Title of Invention | "An isolated antibody or an antigen binding fragment thereof against hCMV" |
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Abstract | Neutralising antibodies which are specific for human cytomegalovirus and bind with high affinity as well as immortalised B cells that produce such antibodies. The antibodies also have a high potency for the neutralisation of infection. Characterization of the epitopes that the antibodies bind to as well as the use of the antibodies and the epitopes in screening methods as well as the diagnosis and therapy of disease. |
Full Text | 1. Field of the Invention The present invention relates to certain dry-type ash discharge equipment for coal-fired boiler. To be specific, it refers to an ash integrated conveying and cooling system suitable for a dry-type ash discharge system. 2. Background of the Invention With the development of science and technology, the demand of high level general ash utilization and environment protection is becoming more and more. In most fuel electric plants, the old hydraulic ash discharge technology has been abandoned during the disposal of coal-fired boiler ash and is widely replaced by dry-type ash discharge system. A dry-type ash discharge system of the existing technology mainly consists of a dry-type air-cooled metal belt conveyor, an integrated conveying system and an ash silo. The main art is that the metal belt conveyor conveys the hot ash discharged by the boiler and meanwhile certain amount of ambient air is sucked into the boiler chamber under the negative pressure to carry out heat exchange between the air and the hot ash, which makes the temperature of ambient air rise and the ash temperature drop. The ambient air having absorbed the heat of the ash returns to the boiler chamber through the ash discharge outlet of the boiler, thereby improving the thermal efficiency of the boiler. The integrated conveying system connected to the metal belt conveyor operates with mechanical means. In most cases, the ash that is conveyed by the metal belt conveyor but does not reach the appropriate temperature needs to be further cooled in the subsequent integrated conveying system in which cool air is usually used. After traveling through the metal belt conveyor, the ambient air having absorbed the ash heat, enters the ash- discharge chute at the ash outlet of the metal belt conveyor and then reaches the integrated conveying system. Therefore, this temperature difference of the heated air and the hot ash becomes relatively small, facilitating significant greatly affected. So the above-mentioned situation leads to the problems existing in the present technology. The first concern is how to effectively deal with and take advantage of the heat transferred at the different conveying stages during the hot ash cooling process. The second is how to block off or guide the hot air generated after the ash is cooled through the metal belt conveyor, so as to let ambient air with room temperature be introduced into the ash integrated conveying and cooling system for better secondary cooling of the ash. In the existing technology, air lock is a common device used for sealing or opening. It effectively solves the problem of air leakage in many technical processes. Because there are different operation modes, the common air locks can be categorized into buffering air lock, electric air lock, sledge air lock, bevel board type air lock, and conical air lock. 3. Summary of Invention Technically, this invention provides an ash integrated conveying and cooling system suitable for dry-type ash discharge system. The said integrated conveying and cooling system can isolate the hot air generated after the ash is cooled inside the metal belt conveyor so that ambient air with room temperature can be introduced into the ash integrated conveying and cooling system for better secondary cooling of the ash. To achieve the invention aim, the ash integrated conveying and cooling system has one enclosure on which an ash inlet and an ash outlet are set. The said ash inlet connects to the exit of a metal belt conveyor via an ash- discharge chute, and the said ash outlet connects to a conveying tube with sealed connection. The said conveying tube leads to the top of an ash silo with sealed connection; characterized in that, an air lock is set at the joint of the ash- discharge chute and the metal belt conveyor, and at least one air inlet is set on the said enclosure. The ash integrated conveying and cooling system includes an air outlet and at least one device generating negative The said device generating negative pressure can be an induced draft fan set on top of the said ash silo. The said air outlet is set on top of the said ash silo. The said air outlet is set on one end of the said ash integrated