Lack of effect of sex on pig embryonic development in vivo

The effect of sex on pig conceptus development to day 12 of gestation was investigated. On day 2 of gestation, reciprocal embryo transfers were performed resulting in four groups (Yorkshire–Yorkshire, Yorkshire–Meishan, Meishan–Yorkshire and Meishan–Meishan). Conceptuses at day 12 were recovered from each recipient and diameter, as well as DNA, protein and oestradiol content were determined for individual conceptuses. The sex of individual conceptuses at day 12 was determined by amplification of a fragment of the pig SRY gene, using the polymerase chain reaction. Embryos developed more rapidly to day 12 in Yorkshire recipients, but there was no detectable effect of sex on the diameter, DNA, protein or oestradiol content of conceptuses from any transfer group. Thus, no sex effect was apparent under conditions either promoting or retarding the rate of early pig blastocyst growth. These results provide strong evidence that pig embryonic development occurs at a rate determined by uterine environment and not by sex of the conceptus

Constraints on the pMSSM from LAT Observations of Dwarf Spheroidal Galaxies

We examine the ability for the Large Area Telescope (LAT) to constrain Minimal Supersymmetric Standard Model (MSSM) dark matter through a combined analysis of Milky Way dwarf spheroidal galaxies. We examine the Lightest Supersymmetric Particles (LSPs) for a set of ~71k experimentally valid supersymmetric models derived from the phenomenological-MSSM (pMSSM). We find that none of these models can be excluded at 95% confidence by the current analysis; nevertheless, many lie within the predicted reach of future LAT analyses. With two years of data, we find that the LAT is currently most sensitive to light LSPs (m_LSP < 50 GeV) annihilating into tau-pairs and heavier LSPs annihilating into b-bbar. Additionally, we find that future LAT analyses will be able to probe some LSPs that form a sub-dominant component of dark matter. We directly compare the LAT results to direct detection experiments and show the complementarity of these search methods.Comment: 24 pages, 9 figures, submitted to JCA

Implications of LHC Searches on SUSY Particle Spectra: The pMSSM Parameter Space with Neutralino Dark Matter

We study the implications of LHC searches on SUSY particle spectra using flat scans of the 19-parameter pMSSM phase space. We apply constraints from flavour physics, g_mu-2, dark matter and earlier LEP and Tevatron searches. The sensitivity of the LHC SUSY searches with jets, leptons and missing energy is assessed by reproducing with fast simulation the recent CMS analyses after validation on benchmark points. We present results in terms of the fraction of pMSSM points compatible with all the constraints which are excluded by the LHC searches with 1 fb^{-1} and 15 fb^{-1} as a function of the mass of strongly and weakly interacting SUSY particles. We also discuss the suppression of Higgs production cross sections for the MSSM points not excluded and contrast the region of parameter space tested by the LHC data with the constraints from dark matter direct detection experiments.Comment: 14 pages, 13 figures. v2: increased statistics, to appear in EPJ

Comprehensive lung injury pathology induced by mTOR inhibitors

Molecular Targets in Oncology[Abstract] Interstitial lung disease is a rare side effect of temsirolimus treatment in renal cancer patients. Pulmonary fibrosis is characterised by the accumulation of extracellular matrix collagen, fibroblast proliferation and migration, and loss of alveolar gas exchange units. Previous studies of pulmonary fibrosis have mainly focused on the fibro-proliferative process in the lungs. However, the molecular mechanism by which sirolimus promotes lung fibrosis remains elusive. Here, we propose an overall cascade hypothesis of interstitial lung diseases that represents a common, partly underlying synergism among them as well as the lung pathogenesis side effects of mammalian target of rapamycin inhibitors

Molecular Features of Cancers Exhibiting Exceptional Responses to Treatment

A small fraction of cancer patients with advanced disease survive significantly longer than patients with clinically comparable tumors. Molecular mechanisms for exceptional responses to therapy have been identified by genomic analysis of tumor biopsies from individual patients. Here, we analyzed tumor biopsies from an unbiased cohort of 111 exceptional responder patients using multiple platforms to profile genetic and epigenetic aberrations as well as the tumor microenvironment. Integrative analysis uncovered plausible mechanisms for the therapeutic response in nearly a quarter of the patients. The mechanisms were assigned to four broad categories—DNA damage response, intracellular signaling, immune engagement, and genetic alterations characteristic of favorable prognosis—with many tumors falling into multiple categories. These analyses revealed synthetic lethal relationships that may be exploited therapeutically and rare genetic lesions that favor therapeutic success, while also providing a wealth of testable hypotheses regarding oncogenic mechanisms that may influence the response to cancer therapy. Profiling multi-platform genomics of 110 cancer patients with an exceptional therapeutic response, Wheeler et al. identify putative molecular mechanisms explaining this survival phenotype in ∼23% of cases. Therapeutic success is related to rare molecular features of responding tumors, exploiting synthetic lethality and oncogene addiction

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

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