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1. A bioassay system comprising: means for dropping a solution of a fluorescence-labeled target substance onto a detection substance existing in a reaction region and causing said detection substance and said target substance to interact with each other in said reaction region to prepare a reaction product; and means for condensing fluorescence, which has been emitted from said fluorescence-labeled substance by irradiating excitation light of a specific wavelength onto said reaction product, on a back side of said reaction region to determine an intensity of said fluorescence. 2. A bioassay system according to claim 1, further comprising a detecting section provided with at least a detection surface, which has been subjected to surface treatment to permit immobilization of said detection substance thereon, and a reaction region which provides a place of an interaction between said detection substance in a state immobilized on said detection surface and said target substance. 3. A bioassay system according to claim 1, wherein a light transmitting layer having translucence to both of said fluorescence and said excitation light is formed on a bottom wall of said reaction region, said excitation light is irradiated onto said detection substance from said back side of said reaction region through said light transmitting layer, and an intensity of fluorescence returned to said back side through said light transmitting layer is determined. 4. A method for manufacturing a bioassay system, which comprises arranging: means for dropping a solution of a fluorescence-labeled target substance onto a detection substance arranged in a reaction region and causing said detection substance and said target substance to interact with each other in said reaction region to prepare a reaction product; and means for condensing fluorescence, which has been emitted from said fluorescence-labeled substance by irradiating excitation light of a specific wavelength onto said reaction product, on a back side of said reaction region to determine an intensity of said fluorescence. 5. A bioassay plate comprising: a detecting section provided with at least a reaction region which provides a place of an interaction between a detection substance and a target substance; and a light transmitting layer having translucence to both of excitation light and fluorescence and formed on a bottom wall of said reaction region in said detecting section. 6. A bioassay plate according to claim 5, further comprising a detecting section provided with at least a detection surface, which has been subjected to surface treatment to permit immobilization of said detection substance thereon, and a reaction region which provides a place of an interaction between said detection substance in a state immobilized on said detection surface and said target substance. 7. A bioassay plate according to claim 5, which is a disk-shaped plate constructed such that position information and focus information on said detecting section can be optically furnished, wherein said light transmitting layer functions as a reflecting layer provided with property of causing reflection of a laser beam. 8. A process for producing a bioassay plate, which comprises: arranging a detecting section provided with at least a reaction region which provides a place of an interaction between a detection substance and a target substance; and forming a light transmitting layer, which has translucence to both of excitation light and fluorescence, on a bottom wall of said reaction region in said detecting section. 9. A bioassay system comprising: means for condensing a laser beam through a lens arranged on a back side of a bioassay plate according to claim 7, irradiating the thus-condensed laser beam onto said reflecting layer, and obtaining focus information by using a reflected laser beam reflected back from said reflecting layer, wherein using said focus information, a focusing servo control system is operated to maintain constant a distance between said lens and said disk-shaped plate. 10. A bioassay system comprising: means for condensing a laser beam through a lens arranged on a back side of a bioassay plate according to claim 7, irradiating the thus-condensed laser beam onto said reflecting layer, and obtaining tracking information by using a reflected laser beam reflected back from said reflecting layer, wherein using said tracking information, a tracking servo control system is operated to allow said lens to precisely track an array of said detecting sections. 11. A bioassay system according to claim 9, wherein said excitation light is also used as said laser beam, and vice versa. 12. A bioassay system according to claim 10, wherein said excitation light is also used as said laser beam, and vice versa. 13. A bioassay system comprising a holding means for holding a bioassay plate according to claim 7 is held facing so that said bioassay plate faces vertically upward. 14. A bioassay system comprising: a nozzle for dropping a fluorescence-labeled substance, which has been obtained by fluorescence-labeling a detection substance, into a reaction region in which a detection substance is arranged; a light source for irradiating excitation light onto a reaction product obtained by causing said detection substance and said fluorescence-labeled substance to interact with each other in said reaction region; and a condenser lens for condensing fluorescence, which is emitted from said reaction product by said excitation light, on a back side of said reaction region. 15. A bioassay process comprising: dropping a solution of a fluorescence-labeled target substance onto a detection substance existing in a reaction region and causing said detection substance and said target substance to interact with each other in said reaction region to prepare a reaction product; and condensing fluorescence, which has been emitted from said fluorescence-labeled substance by irradiating excitation light of a specific wavelength onto said reaction product, on a back side of said reaction region to determine an intensity of said fluorescence.
<SOH> BACKGROUND ART <EOH>Nowadays, molecule-integrated bioassay substrates with predetermined DNAs finely arrayed thereon by microarray techniques, which are generally called DNA chips or DNA microarrays (hereinafter collectively called “DNA chips”), are used in mutation analyses of genes, SNPs (single-base polymorphisms) analyses, gene expression frequency analyses, and the like, and have begun to find utility in a wide variety of fields such as drug developments, clinical diagnoses, pharmacogenomics and forensic medicine. This DNA chip is characterized in that it permits a comprehensive analysis of intermolecular reactions such as hybridizations, because a wide variety of numerous DNA oligosaccharide chains, cDNAs (complementary DNAs) or the like are integrated on a glass substrate or silicon substrate. An illustrative analytical procedure by a DNA chip will be described briefly. To a DNA probe immobilized on a glass substrate or silicon substrate, hybridization is performed on the substrate by subjecting mRNA, which has been extracted from cells, a tissue or the like, to PCR amplification in the presence of a fluorescence-labeled dNTP by reverse transcriptase PCR reaction or the like while integrating the fluorescence-labeled dNTP as a fluorescent probe. Fluorometry is then performed with a prescribed detector. With a view to achieving an increase in the number of target substances to be handled and improvements in detection accuracy and detection speed in a bioassay method making use of the above-described DNA chip, substrate techniques and servo control techniques fostered in connection with optical disks can be proposed. Described specifically, a solution with a detection substance contained therein is dropped to a predetermined position on a substrate while rotating the same, and is immobilized on the substrate. With the substrate kept rotating, a solution with a fluorescence-labeled target substance contained therein is then dropped onto the immobilized detection substance to cause the detection substance and the target substance to interact with each other, and the target substance not contributed to the interaction is washed off. With the substrate kept in rotation, excitation light is subsequently irradiated onto the interacted target substance, fluorescence emitted from the fluorescent label is detected by a detector, and an intensity of the fluorescence so detected is determined to analyze the binding strength between the detection substance and the target substance (see, for example, JP 2001-238674 A). The above-described bioassay method making use of a substrate (hereinafter called “disk assay” for the sake of convenience in description) has a merit in that compared with the conventional one called “DNA chip”, a huge number of detection substances and target substances can be very economically arrayed on a substrate by making use of injection molding techniques, which are employed in the preparation of substrates for optical disks, and surface microprocessing techniques. Further, it is possible to achieve an improvement in detection speed by rotating a substrate at a high speed and performing fluorometric detections with a high-sensitivity detector. There is a further merit in that, if samples of a target substance carried at a high degree of integration on a substrate as described above are repeatedly analyzed by a high-speed assay system, the results can be statistically processed to achieve an improvement in detection accuracy. In the above-described disk assay, however, a sample solution is dropped downwardly from a point above a substrate, which is held in a horizontal position, onto predetermined detecting sections (spot regions). Accordingly, a dropper (for example, an inkjet printing apparatus) is arranged above the substrate. If a construction is adopted such that a detection unit is arranged above the substrate for the detection of the intensity of fluorescence emitted from each fluorescence-labeled target substance, a problem therefore arises in the allocation of spaces for the dropper group and the detection unit, leading to a technical problem that the arrangement of the dropper group becomes complex. Under the current circumstance that the move toward more complex droppers equipped with a greater number of nozzles is expected to advance further, it is crucial to solve the above-described technical problem. In a disk assay, it is important to assure fail-free operations of a focusing servo control system, which serves to maintain constant the distance between the substrate and a condenser lens, and a tracking servo control system, which serves to cause a fluorescence condenser lens to track detection substances and target substances arrayed on the substrate, so that effects of dynamic disturbances caused by eccentricity and warpage of the substrate can be reduced. Servo control information (a servo error signal), which is required to operate these servo control systems, are obtained by irradiating a laser beam onto a surface of the disk through the condenser lens and optically and electrically processing the laser beam reflected back to the condenser lens. On the surface of the substrate, however, the detection substance and the target substance are unevenly present from the optical viewpoint. Therefore, the reflected laser beam returned as a result of upward reflection of the laser beam irradiated from a side above the substrate has been subjected to scattering. As a consequence, the servo error signal includes a large noise, developing a technical problem that the operations of the servo control systems are rendered unstable. A primary object of the present invention is, therefore, to solve the problem in allocating spaces above the detection unit and specifically, to provide a bioassay system which can stabilize servo-controlled operations with respect to a substrate.
<SOH> BRIEF DESCRIPTION OF DRAWINGS <EOH>FIG. 1 is a top plan view of a substrate ( 1 ) suited for use on a bioassay system according to the present invention. FIG. 2 is an enlarged fragmentary view of a detecting section ( 3 ) arranged on the substrate ( 1 ) and its surrounding area. FIG. 3 is a schematic illustration of a state when excitation light (P) is irradiated onto the detecting section ( 3 ) from a point above the substrate ( 1 ). FIG. 4 is a schematic illustration of a state when excitation light (P) is irradiated onto the detecting section ( 3 ) from a point below the substrate ( 1 ). FIG. 5 is a block diagram schematically showing the construction of the bioassay system (U) according to the present invention. FIG. 6A through FIG. 6E are flow diagrams schematically illustrating a bioassay procedure making use of the system (U). detailed-description description="Detailed Description" end="lead"?
Methods for verifying cardholder authenticity and for creating billing address database
Methods and associated structure for verifying the identity of a consumer in a financial card transaction. The method provides for issuing at least one authorization request through standard card transaction networks and protocols. The amount of each transaction and/or the number of transactions is preferably randomly generated. If the purported cardholder confirms the random amounts and or number of transactions the purported cardholder is identified as an authorized cardholder. The authorized transactions are never captured (completed) and hence are removed by the issuing institution in accordance with the institutions rules for the account. Since the transactions are never captured, no funds are transferred to or from the card holder's account by virtue of the verification process. Further, the transactions are communicated to the institution using standard networks and protocols available from all card-issuing (or servicing) institutions and available to all merchants that accept cards for customer purchases. Still further, the same method may be used for verifying cardholder identity in both debit and credit card proposed transactions within a near-real-time environment. A further aspect of the invention provides for verifying an e-mail address associated with the verified authorized cardholder. The verified card account information and the associated, verified e-mail address of the cardholder is recorded in a database of a secured server. A merchant confronted with a proposed transaction using a card account may request verification from the secured server. An e-mail message is sent to the verified cardholder at the verified e-mail address. The cardholder's reply then accepts of rejects the proposed card transaction.
1. A method for authenticating the identity of a consumer as an authorized cardholder of a financial card account comprising the steps of: issuing at least one card authorization request for said financial card account wherein the amount of each authorization request is randomly selected; receiving information from said consumer regarding each of said at least one authorization request; and verifying said consumer as said authenticated cardholder in response to receipt of correct information regarding said each of said at least one authorization request. 2. The method of claim 1 wherein the step of receiving said information comprises the step of: receiving information regarding the amount of said each of said at least one authorization request. 3. The method of claim 1 wherein the step of receiving said information comprises the step of: receiving information regarding the number of authorization requests issued of said at least one authorization request. 4. The method of claim 1 wherein the step of receiving said information comprises the step of: receiving information regarding the total amount of the sum of the amount of said each of said at least one authorization request. 5. The method of claim 1 wherein the step of issuing comprises the step of: issuing two authorization requests to said identified electronic account wherein the amount of each authorization request is randomly selected and the total amount of said two authorization requests equals a predetermined amount. 6. A method for authenticating the identity of a consumer as an authorized cardholder of a financial card account comprising the steps of: dynamically generating a temporary identification code; locating, in a database, information regarding said financial card account wherein said information includes an e-mail account owned by said authorized cardholder; sending an e-mail message to said e-mail account in response to locating said information, wherein said message includes said temporary identification code and wherein said message requests the e-mail message recipient to validate said card transaction request; and receiving a reply from a user of said e-mail account indicating acceptance or rejection of said card transaction, wherein said reply includes said randomly generated information, and wherein the step of authenticating comprises the steps of: determining whether said randomly generated information in said reply matches said randomly generated information in said message; and validating said card transaction in response to receipt of said reply indicating acceptance of said card transaction and in response to a determination that said randomly generated information in said message and in said reply match. 7. The method of claim 6 wherein in response to failure to locate said information in said database, the method further comprises the steps of: verifying the identity of said authorized cardholder; obtaining an e-mail account to be associated with said financial card account; and verifying said e-mail account as associated with said authorized cardholder. 8. The method of claim 7 wherein the step of verifying the identity of said cardholder comprises the steps of: issuing at least one card authorization request on said financial card account wherein the amount of each authorization request is randomly selected; receiving from said consumer information regarding each of said at least one authorization request; and verifying the identity of said consumer as an authenticated cardholder in response to receipt of correct information regarding said each of said at least one authorization request. 9. The method of claim 8 wherein the step of receiving said information comprises the step of: receiving information regarding the amount of said each of said at least one authorization request. 10. The method of claim 8 wherein the step of receiving said information comprises the step of: receiving information regarding the number of authorization requests issued of said at least one authorization request. 11. The method of claim 8 wherein the step of receiving said information comprises the step of: receiving information regarding the total amount of the sum of the amount of said each of said at least one authorization request. 12. The method of claim 8 wherein the step of issuing comprises the step of: issuing two authorization requests to the financial card account wherein the amount of each authorization request is randomly selected and the total amount of said two authorization requests equals a predetermined amount. 13. The method of claim 8 wherein the step of verifying said e-mail account comprises the steps of: presenting a Web page to a user of said e-mail account; sending an e-mail message to said e-mail account wherein said message includes an authorization code; and receiving said authorization code from said user in a field of said Web page. 14. A system for authenticating the identity of a consumer as an authorized cardholder of a financial card account comprising: means for issuing at least one card authorization request for said financial card account wherein the amount of each authorization request is randomly selected; means for receiving information from said consumer regarding each of said at least one authorization request; and means for verifying said consumer as said authenticated cardholder in response to receipt of correct information regarding said each of said at least one authorization request. 15. The system of claim 14 wherein the means for receiving said information comprises: means for receiving information regarding the amount of said each of said at least one authorization request. 16. The system of claim 14 wherein the means for receiving said information comprises: means for receiving information regarding the number of authorization requests issued of said at least one authorization request. 17. The system of claim 14 wherein the means for receiving said information comprises: means for receiving information regarding the total amount of the sum of the amount of said each of said at least one authorization request. 18. The system of claim 14 wherein the means for issuing comprises: means for issuing two authorization requests to said identified electronic account wherein the amount of each authorization request is randomly selected and the total amount of said two authorization requests equals a predetermined amount.
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>FIG. 1 is a flowchart describing a method of the present invention operable to verify the identity of a purported cardholder. FIG. 2 is a flowchart describing a method of the present invention operable to verify an e-mail address to be associated with an authorized cardholder of a card account. FIG. 3 is a flowchart of a method of the present invention operable to verify a particular purchase transaction using the verified account and e-mail information determined in accordance with methods of the present invention. FIG. 4 is a block diagram of systems and data flow there between for systems involved in purchase transaction in accordance with the methods of the present invention. FIG. 5 is a block diagram of systems and data flow there between for systems involved in verification of a purported cardholder's identity as an authorized cardholder in accordance with the present invention. detailed-description description="Detailed Description" end="lead"?
Method for the detection of a polymorphism in cpb2
This invention relates to polymorphisms in the human CPB2 gene and corresponding novel allelic polypeptides encoded thereby. The invention also relates to methods and materials for analysing allelic variation in the CPB2 gene, and to the use of CPB2 polymorphism in treatment of diseases with CPB2 drugs.
1. A method for the detection of a polymorphism in CPB2 in a human, which method comprises determining the sequence of the human at at least one of the following polymorphic positions: positions 310, 549, 682 and 772 in CPB2 polynucleotide as defined by the position in SEQ ID NO: 1; and position 177 in CPB2 polypeptide defined by position in SEQ ID NO: 2. 2. A method according to claim 1 which comprises detection of any one of the following six haplotypes: 310 524 682 697 772 1059 Haplotype allele allele allele allele allele allele 1 C G A C C T 2 C A G C C T 3 C G A C T C 4 T G A T C T 5 C G A C C C 6 C A G C C C 3. Use of a method as defined in claim 1 to assess the pharmacogenetics of a CPB2 drug. 4. A polynucleotide comprising at least 20 bases of the human CPB2 gene and comprising an allelic variant selected from any one of the following: Position in Variant SEQ ID NO 1 allele 310 T 549 G 682 A 772 T 5. A polynucleotide according to claim 4 comprising any one of the following CPB2 haplotypes with reference to positions in SEQ ID NO 1: 310 524 682 697 772 1059 Haplotype allele allele allele allele allele allele 1 C G A C C T 2 C A G C C T 3 C G A C T C 4 T G A T C T 5 C G A C C C 6 C A G C C C 6. A nucleotide primer which can detect a polymorphism as defined in claim 1. 7. An allele specific primer capable of detecting a CPB2 gene polymorphism defined in claim 1. 8. An allele-specific oligonucleotide proA polynucleotide comprising at least 20 bases of the human CPB2 gene and comprising an allelic variant selected from any one of the following: Position in Variant SEQ ID NO 1 allele 310 T 549 G 682 A 772 T 9. Use of a CPB2 polymorphism as defined in claim 1 as a genetic marker in a linkage study. 10. A method of treating a human in need of treatment with a CPB2 drug in which the method comprises: i) detection of a polymorphism in CPB2 in the human, which detection comprises determining the sequence of the human at one or more of the following positions: positions 310, 549, 682 and 772 in CPB2 polynucleotide as defined by the position in SEQ ID NO: 1; and position 177 in CPB2 polypeptide defined by position in SEQ ID NO: 2 and determining the status of the human by reference to polymorphism in CPB2; and ii) administering an effective amount of the drug. 11. An allelic variant of human CPB2 polypeptide comprising a glycine at position 177 of SEQ ID NO 2; or a fragment thereof comprising at least 10 amino acids provided that the fragment comprises at least one allelic variant. 12. An antibody specific for an allelic variant of human CPB2 polypeptide as defined in claim 11.
