system according to the preceding claim 1, characterized in that the transport modules include means for controlling starting acceleration, cruising speed, and deceleration both while slowing down and while braking so as to ensure that the module operates in application of operating parameters that are fixed, independently of the load of the module, of variations in the power supplied by the collector means, and of variations in the gradient profile of the track. 4. A system according to claim 1, characterized in that it includes stations distributed along the track where passengers can board and alight. 5. A system according to claim 4, characterized in that it includes means for detecting when a transport module is approaching a station to deliver a signal to means for causing the module in question to slow down to a slow speed or until it has stopped at the station for allowing passengers to board and/or alight. 6. A system according to claim 1, characterized in that it includes detector means for detecting the presence of a transport module in a power supply block. 7. A system according to claim 1, characterized in that it comprises a single running track, each end of the track being fitted with a device for turning a module around. 8. A system according to claim 1, characterized in that it comprises two tracks interconnected at each end by means for turning a module around, loops interconnecting the corresponding ends of the tracks. 9. A system according to claim 1, characterized in that the power supply blocks are formed by conductor rails mounted on an insulating support, the power supply blocks being electrically insulated from one another, the electric power collector means fitted to the transport modules being collector shoes placed so as to rub along the conductor rails of the power supply blocks. 10. A system according to claim 1, characterized in that the brake means of each transport module comprise a spring-driven mechanical brake. 11. A system according to claim 1, characterized in that it further comprises means for withdrawing transport modules from the running track, or for adding modules thereto. 12. A method of controlling electric self-propelled transport modules travelling individually on a running track provided with guide means, each transport module having collector means for picking up electric power supplied by a power supply system comprising a sequence of power supply blocks, the method being characterized in that the progress of transport modules is controlled by powering or unpowering various blocks, said transport modules being provided with fixed onboard functions controlling starting acceleration, cruising speed, and deceleration, both while slowing down and while braking, of the transport module, said onboard functions being actuated as a function of the presence or absence of a voltage on the electric power supply conductor, the transport modules travelling automatically on the track whenever the collector means are electrically powered and including brake means which come into operation whenever the collector means are no longer electrically powered. 13. A method according to claim 12, characterized in that the presence of a transport module in a power supply block prevents power being applied to one or more blocks behind the occupied block so as to maintain a safety distance between the various transport modules travelling individually on the track. 14. A method according to claim 12, characterized in that those power supply blocks that are not occupied by a transport module are not supplied with electric power, and in that vehicle progression is controlled by feeding power to some of the power supply blocks. 15. A method according to claim 12, characterized in that by default the power supply blocks are electrically powered, and in that the progress of the vehicles is stopped by removing power feed to certain power supply blocks. 16. A method according to claim 12, characterized in that a centralized control unit organizes travel of the transport modules on the basis of information concerning the position of each transport module. |
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>The invention will be better understood and other advantages and features will appear on reading the following description given by way of non-limiting example and accompanied by a drawing which is a diagram showing how a particular embodiment of an automatic and guided system for transporting people of the invention operates. detailed-description description="Detailed Description" end="lead"? |
Glasses |
What is described is a pair of eyeglasses with a bridge that connects the two glass lenses and with flat holders mounted on the lenses to support the side pieces, wherein the lenses are connected to the holders and to the bridge by means of a fixation device (1). The invention is characterized by the fact that at least one fixation device (1) comprises a loop (2) that is inserted into an opening in the glass lens, the length of the loop being adaptable to various thicknesses of the glass. |
1. Eyeglasses with a bridge that connects the two glass lenses and with flat holders mounted on the lenses to support the side pieces, wherein the lenses are connected to the holders and to the bridge by means of a fixation device, wherein at least one fixation device comprises a loop that is inserted into an opening in the glass, the length of the loop being adaptable to various thicknesses of the glass. 2. Eyeglasses according to claim 1, wherein the loop is a wire, a bundle of fine wires or a bundle of fibers. 3. Eyeglasses according to claim 1, wherein the opening is a bore positioned near the edge. 4. Eyeglasses according to claim 1, wherein the opening consists of two bores of the same diameter. 5. Eyeglasses according to claim 1, wherein the length of the loop is continuously adjusted to different thicknesses of the glass. 6. Eyeglasses according to claim 1, wherein the length of the loop can be adjusted in a stepwise manner to different thicknesses of the glass. 7. Eyeglasses according to claim 1, wherein the loops are attached by a catch mechanism. 8. Eyeglasses according to claim 1, wherein the loops are attached by adhesive. 9. Eyeglasses according to claim 8, wherein the adhesive is one that can be activated by radiation, or an epoxide-resin-based adhesive, or a fusion adhesive or a synthetic thermoplastic material. 10. Eyeglasses according to claim 1, wherein the loops are attached by welding. 11. Eyeglasses according to claim 10, wherein the welding procedure is a laser, ultrasound or microresistance welding procedure. 12. Eyeglasses according to claim 1, wherein the loops are attached by soft-soldering. 13. Eyeglasses according to claim 1, wherein the loops are attached by a clamped or crimped connection. 14. Eyeglasses according to claim 2, wherein the opening is a bore positioned near the edge. 15. Eyeglasses according to claim 2, wherein the opening consists of two bores of the same diameter. 16. Eyeglasses according to claim 2, wherein the length of the loop is continuously adjusted to different thicknesses of the glass. 17. Eyeglasses according to claim 2, wherein the length of the loop can be adjusted in a stepwise manner to different thicknesses of the glass. 18. Eyeglasses according to claim 2, wherein the loops are attached by a catch mechanism. 19. Eyeglasses according to claim 2, wherein the loops are attached by adhesive. 20. Eyeglasses according to claim 2, wherein the loops are attached by welding. |
Method of optical fibre preform manufacture |
The present invention provides a method for producing a perform (1) for a holey optical fibre including thermomechanically forming the preform from a unitary body of optically suitable material (20) so that one or more discrete optical elements (30), such as air holes, are formed therein. Each element (30) has a refractive index which is different from the refractive index of the optically suitable material (20). The thermomechanical formation is preferably conducted by extrusion or by injection molding. In a preferred embodiment, the unitary body is a fluid. The method is suitable for production of a preform for a polymer holey optical fibre or an inorganic glass holey optical fibre. |
1. A method of producing a preform for a holey optical fibre, said fibre having one or more light transmitting region(s) therethrough, said method comprising thermomechanically forming said preform from a unitary body of an optically suitable material such that one or more discrete optical elements are formed therein, each element having a refractive index which is different from the refractive index of the optically suitable material. 2. A method as claimed in claim 1, wherein the method produces a preform for a polymer holey optical fibre. 3. A method as claimed in claim 1, wherein the method produces a preform for an inorganic glass holey optical fibre. 4. A method as claimed in any one of claims 1 to 3, wherein the unitary body is fluid. 5. A method as claimed in claim 1, wherein said method further comprises heating said material to obtain said fluid unitary body. 6. A method as claimed in claim 1, wherein said unitary body of optical suitable material is obtained by providing said material in particulate form and melting said material to obtain said fluid unitary body. 7. A method as claimed in claim 1, wherein said preform is formed by extrusion. 8. A method as claimed in claim 1, wherein said preform is formed by injection moulding. 9. A method as claimed in claim 1, wherein the optically suitable material includes a polymeric material. 10. A method as claimed in claim 1, wherein the optically suitable material is a mixture of polymeric and monomeric material mixed together such that, thermomechanically, they act as a single material during formation of the preform. 11. A method as claimed in claim 1, wherein the optically suitable material includes a monomeric material, said method farther comprising a step of polymerisation of said material. 12. A method as claimed in claim 1, wherein the preform is produced with a regular lattice of discrete optical elements. 13. A method as claimed in claim 1, wherein at least some of the discrete optical elements are air holes. 14. A method as claimed in claim 1, wherein at least some of the discrete optical elements are evacuated, filled with fluid or another optical material. 15. A method as claimed in claim 1, wherein at least some of the discrete optical elements include semiconductor materials. 16. A method as claimed in claim 1, wherein at least some of the discrete optical elements include conductive materials. 17. A method of producing a polymer holey optical fibre comprising producing a preform in accordance with claim 1 and drawing said preform to a fibre. 18. A method as claimed in claim 1, wherein the relative cross-sectional position of the discrete optical elements remain constant along the length of the preform or fibre. 19. A method as claimed in claim 1, wherein the relative cross-sectional position of the discrete optical elements varies along the length of the preform or fibre. 20. A method as claimed in claim 1, wherein at least some of the discrete optical elements extend in a mutually spaced apart array, parallel to the axis of the preform or fibre. 21. A method as claimed in claim 1, wherein at least some of the discrete optical elements extend in a helical spiral along the length of the preform or fibre. 22. A method as claimed in claim 1, wherein at least some of the discrete optical elements intersect at various points along the length of the preform or fibre. 23. A method as claimed in claim 1, wherein the cross-sectional size and shape of at least some of the discrete optical elements remain constant along the length of the preform or fibre. 24. A method as claimed in claim 1, wherein the cross-sectional size and shape of at least some of the discrete optical elements vary along the length of the preform or fibre. 25. A method as claimed in any one of claims 17 to 24, wherein, during drawing, said fibre is rotated relative to said preform. 26. A method as claimed in claim 17, wherein production of the preform and drawing of said preform to a fibre is conducted continuously. 27. A method of producing a holey optical fibre comprising thermomechanically altering a unitary body of optically suitable material to form an optical fibre having one or more light transmitting regions including one or more discrete optical elements therein, each optical element having a refractive index which is different from the refractive index of the optically suitable material. 28. A method as claimed in claim 27, wherein the method produces a polymer holey optical fibre. 29. A method as claimed in claim 27, wherein the method produces a inorganic glass holey optical fibre. 30. A method as claimed in any one of claims 27 to 29, wherein the unitary body is fluid. 31. A method as claimed in claim 27, wherein said method further comprises heating said material to obtain said fluid unitary body. 32. A method as claimed in claim 27, wherein said unitary body of optical suitable material is obtained by providing said material in particulate form and melting said material to obtain said fluid unitary body. 33. A method as claimed in claim 27, wherein said fibre is formed by extrusion. 34. A method as claimed in claim 27, wherein the optically suitable material is a polymeric material. 35. A method as claimed in claim 27, wherein the optically suitable material is a mixture of polymeric and monomeric material mixed together such that, thermomechanically, they act as a single material during formation of the fibre. 36. A method as claimed in claim 27, wherein the optically suitable material includes a monomeric material, said method further comprising a step of polymerisation of said material. 37. A method as claimed in claim 27, wherein the fibre is produced with a regular lattice of discrete optical elements. 38. A method as claimed in claim 27, wherein at least some of the discrete optical elements are air holes. 39. A method as claimed in claim 27, wherein at least some of the discrete optical elements are evacuated, filled with fluid or another optical material. 40. A method as claimed in claim 27, wherein at least some of the discrete optical elements include semiconductor or other conductive materials. 41. A method as claimed in claim 27, wherein at least some of the discrete optical elements include conductive materials. 42. A method as claimed in claim 27, wherein the relative cross-sectional position of the discrete optical elements remain constant along the length of the fibre. 43. A method as claimed in claim 27, wherein the relative cross-sectional position of the discrete optical elements varies along the length of the fibre. 44. A method as claimed in claim 27, wherein at least some of the discrete optical elements extend in a mutually spaced apart array parallel to the axis of the fibre. 45. A method as claimed in claim 27, wherein at least some of the discrete optical elements extend in a helical spiral along the length of the fibre. 46. A method as claimed in claim 27, wherein at least some of the discrete optical elements intersect at various points along the length of the fibre. 47. A method as claimed in claim 27, wherein the cross-sectional size and shape of at least some of the discrete optical elements remain constant along the length of the fibre. 48. A method as claimed in claim 27, wherein the cross-sectional size and shape of at least some of the discrete optical elements vary along the length of the fibre. 49. A preform produced in accordance with claim 1. 50. A holey optical fibre produced in accordance with claims 17 or 27. |
<SOH> BACKGROUND OF THE INVENTION <EOH>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. In the late 1990's, Philip Russell from the University of Bath, United Kingdom and his co-workers developed optical fibres which comprised micro structured silica with a series of several hundred air holes running along its length. These fibres were sometimes referred as holey fibres and more lately as crystal fibres due to the complex lattice microstructure of the air holes. Technically, such holey or crystal fibres do not include a ‘core’ or ‘cladding’ as the terms are used when referring to conventional graded index optical fibres. In the art, however, the term ‘cladding’ is sometimes used to refer to the microstructure or lattice of air holes, of the ‘core’ being a reference to the defect or irregularity in this microstructure lattice, ie absence of an air hole through which the fibre transmits light. The first generation of fibres used a simple repeating triangular arrangement of air holes, with a single missing air hole forming the defect through which light was transmitted. More complex structures have now been developed. Originally, Russell and his team developed the fibres to exploit photonic band gap effect. However, it was soon realised that the fibres also operated by simple index guidance due to the high refractive index of the core region or defect compared to the effective index of the surrounding air holes or cladding microstructure. While the performance of crystal fibres via index guiding is well known, their use for transmission via the photonic band gap effect is not as well known. In particular, the size, shape and layout of the air holes must be strictly controlled to first realise and enhance transmission by photonic band gap. Conventional crystal fibres are commonly fabricated by bundling an array of silica (glass) rods and tubes to form the preform. This preform is then drawn into a fibre using a conventional tower set up. The stack and draw process does generally provide the crystal fibre with regular air hole arrangements. These can be quite varied including triangular or hexagonal arrangements, honeycomb type arrangements etc. These crystal fibres, however, have extremely close tolerances. In many cases, the centre to centre spacing of two nearest air holes will be less than a few microns. Accordingly, it would be useful to have an improved production method which not only provides more consistent results but which allows more varied arrangement of the fibre. It is an object of the present invention to overcome or ameliorate at least one of the disadvantages of the prior art, or to provide a useful alternative. |
Data processing terminal, parent substrate, child substrate, terminal design apparatus and method, computer program, and information storage medium |
A second ground plane (18); has one end opposite to a connector (14), which end is connected to a first ground plane (17) by resistor connection means (41). Accordingly, it is possible to lower Q of resonance of the aforementioned ground structure by the resistor connection means (41) and to prevent generation of an intense electromagnetic field attributed to an electromagnetic field of a data processing circuit. Especially when the resistor connection means (41) has a resistance value identical to a characteristic impedance of the ground structure, the ground structure is terminated in a matched way and it is possible to assure prevention of generation of an electromagnetic field attributed to resonance. |
1. A data processing terminal comprising: a first ground plane comprised of a conductor in a predetermined shape for determining a potential reference; a second ground plane comprised of a conductor in a predetermined shape having at least a plurality of edges, and positioned substantially in parallel with said first ground plane; a data processing circuit connected to at least one of said first ground plane and said second ground plane; a connector for connecting a position near one edge of said second ground plane to said first ground plane through a plurality of ground terminals; and resistive connecting means for connecting a position near another edge of said second ground plane opposite to the position of said ground connector to said first ground plane with a predetermined resistance value. 2. The data processing terminal according to claim 1, wherein said first ground plane, a plurality of said ground terminals, and said second ground plane make up a ground structure, said ground structure having a characteristic impedance equivalent to the resistance value of said resistive connecting means. 3. The data processing terminal according to claim 2, wherein: said resistive connecting means has a resistance value “R” which satisfies: [α1×120×π×h/w]<R≦[α2×120×π×h/w](Ω) where “w” represents a length of an edge of said second ground plane near which said resistive connecting means is positioned, “h” represents a spacing between said first ground plane and said second ground plane, and α1 and α2 are predetermined coefficients which satisfy “α1≦1<α2. 4. The data processing terminal according to claim 3, wherein: said resistive connecting means has the resistance value “R” which satisfies: R=120×π×h/w(Ω) 5. The data processing terminal according to claim 4, wherein: said resistive connecting means comprises n resistive connecting means for connecting said first ground plane to said second ground plane in parallel; and each of said n resistive connecting means has a resistance value “R” which satisfies: R=120×π×h/w(Ω) 6. The data processing terminal according to claim 1, wherein one of said resistive connecting means connects a position near a center of an edge of said second ground plane to said first ground plane. 7. The data processing terminal according to claim 2, wherein one of said resistive connecting means connects a position near a center of an edge of said second ground plane to said first ground plane. 8. The data processing terminal according to claim 3, wherein one of said resistive connecting means connects a position near a center of an edge of said second ground plane to said first ground plane. 9. The data processing terminal according to claim 4, wherein one of said resistive connecting means connects a position near a center of an edge of said second ground plane to said first ground plane. 10. The data processing terminal according to claim 1, wherein two of said resistive connecting means connect positions near both ends of an edge of said second ground plane to said first ground plane, respectively. 11. The data processing terminal according to claim 2, wherein two of said resistive connecting means connect positions near both ends of an edge of said second ground plane to said first ground plane, respectively. 12. The data processing terminal according to claim 3, wherein two of said resistive connecting means connect positions near both ends of an edge of said second ground plane to said first ground plane, respectively. 13. The data processing terminal according to claim 4, wherein two of said resistive connecting means connect positions near both ends of an edge of said second ground plane to said first ground plane, respectively. 14. The data processing terminal according to claim 5, wherein two of said resistive connecting means connect positions near both ends of an edge of said second ground plane to said first ground plane, respectively. 15. The data processing terminal according to claim 1, wherein three of said resistive connecting means connect positions near a center and both ends of an edge of said second ground plane to said first ground plane, respectively. 16. The data processing terminal according to claim 2, wherein three of said resistive connecting means connect positions near a center and both ends of an edge of said second ground plane to said first ground plane, respectively. 17. The data processing terminal according to claim 3, wherein three of said resistive connecting means connect positions near a center and both ends of an edge of said second ground plane to said first ground plane, respectively. 18. The data processing terminal according to claim 4, wherein three of said resistive connecting means connect positions near a center and both ends of an edge of said second ground plane to said first ground plane, respectively. 19. The data processing terminal according to claim 5, wherein three of said resistive connecting means connect positions near a center and both ends of an edge of said second ground plane to said first ground plane, respectively. 20. The data processing terminal according to claim 6, wherein: said resistive connecting means is formed in an elongated shape having an overall length equivalent to an edge of said second ground plane; and said resistive connecting means is positioned substantially in parallel with the edge of said second ground plane. 21. The data processing terminal according to claim 7, wherein: said resistive connecting means is formed in an elongated shape having an overall length equivalent to an edge of said second ground plane; and said resistive connecting means is positioned substantially in parallel with the edge of said second ground plane. 22. The data processing terminal according to claim 8, wherein: said resistive connecting means is formed in an elongated shape having an overall length equivalent to an edge of said second ground plane; and said resistive connecting means is positioned substantially in parallel with the edge of said second ground plane. 23. The data processing terminal according to claim 9, wherein: said resistive connecting means is formed in an elongated shape having an overall length equivalent to an edge of said second ground plane; and said resistive connecting means is positioned substantially in parallel with the edge of said second ground plane. 24. The data processing terminal according to claim 1, wherein: said first ground plane is formed on a parent board which has said data processing circuit mounted thereon; said second ground plane is formed on a child board which has a memory circuit mounted thereon for temporarily storing data processed by said data processing circuit; said resistive connecting means comprises a resistor mounted on said parent board and connected to said first ground plane; and said resistor on said parent board is connected to said second ground plane on said child board through a conductor. 25. The data processing terminal according to claim 2, wherein: said first ground plane is formed on a parent board which has said data processing circuit mounted thereon; said second ground plane is formed on a child board which has a memory circuit mounted thereon for temporarily storing data processed by said data processing circuit; said resistive connecting means comprises a resistor mounted on said parent board and connected to said first ground plane; and said resistor on said parent board is connected to said second ground plane on said child board through a conductor. 26. The data processing terminal according to claim 3, wherein: said first ground plane is formed on a parent board which has said data processing circuit mounted thereon; said second ground plane is formed on a child board which has a memory circuit mounted thereon for temporarily storing data processed by said data processing circuit; said resistive connecting means comprises a resistor mounted on said parent board and connected to said first ground plane; and said resistor on said parent board is connected to said second ground plane on said child board through a conductor. 27. The data processing terminal according to claim 4, wherein: said first ground plane is formed on a parent board which has said data processing circuit mounted thereon; said second ground plane is formed on a child board which has a memory circuit mounted thereon for temporarily storing data processed by said data processing circuit; said resistive connecting means comprises a resistor mounted on said parent board and connected to said first ground plane; and said resistor on said parent board is connected to said second ground plane on said child board through a conductor. 28. The data processing terminal according to claim 5, wherein: said first ground plane is formed on a parent board which has said data processing circuit mounted thereon; said second ground plane is formed on a child board which has a memory circuit mounted thereon for temporarily storing data processed by said data processing circuit; said resistive connecting means comprises a resistor mounted on said parent board and connected to said first ground plane; and said resistor on said parent board is connected to said second ground plane on said child board through a conductor. 29. The data processing terminal according to claim 6, wherein: said first ground plane is formed on a parent board which has said data processing circuit mounted thereon; said second ground plane is formed on a child board which has a memory circuit mounted thereon for temporarily storing data processed by said data processing circuit; said resistive connecting means comprises a resistor mounted on said parent board and connected to said first ground plane; and said resistor on said parent board is connected to said second ground plane on said child board through a conductor. 30. The data processing terminal according to claim 10, wherein: said first ground plane is formed on a parent board which has said data processing circuit mounted thereon; said second ground plane is formed on a child board which has a memory circuit mounted thereon for temporarily storing data processed by said data processing circuit; said resistive connecting means comprises a resistor mounted on said parent board and connected to said first ground plane; and said resistor on said parent board is connected to said second ground plane on said child board through a conductor. 31. The data processing terminal according to claim 15, wherein: said first ground plane is formed on a parent board which has said data processing circuit mounted thereon; said second ground plane is formed on a child board which has a memory circuit mounted thereon for temporarily storing data processed by said data processing circuit; said resistive connecting means comprises a resistor mounted on said parent board and connected to said first ground plane; and said resistor on said parent board is connected to said second ground plane on said child board through a conductor. 