Abstract: Compositions and methods are provided for identifying novel therapeutic agents for the treatment of cancer and other cellular proliferative disorders.

Abstract: Novel human MOAT genes and their encoded proteins are provided herein. The MRP-related ABC transporters encoded by the disclosed nucleic acid sequences play a pivotal role in the efflux of pharmacologically beneficial reagents from tumor cells. MOAT genes and their encoded protein provide valuable therapeutic targets for the design of anti-cancer agents which inhibit the aberrant growth of malignant cells.

Abstract: The invention includes a computer implemented process to identify at least one pattern and its distribution in a set of data for the purpose of interpreting the data. The process comprises (a) representing a set of data by an original data matrix D residing in a storage device, and; (b) decomposing the set of data into a set of patterns represented by a matrix F and their distribution represented by a matrix A, wherein the matrix F represents the set of patterns needed to describe the data and the matrix A represents the distribution of the set of patterns within the data matrix D, the decomposing comprising performing a Bayesian-based Monte Carlo calculation using at least the data matrix D to determine the matrices A and F, wherein the matrices A and F reconstruct the data matrix D and are more amenable to analysis than the data matrix D. Application of the process to environmental, biological and medical, econometric, and other fields is included in the invention.

Abstract: Bispecific single chain antibody molecules are disclosed which may be used to advantage to treat various forms of cancer associated with the overexpression of members of the EGFR protein family.

Abstract: Nucleic acid molecules encoding a mismatch endonuclease and its method of use for the detection of mutations in targeted polynucleotide sequences are provided, which facilitate the localization and identification of mutations, mismatches and genetic polymorphisms.

Abstract: An isolated nucleic acid molecule is provided which encodes a mammalian signal mediator protein, HEF-1, involved in regulation of cellular morphological alterations. The encoded protein comprises an amino-terminal SH3 domain, an internal domain containing several SH2 binding motifs, and a carboxy-terminal effector domain that can induce pseudohyphal budding in yeast. The invention also provides the novel signal mediator protein, and antibodies thereto. These biological molecules are useful as research tools and as diagnostic and therapeutic agents in methods for the identification, detection and regulation of complex signaling events leading to morphological, potentially neoplastic, cellular changes.

Abstract: An isolated nucleic acid molecule encoding a human DNA repair enzyme, MED1, is disclosed. Like other mismatch repair genes which are mutated in certain cancers, MED1, encoding nucleic acids, proteins and antibodies thereto may be used to advantage in genetic or cancer screening assays. MED1, which recognizes and cleaves DNA, may also be used for the diagnostic detection of mutations and genetic variants.

Abstract: Novel human BUB genes and their encoded proteins are provided herein. The kinases encoded by the disclosed BUB1A and BUB1B genes play a pivotal role in mitotic checkpoint control. BUB3 is a substrate of these kinases, BUB genes and their encoded proteins provide valuable therapeutic targets for the design of anti-proliferative agents which inhibit the aberrant cellular proliferation observed in tumor cells.

Abstract: Nucleic acid molecules encoding a mismatch endonuclease and its method of use for the detection of mutations in targeted polynucleotide sequences are provided, which facilitate the localization and identification of mutations, mismatches and genetic polymorphisms.

Abstract: The present invention provides an improved yeast interaction trap method and reagents for the detection of novel protein-protein interactions. The invention comprises a dual bait system which improves the accuracy of library screens with an immediate selection to eliminate false positives. The dual bait system of the present invention also allows for comparative, simultaneous assessment of interactions between two related members of a protein family or a wild-type versus mutated form of the same protein.

Abstract: The present invention provides novel chimeric and fusion proteins useful for facilitating site-specific integration of foreign DNA into a host genome. The chimeric enzymes of the invention comprise a DNA binding moiety fused to a retroviral integrase moiety, preferably at the precise N- or C-terminus. Nucleic acids encoding these fusion proteins can be incorporated into standard retroviral vectors, or can be provided as purified proteins. They are capable of exerting the activities of a wildtype retroviral integrase, including processing retroviral DNA termini, nicking double-stranded DNA and integrating a DNA molecule with processed retroviral termini into another DNA strand.

