Abstract: The present invention provides a method of mitigating a symptom of maladaptive substance use in a subject by inhibiting CCKB receptors. In addition, the invention provides a variety of prescreening and screening methods aimed at identifying agents that modulate a symptom of maladaptive substance use. Methods of the invention can involve assaying test agent binding to CCKB receptors. Alternatively, test agents can be screened for their ability to alter the level of CCKB receptor polypeptides, polynucleotides, or function. Finally, the invention also provides a diagnostic method that entails measuring one or more of these levels and determining risk for maladaptive substance use based on comparison to the corresponding level for a control population.

Abstract: This invention pertains to the discoveries that orexin and/or CRF increase NMDAR (N-methyl-D-aspartate receptor)-mediated currents at excitatory synapses onto a subset of dopamine cells in the ventral tegmental area (VTA) in the mammalian brain. The orexin effect can be blocked by an orexin receptor type 1 (OXR1). The CRF effect can be blocked by a CRF receptor 2 (CRF-R2) antagonist or by an inhibitor of the CRF-binding protein (CRF-BP). Methods are provided that exploit these discoveries to modulate NMDAR-mediated currents in vivo and in vitro and to screen for modulators (upregulators or downregulators) of NMDA-mediated currents. In vivo methods include the use of modulators of the orexin and CRF pathways to of mitigate a symptom of substance abuse. The invention also provides methods and compositions for co-administration of modulators that act via the orexin and CRF pathways.

Abstract: Antigenic epitopes of hepatitis C virus (HCV) and mosaic HCV polypeptides useful as reagents in assays for the diagnosis or monitoring of HCV in a biological sample. The antigenic epitopes and mosaic polypeptides are also useful for the construction of immunogenic pharmaceutical compositions, such as vaccines. The mosaic polypeptides are artificial composite proteins constructed from diagnostically relevant antigenic regions derived from different HCV proteins. Preferably, the mosaic polypeptides contain antigenic epitopes from the core protein, NS3 protein, and NS4 protein. The preferred mosaic polypeptides optionally contain an additional antigenic epitope from either the NS4 protein or the NS5a protein or both.

Abstract: A mosaic protein comprising a variety of immunoreactive antigenic epitopes from several genotypes of hepatitis C virus. The mosaic protein provides a sensitive and specific immunological hepatitis detection assay. A restriction enzyme assisted ligation method of making an artificial gene permits controlled construction of mosaic proteins, and allows confirmatory expression of the intermediate gene products.

Abstract: Antigenically reactive regions of the Hepatitis A virus polyprotein are provided. These antigenically reactive regions, and polypeptides and proteins comprising these antigenically reactive regions, provide a sensitive and specific immunological hepatitis A virus detection assay. The specific use of regions derived from the nonstructural regions of the polypeptide provides the basis for determining immunity derived from prior or present infection by the Hepatitis A virus and allows one to distinguish between an immunological response derived from infection and that derived from immunization.

Abstract: Synthetic peptides immunoreactive with hepatitis A virus (HAV) antibodies are provided. The peptides are useful as laboratory reagents to detect or quantify HAV antibodies in biological samples in clinical or research-based assays and for inducing an immune response to HAV when administered to a human or animal. The peptides contain antigenic epitopes, modified antigenic epitopes or combinations of epitopes of the major structural capsid polypeptides or non-structural polypeptides of HAV and contain one or more molecules of the amino acid glutamine (Q) at the carboxyl end of the peptide, which enhances immunoreactivity and immunogenicity, particularly IgM antibody reactivity.

Abstract: The present invention provides immunogenic Hepatitis E Virus polypeptides and methods of use. The polypeptides include at least one neutralizing antigenic epitope and preferably contain at least about fifty amino acids residues between amino acid residues 452 and 617 from the C-terminal of the HEV pORF2 protein. The polypeptides are useful, alone or in combination with other polypeptides of the present invention, as a reagent for studying the pathogenesis of HEV and monitoring treatment efficacy in subjects undergoing treatment for HEV. Further, the polypeptides can be used as a vaccine to treat or prevent HEV.

Abstract: It is to be understood that the above description is intended to be illustrative and not restrictive. Many embodiments will be apparent to those of skill in the art upon reading the above description. The scope of the invention should, therefore, be determined not with reference to the above description, but should instead be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled. The disclosures of all articles and references, including patent applications and publications, are incorporated herein by reference for all purpose.