conveying and cooling system, and connected to the boiler chamber or opened to the atmosphere via hot air ducts which are connected to the said air outlet with sealed connection; the said device generating negative pressure is a cooling fan set on the said hot air ducts. At least two said air inlets are required, each of the said air inlets can be equipped with a one-way intake valve for single-direction air control. These two said air inlets can be set on two sides of the said enclosure respectively and distributed symmetrically with the side centerline of the said enclosure being the symmetry axis. Additionally, in this invention, the position and the number of the air inlets on the sides of the said enclosure of the said ash integrated conveying and cooling system are determined by the length of the said enclosure and its ash capacity. Besides, the said air inlets should be sized in accordance with the length of the said enclosure of the said ash integrated conveying and cooling system. For an ash integrated conveying and cooling system with a specific length, too small air inlets lead to very slow flow rate of internal air, and too large air inlets make it difficult to keep air staying in the said enclosure and cause rapid air loss. Therefore, the size of the said air inlets are determined by thermodynamics equilibrium calculation, by means of which the type of device generating negative pressure can be further confirmed. By selecting proper position, number, and size of the one-way air inlets together with suitable air outlets and the said device generating negative pressure, the air flow rate inside the said ash integrated conveying and cooling system can be improved for better cooling of the ash. In this invention, a single air outlet or plural air outlets can be set on top of the ash silo, and plural devices generating negative pressure will be set on top of the ash silo accordingly. Alternatively, as the air outlets on top of the ash silo, one or more air outlets can be set on one end of the enclosure of the ash integrated conveying and cooling system. The air with the ash heat can be allowed to return from the said air outlets, through hot air ducts connected with the said air outlets, to the chamber, or can be discharged to the atmosphere. The two types of above-mentioned air outlets can be used at the same time or selectively. Advantageously, with the air lock included in the ash integrated conveying and cooling system, the air having absorbed the ash heat inside metal belt conveyor will no longer enter the next cooling stage, so as to ensure the cooling effect; In addition, the said air having absorbed the ash heat can be allowed to enter the boiler chamber as much as possible, which means higher thermal efficiency of the boiler. Plural air inlets equipped with one-way intake valves are set on the enclosure of the ash integrated conveying and cooling system. Also, devices for generating negative pressure inside the enclosure of the ash integrated conveying and cooling system, such as induced draft fans or cooling fans, are adopted. These designs facilitate better airflow inside the ash conveying and cooling equipment. Finally, by selectively setting hot air ducts and cooling fans between the ash integrated conveying and cooling system and the boiler chamber, the air having absorbed heat during heat exchange with the ash in the ash integrated conveying and cooling system can return to the boiler chamber via the hot air ducts to improve thermal efficiency of the boiler. 4. Brief Description of the Drawings The above-mentioned and other features and advantages of this invention, and the manner of attaining them, will become more apparent and the invention itself will be better understood by reference to the following description of an embodiment of the invention taken in conjunction with the accompanying drawings, wherein: FIG 1 illustrates the ash integrated conveying and cooling system with two devices generating negative pressure inside the enclosure of the ash integrated conveying and cooling system; FIG. 2 illustrates the ash integrated conveying and cooling system with an induced draft fan generating negative pressure inside the enclosure of the ash integrated conveying and cooling system set on top of the ash silo; FIG. 3 illustrates the ash integrated conveying and cooling system with a cooling fan generating negative pressure inside the enclosure of the ash integrated conveying and cooling system set on the hot air duct; FIG. 4 illustrates the ash integrated conveying and cooling system with an induced draft fan generating negative pressure inside the enclosure of the ash integrated conveying and cooling system set on top of the ash silo, and with ambient air branch; The arrows in these figures show the flow direction of air in the ash integrated conveying and cooling system. 