Abstract: The present invention relates to the discovery that non-traditional export of certain pro-inflammatory cytokines lacking a signal sequence from a cell can be inhibited by copper chelation and/or administration to the cell of a truncated form of S100A13 lacking the basic residue portion. Further, copper chelation inhibits, inter alia, neointima formation, macrophage infiltration and associated inflammation, cell proliferation, secretion of extracellular matrix, intimal thickening, adventitial angiogenesis, restenosis, and the like, associated with vascular vessel injury. Thus, the present invention provides novel methods of preventing and treating, and for identifying novel compounds also useful as therapeutics for, such conditions.

Abstract: The present invention relates to methods based on the interactions of thrombin as a biological regulator. More specifically, the invention relates to the interactions of thrombin with regard to Notch signaling, Jagged1, PAR1, and cellular effects mediated thereby. The invention relates to the discovery that thrombin cleaves Jagged1 to produce non-membrane soluble Jagged1 (sJ1). The soluble Jagged1 protein can affect Notch signaling and, among other things, mediate the release of FGF-1 and/or IL-1? from a cell. The invention further relates to the role(s) of thrombin and signaling via Notch proteins and the effect on thrombosis, angiogenesis, and/or differentiation, among other processes. Moreover, the invention relates to discovery that thrombin, sJ1, and TRAP mediate, inter alia, rapid non-classical release of FGF-1, and proteins associated therewith (e.g., p40 Syn1 and S100A13, among others), and the effect growth and proliferation of a stem cell without loss of differentiation potential.

Abstract: This invention relates to therapeutic and diagnostic methods and compositions based on Jagged/Notch proteins and nucleic acids, and on their role in the signaling pathway relating to endothelial cell migration and/or differentiation. In addition, this invention provides a substantially purified Jagged protein, as well as a substantially purified nucleic acid or segment thereof encoding Jagged protein, or a functionally equivalent derivative, or allelic or species variant thereof. Further, this invention provides a substantially purified soluble Jagged protein and a substantially purified nucleic acid encoding same as well as a recombinant cell comprising a nucleic acid encoding a soluble Jagged protein. Soluble Jagged provides further therapeutic and diagnostic methods relating to diseases, disorders, and conditions involving Jagged/Notch signaling including, inter alia, angiogenesis, differentiation, and control of gene expression.

Abstract: This invention provides supplemented and unsupplemented tissue sealants as well as methods for their production and use thereof. Disclosed are tissue sealants supplemented with at least one antibody. The composition may be further supplemented with, for example, one or more analgesics, antimicrobial compositions, anticoagulants, antiproliferatives, anti-inflammatory compounds, cytokines, cytotoxins, drugs, growth factors, interferons, hormones, lipids, demineralized bone or bone morphogenetic proteins, cartilage inducing factors, oligonucleotides polymers, polysaccharides, polypeptides, protease inhibitors, vasoconstrictors or vasodilators, vitamins, minerals, stabilizers and the like.

Abstract: This invention provides supplemented and unsupplemented tissue sealants as well as methods for their production and use thereof. Disclosed are tissue sealants supplemented with at least one antimicrobial composition. The composition may be further supplemented with, for example, one or more antibodies, analgesics, anticoagulants, antiproliferatives, anti-inflammatory compounds, cytokines, cytotoxins, drugs, growth factors, interferons, hormones, lipids, demineralized bone or bone morphogenetic proteins, cartilage inducing factors, oligonucleotides polymers, polysaccharides, polypeptides, protease inhibitors, vasoconstrictors or vasodilators, vitamins, minerals, stabilizers and the like.

Abstract: This invention provides a fibrin sealant bandage, wherein said fibrin sealant may be supplemented with at least one composition selected from, for example, one or more regulatory compounds, antibody, antimicrobial compositions, analgesics, anticoagulants, antiproliferatives, anti-inflammatory compounds, cytokines, cytotoxins, drugs, growth factors, interferons, hormones, lipids, demineralized bone or bone morphogenetic proteins, cartilage inducing factors, oligonucleotides polymers, polysaccharides, polypeptides, protease inhibitors, vasoconstrictors or vasodilators, vitamins, minerals, stabilizers and the like. Also disclosed are methods of preparing and/or using the unsupplemented or supplemented fibrin sealant bandage.

