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<SOH> SUMMARY OF THE INVENTION <EOH>Various embodiments of the invention provide purified polypeptides, proteins associated with cell growth, differentiation, and death, referred to collectively as “CGDD” and individually as “CGDD-1,” “CGDD-2,” “CGDD-3,” “CGDD-4,” “CGDD-5,” “CGDD-6,” “CGDD-7,” “CGDD-8,” “CGDD-9,” “CGDD-10,” “CGDD-11,” “CGDD-12,” “CGDD-13,” “CGDD-14,” “CGDD-15,” “CGDD-16,” “CGDD-17,” and “CGDD-18,” and methods for using these proteins and their encoding polynucleotides for the detection, diagnosis, and treatment of diseases and medical conditions. Embodiments also provide methods for utilizing the purified proteins associated with cell growth, differentiation, and death and/or their encoding polynucleotides for facilitating the drug discovery process, including determination of efficacy, dosage, toxicity, and pharmacology. Related embodiments provide methods for utilizing the purified proteins associated with cell growth, differentiation, and death and/or their encoding polynucleotides for investigating the pathogenesis of diseases and medical conditions. An embodiment provides an isolated polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-18, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical or at least about 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-18, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-18, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-18. Another embodiment provides an isolated polypeptide comprising an amino acid sequence of SEQ ID NO:1-18. Still another embodiment provides an isolated polynucleotide encoding a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-18, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical or at least about 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-18, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-18, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-18. In another embodiment, the polynucleotide encodes a polypeptide selected from the group consisting of SEQ ID NO:1-18. In an alternative embodiment, the polynucleotide is selected from the group consisting of SEQ ID NO:19-36. Still another embodiment provides a recombinant polynucleotide comprising a promoter sequence operably linked to a polynucleotide encoding a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-18, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical or at least about 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-18, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-18, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-18. Another embodiment provides a cell transformed with the recombinant polynucleotide. Yet another embodiment provides a transgenic organism comprising the recombinant polynucleotide. Another embodiment provides a method for producing a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-18, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical or at least about 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-18, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-18, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-18. The method comprises a) culturing a cell under conditions suitable for expression of the polypeptide, wherein said cell is transformed with a recombinant polynucleotide comprising a promoter sequence operably linked to a polynucleotide encoding the polypeptide, and b) recovering the polypeptide so expressed. Yet another embodiment provides an isolated antibody which specifically binds to a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-18, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical or at least about 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-18, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-18, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-18. Still yet another embodiment provides an isolated polynucleotide selected from the group consisting of a) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:19-36, b) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 90% identical or at least about 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:19-36, c) a polynucleotide complementary to the polynucleotide of a), d) a polynucleotide complementary to the polynucleotide of b), and e) an RNA equivalent of a)-d). In other embodiments, the polynucleotide can comprise at least about 20, 30, 40, 60, 80, or 100 contiguous nucleotides. Yet another embodiment provides a method for detecting a target polynucleotide in a sample, said target polynucleotide being selected from the group consisting of a) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:19-36, b) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 90% identical or at least about 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:19-36, c) a polynucleotide complementary to the polynucleotide of a), d) a polynucleotide complementary to the polynucleotide of b), and e) an RNA equivalent of a)-d). The method comprises a) hybridizing the sample with a probe comprising at least 20 contiguous nucleotides comprising a sequence complementary to said target polynucleotide in the sample, and which probe specifically hybridizes to said target polynucleotide, under conditions whereby a hybridization complex is formed between said probe and said target polynucleotide or fragments thereof, and b) detecting the presence or absence of said hybridization complex. In a related embodiment, the method can include detecting the amount of the hybridization complex. In still other embodiments, the probe can comprise at least about 20, 30, 40, 60, 80, or 100 contiguous nucleotides. Still yet another embodiment provides a method for detecting a target polynucleotide in a sample, said target polynucleotide being selected from the group consisting of a) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:19-36, b) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 90% identical or at least about 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:19-36, c) a polynucleotide complementary to the polynucleotide of a), d) a polynucleotide complementary to the polynucleotide of b), and e) an RNA equivalent of a)-d). The method comprises a) amplifying said target polynucleotide or fragment thereof using polymerase chain reaction amplification, and b) detecting the presence or absence of said amplified target polynucleotide or fragment thereof. In a related embodiment, the method can include detecting the amount of the amplified target polynucleotide or fragment thereof. Another embodiment provides a composition comprising an effective amount of a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-18, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical or at least about 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-18, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-18, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-18, and a pharmaceutically acceptable excipient. In one embodiment, the composition can comprise an amino acid sequence selected from the group consisting of SEQ ID NO:1-18. Other embodiments provide a method of treating a disease or condition associated with decreased or abnormal expression of functional CGDD, comprising administering to a patient in need of such treatment the composition. Yet another embodiment provides a method for screening a compound for effectiveness as an agonist of a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-18, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical or at least about 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-18, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-18, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-18. The method comprises a) exposing a sample comprising the polypeptide to a compound, and b) detecting agonist activity in the sample. Another embodiment provides a composition comprising an agonist compound identified by the method and a pharmaceutically acceptable excipient. Yet another embodiment provides a method of treating a disease or condition associated with decreased expression of functional CGDD, comprising administering to a patient in need of such treatment the composition. Still yet another embodiment provides a method for screening a compound for effectiveness as an antagonist of a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-18, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical or at least about 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-18, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-18, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-18. The method comprises a) exposing a sample comprising the polypeptide to a compound, and b) detecting antagonist activity in the sample. Another embodiment provides a composition comprising an antagonist compound identified by the method and a pharmaceutically acceptable excipient. Yet another embodiment provides a method of treating a disease or condition associated with overexpression of functional CGDD, comprising administering to a patient in need of such treatment the composition. Another embodiment provides a method of screening for a compound that specifically binds to a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-18, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical or at least about 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-18, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-18, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-18. The method comprises a) combining the polypeptide with at least one test compound under suitable conditions, and b) detecting binding of the polypeptide to the test compound, thereby identifying a compound that specifically binds to the polypeptide. Yet another embodiment provides a method of screening for a compound that modulates the activity of a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-18, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical or at least about 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-18, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-18, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-18. The method comprises a) combining the polypeptide with at least one test compound under conditions permissive for the activity of the polypeptide, b) assessing the activity of the polypeptide in the presence of the test compound, and c) comparing the activity of the polypeptide in the presence of the test compound with the activity of the polypeptide in the absence of the test compound, wherein a change in the activity of the polypeptide in the presence of the test compound is indicative of a compound that modulates the activity of the polypeptide. Still yet another embodiment provides a method for screening a compound for effectiveness in altering expression of a target polynucleotide, wherein said target polynucleotide comprises a polynucleotide sequence selected from the group consisting of SEQ ID NO:19-36, the method comprising a) exposing a sample comprising the target polynucleotide to a compound, b) detecting altered expression of the target polynucleotide, and c) comparing the expression of the target polynucleotide in the presence of varying amounts of the compound and in the absence of the compound. Another embodiment provides a method for assessing toxicity of a test compound, said method comprising a) treating a biological sample containing nucleic acids with the test compound; b) hybridizing the nucleic acids of the treated biological sample with a probe comprising at least 20 contiguous nucleotides of a polynucleotide selected from the group consisting of i) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:19-36, ii) a polynucleotide comprising a naturally occurring-polynucleotide sequence at least 90% identical or at least about 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:19-36, iii) a polynucleotide having a sequence complementary to i), iv) a polynucleotide complementary to the polynucleotide of ii), and v) an RNA equivalent of i)-iv). Hybridization occurs under conditions whereby a specific hybridization complex is formed between said probe and a target polynucleotide in the biological sample, said target polynucleotide selected from the group consisting of i) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:19-36, ii) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 90% identical or at least about 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:19-36, iii) a polynucleotide complementary to the polynucleotide of i), iv) a polynucleotide complementary to the polynucleotide of ii), and v) an RNA equivalent of i)-iv). Alternatively, the target polynucleotide can comprise a fragment of a polynucleotide selected from the group consisting of i)-v) above; c) quantifying the amount of hybridization complex; and d) comparing the amount of hybridization complex in the treated biological sample with the amount of hybridization complex in an untreated biological sample, wherein a difference in the amount of hybridization complex in the treated biological sample is indicative of toxicity of the test compound. |
Method and device for confirming the authenticity of a document and a safe for storing data |
The invention relates to a method for confirming the authenticity of a document. According to the invention, said method is carried out in such a way that the authenticity is confirmed using a digital signature, the signed confirmation of authenticity is integrated into the document by means of a secret watermark and that the document is also provided with a public watermark. |
1. A method for confirming the authenticity of a document, in which the document is provided with a digital signature assigned to the author as well as with a digital watermark, comprising: making the signature with a secret key; inserting the signature into the document by means of a digital watermark that can be read out with a key containing information that is characteristic of the document and; checking the authenticity of the signature by a trust center. 2. The method according to claim 1, comprising additionally marking the document with a watermark that can be read out with a public key. 3. The method according to claim 1, wherein the information that is characteristic of the document contains a hash value. 4. The method according to claim 1, comprising storing the execution of the confirmation of the authenticity in a separate file. 5. The method according to claim 4, comprising transmitting the file and/or the certified data to a trust center. 6. The method according to claim 5, comprising checking by the trust center whether the digital signature belongs to a person who is authorized to confirm the authenticity of documents. 7. The method according to claim 6, comprising performing a checking procedure to ascertain whether the particulars of the person are stored in a separate list. 8. The method according to claim 6, comprising issuing by the trust center a confirmation that the owner of the signature is authorized to confirm the authenticity of documents. 9. The method according to claim 8, comprising signing by the trust center the data to confirm that the certifier is authorized. 10. The method according to claim 1, comprising inserting a watermark that can be read out with a secret key is inserted into the watermark that can be read out with a public key. 11. The method according to claim 1, wherein the watermark that can be read out with a secret key contains metainformation. 12. The method according to claim 1, comprising embedding the watermark that can be read out with a public key in a graphic symbol, wherein the graphic symbol recognizably confirms the authenticity of the document, and wherein the graphic symbol can hold as much information as the watermark can hold security-relevant information. 13. The method according to claim 2, comprising, before additionally marking the document with the watermark that can be read out with a public key, performing a checking procedure to ascertain whether the watermark that can be read out with a public key can hold a sufficient amount of security information. 14. The method according to claim 1, comprising recording the point in time of the confirmation of the authenticity of the data. 15. The method according to claim 14, comprising inserting the point in time into the secret watermark. 16. The method according to claim 14 comprising certifying the point in time by a digital time stamp. 17. The method according to claim 16, comprising carrying out the certification of the point in time by the digital time stamp in a trust center. 18. The method according to claim 1, comprising storing the data whose authenticity has been confirmed in a database. 19. The method according to claim 18, wherein the trust center encompasses the database. 20. The method according to claim 1, comprising carrying out the method for confirming the authenticity of the document at different security levels. 21. The method according to claim 20, wherein higher security levels can be achieved through a higher number of verification elements. 22. The method according to claim 21, comprising using different granularities of the verification elements. 23. The method according to claim 1, comprising inserting a message digest into at least one of the document and the watermark that can be read out with a secret key. 24. An electronic document processed by means of a method according to claim 1. |
Apparatus for capturing an object scene |
An apparatus for capturing an object scene, in particular a seeking head for target-tracking missiles, such that, with a detector 86 in fixed relationship with a structure, it is possible to capture a large spatial angle. For that purpose the imaging optical system (30) has a system portion (28) facing the object scene which is pivotable with a pitch frame (24) about a pitch axis (26) perpendicular to a roll axis (18). The pitch frame (24) is mounted pivotably about the pitch axis (26) in a roll frame (16) which is supported in the structure (10) rotatably about the roll axis (18). The system portion (28) includes first beam deflection structure (36) by which the imaging beam path of the imaging optical system (30) is deflectable in a direction along the pitch axis (26). The imaging optical system (30) further includes second beam deflection structure (52) which are rotatable with the roll frame (16) and by which the deflected beam path is picked up along the pitch axis (26) and deflected in the direction of the roll axis (18). The detector (86) is arranged on the roll axis (18). |
1. Apparatus for capturing an object scene, including an imaging optical system (30) which is pivotable relative to a structure (10) and a detector (86) which is fixed with respect to the structure and on which an image of the object scene is produced by the imaging optical system (30), characterized in that (a) the imaging optical system (30) a system portion (28) facing the object scene which is pivotable with a pitch frame (24) about a pitch axis (26) perpendicular to a roll axis (18), (b) the pitch frame (24) is supported pivotably about the pitch axis (26) in a roll frame (16) which is supported rotatably about the roll axis (18) in the structure (10), (c) the system portion (28) includes first beam deflection means by which the imaging beam path of the imaging optical system (30) is deflectable in a direction along the pitch axis (26), (d) the imaging optical system (30) further includes second beam deflection means (52) which are rotatable with the roll frame (16) and by which the deflected beam path of the first beam deflection means is picked up along the pitch axis (26) and deflected in the direction of the roll axis (18), and (e) the detector (86) is arranged on the roll axis (18). 2. Apparatus as set forth in claim 1 characterized in that (a) the system portion (28) has the first beam deflection means including first reflecting means (36) by which the imaging beam path of the imaging optical system (30) is deflectable in a direction along the pitch axis (26), (b) provided in the roll frame (16) and rotatable therewith on the pitch axis (26) are second reflecting means (54) by which the imaging beam path of the imaging optical system (30) is deflectable in a direction parallel to the roll axis (18), (c) provided in the roll frame (16) and rotatable therewith there are third reflecting means (56) by which the imaging beam path deflected in that way is deflectable towards the roll axis (18) in a direction parallel to the pitch axis (26), and (d) provided in the roll frame (16) and rotatable therewith on the roll axis (18) are fourth reflecting means (58) by which the imaging beam path deflected by the third reflecting means (56) is deflectable in the direction of the roll axis (18) onto the detector (86), the second, third and fourth reflecting means forming the second beam deflection means (52). 3. Apparatus as set forth in claim 1 characterized in that (a) the system portion (28) in the pitch frame (24) has first reflecting means (36) by which the imaging beam path of the imaging optical system (30) is deflectable in a direction parallel to the pitch axis (26), (b) provided in the pitch frame (24) is a second reflecting means (54) by which the imaging beam path of the imaging optical system (30) is deflectable in a direction parallel to the roll axis (18), (c) in the pitch frame (24) there is further a third reflecting means (54) by which the imaging beam path deflected in that way deflected is deflectable towards the roll axis (18) in a direction along the pitch axis (26), the first, second and third reflecting means forming the first beam deflection means, and (d) in the roll frame (16) and rotatable therewith on the roll axis (18) as second beam deflection means there are provided fourth reflecting means (58) by which the imaging beam path deflected by the third reflecting means (56) is deflectable in the direction of the roll axis (18) onto the detector (86). 4. Apparatus as set forth in claim 2 or claim 3 characterized in that the reflecting means are deflection prisms (36, 65, 56, 58) of a cross-section substantially forming an isosceles right triangle, whose totally reflecting hypotenuse surfaces (42, 60, 68, 78) deflect the imaging beam path, wherein the cathetus surfaces (62, 66; 72, 74; 82, 84) are respectively perpendicular to the optical axis of the imaging beam path. 5. Apparatus as set forth in claim 4 characterized in that at least a part of the cathetus surfaces form curved lens surfaces. 6. Apparatus as set forth in claim 4 characterized in that the plurality of deflection prisms forming the first or the second beam deflection means are formed by a continuous body (90). 7. Apparatus as set forth in claim 2 or claim 3, characterized in that (a) the imaging optical system (30) is arranged behind a hemispherical dome (12), (b) the pitch and roll axes (26, 18) perpendicularly intersect at the center point (40) of curvature of said dome (12), and (c) the reflecting surface of the first reflecting means (36) extends at 45° relative to the roll axis (18) through said intersection point (40). 8. Apparatus as set forth in one of claims 1 through 3 characterized in that the imaging optical system (30) produces at least one intermediate image (50) in the region of the beam deflection means (36, 52). 9. Apparatus as set forth in claim 8 characterized in that the intermediate image is produced by the system portion (28) between the first and second beam deflection means (36, 52). 10. A missile which is equipped with an apparatus as set forth in claim 1. |
Bipolar plate of fuel cell and fabrication method thereof |
In a bipolar plate of a fuel cell and a fabrication method thereof, the bipolar plate of the fuel cell includes a plate; a fluid flowing space formed on both sides of the plate; a fluid guide mesh installed on the fluid flowing space; an inflow path formed on the plate to be connected with the fluid flowing space; and an outflow path formed on the plate to be connected with the fluid flowing space. Also, in the fabrication method, the bipolar plate is fabricated with a certain mold and by a processing method. Accordingly, it is possible to uniformize flux distribution and reduce flow resistance of fuel and air respectively flowing into a fuel electrode and an air electrode of a fuel cell. In addition, reaction area with a M.E.A and diffusion zone can be increased, and fabrication can be simplified and facilitated. |
1. A bipolar plate of a fuel cell, comprising: a plate having a certain thickness and area; a fluid flowing space formed on both sides of the plate, the fluid flowing space configured to have a certain width, length and depth; a fluid guide mesh installed in the fluid flowing space, the fluid guide mesh having a certain shape; an inflow path formed on the plate to be connected to the fluid flowing space for introducing a fluid; and an outflow path formed on the plate to be connected to the fluid flowing space for discharging the fluid. 2. The bipolar plate of claim 1, wherein the fluid flowing space is formed as a rectangular shape, and the fluid guide mesh has a rectangular shape not greater than a size of the fluid flowing space. 3. The bipolar plate of claim 1, wherein the fluid guide mesh has a thickness not greater than a depth of the fluid flowing space. 4. The bipolar plate of claim 1, wherein the inflow path and the outflow path are respectively constructed as at least one through hole, and they are formed at a side of the plate. 5. The bipolar plate of claim 1, wherein the inflow path and the outflow path are arranged to be diagonal to each other. 6. The bipolar plate of claim 1, wherein the plate is made of a stainless steel material. 7. A method for fabricating a bipolar plate of a fuel cell, comprising: fabricating a mold for processing a plate on which a fluid flowing space having a certain area and depth is formed at both sides and a mesh is formed to be projected on fluid flowing space; making a plate with the mold; processing an inflow path on the plate for fluid flowing into the fluid flowing space having the mesh; and processing an outflow path on the plate for fluid in the fluid flowing space flowing out. 8. A bipolar plate of a fuel cell, comprising: a plate having a certain thickness and area; a channel region having latticed protrusions by plural latticed grooves formed along a certain area of both sides of the plate; an inflow path formed at a side of the plate to be connected to the latticed grooves for introducing a fluid; and an outflow path formed at a side of the plate to be connected to the latticed grooves for discharging the fluid in the latticed grooves. 9. The bipolar plate of claim 8, wherein the latticed protrusion is formed as a rectangular-cone shape. 10. The bipolar plate of claim 8, wherein the latticed protrusions are formed regularly. 11. The bipolar plate of claim 8, wherein the inflow path and the outflow path are respectively formed at a side of the plate as an open shape having a certain width and depth. 12. The bipolar plate of claim 8, wherein the plate is made of a stainless steel material. 13. A method for fabricating a bipolar plate of a fuel cell, comprising: fabricating a plate having a certain thickness and area; performing mechanical processing for forming latticed grooves by latticed protrusions formed on both sides of the plate; and processing an inflow path and an outflow path on the plate to be connected to the latticed grooves. 14. The bipolar plate of claim 13, wherein the mechanical processing step includes the sub-steps of: scratching both sides of the plate in order to form latticed protrusions; and grinding the scratched both sides of the plate. 15. A bipolar plate of a fuel cell, comprising: a plate having a certain thickness and area in which plural channels consisting of plural ups and downs are formed at both sides on the middle by being pressed so as to have a certain width and length; and a sealing member respectively adhered to the outline of the both sides of the plate so as to form internal channels with the channels of the plate, an inflow path and an outflow path in which a fluid flows in/out through the channels. 16. The bipolar plate of claim 15, wherein the internal channels includes: an inflow buffer channel for distributing a fluid to the channels of the plate; an outflow buffer channel for making the fluid passing the channels of the plate flow into the outflow channel; and a connection channel for connecting the inflow buffer channel and the outflow buffer channel. 17. A method for fabricating a bipolar plate of a fuel cell, comprising: cutting a plate so as to have a certain size; press-processing both sides of the cut plate so as to form plural channels in which a fluid flows; and combining a sealing member with the outline of the press-processed plate. 18. The bipolar plate of claim 17, wherein ups formed by the channels are processed so as to have uniform height in the press-processing step. 19. The bipolar plate of claim 17, wherein the channels are processed so as to be straight and have a certain length in the press-processing step. 20. The bipolar plate of claim 17, wherein the sealing member is combined with the plate so as to encompassed the internal area of the plate. |
<SOH> BACKGROUND ART <EOH>A fuel cell is generally environment-friendly energy, and it has been developed in order to substitute for the conventional fossil energy. As depicted in FIG. 1 , the fuel cell includes a stack 100 to be combined with at least one unit cell 101 in which electrochemical reaction occurs; a fuel supply pipe 200 connected to the stack 100 so as to supply fuel; an air supply pipe 300 connected to the stack 100 so as to supply air; and discharge pipes 400 , 500 for discharging by-products of fuel and air passing the reaction respectively. The unit cell 101 includes a fuel electrode (anode) (not shown) in which fuel flows; and an air electrode (cathode) (not shown) in which air flows. The operation of the fuel cell will be described. First, fuel and air are supplied to the fuel electrode and the air electrode of the stack 100 through the fuel supply pipe 200 and the air supply pipe 300 respectively. Fuel supplied to the fuel electrode is ionized into positive ions and electrons (e−) through electrochemical oxidation reaction in the fuel electrode, the ionized positive ions are moved to the air electrode through an electrolyte, and the electrons are moved to the fuel electrode. The positive ions moved to the air electrode perform electrochemical reduction reaction with air supplied to the air electrode and generate by-products such as reaction heat and water, etc. In the process, by the movement of the electrons, electric energy is generated. The fuel through the reaction in the fuel electrode, and water and additional by-products generated in the air electrode are respectively discharged through the discharge pipes 400 , 500 . The fuel cell can be classified into various types according to electrolyte and fuel, etc. used therein. In the meantime, as depicted in FIG. 2 , the unit cell 101 constructing the stack 100 includes two bipolar plates 10 having an open channel 11 in which air or fuel flows; and a M.E.A (membrane electrode assembly) 20 arranged between the two bipolar plates 10 so as to have a certain thickness and area. The two bipolar plates 10 and the M.E.A 20 arranged therebetween are combined with each other by additional combining means 30 , 31 . A channel formed by a channel 11 of the bipolar plate 10 and a side of the M.E.A 20 constructs a fuel electrode, and oxidation reaction occurs while fuel flows through the channel of the fuel electrode. And, a channel formed by a channel 11 of the other bipolar plate 10 and the other side of the M.E.A 20 constructs an air electrode, and reduction reaction occurs while air flows through the channel of the air electrode. A shape of the bipolar plate 10 , in particular, a shape of the channel 11 affects contact resistance generated in flowing of fuel and air and flux distribution, etc., and contact resistance and flux distribution affect power efficiency. And, the bipolar plates 10 have a certain shape appropriate to processing facilitation and mass production. As depicted in FIG. 3 , in the conventional bipolar plate, through holes 13 , 14 , 15 , 16 are respectively formed at each edge of the plate 12 having a certain thickness and a rectangular shape. And, plural channels 11 are formed on a side of the plate 12 so as to connect the through hole 13 with the diagonally arranged through hole 16 . The channels 11 have a zigzag shape. As depicted in FIG. 4 , in the section of the channel 11 , the channel 11 has a certain width and depth and an open side. Plural channels 11 are formed on the other side of the plate 12 so as to connect the diagonally arranged two through holes 14 , 16 , and the channels 11 have the same shape with the channels formed on the opposite side. The operation of the conventional bipolar plate will be described. First, fuel and air respectively flow into the through holes 13 , 14 , fuel and air passing the through holes 13 , 14 flow into the channels 11 . Fuel or air in the channels 11 flows zigzag along the channels 11 and is discharged to the outside through the through holes 15 , 16 . In that process, oxidation reaction occurs in the M.E.A 20 (shown in FIG. 2 ) in which fuel flows, simultaneously reduction reaction occurs in the M.E.A in which air flows. However, in the conventional bipolar plate, because the channels 11 are formed as zigzag, flux can be distributed evenly to some degree. However, because the channels in which fuel and air flow are complicate and long, flow resistance is increased, and pressure loss for making fuel and air flow is increased. In addition, because processing is complicate and intricate in fabrication, a production cost is high. |