Abstract: An isolated nucleic acid molecule is provided which encodes a mammalian signal mediator protein involved in regulation of cellular morphological alterations. The encoded protein comprises an amino-terminal SH3 domain, an Internal domain containing several SH2 binding motifs, and a carboxy-terminal effector domain that can induce pseudohyphal budding in yeast. The invention also provides the novel signal mediator protein, and antibodies thereto. These biological molecules are useful as research tools and as diagnostic and therapeutic agents for the identification, detection and regulation of complex signaling events leading to morphological, potentially neoplastic, cellular changes.

Abstract: An isolated nucleic acid molecule is provided which encodes a mammalian signal mediator protein involved in regulation of cellular morphological alterations. The encoded protein comprises an amino-terminal SH3 domain, an internal domain containing several SH2 binding motifs, and a carboxy-terminal effector domain that can induce pseudohyphal budding in yeast. The invention also provides the novel signal mediator protein, and antibodies thereto. These biological molecules are useful as research tools and as diagnostic and therapeutic agents for the identification, detection and regulation of complex signaling events leading to morphological, potentially neoplastic, cellular changes.

Abstract: The present invention is based on the discovery of a metabolic pathway in which a specific kinase converts fructose-lysine into fructose-lysine-3-phosphate in an ATP dependent reaction. Fructose-lysine-3-phosphate (FL3P) is then broken down to form free lysine, inorganic phosphate and 3-deoxyglucosone (3DG), the latter being a reactive protein modifying agent. 3DG can be detoxified by reduction to 3-deoxyfructose (3DF), or it can react with endogenous proteins to form advanced glycation end-product modified proteins (AGE-proteins), which are believed to be a cause of diabetic complications. Disclosed is a class of compounds which inhibit the action of FL3P kinase in the above-mentioned pathway.

Abstract: Compositions and methods for the treatment of malignant cells are disclosed, particularly antisense nucleic acid molecules and their use in inhibiting the deregulated cellular proliferation of tumor cells, while not adversely affecting the growth of normal cells.

Abstract: Dendroamide derivatives are disclosed which are useful in cancer therapy, especially in treating multidrug resistant cells.

Abstract: An endonuclease and its method of use for the detection of mutations in targeted polynucleotide sequences are provided, which facilitate the localization and identification of mutations, mismatches and genetic polymorphisms.

Abstract: This invention provides a novel gene, OVCA1, isolated from human chromosome 17p13.3. Disruption of the OVCA1 gene is associated with cellular proliferation and tumor development. The OVCA1 gene, along with its encoded protein and antibodies thereto, provides a biological marker for early diagnosis of metastatic disease. The gene also will be useful in gene replacement therapy for treating various forms of cancer.

Abstract: This invention provides a novel gene, OVCA1, isolated from human chromosome 17p13.3. Disruption of the OVCA1 gene is associated with cellular proliferation and tumor development. The OVCA1 gene, along with its encoded protein and antibodies thereto, provides a biological marker for early diagnosis of metastatic disease. The gene also will be useful in gene replacement therapy for treating various forms of cancer.

Abstract: An isolated nucleic acid is provided, which encodes a stress-responsive subunit of mammalian RNA polymerase II, RPB4. In a preferred embodiment, the human RPB4 subunit (hsRPB4) is provided. Also provided are oligonucleotides that specifically hybridize with the nucleic acid, the purified polypeptide encoded by the nucleic acid and antibodies immunologically specific for the polypeptide. These biological molecules are useful as markers of stress-related responses, which may correspond to the occurrence of malignant disease, and as therapeutic agents to modify resistance of a selected cell population to external stress conditions, such as that resulting from treatment of a patient with chemotherapeutic agents.