Abstract: The present invention relates to the discovery that non-traditional export of certain pro-inflammatory cytokines lacking a signal sequence from a cell can be inhibited by copper chelation and/or administration to the cell of a truncated form of S100A13 lacking the basic residue portion. Further, copper chelation inhibits, inter alia, neointima formation, macrophage infiltration and associated inflammation, cell proliferation, secretion of extracellular matrix, intimal thickening, adventitial angiogenesis, restenosis, and the like, associated with vascular vessel injury. Thus, the present invention provides novel methods of preventing and treating, and for identifying novel compounds also useful as therapeutics for, such conditions.

Abstract: The present invention relates to methods and compositions based on the modulation of Src-mediated cortactin phosphorylation. In particular, the invention features methods and compositions for modulating Src-mediated cortactin phosphorylation using Notch ligands to modulate Notch signaling.

Abstract: The present invention relates to methods based on the interactions of thrombin as a biological regulator. More specifically, the invention relates to the interactions of thrombin with regard to Notch signaling, Jagged1, PAR1, and cellular effects mediated thereby. The invention relates to the discovery that thrombin cleaves Jagged1 to produce non-membrane soluble Jagged1 (sJ1). The soluble Jagged1 protein can affect Notch signaling and, among other things, mediate the release of FGF-1 and/or IL-1? from a cell. The invention further relates to the role(s) of thrombin and signaling via Notch proteins and the effect on thrombosis, angiogenesis, and/or differentiation, among other processes. Moreover, the invention relates to discovery that thrombin, sJ1, and TRAP mediate, inter alia, rapid non-classical release of FGF-1, and proteins associated therewith (e.g., p40 Syn1 and S100A13, among others), and the effect growth and proliferation of a stem cell without loss of differentiation potential.

Abstract: The invention relates to novel degradation resistant FGF-1, and methods for producing and using the same. More specifically, the invention relates to identification of a thrombin degradation resistant FGF-1, an a nucleic acid encoding the same. The thrombin degradation resistant FGF-1 can elicit responses that are otherwise typically impeded by degradation of FGF-1 by thrombin. Thrombin degradation resistant FGF-1 is an important molecule for effecting an FGF-1 response that would be otherwise inhibited by thrombin. Thus, the present invention provides a powerful therapeutic for diseases or disorders wherein an FGF-1 response can mediate a reduction in the frequency or intensity of a symptom of the disease or disorder but for degradation of FGF-1 before it can effect the response.

Abstract: This invention relates to therapeutic and diagnostic methods and compositions based on Jagged/Notch proteins and nucleic acids, and on their role in the signaling pathway relating to endothelial cell migration and/or differentiation. In addition, this invention provides a substantially purified Jagged protein, as well as a substantially purified nucleic acid or segment thereof encoding Jagged protein, or a functionally equivalent derivative, or allelic or species variant thereof. Further, this invention provides a substantially purified soluble Jagged protein and a substantially purified nucleic acid encoding same as well as a recombinant cell comprising a nucleic acid encoding a soluble Jagged protein. Soluble Jagged provides further therapeutic and diagnostic methods relating to diseases, disorders, and conditions involving Jagged/Notch signaling including, inter alia, angiogenesis, differentiation, and control of gene expression.

Abstract: This invention relates to therapeutic and diagnostic methods and compositions based on Jagged/Notch proteins and nucleic acids, and on the role of their signaling pathway in endothelial cell migration and/or differentiation. In addition, this invention provides a substantially purified Jagged protein, as well as a substantially purified nucleic acid molecule or segment thereof encoding Jagged protein, or a functionally equivalent derivative, or allelic or species variant thereof.

Abstract: The present invention relates to the discovery that non-traditional export of certain pro-inflammatory cytokines lacking a signal sequence from a cell can be inhibited by copper chelation and/or administration to the cell of a truncated form of S100A13 lacking the basic residue portion. Further, copper chelation inhibits, inter alia, neointima formation, macrophage infiltration and associated inflammation, cell proliferation, secretion of extracellular matrix, intimal thickening, adventitial angiogenesis, restenosis, and the like, associated with vascular vessel injury. Thus, the present invention provides novel methods of preventing and treating, and for identifying novel compounds also useful as therapeutics for, such conditions.

