Abstract: A mammalian homology of Drosophila Disabled protein has been identified and cloned. In particular, the murine homolog designated mDab1 has been cloned and expressed. mDab1, when tyrosine phosphorylated, binds to the SH2 domain of Src, Abl and Fyn. Antibodies specific for mDab1 are provided as are methods for the screening of agents for their ability to modulate mDab1 activity. Methods for diagnosing Disabled protein associated disease are also provided.

Abstract: The present invention provides agents and compositions for modulating the apoptotic state of a cell. The agents comprise derivatives of antimycins which bind to an anti-apoptotic Bcl-2 family member protein. Further, the agents preferentially induce apoptosis in cells that over-express anti-apoptotic Bcl-2 family member proteins and typically exhibit reduced binding affinity for cytochrome B. Pharmaceutical uses of the agents and compositions include treating apoptosis-associated disease, such as neoplasia and drug resistance, are also disclosed.

Abstract: The present invention relates to a method for inhibiting the adhesion of one cell to another comprising interfering with the interaction between the extracellular matrix receptor and its ligand. The invention is based upon the discovery that the ?4?1 extracellular matrix receptor promotes adhesion of lymphocytes to endothelial cells via attachment to a defined peptide sequence. Prior to the present invention, the ligand of the ?4?1 receptor had not been identified, nor had the function of the ?4?1 receptor in lymphocyte attachment been known. By preventing the interaction between the ?4?1 receptor and its ligands using antibodies or defined peptide sequences, the present invention enables, for the first time, specific intervention in the migration of lymphocytes through the vascular endothelium and into tissues.

Abstract: The present invention provides methods for modulating the growth and/or yield of plants. In particular the methods comprise the use of agents which functionally inhibit the expression of plant D-like cyclin inhibitors including isolated polynucleotide sequences which interact with DNA or RNA encoding proteins capable of binding plant D-like cyclins. Further, the present invention provides recombinant polynucleotide sequences, vectors and host cells which encode proteins capable of binding to and inactivating the activity of plant D-like cyclin/cyclin dependent kinase complexes preventing plant cells from exiting the cell cycle. Methods for determining and agents which are inhibitors of the BRO cyclin dependent kinase inhibitor proteins which are capable of modulating plant cell cycle progression are also provided. Methods for the production of transgenic plant cells and plants with increased growth rates and yields when compared to wild-type plants are also provided.

Abstract: The present invention provides packaging cell lines for the efficient production of an Adeno-associated virus (AAV) vector which does not require “helper” virus function for the replication and encapsidation of the AAV vector particles. Packaging cells, methods for their production and methods for producing recombinant AAV vector particles useful for human gene therapy are provided.

Abstract: Disclosed herein are systems, components, devices and methods for automated yeast pedigree analysis. Systems, components, devices and methods for analyzing microorganisms, cells, particles and molecules are also disclosed.

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: Protein biomarkers that may advantageously be utilized in diagnosing prostate cancer, benign prostate hyperplasia or to make a negative diagnosis are described. Accordingly, in one aspect of the invention, methods for aiding in, or otherwise making, a diagnosis of prostate cancer or benign prostate hyperplasia are provided. In one form of the invention, a method includes detecting various protein biomarkers of defined molecular weight and correlating the detection to a diagnosis of prostate cancer, benign prostate hyperplasia or to a negative diagnosis. In yet another aspect of the invention, kits are provided that may be utilized to detect the biomarkers described herein. In a further of the invention, methods of using a plurality of classifiers to make a probable diagnosis of prostate cancer of benign prostate hyperplasia are provided. In certain forms of the invention, the methods include use of a boosted decision tree analysis. Various computer readable media are also provided.

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: A hose apparatus used as part of an air and water supply system to deliver water and air to a firefighter. The hose apparatus includes an air hose and a water hose with an adaptor at each end of the air and water hoses. The adaptors have an inner passageway with an air groove. The adaptors have a first air hole in fluid communication with the air hose and the air groove and a second air hole in fluid communication with the air groove and the air supply or breathing hose for the firefighter. The second air hole has a coupling which prevents air from exiting the adaptors when the hose apparatus is not in use.

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.