<SOH> BRIEF DESCRIPTION OF DRAWINGS <EOH>The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the principles of the invention. In the drawings: FIG. 1 illustrates the conventional fuel cell system; FIG. 2 is an exploded-perspective view illustrating part of a stack of the conventional fuel cell; FIG. 3 is a plane view illustrating a bipolar plate of the conventional fuel cell; FIG. 4 is a sectional view taken along a line A-B in FIG. 3 ; FIG. 5 is a plane view illustrating a first embodiment of a bipolar plate of a fuel cell in accordance with the present invention; FIG. 6 is an exploded-perspective view illustrating part of the bipolar plate of the fuel cell in accordance with the first embodiment of the present invention; FIG. 7 is a flow chart illustrating a first embodiment of a method for fabricating a bipolar plate of a fuel cell in accordance with the present invention; FIG. 8 is an exploded-perspective view illustrating a stack of the bipolar plate of the fuel cell in accordance with the first embodiment of the present invention; FIG. 9 is a plane view illustrating an operational state of the bipolar plate of the fuel cell in accordance with the first embodiment of the present invention; FIGS. 10 and 11 are a plane view and a front sectional view illustrating a second embodiment of a bipolar plate of a fuel cell in accordance with the present invention; FIG. 12 is a flow chart illustrating a second embodiment of a method for fabricating a bipolar plate of a fuel cell in accordance with the present invention; FIG. 13 is a plane view illustrating an operational state of the bipolar plate of the fuel cell in accordance with the second embodiment of the present invention; FIGS. 14 and 15 are a plane view and a sectional view illustrating a third embodiment of a bipolar plate of a fuel cell in accordance with the present invention; and FIG. 16 is a flow chart illustrating a third embodiment of a method for fabricating a bipolar plate of a fuel cell in accordance with the present invention. detailed-description description="Detailed Description" end="lead"? |
Apparatus and method for establishing tunnel routes to protect paths established in a data network |
A computer readable storage medium containing a program element for execution by a computing device in a network having a plurality of linked nodes, wherein paths for conveying data traffic are defined in the network, each path traversing an ordered set of nodes from among the plurality of nodes. The program element includes a first program component adapted to assign, for a particular node that is intermediate at least one particular path, a particular tunnel route to the protection of a particular subset of the at least one particular path against failures occurring downstream from the particular node along the particular subset of the at least one particular path. By providing protection for portions of a path without requiring that such protection be established on an end-to-end basis, the time, bandwidth and memory required to protect data traffic is reduced. |
1. A computer readable storage medium containing a program element for execution by a computing device in a network having a plurality of linked nodes, wherein paths for conveying data traffic are defined in the network, each path traversing an ordered set of nodes from among the plurality of nodes, said program element comprising: a first program component adapted to assign, for a particular node that is intermediate at least one particular path, a particular tunnel route to the protection of a particular subset of the at least one particular path against failures occurring downstream from the particular node along the particular subset of the at least one particular path. 2. A computer readable storage medium as defined in claim 1, the program element further comprising: a second program component adapted to store in a memory a set of first data elements, each first data element identifying: a respective subset of the at least one particular path for which the particular node is intermediate; and a respective tunnel route assigned to the protection of the respective subset of the at least one particular path against failures occurring downstream from the particular node along the respective subset of at the least one particular path. 3. A computer readable storage medium as defined in claim 2, the program element further comprising a third program element adapted to perform: a) consulting the set of first data elements to determine which, if any, of the tunnel routes identified in the first data elements is also capable of protecting the particular subset of the at least one particular path against failures occurring downstream from the particular node along the particular subset of the at least one particular path; and b) if at least one tunnel route is determined at a), selecting one of the at least one tunnel route so determined as the tunnel route assigned to protect the particular subset of the at least one particular path against failures occurring downstream from the particular node along the particular subset of the at least one particular path. 4. A computer readable storage medium as defined in claim 3, wherein a) includes consulting the set of first data elements to determine which, if any, of the tunnel routes identified in the first data elements satisfies a first condition of including two nodes that are traversed by each path in the particular subset of the at least one particular path. 5. A computer readable storage medium as defined in claim 3, where a) further includes consulting the set of first data elements to determine which, if any, of the tunnel routes found to satisfy the first condition also satisfy a second condition of including a next node that is distinct from a next node of each path in the particular subset of the at least one particular path. 6. A computer readable storage medium as defined in claim 5, wherein each path is associated with a service criterion, wherein each tunnel route is associated with network resources, wherein a) further includes consulting the set of first data elements to determine which, if any, of the tunnel routes found to satisfy the first and second conditions also satisfy a third condition of being associated with network resources that are capable of being utilized to meet the service criterion associated with the particular subset of the at one particular path in addition to the service criterion associated with the subset of the at least one particular path currently assigned to be protected by that tunnel route. 7. A computer readable storage medium as defined in claim 6, wherein the third program component is further adapted to perform: c) if no tunnel route is determined at step a), performing: i) determining which, if any, of the tunnel routes identified in the first data elements is replaceable by an augmented tunnel route associated with network resources that are capable of being utilized to meet the service criterion associated with the particular subset of the at least one particular path, in addition to the service criterion associated with the subset of the at least one particular path currently assigned to be protected by that tunnel route; ii) if at least one tunnel route is determined to be replaceable at step i), replacing one of the at least one tunnel route so determined with the augmented tunnel route. 8. A computer readable storage medium as defined in claim 7, wherein the third program component is further adapted to perform: iii) if no tunnel route is determined at sub-step i), creating a new tunnel route assigned to the protection of the particular subset of the at least one particular path against failures occurring downstream from the particular node along the particular subset of the at least one particular path. 9. A computer readable storage medium as defined in claim 8, wherein the service criterion includes a bandwidth requirement. 10. A computer readable storage medium as defined in claim 9, wherein a) further includes consulting the set of first data elements to determine which, if any, of the tunnel routes identified in the first data elements satisfies a fourth condition of including no more than two nodes that are traversed by any path in the particular subset of the at least one particular path. 11. A computer readable storage medium as defined in claim 10, wherein a) further includes consulting the set of data elements to determine which of the tunnel routes identified in the first data elements satisfying the first, second, third and fourth conditions is the shortest tunnel route. 12. A computer readable storage medium as defined in claim 10, wherein a) further includes consulting the set of first data elements to determine which of the tunnel routes identified in the first data elements satisfying the first, second, third and fourth conditions includes the smallest number of nodes. 13. A computer readable storage medium as defined in claim 10, wherein a) further includes consulting the set of first data element to determine which of the tunnel routes identified in the first data elements satisfying the first, second, third and fourth conditions is associated with the shortest propagation delay. 14. A computer readable storage medium as defined in claim 7, wherein the third program component is further adapted to perform: iii) if at least one tunnel route is determined to be replaceable at i), replacing the identification of the replaced tunnel route in the respective first data element with the identification of the augmented tunnel route. 15. A computer readable storage medium as defined in claim 1, wherein the first program component is responsive to receipt of a protection request associated with the particular subset of the at least one particular path to be protected against failures occurring downstream from the particular node along the particular subset of the at least one particular path. 16. A computer readable storage medium as defined in claim 7, wherein the third program component is adapted to perform iii) upon determining that the creation of at least one new tunnel route is feasible. 17. A computer readable storage medium as defined in claim 7, wherein the third program component is adapted to start a timer upon determining that the creation of at least one new tunnel route is not feasible and to perform iii) upon expiry of the timer. 18. A computer readable storage medium as defined in claim 2, the program element further comprising a third program component adapted to: a) receive a path delete message associated with the deletion of a no longer desired path; and b) upon receipt of the path delete message: i) de-assign the particular tunnel path from having to protect the no longer desired path against failures occurring downstream from the particular node along the no longer desired path. 19. A computer readable storage medium as defined in claim 18, wherein the particular tunnel route is associated with network resources, wherein the third program component is further adapted to, upon receipt of the path delete message: ii) free those network resources associated with the particular tunnel route having to protect the no longer desired path against failures occurring downstream from the particular node along the no longer desired path. 20. A computer readable storage medium as defined in claim 18, wherein the third program component is further adapted to cease identifying the particular tunnel route in any of the data elements if the no longer desired path is the only path in the particular subset of the at least one particular path. 21. A computer readable storage medium as defined in claim 18, wherein the third program component is further adapted to associate a first priority level to the particular tunnel route if the no longer desired path the only path in the particular subset of the at least one particular path, the first priority level being lower than the priority level associated with the creation of a new path. 22. A computer readable storage medium as defined in claim 2, said program element further comprising a third program component adapted to: a) detect a failure occurring downstream from the particular node along the particular subset of the at least one particular path; and b) redirect over the particular tunnel route the data traffic associated with the particular subset of the at least one particular path. 23. A computer readable storage medium as defined in claim 22, wherein each path is a label-switched path (LSP). 24. A computer readable storage medium as defined in claim 22, wherein the paths convey data traffic in the form of packets, each packet including a forwarding label and wherein the third program component is adapted to redirect a particular packet by stacking a redirection label on top of the forwarding label of the packet. 25. A computer readable storage medium as defined in claim 22, wherein the particular tunnel route is characterized by a hold priority level stored in the memory and wherein the third program component is adapted to increase the hold priority level of the particular tunnel route further to redirection of the data traffic over the tunnel route. 26. A computer readable storage medium as defined in claim 25, wherein the third program component is adapted to increase the hold priority level of the particular tunnel route to a maximal value further to redirection of the data traffic over the tunnel route. 27. A computer readable storage medium as defined in claim 8, wherein creating a new tunnel route assigned to the protection of the particular subset of the at least one particular path against failures occurring downstream from the particular node along the particular subset of the at least one particular path includes reserving network resources that are capable of being utilized to meet the service criterion associated with the particular subset of the at least one particular path. 28. A computer readable storage medium as defined in claim 8, wherein creating a new tunnel route assigned to the protection of the particular subset of the at least one particular path against failures occurring downstream from the particular node along the particular subset of the at least one particular path includes reserving network resources that are capable of being utilized to meet the service criterion associated with the particular subset of the at least one particular path in the event of a limited network failure 29. A computer readable storage medium as defined in claim 28, wherein the limited network failure is limited to single-node or single-link failure. 30. A computer readable storage medium as defined in claim 3, whereas a) includes consulting the set of first data elements to determine which, if any, of the tunnel routes identified in the first data elements satisfies a first condition of including two nodes that are traversed by each path in the particular subset of the at least one particular path. 31. A computer readable storage medium as defined in claim 1, wherein said computing device is located in the particular node. 32. A computer readable storage medium as defined in claim 31, wherein the memory is located in the particular node. 33. A computer readable storage medium as defined in claim 4, wherein the two nodes traversed by each path in the particular subset of the at least one particular path include an ingress node located at an upstream extremity of the particular tunnel route and an egress node located at a downstream extremity of the particular tunnel route. 34. A computer readable storage medium as defined in claim 33, wherein said computing device is located in the particular node and wherein the particular node is the ingress node. 35. A node for exchanging packets in a network in which are defined paths for conveying data packets along ordered sets of nodes, said node comprising: at least one input interface for accepting data packets along at least one of the paths; at least one output interface for releasing data packets along the at least one of the paths; and a processing module adapted to assign a particular tunnel route to the protection of a particular subset of the at least one of the paths against failures occurring downstream from said node along the particular subset of the at least one of the paths. 36. A node as defined in claim 35, further comprising: a memory; the processing unit being added to store in the memory a set of first data elements, each firs data element identifying: a respective subset of the at least one of the paths; and a respective tunnel route assigned to the protection of the respective subset of the at least one of the paths against failures occurring downstream from said node along the respective subset of at the least one of the paths. 37. A node as defined in claim 35, the processing module being adapted to: a) consult the set of first data elements to determine which, if any, of the tunnel routes identified the first data elements is also capable of protecting the particular subset of the at least one of the paths against failures occurring downstream from said node along the particular subset of the at least one of the paths; and b) if at least one tunnel route is determined at a), select one of the at least one tunnel route so determined as the tunnel route assigned to protect the particular subset of the at least one of the paths against failures occurring downstream from said node along the particular subset of the at least one of the paths. 38. A node as defined in claim 37, wherein the processing module being adapted to perform a) includes the processing module being adapted to consult the set of first data elements to determine which, if any, of the tunnel routes identified in the first data elements satisfies a first condition of including two nodes that are traversed by each path in particular subset of the at least one of the paths. 39. A node as defined in claim 38, wherein the processing module being adapted to perform a) further includes the processing module being adapted to consult the set of first data elements to determine which, if any, of the tunnel routes found to satisfy the first condition also satisfy a second condition of including a next node that is distinct from the next node of each path in the particular subset of the at least one of the paths. 40. A node as defined in claim 39, wherein the at least one input interface includes a plurality of input interfaces, wherein the at least one output interface includes a plurality of output interfaces, wherein each data packet is identified by a label associated with a corresponding path through the network and by an interface identifier specifying the input interface at which it arrives, wherein the output interface through which a given data packet is released is a function of the label and of the interface identifier identifying the given data packet. 41. A node as defined in claim 40, the processing module being adapted to accept data packets: a) at the input interface identified by the interface identifier associated with the corresponding path when the tunnel route assigned to protect the corresponding path is not conveying protected data traffic; and b) at the input interface identified by the interface identifier associated within the tunnel route assigned to protect the corresponding path when the tunnel route assigned to protect the corresponding path conveys protected data traffic. 42. A node as defined in claim 35, said node including a router. 43. A method for providing path protection in a network having a probity of linked nodes, wherein paths for conveying data traffic are defined in the network, each path traversing an ordered set of nodes from among the plurality of nodes, the method comprising: assigning, for a particular node that is intermediate at least one particular path, a particular tunnel route to the protection of a particular subset of the at least one particular path against failures occurring downstream from the particular node along the particular subset of the at least one particular path. 44. A method as defined in claim 43, further comprising: storing in a memory a set of first data elements, each first data element identifying: a respective subset of the at least one particular path for which the particular node is intermediate; and a respective tunnel route assigned to the protection of the respective subset of the at least one particular path against failures occurring downstream from the particular node along the respective subset of at the least one particular path. 45. A method as defined in claim 44, further comprising: a) consulting the set of first data elements to determine which, if any, of the tunnel routes identified in the first data elements is also capable of protecting the particular subset of the at least one particular path against failures occurring downstream from the particular node along the particular subset of the at least one particular path; and b) if at least one tunnel route is determined at a), selecting one of the at least one tunnel route so determined as the tunnel route assigned to protect the particular subset of the at least one particular path against failures occurring downstream from the particular node along the particular subset of the at least one particular path. 46. A method as defined in claim 45, wherein a) includes consulting the set of first data elements to determine which, if any, of the tunnel routes identified in the first data elements satisfies a first condition of including two nodes that are traversed by each path in the particular subset of the at least one particular path. 47. A method as defined in claim 46, wherein a) further includes consulting the set of first data elements to determine which, if any, of the tunnel routes found to satisfy the first condition also satisfy a second condition of including a next node that is distinct from a next node of each path in the particular subset of the at least one particular path. |
<SOH> BACKGROUND OF THE INVENTION <EOH>In a multi-protocol label switching (MPLS) network, data transmission occurs on label-switched paths (LSPs). Specifically, an LSP is defined as a sequence of labels defined at each and every node along the way from a source to a destination. The labels, which are underlying protocol-specific identifiers, are distributed using protocols such as Label Distribution Protocol (LDP) or Resource Reservation Protocol (RSVP), or are piggybacked onto routing protocols such as Border Gateway Protocol (BGP) and Open Shortest Path First (OSPF). Each data packet encapsulates the labels during its journey from source to destination. High-speed switching is possible because the fixed-length labels are inserted at the very beginning of the packet and can be used by hardware to switch packets quickly between links. In the event of a failure of a link or node through which a particular LSP passes, data packets cannot be forwarded any further downstream along that particular LSP. A solution to this problem is to establish backup routes through which the data packets will be forwarded in case of a node or link failure. An LSP for which such a backup route has been defined is thus commonly referred to as a “protected” LSP. One way of protecting LSPs is to pre-establish backup routes by reserving bandwidth along fixed trajectories in the network. Each such “backup channel” is assigned to protect one or more LSPs. In some cases, a backup channel assigned to protect multiple LSPs is designed to occupy enough bandwidth to maintain the maximum possible quality of service that could be associated with each of N LSPs it is assigned to protect. In other cases, a backup channel may be established so as to occupy only enough bandwidth to maintain the maximum possible quality of service associated with M of the N LSPs it is assigned to protect where M<N. However, either of the above solutions suffers from inherent drawbacks. For example, one problem with the former solution is that it results in the over-consumption of bandwidth, since it always provisions for a “worst-case” scenario. On the other hand, the latter solution, while reducing the overall bandwidth required to provide protection, suffers from problems in the event of a failure of more than M LSPs requiring high quality of service, Moreover, the setup of either variety of backup channel requires time-consuming activities to be performed on the part of highly skilled workers, which makes this approach, expensive and prone to error. Finally, manually changing the backup routes to reflect topological changes in the network is also an expensive and error-prone exercise. An alternate solution to the protection problem in MPLS networks is to create a separate “protection LSP” for each new LSP created. In this case, bandwidth is not reserved a priori for the protection LSPs, as the nodes are merely informed of the existence of protection LSPs in order to be able to react appropriately in the event that they receive a packet having a protection LSP as a label. Therefore, a considerable bandwidth savings can be realized. However, this approach is not without its share of problems. For one, it is known that the establishment and maintenance of an LSP requires intense negotiations between the nodes of the network which is exacerbated by having to create double the number of LSPs than under unprotected conditions. This is especially true if the network approaches its maximal data transportation capacity and will also affect network performance when label distribution is prompted by subsequent topological changes to the network. Moreover, as only a finite number of labels is available for use in a given network, consumption of the available label resources at twice the normal rate can be problematic. Furthermore, it is disadvantageous to modify the signaling protocols to handle differing requirements in establishing the original LSP and the backup channel, also the cooperation of multiple nodes in the network may be needed, which may result in interoperability problems. Against this background, there exists a need to provide novel methods and devices to provide protection for links and nodes in a network. |
<SOH> SUMMARY OF THE INVENTION <EOH>According to a first broad aspect, the present invention may be summarized as a computer readable storage medium containing a program element for execution by a computing device in a network having a plurality of linked nodes, wherein paths for conveying data traffic are defined in the network, each path traversing an ordered set of nodes from among the plurality of nodes. The program element includes a first program component adapted to assign, for a particular node that is intermediate at least one particular path, a particular tunnel route to the protection of a particular subset of the at least one particular path against failures occurring downstream from the particular node along the particular subset of the at least one particular path. In a specific embodiment, the program element further includes a second program component adapted to store in a memory a set of first data elements, each first data element identifying: a respective subset of the at least one particular path for which the particular node is intermediate, and a respective tunnel route assigned to the protection of the respective subset of the at least one particular path against failures occurring downstream from the particular node along the respective subset of at the least one particular path. In a specific embodiment, the program element further includes a third program element adapted to consult the set of first data elements to determine which, if any, of the tunnel routes identified in the first data elements is also capable of protecting the particular subset of the at least one particular path against failures occurring downstream from the particular node along the particular subset of the at least one particular path; and if at least one tunnel route is so determined, select one of the at least one tunnel route so determined as the tunnel route assigned to protect the particular subset of the at least one particular path against failures occurring downstream from the particular node along the particular subset of the at least one particular path. In a specific embodiment, the third program element consults the set of first data elements to determine which, if any, of the tunnel routes identified in the first data elements satisfies a first condition of including two nodes that are traversed by each path in the particular subset of the at least one particular path. In a specific embodiment, the third program element also consults the set of first data elements to determine which, if any, of the tunnel routes identified in the first data elements satisfies a second condition of including a next node that is distinct from a next node of each path in the particular subset of the at least one particular path. The present invention allows protection to be provided for portions of a path, such as an LSP without requiring that such protection be established on an end-to-end basis. Also, by consulting a list of existing tunnel routes prior to the establishment of new tunnel routes, the time required to protect data traffic is reduced. Moreover, since the tunnel routes locally protect the paths of interest, the establishment of such tunnel routes does not consume much bandwidth in the network. According to a second broad aspect, the present invention provides a node for exchanging packets in a network in which are defined paths for conveying data packets along ordered sets of nodes. The node includes at least one input interface for accepting data packets along at least one of the paths; at least one output interface for releasing data packets along the at least one of the paths; and a processing module adapted to assign a particular tunnel route to the protection of a particular subset of the at least one of the paths against failures occurring downstream from the node along the particular subset of the at least one of the paths. In a specific embodiment, the node includes a router. According to a third broad aspect, the present invention may be summarized as a method for providing path protection in a network having a plurality of lined nodes, wherein paths for conveying data traffic are defined in the network, each path traversing an ordered set of nodes from among the plurality of nodes. The method includes assigning, for a particular node that is intermediate at least one particular path, a particular tunnel route to the protection of a particular subset of the at least one particular path against failures occurring downstream from the particular node along the particular subset of the at least one particular path. |
Internal illumination based sign device |
An illuminating unit (28) is presented for use in an internally illuminated sign device (1) for displaying a pattern indicative of certain fixed information within an indicia area. The illuminating unit (28) comprises a light boundary structure (33) for a light source (38) to be mounted thereon. The light boundary structure (33) has an indicia area carrying side (16) having said pattern indicative of the information to be displayed, and has an inner surface made of at least one highly reflective material to thereby increase the amount of light propagating from the light source (38) to said indicia area |
