A genomic portrait of the emergence, evolution, and global spread of a methicillin-resistant staphylococcus aureus pandemic

The widespread use of antibiotics in association with high-density clinical care has driven the emergence of drug-resistant bacteria that are adapted to thrive in hospitalized patients. Of particular concern are globally disseminated methicillin-resistant Staphylococcus aureus (MRSA) clones that cause outbreaks and epidemics associated with health care. The most rapidly spreading and tenacious health-care-associated clone in Europe currently is EMRSA-15, which was first detected in the UK in the early 1990s and subsequently spread throughout Europe and beyond. Using phylogenomic methods to analyze the genome sequences for 193 S. aureus isolates, we were able to show that the current pandemic population of EMRSA-15 descends from a health-care-associated MRSA epidemic that spread throughout England in the 1980s, which had itself previously emerged from a primarily community-associated methicillin-sensitive population. The emergence of fluoroquinolone resistance in this EMRSA-15 subclone in the English Midlands during the mid-1980s appears to have played a key role in triggering pandemic spread, and occurred shortly after the first clinical trials of this drug. Genome-based coalescence analysis estimated that the population of this subclone over the last 20 yr has grown four times faster than its progenitor. Using comparative genomic analysis we identified the molecular genetic basis of 99.8% of the antimicrobial resistance phenotypes of the isolates, highlighting the potential of pathogen genome sequencing as a diagnostic tool. We document the genetic changes associated with adaptation to the hospital environment and with increasing drug resistance over time, and how MRSA evolution likely has been influenced by country-specific drug use regimens

Calorimetry for low-energy electrons using charge and light in liquid argon

Precise calorimetric reconstruction of 5-50 MeV electrons in liquid argon time projection chambers (LArTPCs) will enable the study of astrophysical neutrinos in DUNE and could enhance the physics reach of oscillation analyses. Liquid argon scintillation light has the potential to improve energy reconstruction for low-energy electrons over charge-based measurements alone. Here we demonstrate light-augmented calorimetry for low-energy electrons in a single-phase LArTPC using a sample of Michel electrons from decays of stopping cosmic muons in the LArIAT experiment at Fermilab. Michel electron energy spectra are reconstructed using both a traditional charge-based approach as well as a more holistic approach that incorporates both charge and light. A maximum-likelihood fitter, using LArIAT\u27s well-tuned simulation, is developed for combining these quantities to achieve optimal energy resolution. A sample of isolated electrons is simulated to better determine the energy resolution expected for astrophysical electron-neutrino charged-current interaction final states. In LArIAT, which has very low wire noise and an average light yield of 18 pe/MeV, an energy resolution of σ/E≃9.3%/E 1.3% is achieved. Samples are then generated with varying wire noise levels and light yields to gauge the impact of light-augmented calorimetry in larger LArTPCs. At a charge-readout signal-to-noise of S/N≃30, for example, the energy resolution for electrons below 40 MeV is improved by ≈10%, ≈20%, and ≈40% over charge-only calorimetry for average light yields of 10 pe/MeV, 20 pe/MeV, and 100 pe/MeV, respectively

Volume I. Introduction to DUNE

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

Highly-parallelized simulation of a pixelated LArTPC on a GPU

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

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

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

Exited state formation in low energy ion-atom, ion-molecule interactions With particular reference to the methodology of E.P. Sanders

The technique of Translational Energy Spectrometry (TES) has been used to study electron capture processes for a number of ion-atom and ion-molecule collision systems at energies < 1 keV/amu. The systems studied were: He"2"+ ions in H_2 and CO; helium-like C"4"+, N"5"+ and O"6"+ ions in H and H_2; and hydrogen-like C"5"+, N"6"+, and O"7"+ ions in H and H_2. For each system, the main reaction channels have been identified, and in most cases, their relative importance assessed. For He"2"+ ions in H_2 and CO, dissociative one-electron capture processes have been found to account for almost 100% of the total one-electron capture cross at low energies. Dissociative one-electron capture processes were also observed in the C"5"++H_2 and O"7"++H_2 systems. However, in the case of N"5"++H_2, two electron capture into autoionising states of N"3"+ with subsequent N"4"+(n=2) formation was found to be an important process at low energies, accounting for approximately 50% of the total electron capture cross section at 214 eV/amu. Dissociative capture processes were not found to be important for C"4"+, N"6"+, and O"6"+ systems. In the case of electron capture from an atomic hydrogen target, capture was found to occur predominantly into n=4 levels for the N"5"+, N"6"+, C"5"+, and O"6"++H systems. For the C"4"++H system, C"3"+(n=3) formation was found to be the dominant reaction channel, with O"6"+(n=5) formation the favoured reaction channel in the O"7"++H system. Total charge-changing cross sections have also measured for the N"5"++H_2 system using a simple beam attenuation method. While agreeing with previous PES measurements in the region of overlap, the measurements are in poor agreement with OPIG measurements and theoretical calculations. For some of the systems studied, Landau-Zener and classical over-barrier reaction-windows have been calculated. For N"5"+, O"5"+, and C"3"+ ions colliding with H and H_2, agreement with the present results was found to be goodSIGLEAvailable from British Library Document Supply Centre- DSC:DXN060082 / BLDSC - British Library Document Supply CentreGBUnited Kingdo