Automatic device for turning the pages of a bound document
The invention concerns an automatic device for turning the pages of a bound document comprising a support (11) whereon is arranged the document, means (14) for separating by suction one page from the other pages to be turned and for turning the separated page to bring it on a pile of turned pages. The support (11) consists of two mobile trays (16) mutually linked by a rod (17), each tray consisting of a box (26) whereof the upper side is provided with small holes (27) cooperating with the suction intake orifices (28). The means (14) for separating the document pages consist of suction means (34), displaced by the combination of a vertical movement and a horizontal movement, consisting of the perforated recessed element (36) provided with a diaphragm (37). Said perforated element (36) is provided with holes (38) and the diaphragm (37) comprises two mobile parts for orienting the direction of the suction flow and modify its flow rate and its speed. Said suction means (34) also comprise mobile closure means (44) for longitudinally delimiting the suction surface. The means (14) for turning a page of the document comprise two mobile transparent plates (30) arranged in parallel planes. Control means (13) enable to measure the dimensions of the document and the number of pages turned.
1. An automatic device for turning the pages of a bound document, comprising: support (11) on which the document is placed, first means (14) arranged for separating one page from the other pages of the document by suction, and second means (12) for holding the pages which are to be turned and for turning the separated page in order to bring it onto a stack of turned pages, said support (11) being formed by two movable trays (16) connected together by at least one rod (17), and with the document being placed in a roughly horizontal plane so as to be set on the pages forming the cover of the document, the visible pages being presented towards the top, wherein the first means for separating the pages of the document entail perforated hollow element (36) which houses diaphragm (37) formed by two parts (39, 40) which are movable with respect to one another, each of these parts being provided with an open zone and a closed zone so as to be able to orient the direction of the suction flow and to change its flow rate and its speed by movement of one of the parts with respect to the other. 2. A device according to claim 1 wherein said perforated hollow element (36) is movable with respect to trays (16). 3. A device according to claim 1 wherein said perforated hollow element (36) is provided with closing means (44) arranged so as to longitudinally limit the suction surface. 4. A device according to claim 1 wherein said rod (17) pivots around a horizontal shaft (21), this horizontal shaft being vertically movable, and by the fact that compression component (9) is arranged so as to counterbalance the weight of the elements supported by said horizontal shaft (21) 5. A device according to claim 1 wherein said trays (16) have means (25) for immobilization of their relative position. 6. A device according to claim 5 wherein said each tray (16) is connected with horizontal return element (19) arranged so as to allow centering of the document. 7. A device according to claim 1 wherein each tray (16) is formed by box (26) having a planar upper surface provided with holes (27) and at least one suction intake (28). 8. A device according to claim 7 wherein the upper surface of boxes (26) is provided with a mask adapted to the size of the document whose pages are to be turned. 9. A device according to claim 1 wherein the second means for turning a page of the document comprise at least one transparent plate (30) which is movable with respect to trays (16). 10. A device according to claim 9 wherein the second means for turning a page of the document comprise two transparent plates arranged in parallel planes, which are movable with respect to one another and with respect to trays (16). 11. A device according to claim 1 further comprising a means of control (13) arranged so as to measure the dimensions of the document and the number of pages taken. 12. A device according to claim 1 further comprising a means (50) for measurement of the suction pressure in perforated hollow element (36). 13. A device according to claims 9 wherein at least one transparent plate (30) has, on an edge roughly parallel to the binding of the document, duct (33) arranged so as to expel air in the direction of the pages of said document. 14. A device according to claim 13 wherein the second means for turning page (54) of the document comprise one movable duct (53) perpendicular to the binding of the document and arranged so as to expel air in the direction of the pages of said document. 15. A device according to claim 1 wherein said perforated hollow element (36) is equipped with a removable filtering element in order to protect the turned pages from contamination. 16. A device according to claim 1 further comprising means (15) for recording images of the pages of the document which is being dealt with.
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>The present invention and its advantages will be better understood with reference to a preferred but non-limiting embodiment of the invention and to the appended drawing in which: FIG. 1 is an overall diagrammatic view of the device according to the present invention, FIG. 2 is a section of a part of the device of FIG. 1 , and FIGS. 3 a and 3 b are sections of the element of FIG. 2 in different positions. detailed-description description="Detailed Description" end="lead"?
Wobble piston pump with carbon graphite cylinder
A two-cylinder axial displacement wobble piston air compressor/vacuum pump (10) has a pair of open-ended cylinder sleeves (36) lining the pump chambers (34) of the housing (16).The cylinder sleeves are made of a pressed powder carbon graphite material that is impregnated with a phenolic resin. The wobble pistons (18) include a piston cup (48) made of a PTFE material and having a diameter sized to abut the bore of the cylinder throughout the compression and suction strokes of the piston.
1. In a pump having a housing containing a rotatable shaft extending into a pump chamber having a cylinder through which travels a wobble piston eccentrically mounted at one end to the shaft and having a head at an opposite end that is pivotal with respect to a cylinder axis, the improvement wherein the cylinder is a carbon graphite composition. 2. The improvement of claim 1, wherein the cylinder is an open-ended cylindrical sleeve separate from the housing lining the inside of the pump chamber. 3. The improvement of claim 2, wherein the cylinder is a pressed carbon graphite powder. 4. The improvement of claim 3, wherein the carbon graphite powder is impregnated with a thermoset resin. 5. The improvement of claim 4, wherein the thermoset resin is a phenolic. 6. The improvement of claim 1, wherein the piston head includes a piston cup having a periphery with a diameter larger than the piston head sized to abut an inner diameter of the cylinder throughout compression and suction strokes. 7. The improvement of claim 1, wherein the housing includes multiple pump chambers, each having an associated wobble piston and graphite cylinder. 8. A pump, comprising: a housing defining a pump chamber and housing a rotatable shaft extending into the pump chamber; a carbon graphite cylinder lining the inside of the pump chamber; and a wobble piston mounted to the shaft so as to reciprocate within the cylinder and pivot, with respect to a cylinder axis, wherein the piston includes a piston cup fixedly mounted to a head of the piston opposite its connection to the shaft and having a periphery with a diameter sized to abut an inner diameter of the cylinder throughout compression and suction strokes of the piston. 9. The pump of claim 8, wherein the piston cup is a PTFE composition. 10. The pump of claim 9, wherein the cylinder is a pressed carbon graphite powder. 11. The pump of claim 10, wherein the carbon graphite powder is impregnated with a phenolic resin. 12. The pump of claim 8, wherein the housing includes multiple pump chambers, each having an associated wobble piston and carbon graphite cylinder.
<SOH> BACKGROUND OF THE INVENTION <EOH>This invention relates to pumps and in particular to pumps with improved piston-cylinder arrangements. Pistons pumps have one or more pistons is eccentrically mounted on a rotatable shaft to reciprocate the pistons in a cylindrical pump chamber. As the pistons reciprocate, a suitable valve assembly, having intake and exhaust valves which alternately open and close during the suction and pump strokes, moves air into and out of the pump chamber. As the pistons reciprocate within the cylinders, the pistons (or circumferential piston rings) contact the inner walls of the cylinders. Friction generates heat, which can degrade the cylinders and/or the pistons (or piston rings) over time. The thermal effects can also cause dimensional changes in the pistons or cylinders which are designed to interact within tight tolerances. Various techniques have been developed to reduce these adverse effects. For example, U.S. Pat. No. 1,467,255 discloses a low friction piston composed of monolithic carbon graphite. U.S. Pat. No. 2,792,265 discloses a piston-cylinder arrangement in which the cylinder includes cooling fins, and the piston is constructed with a cast iron core supporting a carrying ring, sealing rings and a sleeve made of self-lubricating material, such as carbon. U.S. Pat. No. 2,860,935 discloses a complex piston arrangement with adjustable rings. These techniques are not applicable to air pumps having axial displacement wobble-type pistons that pivot as they reciprocate. Wobble pistons typically have a thin-cup element mounted to the head of the piston. The outer periphery of the cup slides against the inner diameter of the cylinder. As the piston wobbles, the periphery of the cup flexes to accommodate the pivot of the piston and press tightly against the cylinder to provide a tight seal. Thus, an improved technique is needed for use with wobble-type pistons.
<SOH> SUMMARY OF THE INVENTION <EOH>The invention is a pump providing an improved wobble piston and cylinder arrangement. Specifically, the invention provides a pump with a housing containing a rotatable shaft extending into a pump chamber having a carbon graphite cylinder through which travels a wobble piston eccentrically mounted at one end to the shaft and having a head at an opposite end that is pivotal with respect to a cylinder axis. In one form, the cylinder is an open-ended cylinder sleeve separate from the crankcase and lining the pump chamber. The cylinder sleeve is preferably a pressed powder carbon graphite material that is impregnated with a thermoset resin, such as a suitable phenolic resin. In another form, the invention provides a pump having a housing defining a pump chamber and containing a rotatable shaft extending into the pump chamber. The pump chamber is lined with a carbon graphite cylinders A wobble piston is mounted to the shaft so as to reciprocate within the cylinder and pivot with respect to a cylinder axis. The piston includes a piston cup fixedly mounted to a head of the piston opposite its connection to the shaft. The piston cup has a periphery larger than the piston head so as to abut an inner diameter of the cylinder throughout compression and suction strokes of the piston. The piston cup is preferably a PTFE composition. A multi-cylinder pump, such as a two or four cylinder pump, can also be provided with the crankcase defining multiple pump chambers, each having an associated wobble piston and carbon graphite cylinder. The carbon graphite cylinder can be machined to precise dimensions for interface with the contacting portion of the piston. The graphite material has lower thermal expansion and friction coefficients compared to standard aluminum cylinders, thereby reducing wear and making the cylinder more dimensionally stable. The cylinder also reduces the operating temperatures of the cup, which reduces fatigue and creep that could otherwise lead to permanent deformation, thereby prolonging the life of the cup. The phenolic resin makes the cylinder air tight by filling any voids that may have been present in the graphite. These and other advantages of the invention will be apparent from the detailed description and drawings.
Method and system for cooling the clutch system of a transmission
A method and apparatus for reducing the thermal load on a motor vehicle clutch system. The clutch includes at least a pressure plate, a clutch disk, and a flywheel, by way of which a torque is transmitted. The friction forces that exist on the respective friction surfaces of the clutch disk are unevenly distributed. The clutch is cooled by a flow of cooling air that is led through the clutch bell that encloses the clutch and that defines a housing. The cooling air is conducted from the existing ventilation air inlets of the vehicle, and a jet pump arranged in the exhaust system is disclosed for withdrawing the cooling air from the clutch housing.
1. A method for reducing the thermal load in a clutch system that includes at least a pressure plate, a clutch disk, and a flywheel, said method comprising the steps of: transmitting a torque between respective friction surfaces of the pressure plate, the clutch disk, and the flywheel, and unevenly distributing frictional torque that acts at each friction surface of the clutch disk. 2. A method in accordance with claim 1, including the step of providing different friction linings with different coefficients of friction on respective opposite friction surfaces of the clutch disk. 3. A method in accordance with claim 1, including the step of providing a lower coefficient of friction on a pressure-plate-side friction surface of the clutch disk than on a flywheel-side friction surface of the clutch disk, so that a smaller amount of frictional energy is introduced into the pressure plate than into the flywheel. 4. A method in accordance with claim 3, including the step of providing on the flywheel-side of the clutch disk a friction lining having a higher coefficient of friction at increasing temperature. 5. A method in accordance with claim 1, including the step of providing identical friction linings on respective sides of the clutch disk, and providing different friction characteristics at a pressure-plate to clutch disk interface and at a flywheel to clutch disk interface for a desired frictional torque distribution. 6. A method in accordance with claim 5, wherein the friction characteristics of at least one of the pressure plate and the flywheel are provided by a combination of steel and aluminum friction surfaces. 7. A method in accordance with claim 1, wherein the clutch disk has identical friction linings on respective sides thereof and each friction exhibits such interface has a temperature dependence in the case of identical to provide a lower coefficient of friction with increasing temperature, whereby a higher temperature occurs at the pressure plate than at the flywheel, so that a desired coefficient of friction difference is realized at the pressure plate and the flywheel sides of the clutch disk. 8. A method in accordance with claim 1, wherein a higher coefficient of friction exists at a friction surface on the pressure-plate side of the clutch disk than at a friction surface on the flywheel side when the pressure plate is cooled. 9. A method in accordance with claim 8, wherein a temperature-resistant friction lining is utilized as the friction lining at each friction surface. 10. A method in accordance with claim 1, including the step of introducing a cooling airflow into a housing that surrounds the clutch. 11. A method in accordance with claim 10, including the step of utilizing at least one existing air inlet for the ventilation of the interior of a motor vehicle as an inlet for the cooling airflow, and conducting the cooling airflow through the clutch housing. 12. A method in accordance with claim 10, wherein cooling airflow is withdrawn from the housing to the environment through an existing exhaust system of the vehicle. 13. A method in accordance with e claim 10, wherein the cooling airflow is provided by a pump means positioned in the exhaust gas flow of the exhaust system. 14. A method in accordance with claim 13, wherein the pump means is a jet pump. 15. A method in accordance with claim 10, including the step of Periodically interrupting the cooling airflow by a blocking means to allow a stationary exhaust gas measurement 16. A method in accordance with claim 15, wherein the blocking means is a shutter. 17. A method in accordance with claim 10, wherein the clutch is included in a power train that includes one of a load-shift transmission and a double-clutch transmission. 18. A system for cooling a clutch in a motor vehicle power train, said system comprising: a flywheel, a clutch disk, and a pressure plate, wherein the flywheel and the pressure plate frictionally engage respective opposed surfaces of the clutch disk, a clutch bell that surrounds at least the clutch disk and the pressure plate as a clutch housing, and means for introducing a cooling airflow into the clutch housing. 19. A system in accordance with claim 18, wherein the means for introducing cooling airflow includes as an air inlet at least one existing air inlet for the ventilation of the interior of the motor vehicle. 20. A system in accordance with claim 18, wherein an existing exhaust system of the motor vehicle is in communication with the clutch housing for withdrawal of cooling airflow from the clutch housing. 21. A system in accordance with one claim 20, including pump device is means in the exhaust gas flow of the exhaust system for producing the cooling airflow. 22. A system in accordance with claim 21, wherein the pump means includes at least one jet pump. 23. A system in accordance with claim 20, including blocking is means provided in the exhaust system for blocking flow into an exhaust gas stream of cooling airflow from the clutch housing. 24. A system in accordance with claim 23, wherein the blocking means is a shutter. 25. A system in accordance with claim 18, wherein the system is incorporated into a motor vehicle power train that includes a high-performance clutches clutch and at least one of a load-shift transmission and a double-clutch transmission.
<SOH> BACKGROUND OF THE INVENTION <EOH>1. Field of the Invention The present invention relates to a method for the reduction of thermal loads and a method for cooling clutch systems, as well as a system therefor. 2. Description of the Related Art It has been shown that the thermal economy in clutch systems, such as, for example, a dry friction clutch, is problematic, especially at high power input. A thermal overload is especially to be suspected in a load-shift clutch of an uninterruptible transmission (USG). The components of the clutch, especially the friction lining, have a limited temperature resistance, and the energy input is very high in relation to the available space, whereby the heat transfer to the environment is too low. In addition, the pressure plate, for example, has a smaller heat capacity in contrast to the flywheel of the clutch. Furthermore, the heat flow to the surrounding parts is relatively low and the heat transfer to the surrounding air within the clutch bell housing is also low. Thus, there is a limit relative to the operation of the clutch system as a result of the expected temperature rise in known clutch systems, especially of the pressure plate. Therefore, especially in load-shift transmissions, it is a necessity that the temperature load on the clutch be lowered by cooling measures. In the case of a so-called inline transmission, for example for a rear drive motor vehicle, an open type of construction, which of a certain size makes cooling possible (tunnel assembly, water spray, near the exhaust system), can only be realized with limitations. The object of the present invention is directed to a method and a system of the above-described type that makes possible the optimal cooling of a clutch system of a power train, so that the operating conditions of the clutch system in particular are improved.