1. An illuminating unit for use in an internally illuminated sign device for displaying a pattern indicative of certain fixed information within an indicia area, the illuminating unit comprising a light boundary structure for a light source to be mounted thereon, wherein said light boundary structure has an indicia area having said pattern, and has a highly reflective inner surface, the illuminating unit being characterized in that the light boundary structure is formed of two attachable parts including, respectively, a rear frame and an upper panel structure removably mountable onto the rear frame, said upper panel structure being a multi-layer structure formed by at least two layers patterned in accordance with the information to be displayed, the upper external layer having translucent regions and light blocking regions of the indicia pattern, and the lower inner layer having translucent regions and the highly reflective regions of the indicia pattern, to thereby increase the amount of light propagating from the light source to said indicia area, enable replacing the indicia carrying panel to display various information, and enable visibility of the indicia area via external reflected light. 2. The illuminating unit according to claim 1, wherein the light source includes at least one LED mounted inside the light boundary structure and oriented such that it emits light directly propagating onto the inner surface of the light boundary structure opposite the indicia area carrying side of the light boundary structure, to thereby increase the amount of light propagating from the light source to said indicia area. 3. The illuminating unit according to claim 1, wherein a portion of the highly reflective inner surface within the indicia area carrying side is made of a reflective diffusive material. 4. The illuminating unit according to claim 1, wherein a portion of said highly reflective inner surface located outside the indicia area carrying side includes a specularly reflective material. 5. The illuminating unit according to claim 1, wherein said light boundary structure comprises a diffusive translucent layer located inside the structure underneath the indicia area carrying, side. 6. The illuminating unit according to claim 5, wherein said diffusive translucent layer is a foil plastic such as polyester or PVC. 7. The illuminating unit according to claim 1, wherein the multi-layer structure is patterned in a single fabrication step. 8. The illuminating unit according to claim 1, wherein the multi-layer structure is patterned in a two-step process utilizing the same equipment. 9. The illuminating unit according to claim 1, wherein the indicia area carrying side has a protective coating made of mat varnish to thereby prevent said side from UV radiation. 10. The illuminating unit according to claim 9, wherein said protective coating contains a flame retarding material. 11. The illuminating unit according to claim 1, wherein said highly reflective material within the inner surface of the indicia area carrying side is reflective diffusive and includes 3M Light Enhancement Film. 12. The illuminating unit according to claim 1, wherein said highly reflective material of the inner surface of the light boundary structure outside said indicia area carrying side is specular reflective and includes polished aluminum. 13. The illuminating unit according to claim 1, wherein the light source is mountable onto the light boundary structure aside said indicia area carrying side. 14. The illuminating unit according to claim 1, wherein said light boundary structure is a six-sided box formed by the indicia carrying side, an opposite side, and side walls. 15. The illuminating unit according to claim 14, wherein at least one of the side walls has a curved surface. 16. The illuminating unit according to claim 15, wherein said curved surface is formed by at least two facets. 17. The illuminating unit according to claim 1, wherein a side of the light boundary structure opposite to said indicia area carrying side is also an indicia area carrying side patterned in accordance with information to be displayed. 18. The illuminating unit according to claim 14, wherein the light source comprises at least one LED mountable onto at least one of the side walls of the light boundary structure. 19. The illuminating unit according to claim 18, wherein said at least one LED is oriented such that it emits light directly onto the opposite side. 20. The illuminating unit according to claim 1, wherein at least the indicia area carrying side of the light boundary structure is inclined downward with respect to a vertical plane so as to reduce glare in direct sunlight. 21. An internally illuminated sign device for displaying fixed information, comprising the illuminating unit of claim 1 and a power supply source connectable to the light source, wherein said power supply source comprises a battery assembly. 22. The device according to claim 21, wherein said power supply source comprises a switching circuit for controlling the operation of the battery assembly. 23. The device according to claim 22, wherein said switching circuit comprises a connector shiftable between its operative and inoperative positions, such that when in the operative position the connector actuates the battery assembly, and when in the inoperative position prevents the battery assembly from being actuated, thereby enabling to keep that battery assembly disconnected when the device is not in use. 24. The device according to claim 22, wherein said switching circuit comprises a recharge circuit operable to recharge the battery assembly. 25. The device according to claim 21, wherein said battery assembly comprises a solar panel. 26. The device according to claim 25, wherein said solar panel is inclined upward with respect to a vertical plane so as to increase the amount of collected global solar radiation. 27. The device according to claim 25, wherein said switching circuit comprises a solar cell circuit, and is operable to selectively disconnect the battery assembly from the light source. 28. The device according to claim 21, wherein said switching circuit comprises a voltage limiting circuit operable to limit voltage created by the recharge circuit to thereby provide a desired input voltage to the battery assembly. 29. The device according to claim 21, wherein said switching circuit comprises a current adjusting circuit operable to provide a constant electric current through the light source. 30. The device according to claim 26, wherein said switching circuit comprises a solar cell circuit, and is operable to selectively disconnect the battery assembly from the light source. 31. An illuminating unit for use in an internally illuminated sign device for displaying a pattern indicative of certain fixed information within an indicia area, the illuminating unit comprising a light boundary structure for a light source to be mounted thereon, wherein said light boundary structure has an indicia area having said pattern, and has a highly reflective inner surface, wherein the light source includes at least one LED mounted inside the light boundary structure and oriented such that it emits light directly propagating onto the inner surface of the light boundary structure opposite the indicia area carrying side of the light boundary structure, to thereby increase the amount of light propagating from the light source to said indicia area. 32. A power supply source for use with an internally illuminated sign device to supply power to a light source, the power supply source comprising a battery assembly and a switching circuit for controlling the operation of the battery assembly to provide at least one of the following effects: selective connection and disconnection of the battery assembly to and from the light source; recharge of the battery assembly by means of a solar cell circuit; supply of a constant electric current to the light source. 33. The power supply source according to claim 32, wherein said selective disconnection of the battery assembly utilizes photoswitch element. 34. The power supply source according to claim 32, wherein said switching circuit comprises a voltage limiting circuit operable to limit voltage created by the recharge circuit to thereby provide a desired input voltage to the battery assembly. 35. An illuminating unit for use in an internally illuminated sign device for displaying a pattern indicative of certain fixed information within an indicia area, the illuminating unit comprising a light boundary structure for a light source to be mounted thereon, the light boundary structure having an indicia area with said pattern and having a highly reflective inner surface, the illuminating unit being configured such that at least the indicia area carrying side of the light boundary structure is inclined downward with respect to a vertical plane so as to reduce glare in direct sunlight. 36. An internally illuminated sign device for displaying fixed information, the device comprising: an illuminating unit having a light source and a light boundary structure with an indicia area representative of the fixed information to be displayed; and a power supply source connectable to the light source and including a battery assembly that comprises a solar panel, the device being configured such that the solar panel is inclined upward with respect to a vertical plane so as to increase the amount of collected global solar radiation. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Indoor and outdoor illuminated signs are known devices widely used all over the world for orientation, advertising and other purposes, and are typically installed in public places where a large number of people can see them. Many signs need to be visible at night and this is often accomplished by internally illuminating the information (indicia) presented on a sign panel. Various techniques are used to construct a sign device with substantially uniform illumination of the indicia. Most of the conventional devices of the kind specified utilize fluorescent tubes or incandescent lamps as light sources, which are characterized by up to a 360°-spread of generated light. A light box utilizing such a light source is typically equipped with reflectors and diffusers so as to prevent the creation of “hot spots” and regions of excessively greater than average illumination, and to obtain uniform distribution of light impinging onto the inner surface of the front panel. This results in a drastic reduction in the amount of light emerging from the front, indicia-containing panel of the device towards the viewer. Internally illuminated sign devices utilizing light emitting diodes (LEDs) as light sources have been developed, and are disclosed, for example, in U.S. Pat. Nos. 5,105,568; 5,539,623; 5,388,357; 5,729,925; and 4,952,023. According to U.S. Pat. No. 5,105,568, a plurality of LEDs is aligned along all the parts (letters) of textual information, and high reflective elements are provided on selective areas of the inner surface of the sign panel. According to U.S. Pat. No. 4,952,023, reflectors are used in the optical path of light propagating inside the light box towards the sign panel. Illuminated house signs are generally installed on the outside of the home to show a family name and/or house number and street name. Such signs need to be reasonably priced and suitable for mass production. Such a sign device also needs to be custom-made so as to carry a unique family name and/or a specific house number. Conventionally, this is achieved by making an illuminating box wide enough to encompass several letters and/or numerals, and using a mask, which is supplied in sufficient duplicates of letters and/or numerals to create the specific indicia (address and/or name). When in operation, the mask covers the illuminating box to create indicia showing the desired house number, address or family name. |
<SOH> SUMMARY OF THE INVENTION <EOH>There is a need in the art to improve the operation of internal illumination based sign devices, by providing a novel illuminating unit, power supply unit, and sign device utilizing the same. There is also a need in the art for a modular house sign device that is custom-made without the need for customized manufacture. Sign devices need to be easy to mount by the purchaser himself without the need for a specialist's assistance. They also need to resist environmental hazards such as sun radiation, humidity and rain, etc. to ensure continuous and reliable operation. The device of the present invention provides for effective internal illumination of an indicia area by maximizing the amount of light from a given source reaching the indicia area; effective use of a solar cell panel; and easily assembling the custom-made indicia area within the device. There is thus provided according to one aspect of the present invention, an illuminating unit for use in an internally illuminated sign device for displaying a pattern indicative of certain fixed information within an indicia area, the illuminating unit comprising a light boundary structure for a light source to be mounted thereon, wherein said light boundary structure has an indicia area carrying side having said pattern, and has an inner surface made of at least one highly reflective material to thereby increase the amount of light propagating from the light source to said indicia area. The light boundary structure defines a light containment vessel (volume). Such a vessel may be shaped like a box (i.e., the so-called “light box”). It should be understood that the term “light box” used herein signifies a closed structure, which may or may not have a rectangular cross-section, and may or may not be integral, provided it defines at least one indicia carrying side, patterned in accordance with said information to be displayed. The indicia pattern is formed by translucent regions surrounded by non-translucent regions, which, at the inner surface of the indicia carrying side, are surrounded by the highly reflective regions. For example, such a light boundary structure may be a six-sided box (one- or two part) having a four or five-sided frame (rigid, or flexible, or tape-like), attachable to, respectively, a single indicia area-carrying side or two opposite indicia-carrying sides. As for the sidewalls of such six-sided box, they may have straight or curved surfaces (e.g., formed by two or more facets with sharp or truncated corners). The term “highly reflective material” used herein signifies a highly diffusive (scattering) material or specularly reflective material. The light source preferably comprises at least one light emitting diode (LED), which is preferably mountable aside the indicia carrying side. For example, one or more LED may be mounted on the side wall(s) of the sic-sided light boundary structure. The indicia-carrying side may be removably mountable onto the light boundary structure. By this, a selected indicia area can be mounted in the illuminating unit. The indicia-carrying side may be formed by a first panel patterned in accordance with the information to be displayed and having the highly reflective regions at its inner surface, and a second panel facing the inner surface of the first panel. In this case, the second panel is made of a translucent material. The first panel may be removably mountable onto the second panel of the indicia-carrying side of the light boundary structure. The light boundary structure may be a two-part structure formed by this second panel and a frame attachable thereto. Preferably, the highly reflective material within the inner surface of the indicia-carrying side is diffusive, and the other inner surface outside the indicia carrying side is specularly reflective. According to another aspect of the present invention, there is provided an internally illuminated sign device for displaying a pattern indicative of certain fixed information within an indicia area, the device comprising an illuminating unit having a light boundary structure for a light source to be mounted thereon, said light boundary structure having an indicia area carrying side, and an inner surface made of at least one highly reflective material to thereby increase the amount of light propagating from the light source to said indicia area. According to yet another aspect of the present invention, there is provided an internally illuminated sign device for displaying a pattern indicative of certain fixed information within indicia areas, the device comprising an illuminating unit having a light boundary structure for a light source to be mounted thereon, wherein the light boundary structure is a closed structure formed by two indicia area carrying sides, the inner surface of said structure containing at least one highly reflective material to thereby increase the amount of light propagating from the light source to each of the indicia areas. The sign device preferably comprises a power supply source having a battery assembly connectable to the light source. This power supply source preferably comprises a switching circuit for controlling the operation of the battery assembly. The switching circuit may comprise a connector shiftable between its operative and inoperative positions, such that when in the operative position, the connector actuates the battery assembly, and when in the inoperative position, prevents the battery assembly from being actuated, thereby enabling to keep the battery assembly disconnected when the device is not in use. The switching circuit may comprise a battery recharge circuit operable to selectively disconnect the battery assembly from the light source, and/or recharge the battery assembly, in which case the switching circuit comprises a voltage limiting circuit operable to limit voltage created by the solar cell circuit to thereby provide a desired input voltage to the battery assembly. Preferably, the switching circuit comprises a current adjusting circuit operable to provide a constant electric current through the light source. Thus, according to yet another aspect of the present invention, there is provided a power supply source for use with an internally illuminated sign device to supply power to a light source, the power supply source comprising a battery assembly and a switching circuit for controlling the operation of the battery assembly to provide at least one of the following effects: selective connection and disconnection of the battery assembly to and from the light source; recharge of the battery assembly; supply of a constant electric current to the light source. |
Underpants |
Underpants, provided to be worn particularly underneath sports pants, especially underneath biker pants, comprise a front part and a rear part. In the crotch area, a seat padding is provided. To avoid disturbing seams in the crotch area which possibly would cause pressure sores or grazing, the seat padding is arranged between the front part and the rear part. To achieve this, for instance, a crotch part of the underpants is removed so that only the seat padding is provided in the region of the crotch. The connection of the seat padding with the front part and the rear part of the underpants is realized exclusively in the edge regions outside the seat area. |
1. Underpants, particularly to be worn underneath sports pants, especially underneath biker pants, comprising a front part, a rear part, and a seat padding arranged in the crotch area, characterized in that the seat padding is arranged between the front part and the rear part. 2. The underpants according to claim 1, characterized in that the seat padding comprises an upper and a lower padding portion and that the lower edges of the front and rear parts of the underpants are arranged between the two padding portions. 3. The underpants according to claim 1, characterized in that the front part and the rear part are connected to each other by a web portion which is preferably arranged outside the seat padding. 4. The underpants according to claim 3, characterized in that the width of the web decreases inwards from the edge regions. 5. The underpants according to claim 3, characterized in that the web portion has substantially the shape of the seat padding. 6. The underpants according to claim 3, characterized in that the web portion extends beyond the seat padding on both sides. 7. The underpants according to claim 1, characterized in that the seat padding is connected to the front part and respectively the rear part exclusively in edge regions arranged outside the seat area. 8. The underpants according to claim 1, characterized in that the seat padding is in the edge region connected to the front part and respectively the rear part of the underpants by thermal welding. 9. The underpants according to claim 1, characterized in that the seat padding is connected to the edge regions of the front part and respectively the rear part of the underpants by bonding. 10. Underpants, particularly according to claim 1, characterized in that, in the seat area, the seat padding is laminated with an upper layer of the seat padding of the underpants. |
Reinforcing steel bar typing machine |
A front end of a ball screw shaft driven by a motor is connected with a binding line clamp apparatus (513) including three clamp plates (514, 515, 516). The left and right clamp plates (515, 516) are constituted to be brought into elastic contact with the center clamp plate (515) and close the left and right clamp plates by operation of cams (527, 528) when a sleeve is moved rearward. In a state of opening the clamp plates, a binding line is fed out to an upper side by passing through an interval between the right clamp plate (515) and the center clamp plate (514), formed in a loop shape and moved into an interval between the left clamp plate (516) and the center clamp plate (517). When the sleeve is moved rearward by driving to rotate a ball screw shaft, the left and right clamp plates are closed to grasp a front end and a rear end of the binding line loop and thereafter, the binding line clamp apparatus is rotated to twist the binding line to bind a reinforcing bar. |
1. A binding line clamp apparatus, for a reinforcing bar binder that grasps and twists a loop of binding line fed out by a binding line feed mechanism to a surrounding of a reinforcing bar, comprising: a center clamp plate; a right clamp plate arranged on a right side of the center clamp plate; a left clamp plate arranged on a left side of the center clamp plate; a sleeve outwardly mounted to the center clamp plate, the right clamp plate and the left clamp plate; and a pair of cam mechanisms including cams and guide pins, and provided to respective of the sleeve and the right clamp plate and the sleeve and the left clamp plate; wherein the right clamp plate and the left clamp plate are opened and closed in accordance with movement of the sleeve in a front and rear direction, and the binding line is fed out by passing through one of an interval between the right clamp plate the center clamp plate and an interval between the left clamp plate and the center clamp plate, by the binding line feed mechanism, and after introducing a front end of the binding line formed in a shape of the loop through the other of the interval between the right clamp plate the center clamp plate and the interval between the left clamp plate and the center clamp plate, the binding line is grasped by closing the right clamp plate and the left clamp plate. 2. The binding line clamp apparatus according to claim 1, wherein the right clamp plate is brought into elastic contact with the center clamp plate by a first spring, and the left clamp plate is brought into elastic contact with the center clamp plate by a second spring. 3. The binding line clamp apparatus according to claim 1, wherein the binding line feed mechanism feeds out the binding line passing through one of the interval between the right clamp plate and the center clamp plate and the interval between the left clamp plate and the center clamp plate to a guide groove formed at a nose of the reinforcing bar binder. 4. The binding line clamp apparatus according to claim 3, wherein the nose of the reinforcing bar binder is constituted by a circular arc shape. 5. The binding line clamp apparatus according to claim 1, wherein the cams of the cam mechanisms are constituted by groove cams. 6. The binding line clamp apparatus according to claim 1, wherein the respective of the sleeve and the right clamp plate and the sleeve and the left clamp plate are connected by the cam mechanisms. 7. The binding line clamp apparatus according to claim 1, wherein the cams of the pair of cam mechanisms are respectively formed at at least one of the sleeve and the right clamp plate and the sleeve and the left clamp plate, and wherein phases of the pair of cams are shifted from each other, and after grasping the front end of the loop of the binding line by the one of the right clamp plate and the left clamp plate, the other of the right clamp plate and the left clamp plate grasps a rear end of the loop of the binding line. 8. The binding line clamp apparatus according to claim 1, wherein a stopper portion projected in a center direction is formed on an upper portion of a face of grasping the binding line of one of the right clamp plate and the left clamp plate, and the front end of the binding line impinges on the stopper portion to stop. 9. The binding line clamp apparatus according to claim 1, wherein a guide groove of the binding line is formed on a face of grasping the binding line of one of the right clamp plate and the left clamp plate constituting a side of feeding out the binding line. 10. A reinforcing bar binder comprising: a binding line feed mechanism that feeds out a binding line in a shape of a loop to wind around a reinforcing bar; a grasping portion that grasps the binding line wound around the reinforcing bar, and includes a center clamp plate, a right clamp plate arranged on a right side of the center clamp plate, and a left clamp plate arranged on a left side of the center clamp plate; a binding line twist mechanism that twists the binding line to bind the reinforcing bar by driving to rotate the grasping portion; wherein the right clamp plate and the left clamp plate are arranged openably and closably relative to the center plate; and wherein the binding line fed out by the binding line feed mechanism is passed through one of an interval between the right clamp plate and the center clamp and an interval between the left clamp plate and the center clamp plate, and wherein the right clamp plate and the left clamp plate are closed to grasp the loop of the binding line fed out thereby, after the a front end of a loop of binding line is introduced into the other interval. 11. The reinforcing bar binder according to claim 10, wherein after grasping a front end of the loop of the binding line by closing the one of the right clamp plate and the left clamp plate constituting a side of grasping the front end of the loop of the binding line, the binding line is pulled back by reversely driving to rotate the binding line feed mechanism, and a length of the loop of the binding line is adjusted in accordance with a diameter of the reinforcing bar. 12. The reinforcing bar binder according to claim 10, wherein one of an inclined face portion and a projected portion, that is brought into contact with an upper end face or a lower end face of the center clamp plate when the binding line is clamped, is formed on one of the right clamp plate and the left clamp plate, and wherein when the binding line is clamped, the binding line is bent and deformed. 13. A reinforcing bar binder comprising: a nose including a guide groove at an inner periphery thereof; a feed mechanism that feeds out a binding line along the guide groove to wind around a reinforcing bar; a grasp mechanism that grasps the binding line wound around the reinforcing bar; a twist mechanism that twists the binding line to bind the reinforcing bar by driving to rotate the grasp mechanism; and a guide plate that contacts with the binding line fed along the guide groove by the feed mechanism, and curls the binding line; wherein the guide plate is formed movably to a position opposed to the guide groove and a position separated from the guide groove. 14. The reinforcing bar binder according to claim 13, wherein in a step of feeding out the binding line, the guide plate is opposed to the guide groove, and curls the binding line brought into contact with the guide plate, and after the step of feeding out the binding line, the guide plate is moved to the position separated from the guide groove, the binding line is pulled back by reversely driving to rotate the feed mechanism, and a length of the binding line is controlled in accordance with a diameter of the reinforcing bar. |
<SOH> BACKGROUND ART <EOH>A reinforcing bar binder is comprising a binding line feed mechanism for feeding out a binding line of a wire or the like wound around a reel to be wound around a reinforcing bar, and a binding line twist mechanism for twisting the binding line wound around the reinforcing bar to bind, and the binding line feed mechanism and the binding line twist mechanism are successively operated by trigger operation to carry out binding operation of 1 cycle. When a circular arc shape nose of the reinforcing bar binder is hung around the reinforcing bar and a trigger lever is pulled, the binding line is fed out around an inner peripheral face of a nose by the binding line feed mechanism to form a biding line loop at a surrounding of the reinforcing bar, a rear end of the binding line loop is cut by a cutter mechanism, a pair of hook type hooks of the binding line twist mechanism are closed to grasp the binding line loop to thereafter rotate and the binding line loop is twisted to bind the reinforcing bar. The reinforcing bar binder of a prior art is constituted to turn the binding line around the reinforcing bar by two rotations or more and catch a middle portion of the binding line loop remote from a front end and a rear end thereof by the pair of hooks and this is because when portions of the binding line at a vicinity of the front end or the rear end is caught, in rotating the hooks, the front end or the rear end is drawn out from the hooks to disengage the loop and binding cannot be carried out. Therefore, lengths of both end portions of the binding line extended from the portion grasped and twisted by the hooks are prolonged, the portions are projected at the surrounding of the reinforcing bar to bring about a drawback that the binding line is projected from a surface of concrete when concrete is cast and also an amount of consuming the binding line is large. Further, the reinforcing bar binder of the prior art poses a problem that the amount of consuming the binding line is large since the binding line is turned around the reinforcing bar by two rotation or more and the length of the binding line to be fed out is constant regardless of the diameter of the reinforcing bar. Further, when the diameter of the reinforcing bar is small, an amount of twisting the binding line is increased, a long time period required for twisting is taken, the binding line cannot sufficiently be tightened and a restraining force may become insufficient. Further, since the length of the twisted portion is long, when concrete is cast, the binding line may be projected from the surface of the concrete to thereby cause a problem in finishing. Further, according to the reinforcing bar binder of the prior art, when the nose in the circular arc shape of the reinforcing bar binder is hung to the reinforcing bar and the trigger lever is pulled, the binding line is fed out along a guide groove of an inner peripheral face of the nose by the binding line feed mechanism. The nose is provided with a forming portion opposed to the guide groove, the binding line is brought into contact with the forming portion when moving forward along the guide groove to curl to thereby form a loop around the surrounding of the reinforcing bar. Further, the binding line is cut by a binding line cut apparatus at a front end portion of the nose, the pair of hook type hooks of the binding line twist mechanism are closed to grub the binding line loop to thereafter rotate and twist the binding line loop to bind the reinforcing bar. According to the reinforcing bar binder of the prior art, since the binding line is fed out bypassing an interval between the guide groove of the nose and the forming portion opposed to the guide groove, when the binding line cut apparatus is not arranged at the vicinities of the binding line twist mechanism and the forming portion, the binding line loop cannot be twisted by constituting a hindrance by the forming portion disposed on an inner side of the binding line loop. Further, when the binding line cut apparatus is arranged at the vicinity of the forming portion, since the binding line cut apparatus is disposed at a position remote from the binding line twist mechanism, an extra portion from a point of grasping the binding line to a terminal end portion of the loop is long, further, since the binding line needs to be wound around the reinforcing bar by two turns or more, there poses a problem that the amount of consuming the binding line is large and an outlook thereof in finishing to bind is poor. Further, even when the binding line cut apparatus is arranged at the vicinity of the forming portion, there is a case in which the binding line is caught by the fixed forming portion in twisting the binding line to give an unpleasant feeling to an operator. |