32. The data processing terminal according to claim 20, wherein: said first ground plane is formed on a parent board which has said data processing circuit mounted thereon; said second ground plane is formed on a child board which has a memory circuit mounted thereon for temporarily storing data processed by said data processing circuit; said resistive connecting means comprises a resistor mounted on said parent board and connected to said first ground plane; and said resistor on said parent board is connected to said second ground plane on said child board through a conductor. 33. The data processing terminal according to claim 1, wherein: said first ground plane is formed on a parent board which has said data processing circuit mounted thereon; said second ground plane is formed on a child board which has a memory circuit mounted thereon for temporarily storing data processed by said data processing circuit; said resistive connecting means comprises a resistor mounted on said child board and connected to said second ground plane; and said resistor on said child board is connected to said first ground plane on said parent board through a conductor. 34. The data processing terminal according to claim 2, wherein: said first ground plane is formed on a parent board which has said data processing circuit mounted thereon; said second ground plane is formed on a child board which has a memory circuit mounted thereon for temporarily storing data processed by said data processing circuit; said resistive connecting means comprises a resistor mounted on said child board and connected to said second ground plane; and said resistor on said child board is connected to said first ground plane on said parent board through a conductor. 35. The data processing terminal according to claim 3, wherein: said first ground plane is formed on a parent board which has said data processing circuit mounted thereon; said second ground plane is formed on a child board which has a memory circuit mounted thereon for temporarily storing data processed by said data processing circuit; said resistive connecting means comprises a resistor mounted on said child board and connected to said second ground plane; and said resistor on said child board is connected to said first ground plane on said parent board through a conductor. 36. The data processing terminal according to claim 4, wherein: said first ground plane is formed on a parent board which has said data processing circuit mounted thereon; said second ground plane is formed on a child board which has a memory circuit mounted thereon for temporarily storing data processed by said data processing circuit; said resistive connecting means comprises a resistor mounted on said child board and connected to said second ground plane; and said resistor on said child board is connected to said first ground plane on said parent board through a conductor. 37. The data processing terminal according to claim 5, wherein: said first ground plane is formed on a parent board which has said data processing circuit mounted thereon; said second ground plane is formed on a child board which has a memory circuit mounted thereon for temporarily storing data processed by said data processing circuit; said resistive connecting means comprises a resistor mounted on said child board and connected to said second ground plane; and said resistor on said child board is connected to said first ground plane on said parent board through a conductor. 38. The data processing terminal according to claim 6, wherein: said first ground plane is formed on a parent board which has said data processing circuit mounted thereon; said second ground plane is formed on a child board which has a memory circuit mounted thereon for temporarily storing data processed by said data processing circuit; said resistive connecting means comprises a resistor mounted on said child board and connected to said second ground plane; and said resistor on said child board is connected to said first ground plane on said parent board through a conductor. 39. The data processing terminal according to claim 10, wherein: said first ground plane is formed on a parent board which has said data processing circuit mounted thereon; said second ground plane is formed on a child board which has a memory circuit mounted thereon for temporarily storing data processed by said data processing circuit; said resistive connecting means comprises a resistor mounted on said child board and connected to said second ground plane; and said resistor on said child board is connected to said first ground plane on said parent board through a conductor. 40. The data processing terminal according to claim 15, wherein: said first ground plane is formed on a parent board which has said data processing circuit mounted thereon; said second ground plane is formed on a child board which has a memory circuit mounted thereon for temporarily storing data processed by said data processing circuit; said resistive connecting means comprises a resistor mounted on said child board and connected to said second ground plane; and said resistor on said child board is connected to said first ground plane on said parent board through a conductor. 41. The data processing terminal according to claim 20, wherein: said first ground plane is formed on a parent board which has said data processing circuit mounted thereon; said second ground plane is formed on a child board which has a memory circuit mounted thereon for temporarily storing data processed by said data processing circuit; said resistive connecting means comprises a resistor mounted on said child board and connected to said second ground plane; and said resistor on said child board is connected to said first ground plane on said parent board through a conductor. 42. The data processing terminal according to claim 1, wherein: said first ground plane is formed on a parent board which has said data processing circuit mounted thereon; said second ground plane is formed on a child board which has a memory circuit mounted thereon for temporarily storing data processed by said data processing circuit; said resistive connecting means comprises two resistors, one of said resistors being mounted on said parent board and connected to said first ground plane, and the other of said resistors being mounted on said child board and connected to said second ground plane; and said resistors on said parent board and said child board are connected to each other through a conductor. 43. The data processing terminal according to claim 2, wherein: said first ground plane is formed on a parent board which has said data processing circuit mounted thereon; said second ground plane is formed on a child board which has a memory circuit mounted thereon for temporarily storing data processed by said data processing circuit; said resistive connecting means comprises two resistors, one of said resistors being mounted on said parent board and connected to said first ground plane, and the other of said resistors being mounted on said child board and connected to said second ground plane; and said resistors on said parent board and said child board are connected to each other through a conductor. 44. The data processing terminal according to claim 3, wherein: said first ground plane is formed on a parent board which has said data processing circuit mounted thereon; said second ground plane is formed on a child board which has a memory circuit mounted thereon for temporarily storing data processed by said data processing circuit; said resistive connecting means comprises two resistors, one of said resistors being mounted on said parent board and connected to said first ground plane, and the other of said resistors being mounted on said child board and connected to said second ground plane; and said resistors on said parent board and said child board are connected to each other through a conductor. 45. The data processing terminal according to claim 4, wherein: said first ground plane is formed on a parent board which has said data processing circuit mounted thereon; said second ground plane is formed on a child board which has a memory circuit mounted thereon for temporarily storing data processed by said data processing circuit; said resistive connecting means comprises two resistors, one of said resistors being mounted on said parent board and connected to said first ground plane, and the other of said resistors being mounted on said child board and connected to said second ground plane; and said resistors on said parent board and said child board are connected to each other through a conductor. 46. The data processing terminal according to claim 5, wherein: said first ground plane is formed on a parent board which has said data processing circuit mounted thereon; said second ground plane is formed on a child board which has a memory circuit mounted thereon for temporarily storing data processed by said data processing circuit; said resistive connecting means comprises two resistors, one of said resistors being mounted on said parent board and connected to said first ground plane, and the other of said resistors being mounted on said child board and connected to said second ground plane; and said resistors on said parent board and said child board are connected to each other through a conductor. 47. The data processing terminal according to claim 6, wherein: said first ground plane is formed on a parent board which has said data processing circuit mounted thereon; said second ground plane is formed on a child board which has a memory circuit mounted thereon for temporarily storing data processed by said data processing circuit; said resistive connecting means comprises two resistors, one of said resistors being mounted on said parent board and connected to said first ground plane, and the other of said resistors being mounted on said child board and connected to said second ground plane; and said resistors on said parent board and said child board are connected to each other through a conductor. 48. The data processing terminal according to claim 10, wherein: said first ground plane is formed on a parent board which has said data processing circuit mounted thereon; said second ground plane is formed on a child board which has a memory circuit mounted thereon for temporarily storing data processed by said data processing circuit; said resistive connecting means comprises two resistors, one of said resistors being mounted on said parent board and connected to said first ground plane, and the other of said resistors being mounted on said child board and connected to said second ground plane; and said resistors on said parent board and said child board are connected to each other through a conductor. 49. The data processing terminal according to claim 15, wherein: said first ground plane is formed on a parent board which has said data processing circuit mounted thereon; said second ground plane is formed on a child board which has a memory circuit mounted thereon for temporarily storing data processed by said data processing circuit; said resistive connecting means comprises two resistors, one of said resistors being mounted on said parent board and connected to said first ground plane, and the other of said resistors being mounted on said child board and connected to said second ground plane; and said resistors on said parent board and said child board are connected to each other through a conductor. 50. The data processing terminal according to claim 20, wherein: said first ground plane is formed on a parent board which has said data processing circuit mounted thereon; said second ground plane is formed on a child board which has a memory circuit mounted thereon for temporarily storing data processed by said data processing circuit; said resistive connecting means comprises two resistors, one of said resistors being mounted on said parent board and connected to said first ground plane, and the other of said resistors being mounted on said child board and connected to said second ground plane; and said resistors on said parent board and said child board are connected to each other through a conductor. 51. The data processing terminal according to claim 1, further comprising a radio communication circuit removably mounted therein for making radio communications with the outside; wherein said radio communication circuit is in wired communication with said data processing circuit. 52. The data processing terminal according to claim 2, further comprising a radio communication circuit removably mounted therein for making radio communications with the outside; wherein said radio communication circuit is in wired communication with said data processing circuit. 53. The data processing terminal according to claim 3, further comprising a radio communication circuit removably mounted therein for making radio communications with the outside; wherein said radio communication circuit is in wired communication with said data processing circuit. 54. The data processing terminal according to claim 4, further comprising a radio communication circuit removably mounted therein for making radio communications with the outside; wherein said radio communication circuit is in wired communication with said data processing circuit. 55. The data processing terminal according to claim 5, further comprising a radio communication circuit removably mounted therein for making radio communications with the outside; wherein said radio communication circuit is in wired communication with said data processing circuit. 56. The data processing terminal according to claim 6, further comprising a radio communication circuit removably mounted therein for making radio communications with the outside; wherein said radio communication circuit is in wired communication with said data processing circuit. 57. The data processing terminal according to claim 10, further comprising a radio communication circuit removably mounted therein for making radio communications with the outside; wherein said radio communication circuit is in wired communication with said data processing circuit. 58. The data processing terminal according to claim 15, further comprising a radio communication circuit removably mounted therein for making radio communications with the outside; wherein said radio communication circuit is in wired communication with said data processing circuit. 59. The data processing terminal according to claim 20, further comprising a radio communication circuit removably mounted therein for making radio communications with the outside; wherein said radio communication circuit is in wired communication with said data processing circuit. 60. The data processing terminal according to claim 24, further comprising a radio communication circuit removably mounted therein for making radio communications with the outside; wherein said radio communication circuit is in wired communication with said data processing circuit. 61. The data processing terminal according to claim 33, further comprising a radio communication circuit removably mounted therein for making radio communications with the outside; wherein said radio communication circuit is in wired communication with said data processing circuit. 62. The data processing terminal according to claim 42, further comprising a radio communication circuit removably mounted therein for making radio communications with the outside; wherein said radio communication circuit is in wired communication with said data processing circuit. 63. The data processing terminal according to claim 1, further comprising: a radio communication circuit formed integrally therewith for making radio communications with the outside; wherein said radio communication circuit is in wired communication with said data processing circuit. 64. The data processing terminal according to claim 2, further comprising: a radio communication circuit formed integrally therewith for making radio communications with the outside; wherein said radio communication circuit is in wired communication with said data processing circuit. 65. The data processing terminal according to claim 3, further comprising: a radio communication circuit formed integrally therewith for making radio communications with the outside; wherein said radio communication circuit is in wired communication with said data processing circuit. 66. The data processing terminal according to claim 4, further comprising: a radio communication circuit formed integrally therewith for making radio communications with the outside; wherein said radio communication circuit is in wired communication with said data processing circuit. 67. The data processing terminal according to claim 5, further comprising: a radio communication circuit formed integrally therewith for making radio communications with the outside; wherein said radio communication circuit is in wired communication with said data processing circuit. 68. The data processing terminal according to claim 6, further comprising: a radio communication circuit formed integrally therewith for making radio communications with the outside; wherein said radio communication circuit is in wired communication with said data processing circuit. 69. The data processing terminal according to claim 10, further comprising: a radio communication circuit formed integrally therewith for making radio communications with the outside; wherein said radio communication circuit is in wired communication with said data processing circuit. 70. The data processing terminal according to claim 15, further comprising: a radio communication circuit formed integrally therewith for making radio communications with the outside; wherein said radio communication circuit is in wired communication with said data processing circuit. 71. The data processing terminal according to claim 20, further comprising: a radio communication circuit formed integrally therewith for making radio communications with the outside; wherein said radio communication circuit is in wired communication with said data processing circuit. 72. The data processing terminal according to claim 24, further comprising: a radio communication circuit formed integrally therewith for making radio communications with the outside; wherein said radio communication circuit is in wired communication with said data processing circuit. 73. The data processing terminal according to claim 33, further comprising: a radio communication circuit formed integrally therewith for making radio communications with the outside; wherein said radio communication circuit is in wired communication with said data processing circuit. 74. The data processing terminal according to claim 42, further comprising: a radio communication circuit formed integrally therewith for making radio communications with the outside; wherein said radio communication circuit is in wired communication with said data processing circuit. 75. A parent board for the data processing terminal according to claim 24, comprising: said first ground plane formed thereon; and said resistor mounted thereon and connected to said first ground plane to serve as said resistive connecting means. 76. A child board for the data processing terminal according to claim 33, comprising: said second ground plane formed thereon; and said resistor mounted thereon and connected to said second ground plane to serve as said resistive connecting means. 77. A terminal designing apparatus for use in designing a data processing terminal comprising a first ground plane comprised of a conductor in a predetermined shape for determining a potential reference, a second ground plane comprised of a conductor in a predetermined shape having at least a plurality of edges, and positioned substantially in parallel with said first ground plane, a data processing circuit connected to at least one of said first ground plane and said second ground plane, and a connector for connecting a position near one edge of said second ground plane to said first ground plane through a plurality of ground terminals, said apparatus comprising: length input means for receiving a length “w” of the other edge of said second ground plane opposite to a position of said connector; length storing means for storing the length “w” entered through said length input means; spacing input means for receiving a spacing “h” between said first ground plane and said second ground plane; spacing storing means for storing the spacing “h” entered through said spacing input means; and resistance calculating means for calculating a resistance value “R” of resistive connecting means for connecting a position near the other edge of said second ground plane opposite to the position of said connector to said first ground plane in accordance with “R=120×π×h/w (Ω)”. 78. A terminal designing method for designing a data processing terminal comprising a first ground plane comprised of a conductor in a predetermined shape for determining a potential reference, a second ground plane comprised of a conductor in a predetermined shape having at least a plurality of edges, and positioned substantially in parallel with said first ground plane, a data processing circuit connected to at least one of said first ground plane and said second ground plane, and a connector for connecting a position near one edge of said second ground plane to said first ground plane through a plurality of ground terminals, said method comprising: a length input step for receiving a length “w” of the other edge of said second ground plane opposite to a position of said connector; a length storing step for storing the length “w” entered at said length input step; a spacing input step for receiving a spacing “h” between said first ground plane and said second ground plane; a spacing storing step for storing the spacing “h” entered at said spacing input step; and a resistance calculating step for calculating a resistance value “R” of resistive connecting means for connecting a position near the other edge of said second ground plane opposite to the position of said connector to said first ground plane in accordance with “R=120×π×h/w (Ω)”. 79. A computer program for the terminal designing apparatus according to claim 77, said computer program causing said terminal designing apparatus to execute: length input processing for receiving a length “w” of the other edge of said second ground plane opposite to a position of said connector; length storing processing for storing the length “w” entered through said length input processing; spacing input processing for receiving a spacing “h” between said first ground plane and said second ground plane; spacing storing processing for storing the spacing “h” entered through said spacing input processing; and resistance calculating processing for calculating a resistance value “R” of resistive connecting means for connecting a position near the other edge of said second ground plane opposite to the position of said connector to said first ground plane in accordance with “R=120×π×h/w (Ω)”. 80. An information storage medium having a computer program for a terminal designing apparatus, wherein: said information storage medium has the computer program according to claim 79 stored thereon. 81. A data processing terminal comprising: a first board including a first circuit; a second board disposed substantially in parallel with said first board and including a second circuit; a first ground plane disposed on said first board, and comprised of a conductor in a predetermined shape for determining a potential reference for said first board; a second ground plane disposed on said second board, and comprised of a conductor in a predetermined shape for determining a potential reference for said second board; a ground terminal for connecting a position near one end of an edge of said second ground plane to said first ground plane; a signal terminal for communicating an electric signal between said first circuit and said second circuit; a connector including said ground terminal and said signal terminal; and resistive connecting means for connecting a position near one end of the other edge of said second ground plane to said first ground plane, and having a predetermined resistance value. 82. The data processing terminal according to claim 81, wherein: said first circuit comprises a data processing circuit; and said second circuit comprises a memory circuit for temporarily storing data processed by said data processing circuit. |
<SOH> BACKGROUND ART <EOH>At present, a variety of user terminal devices are pervasive. They can serve as PDA (Personal Digital Assistant) to support a variety of users, and communicate data processed thereby to the outside using a wireless communication function such as PHS (Personal Handy-phone System: a registered trademark). Now, a prior art example of such a data processing terminal will be described with reference to drawings. FIG. 1 illustrates data processing terminal 10 as a first prior art example. Data processing terminal 10 comprises a hollow housing (not shown) which contains parent board 11 , child board 15 , and connector 14 for connecting both boards. Parent board 11 is mounted with a variety of data processing circuits (not shown) comprised of integrated circuits, while child board 15 is mounted with a memory circuit (not shown) such as RAM (Random Access Memory), flash memory and the like. A card slot (not shown) is formed at one end of the housing, such that separate card-shaped radio communication unit 12 is removably plugged into the card slot. Radio communication unit 12 comprises a built-in radio communication circuit (not shown), and rod-like antenna 13 attached thereto. Data processing terminal 10 has a user interface (not shown) such as a touch panel, a keyboard and the like on the surface of the housing, such that the data processing circuit on parent board 11 executes a variety of data processing in response to data entered through the user interface and the like. In data processing terminal 10 , as card-shaped radio communication unit 12 is plugged into the card slot of the housing, the radio communication circuit in radio communication unit 12 can be in wired communication with the data processing circuit on parent board 11 , permitting data processing terminal to make radio communications in a frequency band near 1.9 (GHz) using a PHS function through radio communication unit 12 . In other words, data processing terminal 10 can make radio communications with the outside as required with the aid of radio communication unit 12 to transmit data processed by the data processing circuit over the air, as well as to process data received over the air with the aid of the data processing circuit. Further, when data processed by the data processing circuit is stored in the memory circuit on child board 15 , data processing terminal 10 can process a large capacity of data. In data processing terminal 10 as described above, parent board 11 is substantially entirely formed with a metal-made first ground plane, while child board 15 is likewise substantially entirely formed with a metal-made second ground plane (not shown), wherein both ground planes determine potential references for circuits on the respective boards. Connector 14 , which connects the two boards, has a plurality of signal terminals and a plurality of ground terminals arranged in parallel, wherein one ground terminal is inserted, for example, every three signal terminals. With such a structure, as child board 15 is mounted on parent board 11 , data processing circuit on parent board 11 is connected to the memory circuit on child board 15 through the signal terminals of connector 14 , and the first ground plane on parent board 11 is connected to the second ground plane on child board 15 through the ground terminals of connector 14 to connect the potential references provided by the ground planes on both boards. While FIG. 1 illustrates data processing terminal 10 which has child board 15 mounted on parent board 11 through a pair of connectors 14 that are removable in the vertical direction, there is also a product, data processing terminal 20 illustrated in FIG. 2 , which is a second prior art example, wherein child board 15 is mounted to and removed from connector 21 in the transverse direction. Also, as data processing terminal 30 in FIG. 3 , which is a third prior art example, there is a product which comprises connection pads 31 , 32 formed on the front surface and back surface of parent board 11 and child board 15 and electrically connected to the first ground plane and second ground plane, respectively, with connection pads 31 , 32 being electrically connected through tubular metal columns 34 and screws 35 which make up auxiliary connecting means 33 . It should be noted that such metal columns 34 and screws 35 are generally intended to mechanically hold child board 15 , so that they are disposed near a pair of corners at diagonal positions of child board 15 . In the aforementioned data processing terminal 10 , 20 , first ground plane 17 of parent board 11 and second ground plane 18 of child board 15 connected through connectors 14 , 21 are positioned in parallel with each other, as illustrated in FIG. 4 . Also, data processing circuit 19 composed of a multiplicity of electronic parts such as LSIs (Large Scale Integration) and signal wires is mounted on first ground plane 17 of parent board 11 . Since data processing circuit 19 transmits repetitive signals and non-repetitive signals at particular frequencies within the circuit when it processes data, an electromagnetic field is generated in the neighborhood, associated with frequency components and harmonic components of the transmitted signals. This electromagnetic field not only causes a high frequency current to flow into first ground plane 17 of parent board 11 but also induces a high frequency current into second ground plane 18 of child board 15 disposed in the neighborhood. The inventors found that the ground structure comprised of first ground plane 17 of parent board 11 , second ground plane 18 of child board 15 , and the ground terminals of connectors 14 as illustrated in FIG. 4 well resembled an antenna element of a quarter wavelength resonant antenna referred to as an “inverted L-shaped antenna” or an “inverted F-shaped antenna”, as illustrated in FIGS. 5A and 5B (reference: “Small Antennas” K. Fujimoto, A. Henderson and J. R. James, Research Studies Press, Chapter 2.4). In thinking in the foregoing manner, from the fact that connector 14 comprises a plurality of ground terminals, second ground plane 18 of child board 15 has an edge close to connector 14 that corresponds to a short-circuited end of the antenna element, and an edge opposite to connector 14 that corresponds to an open end of the antenna element. If a current induced into second ground plane 18 from data processing circuit 19 includes frequency components which cause second ground plane 18 to generate quarter wavelength resonance, a strong electromagnetic field is generated around second ground plane 18 , thereby irradiating strong electromagnetic waves a long way off. When considering child board 15 that has a memory circuit mounted thereon, child board 15 generally has edges extending over approximately 25 to 75 (mm), so that the quarter wavelength resonance occurs at frequency in a range of approximately 1 to 3 (GHz). Since conventional data processing circuit 19 internally transmits signals at a basic frequency around several MHz, its harmonics are also on the order of 100 (MHz) at most. Thus, data processing circuit 19 is free from the quarter wavelength resonance because harmonic components are largely lower than the frequency at which the quarter wavelength resonance occurs in the ground structure. Recently, however, the trend of increasing the processing speed of integrated circuits has increased the basic frequency of data processing circuit 19 to several hundred MHz, and its harmonics have also spread to as high as several GHz. Since the harmonics overlap the frequency at which the aforementioned ground structure is at the quarter wavelength, the ground structure suffers from the resonance. On the other hand, with the recent development of radio communications, GHz bands are increasingly utilized for radio communications, such as approximately 1.9 (GHz) in PHS; approximately 800 (MHz), approximately 1.5 (GHz), and approximately 2.0 (GHz) in portable telephones; and approximately 2.4 (GHz) in wireless LAN (Local Area Network) and Bluetooth. From the foregoing background, the resonant frequency associated with the ground structure overlaps the frequency bands used for radio communications, giving rise to a problem that radio communications are impeded by the ground structure. While it has been predicted from before that the electromagnetic field generated by data processing circuit 19 would directly affect radio communication unit 12 , and countermeasures have been taken therefor, nobody has been able to predict that the operation of data processing circuit 19 on parent board 11 causes child board 15 and the like to act as a resonant antenna, and an electromagnetic field generated thereby affects radio communication unit 12 . As illustrated in FIG. 3 , in data processing terminal 30 of the third prior art example, first and second ground planes 17 , 18 are each short-circuited by auxiliary connecting means 33 at a corner near an open edge thereof, so that the ground structure in this prior art example is free from the quarter wavelength resonance, but can suffer from half wavelength resonance. Since the half wavelength resonance is induced at frequency on the order of 2-6 (GHz) with the aforementioned size, this range of frequencies, though slightly higher than the previous examples, will impede the communications as well because it is close to the frequency bands used for radio communications. The description made in connection with the aforementioned data processing terminals 10 , 20 , 30 clarifies that radio communications made by removably connected radio communication unit 12 are impeded by the ground structure within the terminal. Such impeded radio communications will be experienced if radio communication unit 12 is disposed near the ground structure. Therefore, communication failures can arise even if a radio communication circuit is connected to the data processing terminal through a connection cable, or when it is placed near the data processing terminal, though not connected thereto (not shown). To solve the problem as mentioned above, child board 15 may be covered with a metal case (not shown), with the metal case being connected to first ground plane 17 of parent substrate 11 , to isolate radio communication unit 12 from a strong electromagnetic field generated by child board 15 . However, even with the structure using the metal case for fully covering child board 15 , the metal case causes a problem of an increase in the size of data processing terminal 10 , 20 , 30 . |
