41 research outputs found

    Development of peptide inhibitors of HIV transmission

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    AbstractTreatment of HIV has long faced the challenge of high mutation rates leading to rapid development of resistance, with ongoing need to develop new methods to effectively fight the infection. Traditionally, early HIV medications were designed to inhibit RNA replication and protein production through small molecular drugs. Peptide based therapeutics are a versatile, promising field in HIV therapy, which continues to develop as we expand our understanding of key protein-protein interactions that occur in HIV replication and infection. This review begins with an introduction to HIV, followed by the biological basis of disease, current clinical management of the disease, therapeutics on the market, and finally potential avenues for improved drug development

    Methamphetamine-Associated Psychosis

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    MPO ANCA-related Nephritis Associated with Membranous Glomerulonephropathy

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    Genetic association between G protein-coupled receptor kinase 6/β-arrestin 2 and dopamine supersensitivity psychosis in schizophrenia

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    Yasunori Oda,1 Nobuhisa Kanahara,2 Hiroshi Kimura,1 Hiroyuki Watanabe,2 Kenji Hashimoto,3 Masaomi Iyo1 1Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan; 2Division of Medical Treatment and Rehabilitation, 3Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan Background/aim: Dopamine supersensitivity psychosis (DSP), clinically characterized by unstable and severe psychosis or tardive dyskinesia and often categorized as treatment-resistant schizophrenia, is promoted by long-term antipsychotic treatment. An upregulation of the dopamine D2 receptor caused by antipsychotic(s) is involved in the development of DSP. The present study explored the potential roles of G protein-coupled receptor kinase 6 (GRK6) and β-arrestin 2 (ARRB2) that are involved in the trafficking of DRD2 in patients with DSP. Methods: We conducted a genetic association study of GRK6/ARRB2 between the patients with DSP episodes [DSP(+) group: N=108] and the patients without DSP(-) episodes [DSP(-) group: N=169] from the total group of patients (N=333). Based on the patients’ treatment history, a DSP episode was defined as withdrawal psychosis, developed tolerance to antipsychotic effect, and tardive dyskinesia (the remaining 56 patients were excluded due to insufficient information). Results: The results revealed that none of the allelic or genotyping distributions of five single nucleotide polymorphisms (SNPs) of GRK6 and three SNPs of ARRB2 showed any significant difference between the DSP(+) and DSP(-) groups. Conclusion: The results suggest that the SNP analyses of these two molecules fail to classify patients into the potential clinical subtype of DSP(+) or DSP(-) group. However, since GRK6 and ARRB2 are surely involved in dopamine D2 receptor metabolism, further studies based on prospective observations of the onset of DSP under specific antipsychotic treatments are needed. Keywords: antipsychotic, dopamine D2 receptor, tardive dyskinesia, treatment-resistan

    Direct detection of a triplet vinylnitrene, 1,4-naphthoquinone-2-ylnitrene, in solution and cryogenic matrices

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    The photolysis of 2-azido-1,4-naphthoquinone (1) in argon matrices at 8 K results in the corresponding triplet vinylnitrene (3)2, which was detected directly by IR spectroscopy. Vinylnitrene (3)2 is stable in argon matrices but forms 2-cyanoindane-1,3-dione (3) upon further irradiation. Similarly, the irradiation of azide 1 in 2-methyltetrahydrofuran (MTHF) matrices at 5 K resulted in the ESR spectrum of vinylnitrene (3)2, which is stable up to at least 100 K. The zero-field splitting parameters for nitrene (3)2, D/hc = 0.7292 cm(-1) and E/hc = 0.0048 cm(-1), verify that it has significant 1,3-biradical character. Vinylnitrene (3)2 (lambda(max) similar to 460 nm, tau = 22 mu s) is also observed directly in solution at ambient temperature with laser flash photolysis of 1. Density functional theory (DFT) calculations support the characterization of vinylnitrene (3)2 and the proposed mechanism for its formation. Because vinylnitrene (3)2 is relatively stable, it has potential use as a building-block for high-spin assemblies

    Production and measurement of the MQXA series of LHC low- beta insertion quadrupoles

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    The inner triplet quadrupole magnets (MQXA) for the LHC low-beta insertion have been developed. The quadrupoles provide a field gradient of 215 T/m at 1.9 K in a coil aperture of 70 mm diameter and with an effective magnetic length of 6.37 m. The series of 20 magnets have been produced in industry, and full testing has been done at KEK. We present an overview of the production and the results from mechanical and magnetic measurements

    Fabrication and mechanical behavior of a prototype for the LHC low-β\beta quadrupole magnets

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    Superconducting low-beta quadrupole magnets for the LHC insertion regions are being developed at KEK as part of the collaboration between CERN and KEK. Magnet production technology developed at KEK has been transferred to a manufacturer of production magnets. In order to verify the production technology, fabrication jigs, tools, and procedures, the first full-scale prototype, MQXA-P1, was fabricated. Mechanical characteristics of MQXA-P1 were measured during the magnet assembly process, and it satisfied specifications needed for the production magnets. The validity of the magnet design and fabrication method was confirmed. (14 refs)
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