Prevalent mutator genotype identified in fungal pathogen Candida glabrata promotes multi-drug resistance.

The fungal pathogen Candida glabrata has emerged as a major health threat since it readily acquires resistance to multiple drug classes, including triazoles and/or echinocandins. Thus far, cellular mechanisms promoting the emergence of resistance to multiple drug classes have not been described in this organism. Here we demonstrate that a mutator phenotype caused by a mismatch repair defect is prevalent in C. glabrata clinical isolates. Strains carrying alterations in mismatch repair gene MSH2 exhibit a higher propensity to breakthrough antifungal treatment in vitro and in mouse models of colonization, and are recovered at a high rate (55% of all C. glabrata recovered) from patients. This genetic mechanism promotes the acquisition of resistance to multiple antifungals, at least partially explaining the elevated rates of triazole and multi-drug resistance associated with C. glabrata. We anticipate that identifying MSH2 defects in infecting strains may influence the management of patients on antifungal drug therapy

Veterinary Science handbook

2000 handbook for the faculty of Veterinary Scienc

Search for Lorentz and CPT violation using sidereal time dependence of neutrino flavor transitions over a short baseline

A class of extensions of the Standard Model allows Lorentz and CPT violations, which can be identified by the observation of sidereal modulations in the neutrino interaction rate. A search for such modulations was performed using the T2K on-axis near detector. Two complementary methods were used in this study, both of which resulted in no evidence of a signal. Limits on associated Lorentz and CPT-violating terms from the Standard Model extension have been derived by taking into account their correlations in this model for the first time. These results imply such symmetry violations are suppressed by a factor of more than 10 20 at the GeV scale

Scintillator ageing of the T2K near detectors from 2010 to 2021

The T2K experiment widely uses plastic scintillator as a target for neutrino interactions and an active medium for the measurement of charged particles produced in neutrino interactions at its near detector complex. Over 10 years of operation the measured light yield recorded by the scintillator based subsystems has been observed to degrade by 0.9–2.2% per year. Extrapolation of the degradation rate through to 2040 indicates the recorded light yield should remain above the lower threshold used by the current reconstruction algorithms for all subsystems. This will allow the near detectors to continue contributing to important physics measurements during the T2K-II and Hyper-Kamiokande eras. Additionally, work to disentangle the degradation of the plastic scintillator and wavelength shifting fibres shows that the reduction in light yield can be attributed to the ageing of the plastic scintillator. The long component of the attenuation length of the wavelength shifting fibres was observed to degrade by 1.3–5.4% per year, while the short component of the attenuation length did not show any conclusive degradation

Construction status and prospects of the Hyper-Kamiokande project

The Hyper-Kamiokande project is a 258-kton Water Cherenkov together with a 1.3-MW high-intensity neutrino beam from the Japan Proton Accelerator Research Complex (J-PARC). The inner detector with 186-kton fiducial volume is viewed by 20-inch photomultiplier tubes (PMTs) and multi-PMT modules, and thereby provides state-of-the-art of Cherenkov ring reconstruction with thresholds in the range of few MeVs. The project is expected to lead to precision neutrino oscillation studies, especially neutrino CP violation, nucleon decay searches, and low energy neutrino astronomy. In 2020, the project was officially approved and construction of the far detector was started at Kamioka. In 2021, the excavation of the access tunnel and initial mass production of the newly developed 20-inch PMTs was also started. In this paper, we present a basic overview of the project and the latest updates on the construction status of the project, which is expected to commence operation in 2027

Prospects for neutrino astrophysics with Hyper-Kamiokande

Hyper-Kamiokande is a multi-purpose next generation neutrino experiment. The detector is a two-layered cylindrical shape ultra-pure water tank, with its height of 64 m and diameter of 71 m. The inner detector will be surrounded by tens of thousands of twenty-inch photosensors and multi-PMT modules to detect water Cherenkov radiation due to the charged particles and provide our fiducial volume of 188 kt. This detection technique is established by Kamiokande and Super-Kamiokande. As the successor of these experiments, Hyper-K will be located deep underground, 600 m below Mt. Tochibora at Kamioka in Japan to reduce cosmic-ray backgrounds. Besides our physics program with accelerator neutrino, atmospheric neutrino and proton decay, neutrino astrophysics is an important research topic for Hyper-K. With its fruitful physics research programs, Hyper-K will play a critical role in the next neutrino physics frontier. It will also provide important information via astrophysical neutrino measurements, i.e., solar neutrino, supernova burst neutrinos and supernova relic neutrino. Here, we will discuss the physics potential of Hyper-K neutrino astrophysics

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

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

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