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>FIG. 1 is a perspective view illustrating the internal structure of a first exemplary conventional data processing terminal; FIG. 2 is a perspective view illustrating the internal structure of a second exemplary conventional data processing terminal; FIG. 3 is a perspective view illustrating the internal structure of a third exemplary conventional data processing terminal; FIG. 4 is a schematic diagram illustrating electric features such as a first ground plane, a second ground plane, and the like in the first exemplary conventional data processing terminal; FIG. 5A is a schematic diagram illustrating the structure of an inverted L-shaped antenna; FIG. 5B is a schematic diagram illustrating the structure of an inverted F-shaped antenna; FIG. 6 is a perspective view illustrating the internal structure of a data processing terminal according to a first embodiment of the present invention; FIG. 7 is a schematic diagram illustrating electric features such as a first ground plane, a second ground plane and, the like; FIG. 8 is a block diagram illustrating the physical structure of a terminal designing apparatus according to the first embodiment of the present invention; FIG. 9 is a schematic diagram illustrating the logical structure of the terminal designing apparatus; FIG. 10 is a flow chart illustrating a terminal designing method associated with the terminal designing apparatus; FIG. 11 is a perspective view illustrating the internal structure of a first exemplary modification to the data processing terminal; FIG. 12 is a perspective view illustrating the internal structure of a second exemplary modification to the data processing terminal; FIG. 13 is a perspective view illustrating the internal structure of a third exemplary modification to the data processing terminal; FIG. 14A is a top plan view illustrating a main portion of a fourth exemplary modification to the data processing terminal; FIG. 14B is a top plan view illustrating a main portion of a fifth exemplary modification to the data processing terminal; FIG. 15A is a top plan view illustrating a main portion of a sixth exemplary modification to the data processing terminal; FIG. 15B is a top plan view illustrating a main portion of a seventh exemplary modification to the data processing terminal; FIG. 16 is a top plan view illustrating a main portion of an eighth exemplary modification to the data processing terminal; FIG. 17 is a perspective view illustrating the internal structure of a data processing terminal according to a second embodiment of the present invention; FIG. 18 is a bottom view illustrating a main portion of a child board; FIG. 19A is a schematic diagram illustrating an electromagnetic simulation model; FIG. 19B is a schematic diagram illustrating an electromagnetic simulation model; and FIG. 20 is a characteristic diagram showing the frequency characteristic of distant radiation electric field strength. detailed-description description="Detailed Description" end="lead"? |
Carbohydrate-associated proteins |
The invention provides human carbohydrate-associated proteins (CHOP) and polynucleotides which identify and encode CHOP. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for diagnosing, treating, or preventing disorders associated with aberrant expression of CHOP. |
1. An isolated polypeptide selected from the group consisting of: a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-10, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-3, SEQ ID NO:5, and SEQ ID NO:7-10, c) a polypeptide comprising a naturally occurring amino acid sequence at least 93% identical to the amino acid sequence of SEQ ID NO:4, d) a polypeptide comprising a naturally occurring amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:6, e) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-10, and f) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-10. 2. An isolated polypeptide of claim 1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-10. 3. n isolated polynucleotide encoding a polypeptide of claim 1. 4. An isolated polynucleotide encoding a polypeptide of claim 2. 5. An isolated polynucleotide of claim 4 comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:11-20. 6. A recombinant polynucleotide comprising a promoter sequence operably linked to a polynucleotide of claim 3. 7. A cell transformed with a recombinant polynucleotide of claim 6. 8. (CANCELED) 9. A method of producing a polypeptide of claim 1, the method comprising: a) culturing a cell under conditions suitable for expression of the polypeptide, wherein said cell is transformed with a recombinant polynucleotide, and said recombinant polynucleotide comprises a promoter sequence operably linked to a polynucleotide encoding the polypeptide of claim 1, and b) recovering the polypeptide so expressed. 10. A method of claim 9, wherein the polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO:1-10. 11. An isolated antibody which specifically binds to a polypeptide of claim 1. 12. An isolated polynucleotide selected from the group consisting of: a) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:11-20, b) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:11-20, c) a polynucleotide complementary to a polynucleotide of a), d) a polynucleotide complementary to a polynucleotide of b), and e) an RNA equivalent of a)-d). 13. (CANCELED) 14. A method of detecting a target polynucleotide in a sample, said target polynucleotide having a sequence of a polynucleotide of claim 12, the method comprising: a) hybridizing the sample with a probe comprising at least 20 contiguous nucleotides comprising a sequence complementary to said target polynucleotide in the sample, and which probe specifically hybridizes to said target polynucleotide, under conditions whereby a hybridization complex is formed between said probe and said target polynucleotide or fragments thereof, and b) detecting the presence or absence of said hybridization complex, and, optionally, if present, the amount thereof. 15. (CANCELED) 16. A method of detecting a target polynucleotide in a sample, said target polynucleotide having a sequence of a polynucleotide of claim 12, the method comprising: a) amplifying said target polynucleotide or fragment thereof using polymerase chain reaction amplification, and b) detecting the presence or absence of said amplified target polynucleotide or fragment thereof, and, optionally, if present, the amount thereof. 17. A composition comprising a polypeptide of claim 1 and a pharmaceutically acceptable excipient. 18. A composition of claim 17, wherein the polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO:1-10. 19. (CANCELED) 20. A method of screening a compound for effectiveness as an agonist of a polypeptide of claim 1, the method comprising: a) exposing a sample comprising a polypeptide of claim 1 to a compound, and b) detecting agonist activity in the sample. 21. (CANCELED) 22. (CANCELED) 23. A method of screening a compound for effectiveness as an antagonist of a polypeptide of claim 1, the method comprising: a) exposing a sample comprising a polypeptide of claim 1 to a compound, and b) detecting antagonist activity in the sample. 24. (CANCELED) 25. (CANCELED) 26. A method of screening for a compound that specifically binds to the polypeptide of claim 1, the method comprising: a) combining the polypeptide of claim 1 with at least one test compound under suitable conditions, and b) detecting binding of the polypeptide of claim 1 to the test compound, thereby identifying a compound that specifically binds to the polypeptide of claim 1. 27. (CANCELED) 28. A method of screening a compound for effectiveness in altering expression of a target polynucleotide, wherein said target polynucleotide comprises a sequence of claim 5, the method comprising: a) exposing a sample comprising the target polynucleotide to a compound, under conditions suitable for the expression of the target polynucleotide, b) detecting altered expression of the target polynucleotide, and c) comparing the expression of the target polynucleotide in the presence of varying amounts of the compound and in the absence of the compound. 29. A method of assessing toxicity of a test compound, the method comprising: a) treating a biological sample containing nucleic acids with the test compound, b) hybridizing the nucleic acids of the treated biological sample with a probe comprising at least 20 contiguous nucleotides of a polynucleotide of claim 12 under conditions whereby a specific hybridization complex is formed between said probe and a target polynucleotide in the biological sample, said target polynucleotide comprising a polynucleotide sequence of a polynucleotide of claim 12 or fragment thereof, c) quantifying the amount of hybridization complex, and d) comparing the amount of hybridization complex in the treated biological sample with the amount of hybridization complex in an untreated biological sample, wherein a difference in the amount of hybridization complex in the treated biological sample is indicative of toxicity of the test compound. 30-75. (CANCELED) |
<SOH> BACKGROUND OF THE INVENTION <EOH>Carbohydrates, including sugars or saccharides, starch, and cellulose, are aldehyde or ketone compounds with multiple hydroxyl groups. Carbohydrates have three important roles in mammalian cells. Carbohydrates function as energy-storage molecules, as fuels, and as metabolic intermediates. Carbohydrates are broken down to release energy in glycolysis or may be stored as glycogen for later use. The importance of carbohydrate metabolism is demonstrated by the sensitive regulatory system in place for maintenance of blood glucose levels. Two pancreatic hormones, insulin and glucagon, promote increased glucose uptake and storage by cells, and increased glucose release from cells, respectively. The sugars deoxyribose and ribose form part of the structural support of DNA and RNA, respectively, providing a second example of carbohydrate function. Third, carbohydrates provide a means for post-translational modification of secreted and membrane proteins and lipids. Indeed, 2-10% of the content of eukaryotic cell membranes are contributed by oligosaccharides on membrane glycoproteins and glycolipids. Carbohydrate modifications on glycoproteins and glycolipids create great structural diversity, and since they are mainly located on the extracellular side of the plasma membrane, they play an important role in intercellular recognition (Stryer, L. (1988) Biochemistry , W. H. Freeman and Company, New York N.Y., pp. 298-299, 331-347). Proteins are associated with carbohydrates in several ways. Carbohydrate-containing macromolecules, which include glycoproteins, glycolipids, glycosaminoglycans, and proteoglycans, are found on the cell surface and in the extracellular matrix. The extracellular matrix is composed of diverse glycoproteins, and carbohydrate-binding proteins which are secreted from the cell and assembled into an organized meshwork in close association with the cell surface. The interaction of the cell with the surrounding matrix profoundly influences cell shape, strength, flexibility, motility, and adhesion. These dynamic properties are intimately associated with signal transduction pathways controlling cell proliferation and differentiation, tissue construction, and embryonic development. Glycoproteins have covalently attached carbohydrates which have been added to the proteins as they traverse the secretory pathway. Some proteins noncovalently associate with carbohydrate-containing macromolecules for purposes of binding, modifying, or degrading the carbohydrates. Glycoproteins include cell adhesion molecules, receptors, blood group antigens, growth factors, and antibodies. These proteins are involved in cellular processes such as cell-cell recognition and signaling, recognition and/or destruction of neurotransmitters, transmission of neural impulses, and immune function. Oligosaccharide modifications can provide great structural diversity. N- and O-linked oligosaccharides are transferred to proteins and modified in a series of enzymatic reactions that occur in the endoplasmic reticulum (ER) and Golgi. Oligosaccharides stabilize the protein during and after folding, orient the protein in the membrane, improve the protein's solubility, and act as a signal for lysosome targeting. Heavily glycosylated glycoproteins are also referred to as proteoglycans. Proteoglycans in the extracellular matrix of connective tissues such as cartilage are essential for distributing the load in weight-bearing joints. Cell-surface-attached proteoglycans anchor cells to the extracellular matrix. Both extracellular and cell-surface proteoglycans bind growth factors, facilitating their binding to cell-surface receptors and subsequent triggering of signal transduction pathways (Lodish, H. et al. (1995) Molecular Cell Biology , Scientific American Books, New York N.Y., pp. 1139-1142). Carbohydrates also form glycosaminoglycans (GAGs), which are linear unbranched polysaccharides composed of repetitive disaccharide units. GAGs exist free or as part of proteoglycans, large molecules composed of a core protein attached to one or more GAGs. GAGs are found on the cell surface, inside cells, and in the extracellular matrix. The GAG hyaluronan (HA) is found in the extracellular matrix of many cells, especially in soft connective tissues, and is abundant in synovial fluid (Pitsillides, A. A. et al. (1993) Int. J. Exp. Pathol. 74:27-34). HA, which functions in water and plasma protein homeostasis, seems to play important roles in cell regulation, development, and differentiation. Glycolipids, along with phospholipids and cholesterol, form the membranes of cells. Examples of glycolipids include blood group antigens on erythrocytes and gangliosides in the myelin sheath of neurons. Modifications to glycoproteins and glycolipids on the extracellular side of the plasma membrane are important for intercellular recognition (Stryer, supra, pp. 298-299, 331-347; Lodish, et al., supra, pp. 612615). Lectins are extracellular glycoproteins which bind cell surface carbohydrates specifically and reversibly, resulting in the agglutination of cells (Drickamer, K. and Taylor, M. E. (1993) Annu. Rev. Cell Biol. 9:237-264). This function is particularly important for activation of the immune response. Lectins mediate the agglutination and mitogenic stimulation of lymphocytes at sites of inflammation (Lasky, L. A. (1991) J. Cell. Biochem 45:139-146; Paietta, E. et al. (1989) J. Immunol. 143:2850-2857). Lectins are classified into subfamilies based on carbohydrate-binding specificity. The galectin subfamily, in particular, includes lectins that bind β-galactoside carbohydrate moieties in a thiol-dependent manner (Hadari, Y. R. et al. (1995) J. Biol. Chem. 270:3447-3453). Galectins are widely expressed and developmentally regulated. Because all galectins lack an N-terminal signal peptide, it is suggested that galectins are externalized through an atypical secretory mechanism. Two classes of galectins have been defined based on molecular weight and oligomerization properties. Galectins contain a characteristic carbohydrate recognition domain (CRD), also known as a galaptin domain, which is about 140 amino acids long and contains several conserved residues (See Prosite PDOC00279 Vertebrate galactoside-binding lectin signature). Another example is intelectin, a Ca 2+ dependent lectin that binds to galactofuranosyl residues and bacterial arabinogalactan. Intelectin may play a role in the recognition of bacterial carbohydrate and induction of the immune response to microorganisms. Carbohydrate-Modifying Enzymes The enzyme glutamine:fructose-6-phosphate amidotransferase (GFAT), also known as aminotransferase, catalyzes the reversible reaction of L-glutamine and D-fructose-6-phosphate to form L-glutamate and D-glucosamine-6-phosphate, which is the rate-limiting step in the hexosamine biosynthetic pathway (ExPASy ENZYME: EC 2.6.1.16). D-glucosamine-6-phosphate acts in the biosynthesis of UDP-N-acetyl-glucosamine (UDP-GlcNAc) and other hexosamines incorporated into glycoproteins and proteoglycans. GFAT regulates the availability of precursors for N- and O-linked glycosylation. Glucosamine enhances the production of transforming growth-factor (TGF)-β1 (Kolrm-Litty, V. et al. (1998) J. Clin. Invest. 101: 160-169). GFAT activity plays a role in insulin resistance in Type II diabetes, and GFAT overexpression leads to insulin resistance. Hexosamine metabolism appears to regulate glycogen synthase, the rate-limiting enzyme in glycogen synthesis, as well as PP1G, a glycogen-bound protein phosphatase, pyruvate kinase, and the glucose transporter GLUT1 (McClain, D. A. and Crook, E. D. (1996) Diabetes 45:1003-1009). The enzyme glucosaminephosphate deaminase (GNPDA), also known as isomerase, catalyzes the reversible reaction of D-glucosamine-6-phosphate with water to form D-fructose-6-phosphate and ammonia (ExPASy ENZYME EC 5.3.1.10). This reaction links hexosamine systems with glycolytic pathways and may provide an energy source from the catabolism of hexosamines in glycoproteins, glycolipids, and sialic-acid-containing macromolecules. GNPDA is expressed in tissues with high energy requirements (Wolosker, H. et al. (1998) FASEB J. 12:91-99). The enzyme UDP-glucose dehydrogenase (UDPGD) catalyzes the reversible reaction of UDP-glucose, 2 NAD + , and water to form UDP-glucuronate and 2 NADH (ExPASy ENZYME EC 1.1.1.22). UDP-glucuronate is needed for the biosynthesis of GAGs, which appear to play a role in signal transduction pathways (Binari, R. C. et al. (1997) Development 124:2623-2632). Man 9 -mannosidase is an α1,2-mannosidase (glycosyl hydrolase) involved in the early processing of N-line oligosaccharides. This enzyme catalyzes the specific cleavage of α1,2-mannosidic linkages in Man 9 -(GlcNAc) 2 and Man 5 -(GlcNAc) 2 . Multiple α1,2-mannosidases have been identified in mammalian cells and may be needed for the processing of distinct classes of N-glycoproteins. Man 9 -mannosidase is a Type II membrane protein with a short cytoplasmic tail, a single transmembrane domain, and a large luminal catalytic domain. The human kidney enzyme is localized to the Golgi (Bause, E. et al. (1993) Eur. J. Biochem. 217:535-540; Bieberich, E. and Bause, E. (1995) Eur. J. Biochern 233:644-649). DPM1 is an enzyme in the endoplasmic reticulum that catalyzes the production of dolichol phosphate-mannose (DPM) from GDP-mannose and dolichol phosphate. The activity of DPM1 is regulated by DPM2, which targets DPM1 to the endoplasmic reticulum (ER) and increases its affinity for dolichol phosphate. DMP2 resides in the (ER) membrane and contains two putative transmembrane domains and a putative ER-localization signal near its C-terminus. Glycosylation Glycosylation refers to the covalent attachment of any number of carbohydrate chains (oligosaccharides) to specific sites (glycosylation sites) on proteins. Glycosylation is a post-translational protein modification essential to the conformation, stability, transport, secretion, antigenicity, clearance and activity of glycosylated proteins (glycoproteins). The composition of the attached oligosaccharides is specific to a protein and may be simple (consisting primarily of mannose residues) or complex (with additional N-acetyl-glucosamine (GlcNAc), sialic acid, and galactose residues). Glycoproteins may have relatively few carbohydrate groups or may contain a larger percentage of carbohydrate than protein (based on molecular weight). These latter, heavily glycosylated glycoproteins are also referred to as proteoglycans to emphasize the predominant carbohydrate composition of the molecules. The type of saccharide bond (e.g., α, β, 1,2-, 1,4-) formed between any two constituent carbohydrate residues is also a critical molecular determinant for the structure and function of the glycoprotein. Glycosylation confers increased hydrophilicity to proteins. Many glycoproteins, such as carrier proteins, antibodies, and lysosomal proteins, are found free in solution (e.g., plasma). Other glycoproteins are membrane-bound. In the case of membrane-associated glycoproteins, the carbohydrate side-chain serves to orient the glycoproteins in the membrane lipid bilayer. The glycosylated regions of the molecule interact with the aqueous environment on the inside or outside of the membrane while the more hydrophobic domains of the glycoprotein (typically consisting of non-polar amino acid residues that are not glycosylated) interact with the phospholipids in the membrane. Addition of oligosaccharide side chains occurs at the —NH 2 group of asparagine (Asn) residues (N-linked glycosylation) or at the —OH group of serine (Ser) residues (O-linked glycosylation). The process of N-linked glycosylation begins in the endoplasmic reticulum (ER) and is completed in the Golgi apparatus of eukaryotic cells. O-linked glycosylation occurs exclusively in the Golgi. Of all characterized glycoproteins, 90% are N-glycosylated, with or without additional O-glycosylation. Only 10% are exclusively O-glycosylated (Apweiler, R. et al. (1999) Biochim Biophys. Acta 1473:4-8). Almost two-thirds of the approximately 75,000 SWISS-PROT protein sequences include putative N-glycosylation sites, underscoring the importance of this protein modification in nature (Apweiler et al., supra). Biochemical steps involved in N-linked glycosylation have been well characterized, and are reviewed below. N-Linked Glycosylation N-linkage of carbohydrates to proteins occurs via a nitrogen atom of asparagine (Asn) residue side-chains in the context of the primary amino acid sequence Asn-X-Ser or Asn-X-Thr (Ser=serine, Thr=threonine, and X=any amino acid residue except proline). While the composition of N-linked oligosaccharides is highly diverse, the pathways responsible for glycosylation have common first steps. A 14-residue core oligosaccharide, containing two N-acetylglucosamine (GlcNAc), nine mannose, and three glucose residues, is transferred as a unit from a dolichol phosphate donor molecule to the —NH 2 group of an acceptor Asn residue on the target protein. Typically, the three glucose residues of the core oligosaccharide are removed by glucosidases I and II resulting in “high mannose oligosaccharides” side chains. These partially processed N-linked glycoproteins are then sequentially transported from the ER through the cis-, medial-, and trans-cisternae of the Golgi (Bonay, P. et al. (1996) 3. Biol. Chem. 271:3719-3726). Further modification to the oligosaccharide chains may occur to remove additional core mannose residues using the enzymes Golgi mannosidase I (cis-cisterna), N-acetyl-glucosaminyltransferase (GluNAcT; medial-cisterna), and Golgi mannosidase II (trans-cisternae). Following the removal of some of the mannose residues by Golgi mannosidase I, the addition of a single GlcNAc by GluNAcT is essential for the removal of the remaining mannose residues of the core oligosaccharide by Golgi mannosidase II. Mannose-1-phosphate guanyltransferases are involved in early steps of protein glycosylation. They participate in sugar metabolism and their enzymatic products are channeled into glycoprotein synthesis. Mannose-1-phosphate guanyltransferase 1 (MPG1), also referred to as NDP-hexose pyrophosphorylase, catalyzes the conversion of GTP and αD-mannose 1-phosphate into diphosphate and CDP-ethanolamine in mannose metabolism. This enzyme is very similar to CDP-glucose pyrophosphorylase and may also be involved in the regulation of cell cycle progression. A cDNA coding for GTP:αD-mannose-1-phosphate guanyltransferase 1 (MPG1) was recently isolated from a cDNA library of a Trichoderma reesei strain (Kruszewska, J. S. et al. (1998) Curr. Genet. 