121 research outputs found

    An IRAK1-PIN1 signalling axis drives intrinsic tumour resistance to radiation therapy

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    Drug-based strategies to overcome tumour resistance to radiotherapy (R-RT) remain limited by the single-agent toxicity of traditional radiosensitizers (for example, platinums) and a lack of targeted alternatives. In a screen for compounds that restore radiosensitivity in p53 mutant zebrafish while tolerated in non-irradiated wild-type animals, we identified the benzimidazole anthelmintic oxfendazole. Surprisingly, oxfendazole acts via the inhibition of IRAK1, a kinase thus far implicated in interleukin-1 receptor (IL-1R) and Toll-like receptor (TLR) immune responses. IRAK1 drives R-RT in a pathway involving IRAK4 and TRAF6 but not the IL-1R/TLR-IRAK adaptor MyD88. Rather than stimulating nuclear factor-κB, radiation-activated IRAK1 prevented apoptosis mediated by the PIDDosome complex (comprising PIDD, RAIDD and caspase-2). Countering this pathway with IRAK1 inhibitors suppressed R-RT in tumour models derived from cancers in which TP53 mutations predict R-RT. Moreover, IRAK1 inhibitors synergized with inhibitors of PIN1, a prolyl isomerase essential for IRAK1 activation in response to pathogens and, as shown here, in response to ionizing radiation. These data identify an IRAK1 radiation-response pathway as a rational chemoradiation therapy target

    Search for jet extinction in the inclusive jet-pT spectrum from proton-proton collisions at s=8 TeV

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    Published by the American Physical Society under the terms of the Creative Commons Attribution 3.0 License. Further distribution of this work must maintain attribution to the author(s) and the published articles title, journal citation, and DOI.The first search at the LHC for the extinction of QCD jet production is presented, using data collected with the CMS detector corresponding to an integrated luminosity of 10.7  fb−1 of proton-proton collisions at a center-of-mass energy of 8 TeV. The extinction model studied in this analysis is motivated by the search for signatures of strong gravity at the TeV scale (terascale gravity) and assumes the existence of string couplings in the strong-coupling limit. In this limit, the string model predicts the suppression of all high-transverse-momentum standard model processes, including jet production, beyond a certain energy scale. To test this prediction, the measured transverse-momentum spectrum is compared to the theoretical prediction of the standard model. No significant deficit of events is found at high transverse momentum. A 95% confidence level lower limit of 3.3 TeV is set on the extinction mass scale

    Search for neutral resonances decaying into a Z boson and a pair of b jets or τ leptons

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    A search is performed for a new resonance decaying into a lighter resonance and a Z boson. Two channels are studied, targeting the decay of the lighter resonance into either a pair of oppositely charged τ leptons or a bb‾ pair. The Z boson is identified via its decays to electrons or muons. The search exploits data collected by the CMS experiment at a centre-of-mass energy of 8 TeV, corresponding to an integrated luminosity of 19.8 fb −1 . No significant deviations are observed from the standard model expectation and limits are set on production cross sections and parameters of two-Higgs-doublet models

    Search for a low-mass pseudoscalar Higgs boson produced in association with a bb⁻ pair in pp collisions at √s=8 TeV

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    A search is reported for a light pseudoscalar Higgs boson decaying to a pair of tau leptons, produced in association with a b (b) over bar pair, in the context of two-Higgs-doublet models. The results are based on pp collision data at a centre-of-mass energy of 8 TeV collected by the CMS experiment at the LHC and corresponding to an integrated luminosity of 19.7 fb(-1). Pseudoscalar boson masses between 25 and 80 GeV are probed. No evidence for a pseudoscalar boson is found and upper limits are set on the product of cross section and branching fraction to tau pairs between 7 and 39 pb at the 95% confidence level. This excludes pseudoscalar A bosons with masses between 25 and 80 GeV, with SM-like Higgs boson negative couplings to down-type fermions, produced in association with bb pairs, in Type II, two-Higgs-doublet models. (C) 2016 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommonnorg/licensesiby/4.01)

    Forward-backward asymmetry of Drell-Yan lepton pairs in pp collisions at root s=8 TeV

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    Search for single production of scalar leptoquarks in proton-proton collisions at root s=8 TeV

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    Correction DOI:10.1103/PhysRevD.95.039906Peer reviewe

    Search for massive WH resonances decaying into the l nu b(b)over-bar final state at root s=8 TeV

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    Search for vectorlike charge 2/3 T quarks in proton-proton collisions at root(s)=8 TeV

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    Pseudorapidity distribution of charged hadrons in proton-proton collisions at root s=13TeV

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