5. Detailed Description of the Preferred Embodiments Referring to FIG. 1, the ash integrated conveying and cooling system includes one enclosure 4 on which an ash inlet 5 and an ash outlet 6 are set. The ash inlet 5 is connected with a metal belt conveyor 2 with sealed connection via an ash- discharge chute 7. An air lock 8 is set at the joint of the ash- discharge chute 7 and the metal belt conveyor 2. The ash outlet 6 is connected to a conveying tube 9 with sealed connection. The said conveying tube 9 leads to the top of an ash silo 3 with sealed connection. To achieve negative pressure inside the enclosure of the ash integrated conveying and cooling system, an induced draft fan 10 and an air outlet 11 are used on top of the ash silo 3. Three air inlets 12 are set on each side of the enclosure 4 of the ash integrated conveying and cooling system. One-way intake valves are used in the said air inlets to allow single-direction air flow control. Besides, an air outlet 11 is set on one end of the enclosure 4 and connected to the hot air ducts 13 with sealed connection. These hot air ducts 13 can be connected to the boiler chamber or opened to the atmosphere. To improve the air flow efficiency inside the ash integrated conveying and cooling system, a cooling fan 14 is set on the hot air ducts 13. When the boiler 1 discharges ash, the hot ash enters the metal belt conveyor 2 via the ash outlet of the boiler 1. The hot ash on the metal belt conveyor 2 moves slowly to the joint with the ash- discharge chute 7 of the ash integrated conveying and cooling system, during this process, heat exchange occurs between the hot ash and the ambient air from the air inlet, and then the temperature of ash drops while the temperature of the air rises. Because an air lock 8 is set at the joint of the metal belt conveyor 2 and the ash- discharge chute 7 of the ash integrated conveying and cooling system, most of the air having absorbed the ash heat inside the metal belt conveyor 2 can enter the boiler chamber to improve thermal efficiency of the boiler 1. The ash conveyed to the ash- discharge chute 7 by the metal belt conveyor 2 enters the ash integrated conveying and cooling system via the ash- discharge chute 7, and then the induced draft fan 10 and the cooling fan 14 set on the hot air duct 13 are started. The hot ash, which has not been completely cooled and has driven by the conveyor of the ash integrated conveying and cooling system, moves slowly to the ash outlet 6. In this process, due to the combined action of the induced draft fan 10 and the cooling fan 14, a negative pressure is generated inside the enclosure 4 of the ash integrated conveying and cooling system, allowing the ambient air into enter the enclosure 4 through the one-way intake valves in the above-mentioned single-direction air inlets 12. This air will circulate sufficiently in the enclosure 4, conveying tube 9 and the ash silo 3 of the ash integrated conveying and cooling system. On its way to the ash outlet 6, the hot ash is cooled by ambient air to ensure that it can reach a safe temperature when entering the ash silo 3. In particular, after the cooled ash enters the ash silo 3, to some extent the said air-cooling system can continue to cool it. In addition, the air heated during heat exchange with the hot ash will partially enter the boiler chamber via the hot air duct 13 to further improve the thermal efficiency of the boiler 1. Alternatively, the said air heated coming out of the hot air ducts 13 can be discharged directly into the atmosphere. Referring to FIG 2, it is the ash integrated conveying and cooling system, on top of the ash silo of which an induced draft fan generating negative pressure inside the enclosure is set. The ash integrated conveying and cooling system includes one enclosure 4 on which an ash inlet 5 and an ash outlet 6 are set. The ash inlet 5 is connected with a metal belt conveyor 2 with seal connection via an ash- discharge chute 7. An air lock 8 is set at the joint of the ash- discharge chute 7 and the metal belt conveyor 2. The ash outlet 6 is connected to the conveying tube 9 with sealed connection. The said conveying tube 9 leads to the top of an ash silo 3 with sealed connection. To achieve negative pressure inside the enclosure of the said ash integrated conveying and cooling system, an induced draft fan 10 and an air outlet 11 are used on top of the ash silo 3. Four air inlets 12 are set on one side of the enclosure 4 of the ash integrated conveying and cooling system, and three air inlets 12 are set on the other side. One-way intake valves are set in the said air inlets for single-direction air control. When the boiler 1 discharges ash, the hot ash enters the metal belt conveyor 2 via the ash