33:445-50). The nucleotide sequence of the 1.6 kb cDNA revealed an ORF which encodes a protein of 364 amino acids. Sequence comparisons demonstrate 70% identity with the yeast Saccharomyces cerevisiae guanyltransferase gene 1 (G1) and 75% identity with the Schizosaccharomyces pombe homologue. Complex oligosaccharide side-chains result from the addition of N-acetyl-glucosamnine, N-acetylneuraminic acid (sialic acid), and galactose, as well as other sugar moieties, to the remaining core sugar moieties on the partially-processed glycoprotein. These modifications occur in the trans-cisterna and trans-Golgi network (TGN), and involve a number of enzymes including N-acetyl-glucosaminyltransferase I (GlcNAcTsI), sialyltransferases (STs), and galactosyltransferases (GalTs). Multiple isoforms of many of these enzymes produce specific α or β, 1,2-, 1,3-, 1,4-, or 1,6-disaccharide bonds between constituent sugar residues of the oligosaccharide side-chain. The stereochemistry and type of bonds in a carbohydrate side-chain contribute to the overall structure and function of the resulting glycoprotein (Lehininger, A. L. et al. (1993) Principles of Biochemistry , Worth Publishers, New York N.Y., pp. 931; Lewin, B. (1997) Genes VI , Oxford University Press, New York N.Y., pp. 1030-1033). Galactosyltransferases are a subset of glycosyltransferases that transfer galactose (Gal) to the terminal N-acetylglucosamine (GlcNAc) oligosaccharide chains that are part of glycoproteins or glycolipids that are free in solution (Kolbinger, F. et al. (1998) J. Biol. Chem. 273:433440; Amado, M. et al. (1999) Biochim. Biophys. Acta 1473:35-53). Galactosyltransferases are found in the Golgi, on the cell surface, and as soluble extracellular proteins, in addition to being present in the Golgi. β1,3-galactosyltransferases form Type I carbohydrate chains with Gal (β1-3)GlcNAc linkages. β1,3-galactosyltransferases appear to have a short cytosolic domain, a single transmembrane domain, and a catalytic domain with eight conserved regions (Kolbinger et al., supra; Hennet, T. et al. (1998) J. Biol. Chem. 273:58-65). In mouse, UDP-galactose: β-N-acetylglucosamine β1,3-galactosyltransferase-I region 1 is located at amino acid residues 78-83, region 2 is located at amino acid residues 93-102, region 3 is located at amino acid residues 116-119, region 4 is located at amino acid residues 147-158, region 5 is located at amino acid residues 172-183, region 6 is located at amino acid residues 203-206, region 7 is located at amino acid residues 236246, and region 8 is located at amino acid residues 264-275. A variant of a sequence found within mouse UDP-galactose:β-N-acetylglucosamine β1,3-galactosyltransferase-I region 8 is also found in bacterial galactosyltransferases, suggesting that this sequence defines a galactosyltransferase sequence motif (Hennet et al., supra). Recent work suggests that brainiac protein is a β1,3-galactosyltransferase. (Yuan, Y. et al. (1997) Cell 88:9-11; Hennet et al., supra). UDP-Gal:GlcNAc-1,4-galactosyltransferase (-1,4-GalT) catalyzes the formation of Type II carbohydrate chains with Gal (β1-4)GlcNAc linkages (Sato, T. et al. (1997) EMBO J. 16:1850-1857). A soluble form of the enzyme is formed by cleavage of the membrane-bound form. Amino acids conserved among β1,4-galactosyltransferases include two cysteines linked through a disulfide-bond and a putative UDP-galactose binding site in the catalytic domain (Yadav, S. P. and Brew, K. (1990) J. Biol. Chem. 265:14163-14169; Yadav, S. P. and Brew, K. (1991) J. Biol. Chem. 266:698-703; Shaper, N. L. et al. (1997) J. Biol. Chem. 272:31389-31399). β1,4-galactosyltransferases have several specialized roles in addition to synthesizing carbohydrate chains on glycoproteins or glycolipids. A β1,4-galactosyltransferase functions as part of a heterodimer with α-lactalbumin in mammary lactose production. A β1,4-galactosyltransferase on the surface of sperm functions as a receptor that specifically recognizes the egg. Cell surface β1,4-galactosyltransferases also function in cell adhesion, cell recognition, cell/basal lamina interaction, and normal and metastatic cell migration (Shur, B. (1993) Curr. Opin. Cell Biol. 5:854-863; Shaper, J. (1995) Adv. Exp. Med. Biol. 376:95-104; Masri, K. A. et al. (1988) Biochem. Biophys. Res. Commun. 157:657-663). Synthetases are another class of carbohydrate-modifying enzymes that have critical roles in proper cell funtioning. For example, production of sialylated glycoconjugates requires the synthesis of cytidine 5′-monophosphate N-acetylneuraminic acid (CMP-Neu5Ac or CMP-sialic acid), a reaction catalyzed by CMP-Neu5Ac synthetase (Munster, A. K. et al. (1998) Proc. Natl. Acad. Sci. USA 95:9140-9145). Sialic acids of cell surface glycoproteins and glycolipids contribute to proper structure and function in a variety of tissues. Sialyltransferases (STs) are a subset of glycosyltransferases that catalyze the transfer of sialic acid (from CMP-sialic acids) to the carbohydrate groups of glycoproteins and glycolipids. A variety of these Type II membrane proteins are present in the Golgi. Cloned members of this gene family share an N-terminal cytoplasmic tail region, a transmembrane region, and a large luminal region containing three sialyl motifs designated large (L), small (S), and very small (VS). The L-sialyl motif contributes to donor substrate binding and consists of eight invariant residues within a highly conserved stretch of 48-49 amino acids. The 23-amino acid S-sialyl motif contributes to the binding of both donor and acceptor substrates (Datta, A. et al. (1997) Indian J. Biochem. Biophys. 34:157-65). In the case of a representative sialytransferase ST3GalI (˜350 amino acids in length), the L, S, and VS, regions correspond to amino acids 138-182, 264-286, and 309-321, respectively. Other cloned members of the family include ST6GalNAcI and ST8SiaI. ST6GalNAcI is larger than the other known sialyltransferases, and is composed of more than 500 amino acid residues (Tsuji, S. et al. (1996) Glycobiology (letter) 6:v-vii; Geremnia, R. et al. (1997) Glycobiology (letter) 7:v-vii; Datta, A. et al. (1995) J. Biol. Chem. 270:1497-1500; Datta, A. et al. (1998) J. Biol. Chem. 273:9608-9618; Tsuji, S. et al. (1998) J. Biochem. 120:1-13). Sialyltransferases are not abundant in cellular extracts, but several have been cloned and expressed. At least one inhibitor has been synthesized (Horenstein, B. et al. (1996) J. Am. Chem. Soc. 118:10371-10379). A variety of other enzymes that are involved in sugar metabolism participate directly or indirectly in glycosylation, upstream of events that occur in the ER and Golgi. Many of these enzymes were originally identified in bacteria and plants and are less well characterized in humans; however, human homologues may exist that perform similar functions. For example, ADP-glucose pyrophosphorylases catalyze a very important step in the biosynthesis of α1,4-glucans (glycogen or starch) in bacteria and plants, namely the synthesis of the activated glucosyl donor, ADP-glucose, from glucose-1-phosphate and ATP. ADP-glucose pyrophosphorylases are tetrameric, allosterically-regulated enzymes. There are a number of conserved regions in the sequence of bacterial and plant ADP-glucose pyrophosphorylase subunits. Additionally, there are three regions which are considered signature patterns. The first two regions are N-terminal and have been proposed to be part of the allosteric and substrate-binding sites in the Escherichia coli enzyme. The third pattern corresponds to a conserved region in the central part of the enzymes. Carbohydrate Metabolism Disorders Carbohydrate metabolism is altered in several disorders. Diabetes mellitus is characterized by abnormally high blood glucose (hyperglycemia). Type I diabetes results from an autoimmune-related loss of pancreatic insulin-secreting cells. Type II diabetes results from insulin resistance and impaired insulin secretory response to glucose, and is associated with obesity. Hypoglycemia, or abnormally low blood glucose levels, has several causes including drug use, genetic deficiencies in carbohydrate metabolism enzymes, cancer, liver disease, and renal disease (Berkow, R. et al. (1992) The Merck Manual of Diagnosis and Therapy , Internet Edition, Section 8, Chapter 91, Diabetes Meritus, Hypoglycemia). Mutations in enzymes involved in protein glycosylation cause severe diseases. For example, alpha mannosidase mutations cause congenital dyserythropoietic anemia Type I and alpha B lysosomal mannosidosis (Isselbacher, K. J. et al. (1994) Harrison's Principles of Internal Medicine, McGraw-Hill, Inc. New York N.Y., pp. 2092-2093; and Online Mendelian Inheritance In Man, 224100). Glucosidases represent another class of carbohydrate-modifying enzymes that catalyze the release of glucose from carbohydrates through hydrolysis of the glycosidic link in various glucosides. The inherited disorder type I Gaucher disease, which is characterized by hematologic abnormalities, can be detected in a heterozygous or homozygous individual through an assay of leukocyte beta-glucosidase levels (Raghavan, S. S. et al. (1980) Am J. Hum. Genet. 32:158-173). Patients with all three types of Gaucher disease exhibit a deficiency of an enzyme called glucocerebrosidase that catalyzes the first step in the biodegradation of glucocerebroside. In the brain, glucocerebroside arises from the turnover of complex lipids during brain development and the formation of the myelin sheath of nerves. In other tissues, glucocerebroside arises mainly from the biodegradation of old red and white blood cells. Galectins play a number of roles in diseases and conditions associated with cell-cell and cell-matrix interactions. For example, certain galectins associate with sites of inflammation and bind to cell surface immunoglobulin E molecules. In addition, galectins may play an important role in cancer metastasis. Galectin overexpression is correlated with the metastatic potential of cancers in humans and mice. Moreover, anti-galectin antibodies inhibit processes associated with cell transformation, such as cell aggregation and anchorage-independent growth. Galectin-8, also known as prostate carcinoma tumor antigen 1 (PCTA-1), is a novel galectin implicated in cancer progression (Su, Z.-Z. et al. (1996) Proc. Natl. Acad. Sci. USA 93:7252-7257). Galectin-8 is expressed in invasive prostate carcinomas and early-stage prostate cancers, but not in normal prostate or benign prostatic hypertrophic tissue. Defects in carbohydrate metabolism are also associated with cancer. Reduced GAG and proteoglycan expression is associated with human lung carcinomas (Nackaerts, K. et al. (1997) Int. J. Cancer 74:335-345). The carbohydrate determinants sialyl-LewisA and sialyl-LewisX are frequently expressed on human cancer cells. These determinants, ligands for the cell adhesion molecule E-selectin, are involved in the adhesion of cancer cells to vascular endothelium and contribute to hematogenous metastasis of cancer (Kannagi, R. (1997) Glycoconj. J. 14:577-584). Alterations of the N-linked carbohydrate core structure of cell surface glycoproteins are linked to colon and pancreatic cancers (Schwarz, R. E. et al. (1996) Cancer Lett. 107:285-291). Reduced expression of the Sda blood group carbohydrate structure in cell surface glycolipids and glycoproteins is observed in gastrointestinal cancer (Dohi, T. et al. (1996) Int. J. Cancer 67:626-631). Changes in glycosaminoglycan levels are associated with several autoimmune diseases. Both increases and decreases in various GAGs occur in patients with autoimmune thyroid disease and autoimmune diabetes mellitus. Antibodies to GAGs were found in patients with systemic lupus erythematosus and autoimmune thyroid disease (Hansen, C. et al. (1996) Clin. Exp. Rheum. 14:S59-S67). The glycosaminoglycan hyaluronan (HA) induces tumor cell adhesion and migration, and its small fragments are angiogenic. Serum HA is diagnostic of liver disease and various inflammatory conditions, such as rheumatoid arthritis. Interstitial edema caused by accumulation of HA may cause dysfimction in various organs (Laurent, T. C. and Fraser, J. R. (1992) FASEB J. 6:2397-2404). Hyaluronidase is an enzyme that degrades HA to oligosaccharides by catalyzing the random hydrolysis of 1,4-linkages between N-acetyl-β-D-glucosamine and D-glucuronate residues. Hyaluronidases may function in cell adhesion, infection, angiogenesis, and signal transduction. Hyaluronidases are associated with reproduction, cancer, and inflammation. Hyaluronidase activity is significantly elevated in prostate tumor tissue compared to that in both normal prostate and benign prostate hyperplasia (Lokeshwar, V. B. et al. (1996) Cancer Res. 56:651-657). PH-20, a protein expressed in the mammalian testis and present on the plasma membrane of mouse and human sperm, has hyaluronidase activity (Lin, Y. et al. (1994) J. Cell Biol. 125:1157-63). PH-20 enables sperm to penetrate the mammalian egg's outer layer, which consists of about 3,000 cumulus cells embedded in an extracellular matrix rich in HA. Penetration of this layer is an essential step in the fertilization process. PH-20 is also expressed in some tumor cells. Non-testicular mammalian hyaluronidases include the HYAL1 hyaluronidase, expressed in human serum, and lysosomal hyaluronidase HYAL2, expressed in many cells (Lepperdinger, G. et al. (1998) J. Biol. Chem. 273:22466-22470). HYAL2 may have a role in producing distinct HA fragments that can induce angiogenesis and the expression of enzymes involved in signal transduction pathways, such as nitric oxide synthase. A lysosomal-type hyaluronidase may degrade HA in lung fibroblasts in a cytokine-regulated process (Sampson, P. M. et al. (1992) J. Clin. Invest. 90:1492-1503). The venom of numerous animals including various snakes, bees, hornets, stone fish, platypus, scorpions, and lizards contain hyaluronidase. Venom hyaluronidase is thought to act as an aid in the diffusion of toxins. A number of human diseases are linked to genetic or acquired deficiencies in protein glycosylation. Carbohydrate-deficient glycoprotein syndromes (CDGSs) include a host of alterations in glycosylation in a number of disorders and diseases. CDGSs are a group of hereditary multisystem disorders (Matthijs, G. et al. (1997) Nat. Genet. 16:88-92) causing severe psychomotor and mental retardation, as well as blood coagulation abnormalities seen in thrombosis, bleeding, or stroke-like episodes. The characteristic biochemical abnormality of CDGSs is the hypoglycosylation (N-linked) of glycoproteins (Freeze, H. and Aebi, M. (1999) Biochim. Biophys. Acta 1455:167-78). Depending on the type of CDGS, the carbohydrate side chains of glycoproteins are either truncated or completely missing from the protein core. Several different types of CDGS have been classified. The most common form, CDGS type 1A, is caused by phosphomannomutase (PMM1) deficiency (Matthijs, G. (1998) Am. J. Hum. Genet. 62:542-50). PMM1 functions upstream of MPG1 (see above) and catalyzes the conversion of D-mannose-6-phosphate to D-mannose-1-phosphate, which is required for the initial steps of protein glycosylation. A second form of CDGS, designated CDGS type 1B, has also been described (Niehues, R. et al. (1998) J. Clin. Invest. 101: 1414-1420). Psychomotor dysfunction and mental retardation are not present in this disease; instead, CDGS type 1B is a gastrointestinal disorder characterized by protein-losing enteropathy, severe hypoglycemia, vomiting, diarrhea, and congenital hepatic fibrosis. Nonetheless, some patients who are affected with CDGS type 1B suffer from thrombosis and life-threatening bleeding. A deficiency of phosphomannose isomerase (PMI) was identified as the most likely cause of this syndrome. Most symptoms can be controlled with dietary mannose supplements (Niehues et al., supra; Freeze and Aebi, supra). This form of CDGS is the first inherited disorder in human metabolism that shows a decrease in available mannose. Defects in glucosyltransferase function also play an important role in some human diseases. Galactosyltransferases may be involved in autoimmune/inflammatory disorders as many humans with autoimmune thyroid disorders have high levels of circulating antibodies directed against the enzymatic product of α1,3-galactosyltransferase (Etienne-Decerf, J. et al. (1987) Acta Endocrinol. 115:67-74). An aberrantly-cleaved, soluble β1,4-galactosyltransferase is secreted by a human ovarian cancer cell line (Uejima, T. et al. (1992) Cancer Res. 52:6158-6163). β1,4-GalT-deficient transgenic mice exhibited growth retardation in one experiment (Asano, M. et al. (1997) EMBO J. 16:1850-1857), while targeted inactivation of the mouse α1,4-GalT in another study was usually lethal (Furukawa, K. et al. (1999) Biochir. Biophys. Acta. 1473:54-66). In a third study, the constitutive overexpression of an α1,3-galactosyltransferase in transgenic mice led to the increased secretion of proteins in the urine, low body weight, partial damage to hair growth, and early death (Ikematsu, S. et al. (1999) Glycoconj. J. 1999 16:73-76). Galactosyltransferases have also been implicated in the regulation of cellular growth, development, and differentiation and may play an important role in embryogenesis as well as tumor development. Secreted galactosyltransferases, derived in some cases from proteolytic cleavage of membrane-bound forms, may trigger cell surface receptors by binding their bound carbohydrates or may modify carbohydrates on cell surface molecules in a regulated fashion. Extracellular carbohydrate moieties are developmentally regulated and are likely involved in the regulation of cell migration (Shur, B. et al. (1984) Mol. Cell. Biochem. 61:143-158; Paulson, J. and Colley, K. (1989) J. Biol. Chem. 264:17615-17618). The expression of β1,6-GlcNAc-bearing N-linked glycoproteins has been used as a marker of tumor progression in human breast and colon cancer, and astrocytes from human glioma specimens were found to contain increased levels of these type of glycoproteins compared to astrocytes from normal individuals (Yamamoto, H. et al. (2000) Cancer Res. 2000 60:134-142). These observations suggest that the dysfunction of another isoform of a glucosyltransferase, a β1,6-GlcNAcT, may also play a role in tumor formation or invasivity. Sialyltransferases have also been implicated in human disease. Elevated levels of 2,6-sialyltransferase (but not 2,3-sialyltransferase) are detected in human choriocarcinoma tissues, apparently the result of upregulation at the transcriptional level (Fukushima, K. (1998) Cancer Res. 58:4301-4306). Transient transfection of 2,6-sialyltransferase into human, tumorigenic, glioma cell line, reduces the invasivity of the cells (Yamamoto, H. (1997) 3. Neurochem. 68:2566-2576). Chronic alcohol (ethanol) consumption causes a decrease in Gal-β1,4-GlcNAc-α2,6-sialyltransferase (α2,6-ST) activity in the livers of rats who obtained at least one-third of their calories from alcohol for a period of one month or longer. Liver α2,6-ST activity returned to normal after a week of abstinence from alcohol consumption. Based on the results of nuclear run-on assays and mRNA stability assays, the reduction in α2,6-ST activity was the result of a 50% decrease in the half-life of α2,6-ST mRNA (Rao, M. (1999) Metabolism 48:797-803). A significant decrease in the plasma α2,6-sialyltransferase activity was also observed in a group of individuals suffering from clinical depression. This particular form of depression was attributed to a change in glucocorticoid receptor (GR) functionality. These findings suggested that α2,6-ST enzyme or activity levels may be a contributing factor in clinical depression or at least a useful biochemical marker of cortisol receptor dysfunction (Maguire, T. et al. (1997) Biological Psychiatry 41:1131-1136). Additional human diseases that involve defects in glycosylation, and the enzyme deficiencies that cause them, include (i) aspartylglycosaminuria, an aspartylglycosaminidase deficiency that causes mental retardation, (ii) GM 1 and GM 2 gangliosidosis, β-galactosidase and β-N-acetylhexosaminidase deficiencies, respectively, that cause glycolipid storage diseases, (iii) α-mannosidosis and β-mannosidosis, caused by a deficiency of α-mannosidase or β-mannosidase, respectively, that cause neurological dysfunction, and (iv) sialidosis, caused by a neuraminidase deficiency, characterized by hepatosplenomegaly as well as impaired neural development. Expression Profiling Array technology can provide a simple way to explore the expression of a single polymorphic gene or the expression profile of a large number of related or unrelated genes. When the expression of a single gene is examined, arrays are employed to detect the expression of a specific gene or its variants. When an expression profile is examined, arrays provide a platform for examining which genes are tissue specific, carrying out housekeeping functions, parts of a signaling cascade, or specifically related to a particular genetic predisposition, condition, disease, or disorder. The potential application of gene expression profiling is particularly relevant to improving diagnosis, prognosis, and treatment of disease. For example, both the levels and sequences expressed in tissues from subjects with colon cancer may be compared with the levels and sequences expressed in normal tissue. Colon cancer is causally related to both genes and the environment. Several molecular pathways have been linked to the development of colon cancer, and the expression of key genes in any of these pathways may be lost by inherited or acquired mutation or by hypermethylation. There is a particular need to identify genes for which changes in expression may provide an early indicator of colon cancer or a predisposition for the development of colon cancer. For example, it is well known that abnormal patterns of DNA methylation occur consistently in human tumors and include, simultaneously, widespread genomic hypomethylation and localized areas of increased methylation. In colon cancer in particular, it has been found that these changes occur early in tumor progression such as in premalignant polyps that precede colon cancer. Indeed, DNA methyltransferase, the enzyme that performs DNA methylation, is significantly increased in histologically normal mucosa from patients with colon cancer or the benign polyps that precede cancer, and this increase continues during the progression of colonic neoplasms (Wafik, S. et al. (1991) Proc. Nati. Acad. Sci. USA 88:3470-3474). Increased DNA methylation occurs in G+C rich areas of genomic DNA termed “CpG islands” that are important for maintenance of an “open” transcriptional conformation around genes, and hypermethylation of these regions results in a “closed” conformation that silences gene transcription. It has been suggested that the silencing or downregulation of differentiation genes by such abnormal methylation of CpG islands may prevent differentiation in immortalized cells (Antequera, P. et al. (1990) Cell 62:503-514). Familial Adenomatous Polyposis (FAP) is a rare autosomal dominant syndrome that precedes colon cancer and is caused by an inherited mutation in the adenomatous polyposis coli (APC) gene. FAP is characterized by the early development of multiple colorectal adenomas that progress to cancer at a mean age of 44 years. The APC gene is a part of the APC-β-catenin-Tcf (T-cell factor) pathway. Impairment of this pathway results in the loss of orderly replication, adhesion, and migration of colonic epithelial cells that results in the growth of polyps. A series of other genetic changes follow activation of the APC-β-catenin-Tcf pathway and accompanies the transition from normal colonic mucosa to metastatic carcinoma. These changes include mutation of the K-ras proto-oncogene, changes in methylation patterns, and mutation or loss of the tumor suppressor genes p53 and Smad4/ DPC4. While the inheritance of a mutated APC gene is a rare event, the loss or mutation of APC and the consequent effects on the APC-β-catenin-Tcf pathway is believed to be central to the majority of colon cancers in the general population. Hereditary nonpolyposis colorectal cancer (HNPCC) is another inherited autosomal dominant syndrome with a less well defined phenotype than FAP. HNPCC, which accounts for about 2% of colorectal cancer cases, is distinguished by the tendency to early onset of cancer and the development of other cancers, particularly those involving the endometrium, urinary tract, stomach and biliary system. HNPCC results from the mutation of one or more genes in the DNA mismatch-repair (MMR) pathway. Mutations in two human MMR genes, MSH2 and MLH1, are found in a large majority of HNPCC families identified to date. The DNA MMR pathway identifies and repairs errors that result from the activity of DNA polymerase during replication. Furthermore, loss of MMR activity contributes to cancer progression through accumulation of other gene mutations and deletions, such as loss of the BAX gene which controls apoptosis, and the TGF-β receptor II gene which controls cell growth. Because of the potential for irreparable damage to DNA in an individual with a DNA MMR defect, progression to carcinoma is more rapid than usual. Although ulcerative colitis is a minor contributor to colon cancer, affected individuals have about a 20-fold increase in risk for developing cancer. Progression is characterized by loss of the p53 gene which may occur early, appearing even in histologically normal tissue. The progression of the disease from ulcerative colitis to dysplasia/carcinoma without an intermediate polyp state suggests a high degree of mutagenic activity resulting from the exposure of proliferating cells in the colonic mucosa to the colonic contents. Almost all colon cancers arise from cells in which the estrogen receptor (ER) gene has been silenced. The silencing of ER gene transcription is age related and linked to hypermethylation of the ER gene (Issa, J. P. et al. (1994) Nat. Genet. 7:536-540). Introduction of an exogenous ER gene into cultured colon carcinoma cells results in marked growth suppression. The connection between loss of the ER protein in colonic epithelial cells and the consequent development of cancer has not been established. Clearly there are a number of genetic alterations associated with colon cancer and with the development and progression of the disease, particularly the downregulation or deletion of genes, that potentially provide early indicators of cancer development, and which may also be used to monitor disease progression or provide possible therapeutic targets. The specific genes affected in a given case of colon cancer depend on the molecular progression of the disease. Identification of additional genes associated with colon cancer and the precancerous state would provide more reliable diagnostic patterns associated with the development and progression of the disease. The discovery of new carbohydrate-associated proteins, and the polynucleotides encoding them, satisfies a need in the art by providing new compositions which are useful in the diagnosis, prevention, and treatment of carbohydrate metabolism, cell proliferative, autoimmune/inflammatory, reproductive, genetic, transport, and neurological disorders and cancer, and in the assessment of the effects of exogenous compounds on the expression of nucleic acid and amino acid sequences of carbohydrate-associated proteins. |
<SOH> SUMMARY OF THE INVENTION <EOH>The invention features purified polypeptides, carbohydrate-associated proteins, referred to collectively as “CHOP” and individually as “CHOP-1,” “CHOP-2,” “CHOP-3,” “CHOP4,” “CHOP-5,” “CHOP-6,” “CHOP-7,” “CHOP-8,” “CHOP-9,” and “CHOP-10.” In one aspect, the invention provides an isolated polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1-10, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 1-10, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 1-10, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-10. In one alternative, the invention provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 1-10. The invention further provides an isolated polynucleotide encoding a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1-10, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-10, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-10, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-10. In one alternative, the polynucleotide encodes a polypeptide selected from the group consisting of SEQ ID NO:1-10. In another alternative, the polynucleotide is selected from the group consisting of SEQ ID NO:11-20. Additionally, the invention provides a recombinant polynucleotide comprising a promoter sequence operably linked to a polynucleotide encoding a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-10, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-10, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-10, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-10. In one alternative, the invention provides a cell transformed with the recombinant polynucleotide. In another alternative, the invention provides a transgenic organism comprising the recombinant polynucleotide. The invention also provides a method for producing a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-10, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-10, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-10, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-10. The method comprises a) culturing a cell under conditions suitable for expression of the polypeptide, wherein said cell is transformed with a recombinant polynucleotide comprising a promoter sequence operably linked to a polynucleotide encoding the polypeptide, and b) recovering the polypeptide so expressed. Additionally, the invention provides an isolated antibody which specifically binds to a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-10, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-10, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ I) NO:1-10, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-10. The invention further provides an isolated polynucleotide selected from the group consisting of a) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:11-20, b) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:11-20, c) a polynucleotide complementary to the polynucleotide of a), d) a polynucleotide complementary to the polynucleotide of b), and e) an RNA equivalent of a)-d). In one alternative, the polynucleotide comprises at least 60 contiguous nucleotides. Additionally, the invention provides a method for detecting a target polynucleotide in a sample, said target polynucleotide having a sequence of a polynucleotide selected from the group consisting of a) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:11-20, b) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:11-20, c) a polynucleotide complementary to the polynucleotide of a), d) a polynucleotide complementary to the polynucleotide of b), and e) an RNA equivalent of a)-d). The method comprises a) hybridizing the sample with a probe comprising at least 20 contiguous nucleotides comprising a sequence complementary to said target polynucleotide in the sample, and which probe specifically hybridizes to said target polynucleotide, under conditions whereby a hybridization complex is formed between said probe and said target polynucleotide or fragments thereof, and b) detecting the presence or absence of said hybridization complex, and optionally, if present, the amount thereof. In one alternative, the probe comprises at least 60 contiguous nucleotides. The invention further provides a method for detecting a target polynucleotide in a sample, said target polynucleotide having a sequence of a polynucleotide selected from the group consisting of a) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:11-20, b) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:11-20, c) a polynucleotide complementary to the polynucleotide of a), d) a polynucleotide complementary to the polynucleotide of b), and e) an RNA equivalent of a)-d). The method comprises a) amplifying said target polynucleotide or fragment thereof using polymerase chain reaction amplification, and b) detecting the presence or absence of said amplified target polynucleotide or fragment thereof, and, optionally, if present, the amount thereof. The invention further provides a composition comprising an effective amount of