Abstract: This invention relates to the regulation of FGF-1 export by cells. In addition, this invention provides methods of regulating the export of FGF-1 from the cell membrane, which methods include regulating the Syn-1 molecule to affect the formation of the FGF-Syn-1 complex, regulating the enzyme or protease which cleaves Syn-1 in the FGF-1 :Syn-1 complex to effect the release of FGF-1 from the cell membrane, or regulating the FGF-1:Syn-1 complex itself at or near the cell membrane. S100A13 is identified as an additional component of the FGF-1 export complex. Syn-1 truncation deletion mutants are also provided and functionally characterized. The invention also provides compositions related to the regulation of FGF-1 export.

Abstract: This invention relates to therapeutic and diagnostic methods and compositions based on Jagged/Notch proteins and nucleic acids, and on their role in the signaling pathway relating to endothelial cell migration and/or differentiation. In addition, this invention provides a substantially purified Jagged protein, as well as a substantially purified nucleic acid or segment thereof encoding Jagged protein, or a functionally equivalent derivative, or allelic or species variant thereof. Further, this invention provides a substantially purified soluble Jagged protein and a substantially purified nucleic acid encoding same as well as a recombinant cell comprising a nucleic acid encoding a soluble Jagged protein. Soluble Jagged provides further therapeutic and diagnostic methods relating to diseases, disorders, and conditions involving Jagged/Notch signaling including, inter alia, angiogenesis, differentiation, and control of gene expression.

Abstract: This invention relates to the regulation of FGF-1 export. In addition, this invention provides methods of regulating the export of FGF-1 from the cell membrane, which methods include regulating the Syn-1 molecule to affect the formation of the FGF-1:Syn-1 complex, regulating the enzyme or protease which cleaves Syn-1 in the FGF-1:Syn-1 complex to effect the release of FGF-1 from the cell membrane, or regulating the FGF-1:Syn-1 complex itself at or near the cell membrane. The invention also provides compositions related to the regulation of FGF-1 export.

Abstract: This invention provides supplemented tissue sealants, methods for their production and use thereof. Disclosed are tissue sealants supplemented with at least one cytotoxin or cell proliferation inhibiting composition. The composition may be further supplemented with, for example, one or more antibodies, analgesics, anticoagulants, anti-inflammatory compounds, antimicrobial compositions, cytokines, drugs, growth factors, interferons, hormones, lipids, deminearlized bone or bone morphogenetic proteins, cartilage inducing factors, oligonucleotides polymers, polysaccharides, polypeptides, protease inhibitors, vasoconstrictors or vasodilators, vitamins, minerals, stabilizers and the like.

Abstract: This invention provides methods for the localized delivery of supplemented tissue sealants, wherein the supplemented tissue sealants comprise at least one composition which is selected from one or more antibodies, analgesics, anticoagulants, anti-inflammatory compounds, antimicrobial compositions, antiproliferatives, cytokines, cytotoxins, drugs, growth factors, interferons, hormones, lipids, demineralized bone or bone morphogenetic proteins, cartilage inducing factors, oligonucleotides polymers, polysaccharides, polypeptides, protease inhibitors, vasoconstrictors or vasodilators, vitamins, minerals, stabilizers and the like. Further provided are methods of using the site-specific supplemented tissue sealants, including preparation of a biomaterial.

Abstract: This invention provides a fibrin sealant dressing, wherein said fibrin sealant may be supplemented with at least one composition selected from, for example, one or more regulatory compounds, antibody, antimicrobial compositions, analgesics, anticoagulants, antiproliferatives, antiinflammatory compounds, cytokines, cytotoxins, drugs, growth factors, interferons, hormones, lipids, demineralized bone or bone morphogenetic proteins, cartilage inducing factors, oligonucleotides polymers, polysaccharides, polypeptides, protease inhibitors, vasoconstrictors or vasodilators, vitamins, minerals, stabilizers and the like. Also disclosed are methods of preparing and/or using the unsupplemented or supplemented fibrin sealant dressing.

Abstract: The present invention is directed to DNA encoding human endothelial cell growth factors, and to plasmids comprising said DNA. In particular, the invention relates to DNA encoding a cleavable signal peptide and an endothelial cell growth factor, wherein removal of said signal peptide yields a mature form of the growth factor.