Abstract: Methods of inhibiting various enzymes and treating various conditions are provided that include administering to a subject a compound of Structure I or IB, a pharmaceutically acceptable salt thereof, a tautomer thereof, or a pharmaceutically acceptable salt of the tautomer. Compounds having the Structure I and IB have the following structures and have the variables described herein. Such compounds may be used to prepare medicaments for use in inhibiting various enzymes and for use in treating conditions mediated by such enzymes.

Abstract: Gene delivery vectors, for example, recombinant FIV vectors, and methods of using such vectors are provided for use in treating or preventing retinal diseases of the eye and diseases of the brain associated with lysosomal storage disorders.

Abstract: Estrogen receptor-modulating pyrazole compounds are described in addition to methods and compositions for treating or preventing estrogen receptor-mediated disorders. The compounds described have been found to have unexpected and surprising activity in modulating estrogen receptor activity. Thus, the compounds of the present invention have utility in preventing or treating estrogen receptor-mediated disorders such as osteoporosis, breast and endometrial cancers, atherosclerosis, and Alzheimer's disease.

Abstract: This invention provides methods of generating cells that stably replicate sub-genomic virus replicons. This invention also provides methods of generating cells that have disabled PKR activity and that stably replicate HCV sub-genomic replicons. The invention also provides methods of using the cells of the invention to screen for compounds that modulate viral RNA replication, including HCV RNA replication.

Abstract: Novel bactericidal antibodies against Neisseria meningitidis serogroup B (“MenB”) are disclosed. The antibodies either do not cross-react or minimally cross-react with host tissue polysialic acid and hence pose minimal risk of autoimmune activity. The antibodies are used to identify molecular mimetics of unique epitopes found on MenB or E. coli Kl. Examples of such peptide mimetics are described that elicit serum antibody capable of activating complement-mediated bacteriolysis of MenB. Vaccine compositions containing such mimetics can be used to prevent MenB or E. coli Kl disease without the risk of evoking autoantibody.

Abstract: A human gene encoding a novel cyclin-dependent kinase termed hPNQALRE and its expression products can be used to provide reagents and methods for detecting neoplasia. Compositions and methods for treating proliferative disorders and neoplasia are also provided.

Abstract: Gene sequences as shown in SEQ ID NO:1-18 have been discovered and isolated, and found to be significantly associated with metastatic spread of breast and colon cancer cells to other organs. Methods are provided for determining the risk of metastasis of a breast or colon tumor, which involve determining whether a tissue sample from a tumor expresses a polypeptide encoded by a gene as shown in SEQ ID NOS:1-18, or a substantial portion thereof. One of the gene sequences encodes a novel aspartyl protease termed CSP56, which can be used to provide reagents and methods for determining which tumors are likely to metastasize and for suppressing metastases of these tumors. Clinicians can use this information to predict which tumors will metastasize to other organs and to provide relevant therapies to appropriate patients.

Abstract: Estrogen receptor-modulating pyrazole compounds are described in addition to methods and compositions for treating or preventing estrogen receptor-mediated disorders. The compounds described have been found to have unexpected and surprising activity in modulating estrogen receptor activity. Thus, the compounds of the present invention have utility in preventing or treating estrogen receptor-mediated disorders such as osteoporosis, breast and endometrial cancers, atherosclerosis, and Alzheimer's disease.

Abstract: The invention provides truncated GSK3 polypeptides capable of crystallization, including GSK3&agr; and GSK3&bgr; polypeptides, and use of these polypeptides to identify and optimize GSK3 inhibitors. Also provided are GSK3 polypeptides having at least one substituted amino acid that differs from wild-type GSK3, wherein the substituted amino acid is incapable of being phosphorylated. The invention finds use in providing methods of identifying and optimizing compounds useful for treating diseases mediated by GSK3 activity, including Alzheimer's disease, type 2 diabetes, and inflammation.

Abstract: This invention relates to human fibroblast growth factor (hFGF-21), and to variants thereof and to polynucleotides encoding FGF-21. The invention also relates to diagnostic and therapeutic agents related to the polynucleotides and proteins, including probes and antibodies, and to methods of treating liver disease such as cirrhosis and cancer, methods of treating conditions related to thymic function, and methods of treating conditions of the testis. The invention also relates to mouse fibroblast growth factor (mFGF-21), and to variants thereof and polynucleotides encoding mFGF-21.