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>FIG. 1 is a disassembled plane view of a binding line clamp apparatus of a reinforcing bar binder showing an embodiment of the invention. FIG. 2 is a disassembled side view of the bind line clamp apparatus. FIG. 3 is a front view of the three pieces of clamp plates. FIG. 4 ( a ) through FIG. 4 ( c ) show an initial state of the binding line clamp apparatus, FIG. 4 ( a ) is a plane sectional view, FIG. 4 ( b ) is a front sectional view and FIG. 4 ( c ) is a side sectional view. FIG. 5 ( a ) through FIG. 5 ( c ) show a step of grasping a front end of a binding line of the binding line clamp apparatus, FIG. 5 ( a ) is a plane sectional view, FIG. 5 ( b ) is a front sectional view and FIG. 5 ( c ) is a side sectional view. FIG. 6 ( a ) through FIG. 6 ( c ) show a step of grasping a rear end of the binding line of the binding line clamp apparatus, FIG. 6 ( a ) is a plane sectional view, FIG. 6 ( b ) is a front sectional view and FIG. 6 ( c ) is a side sectional view. FIG. 7 ( a ) and FIG. 7 ( b ) show a step of feeding the binding line of the reinforcing bar binder, FIG. 7 ( a ) is a plane view of a binding line guide apparatus and FIG. 7 ( b ) is a side view of the reinforcing bar binder. FIG. 8 ( a ) and FIG. 8 ( b ) show a step of pulling back the binding line of the reinforcing bar binder, FIG. 8 ( a ) is a plane view of the binding line guide apparatus and FIG. 8 ( b ) is a side view of the reinforcing bar binder. FIG. 9 ( a ) and FIG. 9 ( b ) show a step of grasping the rear end of the binding line of the reinforcing bar binder, FIG. 9 ( a ) is a plane view of the binding line guide apparatus and FIG. 9 ( b ) is the side view of the reinforcing bar binder. FIG. 10 ( a ) and FIG. 10 ( b ) show a step of cutting the binding line of the reinforcing bar binder, FIG. 10 ( a ) is a plane view of the binding line guide apparatus and FIG. 10 ( b ) is a side view of the reinforcing bar binder. FIG. 11 ( a ) and FIG. 11 ( b ) show a step of twisting the binding line of the reinforcing bar binder, FIG. 11 ( a ) is a plane view of the binding line guide apparatus and FIG. 11 ( b ) is a side view of the reinforcing bar binder. FIG. 12 ( a ) and FIG. 12 ( b ) show a step of twisting the binding line of the reinforcing bar binder, FIG. 12 ( a ) is a plane view of the binding guide apparatus and FIG. 12 ( b ) is a side view of the reinforcing bar binder. FIG. 13 ( a ) and FIG. 13 ( b ) show a step of releasing the binding line of the reinforcing bar binder, FIG. 13 ( a ) is a plane view of the binding line guide apparatus and FIG. 13 ( b ) is a side view of the reinforcing bar binder. FIG. 14 is a disassembled plane view showing other embodiment of a binding line clamp apparatus. FIG. 15 is a plane sectional view showing the other embodiment of the binding line clamp apparatus. FIG. 16 is a side view of constituent parts of the binding line clamp apparatus of FIG. 14 . FIG. 17 is a plane sectional view of the binding line clamp apparatus of FIG. 14 . FIG. 18 is a side sectional view of a mechanism portion of a reinforcing bar binder. FIG. 19 is a disassembled plane view of a binding line clamp apparatus according to the invention. FIG. 20 is a disassembled side view of the binding line clamp apparatus according to the invention. FIG. 21 is a disassembled front view of the binding line clamp apparatus according to the invention. FIG. 22 ( a ) through FIG. 22 ( c ) show the binding line clamp apparatus in an initial state, FIG. 22 ( a ) is a plane view, FIG. 22 ( b ) is a front view and FIG. 22 ( c ) is a side sectional view. FIG. 23 ( a ) through FIG. 23 ( c ) show the binding line clamp apparatus in a clamp state, FIG. 23 ( a ) is a plane view, FIG. 23 ( b ) is a front view and FIG. 23 ( c ) is a side sectional view. FIG. 24 is a front explanatory view showing an arrangement of a binding line feed mechanism. FIG. 25 ( a ) and FIG. 25 ( b ) show a binding line clamp apparatus in an initial state, FIG. 25 ( a ) is a front view and FIG. 25 ( b ) is a side sectional view. FIG. 26 ( a ) and FIG. 26 ( b ) show the binding line clamp apparatus in a step of feeding the binding line, FIG. 26 ( a ) is a front view and FIG. 26 ( b ) is a side sectional view. FIG. 27 ( a ) and FIG. 27 ( b ) show the binding line clamp apparatus in a step of pulling back the binding line, FIG. 27 ( a ) is a front view and FIG. 27 ( b ) is a side sectional view. FIG. 28 ( a ) and FIG. 28 ( b ) show the binding line clamp apparatus in a step of grasping the binding line, FIG. 28 ( a ) is a front view and FIG. 28 ( b ) is a side sectional view. FIG. 29 ( a ) and FIG. 29 ( b ) show the binding line clamp apparatus in a step of cutting the binding line, FIG. 29 ( a ) is a front view and FIG. 29 ( b ) is a side sectional view. FIG. 30 ( a ) and FIG. 30 ( b ) show the binding line clamp apparatus in a step of twisting the binding line, FIG. 30 ( a ) is a front view and FIG. 30 ( b ) is a side sectional view. FIG. 31 ( a ) and FIG. 31 ( b ) show the binding line clamp apparatus in a state of finishing to twist the binding line, FIG. 31 ( a ) is a front view and FIG. 31 ( b ) is a side sectional view. FIG. 32 ( a ) and FIG. 32 ( b ) show the binding line clamp apparatus in a step of releasing clamp plates, FIG. 32 ( a ) is a front view and FIG. 32 ( b ) is a side sectional view. FIG. 33 ( a ) and FIG. 33 ( b ) show an embodiment of the invention, FIG. 33 ( a ) is a plane view of a binding line guide apparatus and FIG. 33 ( b ) is a side view of a mechanism portion of a reinforcing bar binder. FIG. 34 ( a ) and FIG. 34 ( b ) show a step of pulling back the binding line of the reinforcing bar binder, FIG. 34 ( a ) is a plane view of the binding line guide apparatus and FIG. 34 ( b ) is a side view of the reinforcing bar binder. FIG. 35 is a disassembled plane view of a binding line clamp apparatus. FIG. 36 is a disassembled side view of the binding line clamp apparatus. FIG. 37 is a front view of three pieces of clamp plates. FIG. 38 ( a ) through FIG. 38 ( c ) show an initial state of the binding line clamp apparatus, FIG. 38 ( a ) is a plane sectional view, FIG. 38 ( b ) is a front sectional view and FIG. 38 ( c ) is a side sectional view. FIG. 39 ( a ) through FIG. 39 (C) show a step of grasping a front end of the binding line of the binding line clamp apparatus, FIG. 39 ( a ) is a plane sectional view, FIG. 39 ( b ) is a front sectional view and FIG. 39 ( c ) is a side sectional view. FIG. 40 ( a ) through FIG. 40 ( c ) show a step of grasping a rear end of the binding line of the binding line clamp apparatus, FIG. 40 ( a ) is a plane sectional view, FIG. 40 ( b ) is a front sectional view and FIG. 40 ( c ) is a side sectional view. FIG. 41 ( a ) and FIG. 41 ( b ) show a step of grasping the rear end of the binding line of the reinforcing bar binder, FIG. 41 ( a ) is a plane view of a blind line guide apparatus and FIG. 41 ( b ) is a side view of the reinforcing bar binder. FIG. 42 ( a ) and FIG. 42 ( b ) show a step of cutting the binding line of the reinforcing bar binder, FIG. 42 ( a ) is a plane view of the binding line guide apparatus and FIG. 42 ( b ) is a side view of the reinforcing bar binder. FIG. 43 ( a ) and FIG. 43 ( b ) show a step of twisting the binding line of the reinforcing bar binder, FIG. 43 ( a ) is a plane view of the binding line guide apparatus and FIG. 43 ( b ) is a side view of the reinforcing bar binder. FIG. 44 ( a ) and FIG. 44 ( b ) show a step of twisting the binding line of the reinforcing bar binder, FIG. 44 ( a ) is a plane view of the binding line guide apparatus and FIG. 44 ( b ) is a side view of the reinforcing bar binder. FIG. 45 ( a ) and FIG. 45 ( b ) show a step of releasing the biding line of the reinforcing bar binder, FIG. 45 ( a ) is a plane view of the binding line guide apparatus and FIG. 45 ( b ) is a side view of the reinforcing bar binder. detailed-description description="Detailed Description" end="lead"? Note that in the drawings, numeral 1 designates a binding line clamp apparatus, numeral 2 designates a center clamp plate, numeral 3 designates a right clamp plate, numeral 4 designates a left clamp plate, numeral 5 designates a sleeve, numerals 9 , 10 designate groove cams, numerals 11 , 12 designate guide pins, numeral 13 designates a ball screw shaft, numeral 14 designates a stopper portion, numeral 18 designates a shifter plate, numeral 19 designates a binding line cut apparatus, numeral 20 designates a binding line guide apparatus, numeral 501 designates a binding line twist mechanism, numeral 502 designates a binding line feed mechanism, numeral 506 designates a circular arc shape nose, numeral 507 designates a twist motor, numeral 508 designates a slide motor, numeral 511 designates a ball screw shaft, numeral 513 designates a binding line clamp apparatus, numeral 514 designates a center clamp plate, numeral 5115 designates a right clamp plate, numeral 516 designates a left clamp plate, numeral 517 designates a sleeve, numeral 523 designates a binding line guide groove, numeral 524 designates a recess, numerals 525 , 526 designate guide pins, numerals 527 , 528 designate cams, numerals 531 , 532 designate pushers, numeral 533 designates a compression coil spring, numeral 701 designates a binding line guide apparatus, numeral 702 designates a binding line cut apparatus, numeral 703 designates a binding line clamp apparatus, numeral 707 designates a sleeve, numeral 709 designates a shifter plate, numeral 710 designates guide plate cam, numeral 711 designates a slide cam plate, numeral 712 designates a shaft (guide plate), numeral 713 designates a support frame, numeral 714 designates a nose, numeral 715 designates a guide groove (nose), numeral 716 designates a forming portion (guide plate), numeral 717 designates a long hole (slide cam plate) and numeral 718 designates a compression coil spring. |
Binding agents with differential activity |
Binding agents with differential activity can be provided, whereby certain activities of a first part of the binding agent are reduced or prevented until binding to a target occurs. This is useful if the binding agent is intended to bind both an effector cell and a target to be destroyed, because the effector cell can be protected from significant cell damage that might otherwise occur (e.g. due to premature activation of complement and/or ADCC). Such binding agents are useful in the treatment of cancer, for example. |
1. A binding agent comprising: (a) a first part that comprises one or more of the biological activities of an antibody Fc region when the binding agent is bound to a biological target; (b) a second part that is capable of binding to the biological target with a valency of two or more; and (c) a third part that is capable of monovalent binding to an effector cell so that the effector cell can act upon the biological target when the second part is bound to the biological target. 2. A binding agent according to claim 1, in which the effector cell is capable of destroying, damaging, altering or removing the biological target. 3. A binding agent according to claim 1, in which the biological target is deleterious to a human or non-human animal. 4. A binding agent according to claim 1, in which the biological target is a cancer cell or a part thereof. 5. A binding agent according to claim 1, in which at least one of the biological activities of the first part is modulated when the binding agent is bound to the biological target in comparison with when the binding agent is bound to the effector cell only. 6. A binding agent according to claim 1, in which at least one of the biological activities of the first part is at least ten times higher when the binding agent is bound to the biological target in comparison with when the binding agent is bound to the effector cell only. 7. A binding agent according to claim 1, in which, in the absence of binding of the second part to the biological target, the binding agent is configured so that at least one biological activity of the first part is prevented or reduced due to steric hindrance, and in which the steric hindrance is removed or reduced when the second part binds to the biological target. 8. A binding agent according to claim 1, in which the first part comprises an FcRn docking site that is not sterically hindered in the absence of binding of the second part to the biological target. 9. A binding agent according to claim 1, in which the first part comprises one or more of the following biological activities when the binding agent is bound to a biological target: (a) complement activation; and (b) binding to the neonatal or Brambell Fc-receptor (FcRn). 10. A binding agent according to claim 9, which is modified to reduce activation of an effector cell in the absence of binding of the binding agent to a biological target. 11. A binding agent according to claim 9, which is modified to reduce binding to an FcRI, FcRII and/or an FcRIII receptor in the absence of binding of the binding agent to a biological target. 12. A binding agent according to claim 9, in which the first part comprises an Fc region which lacks one or more glycans normally associated with a natural Fc molecule. 13. A binding agent according to claim 12, in which the first part comprises an Fc region which is enzymatically deglycosylated, preferably with glycoamidase PNGaseF. 14. A binding agent according to claim 12, in which the first part comprises a recombinant Fc region in which the asparagine residue corresponding to position 297 of the IgG heavy chain is replaced with a non-gylcosylatable amino acid residue. 15. A binding agent according to claim 9, in which the first part further comprises one or more of the following biological activities when the binding agent is bound to a biological target: (c) induction or stimulation of phagocytosis by phagocytic cells; and (d) antibody-dependent cellular cytotoxicity (ADCC). 16. A binding agent according to claim 9, in which the at least one biological activity includes binding with FcRI, FcRII and/or FcRIII receptors. 17. A binding agent according to claim 1, in which endosomal binding to the first part so as to reduce lysosomal degradation of the binding agent in vivo is not prevented. 18. A binding agent according to claim 1, in which the second part is capable of binding to a plurality of different biological targets or to a plurality of different parts of the same biological target. 19. A binding agent according to claim 1 comprising one or more Fab, Fab′ or F(ab′)2 regions or parts thereof. 20. A binding agent according to claim 1 comprising one or more Fc regions, or parts thereof. 21. A binding agent according to claim 1, comprising at least one anti-target Fab, Fab′ or F(ab′)2 regions or parts thereof, at least one anti-effector cell Fab, or Fab′ regions or parts thereof, and at least one Fc region or a part thereof. 22. A binding agent according to claim 21, which comprises at least two anti-target Fab, Fab′ or F(ab′)2 regions or parts thereof. 23. A binding agent according to claim 1, in which any one or more of the first, second and third parts of the binding agent are derived from an IgG molecule. 24. A binding agent according to claim 1, in which any one or more of the first, second and third parts are covalently linked to each other. 25. A binding agent according to claim 1 comprising one or more tandem thioether links that interconnect cysteine residues. 26. A binding agent according to claim 1, in which the second part binds specifically to the biological target. 27. A binding agent according to claim 1, in which the second part comprises anti-CD 20 and/or anti CD-37 binding activity. 28. A binding agent according to claim 1, in which the third part binds specifically to the effector cell. 29. A binding agent according to claim 1, in which the third part comprises anti-CD 16 binding activity. 30. A binding agent according to claim 1, having a modular structure, in which one modules is capable of binding to a biological target, one module is capable of binding to an effector cell and another module comprises one or more of the biological activities of an antibody Fc region when the binding agent is bound to a biological target. 31. A binding agent according to claim 30, comprising two modules capable of binding to the same biological target. 32. A binding agent according to claim 1, when bound to an effector cell. 33. A part, component or module for use in the manufacture of a binding agent according to claim 1. 34. A method of providing a binding agent according to claim 1, comprising providing a plurality of modules and connecting them via tandem thioether linkages between cysteine residues. 35. A method of providing a binding agent, comprising the steps of: (a) providing a first part comprising one or more of the biological activities of an antibody Fc region when the binding agent is bound to a biological target; (b) providing a second part capable of binding to the biological target with a valency of two or more; (c) providing a third part capable of monovalent binding to an effector cell so that the effector cell can act upon the biological target when the second part is bound to the biological target; and covalently joining the first, second and third parts. 36. A method according to claim 34, in which the modules or parts of the binding agent are as set out in any preceding claim. 37. A method according to claim 34, in which the modules or parts are linked via a maleimide linker (e.g. o-phenylenedimaleimide (PDM)). 38. A binding agent according to claim 1, for use in medicine. 39. The use of a binding agent according to claim 1 in the preparation of a medicament for treating a disease or disorder caused by or involving the biological target. 40. The use according to claim 39, in which the disease or disorder is selected from the group consisting of: cancer, a lymphoma (e.g. a B-cell lymphoma), an infectious disease or disorder and an autoimmune disease or disorder. 41. A pharmaceutical composition comprising a binding agent according to claim 1; the composition optionally comprising a pharmaceutically acceptable carrier, diluent or excipient. 42. An image or model, preferably a computer generated image or model, of a binding agent according to claim 1. 43. A data carrier that comprises data for an image or model according to claim 42. 44. A computer that comprises data for an image or model of a binding agent that comprises a data carrier according to claim 43. 45. A method comprising providing an image or model according to claim 42 and using it to predict the structure and/or function of potential new therapeutic binding agents. 46. A method comprising providing a data carrier according to claim 43 and using it to predict the structure and/or function of potential new therapeutic binding agents. 47. A method comprising providing a computer according to claim 44 and using it to predict the structure and/or function of potential new therapeutic binding agents. 48. A method comprising providing an image or model according to claim 42, making one or more changes to it and, optionally, predicting or analysing an effect of those changes. 49. A drug development program that uses a binding agent according to claim 1. 50. A drug development program that uses an image or model according to claim 42. 51. A drug development program that uses a data carrier according to claim 43. 52. A drug development program that uses a computer according to claim 44. 53. A drug development program that uses a method according to claim 45. 54. A drug or drug candidate obtained or identified using a drug development program according to claim 49. 55. A method comprising providing a binding agent according to claim 1 and testing in vivo or in vitro the activity and/or binding of the binding agent, drug, or drug candidate against a biological target. 56. A method comprising providing a drug or drug candidate according to claim 54 and testing in vivo or in vitro the activity and/or binding of the binding agent, drug, or drug candidate against a biological target. 57. A method comprising providing a binding agent according to claim 1 and testing in vivo or in vitro the toxicity of the binding agent, drug, or drug candidate. 58. A method comprising providing a drug or rug candidate according to claim 54 and testing in vivo or in vitro the toxicity of the binding agent, drug, or drug candidate. 59. A binding agent according to claim 1, when in immobilised form. 60. A drug or drug candidate according to claim 54, when in immobilised form. 61. An array comprising a binding agent according to claim 1, or a drug or drug candidate according to claim 48. 62. An array comprising a drug or drug candidate according to claim 54. 63. A method comprising the steps of: (a) exposing a Fc-containing polypeptide to a matrix; (b) allowing the Fc-containing polypeptide to bind to the matrix by a hydrophobic interaction; (c) removing the Fc-containing polypeptide from the matrix by disrupting the hydrophobic interaction. 64. A method of separating an Fc-containing polypeptide from other components in a sample, the method comprising: (a) exposing the sample to a matrix; (b) allowing the Fc-containing polypeptide to bind to the matrix by a hydrophobic interaction; and optionally removing one or more components of the sample by washing the matrix; and (c) removing the Fc-containing polypeptide from the matrix by disrupting the hydrophobic interaction. 65. A method according to claim 63, in which the matrix comprises Toyopearl TSK-butyl-650. 66. A method according to claim 64, in which the matrix comprises Toyopearl TSK-butyl-650. |
<SOH> BACKGROUND <EOH>Antibodies and derivatives thereof have been used to target biological targets, including cancer cells, for many years. The predominant class of antibody is the IgG class, which has 3 globular modules, 2 Fab and one Fc, joined by an extended and flexible hinge. The Fab modules each display an integral antigen-binding site, while the Fc is responsible (a) for recruiting the molecular and cellular effectors needed to destroy an antibody-coated target cell and (b) for directing certain trafficking and metabolic characteristics of each antibody class. The cells recruited by the Fc module display molecules called Fc-receptors (FcR), which dock at sites on the surface of the Fc. A mouse IgG1 molecule is shown in FIGS. 1A and 1B . FIG. 1A illustrates the disposition of chains and interchain disulfide (SS) bonds. Chains (2 light, 2 heavy, N termini at the top, C termini at the bottom) are represented by black ribbons. Sets of interchain noncovalent bonds are depicted by hatched rectangles, and the two antibody sites by dashed arcs. Human IgG differs only in having 2 rather than 3 inter-heavy chain SS bonds. FIG. 1B shows a 2-dimensional diagrammatic representation of the overall protein conformation. Antibody sites are represented by triangular indentations, and noncovalent interactions between the chains by dashed lines. The chains are seen to be organized into 3 globular regions joined by a hinge comprising an extended sequence of each heavy chain. The Fc region displays sequences for recruitment of effector molecules (a set known as complement) and effector cells (chiefly macrophages and NK lymphocytes). The Fc contains a further set of sequences which prolong the metabolic life of the IgG molecule by sequestering it away from lysosomal enzymes. Soon after monoclonal antibody technology was described in the mid-70s antibodies, generally of the IgG class, were tried in the treatment of cancer, being aimed at molecules on the surfaces of the tumour cells. For about 15 years little success was achieved. Some of the reasons for this are set out below: (a) The docking sites for FcRI, II and III on mouse Fc have low and variable affinities for human effector cells (G T Stevenson. Immunotherapy of Tumours in Clinical Aspects of Immunology, ed P J Lachmann et al, Blackwell Scientific Publications, 1993, pp 1799-1830), which are now thought to be the principal agents involved in destroying antibody-coated tumour targets (R Clynes et al. Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets. Nature Medicine 6:443, 2000). (b) The docking site on mouse Fc for FcRn has no detectable affinity for human FcRn, so the therapeutic mouse IgG antibody has a very short survival in man. (c) The mouse IgG molecule is seen as foreign by the human immune system, which after about 10 days often produces antibodies against it, frequently against its Fc zone, thus further shortening the survival of the mouse antibody in the human host. These difficulties were largely overcome by the advent of chimeric antibodies that retained mouse amino acid sequences in their antigen-binding sites, but had human IgG sequences for all or much of the remainder of the antibody. The recruitment of human effector cells and metabolic survival in the human host were thereby improved, while any immune response to the antibody was on a much less serious scale. Several chimeric antibodies are now licensed for clinical use but their effectiveness still leaves much to be desired. (D G Maloney et al. IDEC-C2B8 (rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin's lymphoma. Blood 90:2188-2195, 1997). This is because cancer cells, like mammalian cells in general, have a variety of good defences against antibody attack, these apparently having evolved to deal with untoward auto-immune responses. Many attempts have been made to improve the efficacy of antibody attack and so to overwhelm or circumvent the defences of cancer cells. Prominent among these have been bispecific antibodies, which have two different rather than identical antibody sites. One site remains specific for a tumour while the other has been used for a variety of purposes. Frequently it targets an FcR on a human effector cell. The effector cell is thereby drawn into contact with the tumour cell and if suitably activated will destroy it. Effector cell recruitment by this means is much more tenacious than the normal recruitment by Fc. The affinity of the antibody site for the FcR (K A =10 7 -10 8 ) is typically about 100-fold greater than the Fc-FcR affinity. The two most common designs for bispecific antibodies are shown in FIGS. 2A and 2B . Each has been the subject of clinical trials, but with only limited success. The construct shown in FIG. 2A binds only weakly to tumour cells and has a limited half-life of only about 24 hours. The construct shown in FIG. 2B also binds only weakly to tumour cells. Additionally, if attached to effector cells only, it can cause damage due to recruitment of effectors by the Fc portion of the construct. From the foregoing discussions it will be appreciated that there is a great need to is develop improved binding agents against biological targets, especially binding agents useful in the treatment of cancer. |
<SOH> SUMMARY <EOH>According to a first aspect of the present invention, we provide a binding agent comprising: (a) a first part that comprises one or more of the biological activities of an antibody Fc region when the binding agent is bound to a biological target; (b) a second part that is capable of binding to the biological target with a valency of two or more; and (c) a third part that is capable of monovalent binding to an effector cell so that the effector cell can act upon the biological target when the second part is bound to the biological target. In a preferred embodiment, the effector cell is capable of destroying, damaging, altering or removing the biological target. Preferably, the biological target is deleterious to a human or non-human animal. Preferably, the biological target is a cancer cell or a part thereof. Preferably, at least one of the biological activities of the first part is modulated when the binding agent is bound to the biological target in comparison with when the binding agent is bound to the effector cell only. More preferably, at least one of the biological activities of the first part is at least ten times higher when the binding agent is bound to the biological target in comparison with when the binding agent is bound to the effector cell only. The binding agent may be such that, in the absence of binding of the second part to the biological target, the binding agent is configured so that at least one biological activity of the first part is prevented or reduced due to steric hindrance, and in which the steric hindrance is removed or reduced when the second part binds to the biological target. Preferably, the first part comprises an FcRn docking site that is not sterically hindered in the absence of binding of the second part to the biological target. Preferably, the first part comprises one or more of the following biological activities when the binding agent is bound to a biological target: (a) complement activation; and (b) binding to the neonatal or Brambell Fc-receptor (FcRn). In a preferred embodiment, the binding agent is modified to reduce activation of an effector cell in the absence of binding of the binding agent to a biological target. Preferably, it is modified to reduce binding to an FcRI, FcRII and/or an FcRIII receptor in the absence of binding of the binding agent to a biological target. Preferably, the first part comprises an Fc region which lacks one or more glycans, preferably two glycans, normally associated with a natural Fc molecule. Preferably, the glycans are those linked to asparagine corresponding to position 297 of the IgG heavy chain. Preferably, the first part comprises an Fc region which is enzymatically deglycosylated, preferably with glycoamidase PNGaseF. Alternatively, or in addition, the first part comprises a recombinant Fc region in which the asparagine residue corresponding to position 297 of the IgG heavy chain is replaced with a non-gylcosylatable amino acid residue. In another embodiment, the first part further comprises one or more of the following biological activities when the binding agent is bound to a biological target: (c) induction or stimulation of phagocytosis by phagocytic cells; and (d) antibody-dependent cellular cytotoxicity (ADCC). Futhermore, the at least one biological activity may include binding with FcRI, FcRII and/or FcRIII receptors. Preferably, endosomal binding to the first part so as to reduce lysosomal degradation of the binding agent in vivo is not prevented. Preferably, the second part is capable of binding to a plurality of different biological targets or to a plurality of different parts of the same biological target. In preferred embodiments, the binding agent comprises one or more Fab, Fab′ or F(ab′) 2 regions or parts thereof. Preferably, it comprises one or more Fc regions, or parts thereof. Preferably, it comprises at least one anti-target Fab, Fab′ or F(ab′) 2 regions or parts thereof, at least one anti-effector cell Fab, or Fab′ regions or parts thereof, and at least one Fc region or a part thereof. In preferred embodiments, the binding agent comprises at least two anti-target Fab, Fab′ or F(ab′) 2 regions or parts thereof Preferably, any one or more of the first, second and third parts of the binding agent are derived from an IgG molecule. Any one or more of the first, second and third parts may be covalently linked to each other. The binding agent may comprise one or more tandem thioether links that interconnect cysteine residues. Preferably the second part binds specifically to the biological target. Preferably, the second part comprises anti-CD 20 and/or anti CD-37 binding activity. Preferably, the third part binds specifically to the effector cell. Preferably, the third part comprises anti-CD 16 binding activity. The binding agent may comprise a modular structure, in which one module is capable of binding to a biological target, one module is capable of binding to an effector cell and another module comprises one or more of the biological activities of an antibody Fc region when the binding agent is bound to a biological target. Preferably, it comprises two modules capable of binding to the same biological target. We provide, according to a third aspect of the present invention, a binding agent as described, when bound to an effector cell. As a fourth aspect of the present invention, there is provided a part, component or module of a binding agent, for use in the manufacture of a binding agent as described. We provide, according to a fifth aspect of the present invention, a method of providing a binding agent, comprising providing a plurality of modules and connecting them via tandem thioether linkages between cysteine residues. There is provided, according to a sixth aspect of the present invention, a method of providing a binding agent, comprising the steps of: (a) providing a first part comprising one or more of the biological activities of an antibody Fc region when the binding agent is bound to a biological target; (b) providing a second part capable of binding to the biological target with a valency of two or more; (c) providing a third part capable of monovalent binding to an effector cell so that the effector cell can act upon the biological target when the second part is bound to the biological target; and covalently joining the first, second and third parts. Preferably, the modules or parts of the binding agent are as set out in any preceding aspect of the invention. Preferably, the modules or parts are linked via a maleimide linker (e.g. o-phenylenedimaleimide (PDM)). In a seventh aspect of the present invention, there is provided a binding agent according to any preceding aspect of the invention for use in medicine. According to an eighth aspect of the present invention, we provide the use of a binding agent in the preparation of a medicament for treating a disease or disorder caused by or involving the biological target. Preferably, the disease or disorder is selected from the group consisting of: cancer, including a lymphoma (e.g. a B-cell lymphoma), an infectious disease or disorder and an autoimmune disease or disorder. There is provided, in accordance with a tenth aspect of the present invention, a pharmaceutical composition comprising a binding agent as described; the composition optionally comprising a pharmaceutically acceptable carrier, diluent or excipient. As an eleventh aspect of the invention, we provide an image or model, preferably a computer generated image or model, of a binding agent as described. We provide, according to a twelfth aspect of the invention, there is provided a data carrier that comprises data for such an image or model. According to a thirteenth aspect of the present invention, we provide a computer that comprises data for such an image or model, and/or that comprises such a data carrier. We provide, according to a fourteenth aspect of the invention, there is provided a method comprising providing an image or model as described, a data carrier as described, or a computer as described and using it to predict the structure and/or function of potential new therapeutic binding agents. Preferably, the method comprises making one or more changes to the image or model and, optionally, predicting or analysing an effect of those changes. According to a fifteenth aspect of the present invention, we provide a drug development program that uses a binding agent as described, an image or model as described, a data carrier as described, a