Dysregulation of ubiquitin homeostasis and β-catenin signaling promote spinal muscular atrophy

Acknowledgements The authors are grateful to Nils Lindstrom and members of the Gillingwater laboratory for advice and assistance with this study and helpful comments on the manuscript; Neil Cashman for the NSC-34 cell line; and Ji-Long Liu for the DrosophilasmnA and smnB lines. This work was supported by grants from the SMA Trust (to T.H. Gillingwater, P.J. Young, and R. Morse), BDF Newlife (to T.H. Gillingwater and S.H. Parson), the Anatomical Society (to T.H. Gillingwater and S.H. Parson), the Muscular Dystrophy Campaign (to T.H. Gillingwater), the Jennifer Trust for Spinal Muscular Atrophy (to H.R. Fuller), the Muscular Dystrophy Association (to G.E. Morris), the Vandervell Foundation (to P.J. Young), the Medical Research Council (GO82208 to I.M. Robinson), Roslin Institute Strategic Grant funding from the BBSRC (to T.M. Wishart), the BBSRC (to C.G. Becker), the Deutsche Forschungsgemeinschaft and EU FP7/2007-2013 (grant no. 2012-305121, NeurOmics, to B. Wirth), the Center for Molecular Medicine Cologne (to B. Wirth and M. Hammerschmidt), and SMA Europe (to M.M. Reissland). We would also like to acknowledge financial support to the Gillingwater lab generated through donations to the SMASHSMA campaign.Peer reviewedPublisher PD

Mobility: Ideological Discourse and Individual Narratives

info:eu-repo/semantics/publishe

The management of HCV infected pregnant women and their children European paediatric HCV network

Background/Aims: As evidence accumulates relating to mother-to-child (vertical) transmission of hepatitis C virus (HCV), it is timely to draw up guidelines for the clinical management of HCV infected pregnant women and their children. Methods: A review of evidence from the European Paediatric HCV Network (EPHN) prospective study of HCV infected women and their children and other published studies. Meeting of EPHN clinical experts to reach a consensus on recommendations for management. Each recommendation was graded according to the level of evidence. Results/conclusions: Although several risk factors for mother-to-child transmission have been identified, none are modifiable and there are currently no interventions available to prevent vertical transmission of HCV. Data on timing of loss of maternal antibodies and reliability of diagnostic tests inform the optimum follow-up schedule for confirmation or exclusion of infection in children born to HCV infected women. Based on the current evidence, routine antenatal screening for HCV should not be introduced and neither elective caesarean section nor avoidance of breastfeeding should be recommended to HCV infected women to prevent mother-to-child transmission of HCV. HCV/HIV co-infected women should follow existing HIV guidelines. \ua9 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved

High-energy neutrino follow-up search of gravitational wave event GW150914 with ANTARES and IceCube

We present the high-energy-neutrino follow-up observations of the first gravitational wave transient GW150914 observed by the Advanced LIGO detectors on September 14, 2015. We search for coincident neutrino candidates within the data recorded by the IceCube and Antares neutrino detectors. A possible joint detection could be used in targeted electromagnetic follow-up observations, given the significantly better angular resolution of neutrino events compared to gravitational waves. We find no neutrino candidates in both temporal and spatial coincidence with the gravitational wave event. Within ±500  s of the gravitational wave event, the number of neutrino candidates detected by IceCube and Antares were three and zero, respectively. This is consistent with the expected atmospheric background, and none of the neutrino candidates were directionally coincident with GW150914. We use this nondetection to constrain neutrino emission from the gravitational-wave event.by Anand Sengupta et al

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

International audienceSpinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signal-to-noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far

Model comparison from LIGO–Virgo data on GW170817’s binary components and consequences for the merger remnant