Abstract: A putter includes a shaft, a head having a front face for striking a golf ball and a rear face, and a connector interconnecting the shaft and the head. The connector has a rear edge that can be aligned visually with the rear face of the head by a golfer holding the shaft. The putter head has a toe and a heel, the heel being the end portion of the head that is closer to the golfer when putting and the toe being the end portion of the head that is remote from the golfer when putting. The shaft of the putter is connected to the head of the putter at or adjacent the “toe” end of the head of the putter. This allows a golfer to be able to obtain an accurate visual sighting by looking at that part of the head of the putter that is furthest from him.

Abstract: Antigenic epitopes of hepatitis C virus (HCV) and mosaic HCV polypeptides useful as reagents in assays for the diagnosis or monitoring of HCV in a biological sample. The antigenic epitopes and mosaic polypeptides are also useful for the construction of immunogenic pharmaceutical compositions, such as vaccines. The mosaic polypeptides are artificial composite proteins constructed from diagnostically relevant antigenic regions derived from different HCV proteins. Preferably, the mosaic polypeptides contain antigenic epitopes from the core protein, NS3 protein, and NS4 protein. The preferred mosaic polypeptides optionally contain an additional antigenic epitope from either the NS4 protein or the NS5a protein or both.

Abstract: The present invention is concerned with a crystalline, polymorphic form of a compound of formula (I) characterized by a powder X-ray diffraction pattern obtained using copper K-alpha1 radiation (&lgr;=0.15046 nm) which shows main peaks at 9.28, 10.38, 11.37, 12.40, 16.84, 17.46, 17.53, 17.78, 17.98, 19.48, 20.70, 21.29, 21.45, 22.21, 22.64, 23.08, 25.20 and 25.79. The invention also relates to processes for the preparation of said form, to pharmaceutical compositions containing same and to its use in medicine, particularly the treatment of conditions for which an agonist of 5-HT1 receptors is indicated, for example, migraine.

Abstract: A mosaic protein comprising a variety of immunoreactive antigenic epitopes from several genotypes of hepatitis C virus. The mosaic protein provides a sensitive and specific immunological hepatitis detection assay. A restriction enzyme assisted ligation method of making an artificial gene permits controlled construction of mosaic proteins, and allows confirmatory expression of the intermediate gene products.

Abstract: The present invention provides antigenic peptides and polypeptides of hepatitis E virus. Also provided are mixtures of conjugated and unconjugated peptides of the present invention. Methods of detecting hepatitis E viral infection in a subject using the peptides and peptide mixtures of the present invention are also contemplated.

Abstract: The present invention provides antigenic peptides and polypeptides of hepatitis E virus. Also provided are mixtures of conjugated and unconjugated peptides of the present invention. Methods of detecting hepatitis E viral infection in a subject using the peptides and peptide mixtures of the present invention are also contemplated.

Abstract: The present invention provides antigenic peptides which bind anti-HCV antibodies for the differential diagnosis of acute and chronic HCV infection.

Abstract: A nucleic acid encoding a mosaic hepatitis E virus (HEV) polypeptide, consisting of the nucleotide sequence defined in the Sequence Listing as SEQ ID NO:1 is provided. A nucleic acid encoding epitopes 5, 6, 22, 23, 28 and 29 of hepatitis E virus and substantially lacking the nucleic acids intervening the epitope-coding nucleic acids in the native hepatitis E virus is also provided. An isolated nucleic acid that selectively hybridizes under stringent conditions with the mosaic polypeptide-encoding nucleic acid and has at least 70% sequence identity with SEQ ID NO:1 is provided. Also provided are such nucleic acids having at least 80%, 90% and 95% sequence identity. A polypeptide consisting essentially of the amino acid sequence defined in the Sequence Listing as SEQ ID NO:2 is provided.

Abstract: The invention provides a method for the synthesis of DNA based on a cyclic mechanism of combining deoxyoligonucleotides comprising combining: (a) a series of unique single-stranded deoxypolynucleotides, each having a 5' sequence which, when in double-stranded form, can be enzymatically treated to form a unique 3' single-stranded protrusion for selective cyclic hybridization with another unique single-stranded deoxypolynucleotide of the series; (b) a unique deoxypolynucleotide having a 3' sequence which can selectively hybridize with one of the unique single-stranded deoxypolynucleotides of (a); (c) a polymerase which can direct the formation of double-stranded deoxypolynucleotides from the single-stranded deoxypolynucleotides; and (d) an enzyme which can form a unique single-stranded 3' protrusion from the double-stranded deoxypolynucleotides; under conditions which hybridize the unique single-stranded deoxypolynucleotides in a cyclic manner to form the DNA.

Abstract: Reagents and methods for the detection of a marker which is associated with severe forms of hepatitis delta virus infection are described. A vaccine comprising immunogenically active HDAg' polypeptides is also described.