125 research outputs found

    A Three-Hybrid Approach to Scanning the Proteome for Targets of Small Molecule Kinase Inhibitors

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    AbstractIn this study, we explored the application of a yeast three-hybrid (Y3H)-based compound/protein display system to scanning the proteome for targets of kinase inhibitors. Various known cyclin-dependent kinase (CDK) inhibitors, including purine and indenopyrazole analogs, were displayed in the form of methotrexate-based hybrid ligands and deployed in cDNA library or yeast cell array-based screening formats. For all inhibitors, known cell cycle CDKs as well as novel candidate CDK-like and/or CDK-unrelated kinase targets could be identified, many of which were independently confirmed using secondary enzyme assays and affinity chromatography. The Y3H system described here may prove generally useful in the discovery of candidate drug targets

    Barriers and opportunities for implementation of a brief psychological intervention for post-ICU mental distress in the primary care setting – results from a qualitative sub-study of the PICTURE trial

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    Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

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    A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

    Measurement of the W boson polarisation in ttˉt\bar{t} events from pp collisions at s\sqrt{s} = 8 TeV in the lepton + jets channel with ATLAS

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    Measurements of top-quark pair differential cross-sections in the eμe\mu channel in pppp collisions at s=13\sqrt{s} = 13 TeV using the ATLAS detector

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    Measurement of the charge asymmetry in top-quark pair production in the lepton-plus-jets final state in pp collision data at s=8TeV\sqrt{s}=8\,\mathrm TeV{} with the ATLAS detector

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    Measurement of the bbb\overline{b} dijet cross section in pp collisions at s=7\sqrt{s} = 7 TeV with the ATLAS detector

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    Search for single production of vector-like quarks decaying into Wb in pp collisions at s=8\sqrt{s} = 8 TeV with the ATLAS detector

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    ATLAS Run 1 searches for direct pair production of third-generation squarks at the Large Hadron Collider

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