a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-10, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-10, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-10, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-10, and a pharmaceutically acceptable excipient. In one embodiment, the composition comprises an amino acid sequence selected from the group consisting of SEQ ID NO:1-10. The invention additionally provides a method of treating a disease or condition associated with decreased expression of functional CHOP, comprising administering to a patient in need of such treatment the composition. The invention also provides a method for screening a compound for effectiveness as an agonist of a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-10, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-10, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-10, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-10. The method comprises a) exposing a sample comprising the polypeptide to a compound, and b) detecting agonist activity in the sample. In one alternative, the invention provides a composition comprising an agonist compound identified by the method and a pharmaceutically acceptable excipient. In another alternative, the invention provides a method of treating a disease or condition associated with decreased expression of functional CHOP, comprising administering to a patient in need of such treatment the composition. Additionally, the invention provides a method for screening a compound for effectiveness as an antagonist of a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-10, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-10, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-10, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-10. The method comprises a) exposing a sample comprising the polypeptide to a compound, and b) detecting antagonist activity in the sample. In one alternative, the invention provides a composition comprising an antagonist compound identified by the method and a pharmaceutically acceptable excipient. In another alternative, the invention provides a method of treating a disease or condition associated with overexpression of functional CHOP, comprising administering to a patient in need of such treatment the composition. The invention further provides a method of screening for a compound that specifically binds to a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-10, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-10, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-10, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-10. The method comprises a) combining the polypeptide with at least one test compound under suitable conditions, and b) detecting binding of the polypeptide to the test compound, thereby identifying a compound that specifically binds to the polypeptide. The invention further provides a method of screening for a compound that modulates the activity of a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-10, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-10, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-10, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-10. The method comprises a) combining the polypeptide with at least one test compound under conditions permissive for the activity of the polypeptide, b) assessing the activity of the polypeptide in the presence of the test compound, and c) comparing the activity of the polypeptide in the presence of the test compound with the activity of the polypeptide in the absence of the test compound, wherein a change in the activity of the polypeptide in the presence of the test compound is indicative of a compound that modulates the activity of the polypeptide. The invention further provides a method for screening a compound for effectiveness in altering expression of a target polynucleotide, wherein said target polynucleotide comprises a polynucleotide sequence selected from the group consisting of SEQ ID NO:11-20, the method comprising a) exposing a sample comprising the target polynucleotide to a compound, b) detecting altered expression of the target polynucleotide, and c) comparing the expression of the target polynucleotide in the presence of varying amounts of the compound and in the absence of the compound. The invention farther provides a method for assessing toxicity of a test compound, said method comprising a) treating a biological sample containing nucleic acids with the test compound; b) hybridizing the nucleic acids of the treated biological sample with a probe comprising at least 20 contiguous nucleotides of a polynucleotide selected from the group consisting of i) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:11-20, ii) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:11-20, iii) a polynucleotide having a sequence complementary to i), iv) a polynucleotide complementary to the polynucleotide of ii), and v) an RNA equivalent of i)-iv). Hybridization occurs under conditions whereby a specific hybridization complex is formed between said probe and a target polynucleotide in the biological sample, said target polynucleotide selected from the group consisting of i) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:11-20, ii) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:11-20, iii) a polynucleotide complementary to the polynucleotide of i), iv) a polynucleotide complementary to the polynucleotide of ii), and v) an RNA equivalent of i)-iv). Alternatively, the target polynucleotide comprises a fragment of a polynucleotide sequence selected from the group consisting of i)-v) above; c) quantifying the amount of hybridization complex; and d) comparing the amount of hybridization complex in the treated biological sample with the amount of hybridization complex in an untreated biological sample, wherein a difference in the amount of hybridization complex in the treated biological sample is indicative of toxicity of the test compound. |
Slave network slave processing method and apparatus information collection method |
A network system is constructed by connecting a safety PLC constituting a master unit and safety slaves 2 to each other through a safety network 3. The safety slaves each have a device information storage unit 25 for storing individual information and status information of the safety devices connected. The individual information is acquired and stored in advance, while the stored contents of the status information are updated based on the result of monitoring the status of the safety devices in operation. These processes are executed by a MPU 23. In response to a request from the safety PLC, the device information stored are transmitted, so that the safety PLC can collect and manage the device state as well as the normal state of the slave units. |
1. A slave unit connectable to a network, comprising: information collecting means for collecting the information on devices connected; device information storage means for storing the information on said devices collected by said information collecting means; and means for outputting the information stored in said device information storage means through the network. 2. A slave unit according to claim 1, characterized in that said device information include at least one of individual information for specifying the devices and status information indicating the status of the devices. 3. A network system constructed by connecting a controller and the slave unit according to claim 1 to each other through a network, characterized in that said device information output from said slave unit is transmitted to said controller. 4. A method of processing a slave unit connected to a network to execute: the collecting process for collecting the information on the devices connected to the particular slave unit; the process of storing in the device information storage means said device information obtained by executing said collecting process; and the process of outputting through said network the information stored in said device information storage means. 5. A device information collecting method for a network system constructed by connecting a controller and a slave unit through a network, characterized in that said slave unit executes: the collecting process for collecting the information on the devices connected to the particular slave unit, the process of storing in the device information storage means said device information obtained by executing said collecting process, and the process of outputting through said network the information stored in said device information storage means, and said controller acquires and stores said device information output from said slave unit. 6. A device information collecting method for a network system constructed by connecting a controller and a slave unit through a network, characterized in that said network system is connected with a monitoring device, said controller and said slave unit perform the control operation by transmitting and receiving the control information such as the I/O information, said slave unit executes the collecting process for collecting the information on the devices connected to the particular slave unit, the process of storing in the device information storage means said device information obtained by executing said collecting process, and the process of outputting through said network the information stored in said device information storage means, and said monitoring device acquires and stores said device information output from said slave unit. |
<SOH> BACKGROUND ART <EOH>In the programmable controller (hereinafter, referred to as “PLC”) used for the factory automation (hereinafter, referred to as “FA”), the on/off information is input from an input device such as a switch or a sensor, and the logic operation is executed according to a sequence program (also referred to as the user program) written in the ladder language or the like. In accordance with the operation result obtained, the signal of on/off information is output to an output device such as a relay, a valve or an actuator thereby to perform the control operation. The PLC is connected to the input device and the output device either directly or through a network. In the case where a network system connected by a network is constructed, the on/off information is transmitted or received through the particular network. In the process, the information is transmitted by the master-slave method in which the PLC normally acts a master unit and the device as a slave unit. Recently, on the other hand, a fail-safe system has been introduced in the control operation with PLC. Specifically, the network as well as the PLC and each device are configured of a built-in safety function. The safety function is defined as a function to confirm safety and output data. The safety system is such that in the case where an emergency stop switch is depressed or a sensor such as a light curtain detects the intrusion of a person (a part of the human body) and the network system faces a dangerous situation, the fail-safe function works and the system turns to the safety side, thereby stopping the operation. In other words, the safety function described above allows a signal to be output only in the case where safety is secured in storage and to start the operation of a machine. In the case where no safety is assured, therefore, the machine stops. The state of a given slave unit can be returned as a response by the slave unit that has received the request from PLC (master unit). As a result, PLC can acquire the status of the slave units connected to a network. In the conventional network system, though the informed on the slave units connected can be recognized, the information on the input device or the output device connected to a slave unit cannot be recognized from PLC (master unit). The slave unit can be informed of the fact that a malfunction or a fault has occurred. In case of a malfunction, therefore, it is necessary to resort to the site of installation and specify the cause of the malfunction. In the case where a given part is required to be changed, an order for the part is issued and, with the newly acquired part, the installation site is visited again to change the part. This maintenance is complicated, and makes it difficult to take the necessary action quickly. It is still more difficult to monitor the life of the input and output devices connected to a slave unit from PLC, and therefore, a malfunction or fault is often handled only after it has actually occurred. Even in the case where the installation site of a slave unit or a device connected with the slave unit is visited upon occurrence of a fault or the like, therefore, the status cannot be easily checked if the device is small or installed in the depth or behind other devices. As a result, the status of these input and output devices cannot be accurately grasped, and therefore the cause of a malfunction or fault may not be analyzed sufficiently. Further, in the case of a network system having security means, the safety devices, though high in reliability and redundancy, are often shorter in life than the devices making up the conventional normal network. Once a malfunction of these safety devices occurs, it leads to the stoppage of the whole system, and therefore has a great disadvantageous effect on the whole system. Consequently, the function of monitoring the devices connected to a slave unit is more crucial than in the conventional system. An object of this invention is to provide a slave unit and a network system as well as a slave unit processing method and a device information collecting method, in which the information on each device connected to a slave unit can be collected through a network. |
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>FIG. 1 is a diagram showing a network system according to an embodiment of this invention. FIG. 2 is a diagram showing a slave unit according to an embodiment of the invention. FIG. 3 is a diagram showing the data structure of a device information storage unit. FIG. 4 is a flowchart showing the functions of a MPU. FIG. 5 is a flowchart showing the functions of a MPU. FIG. 6 is a diagram showing an example of a system configuration for initial registration in a slave unit. FIG. 7 is a diagram showing an example of the internal data structure of a data base. FIG. 8 is a flowchart showing a specific processing function for the initial registration process. FIG. 9 is a diagram showing an example of the data structure stored in a device information storage unit 25 . FIG. 10 is a diagram showing a network system according to another embodiment of the invention. detailed-description description="Detailed Description" end="lead"? |
Optically active compounds clearing malformed proteins |
The invention is drawn to compositions and methods for inhibiting and treating malformed forms of proteins causing neurodegenerative disease, such as protease resistant prion proteins (PrPSc) and those associated with transmissible spongiform encephalopathies (TSEs). The compounds disclosed herein can be present as racemic mixtures or as compositions consisting essentially only of the optically active isomer in a higher percentage amount e.g. 60% or more, 70% or more, 80% or more, 90% or more or 100% of the optically active isomer and specifically the dextrorotary isomer of quinacrine. |
1. A method of treating disease resulting from malformed proteins from a mammal comprising: administering to said mammal a compound selected from the group consisting of quinacrine and chlorpromazine; wherein said compound is characterized by clearing malformed proteins and by an ability to cross a blood brain barrier of said mammal. 2. The method of claim 1, wherein said mammal is selected from the group consisting of a cow, pig, sheep and goat. 3. The method of claim 1, wherein the compound is quinacrine and the quinacrine consists of the dextrorotary optical isomer. 4. A method of treating a human having a malformed protein, comprising: administering to said human a compound comprising a pharmaceutically acceptable carrier, and a compound selected from the group consisting of quinacrine and chlorpromazine, wherein said administration is in a therapeutically effective amount. 5. The method of claim 4, wherein the administration is an oral administration. 6. The method of claim 4, wherein the malformed protein and its associated disease is selected from the group consisting of: Disease Insoluble Proteins Alzheimer's Disease APP, Aβ peptide, α1-antichymotrypsin, tan, non-Aβ component Prion diseases, Creutzfeld Jakob disease, scrapie and bovine spongeform Encephalopathy PrPSc ALS SOD and neurofilament Pick's disease Pick body Parkinson's disease Lewy body Diabetes Type 1 Amylin Multiple myeloma— IgGL-chain plasma cell dyscrasias Familial amyloidotic Transthyretin polyneuropathy Medullary carcinoma of Procalcitonin thyroid Chronic renal failure β2—microglobulin Congestive heart failure Atrial natriuretic factor Senile cardiac and Transthyretin systemic amyloidosis Chronic inflammation Serum amyloid A Atherosclerosis ApoA1 Familial amyloidosis Gelsolin. 7. The method of claim 4, wherein the disease and its associated malformed prion is selected from the group consisting of Alzheimer's Disease APP, Aβ peptide, α1- antichymotrypsin, tan, non- Aβ component Prion diseases, Creutzfeld Jakob disease, scrapie and bovine spongeform Encephalopathy PrPSc Parkinson's disease Lewy body Diabetes Type 1 Amylin Familial amyloidotic Transthyretin. polyneuropathy 8. The method according to claim 5, wherein the oral administration step is in an amount of about 100 mg to 10,000 mg/day/75 kg of body weight. 9. The method of claim 4, wherein the administration step comprises administration by injection. 10. The method of claim 4, wherein the administration step comprises a technique selected from the group consisting of transdermal administration, subcutaneous injection, intravenous injection, intraperitoneal injection, intramuscular injection, intrasternal injection, intrathecal injection, intranasal, and infusion techniques. 11. The method as claimed in claim 4, wherein the compound is quinacrine and the quinacrine is 100% dextrorotary quinacrine. 12. A method of treating a disease resulting from malformed proteins comprising: administering to said mammal a pharmacologically effective amount of a combination of quinacrine and chlorpromazine. 13. The method as claimed in claim 12, wherein the quinacrine consists of dextrorotary quinacrine. 14. The method of claim 12, wherein the mammal is suffering from Creutzfeldt-Jakob disease. 15. The method of claim 12, wherein the mammal is suffering from a disease selected from the group consisting of scrapie, transmissible spongioform encephalopathy (TSE), Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, autism, schizophrenia, bipolar disorders, fronto-temporal dementia, Pick's disease, progressive supranuclear palsy, diffuse Lewy body disease, systemic lupus erythematosus, rheumatoid arthritis, Huntington's disease, spinocerebellar ataxias, diabetes mellitus, Types I and II, Crohn's disease, ulcerative colitis, systemic amyloidosis, primary amyloidosis, polyneuropathy and AIDS. 16. A composition for treating livestock with malformed proteins comprising: livestock feed; and quinacrine and chlorpromazine. 17. A composition for treating livestock with malformed proteins comprising: livestock feed; and a compound selected from the group consisting of quinacrine and chlorpromazine. 18. A method for clearing malformed proteins from livestock, said method comprising: a. administering a pharmaceutically effective amount of the composition of claim 16; and b. continuously providing said livestock feed to livestock. 19. A method for clearing malformed proteins from livestock, said method comprising: a. administering a pharmaceutically effective amount of the composition of claim 17; and b. continuously providing said livestock feed to livestock. 20. The composition of claim 16, wherein the quinacrine is 60% dextrorotary and 40% laevorotary. 21. A composition, comprising: livestock feed; and quinacrine. 22. The composition of claim 21, wherein the quinacrine is 60% or more dextrorotary quinacrine with the remainder being laevorotary quinacrine. 23. The composition of claim 16, wherein the quinacrine is 70% or more dextrorotary quinacrine with the remainder being laevorotary quinacrine. 24. The composition of claim 16, wherein the quinacrine is 80% or more dextrorotary quinacrine with the remainder being laevorotary quinacrine. 25. The composition of claim 16, wherein the quinacrine is 90% or more dextrorotary quinacrine with the remainder being laevorotary quinacrine. 26. The composition of claim 16, wherein the quinacrine is 100% dextrorotary quinacrine. 27. A composition for treating disease resulting from malformed proteins from a mammal comprising: a compound selected from the group consisting of quinacrine and chlorpromazine; wherein said compound is characterized by clearing malformed proteins and by an ability to cross a blood brain barrier of said mammal. 28. The composition of claim 27, wherein the compound is quinacrine or a compound where the quinacrine consists of the dextrorotary optical isomer. 29. A composition for treating a human having a malformed protein, comprising: a compound comprising a pharmaceutically acceptable carrier, and a compound selected from the group consisting of quinacrine and chlorpromazine, wherein the compound is present in the composition is in a therapeutically effective amount. 30. A method of treating a disease resulting from malformed proteins, comprising: administering to a patient a compound having the following general structural formula I: wherein each A, B and C are each independently a cyclic moiety and is optionally, substituted with X1, X2 and X3 which are each independently hydrocarbyl. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Diseases associated with pathogenic forms of proteins, e.g., PrP Sc , have received increased public attention since the outbreak of bovine spongiform encephalopathy (BSE) in Great Britain in 1984 and the subsequent discovery of its transmissibility to humans causing a variant of Creutzfeldt-Jakob disease (CJD). Many other diseases are known to be associated with pathogenic proteins, such as systemic lupus erythematosus, arthritis, multiple sclerosis, etc. See, Wojtowicz, S., Med Hypotheses 40(1):48-54 (1993) and Weller, R. O., J. Neuropathol. Exp. Neurol. 57(10):885-894 (1998). As with many other neurodegenerative diseases, no cure is known at this time. As such, a need exists for the discovery of therapeutic compounds and methods of their use so that these neurodegenerative diseases can be treated. See, Prusiner, S. B., N Engl. J. Med. 344(20):1548-1551 (May 17, 2001). PrP Sc is an infectious protein that causes central nervous system spongiform encephalopathies in humans and animals. It has been shown that a scrapie isoform of the prion protein (PrP Sc ) is necessary for both the transmission and pathogenesis of the transmissible neurodegenerative diseases of animals and humans. See, Prusiner, S. B., Science 252:1515-1522 (1991). The most common prion diseases of animals are scrapie of sheep and goats and bovine spongiform encephalopathy (BSE) of cattle. See, Wilesmith and Wells, Microbiol. Immunol. 172:21-38 (1991). Examples of human neurodegenerative prion-related diseases include: (1) kuru, (2) Creutzfeldt-Jakob Disease (CJD), (3) Gerstnann-Strassler-Scheinker Disease (GSS), and (4) fatal familial insomnia (FFI). These diseases are characterized by the formation and accumulation of an abnormal protease resistant isoform (PrP Sc ) of a normal protease-sensitive endogenous prion protein (PrP C ). The protease-resistant isoform accumulates in the CNS and other tissues. As such, it would be desirable to identify compounds and methods for treating neurodegenerative diseases wherein the formation or accumulation of pathogenic forms of proteins, such as, protease resistant PrP Sc proteins, can be circumvented by suitable therapeutic intervention with pharmaceuticals. It would also be desirable to identify methods for screening test compounds for the ability to inhibit formation or accumulation of these pathogenic proteins. Based on the foregoing, it is clear that a need exists for identification of compounds that may treat neurodegenerative diseases, and methods of their use. The present invention fulfills these and other needs in the art. |
<SOH> SUMMARY OF THE INVENTION <EOH>The invention comprises a method of clearing pathogenic forms of proteins from cells, by contacting the cells with a therapeutically effective amount of a compound having a multicyclic scaffold and a side chain, wherein the scaffold has at least two, preferably, three cyclic moieties. With regard to all structures shown here and compounds named all stereoisomers are included when such exist including optical isomers, racemic mixtures and pure enantramers. The method of the present invention comprises administering a compound having can have the following general structural formula I: wherein “A,” “B” and “C” are each independently a cyclic moiety comprised of atoms selected from the group consisting of carbon, nitrogen and sulfur, any of which cyclic moieties may be substituted at any position, and each of X 1 , X 2 and X 3 is independently a hydrocarbyl as defined here and is preferably a nitrogen containing non-cyclic hydrocarbyl moiety covalently bound to B. Preferably A, B and C are six-membered rings and A and C are comprised only of carbon and hydrogen and B preferably comprises carbons and a nitrogen or sulfur atom. The compound which is administered can also have the following general structural formula II: wherein “A” and “B” are each independently a cyclic moiety comprised of atoms selected from the group consisting of carbon, nitrogen and sulfur, any of which cyclic moieties may be substituted at any position and “X” is a hydrocarbyl as defined here and is preferably a nitrogen containing non-cyclic hydrocarbyl moiety covalently bound to A. Preferably A and B are five-membered rings comprised of carbon and hydrogen and B preferably comprises a nitrogen and/or sulfur. Preferably, the cyclic moieties of the compound are fused rings, more preferred is that the moieties be six-membered rings. The rings can be comprised of unsaturated carbons and it is preferred that moiety B is heterocyclic with the heteroatoms comprising nitrogen, sulfur and oxygen most preferably a single nitrogen or sulfur atom. Examples of the cyclic moieties of the compound comprise the following structures: It is preferred that a side chain, X, is bound to B via a carbon or a nitrogen atom of B and X is alkyl (comprising a hetero atom which is N, S or O) comprising 1 to 8 carbon atoms having the general formula C n H 2n+2 preferably having a hydrocarbon chain of at least about C 3 H 8 more preferably C 4 H 10 . More preferably, X further comprises an amine substituent, such as, for example, a dimethylamino group. It is preferred that the amine substituent further comprises at least two substituents, preferably, two methyl groups. As such, several examples of amine substituents of X comprise a methylamine, an ethylamine, 1-propylamine and 1-butylamine. The amine substituent may be bifurcated or unbifurcated, as in for example, a methyl bifurcation. Preferred structural formulae of side chain X comprise: Compounds administered in the method of the present invention comprise phenothiazine and acridine derivatives, e.g., phenothiazine, promazine, chlorpromazine, acepromazine, quinacrine and pamaquine. The most preferred compounds are quinacrine and chlorpromazine. An unexpected finding is that compounds with a multicyclic scaffold and a side chain, especially a tricyclic scaffold with a side chain substituted middle ring, are effective inhibitors of the formation of protease resistant prions, PrP Sc , and as such, these compounds can be used to treat pathogenic protein diseases. The invention further comprises a method of treating a disease characterized by pathogenic protein formation, by administering a pharmaceutically effective amount of a combination of quinacrine and chlorpromazine to a subject. The use of these compounds in combination has a synergistic effect, and is not simply additive. This finding was unexpected. The invention also includes a pharmaceutical composition comprising a compound of the above described general formulae (I and II), or a variant or mimetic thereof, and a pharmaceutically acceptable carrier or diluent. Compounds of the present invention can be administered in a pharmacological composition with pharmaceutically acceptable carriers, fillers or excipients. Such a composition can also include a lipophilic solvent or carrier, such as DMZ, an organic solvent, phosphatidyl choline or cholesterol. Treatment is by administering a therapeutically effective amount of the pharmaceutical composition, either singly or in combination, to a mammal that has been exposed to and/or is in danger of being exposed to the transmissible agent, such as PrP Sc , or which is exhibiting signs, symptoms or laboratory evidence of a TSE. If the mammal is merely suspected of having been exposed to a TSE, the treatment is a prophylactic method of preventing the progression of the disease. In a situation where the mammal is already believed to be exhibiting signs or symptoms of the disease, the treatment is also a method of improving the neurological or other biological condition of the animal. The invention also includes in vitro methods for the inhibition of the conversion of prPc to PrP Sc , and a method of screening for such compounds and including variants, analogs and mimetics of the inhibitory compounds that inhibit the conversion reaction. The screening method includes contacting PrP C with PrP Sc or analogs, derivatives or mimetics thereof in the presence of a test compound, and determining whether the test compound, analog, derivative or mimetic inhibits conversion of PrP C to PrP Sc . Specific preferred embodiments of the present invention will become more evident from the following detailed description. An aspect of the present invention includes methods of administering to a mammal, one or more compounds from a class of compounds, having a general structural formula I or II or compounds from both