<SOH> SUMMARY OF THE INVENTION <EOH>The object of the invention is particularly achieved by providing a method for the reduction of the thermal load on a clutch system with which torque is transmitted. The clutch system includes at least a pressure plate, a clutch disk, and a flywheel, whereby the frictional torque that exists at the time on the friction surfaces of the clutch disk is unevenly distributed. The frictional load generated in the clutch system is determined by the frictional torque that acts and the relative speed. In known clutch systems an identical speed condition at both friction surfaces of the clutch disk is preferred. A solution can consequently lie in producing uneven frictional torques on the respective friction surfaces. In that way, the pressure plate, for example, can be supplied with a smaller portion of the frictional energy that occurs, so that the thermal load is reduced. Within the scope of the invention a further embodiment can be provided in which different friction linings with different coefficients of friction can be utilized at the two friction surfaces of the clutch disk. The frictional load that is produced is thereby introduced unequally to the two friction surfaces by providing different friction parameters at both frictional sides of the clutch disk. The frictional torque that is generated depends on the effective friction radius, the contact pressure of the pressure plate, and the coefficient of friction of the respective friction surfaces. Influencing the clutch system coefficient of friction conditions provides the possibility to suitably distribute the thermal load. It is also conceivable that the other influence values could be changed. In the method in accordance with the invention several possibilities are provided for influencing the coefficient of friction conditions in the clutch system, which are described below. For example, a lower coefficient of friction can be utilized on the pressure-plate-side friction surface of the clutch disk than on the flywheel-side friction surface, so that a lesser amount of frictional energy is introduced on the pressure plate than on the flywheel. In that way, a desired distribution of the frictional load can be realized. Thereby, in an advantageous way, lower thermal loads arise on the pressure plate. In accordance with the invention, by the use of different friction linings on the clutch disk it can be provided that the respective friction partners on the flywheel-side are selected in such a way that a higher coefficient of friction arises when the temperature increases. For example, the clutch disk can have different friction linings on its two friction surfaces. The friction partners on the flywheel-side have such a type of temperature dependence that a higher coefficient of friction arises with increasing temperature. If, as expected, a higher temperature arises at the friction point during the operation of the clutch, the coefficient of friction on the pressure plate side decreases, so that the desired coefficient of friction difference is adjusted. In addition, in accordance with the invention it can be provided that in the case of identical friction linings on the clutch disk two friction partners with different characteristics are utilized, so that the desired coefficient of friction difference or frictional torque distribution results. For example, the pressure plate and the flywheel can be made from combinations of the materials steel and aluminum. Furthermore, in the case of identical friction linings on the clutch disk, it can be provided that the respective friction partners have such a temperature dependence that a lower coefficient of friction arises with increasing temperature, whereby a higher temperature exists on the pressure plate than on the flywheel, so that the desired coefficient of friction difference is realized. The previously-described possibilities can also be arbitrarily combined in order to further improve the proposed method. Alternatively, in the method in accordance with the invention it can also be provided that a higher coefficient of friction is utilized on the pressure-plate-side friction surface of the clutch disk, for example, than on the flywheel-side friction surface if the pressure plate is suitably cooled. In that way, under certain circumstances, namely when cooling measures are carried out at the pressure plate, a reverse friction load distribution is also conceivable. Thereby, a higher temperature of the pressure plate, for example, can lead to an altogether better heat elimination at the clutch system by reason of a higher temperature differential. At the same time, it must be noted, however, that a temperature-resistant friction lining must be utilized at each friction surface as the friction lining. Furthermore, the underlying object of the invention is also especially achieved in that a method is proposed for cooling the clutch in a power train of a motor vehicle, in which a flow of cooling air for the clutch is utilized. Furthermore, particularly for carrying out the method, a system for cooling the clutch of a power train of a motor vehicle is proposed, wherein a flow of cooling air is provided that can be conducted through the clutch bell surrounding the clutch as a housing. Advantages and additional embodiments of the system and the method in accordance with the invention for cooling the clutch of a power train are described in greater detail below. In accordance with an advantageous further development of the invention, the already-existing air inlets of the motor vehicle, for example for the ventilation of the interior, can be utilized as a cooling airflow to cool the clutch. Preferably, the flow of cooling air can be guided through the clutch bell that surrounds the clutch as a housing. For that purpose, the inlets, for example, could be designed and dimensioned accordingly. All together, the advantage of using already-existing air inlets is that, for example, filters, dirt pans, water drains, and the like, only have to be provided once in a motor vehicle because of their dual usage. In addition, by means of the air passages provided, acoustic advantages can be realized in contrast with open clutches. Within the scope of an arrangement of the invention, the exiting cool air flow can be carried off to the environment using the existing exhaust gas system of the motor vehicle. The cool air flow can thus be carried off through the exhaust gas system together with the exhaust gas. Especially in motor vehicles with rear drive, the exhaust system is located near the transmission. In accordance with that arrangement there results the advantage that in that way clutch noises are not considered to be disturbing in the surrounding area because of the muffler. Preferably, the cool air flow can be provided by a pump device provided in the exhaust gas flow of the exhaust gas system. The cool airflow can thereby be drawn off through the clutch bell. The pump device can especially be a jet pump, or the like, which is preferably provided in the exhaust gas stream. In that way, other necessary (active) cooling measures can be avoided. It is also possible that the cool airflow is interrupted at least periodically through a shutter device in the exhaust system, so that an independent stationary exhaust gas measurement is made possible. Preferably, at least a flap, or the like, can be utilized as a shutter device. Preferably, the proposed system and method can be utilized in high performance clutches, especially in a load-shift transmission (USG) and/or a double-clutch transmission (DKG).
Collapsible container for the transport of air cargo
What is disclosed is a collapsible container for the transport of air cargo, consisting of a bottom panel, a cover panel and four side walls which are detachably connected to said bottom panel and said cover panel, wherein the bottom panel and the cover panel adjoin each other in the collapsed position of the container, retaining the four side walls between them. The bottom panel is provided with profiled members at two opposed first edges, which profiled members can be inserted into complementary profiled members at two corresponding opposed first edges of the cover panel by moving said profiled members in longitudinal direction relative to each other, and two first opposed side walls are provided with profiled members at their horizontal edges, which profiled members are complementary to the corresponding first opposed edges, which profiled members can be inserted into complementary profiled members at the corresponding vertical side walls by moving said profiled members in longitudinal direction relative to each other.
1. A collapsible container for the transport of air cargo, comprising of a bottom panel, a cover panel and four side walls which are detachably connected to said bottom panel and said cover panel, wherein the bottom panel and the cover panel adjoin each other in a collapsed position of the container, retaining the four side walls between them, and wherein the bottom panel is provided with profiled members at two opposed first edges, which profiled members can be inserted into complementary profiled members at two corresponding opposed first edges of the cover panel by moving said profiled members in longitudinal direction relative to each other; two first opposed side walls are provided with profiled members at their horizontal edges, which profiled members are complementary to the corresponding profiled members of the bottom panel and the cover panel, and in that said first opposed side walls are provided with profiled members at their vertical edges, which profiled members can be inserted into complementary profiled members at the corresponding vertical edges of two second opposed side walls by moving said profiled members in longitudinal direction relative to each other. 2. The container according to claim 1, and further comprising locking devices adapted to lock component parts of the container in the fully collapsed position (engagement between corresponding profiled members of the bottom panel and the cover panel) or in the fully unfolded position (engagement between corresponding profiled members of the bottom panel and the cover panel and of the first side walls and engagement between corresponding profiled members of the first and the second side walls). 3: The container according to claim 2, wherein the bottom panel on the one hand and a corresponding second side wall on the other hand are provided with identical profiled members at one of the second edges and at the horizontal edge facing away from the bottom panel, respectively, while the cover panel is likewise provided with a profiled member at a corresponding second edge, wherein the container further comprises a locking strip comprising corresponding, complementary profiled members can be insertable into the aforesaid profiled members of the bottom panel and the cover panel (in the collapsed position), or into the aforesaid profiled members of said second side wall and the cover panel (in the unfolded position), and wherein locking strip includes a locking mechanism adapted to lock the locking strip in its inserted position. 4: The container according to claim 3, wherein the locking mechanism comprises a locking pin to be operated by a key, which, in a locking position, effects a connection between the locking strip and an adjacent part of the container. 5: The container according to claim 4, wherein the cover panel is provided with a profiled member at its rear second edge (seen in the direction of movement for unfolding), which profiled member is capable of hooked engagement of a corresponding profiled member of the bottom panel or of the upper horizontal edge of the corresponding second side wall. 6: The container according to claim 5, wherein the side walls each consist of at least two side wall segments. 7: The container according to claim 6, wherein the side walls segments of the first side walls are provided with corresponding profiled members at their adjoining horizontal edges, which profiled members can be slid into each other in their longitudinal direction. 8: The container according to claim 1, wherein the bottom panel includes quick-action couplings. 9: The container according to claim 1, wherein the cover panel is provided with a profiled member at its rear second edge (seen in the direction of movement for unfolding), which profiled member is capable of hooked engagement of a corresponding profiled member of the bottom panel or of the upper horizontal edge of the corresponding second side-wall. 10: The container according to claim 2, wherein the cover panel is provided with a profiled member at its rear second edge (seen in the direction of movement for unfolding), which profiled member is capable of hooked engagement of a corresponding profiled member of the bottom panel or of the upper horizontal edge of the corresponding second side wall. 11: The container according to claim 3, wherein the cover panel is provided with a profiled member at its rear second edge (seen in the direction of movement for unfolding), which profiled member is capable of hooked engagement of a corresponding profiled member of the bottom panel or of the upper horizontal edge of the corresponding second side wall. 12: The container according to claim 1, wherein the side walls each consist of at least two side wall segments. 13: The container according to claim 2, wherein the side walls each consist of at least two side wall segments. 14: The container according to claim 3, wherein the side walls each consist of at least two side wall segments. 15: The container according to claim 4, wherein the side walls each consist of at least two side wall segments.
<SOH> BACKGROUND OF THE INVENTION <EOH>The invention relates to a collapsible container for the transport of air cargo, consisting of a bottom panel, a cover panel and four side walls which are detachably connected to said bottom panel and said cover panel, wherein the bottom panel and the cover panel adjoin each other in the collapsed position of the container, retaining the four side walls between them. In a fully unfolded position, such a container has a certain transport volume, which will generally be adapted to the standard dimensions of the cargo space of an aeroplane. When the container is not being used, it can be collapsed, in which position the bottom panel and the cover panel adjoin each other, retaining the four side walls between them. In this collapse position, the container has a minimum transport volume. A known container of the type to which the present invention relates is disclosed in international patent application WO 01/05668.
<SOH> SUMMARY OF THE INVENTION <EOH>It is an object of the present invention to further improve a collapsible container of the present type. In order to accomplish that objective, the collapsible container according to the invention is includes: a bottom panel that is provided with profiled members at two opposed first edges, which profiled members can be inserted into complementary profiled members at two corresponding opposed first edges of the cover panel by moving said profiled members in longitudinal direction relative to each other; two first opposed side walls that are provided with profiled members at their horizontal edges, which profiled members are complementary to the corresponding profiled members of the bottom panel and the cover panel, and in that said first opposed side walls are provided with profiled members at their vertical edges, which profiled members can be inserted into complementary profiled members at the corresponding vertical edges of two second opposed side walls by moving said profiled members in longitudinal direction relative to each other. In the fully collapsed position, in which the four side walls are retained between the bottom panel and the cover panel, the bottom panel engages into the complementary profiled members of the cover panel with the aforesaid profiled members. Said joining of the bottom panel and the cover panel takes place by moving the two panels relative to each other. When the container is to be brought into its fully collapsed position (i.e. the position of use), the bottom panel is slid out of the cover panel, after which the profiled members of the two first side walls are slid into the profiled members at the first edges of the bottom panel. Then the profiled members at the vertical edges of the second side walls are slid into the profiled members of the vertical edges of the first side walls. Finally, the cover panel can be slid into the upper horizontal profiled members of the first side walls, so that the container is in principle ready for use. It is noted within the framework of this invention that the term “collapsible” does not mean that the container comprises parts that can be folded about hinges. The term is only used to indicate that the container can be moved from a position in which it takes up relatively little space (the “collapsed position”) to a position in which it takes up a large volume (the “unfolded position”). As a result of the mating interaction between complementary profiled members (in which longitudinal movements between adjoining parts take place), the transition of the collapsible container from one position to the other position can take place in an extremely quick and simple manner. Special tools are not required, nor is specialist knowledge on the part of the user. In a preferred embodiment of the container according to the invention, locking devices are used for interlocking the component parts of the container in the fully collapsed position (engagement between corresponding profiled members of the bottom panel and the cover panel) or in the fully unfolded position (engagement between corresponding profiled members of the bottom panel and the cover panel and of the first side walls and engagement between corresponding profiled members of the first and the second side walls). As a result of the use of such locking devices, the contents (air cargo) of the container are protected against theft in the fully unfolded position thereof. Only authorized persons can remove the locking devices. Such a locking devices can serve a useful purpose in the collapsed position of the container as well, since it can prevent theft of parts of the container. Such locking devices can be realised in that the bottom panel on the one hand and a corresponding second side wall on the other hand are provided with identical profiled members at one of the second edges and at the horizontal edge facing away from the bottom panel, respectively, whilst the cover panel is likewise provided with a profiled member at a corresponding second edge, wherein a locking strip comprising corresponding, complementary profiled members can be inserted into the aforesaid profiled members of the bottom panel and the cover panel (in the collapsed position), or into the aforesaid profiled members of said second side wall and the cover panel (in the unfolded position), which locking strip is fitted with a locking mechanism for locking the locking strip in its inserted position. After the cover panel has been slid onto the bottom panel in the above-described manner, or after the cover panel has been combined with the bottom panel, with the interposition of the four side walls, into a container, the locking strip is finally inserted into said profiled members, thus functioning as a closing member, as it were. The locking strip, when fitted, prevents the cover panel being moved with respect to the bottom panel for disassembly of the container. The locking strip itself is secured against being removed by the aforesaid locking mechanism. The locking of the locking strip can take place in an advantageous manner, in that the locking mechanism comprises a locking pin to be operated by a key, which, in a locking position, effects a connection between the locking strip and an adjacent part of the container. Movement of the locking strip with respect to an adjacent part of the container is not possible in a locking position of the locking pin, so that the cover panel cannot be moved with respect to the bottom panel (or with respect to the side walls) for the purpose of disassembling the container, either. The locking strip cannot be removed until the locking pin has been moved to a releasing position by means of the key, after which the cover panel and possibly the side walls can be moved apart, thus making it possible to disassemble the container and, if desired, bring it into the collapsed position. The aforesaid key, and consequently the locking mechanism, may be designed as an entirely mechanical unit, but also as an entirely or partially electric or electronic unit. The use of a smart chip with all the possibilities it provides is within the bounds of the possible. In this connection, the integration of a follow function, in which the position of the container can be established at all times, for example via GPS may be considered. In the foregoing, the use of mating profiled members being movable in longitudinal direction relative to each other has been discussed. According to another possibility, however, the cover panel is provided with a profiled member at its rear second edge (seen in the direction of movement for unfolding), which profiled member is capable of hooked engagement of a corresponding profiled member of the bottom panel or of the upper horizontal edge of the corresponding second side wall. When the cover panel is moved into the corresponding profiled members of the bottom panel or of the second side walls by means of its profiled members at the first edges, the profiled member will engage the aforesaid corresponding profiled member of the bottom panel or of the second side wall in question at a right angle, as a result of which the integrity of the container in this position (the collapsed position of the unfolded position) is further improved. Whereas a container having four side walls has so far been discussed in the foregoing, it should be noted that it is possible within this framework for each side wall to consist of at least two side wall segments. If the side walls segments of the first side walls are provided with corresponding profiled members at their adjoining horizontal edges, for example, which profiled members can be slid into each other in their longitudinal direction, the side wall segments form smaller-scale copies of the side walls themselves, as it were. If not all the side wall segments are used, a container having a smaller height can be formed. In this way, a container is obtained whose height can be adapted to the purpose for which it is intended. The container may furthermore be provided with quick-action couplings at its bottom panel, which are capable of effecting a connection to fixing elements present in a cargo space (such as the cargo space of an aeroplane). In this way, the container can be placed or be removed very quickly. The container according to the invention exhibits an advantageous ratio between its collapsed volume and its fully unfolded volume. In a specific case, said ratio is 1:7. When suitable materials are used (such as the materials described in the aforesaid international patent application WO 01/05668), it is furthermore possible to realise an advantageous ratio between the container's self-weight and the weight of the useful load (in a practical application said ratio is 1:16). One of the main advantages of the container according to the invention is its so-called multi-modal character: cargo can be transported from door to door, using different means of transport (truck, train, ship and plane) without having to repack the cargo.
Hetrocyclic aryl sulphonamides
The invention relates to novel sulfonamides of general formula (I) where the substituents R1, R2, R3, R4, A and X have the given meanings, pharmaceutical compositions containing them, and a method of using them as antiviral agents, in particular against cytomegaloviruses.
