39 research outputs found

    USP50 suppresses alternative RecQ helicase use and deleterious DNA2 activity during replication.

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    Mammalian DNA replication relies on various DNA helicase and nuclease activities to ensure accurate genetic duplication, but how different helicase and nuclease activities are properly directed remains unclear. Here, we identify the ubiquitin-specific protease, USP50, as a chromatin-associated protein required to promote ongoing replication, fork restart, telomere maintenance, cellular survival following hydroxyurea or pyridostatin treatment, and suppression of DNA breaks near GC-rich sequences. We find that USP50 supports proper WRN-FEN1 localisation at or near stalled replication forks. Nascent DNA in cells lacking USP50 shows increased association of the DNA2 nuclease and RECQL4 and RECQL5 helicases and replication defects in cells lacking USP50, or FEN1 are driven by these proteins. Consequently, suppression of DNA2 or RECQL4/5 improves USP50-depleted cell resistance to agents inducing replicative stress and restores telomere stability. These data define an unexpected regulatory protein that promotes the balance of helicase and nuclease use at ongoing and stalled replication forks

    Volume I. Introduction to DUNE

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    The preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay—these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. The Deep Underground Neutrino Experiment (DUNE) is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- and dual-phase DUNE liquid argon TPC far detector modules. This TDR is intended to justify the technical choices for the far detector that flow down from the high-level physics goals through requirements at all levels of the Project. Volume I contains an executive summary that introduces the DUNE science program, the far detector and the strategy for its modular designs, and the organization and management of the Project. The remainder of Volume I provides more detail on the science program that drives the choice of detector technologies and on the technologies themselves. It also introduces the designs for the DUNE near detector and the DUNE computing model, for which DUNE is planning design reports. Volume II of this TDR describes DUNE\u27s physics program in detail. Volume III describes the technical coordination required for the far detector design, construction, installation, and integration, and its organizational structure. Volume IV describes the single-phase far detector technology. A planned Volume V will describe the dual-phase technology

    Deep Underground Neutrino Experiment (DUNE), far detector technical design report, volume III: DUNE far detector technical coordination

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    The preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay—these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. The Deep Underground Neutrino Experiment (DUNE) is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- and dual-phase DUNE liquid argon TPC far detector modules. Volume III of this TDR describes how the activities required to design, construct, fabricate, install, and commission the DUNE far detector modules are organized and managed. This volume details the organizational structures that will carry out and/or oversee the planned far detector activities safely, successfully, on time, and on budget. It presents overviews of the facilities, supporting infrastructure, and detectors for context, and it outlines the project-related functions and methodologies used by the DUNE technical coordination organization, focusing on the areas of integration engineering, technical reviews, quality assurance and control, and safety oversight. Because of its more advanced stage of development, functional examples presented in this volume focus primarily on the single-phase (SP) detector module

    Long-Baseline Neutrino Facility (LBNF) and Deep Underground Neutrino Experiment (DUNE) Conceptual Design Report Volume 2: The Physics Program for DUNE at LBNF

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    The Physics Program for the Deep Underground Neutrino Experiment (DUNE) at the Fermilab Long-Baseline Neutrino Facility (LBNF) is described

    Highly-parallelized simulation of a pixelated LArTPC on a GPU

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    The rapid development of general-purpose computing on graphics processing units (GPGPU) is allowing the implementation of highly-parallelized Monte Carlo simulation chains for particle physics experiments. This technique is particularly suitable for the simulation of a pixelated charge readout for time projection chambers, given the large number of channels that this technology employs. Here we present the first implementation of a full microphysical simulator of a liquid argon time projection chamber (LArTPC) equipped with light readout and pixelated charge readout, developed for the DUNE Near Detector. The software is implemented with an end-to-end set of GPU-optimized algorithms. The algorithms have been written in Python and translated into CUDA kernels using Numba, a just-in-time compiler for a subset of Python and NumPy instructions. The GPU implementation achieves a speed up of four orders of magnitude compared with the equivalent CPU version. The simulation of the current induced on 10^3 pixels takes around 1 ms on the GPU, compared with approximately 10 s on the CPU. The results of the simulation are compared against data from a pixel-readout LArTPC prototype