outlet of the boiler 1. The hot ash driven by the metal belt conveyor 2 moves slowly to the connection with the ash- discharge chute 7 of the ash integrated conveying and cooling system. During this process, heat exchange occurs between the hot ash and the ambient air from the air inlet, and then the temperature of ash drops while the temperature of the air rises. Because an air lock 8 is set at the joint of the metal belt conveyor 2 and the ash- discharge chute 7 of the ash integrated conveying and cooling system, most of the air having absorbed the ash heat inside the metal belt conveyor 2 can enter the boiler chamber to improve thermal efficiency of the boiler 1. The ash conveyed to the ash- discharge chute 7 by the metal belt conveyor 2 enters the ash integrated conveying and cooling system via the ash- discharge chute 7, and then the induced draft fan 10 is started. The hot ash, which has not been completely cooled, drove by the conveyor of the ash integrated conveying and cooling system, moves slowly to the ash outlet 6. During the process, due to the effect of the induced draft fan 10, a negative pressure is generated inside the enclosure 4 of the ash integrated conveying and cooling system, allowing the ambient air to enter the enclosure 4 through the one-way intake valves in the above-mentioned single-direction air inlets 12. This air will circulate sufficiently in the enclosure 4, conveying tube 9 and the ash silo 3 of the ash integrated conveying and cooling system. On its way to the ash outlet 6, the hot ash is cooled by ambient air to ensure that it can reach a safe temperature when entering the ash silo 3. In particular, after the cooled ash enters the ash silo 3, the said air-cooling system can to some extent continue to cool it. It can be known from the above description that the air lock 8 can prevent the air heated inside the metal belt conveyor 2 from entering the ash integrated conveying and cooling system, and thus will not affect ash cooling efficiency of the ambient air entering the system. Theoretically, the aim of the present invention can be achieved, as long as at least one air inlet 12, one induced draft fan 10 and an air outlet 11 are set on the enclosure 4. Therefore, the manner of setting air inlet 12, induced draft fan 10 and the air outlet can vary, but the alternatives are still within the protection scope of this invention. Referring to FIG. 3, it is the ash integrated conveying and cooling system, on the hot air duct of which a cooling fan generating negative pressure inside the enclosure is set. The ash integrated conveying and cooling system includes one enclosure 4 on which an ash inlet 5 and an outlet 6 are set. The ash inlet 5 is connected with a metal belt conveyor 2 with sealed connection via an ash- discharge chute 7. An air lock 8 is set at the joint of the ash- discharge chute 7 and the metal belt conveyor 2. The ash outlet 6 is connected to a conveying tube 9 with sealed connection. The said conveying tube 9 leads to the top of an ash silo 3 with sealed connection. Three air inlets 12 are set on each side of the enclosure 4 of the ash integrated conveying and cooling system. One-way intake valves are used in the said air inlets to allow single-direction airflow control. Besides, an air outlet 11 is set on one end of the enclosure 4 of the ash integrated conveying and cooling system and connected to the hot air ducts 13. This hot air ducts can be connected to the boiler chamber or opened to the atmosphere. To improve the air flow efficiency inside the ash integrated conveying and cooling system, a cooling fan 14 is set on the hot air ducts 13. When the boiler 1 discharges ash, the hot ash enters the metal belt conveyor 2 via the ash outlet of the boiler 1. The hot ash driven by the metal belt conveyor 2 moves slowly to the connection with the ash- discharge chute 7 of the ash integrated conveying and cooling system. During this process, heat exchange occurs between the hot ash and the ambient air from the air inlet, and then the temperature of ash drops while the temperature of the air rises. Because an air lock 8 is used at the connection of the metal belt conveyor 2 and the ash- discharge chute 7 of the ash integrated conveying and cooling system, most of the air heated in the metal belt conveyor 2 can enter the boiler 1 chamber to improve thermal efficiency of the boiler 1. The ash conveyed to the ash- discharge chute 7 by the metal belt conveyor 2 enters the ash integrated conveying and cooling system via the ash- discharge chute 7, then the cooling fan 14 set on the hot air duct 13 is started. The hot ash, which has not been completely cooled and has driven by the conveyor of the ash integrated conveying and cooling system, moves slowly to the ash outlet 6. During this process, due to the