computer as described, or a method as described. According to a sixteenth aspect of the present invention, we provide a drug or drug candidate obtained or identified using such a drug development program. There is provided, according to a seventeenth aspect of the present invention, a method comprising providing a binding agent as described, or a drug or drug candidate as described and testing in vivo or in vitro the activity and/or binding of the binding agent, drug, or drug candidate against a biological target. We provide, according to a eighteenth aspect of the present invention, a method comprising providing a binding agent as described, or a drug or drug candidate as described and testing in vivo or in vitro the toxicity of the binding agent, drug, or drug candidate. According to a nineteenth aspect of the present invention, we provide a binding agent as described, or a drug or drug candidate as described, when in immobilised form. According to a twentieth aspect of the present invention, we provide an array comprising a binding agent as described, or a drug or drug candidate as described. There is provided, according to a twenty-first aspect of the present invention, a method comprising the steps of: (a) exposing a Fc-containing polypeptide to a matrix; (b) allowing the Fc-containing polypeptide to bind to the matrix by a hydrophobic interaction; (c) removing the Fc-containing polypeptide from the matrix by disrupting the hydrophobic interaction. We provide, according to a twenty-second aspect of the invention, a method of separating an Fc-containing polypeptide from other components in a sample, the method comprising: (a) exposing the sample to a matrix; (b) allowing the Fc-containing polypeptide to bind to the matrix by a hydrophobic interaction; and optionally removing one or more components of the sample by washing the matrix; and (c) removing the Fc-containing polypeptide from the matrix by disrupting the hydrophobic interaction. Preferably, the matrix comprises Toyopearl TSK-butyl-650. In many cases the target will be deleterious to a human or non-human animal. It is therefore preferred that the effector cell is capable of destroying, damaging, altering or removing the target. The effector cell may do this directly and/or indirectly (e.g. via the recruitment of other moieties, such as cytokines or other cells). As used herein, an “effector cell” may thus be any cell capable of giving rise to or promoting a desired biological effect. Preferred cells include cytotoxic T-cells, natural killer (NK) cells, monocytes and dendritic cells. The effector cell is advantageously protected from the antibody Fc biological activities mediated by the first part of the molecule. In a preferred embodiment, the activity of the Fc module is hindered in the absence of target binding, for example by steric means, such that the antibody Fc activity of the binding agent-effector cell complex is relatively low in the absence of target cell binding. Advantageously, at least one antibody Fc activity is increased by 10 times on target binding, preferably by 20 times, 40 times, 60 times, 100 times or more. In a further preferred aspect more than one antibody Fc activity may be so increased, for example 2, 3, 4 or more such activities. In a preferred aspect, the binding agent is constructed by covalently linking together antibody fragments. Preferably, the first part comprises an antibody Fc region, and the second and third parts are selected from antibody binding fragments, such as Fv, scFv, Fab, F(ab′) 2 and Fab′. The fragments are linked together advantageously via a maleimide linker, such as o-phenylenedimaleimide. The methods and compositions described here are variously applicable to medicine, as described below, including veterinary medicine and diagnostics. The molecules as described here may moreover be represented in silico for use in molecular modelling and drug design. Thus, we provide in silico models of the molecules as described. In the above aspects, preferably a structural model of the binding agent is generated using molecular modelling techniques. Advantageously these are computer implemented modelling techniques. Suitable programs include grid-based techniques and/or multiple copy simultaneous search (MCSS) methods. These will be familiar to those skilled in the art. Alternatively, visual inspection of a computer model of a binding agent can be used, in association with manual docking of models of functional groups into its binding pockets. Once a structural model has been generated as herein described, possible targets and/or effector groups to simulate or modulate target binding may for example be identified by one or more of the following techniques: de novo compound design, by defining a pharmacophore as herein defined, and/or by using automated docking algorithms as herein described. In the first aspect (de novo compound design) may be performed using suitable computer software. In a preferred embodiment of this aspect, the software is selected from the group consisting of: QUANTA, SYBYL, HOOK and CAVEAT. Alternatively, linking the functional groups may be performed manually. Suitable in silico libraries for use in the methods and compositions described here will be familiar to those skilled in the art, and includes the Available Chemical Directory (MDL Inc), the Derwent World Drug Index (WDI), BioByteMasterFile, the National Cancer Institute database (NCI), and the Maybridge catalogue. In a further aspect, we provide a compound identifiable using one or more of the methods as described here. In a further aspect still, we provide a computer readable medium for a computer, characterised in that the medium contains the atomic-co-ordinates of a binding agent as described herein. The methods and compositions described here may employ, unless otherwise indicated, conventional techniques of chemistry, molecular biology, microbiology, recombinant DNA and immunology, which are within the capabilities of a person of ordinary skill in the art. Such techniques are explained in the literature. See, for example, J. Sambrook, E. F. Fritsch, and T. Maniatis, 1989 , Molecular Cloning: A Laboratory Manual , Second Edition, Books 1-3, Cold Spring Harbor Laboratory Press; Ausubel, F. M. et al. (1995 and periodic supplements; Current Protocols in Molecular Biology , ch. 9, 13, and 16, John Wiley & Sons, New York, N.Y.); B. Roe, J. Crabtree, and A. Kahn, 1996 , DNA Isolation and Sequencing: Essential Techniques , John Wiley & Sons; J. M. Polak and James O'D. McGee, 1990 , In Situ Hybridization: Principles and Practice ; Oxford University Press; M. J. Gait (Editor), 1984 , Oligonucleotide Synthesis: A Practical Approach , Irl Press; D. M. J. Lilley and J. E. Dahlberg, 1992 , Methods of Enzymology: DNA Structure Part A: Synthesis and Physical Analysis of DNA Methods in Enzymology, Academic Press; Using Antibodies: A Laboratory Manual: Portable Protocol NO. I by Edward Harlow, David Lane, Ed Harlow (1999, Cold Spring Harbor Laboratory Press, ISBN 0-87969-544-7); Antibodies: A Laboratory Manual by Ed Harlow (Editor), David Lane (Editor) (1988, Cold Spring Harbor Laboratory Press, ISBN 0-87969-314-2), 1855. Handbook of Drug Screening, edited by Ramakrishna Seethala, Prabhavathi B. Fernandes (2001, New York, N.Y., Marcel Dekker, ISBN 0-8247-0562-9); and Lab Ref: A Handbook of Recipes, Reagents, and Other Reference Tools for Use at the Bench, Edited Jane Roskams and Linda Rodgers, 2002, Cold Spring Harbor Laboratory, ISBN 0-87969-630-3. Each of these general texts is herein incorporated by reference. The details of one or more embodiments are set forth in the accompanying drawings and the description below. Other features, objects, and advantages will be apparent from the description and drawings, and from the claims. |
Black perylene pigment and process for producing the same |
A black perylene-based pigment produced by calcining at least one compound selected from the group consisting of diimide derivatives of perylene tetracarboxylic acid and diimide derivatives of perylene diiminodicarboxylic acid, at a temperature of 200 to 600° C. in vacuum or in an inert gas atmosphere, exhibits an excellent blackness, an excellent heat resistance and an excellent weather fastness as well as a high resistance and a high safety. |
1. A black perylene-based pigment produced by calcining at least one compound selected from the group consisting of compounds represented by the following formulae (I) to (III), at a temperature of 200 to 600° C. in vacuum or in an inert gas atmosphere. wherein R1 and R2 are identical to each other and are independently butyl group, phenylethyl group, methoxyethyl group and 4-methoxyphenylmethyl group; and R3 and R4 may be same or different and are independently phenylene group, alkylphenylene group, alkoxyphenylene group, hydroxyphenylene group, halogenated phenylene group, pyridinediyl group, alkylpyridinediyl group, alkoxypyridinediyl group, halogenated pyridinediyl group and naphthalenediyl group, said R3 and R4 being bonded to adjacent positions of the aromatic ring, respectively. 2. A process for producing a black perylene-based pigment, comprising: calcining at least one compound selected from the group consisting of those compounds represented by the formulae (I) to (III) at a temperature of 200 to 600° C. in vacuum or in an inert gas atmosphere. |
<SOH> BACKGROUND ART <EOH>As black pigments, there have been conventionally used carbon black, perylene-based pigments and the like. Among these black pigments, carbon black has been most widely used because of its high tinctorial strength as well as an excellent blackness, an excellent acid resistance and an excellent weather fastness. However, carbon black has a very small particle size and a large bulk density and, therefore, tends to suffer from problems such as poor handling property and workability. Also, it may be difficult to use such carbon black in applications requiring a high electrical resistance, such as black matrix materials for liquid crystal color filters, because of a low electrical resistance thereof. Further, the carbon black may contain carcinogenic polycyclic condensation compounds and, therefore, has a problem concerning a safety. Although the perylene-based pigments extensively used as fast pigments exhibit red-violet-brown-black colors in a solid state, the color tone thereof is not necessarily kept thermally stable (W. Herbst & K. Hunger “Industrial Organic Pigments”, VCH Press, pp. 467-480). An object of the present invention is to provide a black perylene-based pigment exhibiting an excellent blackness, an excellent heat resistance and an excellent weather fastness as well as a high safety, which is usable as black matrix pigments for liquid crystal color filters. |
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>FIG. 1 is a graph showing an X-ray diffraction diagram of the black pigment obtained in Example 1. FIG. 2 is a graph showing a light absorption spectrum of the black pigment obtained in Example 1. detailed-description description="Detailed Description" end="lead"? |
Side view mirror assembly wit quiet drain feature |
A vehicle mounted mirror assembly (10) is provided, including a housing (14), a drain hole (16), and an air flow disruption member (18) positioned upwind of the drain hole (16) creating turbulence in the air passing over the drain hole (16) and thereby reducing wind noise. |
1. A vehicle mounted mirror assembly comprising: a housing; a drain hole positioned within said housing allowing water trapped within said housing to exit the vehicle mounted mirror assembly; and an air flow disruption member positioned upwind of said drain hole, said air flow disruption member creating turbulence in air passing over said drain hole and thereby reducing wind noise. 2. A vehicle mounted mirror assembly as described in claim 1 wherein said air flow disruption member includes a wedge element. 3. A vehicle mounted mirror assembly as described in claim 1 wherein said air flow disruption member includes a dimple element. 4. A vehicle mounted mirror assembly as described in claim 1 wherein said air flow disruption member includes a simple geometric shape. 5. A vehicle mounted mirror assembly as described in claim 1 wherein said air flow disruption member is formed integrally with said housing. 6. A vehicle mounted mirror assembly as described in claim 1 wherein said air flow disruption member is formed on said housing through an injection molded process. 7. A vehicle mounted mirror assembly as described in claim 1 wherein said air flow disruption member is formed on said housing through a stamping process. 8. A vehicle mounted mirror assembly as described in claim 1 wherein said air flow disruption member is formed as a separate element and affixed to said housing. 9. A method of reducing wind noise generated by a drain hole formed within the housing of a vehicle mounted mirror assembly comprising: creating turbulence in the air upwind of the drain hole. 10. A method as described in claim 9 wherein said creating turbulence is performed in a localized area immediately upwind of the drain hole. 11. A method as described in claim 9 wherein said creating turbulence in the air is accomplished through the use of a wedge-shaped element. 12. A method as described in claim 9 wherein said creating turbulence in the air is accomplished through the use of a dimple-shaped element. 13. A method as described in claim 9 wherein said creating turbulence in the air is accomplished through the use of a simple geometrically-shaped element. 14. A method as described in claim 9 wherein said creating turbulence is accomplished through the use of a plurality of air flow disruption elements positioned immediately upwind of the drain hole. |
<SOH> BACKGROUND OF THE INVENTION <EOH>The design of automotive components is often dictated by a wide variety of design considerations. Often, it is not sufficient that an automotive component simply perform its intended function. Instead, modern automotive components must be designed with a variety of factors in mind. These design considerations include, but are not limited to, cost, weight, efficiency, style, manufacturing simplicity, vibrational characteristics, and noise characteristics. A successful design is often one that optimizes these design characteristics while still accomplishing the component's primary function. Such is the case with automotive components mounted on the exterior of the vehicle. One of these components is the automotive side view mirror. The primary function of automotive side view mirrors is to increase the driver's visual field while allowing-him to concentrate on the road ahead. When designing automotive side view mirrors, however, a host of secondary design considerations must often be incorporated. Reductions in cost, manufacturing complexity, and weight are beneficial. Structural strength and style must also be considered. One area of design that should not be overlooked is the reduction of wind noise. Advancements in the design of automotive side view mirrors have lead to aerodynamic shapes that reduce the amount of wind noise generated. Although the aerodynamic shapes have reduced the level of wind noise generated, there is still room for further improvement. For example, often small drainage holes are formed in the mirror housing to allow condensation or other water accumulation to drain from the mirror assembly. These drain holes, while highly effective, often catch the wind as it passes by the mirror assembly and lead to unacceptable noise generation. It is known that by placing these holes on a surface, angled away from the oncoming wind, wind noise generation may be effectively reduced. This solution, however, can require adjusting the design of the side view mirror housing to accommodate such hole placement. Thus it is possible for the use of a drainage hole to reduce the flexibility of the mirror housing design. It may be more desirable to have the shape of the side view mirror housing dictated by design and style considerations rather than by the necessity of having a non-planar drainage hole. In addition, it is possible for such alterations in housing design to increase the cost and time of mirror production. It would, therefore, be highly desirable to have a side-view mirror assembly, including a drainage hole, which provided increased flexibility in design while reducing wind noise generation. It would additionally be desirable to have such a low wind noise drain hole that could be inexpensively incorporated into known side view mirror designs at a low cost and without the necessity of significantly altering present aerodynamic or style-based shapes. |
<SOH> SUMMARY OF THE INVENTION <EOH>It is, therefore, an object of the present invention to provide a side view mirror assembly with a low wind noise generating drain hole. It is a further object of the present invention to provide such a side view mirror assembly with a low wind noise drain hole with increased flexibility for side view mirror styling. In accordance with the objects of the present invention, a vehicle mounted mirror assembly is provided. The vehicle mounted mirror assembly includes a housing. A drain hole is positioned within the housing to allow water trapped within the housing to exit the vehicle mounted mirror assembly. An air flow disruption member is positioned upwind of the drain hole, creating turbulence in air passing over the drain hole and thereby reducing wind noise. Other objects and features of the present invention will become apparent when viewed in light of the detailed description of the preferred embodiment when taken in conjunction with the attached drawings and appended claims. |
Cyclohexyl silyl or phenyl silyl substituted poly (phenylenevinylene) derivative, electroluminescence device using the same and production method thereof |
Disclosed is a luminescent polymer applicable to various electroluminescence devices, and more specifically, a novel poly(p-phenylvinylene) derivative with cyclohexyl or phenyl substituted silyl group on the side chain thereof, represented by the following formula 1. The luminescent polymer is excellent in thermal properties and luminance efficiency, and radiates at a green light wavelength range due to electronic properties of the silyl substituent, thus serving as an electroluminescence device material. wherein R is a cyclohexyl or phenyl substituted silyl group; and m is an integer of 1-4. |
1. A luminescent polymer represented by the following formula 1: wherein R is a cyclohexyl or phenyl substituted silyl group; and m is an integer of 1-4: 2. The polymer as defined in claim 1, wherein the silyl group contains C1 to C20 linear or branched alkyl groups. 3. A method of producing a luminescent polymer represented by the formula 1, comprising the step of polymerizing a monomer compound represented by the following formula 2: wherein R is a cyclohexyl or phenyl substituted silyl group; m is an integer of 1-4; and A is a halogen element. 4. The method as defined in claim 3, wherein the polymerizing step is performed by halogen precursor route or Gilch polymerization route. 5. The method as defined in claim 3, wherein A is bromine. 6. An electroluminescence device comprising a polymer light-emitting layer formed with the luminescent polymer of claim 1. 7. The device as defined in claim 6, wherein a semitransparent electrode layer, the polymer light-emitting layer and a metal electrode layer are successively formed on a substrate. 8. The device as defined in claim 6, wherein a semitransparent electrode layer, a hole injecting layer, the polymer light-emitting layer, an electron injecting layer and a metal electrode layer are successively formed on a substrate. 9. The device as defined in claim 8, wherein the hole injecting layer is poly(styrenesulfonic acid) doped poly(3,4-ethylenedioxythiophene). 10. The device as defined in claim 8, wherein the electron injecting layer is formed with an alkali metal compound. 11. The device as defined in any one of claims 6 to 10, wherein the polymer light-emitting layer is formed by blending the luminescent polymer with an electron or a hole transporting polymer. 12. The device as defined in claim 11, wherein the hole transporting polymer is poly(9-vinylcarbazol). |
<SOH> TECHNICAL FIELD <EOH>The present invention pertains, in general, to luminescent polymers applicable for various electroluminescence devices. More specifically, the present invention discloses a novel poly(p-phenylenevinylene) derivative having a cyclohexyl or phenyl substituted silyl group on the side chain thereof. |
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>FIG. 1 is a reaction scheme showing a preparation process of the luminescent polymer of the present invention. FIG. 2 is a schematic diagram showing a configuration of an electroluminescence device comprising the luminescent polymer of the present invention applied to a polymer light-emitting layer. FIG. 3 is a graph showing the weight of the luminescent polymer of the present invention according to thermogravimetry. FIG. 4 is a graph showing the heat flow of the luminescent polymer of the present invention according to differential scanning calorimetry (DSC). FIG. 5 is a graph showing the UV absorption spectrum of the luminescent polymer of the present invention. FIG. 6 is a graph showing the photoluminescence (PL) spectrum of the luminescent polymer of the present invention. FIG. 7 is a graph showing the current of the luminescent polymer of the present invention according to cyclic voltammetry (CV). FIG. 8 is a graph showing the electroluminescence (EL) spectrum obtained from the EL device comprising ITO/polymer light-emitting layer/Al electrode layer. FIG. 9 a is a graph showing the current-voltage curve of each of a single-layer electroluminescence device comprising an ITO/polymer light-emitting layer/Al electrode layer and a double-layer EL device comprising an ITO/PVK/polymer light-emitting layer/Al electrode layer. FIG. 9 b is a graph showing the luminance density-voltage curve of each of a single-layer EL device comprising an ITO/polymer light-emitting layer/Al electrode layer and a double-layer EL device comprising an ITO/PVK/polymer light-emitting layer/Al electrode layer. FIG. 10 a is a graph showing the external quantum efficiency of each of the single-layer and the double-layer EL devices according to the present invention. FIG. 10 b is a graph showing the power efficiency of each of the single-layer and the double-layer EL devices according to the present invention. FIG. 11 is a graph showing the current-luminance density-voltage curve of the multi-layer EL device according to the present invention. detailed-description description="Detailed Description" end="lead"? |
Pyrrole-type compounds, compositions, and methods for treating cancer, treating viral diseases and causing immunosuppression |
The present invention relates to novel Pyrrole-Type compounds, compositions comprising Pyrrole-Type compounds, and methods useful for treating or preventing cancer or a neoplastic disorder comprising administering a Pyrrole-Type compound. The compounds, compositions, and methods of the invention are also useful for inhibiting the growth of a cancer cell or neoplastic cell. The present invention also relates to novel Pyrrole-Type compounds, compositions, and methods useful for treating or preventing a viral infection. The compounds, compositions, and methods of the invention are also useful for inhibiting the replication and/or infectivity of a virus. The present invention also relates to novel Pyrrole-Type compounds, compositions, and methods useful for causing immunosuppression. The present invention also relates to novel Pyrrole-Type compounds, compositions, and methods useful for treating or preventing an autoimmune disease. |
1. A compound having the general Formula (I): or a pharmaceutically acceptable salt thereof, wherein: each R1 is independently selected from the group consisting of —H, —CH3, —CH2C6H5, —C(O)OC(CH3)3, and —C(O)OCH2C6H5; and n is an integer ranging from 1 and 5. 2. The compound of claim 1, wherein: each R1 is independently selected from the group consisting of —H and —CH3; and n is an integer ranging from 1 to 5. 3. The compound of claim 2, wherein: R1 is —H; and n is an integer ranging from 1 to 3. 4. A compound having the general Formula (II): or a pharmaceutically acceptable salt thereof, wherein: each R1 is independently selected from the group consisting of —H, —CH3, —CH2C6H5, —C(O)OC(CH3)3, and —C(O)OCH2C6H5; and n is an integer ranging from 1 and 5. 5. The compound of claim 4, wherein: each R1 is independently selected from the group consisting of —H and —CH3; and n is an integer ranging from 1 to 5. 6. The compound of claim 5, wherein: R1 is —H; and n is an integer ranging from 1 to 3. 7. A compound having the general Formula (III): or a pharmaceutically acceptable salt thereof, wherein: each R1 is independently selected from the group consisting of —H, —CH3, —CH2C6H5, —C(O)OC(CH3)3, and —C(O)OCH2C6H5; R2 is a C1-C10 straight chain alky or —CH2C6H5, the —CH2C6H5 being unsubstituted or substituted on the phenyl with one or more methoxyl, halogen, methyl, nitro, trifluoromethyl, or methoxylcarbonyl groups; R3 is —CH3, —CH2CH3, or —C6H5; R4 is —H, a C1-C15 straight chain alkyl, -2-pyrrolyl, -3-pyrrolyl, -2-furanyl, -3-furanyl, or —C6H5, the —C6H5 being unsubstituted or substituted with one or more methyl, methoxyl, halogen, trifluoromethyl, or methoxycarbonyl groups; R5 is —H, a C1-C12 straight chain alkyl, i-C3H7, or —C6H5; R6 is —H, a C1-C12 straight chain alkyl, i-C3H7, C3-C7 cycloalkyl, or —C6H5. 8. The compound of claim 7, wherein: R1 is —H; R2 is —CH3, —CH2C6H5; R3 is —CH3; R4 is —H or a C1-C15 straight chain alkyl; R5 is —H or a C1-C5 straight chain alkyl; and R6 is —H or —CH3; 9. The compound of claim 8, wherein: R1 is —H; R2 and R3 is —CH3; R4 is —H or —(CH2)14CH3; R5is —H or -n-C5H11; and R6is —H. 10. A compound having the general Formula (IV): or a pharmaceutically acceptable salt thereof, wherein: each R1 is independently selected from the group consisting of —H, —CH3, —CH2C6H5, —C(O)OC(CH3)3, and —C(O)OCH2C6H5; R2 is a C1-C10 straight chain alkyl, or —CH2C6H5, the —CH2C6H5 being unsubstituted or substituted on the phenyl with one or more methoxyl, halogen, methyl, nitro, trifluoromethyl, or methoxylcarbonyl groups; R3 is —CH3, —CH2CH3, or —C6H5; R4 is a C1-C15 straight chain alkyl, -2-pyrrolyl, -3-pyrrolyl, -2-furanyl, -3-furanyl, or —C6H5, the —C6H5 being unsubstituted or substituted with one or more methyl, methoxyl, halogen, trifluoromethyl, or methoxycarbonyl groups, R8 is —H, —CH3, —CH2CH3, —CH2CH2CH3, or —(CH2)3CH3; and m is 1 to 4. 11. The compound of claim 10, wherein: R1 is —H; R2 is —CH3 or —CH2C6H5; R3 is —CH3; R4 is —H or a C1-C15 straight chain alkyl; R8 is —H or —CH3; and m is 2. 12. The compound of claim 11, wherein: R1 is —H; R2, R3, and R4 is —CH3; R8 is —H or CH3; and m is 2. 13. A compound having the general Formula (V): or a pharmaceutically acceptable salt thereof, wherein: each R1 is independently selected from the group consisting of —H, —CH3, —CH2C6H5, —C(O)OC(CH3)3, and —C(O)OCH2C6H5; R2 is a C1-C10 straight chain alkyl, or —CH2C6H5, the —CH2C6H5 being unsubstituted substituted on the phenyl with one or more methoxyl, halogen, methyl, nitro, trifluoromethyl, or methoxylcarbonyl groups; R3 is —CH3, —CH2CH3, or —C6H5; R7 is —H, a C1-C10 straight chain alkyl, or —CH(CH3)2; and n is 4 to 8. 14. The compound of claim 13, wherein: R1 is —H; R2 is —CH3, or —CH2C6H5; R3 is —CH3; R7 is —H or a C1-C4 straight or branched chain alkyl; and n is 4. 15. The compound of claim 14, wherein: R1 is —H; R2 and R3 is —CH3; R7 is —H, —C2H5, or -n-C4H9; and n is 4. 16. A compound of general Formula (VI): or a pharmaceutically acceptable salt thereof, wherein: R2 is a C1-C10 straight chain alkyl or —CH2C6H5; R3 is a C1-C10 straight chain alkyl, —CH(CH3)2, —CH(CH3)CH2CH3, —CH(CH3)CH2CH2CH3, —CH(OH)CH2CH2CH3, —CH(Cl)CH2CH2CH3, or —CH2C6H5; and n is 1 to 5. 17. The compound of claim 16, wherein: R2 is —CH3, or —CH2C6H5; R3 is —H or C1-C4 straight or branched chain alkyl; and n is 1. 18. The compound of claim 17, wherein: R2 is —CH3; R3 is -n-C4H9; and n is 1. 19. A compound of general Formula (VII): or a pharmaceutically acceptable salt thereof, wherein: R2 is a C1-C10 straight chain alkyl or —CH2C6H5; and R4 is —H or a C1-C15 straight chain alkyl. 20. The compound of claim 19, wherein: R2 is —CH3 or —CH2C6H5; and R4 is —H, —CH3, or (CH2)14CH3. 21. The compound of claim 20, wherein: R2 is —CH3; and R4 is —H, —CH3, or (CH2)14CH3. 22. A compound of general Formula (VIII): or a pharmaceutically acceptable salt thereof, wherein: R2 is a C1-C10 straight chain alkyl or —CH2C6H5; R4 is —H or a C1-C10 straight chain alkyl; R5 is —H or a C1-C10 straight chain alkyl; and m is 1 to 4. 23. The compound of claim 22, wherein: R2 is —CH3 or —CH2C6H5; R4 and R5 is —H or —CH3; and m is 2. 24. The compound of claim 23, wherein: R2 and R5 is —CH3; R4 is —H or —CH3; and m is 2. 25. A compound of general Formula (IX): or a pharmaceutically acceptable salt thereof, wherein: R1 is —H, —CH3, —SO2-4-methylphenyl, —CH2C6H5, —Si(R5R6R7), —CH2OCH2CH2SiCH3, —C(O)OC(CH3)3, or —C(O)CH2C6H5; R2is —CH3, —CH2CH3, —CH2CH2CH3, or —CH2C6H5; R3 is —H or Cl; R4 is —H or a C1-C10 straight chain alkyl; R5 is a C1-C4 straight or branched chain alkyl or —C6H5; R6 is a C1-C3 straight or branched chain alkyl; R7 is a C1-C3 straight or branched chain alkyl; and n is 1 to 5. 26. The compound of claim 25, wherein: R1 is —H; R2 is —CH3 or —CH2C6H5; R3 is —H; R4 is —H or a C1-C4 straight or branched chain alkyl; and n is 1 to 3. 27. The compound of claim 26, wherein: R1 is —H; R2 is —CH3; R3 is —H; R4 is —C4H9; and n is 1. 28. The compound of claim 26, wherein: R1 is —H; R2 is —CH3; R3 is —H; R4 is —C2H5; and n is 3. 29. A compound of general Formula (X): or a pharmaceutically acceptable salt thereof, wherein: R1 is —H, —CH3, —CH2C6H5, —COCH3, —C(O)OC(CH3)3, or —C(O)CH2C6H5; R2 is a C1-C10 straight chain alkyl or —CH2C6H5, the —CH2C6H5 being unsubstituted or substituted with one or more halo, methoxyl, methyl, methoxycarbonyl, or nitro groups; R3 is —H, —CH3, —CH2C6H5, or —C(O)OC(CH3)3; R4 is —H or —CH3; R5 is —H, —CH3, —OCH3, —F, —Cl, —Br, —I, —CN, —NH2; —NH(C1-C3 straight or branched chain alkyl), —NHCOCH3, —NO2, —COOH, —COOR6, —OH, or —OCH2C6H5; and R6 is a C1-C6 straight chain alkyl. 30. The compound of claim 29, wherein: R1 is —H; R2 is —CH3 or —CH2C6H5; R3 is —H; R4 is —H or —CH3; R5 is —H, halogen, or —COOR6; and R6 is —CH3. 31. The compound of claim 30, wherein: R1 is —H; R2 is —CH3; R3 is —H; R4 is —H or —CH3; and R5 is —H. 32. A compound of general Formula (XI): or a pharmaceutically acceptable salt thereof, wherein: R1 is —H, —CH3, —CH2C6H5, —COCH3, —C(O)OC(CH3)3, or —C(O)CH2C6H5; R2 is a C1-C10 straight chain alkyl or —CH2C6H5; R3 is —H, —CH3, —CH2C6H5, —C(O)OC(CH3)3, or —C(O)CH2C6H5; R4 is —H or —CH3; R5 is —H, a C1-C10 straight chain alkyl, —OR6, —F, —Cl, —Br, —I, —CN, —COOH, —COOR6, —NH2; —NHCOR6, —NO2, —OH, or —OCH2C6H5; and R6 is a C1-C6 straight chain alkyl. 33. The compound of claim 32, wherein: R1 is —H; R2 is —CH3 or —CH2C6H5; R3 is —H; R4 is —H or —CH3; R5 is —H, —CH3, halogen, or COOR6; and R6 is —CH3. 34. The compound of claim 33, wherein: R1 is —H; R2 is —CH3; R3 is —H; R4 is —CH3; and R5 is —H or Cl. 35. A compound of general Formula (XII): or a pharmaceutically acceptable salt thereof, wherein: R1 is —H, —CH3, —CH2C6H5, or —C(O)OC(CH3)3; R2 is a C1-C10 straight chain alkyl or —CH2C6H5; R3 is —H, —SO2CH3, —SO2C6H5, —C(O)OC(CH3)3, —COCH3, —CO(CH2)4CH3, —CO(CH2)8,CH3, —COC6H5, —CO-4-(NHCOC6H5)C6H4, —CO-2-pyridyl, —CO-2-napthyl, —CO-2-quinolyl, —CO-6-(NHCO(CH2)4CH3)-2-quinolyl, —CO-2-pyrrolyl, -2-CO-2-indolyl, —CO-1-methyl-2-indolyl, —CO-2-benzofuranyl, —CO-2-benzothiophenyl, —CO-3-methyl-2-indenyl, or —CO—R4-2-indolyl; and R4 is -5-OCH3, -6-OH-7-OCH3, -5-NHCONH2, 5-NHCOC6H5, -5-NHCO-indolyl, -5-NHCO-2-benzofuranyl, -5-NHCO-5(NHCONH2)-2-indolyl, or -5-NHCO-5(NHCOC6H5)-2-indolyl. 36. The compound of claim 35, wherein: R1 is —H; R2 is —CH3 or —CH2C6H5; R3 is —H, —COCH3, —CO-2-quinolyl, —CO-6-(NHCO(CH2)4CH3)-2-quinolyl, -2-CO-2-indolyl, or —CO—R4-2-indolyl; and R4 is -5-NHCO-indolyl, -5-NHCO-2-benzofuranyl, or -5-NHCO-5(NHCONH2)-2-indolyl. 37. The compound of claim 36, wherein: R1 is —H; R2 is —CH3; R3 is —H, —COCH3, or —CO—R4-2-indolyl; and; R4 is -5-NHCO-indolyl. 38. A compound of general Formula (XIII): or a pharmaceutically acceptable salt thereof, wherein: each R1 is independently selected from the group consisting of —H, —CH3, —CH2C6H5, —C(O)OC(CH3)3, or —C(O)OCH2C6H5; R2 is —H or a C1-C10 straight chain alkyl; and n is 1 to 4. 39. The compound of claim 38, wherein: R1 is —H; R2 is —H or —CH3; and n is 1 to 4. 40. The compound of claim 39, wherein: R1 is —H; R2 is —H or —CH3; and n is 2. 41. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 1. 42. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 2. 43. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 3. 44. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 4. 45. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 5. 46. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 6. 47. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 7. 48. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 8. 49. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 9. 50. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 10. 51. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 11. 52. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 12. 53. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 13. 54. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 14. 55. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 15. 56. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 16. 57. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 17. 58. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 18. 59. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 19. 60. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 20. 61. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 21. 62. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 22. 63. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 23. 64. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 24. 65. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 25. 66. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 26. 67. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 27. 68. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 28. 69. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 29. 70. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 30. 71. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 31. 72. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 32. 73. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 33. 74. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 34. 75. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 35. 76. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 36. 77. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 37. 78. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 38. 79. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 39. 80. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 40. 81. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 1. 82. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 2. 83. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 3. 84. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 4. 85. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 5. 86. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 6. 87. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 7. 88. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 8. 89. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 9. 90. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 10. 91. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 11. 92. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 12. 93. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 13. 94. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 14. 95. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 15. 96. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 16. 97. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 17. 98. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 18. 99. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 19. 100. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 20. 101. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 21. 102. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 22. 103. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 23. 104. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 24. 105. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 25. 106. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 26. 107. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 27. 108. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 28. 109. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 29. 110. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 30. 111. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 31. 112. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 32. 113. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 33. 114. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 34. 115. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 35. 116. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 36. 117. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 37. 118. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 38. 119. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 39. 120. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of the compound of claim 40. 121. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 1. 122. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 2. 123. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 3. 124. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 4. 125. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 5. 126. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 6. 127. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 7. 128. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 8. 129. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 9. 130. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 10. 131. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 11. 132. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 12. 133. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 13. 134. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 14. 135. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 15. 136. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 16. 137. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 17. 138. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 18. 139. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the 10 compound of claim 19. 140. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 20. 141. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 21. 142. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 22. 143. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 23. 144. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 24. 145. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 25. 146. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 26. 147. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 27. 148. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 28. 149. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 29. 150. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 30. 151. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 31. 152. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 32. 153. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 33. 154. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 34. 155. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 35. 156. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 36. 157. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 37. 158. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 38. 159. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 39. 160. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 40. 161. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 1. 162. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 2. 163. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 3. 164. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 4. 165. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 5. 166. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 6. 167. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 7. 168. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 8. 169. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 9. 170. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 10. 171. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 11. 172. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 12. 173. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 13. 174. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 14. 175. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 15. 176. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 16. 177. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 17. 178. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 18. 179. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 19. 180. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 20. 181. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 21. 182. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 22. 183. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 23. 184. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 24. 185. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 25. 186. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 26. 187. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 27. 188. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 28. 189. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 29. 190. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 30. 191. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 3 1. 192. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 32. 193. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 33. 194. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 34. 195. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 35. 196. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 36. 197. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 37. 198. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 38. 199. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 39. 200. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of the compound of claim 40. 201. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 1. 202. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 2. 203. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 3. 204. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 4. 205. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 5. 206. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 6. 207. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 7. 208. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 8. 209. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 9. 210. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 10. 211. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 11. 212. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 12. 213. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 13. 214. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 14. 215. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 15. 216. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 16. 217. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 17. 218. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 18. 219. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 19. 220. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 20. 221. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 21. 222. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 22. 223. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 23. 224. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 24. 225. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 25. 226. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 26. 227. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 27. 228. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 28. 229. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 29. 230. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 30. 231. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 31. 232. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 32. 233. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 33. 234. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 34. 235. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 35. 236. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 36. 237. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 37. 238. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 38. 239. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 39. 240. A method for causing immunosuppression in a patient comprising administering to a patient in need thereof an effective amount of the compound of claim 40. 241. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 1. 242. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 2. 243. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 3. 244. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 4. 245. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 5. 246. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 6. 247. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 7. 248. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 8. 249. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 9. 250. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 10. 251. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 11. 252. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 12. 253. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 13. 254. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 14. 255. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 15. 256. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 16. 257. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 17. 258. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 18. 259. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 19. 260. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 20. 261. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 21. 262. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 22. 263. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 23. 264. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 24. 265. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 25. 266. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 26. 267. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 27. 268. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 28. 269. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 29. 270. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 30. 271. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 31. 272. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 32. 273. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 33. 274. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 34. 275. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 35. 276. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 36. 277. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 37. 278. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 38. 279. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 39. 280. A method for treating or preventing an autoimmune disease in a patient comprising administering to a patient in need of such treatment or prevention an effective amount of the compound of claim 40. 281. The method of claim 241, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 282. The method of claim 242, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 283. The method of claim 243, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 284. The method of claim 244, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 285. The method of claim 245, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 286. The method of claim 246, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 287. The method of claim 247, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 288. The method of claim 248, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 289. The method of claim 249, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 290. The method of claim 250, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 291. The method of claim 251, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 292. The method of claim 252, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 293. The method of claim 253, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 294. The method of claim 254, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 295. The method of claim 255, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 296. The method of claim 256, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 297. The method of claim 257, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 298. The method of claim 258, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 299. The method of claim 259, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 300. The method of claim 260, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoinimune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 301. The method of claim 261, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 302. The method of claim 262, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 303. The method of claim 263, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 304. The method of claim 264, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 305. The method of claim 265, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 306. The method of claim 266, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 307. The method of claim 267, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 308. The method of claim 268, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 309. The method of claim 269, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 310. The method of claim 270, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 311. The method of claim 271, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 312. The method of claim 272, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 313. The method of claim 273, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 314. The method of claim 274, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 315. The method of claim 275, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 316. The method of claim 276, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 317. The method of claim 277, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 318. The method of claim 278, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 319. The method of claim 279, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderma, Sezary's disease, uveitis, or mumps orchitis. 320. The method of claim 280, wherein the autoimmune disease is rheumatoid arthritis, insulin-dependent diabetes mellitus, hemolytic anemia, rheumatic fever, thyroiditis, ulceractive colitis, myesthethia gravis, glomerulonephritis, allergic encephalomyelitis, continuing nerve and liver destruction following viral hepatitis, multiple sclerosis, systemic lupus erythematosus, juvenile diabetes, autoimmune haemolytic anaemia, psoriasis, idiopathic thrombocytopenic purpura, active chronic hepatitis, idiopathic leucopenia, primary biliary cirrhosis, thyrotoxicosis, dermatomyositis, discoid lupus erythematosus, psoriatic arthritis, regional enteritis, nephrotic syndrome, lupus nephritis, lupoid hepatitis, Sjogren's syndrome, Goodpasture's syndrome, Wegener's granulomatosis, scleroderna, Sezary's disease, uveitis, or mumps orchitis. 321. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier. 322. A pharmaceutical composition comprising the compound of claim 2 and a pharmaceutically acceptable carrier. 323. A pharmaceutical composition comprising the compound of claim 3 and a pharmaceutically acceptable carrier. 324. A pharmaceutical composition comprising the compound of claim 4 and a pharmaceutically acceptable carrier. 325. A pharmaceutical composition comprising the compound of claim 5 and a pharmaceutically acceptable carrier. 326. A pharmaceutical composition comprising the compound of claim 6 and a pharmaceutically acceptable carrier. 327. A pharmaceutical composition comprising the compound of claim 7 and a pharmaceutically acceptable carrier. 328. A pharmaceutical composition comprising the compound of claim 8 and a pharmaceutically acceptable carrier. 329. A pharmaceutical composition comprising the compound of claim 9 and a pharmaceutically acceptable carrier. 330. A pharmaceutical composition comprising the compound of claim 10 and a pharmaceutically acceptable carrier. 331. A pharmaceutical composition comprising the compound of claim 11 and a pharmaceutically acceptable carrier. 332. A pharmaceutical composition comprising the compound of claim 12 and a pharmaceutically acceptable carrier. 333. A pharmaceutical composition comprising the compound of claim 13 and a pharmaceutically acceptable carrier. 334. A pharmaceutical composition comprising the compound of claim 14 and a pharmaceutically acceptable carrier. 335. A pharmaceutical composition comprising the compound of claim 15 and a pharmaceutically acceptable carrier. 336. A pharmaceutical composition comprising the compound of claim 16 and a pharmaceutically acceptable carrier. 337. A pharmaceutical composition comprising the compound of claim 17 and a pharmaceutically acceptable carrier. 338. A pharmaceutical composition comprising the compound of claim 18 and a pharmaceutically acceptable carrier. 339. A pharmaceutical composition comprising the compound of claim 19 and a pharmaceutically acceptable carrier. 340. A pharmaceutical composition comprising the compound of claim 20 and a pharmaceutically acceptable carrier. 341. A pharmaceutical composition comprising the compound of claim 21 and a pharmaceutically acceptable carrier. 342. A pharmaceutical composition comprising the compound of claim 22 and a pharmaceutically acceptable carrier. 343. A pharmaceutical composition comprising the compound of claim 23 and a pharmaceutically acceptable carrier. 344. A pharmaceutical composition comprising the compound of claim 24 and a pharmaceutically acceptable carrier. 345. A pharmaceutical composition comprising the compound of claim 25 and a pharmaceutically acceptable carrier. 346. A pharmaceutical composition comprising the compound of claim 26 and a pharmaceutically acceptable carrier. 347. A pharmaceutical composition comprising the compound of claim 27 and a pharmaceutically acceptable carrier. 348. A pharmaceutical composition comprising the compound of claim 28 and a pharmaceutically acceptable carrier. 349. A pharmaceutical composition comprising the compound of claim 29 and a pharmaceutically acceptable carrier. 350. A pharmaceutical composition comprising the compound of claim 30 and a pharmaceutically acceptable carrier. 351. A pharmaceutical composition comprising the compound of claim 31 and a pharmaceutically acceptable carrier. 352. A pharmaceutical composition comprising the compound of claim 32 and a pharmaceutically acceptable carrier. 353. A pharmaceutical composition comprising the compound of claim 33 and a pharmaceutically acceptable carrier. 354. A pharmaceutical composition comprising the compound of claim 34 and a pharmaceutically acceptable carrier. 355. A pharmaceutical composition comprising the compound of claim 35 and a pharmaceutically acceptable carrier. 356. A pharmaceutical composition comprising the compound of claim 36 and a pharmaceutically acceptable carrier. 357. A pharmaceutical composition comprising the compound of claim 37 and a pharmaceutically acceptable carrier. 358. A pharmaceutical composition comprising the compound of claim 38 and a pharmaceutically acceptable carrier. 359. A pharmaceutical composition comprising the compound of claim 39 and a pharmaceutically acceptable carrier. 360. A pharmaceutical composition comprising the compound of claim 40 and a pharmaceutically acceptable carrier. |
<SOH> 2. BACKGROUND OF THE INVENTION <EOH> |
<SOH> 3. SUMMARY OF THE INVENTION <EOH> |
Method and device for applying compressive and/or tractional forces to essentially rod-shaped workpieces consisting of electroconductive and/or magnetisable material |
The disclosure relates to a method for applying compressive and/or tractional forces to an essentially rod-shaped workpiece, according to which a mechnical engagement in the rod-shaped workpiece can be avoided. To this end, the method involves applying compressive and/or tractional forces to an essentially rod-shaped workpiece including an electroconductive and/or magnetizable material. A magnetic field is applied to the workpiece, including a gradient in the direction of the force to be applied. The disclosure also relates to a device for applying compressive and/or tractional forces to an essentially rod-shaped workpiece including electroconductive and/or magnetizable material. The device includes a coil arrangement that is supplied by a current and is designed to produce a magnetic field having a gradient. |
1-13. (Cancel) 14. Method for applying compressive and/or tractive forces on a rod-shaped workpiece comprising electrically conductive and/or magnetizable material, the method comprising: applying a magnetic field on the workpiece comprising a gradient pointing in a direction of a force to be applied, wherein a current flowing through a coil arrangement is modified periodically as a function of time with a frequency that corresponds to a resonance frequency for a maximum force to be applied on the workpiece. 15. Method pursuant to claim 14, wherein the magnetic field is generated by the coil arrangement comprising at least two coils that are arranged around the workpiece axially spaced from each other, wherein wherein the at least two coils are flowed through by a current, respectively, for the purpose of generating different magnetic fields. 16. Method pursuant to claim 15, wherein the at least two coils each are flowed through by a current, wherein the currents flowing through the individual coils are out-of-phase and/or have different current strengths. 17. Method pursuant to claim 15, wherein the current flowing through the coil arrangement is modified as a function of time. 18. Method pursuant to claim 15, wherein the coil arrangement is cooled. 19. Method pursuant to claim 14, wherein the workpiece is electrically conductive and subjected to current through flow. 20. Method pursuant to claim 14, wherein the workpiece is cooled. 21. Method pursuant to claim 14, wherein the compressive and/or tractive forces are applied to the workpiece for the purpose of transporting and/or forming the same. 22. Device for applying compressive and/or tractive forces on a rod-shaped workpiece comprising electrically conductive and/or magnetizable material, the device comprises: a coil arrangement that is adapted to be acted upon by current for generating a magnetic field comprising a gradient pointing in the direction of the force to be applied on the workpiece. 23. Device pursuant to claim 22, wherein the coil arrangement comprises at least two coils, which can be acted upon by a current that can be adjusted individually for each coil by means of a control unit. 24. Device pursuant to claim 23, wherein the coils are arranged around a workpiece path in a concentric manner and in the axial direction of the rod-shaped workpiece at a distance from each other, wherein along said path compressive and/or tractive forces are supposed to be applied on the workpiece. |
Illuminated signage employing light emitting diodes |
An illuminated sign (88) includes a flexible electrical power cord (100) including first and second parallel conductors (112, 114) surroundingly contained within an insulating sheath defining a constant separation distance between the parallel conductors (112, 114). A plurality of light emitting diode (LED) devices (102) are affixed to the cord (100). Each LED device (102) includes an LED (104) having a positive lead (130p) electrically communicating with the first parallel conductor (112) and a negative lead (130p) electrically communicating with the second parallel conductor (114). A stencil (92) defines a selected shape, and the electrical cord (100) is arranged on the stencil (92). Power conditioning electronics (210, 220) disposed away from the stencil (92) electrically communicate with the first and second parallel conductors (112, 114) of the electrical power cord (100). The power conditioning electronics (210, 220) power the LED devices (102) via the parallel conductors (112, 114). |
1. An illuminated sign comprising: a flexible electrical power cord including first and second parallel conductors surroundingly contained within an insulating sheath defining a constant separation distance between the parallel conductors; a plurality of light emitting diode (LED) devices affixed to the cord, each LED device including an LED having a positive lead electrically communicating with the first parallel conductor and a negative lead electrically communicating with the second parallel conductor; a stencil defining a selected shape and onto which the electrical cord is arranged; and power conditioning electronics disposed away from the stencil and electrically communicating with the first and second parallel conductors of the electrical power cord, the power conditioning electronics powering the LED devices via the parallel conductors. 2. The illuminated sign as set forth in claim 1, further including: a housing inside which the stencil, LED devices, and electrical power cord are arranged, the power conditioning electronics disposed outside of and away from the housing, the housing further defining the selected shape and including a light transmissive region arranged to transmit light generated by the plurality of LED devices. 3. The illuminated sign as set forth in claim 1, wherein each LED device includes: a connector including: a first region onto which an LED is secured, and a second region that mechanically connects with the electrical power cord, the second region including a positive prong that electrically contacts the positive LED lead and the first parallel conductor, and a negative prong that electrically contacts the negative LED lead and the second parallel conductor. 4. The illuminated sign as set forth in claim 3, wherein each connector further includes: a flange adapted for affixing the connector to the stencil. 5. The illuminated sign as set forth in claim 3, wherein the second region includes a fastener that mechanically secures onto the electrical power cord, the mechanical securing simultaneously electrically contacting the positive and negative prongs with the first and second conductors, respectively. 6. The illuminated sign as set forth in claim 1, wherein the flexible electrical power cord further includes: a plurality of cords each including first and second parallel conductors surroundingly contained within a continuous insulating sheath defining a constant separation distance between the parallel conductors; and at least one splice connector that mechanically joins the plurality of cords, the splice connector electrically connecting the first conductors of the plurality of cords, and electrically connecting the second conductors of the plurality of cords. 7. An article of manufacture for installing a plurality of light emitting diodes (LEDs) into a channel letter housing having at least one light-transmissive surface, the article of manufacture comprising: a substantially rigid structure which is pre-formed or formable for arrangement in the channel letter housing; a flexible cable including at least two flexible parallel conductors arranged to support an electrical potential difference therebetween; a plurality of LEDs electrically parallel-interconnected by communication of the anode and cathode of each LED with the at least two conductors of the flexible cable; a fastener that secures at least a portion of the flexible cable onto the rigid structure; and a power module that receives power having first characteristics and converts the received power to a supply power having second characteristics which is communicated to the at least two conductors of the flexible cable to power the plurality of parallel-interconnected LEDs. 8. The article of manufacture as set forth in claim 7, further including: a plurality of connectors corresponding to the plurality of LEDs, each connector retaining an LED and mechanically connecting with the cable, and each connector including a first conductive element that contacts the LED anode and one of the at least two conductors, each connector further including a second conductive element that contacts the LED cathode and another of the at least two conductors. 9. The article of manufacture as set forth in claim 8, wherein the fastener for securing at least a portion of the flexible cable onto the rigid structure includes: a bracket arranged on each of the plurality of connectors for securing the connector to the rigid structure. 10. The article of manufacture as set forth in claim 8, wherein the connector further includes: first and second connector sections that snap together about a portion of the flexible cable to secure the connector to the cable portion. 11. The article of manufacture as set forth in claim 10, wherein the connecting region includes: ends of the first and second conductive elements that extend outward from the first connector section toward the second connector section, the ends including insulation-piercing tips that displace an insulative coating of the flexible cable to contact the respective two cable conductors. 12. The article of manufacture as set forth in claim 11, wherein the insulation-piercing tips each include: a bifurcated portion that receives the respective cable conductor. 13. A light emitting diode (LED) light engine, comprising: an electrical cable including: at least two flexible electrical conductors, and a flexible, electrically insulating covering surrounding the electrical conductors, the conductors arranged substantially parallel with a selected separation therebetween; and an LED with a plurality of electrical leads separated by the selected separation which electrically contact the electrical conductors and mechanically pierce the insulating covering to mechanically secure the LED to the electrical cable. 14. The LED light engine as set forth in claim 13, wherein each of the conductors includes a plurality of strands and is about 14 gauge. 15. The LED light engine as set forth in claim 13, wherein each of the electrical leads is wedge-shaped. 