Abstract: The present invention is directed to novel methods for assaying for modulators of GADD45 polypeptide activity. The invention also provides means to sensitize a proliferating cell to a DNA base-damaging agent by administration of novel inhibitors of GADD45 polypeptide activity. The invention further provides polypeptides which interfere with the ability of Cdc2/cyclin B1 complexes to cause a pause at the G2/M stage of the cell cycle in response to GADD45, and nucleic acids which encode such polypeptides.

Abstract: A compound of formula: in which (i) aa1 is Adi and aa4 is Glu or (ii) each of aa1 and aa4 is Adi, L is sulfur, sulfoxide, oxygen or methylene, which compound (and its conjugates) bind to an SH2 domain in a protein comprising an SH2 domain, is non-phosphorylated, is redox-stable in vivo, is characterized by an IC50 in vivo of less than about 4.0 ?M with respect to the SH2 domain in Grb2, and, upon binding to the SH2 domain of Grb2, has a turn conformation. A conjugate comprising a compound as described above and a carrier agent, a composition comprising (i) a compound or a conjugate as described above and (ii) a carrier, a method of inhibiting binding of an SH2 domain in a protein comprising an SH2 domain to a target protein in an animal, wherein the SH2 domain is contacted with a target protein-binding inhibiting effective amount of a compound or a conjugate as described above, and a method of synthesizing such conjugates.

Abstract: The invention provides compounds that inhibit epoxide hydrolase in therapeutic applications for treating hypertension. A preferred class of compounds for practicing the invention have the structure shown by Formula I wherein Z is oxygen or sulfur, W is carbon phosphorous or sulfur, X and Y is each independently nitrogen, oxygen, or sulfur, and X can further be carbon, at least one of R1—R4 is hydrogen, R2 is hydrogen when X is nitrogen but is not present when X is sulfur or oxygen, R4 is hydrogen when Y is nitrogen but is not present when Y is sulfur or oxygen, R1 and R3 is each independently C1-C20 substituted or unsubstituted alkyl, cycloalkyl, aryl, acyl, or heterocyclic.

Abstract: The invention provides a device and method for monitoring inflammation of the epithelium. The device consists of a head region, a handle region and an optical bundle. At least two of the optical fibers in the bundle are utilized as a source of radiation, these two fibers are at two different angles from normal. At least one of the other optical fibers is utilized as a detector for the reflected radiation, or alternatively an image guide can be used as the detector. The device of the invention can be part of an external or internal system that can include a light source, the device, a multiplexer, a spectrometer, and a computer for data analysis. The method of the invention allows for the detection and monitoring of general inflammation of the oral epithelium. The inflammation of the epithelium can be detected or monitored to diagnose diseases of the oral epithelium, monitor such diseases, monitor treatment of such diseases, or pre-screen for and monitor preventative treatments of such diseases.

Abstract: The present invention provides isolated nucleic acid and amino acid sequences of sweet taste receptors, the receptors comprising consisting of a monomer or homodimer of a T1R3 G-protein coupled receptor polypeptide, antibodies to such receptors, methods of detecting such nucleic acids and receptors, and methods of screening for modulators of sweet and amino acid taste receptors.

Abstract: Recombinant HMPV (rHMPV) and related immunogenic compositions and methods are provided. The rHMPVs, including chimeric and chimeric HMPV vectors viruses, provided according to the current disclosure are infectious and attenuated in permissive mammalian subjects, including humans. The rHMPVs are useful in immunogenic compositions for eliciting an immune response against HPIV, against one or more non-HMPV pathogens, or against a HMPV and a non-HMPV pathogen. Also provided are isolated polynucleotide molecules and vectors incorporating a recombinant HMPV genome of antigenome.

Abstract: The invention provides a method of inhibiting prophylactically or therapeutically an influenza viral infection in a host. The method comprises instilling into or onto a host a cell producing an antiviral protein, antiviral peptide, or antiviral conjugate comprising at least nine contiguous amino acids of SEQ ID NO: 2, wherein the at least nine contiguous amino acids are nonglycosylated and have antiviral activity, whereupon the influenza viral infection is inhibited.

Abstract: The invention provides a method of treating cancer in a mammal that expresses the same level or a higher level of Wip1 as compared to a mammal of the same species that does not have cancer, and a method of inhibiting Wip1 in a cell. The invention also provides pharmaceutical compositions comprising a compound selected from the group consisting of Compounds A-N, and a method of making a cancer therapeutic composition. Also provided is a compound selected from the group consisting of Compounds A-N, a method of screening a compound for Wip1-inhibiting activity, and a method of determining the efficacy with which a test compound inhibits Wip1.

Abstract: Apoptosis-modifying fusion polypeptides, and the corresponding nucleic acid molecules, are disclosed. Pharmaceutical compositions comprising these polypeptides, and the use of these polypeptides to modify apoptosis are also provided.