effect of the cooling fan 14, a negative pressure is generated inside the enclosure 4 of the ash integrated conveying and cooling system, allowing the ambient air to enter the enclosure 4 through the one-way intake valves in the above-mentioned single-direction air inlets. This air will circulate sufficiently in the enclosure 4, conveying tube 9 and the ash silo 3 of the ash integrated conveying and cooling system. On its way to the ash outlet 6, the hot ash is cooled by ambient air to ensure that it can reach a safe temperature when entering the ash silo 3. In addition, the ambient air heated during heat exchange with the hot ash will enter the boiler chamber via the hot air ducts 13 to further improve the thermal efficiency of the boiler 1, or be discharged directly into the atmosphere. It should be noted that in some projects, if the system ash discharge amount fails to match the ash outlet size, the discharged ash might be excessive, and will stay at the said ash outlet, which may facilitate that the ambient air will be prevented from circulating normally in the conveying tube. To solve the above-mentioned problems, another ambient air branch can be used next to the ash outlet and connected to the conveyor tube (see FIG 4). This design can be applies to any of the above-mentioned examples for this invention. The air lock 8 used in this invention can be any air-locking device in the market that provides single-direction start/stop under the gravity of the ash. Any air lock can be used as long as it can achieve the aim of this invention. While this invention has been described as having a preferred design, the present invention can be further modified within the spirit and scope of this disclosure. This application is therefore intended to cover any variations, uses, or adaptations of the invention using its general principles. Further, this application is intended to cover such departures from the present disclosure as come within known or customary practice in the art to which this invention pertains and which fall within the limits of the appended claims. We Claim: 1. An antibody or an antigen binding fragment thereof, that neutralizes infection of endothelial cells, epithelial cells, retinal cells, myeloid cells, or dendritic cells by human cytomegalovirus (hCMV), wherein the concentration of antibody required for 50% neutralisation of hCMV is 0.3 ug/ml or less. 2. The antibody of claim 1 or an antigen binding fragment thereof, wherein the antibody neutralizes infection of endothelial cells, epithelial cells, retinal cells, myeloid cells, and dendritic cells by hCMV, and wherein the concentration of antibody required for 50% neutralisation of hCMV is 0.01 ug/ml or less. 3. The antibody of claim 2 or an antigen binding fragment thereof, wherein the concentration of antibody required for 50% neutralisation of hCMV is 0.003 ug/ml or less. 4. An antibody or an antigen binding fragment thereof, that binds to an epitope formed upon expression of the hCMV proteins UL130 and UL131A, wherein the antibody neutralizes hCMV infection. 5. An antibody or an antigen binding fragment thereof, that binds to an epitope formed by the hCMV proteins UL130 and UL131 A, wherein the antibody neutralizes hCMV infection. 6. An antibody or an antigen binding fragment thereof, comprising at least one complementarity determining region (CDR) sequence having at least 95% sequence identity to any one of SEQ ID NO: 1-6, 11-16, or 33-38, wherein the antibody neutralizes hCMV infection. 7. An antibody or an antigen binding fragment thereof, comprising a heavy chain CDRl selected from the group consisting of SEQ ID NOs: 1,11, and 33; a heavy chain CDR2 selected from the group consisting SEQ ID NOs: 2, 12, and 34; and a heavy chain CDR3 selected from the group consisting SEQ ID NOs: 3, 13, and, 35, wherein the antibody neutralizes hCMV infection. 8. An antibody or an antigen binding fragment thereof, comprising a light chain CDRl selected from the group consisting SEQ ID NOs: 4, 14, and 36; a light chain CDR2 selected from the group consisting SEQ ID NOs: 5, 15, and 37; and a light chain CDR3 selected from the group consisting SEQ ID NOs: 6, 16, and 38, wherein the antibody neutralizes hCMV. 9. The antibody of claim 7 or an antigen binding fragment thereof, wherein said antibody comprises a heavy chain comprising a polypeptide with SEQ ID NO: 1 for CDRH1, SEQ ID NO: 2 for CDRH2 and SEQ ID NO: 3 for CDRH3; or SEQ ID NO: 11 for CDRH1, SEQ ID NO: 12 for CDRH2 and SEQ ID NO: 13 for CDRH3; or SEQ ID NO: 33 for CDRH1, SEQ ID NO: 34 for CDRH2 and SEQ ID NO: 35 for CDRH3. 10. The antibody of claim 8 or an antigen binding fragment thereof, wherein the antibody comprises a light chain comprising a polypeptide with SEQ ID NO: 4 for CDRL1, SEQ ID NO: 5 for CDRL2 and SEQ ID NO: 6 for CDRL3; or SEQ ID NO: 14 for CDRL1, SEQ ID NO: 15 for CDRL2 and SEQ ID NO: 16 for CDRL3; or SEQ ID NO: 36 for CDRL1, SEQ ID NO: 37 for CDRL2 and SEQ ID NO: 38 for CDRL3. 