International audienceGW170817 is the very first observation of gravitational waves originating from the coalescence of two compact objects in the mass range of neutron stars, accompanied by electromagnetic counterparts, and offers an opportunity to directly probe the internal structure of neutron stars. We perform Bayesian model selection on a wide range of theoretical predictions for the neutron star equation of state. For the binary neutron star hypothesis, we find that we cannot rule out the majority of theoretical models considered. In addition, the gravitational-wave data alone does not rule out the possibility that one or both objects were low-mass black holes. We discuss the possible outcomes in the case of a binary neutron star merger, finding that all scenarios from prompt collapse to long-lived or even stable remnants are possible. For long-lived remnants, we place an upper limit of 1.9 kHz on the rotation rate. If a black hole was formed any time after merger and the coalescing stars were slowly rotating, then the maximum baryonic mass of non-rotating neutron stars is at most , and three equations of state considered here can be ruled out. We obtain a tighter limit of for the case that the merger results in a hypermassive neutron star

Search for intermediate mass black hole binaries in the first observing run of Advanced LIGO

International audienceDuring their first observational run, the two Advanced LIGO detectors attained an unprecedented sensitivity, resulting in the first direct detections of gravitational-wave signals produced by stellar-mass binary black hole systems. This paper reports on an all-sky search for gravitational waves (GWs) from merging intermediate mass black hole binaries (IMBHBs). The combined results from two independent search techniques were used in this study: the first employs a matched-filter algorithm that uses a bank of filters covering the GW signal parameter space, while the second is a generic search for GW transients (bursts). No GWs from IMBHBs were detected; therefore, we constrain the rate of several classes of IMBHB mergers. The most stringent limit is obtained for black holes of individual mass 100  M⊙, with spins aligned with the binary orbital angular momentum. For such systems, the merger rate is constrained to be less than 0.93  Gpc−3 yr−1 in comoving units at the 90% confidence level, an improvement of nearly 2 orders of magnitude over previous upper limits

Search for intermediate-mass black hole binaries in the third observing run of Advanced LIGO and Advanced Virgo

International audienceIntermediate-mass black holes (IMBHs) span the approximate mass range 100−105 M⊙, between black holes (BHs) that formed by stellar collapse and the supermassive BHs at the centers of galaxies. Mergers of IMBH binaries are the most energetic gravitational-wave sources accessible by the terrestrial detector network. Searches of the first two observing runs of Advanced LIGO and Advanced Virgo did not yield any significant IMBH binary signals. In the third observing run (O3), the increased network sensitivity enabled the detection of GW190521, a signal consistent with a binary merger of mass ∼150 M⊙ providing direct evidence of IMBH formation. Here, we report on a dedicated search of O3 data for further IMBH binary mergers, combining both modeled (matched filter) and model-independent search methods. We find some marginal candidates, but none are sufficiently significant to indicate detection of further IMBH mergers. We quantify the sensitivity of the individual search methods and of the combined search using a suite of IMBH binary signals obtained via numerical relativity, including the effects of spins misaligned with the binary orbital axis, and present the resulting upper limits on astrophysical merger rates. Our most stringent limit is for equal mass and aligned spin BH binary of total mass 200 M⊙ and effective aligned spin 0.8 at 0.056 Gpc−3 yr−1 (90% confidence), a factor of 3.5 more constraining than previous LIGO-Virgo limits. We also update the estimated rate of mergers similar to GW190521 to 0.08 Gpc−3 yr−1.Key words: gravitational waves / stars: black holes / black hole physicsCorresponding author: W. Del Pozzo, e-mail: [email protected]† Deceased, August 2020

Open data from the first and second observing runs of Advanced LIGO and Advanced Virgo

Advanced LIGO and Advanced Virgo are monitoring the sky and collecting gravitational-wave strain data with sufficient sensitivity to detect signals routinely. In this paper we describe the data recorded by these instruments during their first and second observing runs. The main data products are gravitational-wave strain time series sampled at 16384 Hz. The datasets that include this strain measurement can be freely accessed through the Gravitational Wave Open Science Center at http://gw-openscience.org, together with data-quality information essential for the analysis of LIGO and Virgo data, documentation, tutorials, and supporting software