25 research outputs found

    The CST Complex Mediates End Protection at Double-Strand Breaks and Promotes PARP Inhibitor Sensitivity in BRCA1-Deficient Cells

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    Selective elimination of BRCA1-deficient cells by inhibitors of poly(ADP-ribose) polymerase (PARP) is a prime example of the concept of synthetic lethality in cancer therapy. This interaction is counteracted by the restoration of BRCA1-independent homologous recombination through loss of factors such as 53BP1, RIF1, and REV7/MAD2L2, which inhibit end resection of DNA double-strand breaks (DSBs). To identify additional factors involved in this process, we performed CRISPR/SpCas9-based loss-of-function screens and selected for factors that confer PARP inhibitor (PARPi) resistance in BRCA1-deficient cells. Loss of members of the CTC1-STN1-TEN1 (CST) complex were found to cause PARPi resistance in BRCA1-deficient cells in vitro and in vivo. We show that CTC1 depletion results in the restoration of end resection and that the CST complex may act downstream of 53BP1/RIF1. These data suggest that, in addition to its role in protecting telomeres, the CST complex also contributes to protecting DSBs from end resection. Using CRISPR/SpCas9-based loss-of-function screens, Barazas et al. show that loss of the CTC1-STN1-TEN1 (CST) complex promotes PARP inhibitor resistance in BRCA1-deficient cells. Mechanistically, the CST complex maintains double-strand break end stability in addition to its role in protecting telomeric ends

    Study of Z → llγ decays at √s = 8 TeV with the ATLAS detector

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    This paper presents a study of Z → llγ decays with the ATLAS detector at the Large Hadron Collider. The analysis uses a proton–proton data sample corresponding to an integrated luminosity of 20.2 fb−1 collected at a centre-ofmass energy √s = 8 TeV. Integrated fiducial cross-sections together with normalised differential fiducial cross-sections, sensitive to the kinematics of final-state QED radiation, are obtained. The results are found to be in agreement with stateof-the-art predictions for final-state QED radiation. First measurements of Z → llγ γ decays are also reported

    Constraints on spin-0 dark matter mediators and invisible Higgs decays using ATLAS 13 TeV pp collision data with two top quarks and missing transverse momentum in the final state

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    This paper presents a statistical combination of searches targeting final states with two top quarks and invisible particles, characterised by the presence of zero, one or two leptons, at least one jet originating from a b-quark and missing transverse momentum. The analyses are searches for phenomena beyond the Standard Model consistent with the direct production of dark matter in pp collisions at the LHC, using 139 fb−1 of data collected with the ATLAS detector at a centre-of-mass energy of 13 TeV. The results are interpreted in terms of simplified dark matter models with a spin-0 scalar or pseudoscalar mediator particle. In addition, the results are interpreted in terms of upper limits on the Higgs boson invisible branching ratio, where the Higgs boson is produced according to the Standard Model in association with a pair of top quarks. For scalar (pseudoscalar) dark matter models, with all couplings set to unity, the statistical combination extends the mass range excluded by the best of the individual channels by 50 (25) GeV, excluding mediator masses up to 370 GeV. In addition, the statistical combination improves the expected coupling exclusion reach by 14% (24%), assuming a scalar (pseudoscalar) mediator mass of 10 GeV. An upper limit on the Higgs boson invisible branching ratio of 0.38 (0.30+0.13−0.09) is observed (expected) at 95% confidence level

    Search for long-lived neutral particles in pp collisions at s√=13 TeV that decay into displaced hadronic jets in the ATLAS calorimeter

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    This paper describes a search for pairs of neutral, long-lived particles decaying in the ATLAS calorimeter. Long-lived particles occur in many extensions to the Standard Model and may elude searches for new promptly decaying particles. The analysis considers neutral, long-lived scalars with masses between 5 and 400 GeV, produced from decays of heavy bosons with masses between 125 and 1000 GeV, where the long-lived scalars decay into Standard Model fermions. The analysis uses either 10.8 fb−1 or 33.0 fb−1 of data (depending on the trigger) recorded in 2016 at the LHC with the ATLAS detector in proton–proton collisions at a centre-of-mass energy of 13 TeV. No significant excess is observed, and limits are reported on the production cross section times branching ratio as a function of the proper decay length of the long-lived particles

    Deep generative models for fast photon shower simulation in ATLAS

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    The need for large-scale production of highly accurate simulated event samples for the extensive physics programme of the ATLAS experiment at the Large Hadron Collider motivates the development of new simulation techniques. Building on the recent success of deep learning algorithms, variational autoencoders and generative adversarial networks are investigated for modelling the response of the central region of the ATLAS electromagnetic calorimeter to photons of various energies. The properties of synthesised showers are compared with showers from a full detector simulation using geant4. Both variational autoencoders and generative adversarial networks are capable of quickly simulating electromagnetic showers with correct total energies and stochasticity, though the modelling of some shower shape distributions requires more refinement. This feasibility study demonstrates the potential of using such algorithms for ATLAS fast calorimeter simulation in the future and shows a possible way to complement current simulation techniques

    Search for doubly charged Higgs boson production in multi-lepton final states using 139 fb−1 of proton–proton collisions at s√ = 13 TeV with the ATLAS detector

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    A search for pair production of doubly charged Higgs bosons (H±± ), each decaying into a pair of prompt, isolated, and highly energetic leptons with the same electric charge, is presented. The search uses a proton–proton collision data sample at a centre-of-mass energy of 13 TeV corresponding to an integrated luminosity of 139 fb−1 recorded by the ATLAS detector during Run 2 of the Large Hadron Collider (LHC). This analysis focuses on same-charge leptonic decays, H±±→ℓ±ℓ′± where ℓ,ℓ′=e,μ,τ, in two-, three-, and four-lepton channels, but only considers final states which include electrons or muons. No evidence of a signal is observed. Corresponding upper limits on the production cross-section of a doubly charged Higgs boson are derived, as a function of its mass m(H±±), at 95% confidence level. Assuming that the branching ratios to each of the possible leptonic final states are equal, B(H±±→e±e±)=B(H±±→e±μ±)=B(H±±→μ±μ±)=B(H±±→e±τ±)=B(H±±→μ±τ±)=B(H±±→τ±τ±)=1/6, the observed (expected) lower limit on the mass of a doubly charged Higgs boson is 1080 GeV (1065 GeV) within the left-right symmetric type-II seesaw model, which is the strongest limit to date produced by the ATLAS Collaboration. Additionally, this paper provides the first direct test of the Zee–Babu neutrino mass model at the LHC, yielding an observed (expected) lower limit of m(H±±) = 900 GeV (880 GeV)

    Detection of varicella-zoster virus and herpes simplex virus by the polymerase chain reaction with degenerate primers

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    Varicella-zoster virus (VZV) and herpes simplex virus (HSV) are human pathogens of significance involved in multiple diseases with either typical or atypical clinical features. In neonates and immunocompromised patients these alphaherpesviruses may cause life-threatening diseases such as encephalitis. Detection of VZV by virus culture is difficult. Polymerase chain reaction (PCR) is quicker and more sensitive and applicable in most clinical microbiological laboratories. Using degenerate primers, glycoprotein B (gB) DNA was amplified from all alphaherpesvirus field strains present in clinical samples. The amplification of gB allowed virus typing of VZV, HSV-1 and HSV-2 using restriction enzyme digestion of the PCR products. Degenerate primers can replace conventional primers in diagnostic PCR without loss of sensitivity and specificity
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