    The Hippo pathway regulates stem cell proliferation, self-renewal, and differentiation

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    Measurement of the ΜΌ\nu_{\mu} charged-current cross sections on water, hydrocarbon, iron, and their ratios with the T2K on-axis detectors

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    We report a measurement of the flux-integrated ΜΌ\nu_{\mu} charged-current cross sections on water, hydrocarbon, and iron in the T2K on-axis neutrino beam with a mean neutrino energy of 1.5 GeV. The measured cross sections on water, hydrocarbon, and iron are σCCH2O\sigma^{\rm{H_{2}O}}_{\rm{CC}} = (0.840±0.010\pm 0.010(stat.)−0.08+0.10^{+0.10}_{-0.08}(syst.))×\times10−38^{-38}cm2^2/nucleon, σCCCH\sigma^{\rm{CH}}_{\rm{CC}} = (0.817±0.007\pm 0.007(stat.)−0.08+0.11^{+0.11}_{-0.08}(syst.))×\times10−38^{-38}cm2^2/nucleon, and σCCFe\sigma^{\rm{Fe}}_{\rm{CC}} = (0.859±0.003\pm 0.003(stat.) −0.10+0.12^{+0.12}_{-0.10}(syst.))×\times10−38^{-38}cm2^2/nucleon respectively, for a restricted phase space of induced muons: ΞΌ<45∘\theta_{\mu}<45^{\circ} and pÎŒ>p_{\mu}>0.4 GeV/cc in the laboratory frame. The measured cross section ratios are σCCH2O/σCCCH{\sigma^{\rm{H_{2}O}}_{\rm{CC}}}/{\sigma^{\rm{CH}}_{\rm{CC}}} = 1.028±0.016\pm 0.016(stat.)±0.053\pm 0.053(syst.), σCCFe/σCCH2O{\sigma^{\rm{Fe}}_{\rm{CC}}}/{\sigma^{\rm{H_{2}O}}_{\rm{CC}}} = 1.023±0.012\pm 0.012(stat.)±0.058\pm 0.058(syst.), and σCCFe/σCCCH{\sigma^{\rm{Fe}}_{\rm{CC}}}/{\sigma^{\rm{CH}}_{\rm{CC}}} = 1.049±0.010\pm 0.010(stat.)±0.043\pm 0.043(syst.). These results, with an unprecedented precision for the measurements of neutrino cross sections on water in the studied energy region, show good agreement with the current neutrino interaction models used in the T2K oscillation analyses

    First joint oscillation analysis of Super-Kamiokande atmospheric and T2K accelerator neutrino data

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    International audienceThe Super-Kamiokande and T2K collaborations present a joint measurement of neutrino oscillation parameters from their atmospheric and beam neutrino data. It uses a common interaction model for events overlapping in neutrino energy and correlated detector systematic uncertainties between the two datasets, which are found to be compatible. Using 3244.4 days of atmospheric data and a beam exposure of 19.7(16.3)×102019.7(16.3) \times 10^{20} protons on target in (anti)neutrino mode, the analysis finds a 1.9σ\sigma exclusion of CP-conservation (defined as JCP=0J_{CP}=0) and a preference for the normal mass ordering

    First joint oscillation analysis of Super-Kamiokande atmospheric and T2K accelerator neutrino data

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    The Super-Kamiokande and T2K collaborations present a joint measurement of neutrino oscillation parameters from their atmospheric and beam neutrino data. It uses a common interaction model for events overlapping in neutrino energy and correlated detector systematic uncertainties between the two datasets, which are found to be compatible. Using 3244.4 days of atmospheric data and a beam exposure of 19.7(16.3)×102019.7(16.3) \times 10^{20} protons on target in (anti)neutrino mode, the analysis finds a 1.9σ\sigma exclusion of CP-conservation (defined as JCP=0J_{CP}=0) and a preference for the normal mass ordering
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