of these classes. In another aspect of the invention, a mammal in need of this treatment is identified, and a pharmacologically effective amount of a compound is administered to the mammal in an amount sufficient to interfere with PrP Sc formation or accumulation in cells. The present invention includes still another aspect comprising treating a mammal, such as a human, having a condition associated with PrP Sc . In this aspect, such a mammal is identified and treated with a compound, either singly or in combination, of the present invention in a manner, such as that described above in the foregoing aspects of the invention. A method of the invention comprises administering a compound to a cell population, wherein said cell population is exposed to an amount of stimulus capable of inducing the formation of protease resistant prion proteins in the cell population, and determining whether the presence of said compound inhibits PrP Sc formation or accumulation and, typically, also produces a detectable reduction in the amount and/or rate of PrP Sc in the cell population; if said agent produces PrP Sc inhibition in cells and/or inhibits conversion of PrP C to PrP Sc , the compound is thereby identified as a therapeutic compound. Preferably, the method is used to demonstrate that the compound inhibits PrP Sc formation or accumulation and also inhibits neuronal degenerative diseases (e.g., transmissible spongiforn encephalopathies). In a variation of the method, the agent is initially selected from a bank (or library) of compounds on the basis of the agent's chemical structure for inhibiting PrP Sc in vitro; an agent which is thus initially selected is administered to a cell population, wherein said cell population is exposed to an amount of stimulus capable of inducing protease resistant prion proteins in the cell population, and the capacity of said compound to produce a detectable reduction in the amount and/or rate of PrP Sc in the cell population is determined, with compounds capable of reducing PrP Sc being thereby identified as active agents. In this variation, the capacity of the agent to selectively or specifically inhibit PrP Sc in a cultured cell population can optionally be determined. In a further aspect, the invention also provides a method for identifying an active agent which significantly inhibits neuronal degeneration in a transgenic animal model; such active agents can be sold commercially to control the disease in animals for any purpose desired by an end-user of such animals, and can serve as candidate pharmaceuticals for therapy of neurodegenerative disease, among other uses. The method comprises initially selecting an PrP Sc -inhibiting agent from a bank (or library) of compounds on the basis of: (1) the agent's capacity, selectivity, or specificity for inhibiting PrP Sc in vitro, such as by its ability to inhibit PrP Sc formation or accumulation in an in vitro assay and/or (2) the capacity of the agent to selectively inhibit PrP Sc in a cultured cell population; and administering the selected agent to a transgenic animal capable of developing detectable pathology characteristic of a PrP Sc related neurodegenerative disease, and determining whether administration of the selected agent inhibits or retards development of said detectable pathology as compared to a substantially identical identifying control transgenic animal which lacks the agent; an agent which retards or inhibits development of neuropathology is thereby identified as an active agent. In a further aspect, the invention provides a method for reducing or retarding neurodegeneration in a cell population comprising neurons which have been exposed to an amount of a stimulus sufficient to produce partially protease resistant proteins resulting in neurodegeneration; said method comprising administering an efficacious dose of a PrP Sc inhibitor predetermined to retard or inhibit neuronal degeneration. In one embodiment, the cell population may reside in the central nervous system of a mammal and the PrP Sc inhibitor is administered in vivo. The invention also provides the use of a PrP Sc inhibitor to treat neurodegenerative disease pathology in a mammal. In a still further aspect, the invention provides a method for retarding or inhibiting neurodegeneration in a cell population comprising neurons exposed to an amount of stimulus sufficient to produce protease resistant protein related neurodegeneration; said method comprising administering to the cell population an efficacious dose of a compound capable of inhibiting expression of PrP Sc . In one embodiment, the cell population may reside in the central nervous system of a mammal and the PrP Sc inhibitor is administered in vivo. Also provided by the invention is a method for inhibition of neuronal cell death in a cell population. The method comprises delivering an effective dosage of a PrP Sc inhibitor to a cell population that is exposed to a protease resistant prion protein stimulus. Another aspect of the invention is that a compound of the invention which is characterized by its ability to inhibit prion formation and allow for clearing of prions can be combined with a pharmaceutical product; in a particular a product derived from a human source such as organs, tissue, blood, and related blood derived products. In another aspect of the invention is a method of treating tissue, organs, blood and blood derived products by combining such with a compound of the invention. In another aspect of the invention is the combination of livestock feed with a compound of the invention, which is particularly useful in connection with livestock feed which includes meat, bone meal or any material derived from an animal that might be infected with prions. In another aspect of the invention is a method of treating farm animals by administering to farm animals a compound of the invention which compound of the invention may be combined with livestock feed thereby preventing prion infections and/or treating prion diseases such as “mad cow” disease in animals consuming the treated livestock feed. These and other aspects of the invention will be understood by those skilled in the art upon reading this disclosure. |
Engine management |
An engine management system for an internal combustion engine, which has at least one cylinder pressure sensor and at least one engine actuator, includes a data processor arranged to receive and process cylinder pressure data from the cylinder pressure sensor and the actuator controller arranged to control the actuator to optimize engine performance based on the processed data, in which the cylinder pressure data is obtained during a performance optimized engine cycle or cycles. The processor processes the data to construct a cylinder pressure variation function for the engine cycle or cycles and derive control data therefrom for the actuator controller. |
1. An engine management system for an internal combustion engine having at least one cylinder pressure sensor and at least one engine actuator, the system comprising a data processor arranged to receive and process cylinder pressure data from the cylinder pressure sensor and an actuator controller arranged to control the actuator to optimize engine performance based on the processed data, in which the cylinder pressure data is obtained during a performance optimized engine cycle or cycles and the processor processes the data to construct a cylinder pressure variation function for the engine cycle or cycles and derive control data therefrom for the actuator controller. 2. A system as claimed in claim 1 in which the processor processes cylinder pressure data for each cylinder in the engine. 3. A system as claimed in claim 1 in which the processor processes cylinder pressure data for each engine cycle. 4. A system as claimed in claim 3 in which the actuator controller controls actuation for an engine cycle based on the processed cylinder pressure data from the engine cycle immediately preceding. 5. A system as claimed in claim 1 in which the processor further processes crank angle data. 6. A system as claimed in claim 5 for a multi-cylinder engine in which data is obtained for each cylinder at a respective crank angle position in the cycle or cycles of each cylinder. 7. A system as claimed in claim 1 further including an in cylinder pressure sensor for providing cylinder pressure data to the data processor. 8. A system as claimed in claim 1 further comprising an engine actuator comprising at least one of: a spark plug; a fuel injector. 9. A system as claimed in claim 1 in which the processor derives an offset pressure value from the cylinder pressure data and preferably filtered pressure sensor data. 10. A system as claimed in claim 9 in which the offset pressure value is derived from the polytropic gas law PVn=K using cylinder pressure data and corresponding volume data to obtain n and K. 11. A system as claimed in claim 1 in which the processor derives a pressure ratio function from the constructed pressure variation function comprising a ratio between combustion and motoring pressure. 12. A system as claimed in claim 11 in which the processor derives the motoring pressure for each engine cycle or cycles from the pressure sensor data in a pre-combustion phase of the engine cycle(s). 13. A system as claimed in claim 12 in which the motoring pressure derivation is based on filtered pressure sensor data. 14. A system as claimed in claim 11 in which the engine actuator comprises a spark plug and the actuator controller controls the timing of firing the spark plug based on closed loop control of a pressure ratio control variable. 15. A system as claimed in claim 14 in which the pressure ratio control variable is a fixed proportion of the fuel Mass Fraction Burnt (MFB), for example 50% MFB. 16. A system as claimed in claim 11 for a multi-cylinder engine in which the pressure ratio is derived for each engine cylinder and the actuator controller controls an actuator for each engine cylinder. 17. A system as claimed in claim 11 in which the processor processes the pressure sensor data to obtain the indicated mean effective pressure (IMEP). 18. A system as claimed in claim 17 for a multi-cylinder engine in which the processor obtains the IMEP for each cylinder, identifies as the weakest cylinder the cylinder having the lowest IMEP and the actuator control controls each cylinder to balance the IMEP to that of the weakest cylinder. 19. A system as claimed in claim 18 in which the cylinders are controlled by adjusting the spark timing for each cylinder. 20. A system as claimed in claim 19 in which the cylinder balancing is based on closed loop control. 21. A system as claimed in claim 17 in which the processor obtains the gross IMEP and detects misfire if the gross IMEP falls below a threshold value. 22. A system as claimed in claim 21 in which, on misfire detection, the actuator controller resets to an actuator controller state prior to misfire detection. 23. A system as claimed in claim 18 in which the processor further derives a function of the variance of IMEP between engine cycles and compares the function against a threshold value to determine whether a steady state condition exists. 24. A system as claimed in claim 23 in which the processor switches from IMEP balancing if non-steady state is determined. 25. A system as claimed in claim 17 in which, in a start-up mode, the processor derives a function of the variability of IMEP between engine cycles and compares the function against a threshold value, and the actuator controller controls the actuator based on this comparison. 26. A system as claimed in claim 25 in which the actuator is a spark plug and the actuator controller retards the spark plug timing based on the comparison. 27. A system as claimed in claim 25 which a further actuator comprises a fuel injector and the actuator controller controls fuel injection based on the function of the IMEP variability. 28. A system as claimed in claim 25 in which the actuator control is performed under closed loop control to a target IMEP variability. 29. A system as claimed in claim 25 in which the start-up mode is entered based on engine coolant temperature sensor data. 30. A system as claimed in claim 23 in which the IMEP variance or variability is derived iteratively as a function of a preceding variance or variability value and a current IMEP value coupled with a forgetting factor. 31. A system as claimed in claim 30 in which the IMEP variance or variability iteration includes an initialization sequence in which the forgetting factor is successively increased for each iteration to a target value. 32. A system as claimed in claim 21 in which the threshold value is based on an average of the IMEPs obtained for all cylinders, other than the current cylinder for which misfire is being detected, during the same cycle. 33. A system as claimed in claim 1 in which the processor further processes pressure sensor data to detect cylinder knock. 34. A system as claimed in claim 33 in which the actuator comprises a spark plug, and the processor and actuator controller, upon knock detection, retard the spark plug timing and incrementally increase the timing for subsequent engine cycles until a spark timing threshold is reached. 35. A system as claimed in claim 34 in which the actuator controller resets an actuator controller state prior to knock detection once the spark timing threshold is reached. 36. An engine management system for an internal combustion engine having a plurality of cylinders each having at least one cylinder pressure sensor and at least one engine actuator, the system comprising a data processor arranged to process cylinder pressure data from each pressure sensor in which the processor constructs a cylinder pressure variation function for each cylinder from the cylinder pressure data, derives a measure of the performance of each cylinder from the respected pressure variation function and balances the cylinder performances. 37. A system as claimed in claim 36 further comprising an actuator controller arranged to control each cylinder actuator to balance cylinder performance. 38. A system as claimed in claim 37 in which the actuator controller controls the cylinder spark timing. 39. An engine management system for an internal combustion engine having at least one cylinder pressure sensor and at least one engine actuator, the system comprising a data processor arranged to process cylinder pressure data from the pressure sensor and an actuator controller arranged to control the actuator based on the processed data in which the processor processes the cylinder pressure data to construct a cylinder pressure variation function and derive a pressure ratio control variable therefrom for the actuator controller. 40. An internal combustion engine including at least one cylinder pressure sensor, at least one engine actuator and an engine management system as claimed in claim 1. 41. A method of managing an internal combustion engine based on cylinder pressure data from a cylinder pressure sensor comprising the steps of obtaining the cylinder pressure data across one or more performance optimized engine cycles, processing the cylinder pressure data to construct a pressure variation function for the engine cycle or cycles and controlling an engine actuator to optimize engine performance based on the constructed pressure variation function. 42. An engine management system for an internal combustion engine having at least one cylinder pressure sensor, the system comprising a sensor controller arranged to retrieve a plurality of cylinder pressure readings per cylinder cycle and a processor arranged to process the readings to construct a cylinder pressure variation function in which sufficient readings are retrieved per cycle to allow noise filtering in the pressure variation function. 43. An engine management system as claimed in claim 42 further comprising a processor for processing the constructed cylinder pressure variation function to identify at least one of engine faults, inlet manifold leaks, inlet or exhaust valve leaks, piston ring failure or leakage and head gasket leakage. 44. A diagnostic system for an internal combustion engine having at least one cylinder pressure sensor and a processor arranged to process sensed cylinder pressures over a cylinder cycle and construct a cylinder pressure variation function, the system further comprising a processor arranged to detect engine misoperation from the constructed function. 45. A system as claimed in claim 44 in which engine misoperation includes at least one of engine faults, inlet manifold leaks, inlet or exhaust valve leaks, piston ring failure or leakage and head gasket leakage. 46. A system as claimed in claim 44 in which the misoperation processor identifies engine misoperation by comparison of the constructed function with a modelled function. 47. A system as claimed in claim 44 in which the processor identifies engine misoperation using pattern recognition. 48. A system as claimed in claim 44 in which the engine has a plurality of cylinders and respective cylinder pressure sensors, and the processor cross-correlates constructed functions for each cylinder to identify faults common to multiple cylinders. |
Broadband communications |
Disclosed is a provisioning tool and a method for implementing an operating a communications network, particularly a broadband communications network which is arranged to provision a service for a user based on information available via another user connection; this facilitates provision. In a preferred embodiment, a user device address is obtained from a user IP address. Provisioning and other network tools with additional or alternative advantageous features are disclosed and the provisioning tools disclosed may communicate with a variety of other tools including planning and inventory applications and agents associated with equipment, all of which are also independently provided, enabling provision of a variety of novel services and features dealing with a spectrum of problems arising in a communications environment, particularly a broadband environment. |
1-225. (Canceled) 226. An agent for a network component of a broadband network, the agent comprising means for passing equipment status or identification information concerning the network component to a remote network component. 227. An agent according to claim 226 further comprising means for receiving a configuration instruction. 228. An agent according to claim 226 wherein at least a portion of the operation of the agent is configurable by means of a script. 229. An agent according to claim 226 wherein the remote network component is selected from the group comprising: a provisioning tool incorporated into a broadband network; a planning tool incorporated into a broadband network; a network management tool. 230. An agent according to claim 226 wherein at least a portion of the operation of the agent is configurable to simulate user activity at the network component. 231. An agent according to claim 230 wherein the user activity comprises at least one of: connecting to a broadband network; verifying the identity of the user or the network component over the broadband network; accessing a service via the broadband network preferably using configured and/or preset parameters; amending at least one preset parameter and accessing a service via the broadband network usling the at least one amended parameter. 232. An agent according to claim 230 further comprising means for sending a report on the simulated user activity to the remote network component. 233. An agent according to claim 226 wherein the network component is a Set Top Box or a Cable Modem. 234. An agent according to claim 226 further comprising means for accessing a communication service and means for signaling an alarm to a remote network component in the event of detection of a fault condition. 235. A method of operating a network component of a broadband network, comprising passing equipment status or identification information concerning the network component to a remote network component. 236. A method according to claim 235 further comprising receiving a configuration instruction. 237. A method according to claim 235 wherein at least a portion of the operation of the network component is configurable by means of a script. 238. A method according to any of claims 235 to 237 wherein the remote network component is selected from the group comprising: a provisioning tool incorporated into a broadband network; a planning tool incorporated into a broadband network; a network management tool. 239. A method according to claim 235 further comprising configuring at least a portion of the operation of the network component to simulate user activity at the network component. 240. A method according to claim 239 wherein the user activity comprises at least one of: connecting to a broadband network; verifying the identity of the user or the network component over the broadband network; accessing a service via the broadband network using configured and/or preset parameters; amending at least one preset parameter and accessing a service via the broadband network using the at least one amended parameter. 241. A method according to claim 239 further comprising sending a report on the simulated user activity to the remote network component. 242. A method according to claim 235 wherein the network component is a Set Top Box or a Cable Modem. 243. A method according to claim 235 further comprising accessing a communication service and signaling an alarm to a remote network component in the event of detection of a fault condition. 244. A node of a broadband communications network, for receiving one or more communications services from service providers and transmitting the one or more services towards end user equipment, which node comprises an agent or other programmable end user simulation equipment for launching a service request to the network. 245. A node according to claim 244 which further comprises a first signal path for delivering control signals to the simulation equipment and a second path for transmitting a launched service request from the simulation equipment to the network, said first and second paths being different. |
<SOH> BRIEF DESCRIPTION OF DRAWINGS <EOH>The provisioning of services in a communications network and the management of such a network will now be described further, by way of example only, with reference to the accompanying drawings in which: FIG. 1 is a schematic diagram of a network environment for provisioning apparatus in accordance with one example of the system and methods herein described; FIG. 2 is a schematic diagram of message flow in provisioning apparatus carrying out provisioning according to one example of the systems and methods herein described; FIG. 3 is a schematic diagram of an architecture for a service management system using the provisioning apparatus of FIGS. 1 arid 2 ; FIG. 4 is a schematic diagram of message flow in provisioning apparatus carrying out provisioning according to a further example of the systems and methods herein described; FIG. 5 is a schematic diagram of an initial set-up of a network environment for provisioning apparatus in accordance with a further example of the system and methods herein described; FIG. 6 is a schematic diagram of a network environment for provisioning apparatus in accordance with the example illustrated in FIG. 5 after a new customer edge router has been added to the network according to an example process; FIG. 7 is a schematic diagram of a network environment for provisioning apparatus in accordance with the example illustrated in FIG. 5 or 6 after a new customer edge router has been added to the network according to a further example process; FIG. 8 is a schematic diagram of a network environment for provisioning apparatus in accordance with the example illustrated in FIG. 5, 6 or 7 after a new customer edge router has been added to the network according to a further example process; FIG. 9 is a schematic diagram of an initial topology of the network environment for provisioning apparatus, before modification has taken place, according to an example of the system and methods herein described; FIG. 10 is a schematic diagram of a final topology of the network environment for provisioning apparatus, after modification has taken place, according to an example of the system and methods herein described; FIG. 11 is a schematic diagram of how the Set-Top Box Manager application may be incorporated into a network environment for provisioning apparatus according to one embodiment of the systems and methods herein described; FIG. 12 is a schematic diagram of an example of a Set-Top Box Manager screen display according to one embodiment of the systems and methods herein described; FIG. 13 is a schematic diagram of an example of a further Set-Top Box Manager screen display according to one embodiment of the systems and methods herein described; FIG. 14 is a schematic diagram of an example of a further Set-Top Box Manager screen display, which may be used to show ‘Audit’ information, according to one embodiment of the systems and methods herein described; FIG. 15 is a schematic diagram of a ‘Connection Window’ screen display according to one embodiment of the systems and methods herein described; FIG. 16 is a schematic diagram of an ‘Install’ Results List Panel screen display according to one embodiment of the systems and methods herein described; FIG. 17 is a schematic diagram of a ‘Forward Path’ Results List Panel screen display according to one embodiment of the systems and methods herein described; FIG. 18 is a schematic diagram of a ‘Reverse Path’ Results List Panel screen display according to one embodiment of the systems and methods herein described; FIG. 19 is a schematic diagram of a ‘Resources’ Results List Panel screen display according to one embodiment of the systems and methods herein described; FIG. 20 is a schematic diagram of an example of a further Set-Top Box Manager screen display, which may be used to show ‘Audit’ information, according to one embodiment of the systems and methods herein described; FIG. 21 is a schematic diagram of a Set-Top Box Manager Top Bar according to one embodiment of the systems and methods herein described; FIG. 22 is a schematic diagram of a one embodiment of the architecture of the Set-Top Box Manager; FIG. 23 is a schematic diagram of a Cable Modem Manager integrated into a distributed system according to one embodiment of the systems and methods herein described; FIG. 24 is a schematic diagram of a technical architecture overview of the Cable Modem Manager according to one embodiment of the systems and methods herein described; FIG. 25 is a schematic diagram of a screen display which may be generated by the Cable Modem Manager to display data according to one embodiment of the systems and methods herein described; FIG. 26 shows a schematic view of where the network management system sits in relation to interfaces for use by users, including customers, service operators and network operators, and the services and network elements being managed; FIG. 27 shows a schematic view of the primary components of the network management system; FIG. 28 shows a more detailed view of components of the network management system together with tools and other systems with which it interacts; FIG. 29 shows a simulator for use in the network management system of FIG. 26 and its connection into a network to be tested; FIG. 30 shows a screen view from a graphical user interface reviewing an alarm by means of the network management system, with access available to a knowledge management system for further analysis; FIG. 31 shows a screen view from a graphical user interface reviewing an alarm in terms of user impact; FIG. 32 shows a screen view from a graphical user interface reviewing an alarm with reference to its network location, with access available to the knowledge management system for further analysis; FIG. 33 shows a screen view from a graphical user interface providing equipment information, with access available to a knowledge management system for further analysis; FIG. 34 shows the options available for a screen view layout as shown in FIG. 33 ; FIG. 35 shows a screen view from a graphical user interface providing an alarm list with access to the knowledge management system for further analysis of selected alarms; FIG. 36 shows a screen view similar to that of FIG. 30 in which the knowledge management system has been accessed for further relevant information; FIG. 37 shows the options available for a screen view layout as shown in FIG. 36 ; FIG. 38 shows a login screen for a user accessing the knowledge management system; FIG. 39 shows a screen view available to a user of the knowledge management system; FIG. 40 shows a further screen view available to a user of the knowledge management system; FIG. 41 shows the options available for a screen view layout as shown in FIGS. 39 or 40 ; FIG. 42 shows a network context for the network management system in which a global infrastructure provider controls the end-to-end network; FIG. 43 shows a network context for the network management system in which a service provider uses the network management system to control the service provider's part of the network; FIG. 44 shows a sample Hybrid Fibre-Coax manager deployment according to one embodiment of the systems and methods described herein; FIG. 45 illustrates CMTS router and CMTS card relationship's according to one embodiment of the systems and methods described herein; FIG. 46 shows an HFC manager user interface overview for a preferred embodiment of the systems and methods described herein; FIG. 47 illustrates a Knowledge Management System integrated with Imagine Service Emulation Agent modules according to one embodiment of the systems and methods described herein; FIG. 48 illustrates a graphical User Interface structure for a preferred Knowledge Management System according to one embodiment of the systems and methods described herein; FIG. 49 is an XML section of command script for the switch configuration for use with a preferred ISEA according to one embodiment of the systems and methods described herein; FIG. 50 is an XML section of command script for a cable modem configuration for use with a preferred ISEA according to one embodiment of the systems and methods described herein; FIGS. 51 a and 51 b are an XML sections of command script for a scheduler manager configuration for use with a preferred ISEA according to one embodiment of the systems and methods described herein; FIG. 52 is an XML section of command script for a DHCP protocol configuration for use with a preferred ISEA according to one embodiment of the systems and methods described herein; FIGS. 53 a and 53 b are an XML sections of command script for use with a preferred ISEA to configure a scenario named ‘Test’ for one location, containing three services; provisioning, internet access, mail (ISP) according to one embodiment of the systems and methods described herein; FIG. 54 is a continuation of the XML section of command script of FIGS. 53 a and 53 b according to one embodiment of the systems and methods described herein; FIG. 55 illustrates scenario organization for an ISEA according to one embodiment of the systems and methods described herein; FIG. 56 shows a preferred hardware architecture for an ISEA according to one embodiment of the systems and methods described herein; FIG. 57 illustrates the six key components comprising a preferred ISEA architecture according to one embodiment of the systems and methods described herein. detailed-description description="Detailed Description" end="lead"? |
