The Paradox of Muscle Hypertrophy in Muscular Dystrophy

Mutations in the dystrophin gene cause Duchenne and Becker muscular dystrophy in humans and syndromes in mice, dogs, and cats. Affected humans and dogs have progressive disease that leads primarily to muscle atrophy. Mdx mice progress through an initial phase of muscle hypertrophy followed by atrophy. Cats have persistent muscle hypertrophy. Hypertrophy in humans has been attributed to deposition of fat and connective tissue (pseudohypertrophy). Increased muscle mass (true hypertrophy) has been documented in animal models. Muscle hypertrophy can exaggerate postural instability and joint contractures. Deleterious consequences of muscle hypertrophy should be considered when developing treatments for muscular dystrophy

What is the Nature of EUV Waves? First STEREO 3D Observations and Comparison with Theoretical Models

One of the major discoveries of the Extreme ultraviolet Imaging Telescope (EIT) on SOHO were intensity enhancements propagating over a large fraction of the solar surface. The physical origin(s) of the so-called `EIT' waves is still strongly debated. They are considered to be either wave (primarily fast-mode MHD waves) or non-wave (pseudo-wave) interpretations. The difficulty in understanding the nature of EUV waves lies with the limitations of the EIT observations which have been used almost exclusively for their study. Their limitations are largely overcome by the SECCHI/EUVI observations on-board the STEREO mission. The EUVI telescopes provide high cadence, simultaneous multi-temperature coverage, and two well-separated viewpoints. We present here the first detailed analysis of an EUV wave observed by the EUVI disk imagers on December 07, 2007 when the STEREO spacecraft separation was $\approx 45^\circ$. Both a small flare and a CME were associated with the wave cadence, and single temperature and viewpoint coverage. These limitations are largely overcome by the SECCHI/EUVI observations on-board the STEREO mission. The EUVI telescopes provide high cadence, simultaneous multi-temperature coverage, and two well-separated viewpoints. Our findings give significant support for a fast-mode interpretation of EUV waves and indicate that they are probably triggered by the rapid expansion of the loops associated with the CME.Comment: Solar Physics, 2009, Special STEREO Issue, in pres

Advances in Global and Local Helioseismology: an Introductory Review

Helioseismology studies the structure and dynamics of the Sun's interior by observing oscillations on the surface. These studies provide information about the physical processes that control the evolution and magnetic activity of the Sun. In recent years, helioseismology has made substantial progress towards the understanding of the physics of solar oscillations and the physical processes inside the Sun, thanks to observational, theoretical and modeling efforts. In addition to the global seismology of the Sun based on measurements of global oscillation modes, a new field of local helioseismology, which studies oscillation travel times and local frequency shifts, has been developed. It is capable of providing 3D images of the subsurface structures and flows. The basic principles, recent advances and perspectives of global and local helioseismology are reviewed in this article.Comment: 86 pages, 46 figures; "Pulsation of the Sun and Stars", Lecture Notes in Physics, Vol. 832, Rozelot, Jean-Pierre; Neiner, Coralie (Eds.), 201

Genome-wide association meta-analysis identifies five novel loci for age-related hearing impairment

Previous research has shown that genes play a substantial role in determining a person's susceptibility to age-related hearing impairment. The existing studies on this subject have different results, which may be caused by difficulties in determining the phenotype or the limited number of participants involved. Here, we have gathered the largest sample to date (discovery n = 9,675; replication n = 10,963; validation n = 356,141), and examined phenotypes that represented low/mid and high frequency hearing loss on the pure tone audiogram. We identified 7 loci that were either replicated and/or validated, of which 5 loci are novel in hearing. Especially the ILDR1 gene is a high profile candidate, as it contains our top SNP, is a known hearing loss gene, has been linked to age-related hearing impairment before, and in addition is preferentially expressed within hair cells of the inner ear. By verifying all previously published SNPs, we can present a paper that combines all new and existing findings to date, giving a complete overview of the genetic architecture of age-related hearing impairment. This is of importance as age-related hearing impairment is highly prevalent in our ageing society and represents a large socio-economic burden