1. A compound of the general formula (I) in which R2 and R3 are identical or different and represent hydrogen, hydroxyl, halogen, nitro, cyano, trifluoromethyl, trifluoromethoxy, (C1-C6)-alkyl, (C1-C6)-alkoxy or a group of the formula in which R5, R6 and R7 are identical or different and in each case represent hydrogen or (C1-C6)-alkyl, which for its part can be substituted by one or two substituents (selected from the group consisting of hydroxyl, halogen, cyano, trifluoromethyl and trifluoromethoxy, A represents a five- or six-membered heteroaryl linked via a C atom to the adjacent phenyl ring, R1 represents the radical in which R11 represents the side group of an amino acid, and the amino group in R1 can optionally be mono- or polysubstituted by (C1-C6)alkyl, alkylcarbonyl, or phenyl, or R1 represents a straight-chain or branched (C1-C5)-alkyl radical, which for its part can be substituted by one or more groups selected from phenyl, piperidinyl, pyridinyl, thiazolyl, thienyl, or a group in which R12 and R13 are identical or different and can represent hydrogen, (C1-C6)alkyl, alkylcarbonyl, an amino protective group, or phenyl, or R1 represents a radical or R1 represents a straight-chain or branched (C1-C5)-alkyl radical, which for its part is substituted by a group in which R14, R15, R16 are identical or different and represent hydrogen or (C1-C6)alkyl and n can assume the values 2 or 3, or R1 represents piperidinyl or the radical in which R12 and R13 have the meaning indicated above, n represents a number from 1 to 4 and the ring can be up to trisubstituted in an identical or different manner by halogen, (C1-C6)-alkyl, halogeno-(C1-C6)-alkyl, amino, or hydroxyl, R4 represents tert-butyl, which is optionally up to trisubstituted, in an identical or different manner, by hydroxyl, fluorine or chlorine, or represents cyclopropyl or cyclobutyl, which are mono- to trisubstituted in an identical or independent manner by halogen or (C1-C6)-alkyl, (C1-C6)-alkyl optionally being substituted by hydroxyl, fluorine or chlorine, and in which x represents oxygen or sulphur, and in which nitrogen-containing heterocycles can also be present as N-oxides, or a tautomer, stereoisomer, or mixture of stereoisomers of said compound, or a pharmacologically tolerable salt of said compound, tautomer, stereoisomer, or mixture of stereoisomers. 2. The compound of the general formula (I) according to claim 1, in which R2 and R3 are identical or different and represent hydrogen or halogen, A represents the radical (A-I) which is linked via one of the carbon atoms of positions 3 or 5 to the adjacent phenyl ring, and in which Y represents oxygen, or A represents the radical (A-II) which is linked via one of the carbon atoms of positions 2 or 5 to the adjacent phenyl ring, and in which Y represents oxygen, R1 represents the radical in which R11 represents the side group of an amino acid, and the amino group in R1 can optionally be mono- or polysubstituted by (C1-C6)-alkyl, alkylcarbonyl, an amino protective group, or phenyl, or R1 represents a straight-chain or branched (C1-C5)-alkyl radical, which for its part can be substituted by one or more groups selected from phenyl, piperidinyl, pyridinyl, thiazolyl, thienyl, a group in which R12 and R13 are identical or different and can represent hydrogen, (C1-C6)-alkyl, alkylcarbonyl, an amino protective group, or phenyl, or R1 represents a straight-chain or branched (C1-C5)-alkyl radical, which for its part is substituted by a group in which R14, R15, R16 are identical or different and represent hydrogen or methyl and n can assume the values 2 or 3, or R1 represents piperidin-3-yl or the radical R4 represents tert-butyl, which is optionally up to trisubstituted, in an identical or different manner, by hydroxyl, fluorine or chlorine, or represents cyclopropyl or cyclobutyl, which is substituted in the α-position to the carbonyl group or thiocarbonyl group by methyl, which for its part is optionally substituted by hydroxyl, fluorine or chlorine, and in which X represents oxygen, and in which nitrogen-containing heterocycles can also be present as N-oxides, or a tautomer, stereoisomer or mixture of stereoisomers of said compound or a pharmacologically tolerable salt of said compound tautomer, stereoisomer, or mixture of stereoisomers. 3. The compound of the general formula (I) according to claim 1, in which R2 and R3 represent hydrogen, A represents one of the radicals R1 represents the radical in which R11 represents the side group of an amino acid, and the amino group in R1 can optionally be mono- or polysubstituted by methyl, alkylcarbonyl, an amino protective group, or phenyl, or R1 represents a straight-chain or branched (C1-C5)-alkyl radical, which for its part can be substituted by one or more groups selected from phenyl, piperidinyl, pyridinyl, thiazolyl, thienyl, or a group in which R12 and R13 are identical or different and can represent hydrogen, methyl, alkylcarbonyl, an amino protective group, or phenyl, or R1 represents a straight-chain or branched (C1-C5) alkyl radical, which for its part is substituted by a group in which R14, R15, R16 are identical or different and represent hydrogen or methyl and n can assume the values 2 or 3, or R1 represents piperidin-3-yl or the radical R4 represents tert-butyl, which is optionally up to trisubstituted, in an identical or different manner, by hydroxyl, fluorine or chlorine, or represents cyclopropyl or cyclobutyl, which is substituted in the α-position to the carbonyl group or thiocarbonyl group by methyl, which for its part is optionally substituted by hydroxyl, fluorine or chlorine, and in which x represents oxygen, and in which nitrogen-containing heterocycles can also be present as N-oxides, or a tautomer, stereoisomer, or mixture of stereoisomers of said compound or a pharmacologically tolerable salt of said compound, tautomer, stereoisomer, or mixture of stereoisomers. 4. The compound of the general formula (I) according to claim 1, in which R4 represents one of the radicals 5. A compound of the general formula (Ia) in which R1, R2, R3, R4, A and X have the meanings indicated above in claim 1. 6. The compound of the general formula (I) according to claim 1, in which A represents a 3-linked 1,2,4-oxadiazole. 7. The compound of the general formula (I) according to claim 1, which is selected from the group consisting of the following compounds: 8. A process for the preparation of compounds of the general formula (I) according to claim 1, in which a compound of the general formula (D-1) in which X, R2, R3 and R4 have one of the meanings indicated above in claim 1, is acylated with a carboxylic acid of the general formula (E-1) R1—COOH (E-1) in which R1 has the meaning indicated above in claim 1 and free amino groups contained in R1 are present protected by amino protective groups, in the presence of a condensing agent and of a base, and the acylated amidoxime is cyclized to the 1,2,4-oxadiazole. 9. A process for the preparation of compounds of the general formula (I) according to claim 1, in which a compound of the general formula (G-2) in which R1, R2, R3, R4 and X have the meaning indicated above in claim 1, are cyclized. 10. A compound of the general formula (D-1) in which R2, R3, R4 and X have the meanings indicated in claim 1. 11. A compound of the general formula (G-2) in which R1, R2, R3, R4 and X have the meanings indicated in claim 1. 12. (canceled) 13. (canceled) 14. (canceled) 15. (canceled) 16. A pharmaceutical composition comprising a compound of the general formula (I) according to any one of claims 1 to 7. 17. A method for the control of a viral disease, comprising administering an effective amount of a compound of claim 1. 18. The method of claim 17 wherein the viral disease is cytomegalovirus infection.
Human smooth muscle myosin heavy chain
The invention provides novel compositions, methods, and uses of hSMMyHC polypeptides and polynucleotides.
1. An isolated nucleic acid sequence encoding a hSMMyHC 7polypeptide, wherein the polypeptide has the following properties: (i) the polypeptide's activity includes ATPase function or the ability to bind actin; and (ii) the polypeptide has an amino acid sequence which has greater than 70% sequence identity with SEQ ID NO:2; SEQ ID NO:4; SEQ ID NO:6; SEQ ID NO:8: SEQ ID NO:10; SEQ ID NO:12; or SEQ ID NO:14 as measured using a sequence comparison algorithm. 2. An isolated nucleic acid sequence of claim 1, wherein the protein specifically binds to polyclonal antibodies generated against a protein comprising SEQ ID NO:2; SEQ ID NO:4; SEQ ID NO:6; SEQ ID NO:8; SEQ ID NO:10; SEQ ID NO:12; or SEQ ID NO:14. 3. An isolated nucleic acid sequence of claim 1, wherein the nucleic acid encodes SEQ ID NO:2; SEQ ID NO:4; SEQ ID NO:6; SEQ ID NO:8; SEQ ID NO:10 SEQ ID NO:12; or SEQ ID NO:14. 4. An isolated nucleic acid sequence of claim 1, wherein the nucleic acid has a nucleotide sequence of SEQ ID NO:1; SEQ ID NO 3; SEQ ID NO:5; SEQ ID NO:7. SEQ ID NO:9; SEQ ID NO:11; or SEQ ID NO:13. 5. An isolated nucleic acid sequence of claim 1, wherein the nucleic acid selectively hybridizes under stringent hybridization conditions to a nucleic acid having a sequence of or a complementary sequence to SEQ ID NO:1; SEQ ID NO:3; SEQ ID NO:5; SEQ ID NO:7: SEQ ID NO:9; SEQ ID NO:11: or SEQ ID NO:13. 6. An expression vector comprising a nucleic acid encoding an hSMMyHC polypeptide, wherein the protein has the following properties: (i) the protein's activity includes ATPase function or the ability to bind actin; and (ii) the protein has a sequence that has greater than 90% amino acid sequence identity to SEQ ID NO:2; SEQ ID NO:4; SEQ ID NO:6; SEQ ID NO:8; SEQ ID NO:10; SEQ ID NO:12; or SEQ ID NO:14 as measured using a sequence comparison algorithm. 7. A host cell transfected with the vector of claim 6. 8. An isolated hSMMyHC polypeptide, wherein the protein has greater than 90% amino acid sequence identity to SEQ ID NO:2; SEQ ID NO:4; SEQ ID NO:6; SEQ ID NO:8; SEQ ID NO:10; SEQ ID NO:12: or SEQ ID NO:14 as measured using a sequence comparison algorithm. 9. An isolated protein of claim 8, wherein the protein specifically binds to polyclonal antibodies generated against a protein comprising SEQ ED NO:2; SEQ ID NO:4; SEQ ID NO:6; SEQ ID NO:8: SEQ ID NO:10; SEQ ID NO:12; or SEQ ID NO:14. 10. An isolated protein of claim 8, wherein the protein is SEQ ID NO:2; SEQ ID NO:4; SEQ ID NO:6; SEQ ID NO:8: SEQ ID NO:10; SEQ ID NO:12: or SEQ ID NO:14. 11. A method for screening for modulators of an hSMMyHC polypeptide, the method comprising the steps of: (i) providing biologically active hSMMyHC polypeptide, wherein has the following properties: (i) activity including ATPase function or the ability to bind actin; and (ii) sequence that has greater than 90% amino acid sequence identity to SEQ ID NO:2; SEQ ID NO:4; SEQ ID NO:6; SEQ ID NO:8: SEQ ID NO:10: SEQ ID NO:12: or SEQ ID NO:14. as measured using a sequence comparison algorithm; (ii) contacting biologically active hSMMyHC polypeptide with a candidate agent in a test and control concentration; and (iii) assaying for the level of hSMMyHC polypeptide activity, wherein the hSMMyHC polypeptide activity is selected from the group consisting of actin binding activity or ATPase activity, and wherein a change in activity between the test and control concentration indicates a modulator. 12. A method of claim 11, wherein the screening occurs in a multi-well plate as part of a high-throughput screen. 13. A method of claim 12, wherein the biologically active hSMMyHC polypeptide comprises an amino acid sequence of SEQ ID NO:2;SEQ ID NO:4; SEQ ID NO:6; SEQ ID NO:8; SEQ ID NO:10; SEQ ID NO:12; or SEQ ID NO:14. 14. An isolated nucleic acid comprising a sequence which has greater than 80% sequence identity with a nucleotide having a sequence of or a complementary sequence of SEQ ID NO:1; SEQ ID NO:3; SEQ ID NO:5; SEQ ID NO:7; SEQ ID NO:9, SEQ ID NO:11; or SEQ ID NO:13. 15. The nucleic acid of claim 14 having a sequence of or a complementary sequence of SEQ ID NO:1; SEQ ID NO:3; SEQ ID NO:5; SEQ ID NO:7; SEQ ID NO:9; SEQ ID NO:11; or SEQ ID NO:13.
<SOH> BACKGROUND OF THE INVENTION <EOH>Smooth muscle cells form the contractile element found in involuntary contractile organs such as the gastrointestinal tract, the urogenital tract, the vasculature, and the small airways of the lung. Smooth muscle is capable of slow, sustained contractions that require less energy to maintain than other muscle types. Smooth muscle cells are quite different from either skeletal or cardiac muscle cells, beginning with their smaller size. Additionally, no striations are seen in smooth muscle cells, and high-resolution microscopy reveals that smooth muscle cells lack the sarcomeric organization of other muscle cell types. The thick (myosin) and thin (actin) filaments are dispersed throughout the cytoplasm of smooth muscle cells, in contrast to the well-organized parallel bundles seen in skeletal and cardiac sarcomeres. This unique organization has the advantage of allowing smooth muscle cells to contract to less than ⅕ of their resting lengths (L0), compared with ½ L0 for cardiac cells. The contractile apparatus of smooth muscle cells consists of thick filaments of smooth muscle myosin and thin filaments of actin coated with the smooth muscle isoform of tropomyosin. As in other muscle types, the level of intracellular free calcium regulates force production in smooth muscle. The molecular mechanism by which calcium controls force production is different in smooth muscle than in striated muscle. Primary control of smooth muscle myosin activity is via calcium-dependent phosphorylation of myosin, changing inactive thick filaments into an active conformation that can interact with actin and produce force. This differs from skeletal and cardiac muscle, where regulation occurs at the level of actin thin filaments. In these tissues, tropomyosin and the regulatory troponin complex decorate actin filaments and control access to myosin binding sites, and thus force production, in a calcium-sensitive manner. In smooth muscle, there is evidence suggesting that some degree of thin filament regulation occurs in smooth muscle cells, but the regulatory proteins are different (caldesmon, calponin) and their role has been less well defined than for the troponin complex in skeletal and cardiac muscle. Myosin is present in all muscle and non-muscle cells. Of the ten distinct classes of myosin in human cells, myosin-II is the form responsible for contraction of skeletal, cardiac, and smooth muscle. This form of myosin is significantly different in amino acid composition and in overall structure from myosins in the other nine distinct classes (Goodson and Spudich, 1993). Myosin-II consists of two globular head domains, called Subfragment-1 or S1, linked together by a long—helical coiled—coiled tail. Proteolysis of myosin generates either S1 or heavy meromyosin (HMM, a two-headed form with a truncated tail), depending on conditions. S1 contains the ATPase and actin-binding properties of the molecule. S1 has been shown to be sufficient to move actin filaments in vitro, and is therefore clearly the motor domain of the molecule. Although myosin II isoforms from various tissues differ in a number of biological properties, they all share the same basic molecular structure as a dimer of two heavy chains (approximately 200 kDa) noncovlantly associated with two pairs of light chains (approximately 20 and 17 kDa). The two globular amino-terminal heads are tethered together by the carboxyl-terminal alpha-helical coiled-coil that forms a tail. The tails are involved in the assembly of myosin molecules into filaments, whereas the heads contain an actin-activated Mg 2+ -ATPase activity. Each myosin head can be divided by three protease-sensitive regions into peptides of approximately 25, 50, and 20 kDa. The more amino-terminal 25 kDa-50 kDa junction is close to the ATP binding region, whereas the actin-binding domain is near the 50 kDa-20 kDa junction. The high-resolution crystal structure for skeletal S1 is known in both its putative pre-stroke and post-stroke states. The crystal structure of the recombinant chicken smooth muscle myosin motor domain has also been determined. S1 consists of a globular actin binding and nucleotide binding region known as the catalytic domain. This domain is attached at its carboxy-terminus to an alpha-helix that has two light chains of ˜20 kDa each wrapped around it. This light-chain binding domain of S1 is known as the lever arm. Upon transitioning from the pre-stroke to the post-stroke state of the S1, the lever arm swings through an angle of ˜90 degrees about a fulcrum point in the catalytic domain near the nucleotide-binding site. The “power stroke” is driven by the hydrolysis of ATP. The other end of the myosin molecule is an alpha-helical coiled-coiled tail involved in self assembly of myosin molecules into bipolar thick filaments. These thick filaments interdigitate between thinner actin filaments, and the two filament systems slide past one another during contraction of the muscle. This filament sliding mechanism involves conformational changes in the myosin heads causing them to walk along the thin actin filaments at the expense of ATP hydrolysis. Activation of smooth muscle myosin is via phosphorylation of the 20 kDa myosin light chain by myosin light chain kinase (MLCK). Calcium sensitivity is achieved by the absolute requirement for having a Ca2+-calmodulin complex bound to MLCK. An increase in intracellular calcium drives formation of a calcium-calmodulin complex, which is then competent to bind to MLCK and stimulate phosphorylation. When calcium levels fall, the intracellular concentration of the Ca2+-calmodulin complex drops and more Ca2+-calmodulin dissociates from MLCK, causing inactivation. Counterbalancing the action of MLCK is myosin phosphatase, which dephosphorylates the 20 kDa myosin light chain and inactivates myosin. Myosin heavy chain (MyHC) has been studied at the molecular level in striated muscle, where each isoform is encoded by a different member of a multigene family. In contrast, smooth muscle myosin heavy chain isoforms are produced by alternate splicing of a single gene. Of particular interest is the splice varriant that occurs in the myosin head, at the 25/50 kDa junction. B-isoforms contain an extra seven amino acid. insert at this junction; this insertion doubles the rate of ATP hydrolysis as well as the velocity of actin filaments in an in vitro motility assay over that of A-isoforms lacking the insert. Interestingly, although A- and B-isoforms are co-expressed in several smooth muscle types, there appears to be preferential expression of particular isoforms in different tissues. For example, the slower A-isoform predominates in vascular tissue, while the faster B-isoform is the major species in visceral tissues like bladder and intestine. This correlates with the much lower maximal speed of shortening seen for aortic versus intestinal smooth muscle. In addition to this N-terminal diversity, there is also splice site variation in the C-terminal tail of the heavy chain, producing the SM-1 and SM-2 isoforms. The SM-2 isoform contains 9 unique amino acids, whereas the SM-1 isoform contains 43 unique amino acids at the C-terminus. The functional consequences of these C-terminal variations remain unclear, but expression studies indicate that there is differential expression in developing smooth muscle and cultured cells. SM-1 is expressed first in fetal rabbit development, followed by SM-2 expression in late fetal or early neonatal development. Studies of SM-1 and SM-2 isoform composition in different smooth muscle tissues have not established clear tissue expression patterns. Although the art has provided some structural and functional data regarding certain non-primate homologs of SMMyHC genes, mRNAs, and encoded proteins, there is a need in the art for primate, and particularly human, SMMyHC isoform polynucleotide sequences, peptide sequences, isoform proteins, antibodies thereto, and the like, as well as methods employing the aforesaid. The present invention provides those embodiments and others useful to those skilled in the art. The references discussed herein are provided solely for their disclosure prior to the filing date of the present application and are each incorporated herein by reference. Nothing herein is to be construed as an admission that the inventors are not entitled to antedate such disclosure by virtue of prior invention.
