135 research outputs found

    HIVToolbox, an Integrated Web Application for Investigating HIV

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    Many bioinformatic databases and applications focus on a limited domain of knowledge federating links to information in other databases. This segregated data structure likely limits our ability to investigate and understand complex biological systems. To facilitate research, therefore, we have built HIVToolbox, which integrates much of the knowledge about HIV proteins and allows virologists and structural biologists to access sequence, structure, and functional relationships in an intuitive web application. HIV-1 integrase protein was used as a case study to show the utility of this application. We show how data integration facilitates identification of new questions and hypotheses much more rapid and convenient than current approaches using isolated repositories. Several new hypotheses for integrase were created as an example, and we experimentally confirmed a predicted CK2 phosphorylation site. Weblink: [http://hivtoolbox.bio-toolkit.com

    Novel therapeutic strategies targeting HIV integrase

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    Integration of the viral genome into host cell chromatin is a pivotal and unique step in the replication cycle of retroviruses, including HIV. Inhibiting HIV replication by specifically blocking the viral integrase enzyme that mediates this step is an obvious and attractive therapeutic strategy. After concerted efforts, the first viable integrase inhibitors were developed in the early 2000s, ultimately leading to the clinical licensure of the first integrase strand transfer inhibitor, raltegravir. Similarly structured compounds and derivative second generation integrase strand transfer inhibitors, such as elvitegravir and dolutegravir, are now in various stages of clinical development. Furthermore, other mechanisms aimed at the inhibition of viral integration are being explored in numerous preclinical studies, which include inhibition of 3' processing and chromatin targeting. The development of new clinically useful compounds will be aided by the characterization of the retroviral intasome crystal structure. This review considers the history of the clinical development of HIV integrase inhibitors, the development of antiviral drug resistance and the need for new antiviral compounds

    Observation of the diphoton decay of the Higgs boson and measurement of its properties

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    Search for new physics with dijet angular distributions in proton-proton collisions at root S = 13 TeV

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    Precise determination of the mass of the Higgs boson and tests of compatibility of its couplings with the standard model predictions using proton collisions at 7 and 8 TeV

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    Search for light bosons in decays of the 125 GeV Higgs boson in proton-proton collisions at root s=8 TeV

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    Search for single production of vector-like quarks decaying into a b quark and a W boson in proton-proton collisions at root s=13 TeV

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    Measurement of the top quark mass using single top quark events in proton-proton collisions at root s=8 TeV

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    Search for dijet resonances in proton-proton collisions at root s=13 TeV and constraints on dark matter and other models

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    Correction: DOI:10.1016/j.physletb.2017.09.029Peer reviewe
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