16. The LED light engine as set forth in claim 13, wherein the flexible covering includes a plurality of dips positioned for aligning the leads with the flexible elements. 17. A light emitting diode (LED) light engine including: an electrical cable including a positive flexible conductor connected with an associated positive source of electrical power, a negative flexible conductor connected with an associated negative source of electrical power, and an electrically insulating covering surrounding and electrically insulating the positive and negative conductors and holding the conductors separate at a selected separation distance; an LED including positive and negative leads; and a connector mechanically secured to the flexible insulating covering, the connector including positive and negative prongs that pierce the insulating covering and electrically contact the positive and negative conductors, respectively, the connector further having the LED mounted thereon with the positive and negative leads of the LED electrically contacting the positive and negative prongs, respectively. 18. The LED light engine as set forth in claim 17, wherein: each of the connector prongs is V-shaped; and each of the electrical cable conductors is positioned within an opening defined by the respective V-shaped connector prong. 19. The LED light engine as set forth in claim 18, wherein the connector includes a locking tab for securing the connector in a locked position, the cable conductors being positioned within the respective V-shaped connector prongs when the connector is in the locked position. 20. A method of manufacturing an LED light engine, the method comprising: insulating a plurality of conductive elements to form a flexible electrically insulating conductor; mechanically securing an LED to the insulated conductive elements; and simultaneously with the mechanical securing, electrically contacting a plurality of leads of the LED to respective ones of the conductive elements. 21. The method of manufacturing an LED light engine as set forth in claim 20, wherein the securing step includes: displacing an insulating covering over one of the conductive elements; and inserting one of the LED leads into the displaced covering. 22. The method of manufacturing an LED light engine as set forth in claim 21, wherein the conductive elements include a plurality of conductive strands, the contacting step including: passing one of the LED leads through an insulating covering over one of the conductive elements; and inserting the LED lead between the conductive strands of the conductive element. 23. The method of manufacturing an LED light engine as set forth in claim 22, wherein the insulating covering includes a groove, further including, before the passing step: aligning the LED lead with the conductive element via the groove. 24. The method of manufacturing an LED light engine as set forth in claim 20, wherein: the securing step includes: mechanically attaching a connector to an insulating covering on the conductor; and the contacting step includes: passing an electrical contact, secured to the connector, through the insulating covering so that an electrical connection is made between the contact and a respective one of the conductive elements. 25. The method of manufacturing an LED light engine as set forth in claim 24, wherein the electrical contact is V-shaped, the passing step including: securing the conductive element within the V-shaped contact. 26. A flexible lighting device comprising: a flexible cable including an electrically insulating sheath which contains positive and negative conductors electrically isolated from one another, the sheath providing a spacing between the positive and negative conductors; and a plurality of light emitting diode (LED) devices spaced apart from one another on the cable, each of the LED devices having an LED including positive and negative leads mounted on a connector which mechanically secures the LED device to a portion of the flexible cable and electrically connects the positive and negative LED leads to the positive and negative conductors through positive and negative conductive piercing members which pierce the sheath to make electrical contact with the respective conductors. 27. The flexible lighting device as set forth in claim 26, wherein each connector includes: an LED mount region that receives the LED; a clamp region that secures the connector to the portion of the flexible cable, the clamp region aligning the positive and negative conductive piercing members with the positive and negative conductors of the flexible cable, each conductive piercing member including an insulation-piercing end that displaces the insulating sheath when the clamp region is secured to electrically contact with the respective conductor; and a fastening region for fastening the connector onto an associated supporting structure. 28. The flexible lighting device as set forth in claim 27, wherein the fastening region of each connector includes: an opening adapted to cooperate with a fastener to fasten the connector to the associated supporting structure. 29. The flexible lighting device as set forth in claim 26, wherein each conductive piercing member includes: a bifurcated end defining a gap sized to receive the respective conductor. 30. The flexible lighting device as set forth in claim 29, wherein each electrical cable conductor is a multi-stranded conductor, and the conductor is compressively held within the bifurcated end. 31. The flexible lighting device as set forth in claim 26, wherein each connector includes: a first section including an LED mount region that receives the LED; and a second section that cooperates with the first section to define a clamp region; wherein the first and second sections snap together with the flexible cable portion arranged therebetween to secure the connector to the flexible cable, the snapping causing the conductive piercing members to pierce the sheath and make electrical contact with the respective conductors. 32. The flexible lighting device as set forth in claim 31, wherein the insulating sheath of the flexible cable includes: dips arranged on the surface of the sheath and corresponding with the positive and negative electrical conductors, the dips receiving ends of the conductive piercing members to align the flexible cable portion between the first and second connector sections prior to the snapping theretogether. 33. The flexible lighting device as set forth in claim 26, wherein the positive and negative conductors within the insulating sheath define a cable plane, the flexible electrical cable being flexible in a direction out of the cable plane, the LED emitting light substantially directed parallel to the cable plane. 34. The flexible lighting device as set forth in claim 26, wherein intervening cable portions between the spaced apart LED devices are selectively flexed to define a selected channel lettering. 35. The flexible lighting device as set forth in claim 26, wherein the flexible cable includes first and second flexible cables, the flexible lighting device further including: a splice connector that mechanically and electrically connects first and second flexible cables, the splice connector including positive and negative conductive piercing members which pierce the sheaths of the first and second cables to make electrical contact with the respective conductors. 36. A light emitting diode (LED) lighting apparatus comprising: a flexible electrical cable including an anode wire and a cathode wire arranged in an electrically isolating sheath; a plurality of LED devices spaced apart along the cable and mechanically and electrically connected therewith, each LED device including: an LED having at least one anode lead and at least one cathode lead, and a connector including an LED socket that receives the anode and cathode leads, the LED socket mechanically retaining the LED, the connector further including a first electrically conductive path between the anode lead and the anode wire, and a second electrically conductive path between the cathode lead and the cathode wire, the first and second conductive paths displacing portions of the cable sheath. 37. The LED lighting apparatus as set forth in claim 36, wherein the first and second conductive paths each include: an electrically conductive element contacting the LED lead, the conductive element including an insulation-piercing end that displaces a portion of the cable sheath and contacts the respective cable wire. 38. The LED lighting apparatus as set forth in claim 37, wherein the connector includes first and second sections that surroundingly clamp onto a portion of the cable, the insulation piercing ends of the first and second conductive paths extending into the clamp portion such that they pierce the cable sheath responsive to the clamping to effectuate contact with the respective cable wires. 39. The LED lighting apparatus as set forth in claim 37, wherein each insulation piercing end includes a bifurcation that receives a portion of the anode or cathode wire without cutting said wire. 40. The LED lighting apparatus as set forth in claim 37, wherein the LED leads and the conductive elements include an electrically conductive surface material of the same type. 41. The LED lighting apparatus as set forth in claim 37, wherein the anode and cathode wires and the conductive elements include an electrically conductive surface material of the same type. 42. The LED lighting apparatus as set forth in claim 37, wherein the anode and cathode wires, the conductive elements, and the LED leads each include an electrically conductive surface selected to substantially reduce galvanic corrosion at electrically contacting surfaces therebetween. 43. The LED lighting apparatus as set forth in claim 37, wherein the contacting of the electrically conductive element with the LED lead effectuates electrical contact without cooperation of an electrically conductive solder. 44. The LED lighting apparatus as set forth in claim 36, wherein the first and second conductive paths include: an electrically conductive anode prong; an electrically conductive cathode prong; an anode prong recess that receives the anode prong; and a cathode prong recess that receives the cathode prong; wherein the prong recesses communicate with the LED socket such that the LED leads penetrate the prong recesses to contact with the prongs. 45. The LED lighting apparatus as set forth in claim 36, wherein each connector includes one LED socket. 46. The LED lighting apparatus as set forth in claim 36, further including: a stencil defining a selected letter or symbol, the flexible electrical cable arranged on the stencil to light the selected letter or symbol. 47. The LED lighting apparatus as set forth in claim 46, wherein the electrical cable is fastened onto the stencil via the connectors. 48. The LED lighting apparatus as set forth in claim 46, wherein the stencil includes a plurality of stencils defining a plurality of letters or symbols, and the flexible electrical cable includes a plurality of flexible electrical cables arranged on the plurality of stencils, the LED lighting apparatus further including: a power supply having a plurality of individually adjustable power output lines each electrically powering one or more flexible electrical cables, the individually adjustable power output lines selectively adjusted such that the intensities produced by the flexible electrical cables are substantially uniform. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Channel letters are known to those skilled in the art of making commercial signs as the most attractive and expensive form of sign lettering. Briefly, channel letters usually include a plastic or metal backing having the shape of the letter to be formed. Metal channel siding, frequently formed of aluminum with a painted or otherwise finished interior and exterior surface, is attached to and sealed to the letter backing, giving depth to the letter to be formed. Electrical lighting fixtures, such as neon tubing and mounting brackets, are attached to the letter backing. Typically, a colored, translucent plastic letter face is attached to the front edge portion of the channel side material. As discussed above, neon lighting is typically incorporated into channel lettering systems. Neon systems are very fragile and, therefore, tend to fail and/or break during manufacture, shipping or installation. Also, such lighting systems use high voltage (e.g., between about 4,000 and about 15,000 volts) electricity to excite the neon gas within the tubing. High voltage applications have been associated with deaths by electrocution and building damage due to fire. Semiconductor lighting (e.g., light emitting diodes), that overcomes most of these drawbacks, has been used for channel lettering. One such conventional channel lettering device attaches a light emitting diode (“LED”) system to a back of a channel letter such that the LED system emits light toward a translucent face at a front of the device. The LEDs are spaced at regular intervals (e.g., 2 inches) and are pressed into a socket. The socket is designed for a press-fit of a modified Super Flux (Piranha) package. The lead frames of the Piranha are bent 90 degrees to fit into the socket. The connection for the LED is similar to insulation displacement (“IDC”). The socket also has two IDC places for a red and black wire. This system puts all of the LEDs in parallel. Furthermore, the two part power supply (Initial (120VAC to 24VDC) and the Secondary (24VDC to ˜2.3VDC)) have two basic wiring connections. The secondary has a sense circuit, which has one LED attached for determining the voltage applied to the rest of the LEDs that are attached to the second connection. Another conventional channel lettering device attaches to a side of the channel letter and is pointed toward the backing. The diffuse surface of the channel letter walls provides a uniform appearance. Each module has a predetermined number of LEDs electrically connected in series. Furthermore, all of the modules are daisy chained together in a parallel circuit. The LEDs are mounted on an aluminum base for heat sinking purposes. Another conventional channel lettering device uses a plurality of surface mounted LEDs with an integral connector system. Although these conventional LED channel lettering systems overcome some of the drawbacks associated with neon systems, other shortcomings are evident. For example, the conventional LED channel lettering systems offer only limited flexibility. More specifically, the LEDs cannot be easily set into a desired shape involving significant curves or bends (e.g., wrapped around a pole or in a very small radius (<3 inches). Furthermore, the LEDs cannot be easily moved from one lighting application to another. The present invention contemplates an improved apparatus and method that overcomes the above-mentioned limitations and others. |
<SOH> BRIEF SUMMARY OF THE INVENTION <EOH>In accordance with one embodiment of the present invention, an illuminated sign is disclosed. A flexible electrical power cord includes first and second parallel conductors surroundingly contained within an insulating sheath defining a constant separation distance between the parallel conductors. A plurality of light emitting diode (LED) devices are affixed to the cord. Each LED device includes an LED having a positive lead electrically communicating with the first parallel conductor and a negative lead electrically communicating with the second parallel conductor. A stencil defines a selected shape and onto which the electrical cord is arranged. Power conditioning electronics disposed away from the stencil electrically communicate with the first and second parallel conductors of the electrical power cord. The power conditioning electronics power the LED devices via the parallel conductors. In accordance with another embodiment of the present invention, an article of manufacture is disclosed for installing a plurality of light emitting diodes (LEDs) into a channel letter housing which has at least one light-transmissive surface. A substantially rigid structure is pre-formed or formable for arrangement in the channel letter housing. A flexible cable including at least two flexible parallel conductors is arranged to support an electrical potential difference between the parallel conductors. A plurality of LEDs electrically parallel-interconnected by communication of the anode and cathode of each LED with the at least two conductors of the flexible cable. A fastener secures at least a portion of the flexible cable onto the rigid structure. A power module receives power having first characteristics and converts the received power to a supply power having second characteristics which is communicated to the at least two conductors of the flexible cable to power the plurality of parallel-interconnected LEDs. In accordance with another embodiment of the present invention, a light emitting diode (LED) light engine is disclosed. An electrical cable includes at least two flexible electrical conductors. The electrical cable further includes a flexible, electrically insulating covering that surrounds the electrical conductors. The conductors are arranged substantially parallel with a selected separation therebetween. An LED with a plurality of electrical leads separated by the selected separation electrically contacts the electrical conductors and mechanically pierces the insulating covering to mechanically secure the LED to the electrical cable. In accordance with another embodiment of the present invention, a light emitting diode (LED) light engine is disclosed. An electrical cable includes a positive flexible conductor connected with an associated positive source of electrical power, a negative flexible conductor connected with an associated negative source of electrical power, and an electrically insulating covering surrounding and electrically insulating the positive and negative conductors and holding the conductors separate at a selected separation distance. An LED includes positive and negative leads. A connector mechanically secures to the flexible insulating covering. The connector includes positive and negative prongs that pierce the insulating covering and electrically contact the positive and negative conductors, respectively. The connector further has the LED mounted thereon with the positive and negative leads of the LED electrically contacting the positive and negative prongs, respectively. In accordance with another embodiment of the present invention, a method of manufacturing an LED light engine is provided. A plurality of conductive elements are insulated to form a flexible electrically insulating conductor. An LED is mechanically secured to the insulated conductive elements. Simultaneously with the mechanical securing, a plurality of leads of the LED are electrically contacted to respective ones of the conductive elements. In accordance with yet another embodiment of the present invention, a flexible lighting device is disclosed. A flexible cable includes an electrically insulating sheath which contains positive and negative conductors electrically isolated from one another. The sheath provides a spacing between the positive and negative conductors. A plurality of light emitting diode (LED) devices are spaced apart from one another on the cable. Each of the LED devices has an LED including positive and negative leads mounted on a connector which mechanically secures the LED device to a portion of the flexible cable and electrically connects the positive and negative LED leads to the positive and negative conductors through positive and negative conductive piercing members which pierce the sheath to make electrical contact with the respective conductors. In accordance with still yet another embodiment of the present invention, a light emitting diode (LED) lighting apparatus is disclosed. A flexible electrical cable includes an anode wire and a cathode wire arranged in an electrically isolating sheath. A plurality of LED devices are spaced apart along the cable and mechanically and electrically connect therewith. Each LED device includes an LED having at least one anode lead and at least one cathode lead. Each LED device further includes a connector with an LED socket that receives the anode and cathode leads. The LED socket mechanically retains the LED. The connector further includes a first electrically conductive path between the anode lead and the anode wire, and a second electrically conductive path between the cathode lead and the cathode wire. The first and second conductive paths displace portions of the cable sheath. One advantage of the present invention resides in providing a channel lettering having a reduced number of parts compared with past systems. Another advantage of the present invention resides in the use of parallel interconnection of the LEDs which reduces the likelihood that a failed LED will adversely affect performance of other LEDs on the same electrical circuit. Another advantage of the present invention resides in the locating of the conditioning electronics away from the channel lettering, e.g. in a secure and weatherproofed interior location. Another advantage of the present invention is the avoidance of soldering connections in the flexible LED light engine. Yet another advantage of the present invention is that it allows for coupling in the electrical power anywhere along the flexible LED light engine. Still yet another advantage of the present invention resides in its modular nature which allows part or all of a channel lettering to be constructed on-site in a customized manner. Numerous advantages and benefits of the present invention will become apparent to those of ordinary skill in the art upon reading and understanding the following detailed description. |
Warehouse system and a method for temporary storage of articles |
A warehouse system comprising several storage racks each comprising a number of compartments arranged above each other and beside each other, and a unit which is movable along said compartments and which comprises a mechanism which is capable of moving a container from the unit into a compartment and from a compartment onto the unit. The unit can be moved over the storage racks from a space located between two storage racks to another space located between two storage racks. A conveyor is provided, which conveyor is positioned beside the unit in the uppermost position of said unit and which can be moved over the storage racks together with the unit. |
1-9. (canceled) 10. A warehouse system comprising several storage racks each comprising a number of compartments arranged above each other and beside each other, and a unit which is movable along said compartments and which comprises a mechanism which is capable of moving a container from the unit into a compartment and from a compartment onto the unit, which unit can be moved over the storage racks from a space located between two storage racks to another space located between two storage racks, a conveyor positioned beside the unit in the uppermost position of said unit and which can be moved over the storage racks together with the unit, and conveying means extending along the storage racks at the level of the conveyor, to which conveying means the conveyor can deliver containers. 11. The warehouse system according to claim 10, wherein the unit is vertically movable in a frame which can be moved in horizontal direction, wherein the conveyor is likewise arranged in said frame. 12. The warehouse system according to claim 11, wherein the frame comprises one element which extends above the storage racks and two downwardly extending elements on either side of the racks, which elements guide the unit during its vertical movement in the space between the racks. 13. The warehouse system according to claim 10, wherein two conveyors are present, which conveyors are positioned on either side of the unit in the uppermost position of said unit. 14. The warehouse system according to claim 11, wherein two conveyors are present, which conveyors are positioned on either side of the unit in the uppermost position of said unit. 15. The warehouse system according to claim 12, wherein two conveyors are present, which conveyors are positioned on either side of the unit in the uppermost position of said unit. 16. A frame which is movable with respect to warehouse racks, wherein each rack comprises a number of compartments arranged above and beside each other, which frame comprises a unit which is movable with respect to the frame, said unit comprising a mechanism which is capable of moving a container from the unit into a compartment and from a compartment onto the unit, wherein the frame comprises a conveyor onto which the unit can place containers in the uppermost position of the unit, and wherein the conveyor is arranged to deliver containers to conveying means extending along the storage racks at the level of the conveyor. 17. The frame according to claim 16, wherein two conveyors are present, which conveyors are positioned on either side of the unit in the uppermost position of said unit. 18. A method for temporary storage of articles, in which containers with the articles present therein are placed in a number of warehouse rack compartments arranged above and beside each other, in which a mechanism, which is present on a unit which is movable along said compartments, places a container from a compartment onto the unit, whereupon the unit is moved to its uppermost position, in which position the container is placed onto a conveyor, after which the conveyor and the unit are moved in substantially horizontal direction over the storage rack to another warehouse rack, wherein the container is delivered by the conveyor to conveying means extending along the racks at the level of the conveyor. |
Method and apparatus for rapid determination of ligand-protein binding using charcoal adsorption |
A method for evaluating binding of a ligand to a target protein. The method includes the steps of: (a) providing a sample comprising a target protein and a ligand, wherein the target protein and ligand are suspected to be bound reversibly together in a complex; (b) preconditioning activated charcoal with the target protein; (c) contacting the sample with the preconditioned activated charcoal for a time sufficient to allow for adsorption of unbound ligand to the activated charcoal; (d) eluting the sample from the activated charcoal; and (e) determining an amount of ligand in the eluted sample to thereby evaluate binding of the ligand to the target protein. An apparatus useful in carrying out the method, and a method of making the same, are also disclosed. |
1. A method for evaluating binding of a ligand to a target protein, the method comprising: (a) providing a sample comprising a target protein and a ligand, wherein the target protein and ligand are suspected to be bound reversibly together in a complex; (b) preconditioning activated charcoal with the target protein; (c) contacting the sample with the pre-conditioned activated charcoal for a time sufficient to allow for adsorption of unbound ligand to the activated charcoal; (d) eluting the sample from the activated charcoal; and (e) determining an amount of ligand in the eluted sample to thereby evaluate binding of the ligand to the target protein. 2. The method of claim 1 wherein the providing a sample comprises contacting a matrix comprising a target protein with at least one ligand for a time sufficient to allow for binding of the at least one ligand by the target protein. 3. The method of claim 2, wherein contacting a matrix comprising a target protein with at least one ligand comprises creating a suspension of the matrix comprising a target protein and the at least one ligand. 4. The method of claim 2, wherein the time sufficient to allow for binding comprises a duration equal to or less than about 30 minutes. 5. The method of claim 2, wherein the matrix comprises blood plasma. 6. The method of claim 5, wherein the blood plasma comprises human blood plasma. 7. The method of claim 1, wherein the target protein comprises serum albumin or α1-acid-glycoprotein. 8. The method of claim 1, wherein the ligand comprises a chemical compound, a peptide, an oligonucleotide, a small molecule, or combinations thereof. 9. The method of claim 8, wherein the ligand is a candidate drug. 10. The method of claim 1, wherein the ligand further comprises a detectable label. 11. The method of claim 1, wherein the sample comprises a volume of about 200 μl. 12. The method of claim 1, wherein the preconditioning activated charcoal comprises contacting activated charcoal with the target protein or with a protein similar to the target protein for a time sufficient to allow for adsorption of the target protein or of the protein similar to the target protein to the activated charcoal. 13. The method of claim 12, wherein a time sufficient for adsorption of the target protein or of the protein similar to the target protein to the activated charcoal comprises about 1 second. 14. The method of claim 1, wherein the preconditioning comprises: (a) preconditioning activated charcoal immediately prior to contacting the sample with the preconditioned activated charcoal; or (b) preconditioning activated charcoal within 24 hours prior to contacting the sample with the preconditioned activated charcoal and rinsing the preconditioned activated charcoal immediately prior to contacting the sample with the preconditioned activated charcoal. 15. The method of claim 12, wherein preconditioning further comprises: (a) applying the target protein or the protein similar to the target protein to a packed-bed activated charcoal cartridge, and (b) eluting the target protein or the protein similar to the target protein from the packed-bed activated charcoal cartridge, whereby the activated charcoal is pre-conditioned. 16. The method of claim 15, wherein the applying the target protein or the protein similar to the target protein comprises providing a solution having a volume and a concentration -of the target protein or of the protein similar to the target protein, wherein the volume of the solution comprises a volume approximately equal to a volume of the sample, and wherein the concentration of the target protein or of the protein similar to the target protein in the solution comprises a concentration approximately equal to a concentration of the target protein in the sample. 17. The method of claim 1, wherein the activated charcoal comprises dextran-coated charcoal. 18. The method of claim 17, wherein the dextran-coated charcoal comprises dextrans having an average molecular weight of about 35 kDa to about 200 kDa. 19. The method of claim 18, wherein the dextran-coated charcoal comprises dextrans having an average molecular weight of about 50 kDa to about 150 kDa. 20. The method of claim 19, wherein the dextran-coated charcoal comprises dextrans having an average molecular weight of about 75 kDa to about 80 kDa. 21. The method of claim 17, wherein the dextran-coated charcoal comprises a fractional weight of about 10% to about 80% dextran. 22. The method of claim 21, wherein the dextran-coated charcoal comprises a fractional weight of about 10% to about 50% dextran. 23. The method of claim 22, wherein the dextran-coated charcoal comprises a fractional weight of about 10% dextran. 24. The method of claim 17, wherein the dextran-coated charcoal comprises a mass of about 5 mg to about 100 mg. 25. The method of claim 24, wherein the dextran-coated charcoal comprises a mass of about 5 mg to about 50 mg. 26. The method of claim 25, wherein the dextran-coated charcoal comprises a mass of about 20 mg. 27. The method of claim 1, wherein contacting the sample with pre-conditioned activated charcoal further comprises applying the sample to a packed-bed activated charcoal cartridge. 28. The method of claim 1, wherein the time sufficient to allow for adsorption of unbound ligand to the activated charcoal comprises about 1 second. 29. The method of claim 1, wherein eluting the sample comprises applying suction to the sample, whereby the sample is separated from the activated charcoal. 30. The method of claim 1, wherein determining an amount of ligand in the eluted sample comprises performing mass spectrometry analysis of the eluted sample. 31. The method of claim 10, wherein determining an amount of ligand in the eluted sample comprises detecting the detectably labeled ligand in the eluted sample. 32. A method for evaluating binding of a ligand to a target protein, the method comprising: (a) providing a sample comprising a target protein and a first ligand, wherein the first ligand comprises a detectable label, and wherein the target protein and first ligand are suspected to be bound reversibly together in a complex; (b) contacting the sample with a candidate second ligand for a time sufficient for displacement of the first ligand from the complex by the second ligand; (c) preconditioning activated charcoal with the target protein; (d) contacting the sample of (b) with the pre-conditioned activated charcoal for a time sufficient to allow for adsorption of unbound first ligand to the activated charcoal; (e) eluting the sample from the activated charcoal; and (f) determining an amount of first ligand in the eluted sample to thereby evaluate binding of the second ligand to the target protein. 33. The method of claim 32 wherein providing a sample comprises contacting a matrix comprising a target protein with a first ligand for a time sufficient to allow for binding of the first ligand by the target protein. 