Abstract: Novel CSAPL polypeptides, proteins, and nucleic acid molecules are disclosed. In addition to isolated, full-length CSAPL proteins, the invention further provides isolated CSAPL fusion proteins, antigenic peptides and anti-CSAPL antibodies. The invention also provides CSAPL nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced and non-human transgenic animals in which a CSAPL gene has been introduced or disrupted. Diagnostic, screening and therapeutic methods utilizing compositions of the invention are also provided.

Abstract: An entomopathogenic fungus virulent against insects of the grasshopper family is described. The entomopathogenic fungus is a strain Beauveria bassiana. Also, formulations that include the entomopathogenic fungus are described. These formulations can be delivered to grasshopper-infested areas by land or by air. In addition, methods of killing an insect of the grasshopper family using the aforementioned formulation and baits and traps for killing an insect of the grasshopper family containing the formulation are described.

Abstract: Human antibodies, preferably recombinant human antibodies, that specifically bind to human tumor necrosis factor &agr;(hTNF&agr;) are disclosed. These antibodies have high affinity for hTNF&agr; (e.g., Kd=10−8 M or less), a slow off rate for hTNF&agr; dissociation (e.g., Koff=10−3sec−1 or less) and neutralize hTNF&agr; activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. The antibodies, or antibody portions, of the invention are useful for detecting hTNF&agr; and for inhibiting hTNF&agr; activity, e.g., in a human subject suffering from a disorder in which hTNF&agr; activity is detrimental. Nucleic acids, vectors and host cells for expressing the recombinant human antibodies of the invention, and methods of synthesizing the recombinant human antibodies, are also encompassed by the invention.

Abstract: The present invention makes available a rapid, effective assay for screening and identifying pharmaceutically effective compounds that specifically interact with and modulate the activity of a cellular receptor or ion channel. The subject assay enables rapid screening of large numbers of polypeptides in a yeast expression library to identifying those polypeptides which induce or antagonize receptor bioactivity. The subject assay is particularly amenable for identifying surrogate ligands for orphan receptors.

Abstract: The invention provides isolated yeast cells which comprise a mutation in an endogenous yeast CAV1 gene, which exhibit increased signaling via the pheromone response pathway. In a preferred embodiment, the cav1 mutant yeast cells of the invention also express a heterologous G protein coupled receptor that functionally couples to the pheromone response pathway. The instant yeast cells display enhanced sensitivity to ligand induced stimulation of heterologous G protein coupled receptors and, therefore, show improved properties in drug screening assays.

Abstract: Transgenic animals carrying two transgenes, the first coding for a transactivator fusion protein comprising a tet repressor and a polypeptide which directly or indirectly activates in eucaryotic cells, and the second comprising a gene operably linked to a minimal promoter operably linked to at least one tet operator sequence, are disclosed. Isolated DNA molecules (e.g., targeting vectors) for integrating a polynucleotide sequence encoding a transactivator of the invention at a predetermined location within a second target DNA molecule by homologous recombination are also disclosed. Transgenic animals having the DNA molecules of the invention integrated at a predetermined location in a chromosome by homologous recombination are also encompassed by the invention. Methods to regulate the expression of a tet operator linked-gene of interest by administering tetracycline or a tetracycline analogue to an animal of the invention are also disclosed.

Abstract: Methods for preparing organic compounds, such as oligonucleotides, on solid supports are described. Libraries of the compounds and methods of using the compounds are also disclosed.

Abstract: Methods for detecting the presence or absence of an analyte in a sample are disclosed. Kits for performing the analysis methods of the invention are also disclosed.

Abstract: Transgenic animals carrying a transgene comprising a nucleic acid molecule encoding protein useful for regulating the expression of genes in eukaryotic cells and organisms in a highly controlled manner are disclosed. In the regulatory system of the invention, transcription of a tet operator-linked nucleotide sequence is stimulated by a transcriptional activator fusion protein composed of two polypeptides, a first polypeptide which binds to tet operator sequences in the presence of tetracycline operatively linked to a second polypeptide activates transcription in eukaryotic cells. In a preferred embodiment, the transgene encoding the transcriptional activator fusion protein is integrated at a predetermined location within the chromosome of the transgenic animal.

Abstract: Modified forms of human interleukin-1&bgr; converting enzyme (ICE) that display proteolytic activity and, furthermore, have increased stability compared to unmodified human ICE are disclosed. Nucleic acid molecules encoding a modified p10 subunit of ICE, and recombinant vectors and host cells incorporating such nucleic acid molecules, are also disclosed. A modified ICE protein of the invention can be used to cleave proteolytically ICE substrates and to identify modulators of ICE activity in screening assays. Moreover, due to its enhanced stability, the modified ICE of the invention is particularly suitable for use in the preparation of ICE crystals for X-ray crystallography.