<SOH> SUMMARY OF THE INVENTION <EOH>The present invention relates to novel human smooth muscle myosin heavy chain (hSMMyHC) proteins and encoding polynucleotides. Accordingly, an embodiment of the invention involves the formation of a purified and/or isolated primate hSMMyHC protein and fragments thereof. In an embodiment, the hSMMyHC polypeptides have the amino acid sequence of SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, or SEQ ID NO:12, or a substantially identical mutein, homolog, fragment, analog, or fusion protein thereof. In an aspect, the hSMMyHC protein comprises the polypeptide encoded by SEQ ID NO:1; SEQ ID NO:3; SEQ ID NO:5; SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, or SEQ ID NO:13; or a substantially identical mutein, homolog, fragment, analog, or fusion protein thereof. The invention provides muteins comprising a hSMMyHC S1 domain comprising an amino acid sequence having an amino acid substitution, addition, and/or deletion as compared to a naturally-occurring hSMMyHC protein (e.g., a naturally-occurring hSMMyHC protein obtained from a non-pathological mammalian specimen). In a variation, the invention provides hSMMyHC fragments comprising a S1 or RLC binding domain (or fragments thereof), preferably S1, wherein said fragments comprise a naturally-occurring hSMMyHC amino acid sequence and exhibit binding to ATP and/or actin, or wherein such fragments comprise an amino acid substitution, addition, or deletion relative to the naturally-occurring hSMMyHC polypeptide sequence and which substantially lack binding to actin or ATP, and/or have activity as a hSMMyHC competitive antagonist and/or enhance actin-myosin contractile activity or block actin-myosin contractile activity of endogenous hSMMyHC protein. In an aspect, the invention provides recombinant proteins comprising an hSMMyHC sequence and an additional linked amino acid sequence in the form of a fusion protein. In an aspect, the invention provides deletion variants of hSMMyHC wherein up to 90 percent or more of the fall-length hSMMyHC sequence is deleted but the deletion variant retains a detectable biochemical property (e.g., ATPase function, actin binding, etc.) and is structurally distinguishable from a corresponding fragment of a non-primate homolog of hSMMyHC. In an aspect the invention provides sequence variants of hSMMyHC wherein amino acid deletions, additions, and/or substitutions are present and wherein the sequence variant is not sequence identical to any known non-primate SMMyHC sequence of comparable length. In one aspect, the hSMMyHC protein comprises the amino acid sequence—QGPSFAY—(SEQ ID NO:15) (i.e., the insertion in the motor domain derived from the splice variant as described below). The present invention provides compositions comprising recombinant and/or substantially purified hSMMyHC proteins and assay compositions comprising a hSMMyHC protein or variant thereof and a candidate agent which may modulate function of the hSMMyHC protein. The invention also provides antibodies which bind to hSMMyHC with an affinity of about at least 1×10 7 M −1 and which lack specific high affinity binding for non-primate SMMyHC-related polypeptides. Polynucleotide sequences encoding hSMMyHC polypeptides are provided. The characteristics of the cloned sequences are given, including the nucleotide and predicted amino acid sequences. Polynucleotides comprising these sequences can serve as templates for the recombinant expression of quantities of hSMMyHC polypeptides, such as full-length hSMMyHC. Many polynucleotides comprising these sequences can also serve as probes for nucleic acid hybridization. The invention also provides host cells expressing hSMMyHC polypeptides encoded by a polynucleotide other than a naturally-occurring hSMMyHC gene or homolog gene of the host cell (if present). Such a polynucleotide may be an expression vector. The invention provides a method for identifying a candidate agent that modulates a detectable biochemical function of hSMMyHC in vitro. The present invention provides several novel methods and compositions for modulating hSMMyHC activities and for screening for modulators of such activities. The invention also provides methods for identifying agents which modulate hSMMyHC activity in vivo. The present invention also provides a method for diagnosing a disease in a human patient, wherein a diagnostic assay is used to determine if a predetermined pathogenomonic concentration of hSMMyHC polypeptide or its encoding mRNA is present in a biological sample from a human patient. A further understanding of the nature and advantages of the invention will become apparent by reference to the remaining portions of the specification and drawings.
Regulation of the apj receptor for use in the treatment or prophylaxis of cardiac diseases
The invention relates to the use of APJ receptor agonists for producing a medicament for the treatment and/or prophylaxis of coronary heart diseases, in particular stable and unstable angina pectoris, acute myocardial infarction, myocardial infarction prophylaxis, sudden heart death, heart failure, and high blood pressure and the sequelae of atherosclerosis.
1. A method for treating coronary heart diseases, high blood pressure and the sequelae of atherosclerosis, comprising administering to a patient in need thereof an effective amount of an APJ receptor agonist. 2. The method of claim 1, where the coronary heart diseases are stable and unstable angina pectoris, acute myocardial infarction, myocardial infarction prophylaxis, sudden heart death and heart failure. 3. The method as claimed in claim 1, where the APJ receptor agonist has an EC50 of less than 1 μM. 4. The method as claimed in claim 1, where the human APJ receptor agonist has an EC50 of less than 100 μM.
Variable resistance device for an exercise machine
The invention concerns novel pharmaceutical compositions capable of comprising micelles containing at least a very lipophilic principle enabling to enhance bioavailability of active principles insoluble in aqueous solvents called MIDDS® (Micellar Improved Drug Delivery Solutions).
1. A variable resistance device adapted to be incorporated if an exercise machine to provide selectively-variable resistance therefor, the device including: a primary fluid chamber adapted to receive fluid therein, the primary chamber having a primary fluid flow region; a rotation mechanism positioned and adapted to rotate within the primary fluid flow region such that the rotation mechanism upon rotation encounters a degree of resistance dependent on the amount of fluid in the primary fluid chamber, the rotation mechanism being adapted to be rotated by rotational input from the exercise machine; a secondary mechanism adapted to achieve and maintain an appropriate amount of the fluid in the primary fluid chamber to provide a selected degree of resistance for the exercise machine, the secondary mechanism having a secondary fluid flow region; a fluid flow circuit, which includes said primary and secondary fluid flow regions, through which circuit the fluid flows to establish a circuit-flow condition that repetitively cycles around the circuit from the primary fluid flow region into the secondary fluid flow region and then back into the primary fluid flow region, the circuit-flow condition being adapted to establish and maintain said appropriate amount of fluid in the primary fluid chamber during use; and a controller for variably controlling flow of fluid through the circuit to selectively establish different circuit-flow conditions each corresponding to a different appropriate amount of the fluid in the primary fluid chamber to provide a different degree of resistance for the exercise machine. 2. A device of claim 1 wherein the secondary mechanism includes a secondary fluid chamber adapted to receive fluid therein, the secondary fluid chamber having said secondary fluid flow region. 3. A device of claim 2 wherein the amount of fluid in the primary fluid chamber is able to be ascertained by measuring the level of fluid in the secondary fluid chamber. 4. A device of claim 2 wherein the secondary fluid chamber is positioned externally to the primary fluid chamber. 5. A device of claim 2 wherein the secondary fluid chamber is positioned internally within the primary fluid chamber. 6. A device of claim 5 wherein the primary fluid flow region of the primary fluid chamber is defined by inner surfaces of the primary fluid chamber and by outer surfaces of the secondary fluid chamber. 7. A device of claim 6 wherein the inner surfaces of the primary fluid chamber form a first circle, and the outer surfaces of the secondary fluid chamber form a second circle which is concentric and c-axial with the first circle, the primary fluid flow region being generally between the two circles. 8. A device of claim 7 wherein the primary fluid flow region generally surrounds the secondary fluid chamber. 9. A device of claim 7 wherein the primary fluid flow region is arranged substantially horizontally. 10. A device of claim 9 wherein the primary fluid flow region further includes a space which is within the second circle and which is beneath the secondary fluid chamber, the space defining a gap between an external undersurface of the secondary fluid chamber and an inner surface of the primary fluid chamber. 11. A device of claim 10 wherein the gap is insufficient for a fluid whirlpool to be created under the secondary fluid chamber when the fluid flows in the primary fluid flow region. 12. A device of claim 2 wherein the primary fluid flow region is arranged generally upright. 13. A device of claim 12 wherein, in use, when the user provides the rotational input, the fluid moves around the primary fluid flow region of the primary fluid chamber and also through the fluid flow circuit, and wherein, in use, when the user ceases providing the rotational input, the fluid in the uprightly-oriented primary chamber falls to bottom of the primary fluid chamber thereby acting as a body of fluid that stops the rotation of the rotation mechanism. 14. A device of claim 7 wherein the inner surfaces of the primary fluid chamber and/or the outer surfaces of the secondary fluid chamber is/are provided with baffles to hinder the flow of fluid in the primary fluid chamber. 15. A device of claim 10 wherein the gap is sufficient for a fluid whirlpool to be created under the secondary fluid chamber when the fluid swirls around in the primary fluid flow region, the primary fluid flow region being shaped so that the whirlpool is able to continue swirling freely even after cessation of the input from the exercise machine to the rotation mechanism. 16. A device of claim 1 wherein the secondary mechanism is provided with inlet means that allows fluid to flow from the primary flow region into the secondary flow region. 17. A device of claim 16 wherein fluid flows through the inlet means exclusively in one direction. 18. A device of claim 16 wherein the controller provides variation means for variably controlling the flow of fluid through the inlet means. 19. A device of claim 16 wherein the position of the inlet means of the secondary mechanism is arranged so as to meet the direction of part of the fluid flow in the primary fluid flow region. 20. A device of claim 1 wherein the secondary mechanism is provided with outlet means that allows fluid to flow out of the secondary flow region back into the primary flow region. 21. A device of claim 20 wherein the controller provides variation means for variably controllings the flow of fluid through the outlet means. 22. A device of claim 21 wherein the variation means variably controls the flow of fluid through the outlet means by raising or lowering the height position of the outlet means. 23. A device of claim 21 the variation means variably controls the flow of fluid through the outlet means by increasing or decreasing the flow-through size of the outlet means. 24. A device of claim 1 wherein the fluid is water. 25. A device of claim 1 wherein the fluid flow circuit is open to the atmosphere and is not of a hydraulic-nature. 26. A device of claim 1 wherein the fluid in the fluid flow circuit is substantially constant in amount. 27. A device of claim 1 wherein the rotation mechanism is directly connected to the rotational input from the exercise machine without the need for a transmission and/or step-up system. 28. A device of claim 1 wherein the exercise machine is an exercise bicycle. 29. A device of claim 1 wherein the exercise machine is a rowing-simulating exercise machine. 30. An exercise machine incorporating a variable resistance device of claim 1. 31. A device of claim 1 wherein a transmission arrangement is provided to alter the rate of rotation from the exercise machine such that the rotation mechanism receives a different rotational rate of input. 32. A device of claim 1 wherein, instead of including the rotation mechanism, instead a reciprocating mechanism is positioned and adapted to reciprocate within the primary fluid flow region such that the reciprocating mechanism upon reciprocation encounters a degree of resistance dependent on the amount of fluid in the primary fluid chamber, the reciprocating mechanism being adapted to be reciprocate by mechanical input from the exercise machine. 33. A device of claim 1 wherein, in use, the fluid flows substantially continuously between the primary and secondary chambers via the fluid flow circuit. 34. A device of claim 1 wherein the amount of fluid contained in the device remains substantially constant. 35. A device of claim 1 wherein the rotation mechanism, upon rotation, encounters a degree of resistance dependent on the level of fluid in the primary fluid chamber. 36. A device of claim 1 wherein the secondary fluid flow region is separate from the primary fluid flow region. 37. A device of claim 1 wherein a pumping mechanism is used to assist or create the flow of fluid around the fluid flow circuit. 38. A device of claim 32 wherein the secondary mechanism is provided with outlet means that allows fluid to flow from the secondary flow region into the primary flow region. 39. A device of claim 36 wherein fluid flows through the outlet means of the secondary mechanism exclusively in one direction. 40. A device of claim 1 wherein the rotation mechanism is in the form of rotatable vanes. 41. A variable resistance device adapted to be incorporated in an exercise machine to provide selectively-variable resistance therefor, the device including: a primary circular fluid chamber adapted to receive fluid therein, the primary chamber having a circular primary fluid flow region; a rotation mechanism, which includes rotating vanes, being positioned and adapted to rotate within the primary fluid flow region such that the rotation mechanism upon rotation encounters a degree of resistance dependent on the amount of fluid in the primary fluid chamber, the rotation mechanism being adapted to be rotated by rotational input from the user via the exercise machine, the primary fluid chamber being adapted to be positioned upright in use; a secondary fluid chamber positioned substantially within the primary circular fluid chamber, the secondary fluid chamber being adapted to achieve and maintain an appropriate amount of the fluid in the primary fluid chamber to provide a selected degree of resistance for the exercise machine, the secondary chamber having a secondary fluid flow region, the secondary chamber being provided with an inlet positioned, in use, at or substantially close to the top of secondary chamber, the inlet allowing fluid to flow from the primary flow region into the secondary flow region; a fluid flow circuit, which includes said primary and secondary fluid flow regions, through which circuit the fluid flows to establish a circuit-flow condition that repetitively cycles around the circuit from the primary fluid flow region into the secondary fluid flow region and then back into the primary fluid flow region, the circuit-flow condition
<SOH> BACKGROUND OF THE INVENTION <EOH>1. Field of Invention The present invention relates to a variable resistance device adapted to be incorporated in an exercise machine to provide a selectively-variable degree of resistance for the exercise machine. 2. Description of Prior Art An exercise machine, by definition, needs to provide the user with a degree of resistance for muscular exercise. In almost all forms of exercise, there is a requirement in exercise machines for the degree of resistance to be varied. First, there is the need for the user to vary the degree of resistance with a minimum of effort and complexity. Second, another need is for the selected degree of resistance to be precise and repeatable. This is particularly so for resistance machines used by athletes who require a precise calibration of resistance values so that the values can act as a precise reference point for monitoring their exercise routines. As an example, sporting institutions would benefit from a precisely calibrated exercise machine for testing large numbers of athletes over a long period of years, so that there can be confidence that the degree of resistance used in a set of test exercises can be guaranteed to remain constant over the period of years. This degree of repeatability is often difficult to maintain, for instance, in exercise machines that use magnetic resistance, and wind resistance. In the case of magnetic resistance, the calibration of the magnets can alter over time. Wind resistance can be affected by the amount of atmospheric pressure, particularly when the same machine is used at different altitude levels. There is also the need for the user to selectively change the degree of resistance, even within a workout. In PCT/US88/01580, International Publication W088/08735 (Duke), an exercise machine, which simulates rowing, is provided with a resistance device which consists of a paddle that rotates in a cylindrical water-filled container. The degree of fluid in the container determines the degree of resistance experienced by the user. This prior art machine is provided with a handle connected to a drive cord. The user pulls and releases the drive cord, thereby simulating the stroke an oar when rowing a boat. However, in this prior art device, resistance is varied by a cumbersome method of wrapping a greater or lesser quantity of strap around the drive spool. It is believed that this increases or decreases the tangential forces as the circumference is increased or decreased. Moreover, this manner of varying the resistance does not readily provide an accurate repeatable degree of resistance, since the user might not know how much cord has been wrapped, nor how much cord remains unwrapped. Also, the range of resistance-afforded by wrapping and unwrapping a cord-is narrow in range, so that the user does not have the benefit of using a wide range of resistance values. In the prior art, which relate to resistance in the form of paddles that rotate in baths of water, there are systems which involve a first and second chamber, wherein liquid is transferred between the chambers so as to vary the amount of liquid in the primary container in which the paddle rotates, for example U.S. Pat. No. 5,944,637 (Stickler), and U.S. Pat. No. 5,195,936 (Mao). In these prior art, however, the liquid is forced from a first chamber into a second chamber through the same aperture or apertures. In other words, there is a two-way flow of liquid through the same aperture. Thus, these prior art apparatus must be provided with complex mechanisms needed to force the liquid through the same aperture, initially, in a first direction, then back through the same aperture in a second direction. The need for applying such forces means that the exercise machines require complex and thus more expensive mechanisms to force the liquid in and out of the apertures which link the chambers. An objective of the present invention is to overcome or at least ameliorate one or more of the above problems in the prior art, or to provide an improved alternative.
