Abstract: Methods for the treatment of a proliferative disorder are provided in which a subject in need of such treatment is administered an effective amount of a compound selected from: compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein X1 and X2 are independently H, Cl, F, Br, I, CN, CF3 or NO2, and Ar1 is a substituted or unsubstituted aryl or a substituted or unsubstituted heteroaryl; and compounds of formula (II) wherein X3 and X4 are each independently H, Cl, F, Br, I, CN, CF3 or NO2; Y is (C2–C6)alkylene or (C2–C6)heteroalkylene; and Z is Cl, F, Br, I, CN, CF3 or NO2.

Abstract: Immortalized human stromal cell lines sustain and expand human hematopoietic precursor cells. The precursor cells are obtained from a blood product and inoculated into a culture medium conditioned by exposure to a human stromal cell line. Preferred human stromal cell lines secrete SCF, LIF, MIP1?, and IL-6, as exemplified by a human stromal cell line designated HS-1. The conditioned culture medium may be supplemented with additional growth factors, such as interleukin-3. After expansion the human hematopoietic precursor cells are harvested and returned to a patient or frozen and stored. The immortalized human stromal cell lines can also be used as feeder layers in ex vivo bone marrow cultures or in colony forming assays.

Abstract: In one aspect, the invention provides methods for determining the contributions of canid populations to a canid genome. The methods comprise the steps of: (a) obtaining the identity of one or both alleles in a test canid genome for each of a set of markers; and (b) determining the contributions of canid populations to the test canid genome by comparing the alleles in the test canid genome to a database comprising canid population profiles, wherein each canid population profile comprises genotype information for the set of markers in the canid populations.

Abstract: The present invention provides methods for identifying targets of a drug in a cell by comparing (i) the effects of the drug on a wild-type cell, (ii) the effects on a wild-type cell of modifications to a putative target of the drug, and (iii) the effects of the drug on a wild-type cell which has had the putative target modified of the drug. In various embodiments, the effects on the cell can be determined by measuring gene expression, protein abundances, protein activities, or a combination of such measurements. In various embodiments, modifications to a putative target in the cell can be made by modifications to the genes encoding the target, modification to abundances of RNAs encoding the target, modifications to abundances of target proteins, or modifications to activities of the target proteins. The present invention also provides methods for drug development based on the methods for identifying drug targets.

Abstract: The present invention provides methods and combinations of methods for identifying agents that modulate the apoptotic state of a cell by binding to the hydrophobic groove of a Bcl-2 family member anti-apoptotic protein. In certain embodiments, the methods generally comprise the use of Bcl-2 family member proteins having one or more mutations in the hydrophobic groove that, relative to a corresponding protein lacking the mutation, affect, e.g., binding of desired agents or in vitro antimycin sensitivity without substantially altering tertiary protein structure. In these embodiments, the methods comprise the identification of agents that exhibit reduced binding affinities and/or other biological activities for the mutant proteins relative to the corresponding Bcl-2 family member lacking the mutation.

Abstract: Transgenic, non-human animal model of cancer, methods of making such animals and methods of using such animals to screen test compounds are provided.

Abstract: The invention provides HSV antigens that are useful for the prevention and treatment of HSV infection. Disclosed herein are epitopes confirmed to be recognized by T-cells derived from herpetic lesions. T-cells having specificity for antigens of the invention have demonstrated cytotoxic activity against cells loaded with virally-encoded peptide epitopes, and in many cases, against cells infected with HSV. The identification of immunogenic antigens responsible for T-cell specificity provides improved anti-viral therapeutic and prophylactic strategies. Compositions containing antigens or polynucleotides encoding antigens of the invention provide effectively targeted vaccines for prevention and treatment of HSV infection.

Abstract: The present invention provides a method for rapidly detecting the genome-wide presence of palindrome formation. The method has demonstrated that somatic palindromes occur frequently and are widespread in human cancers. Individual tumor types have a characteristic non-random distribution of palindromes in their genome and a small subset of the palindromic loci are associate with gene amplification. The disclosed method can be used to define the plurality of genomic DNA palindromes associated with various tumor types and can provide methods for the classification of tumors, and the diagnosis, early detection of cancer as well as the monitoring of disease recurrence and assessment of residual disease.

Abstract: The present invention relates to a method of identifying one or more secondary drug targets and their use in the identification of drug or drug candidates, particularly for the treatment of cancer. The yeast-based synthetic lethal screens were used to functionally identify and validate new gene targets to kill tumor cells with defects in cell cycle checkpoints and damage response pathways. These newly identified gene targets can be used to develop new cancer chemotherapeutics.