Abstract: Methods for detecting and/or quantifying catalytically-active, serine proteases in a biological fluid are disclosed. The methods are useful for measuring the active enzymes of the coagulation/fibrinolytic system and evaluating the system or components of the system as indicative of thrombosis-related disorders. The methods involve the combined use of halomethyl ketone probes having broad specificity for catalytically-active serine proteases and immunological reagents specific for serine proteases of particular types. The halomethyl ketone probes are active site specific; they are only incorporated into catalytically-active serine proteases. An antibody is used to provide specificity for the particular type of serine protease. By the combined active-site-specificity of the halomethyl ketone probes and the type-specificity of the antibody, the catalytically-active fraction of a particular serine protease is determined.

Abstract: Substances are disclosed which have the property of binding to PCNA, the substances comprising (i) a fragment of the p21WAF1 protein including residues 141 to 160 of the p21WAF1 amino acid sequence, or an active portion or derivative thereof; or (ii) functional mimetics of these protein fragments. In particular, the PCNA binding activity is shown to lie within the sequence motif OTSMTDFY, with the residues shown in bold being critical for PCNA binding, with those underlined being important. These substances are useful in the treatments of disorders in which PCNA is implicated, e.g. hyperproliferative disorders such as cancer and psoriasis, the substances binding to PCNA to inactivate it or functionally deplete its level. Also disclosed is the use of a yeast two hybrid screening technique for screening candidate peptides for binding to PCNA.

Abstract: Pharmaceutical compositions comprising known verotoxins, particularly, verotoxin 1, have been found to be useful in the treatment of mammalian neoplasia, particularly, ovarian cancer and skin cancer. Surprisingly, although verotoxin 1 has previously been shown to have anti-neoplastic activity in vitro, non-lethal doses of verotoxin 1 have been shown to be therapeutically anti-neoplastic in vivo.

Abstract: Pharmaceuticals and Apparatus used in combination for diagnosis and tissue necrosis applicable to provide effective and selective therapy using the Mossbauer absorption phenomenon. Selected pharmaceutical compounds containing a radiation absorber isotope are administered to a tissue and excited by a radiation source which provides energy at the corresponding resonant Mossbauer absorption frequency of isotope containing pharmaceutical, where excitation effects nuclear transitions to cause highly selective energy absorption in the selected target tissue. For diagnostic purposes, de-excitation fluorescence of the isotope is monitored. For therapeutic purposes, the energy is converted to particle radiation by the isotope at the target tissue by internal conversion followed by an Auger electron cascade which results in radiolysis of DNA resulting in lethal double strand breaks in the DNA molecules of the target tissue.

Abstract: Methods, compositions, and kits for modulating the stability of at least one nucleic acid duplex, are disclosed.

Abstract: The present invention is based on the method of treating a patient suffering from leukemia comprising administering a therapeutically effective amount of the compound 2-([(3-hydroxypropyl)amino]-6-benzylamino)-9-isopropylpurine or a pharmaceutically acceptable salt thereof.

Abstract: Improved methods for detecting lesions in dense breast tissue are disclosed. The methods of the invention generally feature administration to a subject of an LHRH antagonist in an amount and for a period of time sufficient to reduce the density of breast tissue prior to generating an image of the breast tissue, for example by mammography, to detect a lesion in the breast tissue. Packaged formulations for reducing breast density in a subject prior to generating an image of the subject's breast tissue, comprising an LHRH antagonist packaged with instructions for using the LHRH antagonist to reduce breast density in a subject prior to imaging the breast tissue, are also disclosed.

Abstract: This invention provides peptide compounds that bind to either a fibroblast growth factor (FGF) or a fibroblast growth factor receptor (FGFR) and, accordingly, are useful for modulating FGFR activity. Preferably, the FGFR is FGFR2-IIIC. Preferably, the FGF is basic FGF. Preferably the peptide compound comprises an amino acid sequence: (Y/F)-(L/F/I)-(R/D/E/S/Y/G)-(Q/L/Y)-Y-(M/L/K/R)-(L/M/D/E/N/S)-(R/L/S/T)-(L/F/M/V) (SEQ ID NO: 1). The invention further comprises pharmaceutical compositions comprising the peptide compounds of the invention and a pharmaceutically acceptable carrier. The invention still further provides methods of modulating FGFR activity using the peptide compounds of the invention.

Abstract: Methods for treating prostate cancer are disclosed. The methods of the invention generally feature administration to a subject of an LHRH-R antagonist, in combination with a second therapy. In one embodiment, this second therapy is performance of a procedure that removes or destroys prostatic tumor tissue, such as a radical prostatectomy, cryosurgery or X-ray therapy (external or interstitial). In another embodiment, the second therapy is treatment with an LHRH-R agonist, either simultaneous with or subsequent to LHRH-R antagonist therapy. The methods of the invention can further involve administering an antiandrogen and/or an inhibitor of sex steroid biosynthesis to the subject in combination with the LHRH-R antagonist.

Abstract: This disclosure relates to a method of specifically decorating selected mammalian chromosomes and of detecting, identifying and and/or quantitating selected individual chromosomes, by means of chromosomal in situ suppression (CISS) hybridization. The method is useful in analyzing cells for the occurrence of chromosomes, chromosome fragments or chromosome aberrations.