TIC 172900988: A transiting circumbinary planet detected in one sector of TESS data

We report the first discovery of a transiting circumbinary planet detected from a single sector of Transiting Exoplanet Survey Satellite (TESS) data. During Sector 21, the planet TIC 172900988b transited the primary star and then five days later it transited the secondary star. The binary is itself eclipsing, with a period P ≈ 19.7 days and an eccentricity e ≈ 0.45. Archival data from ASAS-SN, Evryscope, KELT, and SuperWASP reveal a prominent apsidal motion of the binary orbit, caused by the dynamical interactions between the binary and the planet. A comprehensive photodynamical analysis of the TESS, archival and follow-up data yields stellar masses and radii of M1 = 1.2384 ± 0.0007 Me and R1 = 1.3827 ± 0.0016 Re for the primary and M2 = 1.2019 ± 0.0007 Me and R2 = 1.3124 ± 0.0012 Re for the secondary. The radius of the planet is R3 = 11.25 ± 0.44 R (1.004 ± 0.039RJup). The planet's mass and orbital properties are not uniquely determined-there are six solutions with nearly equal likelihood. Specifically, we find that the planet's mass is in the range of 824 M3 981 M (2.65 M3 3.09MJup), its orbital period could be 188.8, 190.4, 194.0, 199.0, 200.4, or 204.1 days, and the eccentricity is between 0.02 and 0.09. At V = 10.141 mag, the system is accessible for high-resolution spectroscopic observations, e.g., the Rossiter-McLaughlin effect and transit spectroscopy

A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure

Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings

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

Electron and photon energy calibration with the ATLAS detector using LHC Run 2 data

This paper presents the electron and photon energy calibration obtained with the ATLAS detector using 140 fb-1 of LHC proton-proton collision data recorded at √(s) = 13 TeV between 2015 and 2018. Methods for the measurement of electron and photon energies are outlined, along with the current knowledge of the passive material in front of the ATLAS electromagnetic calorimeter. The energy calibration steps are discussed in detail, with emphasis on the improvements introduced in this paper. The absolute energy scale is set using a large sample of Z-boson decays into electron-positron pairs, and its residual dependence on the electron energy is used for the first time to further constrain systematic uncertainties. The achieved calibration uncertainties are typically 0.05% for electrons from resonant Z-boson decays, 0.4% at ET ∼ 10 GeV, and 0.3% at ET ∼ 1 TeV; for photons at ET ∼ 60 GeV, they are 0.2% on average. This is more than twice as precise as the previous calibration. The new energy calibration is validated using J/ψ → ee and radiative Z-boson decays

Performance and calibration of quark/gluon-jet taggers using 140 fb−1 of pp collisions at √s = 13 TeV with the ATLAS detector

The identification of jets originating from quarks and gluons, often referred to as quark/gluon tagging, plays an important role in various analyses performed at the Large Hadron Collider, as Standard Model measurements and searches for new particles decaying to quarks often rely on suppressing a large gluon-induced background. This paper describes the measurement of the efficiencies of quark/gluon taggers developed within the ATLAS Collaboration, using √s = 13 TeV proton–proton collision data with an integrated luminosity of 140 fb-1 collected by the ATLAS experiment. Two taggers with high performances in rejecting jets from gluon over jets from quarks are studied: one tagger is based on requirements on the number of inner-detector tracks associated with the jet, and the other combines several jet substructure observables using a boosted decision tree. A method is established to determine the quark/gluon fraction in data, by using quark/gluon-enriched subsamples defined by the jet pseudorapidity. Differences in tagging efficiency between data and simulation are provided for jets with transverse momentum between 500 GeV and 2 TeV and for multiple tagger working points