Methods of managing the transfer and use of data |
Certain improvements related to the transfer and use of information are disclosed, including a the transfer of information from an existing database to a database used in conjunction with an RFID device of the type that may be used to interrogate RFID tags associated with items associated with entries in the existing database. |
1. A method of transferring and using information, comprising the steps of: (a) obtaining information related to a plurality of items from an existing database; (b) reformatting the information in a desired manner to facilitate the use of the information by an RFID reader; (c) exporting the information to a database stored on a data storage device; and (d) using the information on the data storage device with an RFID reader in conjunction with the interrogation of RFID tags associated with the items. 2. The method of claim 1, wherein the existing database includes information correlating the items to item identifiers. 3. The method of claim 2, wherein the item identifiers comprise barcodes. 4. The method of claim 2, wherein the item identifiers comprise at least one of characters and handwriting. 5. The method of claim 1, wherein the information exported to the data storage device comprises at least one ordered list of items. 6. The method of claim 5, wherein the ordered list is a list of items in an order that the items are to be located in a storage area. 7. The method of claim 1, wherein the information exported to the data storage device comprises at least one search list of items. 8. The method of claim 1, wherein the data storage device is a removable non-volatile data storage device. 9. The method of claim 8, wherein the removable non-volatile data storage device is a solid-state device. 10. The method of claim 9, wherein the removable non-volatile solid-state data storage device is a compact flash memory card. 11. The method of claim 1, wherein the information exported to the data storage device comprises more than one file, each file including at least one database record. 12. The method of claim 11, wherein the method further comprises the step of associating at least two files that include information describing database records related to consecutive items in an ordered list. 13. The method of claim 11, wherein the method further comprises the step of determining that two files do not include information describing database records related to consecutive items. 14. The method of claim 1, wherein the information is reformatted by selecting from each record in the existing database information to be provided in a primary information field and information to be provided in a secondary information field on the database on the data storage device. 15. The method of claim 14, wherein at least one of the information fields comprises information from a record related to a single type of information. 16. The method of claim 14, wherein at least one of the information fields comprises information from a record related to more than one type of information. 17. The method of claim 14, wherein at least one of the information fields comprises information from a record in the existing database that represents only a portion of the information contained in that record. 18. The method of claim 14, wherein the information selected for the primary and secondary information fields is selected from the group consisting of the name or title of the item, the identification number of the item, or the call number of the item. 19. The method of claim 14, wherein the method further comprises the step of displaying information obtained from the primary information field and information obtained from the secondary information field on the RFID device for observation by a user. 20. The method of claim 1, wherein the step of reformatting the data comprises identifying multiple records in the existing database that relate to equivalent items. 21. The method of claim 20, wherein the method further comprises the step of providing only one entry on the database stored on the data storage device relative to that item. 22. The method of claim 20, wherein the method further comprises the step of comparing multiple entries from the existing database to determine whether the multiple entries relate to equivalent items using at least one of a primary information field and a secondary information field. 23. (Cancelled) 24. The method of claim 23, wherein the method further comprises the step of assigning the same storage area location to each identical item. 25. The method of claim 23, wherein the method further comprises the step of assigning a range of storage area locations to each identical item, so that each such item located within the range by the RFID device is considered by the device to be in the proper location. 26. The method of claim 1, wherein the method further comprises the step of previewing the format of at least one entry for the database on the data storage device prior to step (c). 27. The method of claim 26, wherein the entry includes information selected from the group consisting of an item identifier, a primary information field, a secondary information field, and a barcode. 28. The method of claim 1, wherein the method further comprises the step of providing a summary log related to the exportation of information. 29. The method of claim 28, wherein the summary log comprises information selected from a group consisting of a description of the files that were exported, the number of entries that were exported, the elapsed time for the transfer, and the number of errors encountered during the export. 30. The method of claim 28, wherein the method further comprises providing a detailed error log that provides information related to errors detected in the exported information. 31. The method of claim 1, wherein the items are library materials. 32. The method of claim 1, wherein the items are files. 33. The method of claim 1, wherein the items are pieces of evidence. 34. The method of claim 1, wherein the items are pallets or containers. 35. Software comprising instructions for carrying out the method of claim 1. 36. In combination: (a) a data transfer and management system software for reformatting information obtained from an existing database having an arbitrary data management system into reformatted information stored in a database for use by an RFID reader and for reformatting information obtained from a database containing information for use by an RFID reader into reformatted information stored in an existing database having an arbitrary data management system, the databases comprising entries related to items of interest; and (b) an RFID reader that interrogates RFID tags associated with items and stores information related to the interrogated RFID-tagged item in a database used by the RFID reader. 37. The combination of claim 36, wherein the RFID reader is a handheld RFID reader. 38. The combination of claim 36, wherein the RFID reader is a component of a workstation for processing items selected by users. 39. The combination of claim 38, wherein the workstation is a workstation adapted for use by a library employee. 40. The combination of claim 38, wherein the workstation is a self-service station adapted for use by the user who selected the items. 41. The combination of claim 38, wherein the workstation is a conversion station for converting non-RFID-tagged items to RFID-tagged items. 42. The combination of claim 41, wherein the non-RFID-tagged items are barcoded items. 43. The combination of claim 41, wherein the non-RFID-tagged items are identified by characters. 44. The combination of claim 41, wherein the non-RFID-tagged items are items regarding which a user enters information describing the items into the workstation. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Many facilities have computers that include databases with entries describing multiple items. One example is a library, which typically has a computer with a database including entries for each library book, magazine, or other material possessed by the library. The database may be provided by a vendor, such as a library automation vendor. Those databases enable a library to access data related to one, a group of, or all of the materials in the library, as needed. For example, if a patron requests a particular book, the database can provide information regarding the circulation status of the book, such as the most recent date on which it was checked out, and other related information. These types of databases are common in other fields also, including asset tracking and management generally. In some fields, there are a variety of databases that use file formats that are not inter-compatible, and thus retrieving information from the database of one system for use with other systems can be problematic. For example, a particular university library may have a database listing its materials that is different from the corresponding database that a particular public library maintains, which in turn may be different from the database that a particular junior high school library maintains. It therefore becomes difficult for equipment, software, service or other suppliers to interact effectively with each of these different databases without customizing those databases. Because manual customization, or entry or re-entry of the contents of an entire database can be an impossibly large task, there is a need for improvements in the transfer and use of information between different databases. That is the subject of the present invention. |
<SOH> SUMMARY OF THE INVENTION <EOH>The present invention includes a variety of features described herein, including a method of transferring and using information, comprising the steps of obtaining information related to a plurality of items from an existing database; reformatting the information in a desired manner to facilitate the use of the information by an RFID reader; exporting the information to a database stored on a data storage device; and using the information on the data storage device with an RFID reader in conjunction with the interrogation of RFID tags associated with the items. A combination of software for reformatting information obtained from an existing database having an arbitrary data management system into reformatted information stored in a database for use by an RFID reader, the databases comprising entries related to items of interest; and an RFID reader that interrogates RFID tags associated with items and transfers information related to the interrogated RFID-tagged item from the RFID reader to the database, from the database to the RFID reader, or both, is also disclosed. The data transfer and management system of the present invention may be used in conjunction with devices such as a portable RFID reader, self-service terminals and staff workstations for processing tagged items, conversion stations, and other item processing devices. The system may be used not only in connection with RFID-tagged items, but also items that are associated with other item identifiers, such as barcodes, characters, handwritten indicia, and other types of identification. The present invention, which typically uses lists or files created from an existing database, has several advantages over systems that attempt to provide direct access to an existing database. First, direct access systems require detailed knowledge of the structure of the existing database and how to create a connection to that database. Because the structures may differ based on the database, as described above, direct connections may be difficult to obtain. Second, direct access is relatively slow compared to file access (as used herein), because the existing database is generally on a different computer and requested data has to be separated from unrequested data within that database. Extraction into a file provides faster access than by direct query. Third, some existing databases may not support standard access, such as SQL access, but essentially all existing databases should be able to provide some kind of reporting features for generating list files. The items that are the subject of the data may be assets of any kind, including library materials, criminal evidence, documents or files, containers, pallets, boxes, retail goods, rental items, video tapes, or laboratory samples. These and other aspects of the present invention are described in greater detail below. detailed-description description="Detailed Description" end="lead"? |
Method and apparatus for electrochemical reduction of nitrogen oxides in a mixture of nitrogen oxides and oxygen |
A working electrode for an electrochemical reactor, the electrochemical reactor comprising a working electrode, a counter electrode, and an ion-selective electrolyte; the working electrode comprising an electric conductive ceramic oxide material having the general formula: A2A′(1−x)ByB′(1−y)O(3−Δ) wherein A and A′ designate first substitution metals of similar sizes, said first substitution metals having a high efficiency for reducing vacancies for oxygen ions, 0≦x≦1; B and B′ designate second substitution metals of similar sizes, said second substitution metals being of smaller sizes, said second substitution metals being of smaller sizes than those of said first substitution metals, and having a high transition efficiency between oxidation states, 0≦y≦1; O designates oxygen; and Δ is a small number, positive or negative, that allows for compensation of differences in valences of said metals. An electrochemical reactor comprising said working electrode. Methods and an electrochemical reactor for reduction of nitrogen oxides in a mixture og nitrogen oxides and oxygen, the electrochemical reactor comprising a working electrode, a counter electrode, an ion-selective electrolyte, and a nitrogen absorber for absorbing nitrogen oxides; wherein said nitrogen absorber is adapted for electrochemical regeneration thereof. |
1-23. (Cancelled) 24. A method of reducing nitrogen oxides in a mixture of nitrogen oxides and oxygen, by use of an electrochemical reactor comprising a working electrode for reducing nitrogen oxides to nitrogen and oxygen, a counter electrode, and an ion-selective electrolyte; the processes taking place at the electrodes being substantially as follows: at the cathode 2NOx+2xe−->N2+2xO2 (a) O2+4e−->2O2− (b) at the anode 2O2−->O2+4e− (c) said cathode electrode processes (a) and (b) being carried out at a potential between −1500 my and +1500 mV between said working electrode and said counter electrode, and at a temperature within a range of 200 to 500° C.; and said working electrode comprising an electric conductive ceramic material of lanthanum manganite (LaMnO3), lanthanum chromite (LaCrO3), lanthanum ferrite (LaFeO3), lanthanum cobaltite (LaCoO3) or lanthanum nickel oxide (LaNiO3); said material being doped with one or more of metals selected from the group consisting of Sr, Ca, Ba, Eu, Fe, Co and Ni in an effective amount to achieve a faster rate of reduction of nitrogen oxides than the rate of reduction of oxygen at the selected potential and temperature. 25. A method according to claim 24, wherein the potential of the working electrode is between −200 mV and 800 mV, measured versus a hydrogen electrode of 8% H2O and 3% H2 in Ar. 26. A method according to claim 24 or 25, wherein the working electrode is La1−xSrxMnO3 with x being in the range from 0.12 to 0.18. 27. A method according to claim 24, wherein the mixture of nitrogen oxides and oxygen is concentrated with an absorber capable of absorbing nitrogen oxides and selected from the group consisting of Na2O, K2O, MgO, CaO, SrO, and BaO and that the nitrogen oxides absorbed in the absorber are caused to react with the working electrode. 28. A method according to claim 27, wherein the absorber comprises a working electrode and a counter electrode for causing the absorbed nitrogen oxides to react with the working electrode of the electrochemical reactor by establishing an electric potential between said electrodes. 29. A method according to claim 28, wherein the nitrogen oxides are absorbed without applying any electrical potential between the working electrode of the absorbing material and the counter electrode of the absorbing material. 30. A method according to claim 27, wherein nitrogen oxides are reduced at the same time as the absorber is regenerated. 31. A method according to claim 28, wherein said absorber is regenerated by applying an electrical potential between the working electrode of the absorber and the counter electrode of the absorber in the range of from 0 to 1.5V. 32. A method according to claim 30 or 31, wherein said regeneration is carried out at an electrical current density causing more than 80% regeneration of said absorber after a regeneration time in the range from 5 to 40 s. 33. A method according to claim 32, wherein said electrical current density causes more than 90% regeneration of said nitrogen oxide absorber after said regeneration time. 34. A method according to claim 27, wherein said absorber absorbs more than 60%, preferably in the range 60-80% of the nitrogen oxides of the mixture of nitrogen oxides and oxygen. 35. A method according to claim 27, wherein said absorption of nitrogen oxides is continued until the absorber is saturated. 36. A method according to claim 27, wherein said absorber and said working electrode are intermixed. 37. An electrochemical reactor for reducing nitrogen oxides in a mixture of nitrogen oxides and oxygen, comprising a working electrode for reducing nitrogen oxides to nitrogen and oxygen, a counter electrode, an ion-selective electrolyte where said working electrode comprises an electric conductive ceramic material of lanthanum manganite (LaMnO3), lanthanum chromite (LaCrO3), lanthanum ferrite (LaFeO3), lanthanum cobaltite (LaCoO3) or lanthanum nickel oxide (LaNiO3); said material being doped with one or more of metals selected from the group consisting of Sr, Ca, Ba, Eu, Fe, Co and Ni in an effective amount to achieve a faster rate of reduction of nitrogen oxides than the rate of reduction of oxygen, wherein the reactor further comprises means for maintaining a potential between −1500 mV and +1500 mV between said working electrode and said counter electrode and means for maintaining a temperature within a range of 200 to 500° C. 38. A reactor according to claim 37 which further comprises a nitrogen oxide absorber. 39. A reactor according to claim 37 or 38, wherein said nitrogen oxide absorber comprises a material or a combination of materials selected from the group consisting of Na2O, K2O, MgO, CaO, SrO and BaO. 40. A method according to claim 28, wherein the working electrode of the absorber comprises an electric conductive ceramic material of lanthanum manganite (LaMnO3), lanthanum chromite (LaCrO3), lanthanum ferrite (LaFeO3), lanthanum cobaltite (LaCoO3) or lanthanum nickel oxide (LaNiO3); said material being doped with one or more of metals selected from the group consisting of Sr, Ca, Ba, Eu, Fe, Co and Ni in an effective amount to achieve a faster rate of reduction of nitrogen oxides than the rate of reduction of oxygen at the selected potential and temperature. |
<SOH> 1. BACKGROUND OF THE INVENTION <EOH>The present invention relates to a method and apparatus for electrochemical reduction of nitrogen oxides in a mixture of nitrogen oxides and oxygen. In an aspect, the invention relates to a working electrode for an electrochemical reactor, an electro-chemical reactor comprising such a working electrode, a method of reducing nitrogen oxides in a mixture of nitrogen oxides and oxygen using an working electrode comprising an electric conductive ceramic of lanthanum manganite doped with an oxygen ion vacancy quencher. In another aspect, the invention relates to an electro-chemical reactor comprising nitrogen oxide absorber adapted for electrochemical regeneration, and a method of electrochemical reduction of nitrogen oxides in a mixture of nitrogen oxides and oxygen using such an electro-chemical reactor. |
<SOH> 3. BRIEF DESCRIPTION OF THE DRAWINGS <EOH>In the following, by way of examples only, the invention is further disclosed with detailed description of preferred embodiments. Reference is made to the drawings in which FIG. 1 shows an exemplary cyclic voltametric measurement of a working electrode comprising La 0.82 Sr c0.14 Fe 0.3 Mn 0.9 O 3 in presence of nitrogen monooxide, and in presence of oxygen, respectively; FIG. 2 shows an exemplary cyclic voltametric measurement of a comparison working electrode comprising CO 3 O 4 presence of nitrogen monooxide, curve 1 , and in presence of oxygen, curve 2 , respectively; FIG. 3 shows an exempel of cyclic voltametric measurement of a working electrode comprising La 0.85 Sr 0.15 MnO 3 presence of nitrogen monooxide, curve B, and in presence of oxygen, curve A, respectively; FIG. 4 shows five examples of cyclic voltametric measurements of a series of working electrodes in presence of nitrogen monooxide, said working electrodes comprising LSM materials having different degrees of doped strontium as cathode; FIG. 5 shows five examples of cyclic voltametric measurements of a series of working electrodes in presence of oxygen, said working electrodes comprising LSM materials similar to those used for the measurements shown in FIG. 4 ; FIG. 6 shows a cross sectional sketch of an embodiment of an electrochemical reactor according to the invention; FIG. 7 shows a cross sectional sketch of an embodiment of an electrochemical cell for an electrochemical reactor according to the invention; FIG. 8 shows a cross sectional sketch of another embodiment of an electrochemical cell for an electro-chemical reactor according to the invention; and FIG. 9 shows a cross sectional sketch of an experimentel electrochemical set-up for voltametric measurements. detailed-description description="Detailed Description" end="lead"? |
Method for controlling a service-providing device |
For controlling the use of a device (1) performing a service, the authorized persons are issued contactless data carriers (2) that, upon use of the device (1), communicate with a reader (3) storing the personal authorization data in a memory (4). If authorization is ascertained, the reader (3) enables the device (1). The service performed by the device (1) is stored in the memory (4). The particular person's transaction data stored in the memory (4) are read by a control person with a portable reader (5) and transferred to a data center (10) with a terminal (8) by telecommunication. |
1. A method for controlling the use of a device (1) performing a service by which the persons authorized to use the device are issued contactless data carriers (2) that, upon use of the device (1), communicate with a reader (3) storing the personal authorization data in a memory (4) and enabling the device (1) if authorization is ascertained, characterized in that the reader (3) stores the service performed by the device (1) in the memory (4), the particular person's transaction data stored in the memory (4) being read by a control person with a portable reader (5) and transferred with a terminal (8) by telecommunication (9) to a data center (10). 2. A method according to claim 1, characterized in that the billing of the performed service is effected by the data center (10) on the basis of the data transferred with the portable reader (5). 3. A method according to claim 1 2, characterized in that the personal authorization data stored in the data center (10) are read by the control person with the portable reader (5) on the terminal (8) and stored in the memory (4) of the reader (3) of the device (1). 4. An apparatus according to claim 1, characterized in that the device (1) is a device used by a community or similar group of persons. 5. A method according to claim 1, characterized in that the device (1) is an electric power consumer and the billing of the performed service is effected according to the power consumption of the device (1). 6. A method according to claim 5, characterized in that the electric power consumer is a washing machine. |
Channel estimation in cdma communications systems using both lower power pilot channel and higher power date channel |
An iterative arrangement of channel estimator (12), a Kalman filter unit (14), and a soft demodulator (16) is provided for producing an estimate of complex gain of a CDMA communications channel carrying data and pilot channels, and demodulated data of the data channel. An initial channel estimate is produced by the estimator (12) using only the low-power pilot channel. This later is improved by the iterative process using the data channel. The complex gains is represented by a sum of sinusoidal signals with different frequencies and randomly variable amplitude and phase. |
1. A method of estimating complex gain of a communications channel in a CDMA system in which a received signal communicated via the communications channel comprises at least one relatively higher power data channel and a relatively lower power pilot channel, comprising the steps of: producing an estimated complex gain of the communications channel initially from only a pilot channel component of the received signal; and, in successive iterations: estimating demodulated data of the data channel from the received signal and the estimated complex gain of the communications channel; and improving the estimated complex gain of the communications channel in dependence upon the received signal and the estimated demodulated data of the data channel; wherein the estimated complex gain of the communications channel is represented by a sum of a plurality of sinusoidal signals with different frequencies and with randomly variable amplitude and phase. 2. A method as claimed in claim 1 and comprising the step of transforming a vector of complex data samples representing the received signal to scalar complex numeric sequences, wherein the estimated complex gain of the communications channel is produced using said sequences. 3. A method as claimed in claim 2 wherein the step of transforming comprises multiplying the vector of complex data samples representing the received signal by a transposed impulse response matrix and by a vector that is conjugate to a complex PN code vector to produce a resulting vector, multiplying the resulting vector by a Walsh function of the data channel to produce a first scalar complex numeric sequence, and adding components of said resulting vector to produce a second scalar complex numeric sequence. 4. A method as claimed in claim 3 wherein the demodulated data of the data channel is estimated using the estimated complex gain of the communications channel and said first sequence. 5-8. (canceled) 9. A method as claimed in claim 1 wherein the step of producing and improving the estimated complex gain of the communications channel comprise Kalman filtering estimates of the complex gain of the communications channel. 10. A method as claimed in claim 2 wherein the step of producing and improving the estimated complex gain of the communications channel comprise Kalman filtering estimates of the complex gain of the communications channel. 11. A method as claimed in claim 3 wherein the step of producing and improving the estimated complex gain of the communications channel comprise Kalman filtering estimates of the complex gain of the communications channel. 12. A method as claimed in claim 4 wherein the step of producing and improving the estimated complex gain of the communications channel comprise Kalman filtering estimates of the complex gain of the communications channel. 13. A method as claimed in claim 9 and comprising the step of averaging estimates of the complex gain of the communications channel over a plurality of PN code chips prior to said Kalman filtering. 14. A method as claimed in claim 10 and comprising the step of averaging estimates of the complex gain of the communications channel over a plurality of PN code chips prior to said Kalman filtering. 15. A method as claimed in claim 11 and comprising the step of averaging estimates of the complex gain of the communications channel over a plurality of PN code chips prior to said Kalman filtering. 16. A method as claimed in claim 12 and comprising the step of averaging estimates of the complex gain of the communications channel over a plurality of PN code chips prior to said Kalman filtering. 17. Apparatus for carrying out the method of claim 1, comprising a data transform unit for producing two scalar complex numeric sequences from a vector of complex data samples representing the received signal, and an iterative arrangement comprising: a demodulator responsive to one of the two scalar complex numeric sequences and to an estimated complex gain of the communications channel to produce an estimated demodulated symbol of the data channel; a complex gain estimator responsive to the two scalar complex numeric sequences and, except in a first iteration, to the estimated demodulated data symbol produced by the demodulator, for producing an estimated complex gain of the communications channel; and a Kalman filter for filtering the estimated complex gain produced by the complex gain estimator to produce the estimated complex gain for the demodulator. 18. Apparatus as claimed in claim 17 and including an averaging unit for averaging complex gain estimates produced by the complex gain estimator over a plurality of PN code chips and for supplying an averaged complex gain estimate to the Kalman filter at a sampling rate less than a PN code chip rate. |