<SOH> BRIEF SUMMARY OF THE INVENTION <EOH>According to the present invention, there is provided a variable resistance device adapted to be incorporated in an exercise machine to provide selectively variable resistance therefor, the device including: a primary fluid chamber adapted to receive fluid therein, the primary chamber having a primary fluid flow region; a rotation mechanism positioned and adapted to rotate within the primary fluid flow region such that the rotation mechanism upon rotation encounters a degree of resistance dependent on the amount of fluid in the primary fluid chamber, the rotation mechanism being adapted to be rotated by rotational input from the exercise machine; a secondary mechanism adapted to achieve and maintain an appropriate amount of the fluid in the primary fluid chamber to provide a selected degree of resistance for the exercise machine, the secondary mechanism having a secondary fluid flow region; a fluid flow circuit, which includes said primary and secondary fluid flow regions, through which circuit the fluid flows to establish a circuit-flow condition that repetitively cycles around the circuit from the primary fluid flow region into the secondary fluid flow region and then back into the primary fluid flow region, the circuit-flow condition being adapted to establish and maintain said appropriate amount of fluid in the primary fluid chamber during use; and a variation means or controller for variably controlling flow of fluid through the circuit to selectively establish different circuit-flow conditions each corresponding to a different appropriate amount of the fluid in the primary fluid chamber to provide a different degree of resistance for the exercise machine. Preferably, the secondary mechanism includes a secondary fluid chamber adapted to receive fluid therein, the secondary fluid chamber having said secondary fluid flow region. Preferably, the amount of fluid in the primary fluid chamber is able to be ascertained by measuring the level of fluid in the secondary fluid chamber. In one embodiment, the secondary fluid chamber may be positioned externally to the primary fluid chamber. In other embodiments, the secondary fluid chamber may be positioned internally within the primary fluid chamber. Preferably, the primary fluid flow region of the primary fluid chamber is defined by inner surfaces of the primary fluid chamber and by outer surfaces of the secondary fluid chamber. Preferably, the inner surfaces of the primary fluid chamber form a first circle, and the outer surfaces of the secondary fluid chamber form a second circle which is concentric and c-axial with the first circle, the primary fluid flow region being generally between the two circles. Preferably, the primary fluid flow region generally surrounds the secondary fluid chamber. In one embodiments, the primary fluid flow region may be arranged substantially horizontally. Preferably, the primary fluid flow region further includes a space which is within the second circle and which is beneath the secondary fluid chamber, the space defining a gap between an external undersurface of the secondary fluid chamber and an inner surface of the primary fluid chamber. In some embodiments, the gap may be insufficient for a fluid whirlpool to be created under the secondary fluid chamber when the fluid flows in the primary fluid flow region. In some embodiments, the primary fluid flow region may be arranged generally upright. In an example of the upright embodiment, in use, when the user provides the rotational input, the fluid moves around the primary fluid flow region of the primary fluid chamber and also through the fluid flow circuit, and when the user ceases providing the rotational input, the fluid in the uprightly-oriented primary chamber falls to bottom of the primary fluid chamber thereby acting as a body of fluid that stops the rotation of the rotation mechanism. In some embodiments, the inner surfaces of the primary fluid chamber and/or the outer surfaces of the secondary fluid chamber may be provided with baffles to hinder the flow of fluid in the primary fluid chamber. Preferably, the gap is sufficient for a fluid whirlpool to be created under the secondary fluid chamber when the fluid swirls around in the primary fluid flow region, the primary fluid flow region being shaped so that the whirlpool is able to continue swirling freely even after cessation of the input from the exercise machine to the rotation mechanism. Preferably, the secondary mechanism is provided with inlet means that allows fluid to flow from the primary flow region into the secondary flow region. Preferably, the variation means variably controls the flow of fluid through the inlet means. Preferably, the secondary mechanism is provided with outlet means that allows fluid to flow out of the secondary flow region back into the primary flow region. Preferably, the variation means variably controls the flow of fluid through the outlet means. Preferably, the variation means variably controls the flow of fluid through the outlet means by raising or lowering the height position of the outlet means. Alternatively, the variation means variably controls the flow of fluid through the outlet means by increasing or decreasing the flow-through size of the outlet means. The fluid may be water or other suitable fluid. Preferably, the fluid flow circuit is open to the atmosphere and is not of a hydraulic-nature. Preferably, the fluid in the fluid flow circuit is constant in amount. The rotation mechanism may be directly connected to the rotational input from the exercise machine without the need for a transmission and/or step-up system. The exercise machine, for example, may be an exercise bicycle, or a rowing-simulating exercise machine. In some embodiments, a transmission arrangement may be provided to alter the rate of rotation from the exercise machine such that the rotation mechanism receives a different rotational rate of input. According to another aspect of the invention, there is provided a similar variable resistance device except that, instead of including the rotation mechanism, a reciprocating mechanism is positioned and adapted to reciprocate within the primary fluid flow region such that the reciprocating mechanism upon reciprocation encounters a degree of resistance dependent on the amount of fluid in the primary fluid chamber, the reciprocating mechanism being adapted to be reciprocate by mechanical input from the exercise machine. A more detailed explanation of the invention is provided in the following description and appended claims taken in connection with the accompanying drawings.
Packaging container
A packaging container such as a tube, which is characterized in that the head (11) of the tube is inter alia sealed by the interior annular element (18) configured by a film material that engages with the shoulder (15) of the head. The annular element (18) is produced by pre-forming a plastic film annular element (18).
1. A packaging container, especially a packaging tube, comprising a tubular tube body and a tube head arranged on the tube body, said tube head consisting of a shoulder and a discharge and an internal annular element that is arranged on the side of the shoulder facing the interior of the tube body and covers said side, characterized in that the internal annular element (18) is made to engage pre-formed with the shoulder. 2. A packaging container in accordance with claim 1, characterized in that the head (11) is produced by press forming, the head (11) being simultaneously attached to the tube body (10). 3. A packaging container in accordance with claim 1, characterized in that the head (11) is produced by injection moulding, the head (11) being simultaneously attached to the tube body (10). 4. A packaging container in accordance with claim 1, characterized in that the head (11) is designed as a prefabricated part that is to be attached to the tube body (10) in a separate step. 5. A packaging container in accordance with any one of claims 1 to 4, characterized in that the pre-forming degree amounts between 20% and 95%, preferably between 40% and 60%. 6. A packaging container comprising: a tube body having an interior, a tube head arranged on the tube body, the tube head includes a shoulder part and a neck which define an opening, the shoulder part includes a surface which faces the interior of the tube body, and a pre-formed internal annular element arranged on the surface of the shoulder part. 7. A method of producing a packaging container comprising a tube body having an interior, a tube head arranged on the tube body, the tube head includes a shoulder part and a neck which define an opening, the shoulder part includes a surface which faces the interior of the tube body, and a pre-formed internal annular element arranged on the surface of the shoulder part, the method comprises: pre-forming the internal annular element on the surface of he shoulder part. 8. A method according to claim 7, including press forming the tube head while simultaneously attaching the tube head to the tube body. 9. A method according to claim 7, including injector molding the tube head while simultaneously attaching the tube head to the tube body. 10. A method according to claim 7, including pre-fabricating the tube head and thereafter attaching the tube head to the tube body. 11. A method according to claim 7, wherein the pre-forming is to a pre-forming degree of between 20% and 95%. 12. A method according to claim 7, wherein the pre-forming is to a pre-forming degree of between 40% and 60%.
<SOH> BACKGROUND OF THE INVENTION <EOH>The present invention relates to a packaging container, particularly, a packaging tube. Packaging containers, especially packaging tubes, comprise a tubular body, sometimes also referred to as pipe body, a tube head connected with the tubular body and provided with a discharge (dispenser), and a closure cap that opens and closes the discharge and is attached to the tube head, for instance, by means of a screw thread. Various methods have been developed for the production of packaging containers of the type briefly outlined hereinabove. For example, the tubular bodies may be extruded or co-extruded or, starting from a strip of sheeting, they may be produced by so-called longitudinal seam welding in which the edges of the sheeting strip are joined to each other by the application of heat and pressure and thus form the tubular body. As regards the materials for the tube body, use is made of metals, plastic materials with or without barrier layers and combinations of these materials, the actual choice of material being for the most part governed by the merchandise for which the packaging tube is intended. High-quality goods, such as pharmaceuticals, cosmetics and other body-care means—toothpaste being a case in point—that contain volatile active ingredients or react with gases, call for tubular bodies made of diffusion-resisting materials or material combinations, whereas in the case of less demanding merchandise, such as technical lubricants for example, materials without blockage effect will prove sufficient. The term diffusion is here understood as referring to the migration of volatile components from the interior of the tube towards the outside and vice versa. Once the tube bodies have been produced, they are equipped with heads. This operation can be performed by means of press moulding or injection moulding or by the application of a prefabricated head to the tube body. The plastic materials used for the heads and the tubes have to be compatible, because in each of the named methods the plastic materials of the head and the tube have to flow into each other in order to form the joint. When press moulding is employed, a blank of plasticized plastic material is transformed in a press mould and, while this process is going on, one end of the tube body is also joined to the head that is coming into being. Joining by injection moulding is characterized by the fact that one end of the tube body is joined to the head during the mould-filling process. When a prefabricated head is joined to a tube body, the tube body is attached to the shoulder of a head by means of melting and pressure. In the case of packaging tubes for high-quality substances, where the tube body is rendered substantially diffusion-resistant by means of an appropriate choice of material, problems are created by the fact that the diffusion resistance of the head has to be made to match that of the tube body. When the previously named head forming and jointing methods are employed, polyolefins, preferably polyethylene (PE) and polypropylene (PP), are used as materials. When this material is used for the head and the tube consists of a laminate, the material of at least one laminate layer, i.e. of one of the cover layers, must be compatible, so that a head-tube joint can be obtained by means of melting and the application of pressure. The aforementioned polyolefins have the advantage that they can be readily jointed, but the drawback that they absorb the volatile components of the packed substances, aromatics among them, with the consequence that the packed substances suffer a quality reduction, and it can also happen that the head disintegrates, as it were, on account of the material consistency becoming soft, i.e. spongy. Gradual disintegration of the material consistency facilitates increased absorption of volatile components and endangers the strength of the joint between head and tube body. Seals have been developed against this insufficient diffusion resistance. A distinction is made between external seals and internal seals, the former being applied to the external surface of the tube shoulder, the latter to the internal surface of the tube shoulder facing the interior of the tube, covering the shoulder surfaces from the dispenser neck to the joint between tube and head. Seals in the form of annular disks, with a central hole as aperture for the outlet channel, are described as external and internal annular elements according to the place where they are applied. As far as the sealing of tube heads is concerned, external annular elements have not attained the same importance as their internal counterparts. This is due to the fact that, subject to their being made of appropriate materials, they will render the passage of gases (O 2 , CO 2 , etc.) from the outside inwards more difficult or even suppress it altogether, but are not effective against the absorption of gaseous components of the packed substances (aromatics, for instance), whereas internal annular elements will perform both these sealing functions, always provided that the internal annular element covers the internal surface of the tube shoulder without jointing defects. A jointing defect is here understood as a folding or waving of the annular element, so that its open sides will not be joined to the surface of the tube shoulder. Jointing defects often lead to fractures of the seals, i.e. the annular elements, in which case there will be no blockage effect at all. As material for the annular elements, which are produced from film strips, consideration may be given to monofilms (monofilms of plastics or metals), plastic-plastic laminates and plastic-metal laminates. To all intents and purposes, however, only plastic-metal laminates have proved successful among these films, and this for the reason that only annular elements made of this material combination can be joined to the shoulder of a head without jointing defects, while in the case of annular elements made of plastic films, inclusive of plastic laminate films, lack of jointing defects cannot be attained with certainty. Plastic-metal laminates consist of an aluminium film that is sheathed, i.e. covered on both sides with a polyolefin film. In most cases so-called adhesion promoters are also to be found between the aluminium layer and the polyolefin layers. The aluminium layer or aluminium film serves as barrier layer, and constitutes a highly effective barrier layer against migrations any kind, whereas one polyolefin layer serves as means for joining the annular element to the shoulder surface, the other polyolefin layer as separation of the aluminium layer from the packed material. Though they have the advantages of the defect-free mounting on the head and considerable diffusion resistance, annular elements made of plastic-metal laminates are also associated with disadvantages. The elements are cut or, more precisely, punched from a strip of material. At the cutting or punching edge the metal will be bared and remain uncovered. In the built-in position of the annular element, given a difference between the outer diameter of the element and the inner diameter of the tube body, this metallic part of annular element will not be protected against the packed substance and, depending on the type of substance involved, the metal may lead to contamination of the packed material or the packed material can cause corrosion of the metal layer starting from the metallic cutting edge. Further, films of the type described above are prone to become delaminated between the two covering layers and the intermediate metal layer, starting from the cutting edge. Annular elements made of plastic material do not have the drawbacks of contamination and delamination, but their marked tendency to become folded and wavy constitutes an equivalent disadvantage. Bearing in mind this prior art, the inventor set himself the object of developing an annular element (i.e. an internal annular element) with which the disadvantages of the known annular elements will be avoided.
<SOH> SUMMARY OF THE INVENTION <EOH>The foregoing object is achieved by the present invention by providing a packaging tube comprising a tubular tube body and a tube head arranged on the tube body, said tube head consisting of a shoulder and a discharge and an internal annular element that is arranged on the side of the shoulder facing the interior of the tube body and covers said side, characterized in that the internal annular element ( 18 ) is made to engage pre-formed with the shoulder. The advantages of the annular element in accordance with the invention also comprise that fact that it can be used with all the methods for attaching the head and does not call for any constructional modification of the moulds used for attaching the head.
Passenger accommodation cabin for a vehicle
A passenger accommodation cabin (15) for a vehicle, particularly an aircraft, which comprises: wall means (12, 14, 16) defining a passenger accommodation area; plinth means (10) disposed substantially at floor level and adapted to support mattress means (25) within said accommodation area to provide at least one substantially flat bed; false floor means (42) that are selectively movable between a deployed position in which said false floor means at least partially cover the mattress means and a retracted position for allowing use of said bed; and seating means (30) comprising at least one seat and associated supporting structure for supporting said seat within the accommodation area generally above the mattress means.