Abstract: Methods of inhibiting metastasis of a CXCR4-expressing tumor cell in a mammal, which methods comprise administering to the mammal in an amount sufficient to inhibit metastasis of the tumor cell an antagonist of CXCR4, such as a polypeptide of the formula described herein, an antagonist of &bgr;1 integrin, such as an antibody that binds to &bgr;1, an antagonist of CXCL12, such as an antibody that binds to CXCL12, or an antagonist of &agr;4 integrin, such as an antibody that binds to &agr;4; and a method of inhibiting growth of a CXCR4 expressing-tumor cell in a mammal, which method comprises administering to the tumor cell a polypeptide of the formula described herein.

Abstract: The present disclosure relates to oligodeoxynucleotides that suppress an immune response. Methods are disclosed for inhibiting or treating inflammatory lung disease by administering a therapeutically effective amount of a suppressive oligodeoxynucleotide.

Abstract: In one aspect, the disclosure concerns improved methods for the modification of genes in cells. Particular methods accomplish recombination, including targeted homologous recombination of a target gene. In another aspect, the disclosure relates to DNA modifying molecules. In one aspect, DNA modifying molecules comprise DNA targeting agents, including modified oligonucleotides, including triplex forming oligonucleotides, peptide nucleic acids and polyamides. In one embodiment, the DNA modifying molecules comprise a mutagen, and in another embodiment the DNA modifying molecules comprise a mutagen and a DNA targeting agent. The disclosure also describes methods for modifying a nucleotide sequence in the genome of a cell using the DNA targeting agents. The disclosure also relates to cells, tissue, and organisms that have been modified by DNA targeting agents.

Abstract: A novel gene designated as FRAG1 from and its encoded protein is disclosed. A fusion protein called FGFR2-ROS, which is formed by chromosomal rearrangement of rat FRAG1 with FGFR2 is also disclosed. Methods of producing FRAG1 protein, related fusion proteins, and antibodies against FRAG1 are disclosed, as are related pharmaceuticals and methods of using such nucleic acids, polypeptides, and antibodies are also disclosed.

Abstract: The present invention relates to nitric oxide-releasing amidine- and enamine-derived diazeniumdiolates, compositions comprising such compounds, methods of using such compounds and compositions, and to a method for the preparation of nitric oxide-releasing amidine- and enamine-derived diazeniumdiolates via the direct reaction of nitric oxide with amidines and enamines, and to a method of converting amines into such compounds.

Abstract: Sequence variations, such as polymorphisms, are detected by detecting differences between or among melting profiles of plural nucleic acids. Melting profiles are produced by observing the nucleic acids during a temperature change over a period of time. If the nucleic acids are diluted into solutions for analysis, the nucleic acid concentrations between or among the solutions can be substantially the same. The melting profiles and sequence variation can be used to identify changes in a wild-type nucleic acid sequence, such as a single-nucleotide polymorphism (SNP), a small insertion or deletion, or a small inversion.

Abstract: An array-based technology facilitates rapid correlated gene copy number and expression profiling of a very large numbers of human tumors. Hundreds of cylindrical tissue biopsies (diameter 0.6 mm) from morphologically representative regions of individual tumors can be arrayed in a single paraffin block. Consecutive sections from such arrays provide targets for parrallel in situ visualization and quantitation of DNA, RNA or protein targets. For example, amplifications of six loci (mybL2, erbB2, Cyclin-D1, myc, 17q23 and 20q13) were rapidly determined by fluorescence in situ hybridization from 372 ethanol-fixed breast cancers. Stratification of tumors by estrogen receptor and p53 expression data revealed dictinct patterns of gene amplification in the various subgroups of breast cancer that may have prognostic utility.

Abstract: The present invention provides an isolated nucleic acid encoding DRM protein, an isolated DRM polypeptide, and a fusion polypeptide comprising a DRM protein and a green fluorescent protein. The present invention also provides a method of arresting the growth of a cell, comprising administering to the cell an effective amount of DRM protein or an active fragment thereof; a method of inhibiting tumor cell growth, comprising administering to a tumor cell an effective amount of DRM protein or an active fragment thereof; and a method of treating a hyperproliferative cell disorder in a subject diagnosed with a hyperproliferative cell disorder, comprising administering to the subject an effective amount of DRM protein or an active fragment thereof, in a pharmaceutically acceptable carrier.

Abstract: The design, synthesis and antiviral activity of certain antiviral compounds are disclosed examples of which are shown below. These compounds inhibit the reverse transcriptase enzymes of several retroviruses, including human immunodeficiency virus.

Abstract: A molecular motor in which multiple concentric cylinders (or nested cones) rotate around a common longitudinal axis. Opposing complementary surfaces of the cylinders or cones are coated with complementary motor protein pairs (such as actin and myosin). The actin and myosin interact with one another in the presence of ATP to rotate the cylinders or cones relative to one another, and this rotational energy is harnessed to produce work. The concentration of ATP and the number of nested cylinders or cones can be used to control the rotational speed of the motor. The length of the cylinders can also be used to control the power generated by the motor. In another embodiment, the molecular motor includes at least two annular substrates wherein one annular substrate is coated with a first motor protein and the other annular substrate is coated with a second motor protein. The first and second motor proteins interact with each other to move the second annular relative to the first annular substrate.