34. The method of claim 33, wherein contacting a matrix comprising a target protein with a first ligand comprises creating a suspension of the matrix comprising a target protein and the first ligand. 35. The method of claim 33, wherein the time sufficient to allow for binding comprises a duration equal to or less than about 30 minutes. 36. The method of claim 33, wherein the matrix comprises blood plasma. 37. The method of claim 36, wherein the blood plasma comprises human blood plasma. 38. The method of claim 32, wherein the sample comprises a volume of about 200 g. 39. The method of claim 32, wherein the target protein comprises serum albumin or α1-acid-glycoprotein. 40. The method of claim 32, wherein the first ligand and the second ligand each comprise a chemical compound, a peptide, an oligonucleotide, a small molecule, or combinations thereof. 41. The method of claim 32, wherein the first ligand comprises a ligand that binds a specific binding site on a target protein. 42. The method of claim 41, further comprising determining an amount of the first ligand in the eluted sample to thereby evaluate binding of the second ligand to the specific ligand binding site of a target protein. 43. The method of claim 32, wherein the first ligand comprises a ligand that binds a plasma protein. 44. The method of claim 43, wherein the first ligand comprises a ligand that binds serum albumin or α1-acid-glycoprotein. 45. The method of claim 44, wherein the first ligand comprises a ligand that binds site I, site II, or site III of human serum albumin. 46. The method of claim 45, wherein the first ligand comprises a site I-binding ligand selected from the group consisting of a cumarine and a pyrazolidine. 47. The method of claim 46, wherein the first ligand comprises a ligand selected from the group consisting of valproate, diphenylhydantoin, or salicylate. 48. The method of claim 45, wherein the first ligand comprises a site II-binding ligand selected from the group consisting of a benzodiazepine, an arylpropionate, and L-tryptophan. 49. The method of claim 48, wherein the first ligand comprises the site II-binding ligand diazepam. 50. The method of claim 45, wherein the first ligand comprises the site III-binding ligand digitoxin. 51. The method of claim 32 wherein the second ligand is a candidate drug. 52. The method of claim 32, wherein a time sufficient for displacement of the first ligand from the complex by the second ligand comprises a duration less than or equal to about 30 minutes. 53. The method of claim 32 wherein preconditioning activated charcoal comprises contacting activated charcoal with the target protein or with a protein similar to the target protein for a time sufficient to allow for adsorption of the target protein or the protein similar to the target protein to the activated charcoal. 54. The method of claim 53, wherein a time sufficient for adsorption of the target protein or of the protein similar to the target protein to the activated charcoal comprises about 1 second. 55. The method of claim 32, wherein the preconditioning comprises: (c) preconditioning activated charcoal immediately prior to contacting the sample with the preconditioned activated charcoal; or (d) preconditioning activated charcoal within 24 hours prior to contacting the sample with the preconditioned activated charcoal and rinsing the preconditioned activated charcoal immediately prior to contacting the sample with the preconditioned activated charcoal. 56. The method of claim 52, wherein preconditioning further comprises: (a) applying the target protein or the protein similar to the target protein to a packed-bed activated charcoal cartridge, and (b) eluting the target protein or the protein similar to the target protein from the packed-bed activated charcoal cartridge, whereby the activated charcoal is pre-conditioned. 57. The method of claim 56, wherein applying the target protein or the protein similar to the target protein comprises providing a solution having a volume and a concentration of the target protein or of the protein similar to the target protein, wherein the volume of the solution comprises a volume approximately equal to a volume of the sample, and wherein the concentration of the target protein or of the protein similar to the target protein in the solution comprises a concentration approximately equal to a concentration of the target protein in the sample. 58. The method of claim 32, wherein the activated charcoal comprises dextran-coated charcoal. 59. The method of claim 58, wherein the dextran-coated charcoal comprises dextrans having an average molecular weight of about 35 kDa to about 200 kDa. 60. The method of claim 59, wherein the dextran-coated charcoal comprises dextrans having an average molecular weight of about 50 kDa to about 150 kDa. 61. The method of claim 60, wherein the dextran-coated charcoal comprises dextrans having an average molecular weight of about 75 kDa to about 80 kDa. 62. The method of claim 58, wherein the dextran-coated charcoal comprises a fractional weight of about 10% to about 80% dextran. 63. The method of claim 62, wherein the dextran-coated charcoal comprises a fractional weight of about 10% to about 50% dextran. 64. The method of claim 63, wherein the dextran-coated charcoal comprises a fractional weight of about 10% dextran. 65. The method of claim 58, wherein the dextran-coated charcoal comprises a mass of about 5 mg to about 100 mg. 66. The method of claim 65, wherein the dextran-coated charcoal comprises a mass of about 5 mg to about 50 mg. 67. The method of claim 66, wherein the dextran-coated charcoal comprises a mass of about 20 mg. 68. The method of claim 32, wherein contacting the sample with pre-conditioned activated charcoal comprises applying the sample to a packed-bed activated charcoal cartridge. 69. The method of claim 32, wherein the time sufficient to allow for adsorption of unbound first ligand to the activated charcoal comprises about 1 second. 70. The method of claim 32, wherein eluting the sample comprises applying suction to the sample, whereby the sample is separated from the activated charcoal. 71. The method of claim 32, wherein determining an amount of ligand in the eluted matrix comprises detecting the detectable label of the first ligand in the eluted matrix. 72. A method for evaluating the susceptibility of a candidate drug to binding a protein found in the circulating blood of a warm-blooded vertebrate, the method comprising: (a) providing a sample comprising a target protein and a ligand, wherein the ligand comprises a detectable label, and wherein the target protein and ligand are suspected to be bound reversibly together in a complex; (b) contacting the sample with a candidate drug for a time sufficient for displacement of the ligand from the complex by the candidate drug; (c) preconditioning activated charcoal with the target protein; (d) contacting the sample of (b) with the pre-conditioned activated charcoal for a time sufficient to allow for adsorption of unbound ligand to the activated charcoal; (e) eluting the sample from the activated charcoal; and (f) determining an amount of ligand in the eluted sample to thereby evaluate the susceptibility of the candidate drug to binding a protein found in the circulating blood of a warm-blooded vertebrate. 73. The method of claim 72 wherein providing a sample comprises contacting a matrix comprising a target protein with a ligand for a time sufficient to allow for binding of the ligand by the target protein. 74. The method of claim 73, wherein contacting a matrix comprising a target protein with a ligand comprises creating a suspension of the matrix comprising a target protein and the ligand. 75. The method of claim 73, wherein the time sufficient to allow for binding comprises a duration equal to or less than about 30 minutes. 76. The method of claim 73, wherein the matrix comprises blood plasma. 77. The method of claim 76, wherein the blood plasma comprises human blood plasma. 78. The method of claim 72 wherein the sample comprises a volume of about 200 μl. 79. The method of claim 72, wherein the target protein comprises serum albumin or α1-acid-glycoprotein. 80. The method of claim 72, wherein the ligand and the candidate drug each comprise a chemical compound, a peptide, an oligonucleotide, a small molecule, or combinations thereof. 81. The method of claim 72, wherein the first ligand comprises a ligand that binds a specific binding site on a target protein. 82. The method of claim 81, further comprising determining an amount of the first ligand in the eluted sample to thereby evaluate binding of the second ligand to the specific ligand binding site of a target protein. 83. The method of claim 72, wherein the ligand comprises a ligand that binds a plasma protein. 84. The method of claim 83, wherein the ligand comprises a ligand that binds serum albumin or α1-acid-glycoprotein. 85. The method of claim 84, wherein the ligand comprises a ligand that binds site I, site II, or site III of human serum albumin. 86. The method of claim 85, wherein the ligand comprises a site I-binding ligand selected from the group consisting of a cumarine and a pyrazolidine. 87. The method of claim 86, wherein the ligand comprises a ligand selected from the group consisting of valproate, diphenylhydantoin, or salicylate. 88. The method of claim 85, wherein the ligand comprises a site II-binding ligand selected from the group consisting of a benzodiazepine, an arylpropionate, and L-tryptophan. 89. The method of claim 88, wherein the ligand comprises the site II-binding ligand diazepam. 90. The method of claim 85, wherein the ligand comprises the site III-binding ligand digitoxin. 91. The method of claim 72, wherein a time sufficient for displacement of the ligand from the complex by the candidate drug comprises a duration less than or equal to about 30 minutes. 92. The method of claim 72 wherein preconditioning activated charcoal comprises contacting activated charcoal with the target protein or with a protein similar to the target protein for a time sufficient to allow for adsorption of the target protein to the activated charcoal. 93. The method of claim 92, wherein a time sufficient for adsorption of the target protein or the protein similar to the target protein to the activated charcoal comprises about 1 second. 94. The method of claim 72, wherein the preconditioning comprises: (e) preconditioning activated charcoal immediately prior to contacting the sample with the preconditioned activated charcoal; or (f) preconditioning activated charcoal within 24 hours prior to contacting the sample with the preconditioned activated charcoal and rinsing the preconditioned activated charcoal immediately prior to contacting the sample with the preconditioned activated charcoal. 95. The method of claim 92, wherein preconditioning further comprises: (a) applying the target protein or the protein similar to the target protein to a packed-bed activated charcoal cartridge; and (b) eluting the target protein or the protein similar to the target protein from the packed-bed activated charcoal cartridge, whereby the activated charcoal is pre-conditioned. 96. The method of claim 95, wherein applying the target protein or the protein similar to the target protein comprises providing a solution having a volume and a concentration of the target protein or of the protein similar to the target protein, wherein the volume of the solution comprises a volume approximately equal to a volume of the sample, and wherein the concentration of the target protein or of the protein similar to the target protein in the solution comprises a concentration approximately equal to a concentration of the target protein in the sample. 97. The method of claim 72, wherein the activated charcoal comprises dextran-coated charcoal. 98. The method of claim 97, wherein the dextran-coated charcoal comprises dextrans having an average molecular weight of about 35 kDa to about 200 kDa. 99. The method of claim 98, wherein the dextran-coated charcoal comprises dextrans having an average molecular weight of about 50 kDa to about 150 kDa. 100. The method of claim 99, wherein the dextran-coated charcoal comprises dextrans having an average molecular weight of about 75 kDa to about 80 kDa. 101. The method of claim 97, wherein the dextran-coated charcoal comprises a fractional weight of about 10% to about 80% dextran. 102. The method of claim 101, wherein the dextran-coated charcoal comprises a fractional weight of about 10% to about 50% dextran. 103. The method of claim 102, wherein the dextran-coated charcoal comprises a fractional weight of about 10% dextran. 104. The method of claim 97, wherein the dextran-coated charcoal comprises a mass of about 5 mg to about 100 mg. 105. The method of claim 104, wherein the dextran-coated charcoal comprises a mass of about 5 mg to about 50 mg. 106. The method of claim 105, wherein the dextran-coated charcoal comprises a mass of about 20 mg. 107. The method of claim 72, wherein contacting the sample with pre-conditioned activated charcoal comprises applying the sample to a packed-bed activated charcoal cartridge. 108. The method of claim 72, wherein the time sufficient to allow for adsorption of unbound ligand to the activated charcoal comprises about 1 second. 109. The method of claim 72, wherein eluting the sample comprises applying suction to the sample, whereby the sample is separated from the activated charcoal. 110. The method of claim 72, wherein determining an amount of ligand in the eluted matrix comprises detecting the detectable label of the ligand in the eluted matrix. 111. A packed-bed charcoal cartridge for evaluating ligand binding to a target protein, comprising: (a) a column comprising a sample chamber, a sample addition port, and a sample elution port adapted for fluid/gaseous communication with a suction source; and (b) an activated charcoal packed-bed positioned between the sample chamber and the sample elution port, wherein the charcoal packed-bed is in fluid/gaseous communication with the sample chamber and with the sample elution port. 112. The packed-bed charcoal cartridge of claim 111, wherein the column comprises a sample chamber capable of holding about one (1) milliliter of liquid volume. 113. The packed-bed charcoal cartridge of claim 112, wherein the column comprises a PREPSEP® column, and wherein a bottom of the sample chamber comprises a frit. 114. The packed-bed charcoal cartridge of claim 111, wherein the activated charcoal comprises dextran-coated charcoal. 115. The packed-bed charcoal cartridge of claim 114, wherein the dextran-coated charcoal comprises dextrans having an average molecular weight of about 35 kDa to about 200 kDa. 116. The packed-bed charcoal cartridge of claim 115, wherein the dextran-coated charcoal comprises dextrans having an average molecular weight of about 50 kDa to about 150 kDa. 117. The packed-bed charcoal cartridge of claim 116, wherein the dextran-coated charcoal comprises dextrans having an average molecular weight of about 75 kDa to about 80 kDa. 118. The packed-bed charcoal cartridge of claim 114, wherein the dextran-coated charcoal comprises a fractional weight of about 10% to about 80% dextran. 119. The packed-bed charcoal cartridge of claim 118, wherein the dextran-coated charcoal comprises a fractional weight of about 10% to about 50% dextran. 120. The packed-bed charcoal cartridge of claim 119, wherein the dextran-coated charcoal comprises a fractional weight of about 10% dextran. 121. The packed-bed charcoal cartridge of claim 114, wherein the dextran-coated charcoal comprises a mass of about 5 mg to about 100 mg. 122. The packed-bed charcoal cartridge of claim 121, wherein the dextran-coated charcoal comprises a mass of about 5 mg to about 50 mg. 123. The packed-bed charcoal cartridge of claim 121, wherein the dextran-coated charcoal comprises a mass of about 20 mg. 124. The packed-bed charcoal cartridge of claim 111 further comprising a filter positioned adjacent to and below the frit. 125. The packed-bed charcoal cartridge of claim 124 wherein the filter comprises a 1-cm glass filter. 126. An apparatus for high-throughput analysis of ligand binding to a protein comprising an array of packed-bed activated charcoal cartridge units of claim 111. 127. The apparatus of claim 126, wherein the array comprises 96 packed-bed activated charcoal cartridge units or an integer multiple thereof. 128. A method for preparing a packed-bed activated charcoal cartridge unit, the method comprising: (a) providing a column comprising a sample chamber, a sample addition port, a sample elution port adapted for fluid/gaseous communication with a suction source, and a barrier positioned between the sample chamber and the sample elution port; (b) applying activated charcoal in a liquid suspension to the column; and (c) eluting the liquid from the column, whereby the activated charcoal is packed adjacent to the barrier, and whereby a packed-bed activated charcoal cartridge is prepared. 129. The method of claim 128, wherein the column comprises a sample chamber capable of holding a liquid volume comprising about one (1) milliliter. 130. The method of claim 129, wherein the column comprises a PREPSEP® column, and wherein the barrier comprises a frit. 131. The method of claim 128, wherein the activated charcoal comprises dextran-coated charcoal. 132. The method of claim 131, wherein the dextran-coated charcoal comprises dextrans having an average molecular weight of about 35 kDa to about 200 kDa. 133. The method of claim 131, wherein the dextran-coated charcoal comprises dextrans having an average molecular weight of about 55 kDa to about 150 kDa. 134. The method of claim 133, wherein the dextran-coated charcoal comprises dextrans having an average molecular weight of about 75 kDa to about 80 kDa. 135. The method of claim 131, wherein the dextran-coated charcoal comprises a fractional weight of about 10% to about 80% dextran. 136. The method of claim 135, wherein the dextran-coated charcoal comprises a fractional weight of about 10% to about 50% dextran. 137. The method of claim 136, wherein the dextran-coated charcoal comprises a fractional weight of about 10% dextran. 138. The method of claim 131, wherein the dextran-coated charcoal comprises a mass of about 5 mg to about 100 mg. 139. The method of claim 138, wherein the dextran-coated charcoal comprises a mass of about 5 mg to about 50 mg. 140. The method of claim 139, wherein the dextran-coated charcoal comprises a mass of about 20 mg. 141. The method of claim 138, further comprising providing a filter to the column positioned adjacent to and below the barrier to prevent elution of the activated charcoal from the column. 142. The method of claim 141, wherein the filter comprises a 1-cm glass filter. |
<SOH> BACKGROUND ART <EOH>In vitro techniques for the analysis of ligand affinity and the extent of protein binding include equilibrium dialysis, ultrafiltration and ultracentrifugation. In the case of equilibrium dialysis and ultrafiltration, the protein of interest and a ligand are allowed to reach equilibrium binding in the presence of a semi-permeable membrane that permits movement of unbound ligand and restricts movement of bound ligand (Pacifici G M & Viani A, 1992). In the case of ultracentrifugation, protein-bound ligand is separated from unbound ligand by forcing the protein out of solution. However, non-specific binding of ligands to the membrane or to the apparatus can invalidate measurement of the unbound fraction. For some ligands, the extent of binding to a target protein cannot be reliably analyzed using available methods. Further, conventional membrane-based methods are labor-intensive and slow, and therefore not amenable to high throughput analysis. Determination of unbound ligand fraction is particularly relevant to drug biodistribution. In the case of intravenous administration of a drug compound, binding of the drug to plasma proteins can substantially limit delivery of the drug to the site in need of treatment. A determination of the degree of ligand binding to plasma proteins can be used to predict the disposition of the drug in the body. See e.g., Parikh H H et al. (2000) Pharm Res 17:632-637; Trung A H et al. (1984) Biopharm Drug Dispos 5:281-290; Suarez Varela et al. (1992) J Pharm Sci 81:842-844; Ascoli G et al. (1995) J Pharm Sci 84:737-741; Barré J et al. (1985) Clin Chem 31:60-64; Mendel C M (1990) J Steroid Biochem Mol Biol 37:251-255; and Mendel C M et al. (1990) J Steroid Biochem Mol Biol 37:245-250. Thus, there exists a long-felt need in the art for a method for rapid assessment of ligand-protein interactions that is applicable to a substantial variety of ligands. Preferably, the method can be used to determine an unbound ligand fraction for any ligand. To meet this need, the present invention provides an apparatus and method for rapid analysis of ligand binding to a target protein. The apparatus comprises a packed-bed charcoal cartridge that is amenable to high throughput processing of samples. Using such an apparatus, a sample comprising ligand and a target protein can be evaluated to determine the percentage of unbound ligand. |
<SOH> SUMMARY OF INVENTION <EOH>The present invention provides a method for evaluating binding of a ligand to a target protein, the method comprising: (a) providing a sample comprising a target protein and a ligand, wherein the target protein and ligand are suspected to be bound reversibly together in a complex; (b) preconditioning activated charcoal with the target protein; (c) contacting the sample with the pre-conditioned activated charcoal for a time sufficient to allow for adsorption of unbound ligand to the activated charcoal; (d) eluting the sample from the activated charcoal; and (e) determining an amount of ligand in the eluted sample to thereby evaluate binding of the ligand to the target protein. The present invention further provides a method for evaluating binding of a ligand to a target protein, the method comprising: (a) providing a sample comprising a target protein and a first ligand, wherein the first ligand comprises a detectable label, and wherein the target protein and first ligand are suspected to be bound reversibly together in a complex; (b) contacting the sample with a candidate second ligand for a time sufficient for displacement of the first ligand from the complex by the second ligand; (c) preconditioning activated charcoal with the target protein; (d) contacting the sample of (b) with the pre-conditioned activated charcoal for a time sufficient to allow for adsorption of unbound first ligand to the activated charcoal; (e) eluting the sample from the activated charcoal; and (1) determining an amount of first ligand in the eluted sample to thereby evaluate binding of the second ligand to the target protein. In a preferred embodiment of the invention, the method can further comprise employing a first ligand that comprises a ligand that binds a specific binding site of a target protein. In this case, an amount of the first ligand in the eluted sample is determined to thereby evaluate binding of the second ligand to the specific ligand binding site of a target protein. Also provided is a method for evaluating the susceptibility of a candidate drug to binding a protein found in the circulating blood of a warm-blooded vertebrate. In a preferred embodiment, the method comprises: (a) providing a sample comprising a target protein and a ligand, wherein the ligand comprises a detectable label, and wherein the target protein and ligand are suspected to be bound reversibly together in a complex; (b) contacting the sample with a candidate drug for a time sufficient for displacement of the ligand from the complex by the candidate drug; (c) preconditioning activated charcoal with the target protein; (d) contacting the sample of (b) with the pre-conditioned activated charcoal for a time sufficient to allow for adsorption of unbound ligand to the activated charcoal; (e) eluting the sample from the activated charcoal; and (f) determining an amount of ligand in the eluted sample to thereby evaluate the susceptibility of the candidate drug to binding a protein found in the circulating blood of a warm-blooded vertebrate. In accordance with the disclosed method, providing a sample can comprise contacting a matrix comprising a target protein with at least one ligand for a time sufficient to allow for binding of the at least one ligand by the target protein. Such contacting a matrix comprising a target protein with at least one ligand can comprise creating a suspension of the matrix comprising a target protein and the at least one ligand. A time sufficient to allow for binding will typically comprise a duration equal to or less than about 30 minutes. A preferred volume of sample to be used in performing the disclosed method comprises about 200 μl. In a preferred embodiment of the invention, the matrix comprising a target protein is blood plasma, preferably human blood plasma. Representative plasma proteins that are important for binding interactions include but are not limited to serum albumin and α 1 -acid-glycoprotein. A ligand to be evaluated in accordance with the disclosed method can comprise a chemical compound, a peptide, an oligonucleotide, a small molecule, or combinations thereof. In a preferred embodiment, the ligand is a candidate drug. Optionally, the ligand can further comprise a detectable label. Methods of the present invention that employ a detectably labeled first ligand to evaluate ligand binding of a candidate second ligand or drug preferably employ a first ligand that binds a plasma protein. More preferably, the first ligand comprises a ligand that binds to serum albumin or to α 1 -acid-glycoprotein. Even more preferably, the first ligand comprises a ligand that binds to a specific site on serum albumin or to a specific site on α 1 -acid-glycoprotein. glycoprotein. In a more preferred embodiment, the first ligand comprises a ligand that binds a specific binding site of a target protein, preferably site I, site II, or site III of human serum albumin. The first ligand can comprise a site I-binding ligand selected from the group consisting of a cumarin and a pyrazolidine, and is more preferably selected from the group consisting of valproate, diphenylhydantoin, or salicylate. Alternatively, the first ligand can comprise a site II-binding ligand selected from the group consisting of a benzodiazepine, an arylpropionate, and L-tryptophan, more preferably the site II-binding ligand diazepam. The first ligand can also comprise the site III-binding ligand digitoxin. The present invention also provides a method for evaluating ligand binding to a target protein that further comprises a novel preconditioning step. Preconditioning activated charcoal comprises contacting activated charcoal with the target protein or with a protein similar to the target protein for a time sufficient to allow for adsorption of the target protein or of the protein similar to the target protein to the activated charcoal. Preferably, a time sufficient for adsorption to the activated charcoal comprises about 1 second. Also preferably, the preconditioning comprises: (a) preconditioning activated charcoal immediately prior to contacting the sample with the preconditioned activated charcoal; or (b) preconditioning activated charcoal within 24 hours prior to contacting the sample with the preconditioned activated charcoal and rinsing the preconditioned activated charcoal immediately prior to contacting the sample with the preconditioned activated charcoal. Preconditioning can also comprise: (a) applying the target protein or a protein similar to the target protein to a packed-bed activated charcoal cartridge, and (b) eluting the target protein or the protein similar to the target protein from the packed-bed activated charcoal cartridge, whereby the activated charcoal is pre-conditioned. Preferably, applying the target protein or the protein similar to the target protein comprises providing a solution having a volume and a concentration of the target protein or of the protein similar to the target protein, wherein the volume of the solution comprises a volume approximately equal to a volume of the sample, and wherein the concentration of the target protein or of the protein similar to the target protein in the solution comprises a concentration approximately equal to a concentration of the target protein in the sample. In one embodiment of the invention, the disclosed method for evaluating ligand binding to a target protein employs dextran-coated charcoal. Preferably, the dextran-coated charcoal comprises dextrans having an average molecular weight of about 35 kDa to about 200 kDa, more preferably about 50 kDa to about 150 kDa, and even more preferably about 75 kDa to about 80 kDa. Also preferably, the dextran-coated charcoal comprises a fractional weight of about 10% to about 80% dextran, more preferably about 10% to about 50% dextran, and still more preferably about 10% dextran. The dextran-coated charcoal also preferably comprises a mass of about 5 mg to about 100 mg, more preferably about 5 mg to about 50 mg, and still more preferably about 20 mg. In a preferred embodiment of the invention, contacting the sample with pre-conditioned activated charcoal comprises applying the sample to a packed-bed activated charcoal cartridge. A time sufficient to allow for adsorption of unbound ligand to the activated charcoal preferably comprises about 1 second. In another preferred embodiment of the invention, eluting the sample comprises applying suction to the sample, whereby the sample is separated from the activated charcoal. In accordance with the present inventive method, determining an amount of ligand in the eluted sample can comprise performing mass spectrometry analysis of the eluted sample. Alternatively, determining an amount of ligand in the eluted sample can comprise detecting a detectably labeled ligand. The present invention further provides a packed-bed charcoal cartridge for evaluating ligand binding to a target protein. The packed-bed charcoal cartridge comprises: (a) a column comprising a sample chamber, a sample addition port, and a sample elution port adapted for fluid/gaseous communication with a suction source; and (b) an activated charcoal packed-bed positioned between the sample chamber and the sample elution port, wherein the charcoal packed-bed is in fluid/gaseous communication with the sample chamber and with the sample elution port. Preferably, the activated charcoal comprises dextran-coated charcoal. In a preferred embodiment, the column of a packed-bed charcoal cartridge comprises a sample chamber capable of holding about one (1) milliliter of liquid volume. More preferably, the column comprises a 1-ml PREPSEP® column, and a bottom of the sample chamber comprises a frit. In another preferred embodiment, the packed-bed charcoal cartridge further comprises a filter positioned adjacent to and below the frit, preferably a 1-cm glass filter. The present invention further provides an apparatus for high-throughput analysis of ligand binding to a protein. The apparatus comprises an array of packed-bed activated charcoal cartridge units as disclosed herein. Preferably, the array comprises 96 packed-bed activated charcoal cartridge units or an integer multiple thereof (e.g. 2, 3, 4, 5, 10, 40, 100, etc.). Also provided is a method for preparing a packed-bed activated charcoal cartridge unit. The method comprises: (a) providing a column comprising a sample chamber, a sample addition port, a sample elution port adapted for fluid/gaseous communication with a suction source, and a barrier positioned between the sample chamber and the sample elution port; (b) applying activated charcoal in a liquid suspension to the column; and (c) eluting the liquid from the column, whereby the activated charcoal is packed adjacent barrier, and whereby a packed-bed activated charcoal cartridge is prepared. Accordingly, it is an object of the present invention to provide a method for evaluation ligand-protein interactions and a packed-bed dextran-coated charcoal matrix that can be used to perform the disclosed method. The object is achieved in whole or in part by the present invention. An object of the invention having been stated herein above, other objects will become evident as the description proceeds when taken in connection with the accompanying Examples as best described herein below. |
Airborne reconnaissance system |
An airborne reconnaissance system comprising: (1) Gimbals having at least two degrees of freedom; (2) At least one array of light sensors positioned on the gimbals, for being directed by the same within at least two degrees of freedom; (3) Map storage means for storing at least one Digital Elevation Map of an area of interest, divided into portions; (4) Inertial Navigation System for real-time providing to a gimbals control unit navigation and orientation data of the aircraft with respect to a predefined global axes system;(5) Portion selection unit for selecting, one at a time, another area portion from the area of interest; and (6) servo means for directing the gimbals. The system uses data from the inertial navigation system and from the digital elevation map for real-time calculating direction to selected area portions, and for maintaining the direction during integration of light from the terrain, and for producing corresponding images of area portions. |
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