1. A passenger accommodation cabin for a vehicle, particularly an aircraft, which cabin comprises: one or more walls defining a passenger accommodation area; a plinth means disposed substantially at floor level and adapted to support a mattress within said accommodation area to provide at least one substantially flat bed; a false floor that is selectively movable between a deployed position in which said false floor at least partially covers the mattress and a retracted position for allowing use of said bed; and at least one seat and an associated supporting structure for supporting said seat within the accommodation area generally above the mattress. 2. A cabin as claimed in claim 1, wherein said one or more walls serve as a privacy screen around the accommodation area. 3. A cabin as claimed in claim 1, wherein four upstanding walls are provided, which walls completely surround the accommodation area, and wherein the cabin further comprises an access for gaining entry to the accommodation area from outside. 4. A cabin as claimed in claim 3, wherein one or more of said walls are full-height walls. 5. A cabin as claimed in claim 3, wherein at least three walls are full-height walls. 6. A cabin as claimed in claim 5, wherein said cabin includes a fourth wall which is adapted to be disposed adjacent an aisle in a passenger cabin of a vehicle and is a “half” or “three-quarter”-height wall. 7. A cabin as claimed in claim 6, wherein said fourth wall is dimensioned to provide a privacy screen when a passenger lies on the bed within the cabin, but can be seen over when the passenger is seated upon the seat or when the passenger is standing within the cabin. 8. A cabin as claimed in claim 6, wherein said access comprises a closure or a gap between two walls or parts of the same wall. 9. A cabin as claimed in claim 8, wherein said gap is formed in said fourth wall to provide convenient access to and from the cabin from the aisle. 10. A cabin as claimed in claim 1, wherein the dimensions of said plinth corresponds substantially to the dimensions of the cabin. 11. A cabin as claimed in claim 10, wherein said plinth have substantially the same dimensions as said mattress. 12. A cabin as claimed in claim 1, wherein said plinth means defines a recess for accommodating said mattress, such that said plinth forms an elongate tray for supporting said mattress. 13. A cabin as claimed in claim 12, wherein said tray is configured to provide a close fit around the mattress, and the walls of the cabin substantially follow the edges of the tray. 14. A cabin as claimed in claim 1, wherein said cabin has a substantially rectangular footprint having substantially the same dimensions as said bed. 15. A cabin as claimed in claim 1, wherein said seat comprises at least one seat that is positioned at one end of the cabin in juxtaposition with one short side wall thereof. 16. A cabin as claimed in claim 15, comprising two seats, the seats being positioned at opposing ends of the passenger accommodation cabin in juxtaposition with respective, opposing short side walls of the cabin. 17. A cabin as claimed in claim 15, wherein the or each seat comprises a back-rest that is fixed to a wall of the accommodation cabin and a seat-pan that is pivoted to the back-rest or the cabin wall juxtaposed the back-rest for movement between a deployed position and a stowed position. 18. A cabin as claimed in claim 1, wherein said false floor comprises one or more rigid or semi-rigid, substantially flat panels adapted to overlay at least part of said mattress in a deployed position and removable to allow use of said bed. 19. A cabin as claimed in claim 18, wherein said one or more panels are connected by one or more hinges to said plinth means and/or one or more of the walls to allow the or each panel to be hinged between a deployed position and a stowed position in which the or each panel is removed from the mattress and disposed substantially flush with one of the walls or accommodated within a recess adapted for that purpose. 20. A cabin as claimed in claim 18, wherein said false floor comprises one or more transverse panels which are adapted to extend transversely across the bed from one longitudinal side to another. 21. A cabin as claimed in claim 18, wherein said one or more panels overlay the mattress means at least in a zone forwardly of a seat within the cabin. 22. A cabin as claimed in claims 18, wherein the panel(s) cover substantially the entire, internal floor area of the cabin. 23. A cabin as claimed in claim 18, wherein said cabin accommodates two opposing seats, and the one or more panels cover the mattress between said two seats. 24. A cabin as claimed in claim 20, wherein said cabin comprises a longitudinal half or three-quarter height wall having a gap formed therein to allow access to the interior of the cabin, and the or each transverse panel is connected to said tray within said gap by one or more hinges. 25. A cabin as claimed in claim 24, wherein said one or more transverse panels are pivotable between a deployed position in which the or each panel extends transversely across the bed and an intermediate stowed position in which the or each panel is oriented substantially vertically and is received within the gap between two opposing portions of the longitudinal wall. 26. A cabin as claimed in claim 25, wherein said one or more hinges are mounted to the tray on a slide which extends longitudinally relative to the bed, said one or more hinges being adapted to travel along said slide between an extended position, in which the or each panel is disposed in said intermediate stowed position in the gap, and a retracted position in which the or each panel, in the substantially vertical orientation, is received juxtaposed, or within a respective cavity formed, in a respective one of the longitudinal wall portions in a fully stowed position. 27. A cabin as claimed in claim 18, wherein said false floor is reinforced to strengthen the or each floor panel, to enable said false floor to support the weight of at least one passenger. 28. A cabin as claimed in claim 1, wherein said false floor comprises a flexible tambour means selectively moveable between a deployed position and a stowed position. 29. A cabin as claimed in claim 28, wherein said tambour comprise at least one articulated panel comprising a plurality of elongate segments that are pivotally joined to one another along a plurality of respective parallel axes. 30. A cabin as claimed in claim 29, wherein a housing for said tambour is provided juxtaposed, within and beneath said plinth for receiving and accommodating said tambour means when stowed. 31. A cabin as claimed in claim 1, wherein said mattress comprises two spaced mattresses. 32. A cabin as claimed in claim 31, wherein one or more screens are disposed between the two beds to afford privacy to the respective passengers using them. 33. A cabin installation comprising two cabins as claimed in claim 1, wherein two said cabins are arranged contiguously side-by-side and a removable interconnecting side wall that is common to both cabins is provided such that the interconnecting side wall can be removed to create a double-spaced cabin.
Micro flow passage device, connection device, and method of using the devices
A substrate and an elastomer are bonded each other, and then, a ditch is formed at the bonded surface of the substrate or the elastomer to constitute a flow channel and thus, to constitute a minute flow channel device with the flow channel. Then, a through-hole functioning an inlet and/or outlet is formed at the elastomer so as to be communicated with the flow channel. Then, a convex or concave joint is formed at the elastomer with integration so as to be opened outward from the through-hole so that the inclination angle of said joint is set to not less than 45 degrees and less than 90 degrees. Then, a joining device is pressed and joined with the minute flow channel device via the joint. Therefore, the connection for injecting and discharging a substance such as fluid or gas can be easily realized and automatized, and the device exchange can be performed easily.
1. A minute flow channel device comprising a substrate and an elastomer bonded with said substrate, wherein a ditch is formed at either or both of bonded surfaces of said substrate and said elastomer to constitute a flow channel, and a through-hole, which functions as an inlet and/or an outlet of a substance and is communicated with said flow channel, is formed at said elastomer. 2. The minute flow channel device as defined in claim 1, wherein a convex joint is formed at said elastomer with integration so as to be opened outward from said through-hole, and the inclination angle of an inclined side wall of said joint is set to not less than 45 degrees and less than 90 degrees. 3. A joining device for injecting and discharging a substance into and out of a minute flow channel device as defined in claim 2, comprising a rigid member with an opening and a joint matching member provided so as to surround said opening of said rigid member, wherein a joint of said minute flow channel device is pressed against said joint matching member so that an edge of an inner wall of said joint matching member are contacted with a periphery of an inclined side surface of said joint. 4. The minute flow channel device as defined in claim 1, wherein a concave joint is formed at said elastomer with integration so as to be opened outward from said through-hole, and the inclination angle of an inclined side wall of said joint is set to not less than 45 degrees and less than 90 degrees. 5. A joining device for injecting and discharging a substance into and out of a minute flow channel device as defined in claim 4, comprising a rigid member with an opening and a joint matching member provided so as to surround said opening of said rigid member, wherein a joint of said minute flow channel device is pressed against said joint matching member so that an edge of an inner wall of said joint matching member are contacted with a periphery of an inclined side surface of said joint. 6. The minute flow channel device as defined in claim 1, wherein at least a main surface of said elastomer to be bonded with said substrate is made of adhesive material to said substrate. 7. The minute flow channel device as defined in claim 6, wherein said elastomer includes mainly silicon rubber. 8. The minute flow channel device as defined in claim 7, wherein said silicon rubber includes mainly polydimethylsiloxane. 9. The minute flow channel device as defined in any one of claims 1-8, wherein said elastomer is bonded with said substrate detachably. 10. A method for using a minute flow channel device as defined in claim 1, comprising the steps of: bonding a substrate with an elastomer to constitute a flow channel, injecting a substance to be chemically reacted in said flow channel to create a product through a given liquid processing, and directly processing said product which is held at said elastomer and/or said substrate under non-existence of said substrate or said elastomer after the release of said elastomer. 11. The using method as defined in claim 10, wherein said liquid processing is a chemical reaction so that said substance includes a reacting sample, and said product is measured as a reacted product after the release of said elastomer. 12. The using method as defined in claim 10 or 11, wherein a reacting species to be reacted with said product is immobilized in said flow channel. 13. The using method as defined in any one of claims 10-12, wherein said substance includes at least one kind of reacting species. 14. The using method as defined in claim 10, wherein said liquid processing is a separation so that said substance includes a species to be separated, and said product is collected as a separated product after the release of said elastomer. 15. The using method as defined in any one of claims 10-14, wherein either of bonded surfaces of said substrate and said elastomer is formed flat, and said product is processed on said flat bonded surface of said substrate or said elastomer.
<SOH> FIELD OF THE INVENTION <EOH>This invention relates to a minute flow channel device with a minute flow channel, a joining device which is joined with the minute flow channel device for injecting and discharging a substance such as fluid or gas in and out of the minute flow channel of the minute flow channel device, and a method for using the minute flow channel device.
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>For better understanding of the present invention, reference is made to the attached drawings, wherein FIG. 1 is a perspective view illustrating a first embodiment relating to a minute flow channel device according to the present invention, FIG. 2 is a cross sectional view illustrating the combination of the minute flow channel device illustrated in FIG. 1 and a joining device which is joined with the minute flow channel device, FIG. 3 is a perspective view illustrating a second embodiment relating to a minute flow channel device according to the present invention, FIG. 4 is a cross sectional view illustrating the combination of the minute flow channel device illustrated in FIG. 3 and a joining device which is joined with the minute flow channel device, FIG. 5 is a perspective view illustrating the combination of a third embodiment relating to a minute flow channel device according to the present invention and a joining device which is joined with the minute flow channel device, FIG. 6 is a cross sectional view illustrating the combination illustrated in FIG. 5 , FIG. 7 is a perspective view illustrating components of the combination illustrated in FIG. 5 , FIG. 8 is an exploded perspective view illustrating a fourth embodiment relating to a minute flow channel device according to the present invention, FIG. 9 is a perspective view illustrating the combination of a fifth embodiment relating to a minute flow channel device according to the present invention and a joining device which is joined with the minute flow channel device, FIG. 10 is a cross sectional view illustrating the combination illustrated in FIG. 9 , and FIG. 11 is a perspective view illustrating components of the combination illustrated in FIG. 9 . detailed-description description="Detailed Description" end="lead"?
Led light apparatus with instantly adjustable color intensity
An instantly controllable LED light apparatus provides an LED array (34) formed of red, green and blue LEDs in a regular arrangement. The apparatus also provides a unitary power supply/controller (4) disposed within a unitary housing (20) that is coupled only to the LED array (34) and a power source (56) in one embodiment. The power supply/controller (4) includes a memory device (64) such that, when a button (62) is pressed on the control panel (18) of the power supply/controller (4), a desired illumination color is instantly produced by the combination of the red, green and blue LEDs of the LED array (34).
1-26. (Cancelled) 27. A lighting apparatus comprising: a plurality of LEDs defining an array of LEDs including more than one different colored group of LEDs; and an integral power supply/controller unit disposed within a unitary housing and connectible directly between said plurality of LEDs and a power source, and including: a power supply module for receiving power from a power source and providing modulated power to the plurality of LEDs, a memory device, a user interface capable of providing a plurality of signals, each corresponding to a distinct illumination color of a corresponding plurality of distinct illumination colors, and a controller for receiving a signal of said plurality of signals from the user interface and communicating with the memory device and the power supply module to substantially instantly cause the plurality of LEDs to produce a first distinct illumination color of said plurality of distinct illumination colors, independent of externally adjustable settings. 28. The lighting apparatus as in claim 27, in which the integral power supply/controller includes a dimmer capable of uniformly dimming each of the different colored groups of LEDs. 29. The lighting apparatus as in claim 27, in which the user interface includes a plurality of pre-set buttons and the plurality of distinct illumination colors includes a plural number of programmed illumination colors stored within the memory device and selectable by a corresponding set of the pre-set buttons, each programmed illumination color including intensity levels for each of the different colored groups of LEDs. 30. The lighting apparatus as in claim 29, wherein said programmed illumination colors include red, blue, green, cyan, yellow, magenta, daylight 55009° K, tungsten 3200° K, and tungsten 2900° K, each selectable by a corresponding one of the pre-set buttons. 31. The lighting apparatus as in claim 29, in which the plurality of LEDs comprise LEDs operable respectively for emitting light colored red, green and blue. 32. The lighting apparatus as in claim 31, in which a ratio of red LEDs to green LEDs to blue LEDs in the array is 2:1:1. 33. The lighting apparatus as in claim 29, in which the array of LEDs are current controlled and comprise a first plurality of first color LEDs, a second plurality of second color LEDs and a third plurality of third color LEDs, the integral power supply/controller unit providing a respective current to each of the first second and third-pluralities of LEDs, each respective current including a current level producing a corresponding intensity level of the corresponding plurality of LEDs. 34. The lighting apparatus as in claim 27, in which the integral power supply/controller unit is contained within a hand-held housing. 35. The lighting apparatus as in claim 27, in which the power supply module operates within a range of 90 volts AC to 264 volts AC and is capable of delivering modulated power at a DC voltage level of at least one of 24V and 36V. 36. The lighting apparatus as in claim 27, further comprising a computer, and in which the user interface provides the plurality of signals responsive to commands from the computer, the computer having graphics including a color spectrum pad that includes primary colors, secondary colors, and a plurality of color temperatures of white light, each color of the color spectrum pad being selectable and provideable to the user interface by way of said commands. 37. The lighting apparatus as in claim 27, in which the user interface includes a plurality of pre-set buttons, each pre-set button capable of providing one of the plurality of signals. 38. The lighting apparatus as in claim 37, in which the plurality of pre-set buttons comprises 9 pre-set buttons and the plurality of signals comprises greater than 9 signals. 39. A lighting apparatus comprising: an array of LEDs including a first plurality of first color LEDs, a second plurality of second color LEDs, and a third plurality of third color LEDs; and an integral power supply/controller unit disposed within a unitary housing and connectible to the array of LEDs and a power source, and including: a power supply module for receiving power from a power source, and providing modulated power to the array of LEDs, a memory device, a user interface capable of providing a plurality of signals, each corresponding to a distinct illumination color of a corresponding plurality of distinct illumination colors, and a controller for receiving a signal of the plurality of signals from the user interface and communicating with the memory unit and the power supply module to instantly cause the array of LEDs to produce a first distinct illumination color of the plurality of distinct illumination colors, independent of external settings. 40. The lighting apparatus as in claim 39, further comprising a computer and in which the controller is further capable of receiving commands from the computer and communicating with the power supply module to cause the array of LEDs to produce the plurality of distinct illumination colors, the computer including a color spectrum pad that includes individually selectable colors including primary colors, secondary colors, and a plurality of color temperatures of white light. 41. The lighting apparatus as in claim 40 in which the controller further communicates with the computer using DMX protocol. 42. The lighting apparatus as in claim 40, in which the computer and the controller can communicate using one of RS-485 communication standards and RS-232 communication standards.
<SOH> BACKGROUND OF THE INVENTION <EOH>Conventional light sources, such as used for illumination and display purposes in the entertainment and other industries, typically use a white light source. These light sources work on the principle that white light carries the full spectrum of visible rays of light having various wavelengths and associated colors. In conventional lighting systems, the light source is not directly controlled to provide various colors but, instead, filters, gels, and dichroic glass are used in conjunction with the white light source to color the visible illumination. Dichroic light systems include a white light source and red, green, and blue filters and involve a combination of 3 to 4 light sources or mechanical devices to mix colors. Gels and filters are colored transmissive materials placed over the white light source to produce colored illumination. As such, when different colors of light are desired, the filters, gels or dichroic glass that cover the white light source, must be mechanically changed. This is a time consuming process. The different gels, etc. used to provide the different colors of light may include the primary colors of red, green and blue, and the combinations thereof such as the secondary colors of magenta, cyan, and yellow, as well as the different white light colors conventionally designated in terms of Kelvin degrees (° K). Other available lighting systems use many, different colored LEDs (light emitting diodes), in combination, to produce various colors of visible illumination. Such systems typically require multiple connections such as to both a power supply and a separate controller such as a computer. As such, these multiple component systems are rather bulky with decreased portability. Many LED lighting systems also include dip switches or other settings that must be physically adjusted in order to select and control the colors produced by the LED light source. Such a requirement to physically toggle switches in order to change colors, is labor intensive and time consuming. Therefore, the various different colors of illumination cannot be selected or changed in an instant. It would therefore be advantageous to provide an LED lighting apparatus that is lightweight and portable and operates using a minimal number of components. More particularly, it would be advantageous to provide such an apparatus with a single power supply/controller and which can have the illumination color and intensity selected and switched instantly by the press of a button. The present invention addresses these needs.
<SOH> SUMMARY OF THE INVENTION <EOH>To achieve these and other objects, and in view of its purposes, the present invention is directed to providing light of a selectable color using LEDs (light emitting diodes) and other light sources. In one embodiment, the present invention provides a lighting apparatus comprising a plurality of LEDs and an integral power supply/controller disposed within a unitary housing and coupled only to the plurality of LEDs and a power source. The power supply/controller includes a power supply module, a memory device, a user interface and a controller. The power supply module receives power from a power source, modulates the power and provides modulated power to the plurality of LEDs. The user interface has a plurality of pre-set buttons, and the controller receives a signal from each of said pre-set buttons and communicates with the memory unit and the power supply module to instantly cause the plurality of LEDs to produce an illumination color.
Method and computer system for identifying objects for archiving
Methods and computer systems are provided for identifying objects for archiving out of a plurality of objects. A first computer system supplies a plurality of objects for archiving. Each object may have an object type and at least one sub-object. Further, an assignment scheme may be provided, which assigns a plurality of sub-object types to the object type. A computer program may identify at least one sub-object for archiving with the object by using the assignment scheme. A second computer system may receive data for archiving from the first computer system. The data may comprise the object and the at least one sub-object that are identified by the first computer system for archiving. The second computer system may store the data.
