73 research outputs found

    PSS44 USTEKINUMAB IMPROVES WORK PRODUCTIVITY AND DECREASES WORKDAYS MISSED DUE TO PSORIASIS IN PATIENTS WITH MODERATE TO SEVERE PSORIASIS

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    Novel cyclic di-GMP effectors of the YajQ protein family control bacterial virulence

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    Bis-(3 ',5 ') cyclic di-guanylate (cyclic di-GMP) is a key bacterial second messenger that is implicated in the regulation of many critical processes that include motility, biofilm formation and virulence. Cyclic di-GMP influences diverse functions through interaction with a range of effectors. Our knowledge of these effectors and their different regulatory actions is far from complete, however. Here we have used an affinity pull-down assay using cyclic di-GMP-coupled magnetic beads to identify cyclic di-GMP binding proteins in the plant pathogen Xanthomonas campestris pv. campestris (Xcc). This analysis identified XC_3703, a protein of the YajQ family, as a potential cyclic di-GMP receptor. Isothermal titration calorimetry showed that the purified XC_3703 protein bound cyclic di-GMP with a high affinity (K-d similar to 2 mu M). Mutation of XC_3703 led to reduced virulence of Xcc to plants and alteration in biofilm formation. Yeast two-hybrid and far-western analyses showed that XC_3703 was able to interact with XC_2801, a transcription factor of the LysR family. Mutation of XC_2801 and XC_3703 had partially overlapping effects on the transcriptome of Xcc, and both affected virulence. Electromobility shift assays showed that XC_3703 positively affected the binding of XC_2801 to the promoters of target virulence genes, an effect that was reversed by cyclic di-GMP. Genetic and functional analysis of YajQ family members from the human pathogens Pseudomonas aeruginosa and Stenotrophomonas maltophilia showed that they also specifically bound cyclic di-GMP and contributed to virulence in model systems. The findings thus identify a new class of cyclic di-GMP effector that regulates bacterial virulence

    Large Scale Structure of the Universe

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    Galaxies are not uniformly distributed in space. On large scales the Universe displays coherent structure, with galaxies residing in groups and clusters on scales of ~1-3 Mpc/h, which lie at the intersections of long filaments of galaxies that are >10 Mpc/h in length. Vast regions of relatively empty space, known as voids, contain very few galaxies and span the volume in between these structures. This observed large scale structure depends both on cosmological parameters and on the formation and evolution of galaxies. Using the two-point correlation function, one can trace the dependence of large scale structure on galaxy properties such as luminosity, color, stellar mass, and track its evolution with redshift. Comparison of the observed galaxy clustering signatures with dark matter simulations allows one to model and understand the clustering of galaxies and their formation and evolution within their parent dark matter halos. Clustering measurements can determine the parent dark matter halo mass of a given galaxy population, connect observed galaxy populations at different epochs, and constrain cosmological parameters and galaxy evolution models. This chapter describes the methods used to measure the two-point correlation function in both redshift and real space, presents the current results of how the clustering amplitude depends on various galaxy properties, and discusses quantitative measurements of the structures of voids and filaments. The interpretation of these results with current theoretical models is also presented.Comment: Invited contribution to be published in Vol. 8 of book "Planets, Stars, and Stellar Systems", Springer, series editor T. D. Oswalt, volume editor W. C. Keel, v2 includes additional references, updated to match published versio

    Scintillation light detection in the 6-m drift-length ProtoDUNE Dual Phase liquid argon TPC

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    DUNE is a dual-site experiment for long-baseline neutrino oscillation studies, neutrino astrophysics and nucleon decay searches. ProtoDUNE Dual Phase (DP) is a 6  ×  6  ×  6 m 3 liquid argon time-projection-chamber (LArTPC) that recorded cosmic-muon data at the CERN Neutrino Platform in 2019-2020 as a prototype of the DUNE Far Detector. Charged particles propagating through the LArTPC produce ionization and scintillation light. The scintillation light signal in these detectors can provide the trigger for non-beam events. In addition, it adds precise timing capabilities and improves the calorimetry measurements. In ProtoDUNE-DP, scintillation and electroluminescence light produced by cosmic muons in the LArTPC is collected by photomultiplier tubes placed up to 7 m away from the ionizing track. In this paper, the ProtoDUNE-DP photon detection system performance is evaluated with a particular focus on the different wavelength shifters, such as PEN and TPB, and the use of Xe-doped LAr, considering its future use in giant LArTPCs. The scintillation light production and propagation processes are analyzed and a comparison of simulation to data is performed, improving understanding of the liquid argon properties

    Supernova neutrino burst detection with the Deep Underground Neutrino Experiment

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    The Deep Underground Neutrino Experiment (DUNE), a 40-kton underground liquid argon time projection chamber experiment, will be sensitive to the electron-neutrino flavor component of the burst of neutrinos expected from the next Galactic core-collapse supernova. Such an observation will bring unique insight into the astrophysics of core collapse as well as into the properties of neutrinos. The general capabilities of DUNE for neutrino detection in the relevant few- to few-tens-of-MeV neutrino energy range will be described. As an example, DUNE's ability to constrain the Îœe spectral parameters of the neutrino burst will be considered

    Experiment Simulation Configurations Approximating DUNE TDR

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    The Deep Underground Neutrino Experiment (DUNE) is a next-generation long-baseline neutrino oscillation experiment consisting of a high-power, broadband neutrino beam, a highly capable near detector located on site at Fermilab, in Batavia, Illinois, and a massive liquid argon time projection chamber (LArTPC) far detector located at the 4850L of Sanford Underground Research Facility in Lead, South Dakota. The long-baseline physics sensitivity calculations presented in the DUNE Physics TDR, and in a related physics paper, rely upon simulation of the neutrino beam line, simulation of neutrino interactions in the near and far detectors, fully automated event reconstruction and neutrino classification, and detailed implementation of systematic uncertainties. The purpose of this posting is to provide a simplified summary of the simulations that went into this analysis to the community, in order to facilitate phenomenological studies of long-baseline oscillation at DUNE. Simulated neutrino flux files and a GLoBES configuration describing the far detector reconstruction and selection performance are included as ancillary files to this posting. A simple analysis using these configurations in GLoBES produces sensitivity that is similar, but not identical, to the official DUNE sensitivity. DUNE welcomes those interested in performing phenomenological work as members of the collaboration, but also recognizes the benefit of making these configurations readily available to the wider community

    Deep Underground Neutrino Experiment (DUNE), Far Detector Technical Design Report, 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's 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 II: DUNE Physics

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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. 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 II of this TDR, DUNE Physics, describes the array of identified scientific opportunities and key goals. Crucially, we also report our best current understanding of the capability of DUNE to realize these goals, along with the detailed arguments and investigations on which this understanding is based. This TDR volume documents the scientific basis underlying the conception and design of the LBNF/DUNE experimental configurations. As a result, the description of DUNE's experimental capabilities constitutes the bulk of the document. Key linkages between requirements for successful execution of the physics program and primary specifications of the experimental configurations are drawn and summarized. This document also serves a wider purpose as a statement on the scientific potential of DUNE as a central component within a global program of frontier theoretical and experimental particle physics research. Thus, the presentation also aims to serve as a resource for the particle physics community at large
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