11. The antibody of any one of claims 1-10, or an antigen binding fragment thereof, comprising a heavy chain variable region having at least 85% sequence identity to SEQ ID NO: 7,17, or 39. 12. The antibody of any one of claims 1-10, or an antigen binding fragment thereof, comprising a light chain variable region having at least 85% sequence identity to SEQ ID NO: 8, 18, or 40. 13. The antibody of any one of claims 1-10, or an antigen binding fragment thereof, wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 17, or SEQ ID NO: 39; or a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8, SEQ ID NO: 18, or SEQ ID NO: 40. 14. An antibody, or an antigen binding fragment thereof, wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8; or a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 17 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 18; or a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 39 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 40. 15. The antibody or fragment of claim 14, wherein the antibody is human monoclonal antibody 1F11. 16. The antibody of any one of the previous claims, or an antigen binding fragment thereof, wherein the antibody is a human antibody, a monoclonal antibody, a single chain antibody, Fab, Fab', F(ab')2, Fv or scFv. 17. An antibody or an antigen binding fragment thereof that binds to the same epitope as the antibody of any of one of the previous claims, wherein the antibody or antigen binding fragment thereof neutralizes hCMV infection. 18. An antibody or an antigen binding fragment thereof that cross competes with an antibody of any one of the previous claims, wherein the antibody or antigen binding fragment thereof neutralizes hCMV infection. 19. The antibody of any one of the previous claims or an antigen binding fragment thereof for treatment of hCMV infection. 20. A nucleic acid molecule comprising a nucleotide encoding the antibody or antibody fragment of any one of the previous claims. 21. The nucleic acid molecule of claim 20 comprising a nucleotide, wherein the nucleotide sequence is at least 75% identical to any one of SEQ ID NOs: 9, 10,19, 20,21-32, or 41-48. 22. A cell expressing the antibody of any one of claims 1-19. 23. An isolated or purified immunogenic polypeptide comprising an epitope that binds to the antibody of any one of claims 1-19. 24. A pharmaceutical composition comprising the antibody of any one of claims 1-19 or an antigen binding fragment thereof, the nucleic acid of claim 20 or claim 21, or the immunogenic polypeptide of claim 23, and a pharmaceutically acceptable diluent or carrier. 25. A pharmaceutical composition comprising a first antibody or an antigen binding fragment thereof, and a second antibody or an antigen binding fragment thereof, wherein the first antibody is the antibody of any one of claims 1-19, and the second antibody neutralizes hCMV infection. 26. Use of the antibody of any one of claims 1-19 or an antigen binding fragment thereof, an nucleic acid of claim 20 or claim 21, the immunogenic polypeptide of claim 23, or the pharmaceutical composition of claim 24 or claim 25 (i) in the manufacture of a medicament for the treatment of hCMV infection, (ii) in a vaccine, or (iii) in diagnosis of hCMV infection. 27. Use of the antibody of any one of claims 1-19 or an antigen binding fragment thereof, for monitoring the quality of anti-hCMV vaccines by checking that the antigen of said vaccine contains the correct epitope in the correct conformation. 28. An epitope which specifically binds to the antibody of any one of claims 1-19 or an antigen binding fragment thereof, for use (i) in therapy, (ii) in the manufacture of a medicament for treating hCMV infection, (iii) as a vaccine, or (iv) in screening for ligands able to neutralise hCMV infection. |
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Patent Number | 279937 | |||||||||
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Indian Patent Application Number | 5041/DELNP/2009 | |||||||||
PG Journal Number | 06/2017 | |||||||||
Publication Date | 10-Feb-2017 | |||||||||
Grant Date | 03-Feb-2017 | |||||||||
Date of Filing | 03-Aug-2009 | |||||||||
Name of Patentee | INSTITUTE FOR RESEARCH IN BIOMEDICINE | |||||||||
Applicant Address | VIA VINCENZO VELA 6 BELLINZONA, SWITZERLAND CH-6500 | |||||||||
Inventors:
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PCT International Classification Number | C07K 16/08 | |||||||||
PCT International Application Number | PCT/IB2008/001111 | |||||||||
PCT International Filing date | 2008-01-03 | |||||||||
PCT Conventions:
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