1. A computer-implemented method for identifying objects for archiving from a plurality of objects the method comprising the following steps of: supplying a plurality of objects for archiving, wherein an object includes an object type and at least one sub-object; providing an assignment scheme that assigns a plurality of sub-object types to the object type; and identifying the at least one sub-object for archiving with the object, wherein the at least one sub-object has a sub-object type that is assigned to the object type of the object. 2. A method for archiving objects the method comprising the steps of: receiving data for archiving, wherein the data comprise a first portion for an object including an object type and a second portion for at least one sub-object including a sub-object type the sub-object being assigned to the object, wherein the assignment is identified by an assignment scheme that assigns the sub-object type to the object type, respectively; and archiving the data. 3. The method of claim 1, wherein in the supplying step the object is a document and the at least one sub-object is a part of the document. 4. The method of claim 1, further comprising the step of: archiving the at least one sub-object with the object. 5. A computer system for archiving objects the computer system comprising: an application computer including a first memory, the first memory supplying a plurality of objects for archiving, wherein an object includes an object type and at least one sub-object, the first memory providing an assignment scheme that assigns a plurality of sub-object types to the object type, the application computer further including an identifier for identifying the at least one sub-object for archiving with the object, wherein the at least one sub-object includes a sub-object type that is assigned to the object type of the object; and an archiving computer including a second memory for archiving the at least one sub-object with the object. 6. A computer system for identifying objects for archiving, the computer system comprising: a memory that supplies a plurality of objects for archiving, wherein an object includes an object type and at least one sub-object, the memory providing an assignment scheme that assigns a plurality of sub-object types to the object type; and an identifier for identifying the at least one sub-object for archiving with the object, wherein the at least one sub-object includes a sub-object type that is assigned to the object type of the object. 7. The computer system of claim 6, further comprising: an archiver for archiving the at least one sub-object with the object. 8. A computer system for archiving objects, the computer system comprising: an interface for receiving data for archiving from a further computer, wherein the data comprise a first portion for an object having an object type and a second portion for at least one sub-object having a sub-object type, the sub-object being assigned to the object, wherein the assignment is identified by an assignment scheme that assigns the sub-object type to the object type; and a memory for archiving the data. 9. A computer program product comprising a plurality of instructions for causing a processor of a computer to identify objects for archiving, the computer program product causing the computer to execute the steps of: supplying a plurality of objects for archiving, wherein an object includes an object type and at least one sub-object; providing an assignment scheme that assigns a plurality of sub-object types to the object type; and identifying the at least one sub-object for archiving with the object, wherein the at least one sub-object includes a sub-object type that is assigned to the object type of the object. 10. A computer program product comprising a plurality of instructions for causing a processor of a computer to archive objects, the computer program product causing the computer to execute the steps of: receiving data for archiving, wherein the data comprise a first portion for an object including an object type and a second portion for at least one sub-object including a sub-object type, the sub-object being assigned to the object, wherein the assignment is identified by an assignment scheme that assigns the sub-object type to the object type, respectively; and archiving the data. 11. A data carrier readable by a computer, the data carrier storing a plurality of instructions for causing a processor of the computer to identify objects for archiving, the plurality of instructions causing the computer to execute a method according to any of claims 1 and 4. 12. A data carrier readable by a computer; the data carrier storing a plurality of instructions for causing a processor of the computer to archive objects; the plurality of instructions causing the computer to execute a method according to claim 2.
<SOH> BACKGROUND OF THE INVENTION <EOH>In prior art systems, such as Enterprise Resource Planning (ERP) systems (e.g. SAP R/3 from SAP AG) the archiving of data is achieved by providing an archiving program for each different type of data. Typically, the data that are subject to archiving are documents, such as a financial document (e.g. an accounting voucher) or a purchasing document, where items purchased from a certain vendor are listed. Another example of data that can be a subject to archiving is a database table. In the latest prior art systems (e.g. SAP Customer Relationship Management) documents are objects that comprise sub-objects. Each object has a defined object type (e.g. purchasing document, invoice, accounting voucher, etc.). Each sub-object has a defined sub-object type (e.g. business partner, note, product, etc.). An object type includes a specific subset of sub-object types. For example, a purchasing document object comprises sub-objects of type business partner (e.g. address data of a supplier) and of type product (e.g. the line items of the purchasing document). An accounting voucher object would not comprise a product sub-object, because product information has no relevance in financial accounting. However, the accounting voucher object could comprise a business partner sub-object with the bank account of a supplier. Therefore, an assignment scheme defines assignments of sub-object types to object types. One sub-object type can be assigned to multiple object types. New object types can thus be created by composing a new subset of sub-object types. Typically, each object/sub-object type has a unique data structure and the corresponding archiving program has to reflect this unique data structure to archive all data within the object. Whenever the data structure of an object/sub-object type is modified (e.g. a table is added to or removed from an object/sub-object), the corresponding archiving program does not take into account the modifications unless it is manually adjusted to the new data structure of the modified object/sub-object type. Without this adjustment some data within an object/sub-object of the modified object/sub-object type are not subject to archiving. Complex application systems, such as ERP systems, support a large number of different object/sub-object types, which makes it difficult to keep the data structures of the object/sub-object types consistent with the corresponding archiving programs.
<SOH> SUMMARY OF THE INVENTION <EOH>Hence, the present invention provides computer-implemented method, computer program product and computer system to solve the technical problem of inconsistencies between the data structure of objects/sub-objects that are subject to archiving and the corresponding archiving programs. According to a first preferred embodiment of the present invention, the solution to the technical problem is provided by the following characteristics: A first inventive computer-implemented method on an application computer for identifying objects (e.g. application objects) for archiving comprises the steps: a) supplying a plurality of objects, wherein an object for archiving has an object type and has at least one sub-object; b) providing an assignment scheme that assigns a plurality of sub-object types to the object type; and c) identifying the at least one sub-object for archiving with the object, wherein the at least one sub-object has a sub-object type that is assigned to the object type of the object. The first inventive computer-implemented method is complemented by a second inventive computer-implemented method on an archiving computer for archiving the objects that are identified in the first method. The second method comprises the steps: a) receiving data for archiving, wherein the data comprise a first portion for an object having an object type and a second portion for at least one sub-object having a sub-object type. The sub-object is assigned to the object, wherein the assignment is identified by an assignment scheme that assigns the sub-object type to the object type, respectively. b) archiving the data, wherein archiving means storing in a memory of the archiving computer. A further preferred embodiment of the invention is implemented as first and second computer program products. The first computer program product has a plurality of instructions for causing a processor of the application computer to execute the steps of the first method to identify objects for archiving. The second computer program product has a plurality of instructions for causing a processor of the archiving computer to execute the steps of the second method to archive the objects that are identified by the first computer program product. The first and second computer program products can be stored on a first and second data carrier, respectively. An advantage of the present invention is the combination of the enhanced flexibility in defining object types by composing subsets of sub-object types with the improved system control for assuring the completeness of archived objects. The first method always identifies all sub-objects for archiving that belong to an object on the application computer by collecting all sub-objects that have a sub-object type which is assigned to the object type of the object in the assignment scheme. If a new sub-object type gets assigned to the object type, the inventive first method automatically considers all sub-objects having the new sub-object type for archiving. The second method completes the archiving process. A further advantage of the present invention is the independence of archiving programs from object/sub-object data structures. Therefore, the need for manual adjustments to archiving programs after the modification of the data structure of a corresponding object/sub-object type is eliminated. The first computer program product takes advantage of the object oriented nature of the documents. The first computer program product can handle any object having an object type where sub-object types are assigned to in the assignment scheme. Any addition, modification or removal of sub-objects in the assignment scheme is immediately considered by the first computer program product without any modification, because all sub-objects are identified on the base of sub-object type-to-object type assignments. The second computer program product completes the archiving process on the archiving computer. The aspects of the invention will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims. It is to be understood that both, the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention as described.
Gnrh agonist combination drugs
In the field of pharmaceuticals, it is intended to provide drugs whereby the preventive and therapeutic effects of a GnRH agonist on various diseases can be enhanced and QOL can be improved. More specifically, combination of drugs characterized in that the GnRH agonist is combined with a chemical selected from among SERM, SARM, sex hormone synthesis inhibitors, receptor-type tyrosine kinase inhibitors, bone metabolism regulators, drugs for immunotherapy, cytokine/chemokine inhibitors and endothelin receptor antagonists. Owing to these combinations, excellent effects of enhancing the preventive and therapeutic effects of the GnRH agonist on various diseases and relieving side effects can be established. Furthermore, QOL can be improved thereby.
1. A pharmaceutical composition for preventing or treating breast cancer, precocious puberty, endometriosis, hysteromyoma, Alzheimer's disease, circulatory organ disease, menopausal syndrome, equivocal complaint, cancer metastasis, PMS (premenstrual syndrome), dysmenorrhea or calcium/phosphorus bone dysbolism which is a combination of a GnRH agonist and a SERM (selective estrogen receptor modulator) drug. 2. The pharmaceutical composition according to claim 1, wherein the SERM drug is raloxifene, arzoxifene, lasofoxifene, TSE-424, SERM-3339 or SPC-8490. 3. The pharmaceutical composition according to claim 1 which is an improver of a fertilized ovum implantation rate after treatment of endometriosis. 4. A method for preventing or treating breast cancer, precocious puberty, endometriosis, hysteromyoma, Alzheimer's disease, circulatory organ disease, menopausal syndrome, equivocal complaint, cancer metastasis, PMS, dysmenorrhea or calcium/phosphorus bone dysbolism, which comprises administering a combination of an effective amount of a GnRH agonist and an effective amount of a SERM agent to a mammal. 5. An Add-Back therapy which comprises administering a combination of an effective amount of a GnRH agonist and an effective amount of a SERM agent to a mammal. 6. A method for improving a fertilized ovum implantation rate after treatment of endometriosis which comprises administering a combination of an effective amount of a GnRH agonist and an effective amount of a SERM agent to a mammal. 7. A method for treating breast cancer or hysteromyoma which comprises administering a combination of an effective amount of a GnRH agonist and an effective amount of a SERM agent to a mammal to reduce the size of breast cancer or hysteromyoma, followed by a surgical operation or irradiation therapy. 8. A pharmaceutical composition for preventing or treating prostate cancer or prostatic hypertrophy which is a combination of a GnRH agonist and a SARM (selective androgen receptor modulator) drug. 9. The pharmaceutical composition according to claim 8, wherein the SARM drug is LGD2226. 10. A method for treating prostate cancer or prostatic hypertrophy which comprises administering a combination of an effective amount of a GnRH agonist and an effective amount of a SARM drug to a mammal to reduce the size of prostate cancer or prostatic hypertrophy, followed by a surgical operation or irradiation therapy. 11. A pharmaceutical composition for preventing or treating prostate cancer, breast cancer, prostatic hypertrophy, postoperative recurrence of prostate cancer or breast cancer, or metastasis of prostate cancer or breast cancer which is a combination of a GnRH agonist and a sex hormone synthesis inhibitor. 12. The pharmaceutical composition according to claim 11, wherein the sex hormone synthesis inhibitor is a lyase inhibitor. 13. The pharmaceutical composition according to claim 11 which is a MAB (Maximum androgen blockade) therapy agent. 14. A method for preventing or treating prostate cancer, breast cancer, prostatic hypertrophy, postoperative recurrence of prostate cancer or breast cancer, or metastasis of prostate cancer or breast cancer which comprises administering a combination of an effective amount of a GnRH agonist and an effective amount of a lyase inhibitor to a mammal. 15. An MAB (maximum androgen blockade) therapy which comprises administering a combination of an effective amount of a GnRH agonist and an effective amount of a lyase inhibitor to a mammal. 16. A method for treating prostate cancer or breast cancer which comprises administering a combination of an effective amount of a GnRH agonist and an effective amount of a lyase inhibitor to a mammal to reduce the size of prostate cancer or breast cancer, followed by a surgical operation or irradiation therapy. 17. A pharmaceutical composition for preventing or treating prostate cancer, breast cancer, postoperative recurrence of prostate cancer or breast cancer, or metastasis of prostate cancer or breast cancer which is a combination of a GnRH agonist and a receptor-type tyrosine kinase inhibitor. 18. A pharmaceutical composition according to claim 17, wherein the receptor-type tyrosine kinase inhibitor is gefitinib, imatinib, semaxanib, SI-744, SU-6668, SU-101, GW-2016 or CI-1033. 19. A method for preventing or treating prostate cancer, breast cancer, postoperative recurrence of prostate cancer or breast cancer, or metastasis of prostate cancer or breast cancer which comprises administering a combination of an effective amount of a GnRH agonist and an effective amount of a receptor-type tyrosine kinase inhibitor to a mammal. 20. The method according to claim 19, wherein a combination of an effective amount of a GnRH agonist and an effective amount of a receptor-type tyrosine kinase inhibitor is administered according to a blood level of a solubilized HER2. 21. A pharmaceutical composition for preventing or treating prostate cancer, breast cancer, prostatic hypertrophy, postoperative recurrence of prostate cancer or breast cancer, menopausal syndrome or calcium/phosphorus bone dysbolism which is a combination of a GnRH agonist and a bone metabolism modulator. 22. The pharmaceutical composition according to claim 21, wherein the bone metabolism modulator is alendronic acid, etidronic acid, ibandronic acid, incadronic acid, risedronic acid, clodronic acid, pamidronic acid, olpadronic acid, zoledronic acid, tiludronic acid, neridronic acid, EB-1053, YH529, ipriflavone or osteoprotegerin. 23. A method for preventing or treating prostate cancer, breast cancer, prostatic hypertrophy, postoperative recurrence of prostate cancer or breast cancer, menopausal syndrome or calcium/phosphorus bone dysbolism which comprises administering a combination of an effective amount of a GnRH agonist and an effective amount of a bone metabolism modulator to a mammal. 24. A pharmaceutical composition for preventing or treating prostate cancer, breast cancer, prostatic hypertrophy, endometriosis, hysteromyoma, postoperative recurrence of prostate cancer or breast cancer or metastasis of prostate cancer or breast cancer which is a combination of a GnRH agonist and an immunotherapeutic agent. 25. A method for preventing or treating prostate cancer, breast cancer, prostatic hypertrophy, endometriosis, hysteromyoma, postoperative recurrence of prostate cancer or breast cancer or metastasis of prostate cancer or breast cancer which comprises administering a combination of an effective amount of a GnRH agonist and an effective amount of an immunotherapeutic drug to a mammal. 26. The method according to claim 25, wherein a combination of an effective amount of a GnRH agonist and an effective amount of an immunotherapeutic agent is administered according to a blood level of a solubilized HER2. 27. A method for treating prostate cancer, breast cancer or hysteromyoma which comprises administering a combination of an effective amount of a GnRH agonist and an effective amount of an immunotherapeutic drug to a mammal to reduce the size of prostate cancer, breast cancer or hysteromyoma, followed by a surgical operation or irradiation therapy. 28. A pharmaceutical composition for preventing or treating prostate cancer, breast cancer, postoperative recurrence of prostate cancer or breast cancer, or metastasis of prostate cancer or breast cancer which is a combination of a GnRH agonist and a cytokine/chemokine inhibitor. 29. A method for preventing or treating prostate cancer, breast cancer, postoperative recurrence of prostate cancer or breast cancer, or metastasis of the prostate cancer or breast cancer which comprises administering a combination of an effective amount of a GnRH agonist and an effective amount of a cytokine/chemokine inhibitor to a mammal. 30. The method according to claim 29, wherein a combination of an effective amount of a GnRH agonist and an effective amount of a cytokine/chemokine inhibitor is administered according to a blood level of a solubilized HER2. 31. A pharmaceutical composition for preventing or treating prostate cancer, postoperative recurrence of prostate cancer or metastasis of prostate cancer which is a combination of a GnRH agonist and an endothelin receptor antagonist. 32. The pharmaceutical composition according to claim 31, wherein the endothelin receptor antagonist is atrasentan, YM-598, TA-0201, bosentan, SB-217242, SB-209670, TBC-11251, BQ-123, ABT-627 or a peptide represented by the formula: Cyclo[-D-Asp-Asp(R1)-Asp-D-Thg(2)-Leu-D-Trp-] wherein Asp(R1) is an aspartic acid β-4-phenylpiperazineamide residue and Thg(2) is a 2-thienylglycine residue, or a disodium salt thereof. 33. A method for preventing or treating prostate cancer, postoperative recurrence of prostate cancer or metastasis of prostate cancer which comprises administering a combination of an effective amount of a GnRH agonist and an effective amount of an endothelin receptor antagonist to a mammal. 34. The pharmaceutical composition according to claim 1, wherein the GnRH agonist is a peptide represented by the formula: 5-oxo-Pro-His-Trp-Ser-Tyr-Y-Leu-Arg-Pro-Z wherein Y is a residue selected from DLeu, DAla, DTrp, DSer(tBu), D2Nal and DHis(ImBzl) and Z is NH—C2H5 or Gly-NH2, or a salt thereof. 35. The pharmaceutical composition according to claim 34, wherein the GnRH agonist is an acetate of the peptide represented by the formula: 5-oxo-Pro-His-Trp-Ser-Tyr-DLeu-Leu-Arg-Pro-NH—C2H5. 36. The pharmaceutical composition according to claim 1, wherein the GnRH agonist is used as a sustained release preparation or an implant. 37. The pharmaceutical composition according to claim 36, wherein the sustained release preparation is a sustained release microcapsule.
<SOH> BACKGROUND OF THE INVENTION <EOH>A luteinizing hormone-releasing hormone which is known as an LHRH (or GnRH) is secreted from a hypothalamus and bound to a pituitary receptor. As a result, an LH (luteinizing hormone) and an FSH (follicle-stimulating hormone) are secreted and act on a gonad whereby synthesizing steroidal sex hormones. A continuous administration of a compound having a potent luteinizing hormone-releasing hormone activity results in a reduction in the number of available receptors, which reduces the formation of gonad-derived steroidal sex hormones. Utilizing such a behavior, a compound having a GnRH activity is applied clinically as a drug for treating sex hormone-dependent diseases such as prostate cancer, benign prostatic hypertrophy, endometriosis, hysteromyoma, uterine fibrosis, precocious puberty, breast cancer and the like.