Abstract: The invention provides HSV antigens that are useful for the prevention and treatment of HSV infection. Disclosed herein are epitopes confirmed to be recognized by T-cells derived from herpetic lesions. T-cells having specificity for antigens of the invention have demonstrated cytotoxic activity against cells loaded with virally-encoded peptide epitopes, and in many cases, against cells infected with HSV. The identification of immunogenic antigens responsible for T-cell specificity provides improved anti-viral therapeutic and prophylactic strategies. Compositions containing antigens or polynucleotides encoding antigens of the invention provide effectively targeted vaccines for prevention and treatment of HSV infection.

Abstract: Disclosed are 2-methoxy antimycin derivatives or analogs that modulate apoptosis by binding to the hydrophobic groove of a Bcl-2 family member protein (e.g., Bcl-2 or BCl-xL). The 2-methoxy antimycin derivatives or analogs are used in disclosed methods for treating apoptosis-associated diseases such as, for example, neoplastic disease (e.g., cancer) or other proliferative diseases associated with the over-expression of a Bcl-2 family member protein.

Abstract: The present invention provides prognostic and diagnostic methods for cancer, as well as methods for monitoring or staging cancer. Methods involve assaying for tumor-derived soluble MIC polypeptide—either MICA or MICB or both—in a sample from a subject. Assays can be implemented with a MIC polypeptide binding agent such as a MIC polypeptide antibody or recombinant NKG2D. An ELISA sandwich assay is employed in some embodiments of the invention to identify a soluble MIC polypeptide. In additional embodiments, a sample is assayed for tumor cell-surface bound MIC in addition to assaying for soluble MIC. The invention also provides methods of cancer therapy involving detecting cancer in the subject by assaying for soluble MIC polypeptide and then administering a cancer therapy.

Abstract: The invention relates to a method of expressing proteins in higher eukaryotes in vitro. In general, the invention sets forth a method of expressing exogenous proteins as fusion partners with the immunoglobulin molecules of avian species specifically chickens. The technology involves, in one embodiment, retroviral-mediated gene transfer and transplantation of stem cells from the Bursa of Fabricus in chickens.

Abstract: The invention relates to novel nucleotide sequences and the polypeptide sequences derived therefrom, which are involved in yeast and mammalian telomere regulation. Methods for screening drugs and compositions are also provided. The invention furthermore relates to methods involving a diagnostic and/or therapeutic use of these gene(s)/protein(s), principally for treating cancer and aging.

Abstract: Methods for identifying Rheb effectors are provided. The Rheb effectors can be Rheb agonists or antagonists and can be utilized as lead compounds for the development of drugs for the treatment of diabetes or diseases associated with abnormal cell growth. Non-human, transgenic animals over-expressing Rheb protein, and methods of making such transgenic animals, are also provided.

Abstract: Polynucleotide sequences encoding eukaryotic Rrn3 polypeptides are provided. Rrn3 is a eukaryotic RNA polymerase I transcription factor. The Rrn3 polypeptides, and antibodies thereto, can be used as diagnostic tools, as therapeutic agents and to identify agonist and antagonists of Rrn3.

Abstract: The present invention provides various methods for stimulating a cell expressing an NKG2D receptor, including artificially engineered cell populations. Provided, in accordance with the invention. are monoclonal antibodies that bind to NKG2D extracellular domains and facilitate the interaction of other NKG2D domains with DAP10. Of particular interest are treating cancers and viral infections, and the stimulation, both in vivo and ex vivo, of cytokine secretion.

Abstract: Hypercellular nonhuman organisms have functionally inactivated expression of a cyclin inhibitor gene, especially p27. The growth rate of nonhuman organisms are increased such that a desired size is attained more quickly than as compared to nonvariant organisms. Inhibitors of the p27 cyclin dependent kinase inhibitor protein or sequences encoding the protein modulate vertebrate cell cycle progression and increase the proportion of dividing cells to non-dividing cells in a population of treated cells. As the proportion of dividing cells increases, the cell population, e.g., hematopoietic progenitor (stem) cells, is more efficiently used for gene therapy applications. Transgenic animals and plants, and knockout alleles are provided.

Abstract: A method for analyzing large data arrays is provided. In one aspect, the invention provides a method for analyzing data from two or more data arrays. Each array includes a plurality of members, each member provides a signal, and the data is indexed by one or more parameters. In one embodiment, the method includes fitting a model to the data; determining the goodness of the fit by evaluating the statistical significance of the fit; and determining the statistical significance of the signal. In another embodiment, the method further includes correcting the data for heterogeneity among members prior to fitting the model to the data.

Abstract: The present invention provides various methods by which the use of certain MHC-related molecules can be exploited in understanding and regulating the immune response. More particularly, the present invention describes the use of molecules expressed by certain cell types as markers, reagents and targets in the diagnosis and treatment of certain disease states including GVHD, cancer and the like.