Modulation of host cell processes by T3SS effectors

Two of the enteric Escherichia coli pathotypes-enteropathogenic E. coli (EPEC) and enterohaemorrhagic E. coli (EHEC)-have a conserved type 3 secretion system which is essential for virulence. The T3SS is used to translocate between 25 and 50 bacterial proteins directly into the host cytosol where they manipulate a variety of host cell processes to establish a successful infection. In this chapter, we discuss effectors from EPEC/EHEC in the context of the host proteins and processes that they target-the actin cytoskeleton, small guanosine triphosphatases and innate immune signalling pathways that regulate inflammation and cell death. Many of these translocated proteins have been extensively characterised, which has helped obtain insights into the mechanisms of pathogenesis of these bacteria and also understand the host pathways they target in more detail. With increasing knowledge of the positive and negative regulation of host signalling pathways by different effectors, a future challenge is to investigate how the specific effector repertoire of each strain cooperates over the course of an infection

Design, construction and operation of the ProtoDUNE-SP Liquid Argon TPC

The ProtoDUNE-SP detector is a single-phase liquid argon time projection chamber (LArTPC) that was constructed and operated in the CERN North Area at the end of the H4 beamline. This detector is a prototype for the first far detector module of the Deep Underground Neutrino Experiment (DUNE), which will be constructed at the Sandford Underground Research Facility (SURF) in Lead, South Dakota, U.S.A. The ProtoDUNE-SP detector incorporates full-size components as designed for DUNE and has an active volume of 7 × 6 × 7.2 m3. The H4 beam delivers incident particles with well-measured momenta and high-purity particle identification. ProtoDUNE-SP's successful operation between 2018 and 2020 demonstrates the effectiveness of the single-phase far detector design. This paper describes the design, construction, assembly and operation of the detector components

Low exposure long-baseline neutrino oscillation sensitivity of the DUNE experiment

The Deep Underground Neutrino Experiment (DUNE) will produce world-leading neutrino oscillation measurements over the lifetime of the experiment. In this work, we explore DUNE's sensitivity to observe charge-parity violation (CPV) in the neutrino sector, and to resolve the mass ordering, for exposures of up to 100 kiloton-megawatt-years (kt-MW-yr). The analysis includes detailed uncertainties on the flux prediction, the neutrino interaction model, and detector effects. We demonstrate that DUNE will be able to unambiguously resolve the neutrino mass ordering at a 3σ (5σ) level, with a 66 (100) kt-MW-yr far detector exposure, and has the ability to make strong statements at significantly shorter exposures depending on the true value of other oscillation parameters. We also show that DUNE has the potential to make a robust measurement of CPV at a 3σ level with a 100 kt-MW-yr exposure for the maximally CP-violating values \delta_{\rm CP}} = \pm\pi/2. Additionally, the dependence of DUNE's sensitivity on the exposure taken in neutrino-enhanced and antineutrino-enhanced running is discussed. An equal fraction of exposure taken in each beam mode is found to be close to optimal when considered over the entire space of interest