Abstract: Compounds having the general structure I are provided: X and Y are independently selected from the group consisting of CH2, N, NR9, C═O, C═S, S═O, SO2, S, O, (CR6R7)n, C(═O)—(CR6R7)n, and C(═S)—(CR6R7)n, where n is 1, 2, or 3. W is selected from the group consisting of and L is selected from the group consisting of N, O, S, S═O, SO2, C(O), NC(O), NC(S), OC(O), OC(S), C(NR10), C(NOR10), and a covalent bond. Z1, Z2, and Z3 are independently selected from the group consisting of substituted carbon and nitrogen. Compounds of formula I are agonists of the melanocortin-4 receptor (“MC-4r”) and therefore may have useful properties for controlling diseases related to MC-4r action in humans, such as obesity and type II diabetes.

Abstract: The invention relates to compositions and methods for inhibiting cell proliferation, especially angiogenesis. The invention specifically relates to fusions of the extracellular domain of a fibroblast growth factor receptor (FGFR) with a heterologous oligomerization domain, such as that contained in an immunoglobulin, to provide potent FGFR antagonists.

Abstract: HCV immunoassays comprising an NS3/4a conformational epitope and a multiple epitope fusion antigen are provided, as well as immunoassay solid supports for use with the immunoassays.

Abstract: The invention provides a method of activating hepatitis C virus (HCV)-specific T cells, including CD4+ and CD8+ T cells. HCV-specific T cells are activated using fusion proteins comprising HCV NS3, NS4, NS5a, and NS5b polypeptides, polynucleotides encoding such fusion proteins, or polypeptide or polynucleotide compositions containing the individual components of these fusions. The method can be used in model systems to develop HCV-specific immunogenic compositions, as well as to immunize a mammal against HCV.

Abstract: The present invention pertains generally to novel Neisseria meningitidis serogroup B glycoconjugates. More particularly, the invention pertains to glycoconjugates formed from a Neisseria meningitidis serogroup B capsular oligosaccharide derivative (MenB OS derivative) in which sialic acid residue N-acetyl groups are replaced with N-acyl groups. The invention also pertains to vaccine formulations containing the glycoconjugates, methods of making the vaccine formulations, and methods of using the vaccine formulations to treat or prevent Neisseria meningitidis serogroup B or E. coli K1 disease in a mammalian subject.

Abstract: Compositions and methods for expression of heterologous mammalian proteins and their secretion in the biologically active mature form using a yeast host cell as the expression system are provided. Compositions of the invention are nucleotide sequences encoding a signal peptide sequence for a yeast secreted protein, an optional leader peptide sequence for a yeast secreted protein, a native propeptide leader sequence for a mature protein of interest, and a sequence for the mature protein of interest, all operably linked to a yeast promoter. Each of these elements is associated with a processing site recognized in vivo by a yeast proteolytic enzyme. Any or all of these processing sites may be a preferred processing site that has been modified or synthetically derived for more efficient cleavage in vivo. The compositions are useful in methods for expression of heterologous mammalian proteins and their secretion in the biologically active mature form.

Abstract: The invention provides polynucleotides encoding Notch receptor ligands, encoded polypeptides, and antibodies specific to the polypeptides. Also provided are methods and compositions for enhancing or inhibiting angiogenesis as well as modulating immune responses.

Abstract: Methods of treating cancer by administration of FMdC followed by administration of a platinate are disclosed.

Abstract: Estrogen receptor-modulating pyrazole compounds are described in addition to methods and compositions for treating or preventing estrogen receptor-mediated disorders. The compounds described have been found to have unexpected and surprising activity in modulating estrogen receptor activity. Thus, the compounds of the present invention have utility in preventing or treating estrogen receptor-mediated disorders such as osteoporosis, breast and endometrial cancers, atherosclerosis, and Alzheimer's disease.

Abstract: The hypervariable region (E2HV) of the putative hepatitis C virus (HCV) glycoprotein E2/NS1, between about amino acid 384 to about amino acid 414, is a rapidly evolving region of HCV, and is likely to be under positive immune selection. A newly discovered motif within this hypervariable region is immunogenic and conserved with respect to the character of the amino acids. In many isolates, this motif falls between amino acids 401 to 406 or 407. The discovery of this motif allows for additional materials and methods to treat and diagnose HCV.