<SOH> BACKGROUND <EOH>It is desirable to provide coherent reception of transmitted signals in a communications system, for which it is necessary to estimate parameters (amplitude, phase, frequency offset, and delay) of the communications channel which affect signal synchronization. A wireless CDMA system typically has multiple paths with multi-path fading, so that such parameters continuously change and must be estimated in an ongoing manner. Accordingly, accurate channel estimation in a CDMA system presents a substantial challenge. In current CDMA systems, it has been proposed to allocate four channels for each user for synchronization and data communication. These channels are referred to as the pilot channel (P), for synchronization purposes; the fundamental channel (F), for voice signals and low-rate data transmission; the supplemental channel (S), for high-rate data communication, and the control channel (C), for very low-rate data communication for control purposes. One or more of the last three channels, i.e. the data channels, need not be used by a particular user at any time. For simplicity the following description refers primarily to the fundamental channel, but it should be understood that the same comments apply for any one or more of the data channels. For efficient operation of the CDMA system, it is desirable for the transmit signal power allocated to the pilot channel (i.e. the relative gain of the pilot channel) to be small relative to that of the data channels. The pilot channel can be used for channel estimation, but its relatively low power can result in poor phase accuracy and poor amplitude tracking, so that channel estimation accuracy is not sufficient. For example, the much stronger fundamental channel constitutes interference when estimating the channel parameters from the pilot channel. Increasing the power allocated to the power channel to improve channel estimation is undesirable. Channel estimation can also conceivably be based on the signals of one or more of the higher-power data channels, for example the fundamental channel. The complexity of such an arrangement has made it undesirable or impractical in a CDMA system, and it may provide slow convergence, or no convergence, due to poor estimates of information symbols. Accordingly, there is a need to provide improved channel estimation in CDMA systems. |
<SOH> SUMMARY OF THE INVENTION <EOH>According to one aspect, this invention provides a method of estimating complex gain of a communications channel in a CDMA system in which a received signal communicated via the communications channel comprises at least one relatively higher power data channel and a relatively lower power pilot channel, comprising the steps of: producing an estimated complex gain of the communications channel initially from only a pilot channel component of the received signal; and, in successive iterations: estimating demodulated data of the data channel from the received signal and the estimated complex gain of the communications channel; and improving the estimated complex gain of the communications channel in dependence upon the received signal and the estimated demodulated data of the data channel; wherein the estimated complex gain of the communications channel is represented by a sum of a plurality of sinusoidal signals with different frequencies and with randomly variable amplitude and phase. The representation of the complex gain of the communications channel in this manner enables an accurate estimate of the channel to be provided iteratively from the estimated demodulated data due to the higher power of the data channel, despite a relatively poor accuracy of the initial channel estimate using only the pilot channel. However, the initial channel estimate can be determined relatively easily because it is based only on the pilot channel (i.e. it is not dependent the information of the data channel or the accuracy with which such information is estimated), and the convergence problem discussed above is avoided. The method preferably comprises the step of transforming a vector of complex data samples representing the received signal to scalar complex numeric sequences, the estimated complex gain of the communications channel being produced using said sequences. This input data transformation enables the complexity of an implementation of the method to be considerably reduced. Preferably, the step of producing and improving the estimated complex gain of the communications channel comprise Kalman filtering estimates of the complex gain of the communications channel. Estimates of the complex gain of the communications channel are preferably over a plurality of PN code chips prior to the Kalman filtering, so that the Kalman filtering can take place at a sampling rate less than a PN code chip rate. The invention also provides apparatus for carrying out the above method, comprising a data transform unit for producing two scalar complex numeric sequences from a vector of complex data samples representing the received signal, and an iterative arrangement comprising: a demodulator responsive to one of the two scalar complex numeric sequences and to an estimated complex gain of the communications channel to produce an estimated demodulated symbol of the data channel; a complex gain estimator responsive to the two scalar complex numeric sequences and, except in a first iteration, to the estimated demodulated data symbol produced by the demodulator, for producing an estimated complex gain of the communications channel; and a Kalman filter for filtering the estimated complex gain produced by the complex gain estimator to produce the estimated complex gain for the demodulator. |
Hab18g/cd147 its antagonist and application |
The present invention relates to a new protein molecule HAb18G/CD147 which is derived from hepatocellular carcinoma tissue and can be used as a drug target. The invention also relates to the antisense RNA directed to HAb18G/CD147 transcript, and antagonistic peptides for HAb18G/CD147. |
1. A protein molecule HAb18G/CD147 identified from hepatocellular carcinoma tissue and responsible for the metastasis of cancers such as hepatocellular carcinoma, which belongs to CD147 family and comprises an amino acid sequence as set forth in SEQ ID NO:1 which is highly homologous to that of the leukocyte differentiation antigen CD147 molecule, said protein molecule is a purified native antigen prepared from a crude sample of memberane antigens of hepatocellular carcinoma by affinity chromatography using a hepatocellular carcinoma specific monoclonal antibody HAb18 as ligand, or an antigen obtained by immunoscreening human hepatocellular carcinoma cDNA expression library with HAb18 followed by the expression of the corresponding coding sequence. 2. An antisense RNA plasmid vector PCl-as HAb18G capable of blocking the translation of HAb18G/CD147 mRNA, which is constructed by a reverse insertion of the full length cDNA fragment of HAb18G/CD147 in a eukaryotic expressing vector PCl-neo. 3. An antagonistic peptide for HAb18G/CD147 comprising an amino acid sequence selected from: (1) Met Thr His Asp Pro Val Ile Ser Leu Pro Thr Thr; (SEQ ID NO: 2) (2) Leu His Arg His Ser His Gly His Ser Tyr Lys Ser; (SEQ ID NO: 3) (3) Gly His Trp His Asn His Arg His Gln Ala Pro Leu; (SEQ ID NO: 4) (4) Lys Tyr Pro His Gln His Leu His Met His Asp Ser; (SEQ ID NO: 5) (5) Ile Gly Trp His Tyr Tyr Leu Arg Thr Gln His Ser; (SEQ ID NO: 6) (6) Tyr Pro Phe His His Lys His Trp His Arg Pro Asn; (SEQ ID NO: 7) (7) Ala Asn Ile Val Pro Ile His Ala Asn His Phe Gln; (SEQ ID NO: 8) (8) Met His Lys His Pro His Gly Ser Gln Gly Pro Thr; (SEQ ID NO: 9) and (9) Tyr Lys Leu Pro Gly His His His His Tyr Arg Pro. (SEQ ID NO: 10) 4. The antagonistic peptide for HAb18G/CD147 according to claim 3, wherein the antagonistic peptide is synthesized by solid phase synthesis. 5. The antagonistic peptide for HAb18G/CD147 according to claim 3, wherein the amino acids of said antagonistic peptide are L-amino acids. 6. The antagonistic peptide for HAb18G/CD147 according to claim 3, wherein the amino acids of said antagonistic peptide are D-amino acids. 7. A method for preventing and treating the recurrence and metastasis of cancer, for preventing and treating RA and osteoarthritis, for preventing and treating HIV infection and AIDS, or for preventing and treating arteriosclerosis and dilated cardiomyopathy in a subject in need of such treatment, comprising administering to the subject an effective dose of the antisense vector PCl-as HAb18G of claim 2. 8. A pharmaceutical composition for preventing and treating the recurrence and metastasis of cancer, for preventing and treating RA and osteoarthritis, for preventing and treating HIV infection and AIDS, or for preventing and treating arteriosclerosis and dilated cardiomyopathy in a subject in need of such treatment, comprising an effective dose of the antisense vector PCl-as HAb18G of claim 2, and a pharmaceutically acceptable carrier. 9. (Cancelled) 10. A method for preventing and treating the recurrence and metastasis of cancer, for preventing and treating RA and osteoarthritis, for preventing and treating HIV infection and AIDS, or for preventing and treating arteriosclerosis and dilated cardiomyopathy in a subject in need of such treatment, comprising administering to subject an effective dose of an antagonistic peptide for HAb18G/CD147 comprising an amino acid sequence selected from: (1) Met Thr His Asp Pro Val Ile Ser Leu Pro Thr Thr; (SEQ ID NO: 2) (2) Leu His Arg His Ser His Gly His Ser Tyr Lys Ser; (SEQ ID NO: 3) (3) Gly His Trp His Asn His Arg His Gln Ala Pro Leu; (SEQ ID NO: 4) (4) Lys Tyr Pro His Gln His Leu His Met His Aso Ser; (SEQ ID NO: 5) (5) Ile Gly Trp His Tyr Tyr Leu Arg Thr Gln His Ser; (SEQ ID NO: 6) (6) Tyr Pro Phe His His Lys His Trp His Arg Pro Asn; (SEQ ID NO: 7) (7) Ala Asn Ile Val Pro Ile His Ala Asn His Phe Gln; (SEQ ID NO: 8) (8) Met His Lys His Pro His Gly Ser Gln Gly Pro Thr; (SEQ ID NO: 9) and (9) Tyr Lys Leu Pro Gly His His His His Tyr Arg Pro. (SEQ ID NO: 10) 11. A pharmaceutical composition for preventing and treating the recurrence and metastasis of cancer, for preventing and treating RA and osteoarthritis, for preventing and treating HIV infection and AIDS, or for preventing and treating arteriosclerosis and dilated cardiomyopathy in a subject in need of such treatment, comprising an effective dose of the antagonistic peptide for HAb18G/CD147 comprising an amino acid sequence selected from: (1) Met Thr His Asp Pro Val Ile Ser Leu Pro Thr Thr; (SEQ ID NO: 2) (2) Leu His Arg His Ser His Gly His Ser Tyr Lys Ser; (SEQ ID NO: 3) (3) Gly His Trp His Asn His Arg His Gln Ala Pro Leu; (SEQ ID NO: 4) (4) Lys Tyr Pro His Gln His Leu His Met His Asp Ser; (SEQ ID NO: 5) (5) Ile Gly Trp His Tyr Tyr Leu Arg Thr Gln His Ser; (SEQ ID NO: 6) (6) Tyr Pro Phe His His Lys His Trp His Arg Pro Asn; (SEQ ID NO: 7) (7) Ala Asn Ile Val Pro Ile His Ala Asn His Phe Gln; (SEQ ID NO: 8) (8) Met His Lys His Pro His Gly Ser Gln Gly Pro Thr; (SEQ ID NO: 9) and (9) Tyr Lys Leu Pro Gly His His His His Tyr Arg Pro. (SEQ ID NO: 10) 12. The pharmaceutical composition according to claim 11, wherein the antagonistic peptide is entrapped within nanometer liposomes. 13. A pharmaceutical composition comprising an effective dose of the antagonistic peptide of claim 4, wherein the antagonistic peptide is entrapped within nanometer liposomes. 14. A pharmaceutical composition, comprising an effective dose of the antagonistic peptide of claim 5, wherein the amino acids of said antagonistic peptide is entrapped within nanometer liposomes. 15. A pharmaceutical composition comprising the antagonistic peptides of claim 6, wherein the antagonistic peptide is entrapped within nanometer liposomes. 16. The method according to claim 10, wherein the antagonistic peptide is administered with an effective dose of an antisense RNA plasmid vector PCl-as HAb18G capable of blocking the translation of HAb18G/CD147 mRNA, which is constructed by a reverse insertion of the full length cDNA fragment of HAb18G/CD147 in a eukaryotic expressing vector PCl-neo. 17. The pharmaceutical composition according to claim 11, wherein said composition further comprises an effective dose of an antisense RNA plasmid vector PCl-as HAb18G capable of blocking the translation of HAb18G/CD147 mRNA, which is constructed by a reverse insertion of the full length cDNA fragment of HAb18G/CD147 in a eukaryotic expressing vector PCl-neo. |
<SOH> BACKGROUND OF THE INVENTION <EOH>It is estimated that the total incidence of various types of cancer is about 10 million new cases per year, including 1.8 million in China with mortality up to 77.8% (on average, 1.3 people die of cancer in every minute). Moreover, the incidence still tends to increase. It is estimated by WHO that there are about 6 million cases dying of cancer every year, which accounts for 12% of the total number of deaths worldwide. In China, malignant tumor is the second leading cause of death with mortality accounting for 21.85% of the total in 1995. Some cancers have high incidence such as gastric carcinoma (21.76%), hepatocellular carcinoma (17.83%), lung cancer (15.19%), esophageal carcinoma (15.02%) and so on. Tumor's high recurrence and high metastasis has long been a challenge, for which no effective therapy has yet been developed. At present, one of the focuses on antitumor therapy is to inhibit tumor invasion and metastasis. Tumor invasion and metastasis is a complex process involving multi-phases and multi-factors, including protease; angiogenesis factor, adhesion molecules (such as integrin, selection and E-cadherin); migration factor; signal transduction pathway and related molecules, etc. During invasion and metastasis, tumor cells induce interstitial cells to secrete proteinase, which degrades extracelluar matrix (ECM). Four major proteinases involved are serine proteinases (such as PAS), cysteine proteinases (such as cathepsin B), aspartic acid proteinases (such as pepsin) and matrix metalloproteinase (MMPs). Among these proteinases, MMPs are of the most importance. Many experimental evidences have shown that the expression and activity of MMPs in malignant tumor tissue are higher than those in normal tissue and show a positive correlation with the degree of the malignancy of tumors. (Davie a B, Miles D W, et al. British cancer, 1993; 67:1126-1131, the entire content of which is incorporated by reference) The MMP family consists of at least 20 enzymes and has the potential to degrade all of the protein and proteoglycan components of the ECM. The roles of MMPs can be summarized as follows: (1) MMPs degrade the components of the ECM and disrupt the barrier of tumor growth. (2) MMPs cleavage basement membrane and promote cancer to cross blood vessel and enter circulation. (3) MMPs promote tumor angiogenesis or the formulation of the metastatic foci by remodeling the ECM. Since MMPs play a pivotal role in facilitating the metastasis of cancer, the source of MMPs remains the hot spot of research. The findings of many laboratories show that CD147 molecule relates to tumor cell membrane and CD147 stimulates tumor interstitial cells to produce MMPs. CD147 not only stimulates the production of MMPs but also forms a complex with MMPs at the tumor cell surface. Presentation of MMPs complexed to EMMPRIN at the tumor cell surface may be important in modifying the tumor cell pericellular matrix to promote invasion. (Guo H, et al. Cancer Res, 2000; 60(4): 888-891, the entire content of which is incorporated by reference). At present, proteinase inhibitors were employed to block the degradation of ECM. Natural proteinase inhibitors-tissue inhibitors of metalloproteinases (TIMPs) can bind with MMPs and inhibit the activities of MMPs. However, TIMPs are difficult to be extracted because their contents in tissues are very low. Recombinant TIMPs also have some disadvantages such as prone to degradation as well as malabsorption when administered orally. Synthetic pseudopeptide inhibitors of metalloproteinases, such as Batimastat (BB-94), can inhibit MMPs induced by tumor cells only at early stage and can hardly inhibit the activity of quantities of MMPs at the advanced stage, which results in phase III clinical trial failure. The inventors have been engaged in the research for hepatocellular carcinoma and immumo-targeted drugs for many years and successfully obtained the specific anti-hepatocellular carcinoma monoclonal antibody HAb18 by immunizing mice with fresh human hepatocellular carcinoma tissue to obtain hybridoma. Using HAb18 as a ligand, hepatocellular carcinoma-associated antigen HAb18G was purified by affinity chromatography. HAb18 was used to screen human hepatocellular carcinoma cDNA expression library and the corresponding coding sequence was obtained. By searching Genebank, it is found that the amino acid sequence of HAb18G is homologous to that of the leukocyte differentiation antigen CD147 molecule, so the HAb18G molecule belongs to CD147 family. Therefore, the HAb18G molecule was named HAb18G/CD147. Similar molecules were also found in several tissues with different functions such as the surface of the peripheral blood granulocyte of the rheumatoid arthritis and reactive arthritis (Watcharak, Eddafiebiger, Stepanoval. J. Immunology. 1992 (3): 847, the entire content of which is incorporated by reference), lung cancer (Guo H, Zucker S et al. J Biol Chem, 1997; 272(1): 24), brain (Schlosshauer B, Herzog K. H. J Cell Biol. 1990; 110(4): 1261, the entire content of which is incorporated by reference) and so on. The finding of Matrigel-boyden chamber and gelatin zymography showed that the role of HAb18G/CD147 in hepatocellular carcinoma is to promote hepatocellular carcinoma cells invasion and metastasis, which is identical to the roles of CD147 in other tumors. The mechanism is that HAb18G/CD147 induces hepatocellular carcinoma interstitial cells to produce MMPs, which degrades pericellular matrix components to promote hepatocellular carcinoma cells metastasis. HAb18G/CD147 is abundantly expressed in hepatocellular carcinoma and other tumor tissues while scarcely in normal tissues, so blocking the activity of HAb18G/CD147 may inhibit tumor metastasis. Rheumatoid arthritis (RA) is characterized by high disable rate, and affects more than 3 million Chinese adults every year with incidence of about 0.3%. In addition, childhood rheumatoid arthritis is the common connective tissue disease in children and its clinical features include hypertrophic and corroding synovitis involving joints of all over the body with recurrent and progressive pathological changes. RA is considered as a “limited malignant tumor” with hypertrophic and destructive pathological changes, and the spontaneous remission is extremely rare. At the advanced stage, the damage of the articular cartilage and bone results in ankylosis, deformity and dysfunction. The pathological changes can also offend the connective tissues, such as serous membrane, heart and lungs, artery, nerve and eyes. So far there is no effective cure for RA. Since the 1990s, researchers have adopted the combined treatment which has shown some advantages in alleviating patients' symptoms and improving their life quality. But the disease is not cured. Therefore, the urgent problem to be solved in the therapy of RA is to find ways to inhibit corrosion to cartilage and bone. The histopathologic characteristic of RA is over-hyperplasia of synovial lining and infiltration of a large number of inflammatory mononuclear cells under the synovial lining. Fibroblasts like synovial cells and synovial tissue macrophage play a very important role in joint damage and both cells can produce a great deal of MMPs. MMPs can degrade all ECM components of synovium, articular cartilage and bone under cartilage with synergy manner. The up-regulation of CD147 expression induces MMP-1, MMP-2 and MMP-3 production and results in the imbalance between MMPs and TIMPs, and in the end causes RA joint damage. MMPs involves in RA joint damage by directly degrading cartilage, bone tissue and indirectly accelerating angiogenesis. Inhibiting MMPs production is one of the pathway for therapy of RA. In addition, incidence of osteoarthritis is on the rise because it relates to aging. With the elongation of the life span and the incidence rate rising, MMPs produced by chondrocyte, synovial cell and fibroblast also play an important role in osteoarthritis. However, the clinical trial results of anti-ECM degradation of the proteinase inhibitor are disappointing. Therefore, screening effective CD147 antagonistic peptides to inhibit MMPs production is a new road and a new trend for RA and osteoarthritis therapy. Acquired immunodeficiency syndrome (AIDS) has emerged as one of the most deadly diseases of mankind. Since the epidemic of AIDS, about 60 million people have been infected. AIDS has become the fourth deadly disease in the world and there is no specific therapy for it so far. Several reports suggested that CD147 is a cell surface receptor for extracellular Cyclophlin A (CyPA). Human immunodeficiency virus (HIV-1) binds with CyPA to form a complex, HIV-1-associated CyPA. And the interaction between HIV-1-associated CyPA and CD147 on target cells significantly enhances the HIV-1 infection. And it is a key step for the prevention and treatment of AIDS to inhibit HIV-1 to enter cells. HIV is the pathogen for AIDS and CD147 appears to be required for efficient infection by HIV-1. So using effective CD147 antagonistic peptides to prevent HIV from binding with CD147 may provide a new means for the prevention and therapy of AIDS. Several studies showed that CD147 was involved in arteriosclerosis and dilated cardiomyopathy. Therefore, CD147 antagonistic peptides also have potential application for the prevention and treatment of arteriosclerosis and dilated cardiomyopathy. |
<SOH> SUMMARY OF THE INVENTION <EOH>In a first aspect, the present invention provides a protein molecule HAb18G/CD147 identified from hepatocellular carcinoma tissue comprising the amino acid sequence as set forth in SEQ ID NO:1. In a second aspect, the present invention provides an antisense vector PCI-as HAb18G directed to the HAb18G/CD147 transcript. In a third aspect, the present invention provides an antagonistic peptide for the HAb18G/CD147. The antagonistic peptide comprises an amino acid sequence selected from: (1) Met Thr His Asp Pro Val Ile Ser Leu Pro Thr Thr; (SEQ ID NO: 2) (2) Leu His Arg His Ser His Gly His Ser Tyr Lys Ser; (SEQ ID NO: 3) (3) Gly His Trp His Asn His Arg His Gln Ala Pro Leu; (SEQ ID NO: 4) (4) Lys Tyr Pro His Gln His Leu His Met His Asp Ser; (SEQ ID NO: 5) (5) Ile Gly Trp His Tyr Tyr Leu Arg Thr Gln His Ser; (SEQ ID NO: 6) (6) Tyr Pro Phe His His Lys His Trp His Arg Pro Asn; (SEQ ID NO: 7) (7) Ala Asn Ile Val Pro Ile His Ala Asn His Phe Gln; (SEQ ID NO: 8) (8) Met His Lys His Pro His Gly Ser Gln Gly Pro Thr; (SEQ ID NO: 9) and (9) Tyr Lys Leu Pro Gly His His His His Tyr Arg Pro. (SEQ ID NO: 10) In a fourth aspect, the present invention provides a method for preventing and treating the recurrence and metastasis of cancer, for preventing and treating RA and osteoarthritis, for preventing and treating HIV infection and AIDS, or for preventing and treating arteriosclerosis and dilated cardiomyopathy in a subject, by administering to the subject an effective dose of the antisense vector PCI-as HAb18G of the invention or the antagonistic peptide for HAb18G/CD147 of the invention or the combination thereof. And in a fifth aspect, the present invention provides a pharmaceutical composition for preventing and treating the recurrence and metastasis of cancer, for preventing and treating RA and osteoarthritis, for preventing and treating HIV infection and AIDS, or for preventing and treating arteriosclerosis and dilated cardiomyopathy in a subject, which comprises an effective dose of the antisense vector PCI-as HAb18G of the invention or the antagonistic peptide of the invention or the combination thereof, and a pharmaceutically acceptable carrier. |
Theft protection plug for electrical devices |
The invention relates to a theft protection plug which is mounted externally on electrical devices having a corresponding receptacle, and which, in addition to being capable of functioning as a connector plug, has a theft protection function, where the alarm electronics are encapsulated in the rear part of the theft protection plug. According to the invention, an anti-theft alarm is incorporated into a plug of any type—which thus protects the piece of equipment to which the theft protection plug is connected against theft or unauthorized removal, and can provide control over the location of different types of equipment in a chosen area. The degree of theft protection is higher if the plug is held in place in its respective receptacle by a locking mechanism. |
1. The TPP can be controlled by the piece of equipment it protects via the port to which it connected. This allows, inter alia, a reduction in the size of the unit. 2. The TPP is simple to disconnect from and connect to the piece of equipment to be protected, which is necessary for mobile equipment (portable electrical units). 3. The user has the opportunity to lock the contact with the alarm electronics in a communication port on the piece of equipment to be protected in such manner that the thief would have to destroy essential parts of the product in order to be able to steal it. 4. The alarm device is protected from an unauthorised person dampening the alarm signal by putting the alarm device in a bucket of water or the like. If the alarm device had been placed on the outside of the piece of equipment to be protected or, e.g., merely been fastened to the piece of equipment with a wire, chain, adhesive, tape or in some other manner which makes it easily accessible to the thief, the thief could have put the alarm device in a vessel containing water, thereby preventing the alarm signal from reaching the desired receiver, when he pulled it out or in some other way removed the theft protection unit from the device to be protected. 5. Physical destruction of the alarm device by using, e.g., blows of a hammer sledgehammer, by drilling, using pliers etc. will be made difficult. The device to be protected stands in the way of the tool when the attempt is made, thereby preventing the tool from reaching the critical components. The device to be protected may be destroyed instead of the alarm device during an attempt of this kind to tamper with the device 6. It is more difficult to dampen the alarm signals by covering the alarm device with alarm signal muffling material as for instance a bundle of wet cloth, metal cladding or the like: Because the alarm signal muffling material does not reach around the whole alarm device. Because the area around the theft protection plug receptacle on the electrical device is not normally completely level (because of the frame around the receptacle, other contacts/cables and chassis screws etc.), which makes it difficult to suppress the alarm signal even with an efficient muffling material. On a number of electrical devices in the area of application of the theft protection plug, there are gaps and holes around the receptacle which will admit the alarm signals into the actual casing around the device to be protected, so that the alarm signals from the alarm device are not dampened sufficiently in all instances, provided that the alarm device is located in the theft protection plug. 7. If the alarm signal is an audible signal, the sound from the signal unit will be amplified by reflection against the device chassis (in the area around the theft protection plug receptacle). Sound holes or a sound diaphragm in connection with the alarm device can be directed towards the chassis of the device, so that the amplitude of the sound waves reflected from the chassis will be amplified by interference in the points of intersection between the sound waves which cross. 8. Sound holes can be made in front of the rear part of the theft protection plug, so that when an unauthorised person begins to pull the theft protection plug out of the device to be protected, the following happens: The sound is amplified considerably in that it is passed directly from the resonance chamber in the rear part of the theft protection plug out through open holes. The sound from the resonance chamber is passed directly into the wall of the device chassis, which reflects it so that the amplitude is further amplified because of interference. According to the inventor, open sound holes are only suitable when placed in front of the rear part of the theft protection plug or in the front part of the theft protection plug, because unauthorised persons could otherwise fill the resonance chamber with sound-dampening material, as for instance foam, liquid or the like. There is 1-3 mm of air in this gap also, which lets sound out straight out of the resonance chamber even when the theft protection plug is fully inside the device receptacle. |
Colored, radiation-curable compositions |
Radiation-curable compositions, and methods of making the same, for providing a wide variety of substrates with a durable, colored coating or colorant are disclosed. The color is at least in part provided by chromophore molecules that are covalently bonded to other components within the radiation-curable composition. A telecommunication element having a durable color identifying polymeric coating thereon is also disclosed. The telecommunication element comprises an elongated communication transmission medium, such as an optical fiber or an optical fiber ribbon, and a radiation-cured polymeric coating having an identifying color applied on at least a portion of the transmission medium. |
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