321 research outputs found

    Differential Modulation of Retinal Degeneration by Ccl2 and Cx3cr1 Chemokine Signalling

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    Microglia and macrophages are recruited to sites of retinal degeneration where local cytokines and chemokines determine protective or neurotoxic microglia responses. Defining the role of Ccl2-Ccr2 and Cx3cl1-Cx3cr1 signalling for retinal pathology is of particular interest because of its potential role in age-related macular degeneration (AMD). Ccl2, Ccr2, and Cx3cr1 signalling defects impair macrophage trafficking, but have, in several conflicting studies, been reported to show different degrees of age-related retinal degeneration. Ccl2/Cx3cr1 double knockout (CCDKO) mice show an early onset retinal degeneration and have been suggested as a model for AMD. In order to understand phenotypic discrepancies in different chemokine knockout lines and to study how defects in Ccl2 and/or Cx3cr1 signalling contribute to the described early onset retinal degeneration, we defined primary and secondary pathological events in CCDKO mice. To control for genetic background variability, we compared the original phenotype with that of single Ccl2, Cx3cr1 and Ccl2/Cx3cr1 double knockout mice obtained from backcrosses of CCDKO with C57Bl/6 mice. We found that the primary pathological event in CCDKO mice develops in the inferior outer nuclear layer independently of light around postnatal day P14. RPE and vascular lesions develop secondarily with increasing penetrance with age and are clinically similar to retinal telangiectasia not to choroidal neovascularisation. Furthermore, we provide evidence that a third autosomal recessive gene causes the degeneration in CCDKO mice and in all affected re-derived lines and subsequently demonstrated co-segregation of the naturally occurring RD8 mutation in the Crb1 gene. By comparing CCDKO mice with re-derived CCl2−/−/Crb1Rd8/RD8, Cx3cr1−/−/Crb1Rd8/RD8 and CCl2−/−/Cx3cr1−/−/Crb1Rd8/RD8 mice, we observed a differential modulation of the retinal phenotype by genetic background and both chemokine signalling pathways. These findings indicate that CCDKO mice are not a model of AMD, but a model for an inherited retinal degeneration that is differentially modulated by Ccl2-Ccr2 and Cx3cl1-Cx3cr1 chemokine signalling

    Long-Range Intra-Protein Communication Can Be Transmitted by Correlated Side-Chain Fluctuations Alone

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    Allosteric regulation is a key component of cellular communication, but the way in which information is passed from one site to another within a folded protein is not often clear. While backbone motions have long been considered essential for long-range information conveyance, side-chain motions have rarely been considered. In this work, we demonstrate their potential utility using Monte Carlo sampling of side-chain torsional angles on a fixed backbone to quantify correlations amongst side-chain inter-rotameric motions. Results indicate that long-range correlations of side-chain fluctuations can arise independently from several different types of interactions: steric repulsions, implicit solvent interactions, or hydrogen bonding and salt-bridge interactions. These robust correlations persist across the entire protein (up to 60 Å in the case of calmodulin) and can propagate long-range changes in side-chain variability in response to single residue perturbations

    Alignment of the CMS tracker with LHC and cosmic ray data

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    © CERN 2014 for the benefit of the CMS collaboration, published under the terms of the Creative Commons Attribution 3.0 License by IOP Publishing Ltd and Sissa Medialab srl. Any further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation and DOI.The central component of the CMS detector is the largest silicon tracker ever built. The precise alignment of this complex device is a formidable challenge, and only achievable with a significant extension of the technologies routinely used for tracking detectors in the past. This article describes the full-scale alignment procedure as it is used during LHC operations. Among the specific features of the method are the simultaneous determination of up to 200 000 alignment parameters with tracks, the measurement of individual sensor curvature parameters, the control of systematic misalignment effects, and the implementation of the whole procedure in a multi-processor environment for high execution speed. Overall, the achieved statistical accuracy on the module alignment is found to be significantly better than 10μm

    Diving below the spin-down limit:constraints on gravitational waves from the energetic young pulsar PSR J0537-6910

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    We present a search for continuous gravitational-wave signals from the young, energetic X-ray pulsar PSR J0537-6910 using data from the second and third observing runs of LIGO and Virgo. The search is enabled by a contemporaneous timing ephemeris obtained using NICER data. The NICER ephemeris has also been extended through 2020 October and includes three new glitches. PSR J0537-6910 has the largest spin-down luminosity of any pulsar and is highly active with regards to glitches. Analyses of its long-term and inter-glitch braking indices provided intriguing evidence that its spin-down energy budget may include gravitational-wave emission from a time-varying mass quadrupole moment. Its 62 Hz rotation frequency also puts its possible gravitational-wave emission in the most sensitive band of LIGO/Virgo detectors. Motivated by these considerations, we search for gravitational-wave emission at both once and twice the rotation frequency. We find no signal, however, and report our upper limits. Assuming a rigidly rotating triaxial star, our constraints reach below the gravitational-wave spin-down limit for this star for the first time by more than a factor of two and limit gravitational waves from the l = m = 2 mode to account for less than 14% of the spin-down energy budget. The fiducial equatorial ellipticity is limited to less than about 3 x 10⁻⁵, which is the third best constraint for any young pulsar

    Search for anisotropic gravitational-wave backgrounds using data from Advanced LIGO and Advanced Virgo's first three observing runs

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    We report results from searches for anisotropic stochastic gravitational-wave backgrounds using data from the first three observing runs of the Advanced LIGO and Advanced Virgo detectors. For the first time, we include Virgo data in our analysis and run our search with a new efficient pipeline called {\tt PyStoch} on data folded over one sidereal day. We use gravitational-wave radiometry (broadband and narrow band) to produce sky maps of stochastic gravitational-wave backgrounds and to search for gravitational waves from point sources. A spherical harmonic decomposition method is employed to look for gravitational-wave emission from spatially-extended sources. Neither technique found evidence of gravitational-wave signals. Hence we derive 95\% confidence-level upper limit sky maps on the gravitational-wave energy flux from broadband point sources, ranging from Fα,Θ<(0.0137.6)×108ergcm2s1Hz1,F_{\alpha, \Theta} < {\rm (0.013 - 7.6)} \times 10^{-8} {\rm erg \, cm^{-2} \, s^{-1} \, Hz^{-1}}, and on the (normalized) gravitational-wave energy density spectrum from extended sources, ranging from Ωα,Θ<(0.579.3)×109sr1\Omega_{\alpha, \Theta} < {\rm (0.57 - 9.3)} \times 10^{-9} \, {\rm sr^{-1}}, depending on direction (Θ\Theta) and spectral index (α\alpha). These limits improve upon previous limits by factors of 2.93.52.9 - 3.5. We also set 95\% confidence level upper limits on the frequency-dependent strain amplitudes of quasimonochromatic gravitational waves coming from three interesting targets, Scorpius X-1, SN 1987A and the Galactic Center, with best upper limits range from h0<(1.72.1)×1025,h_0 < {\rm (1.7-2.1)} \times 10^{-25}, a factor of 2.0\geq 2.0 improvement compared to previous stochastic radiometer searches.Comment: 23 Pages, 9 Figure

    The population of merging compact binaries inferred using gravitational waves through GWTC-3

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    We report on the population properties of 76 compact binary mergers detected with gravitational waves below a false alarm rate of 1 per year through GWTC-3. The catalog contains three classes of binary mergers: BBH, BNS, and NSBH mergers. We infer the BNS merger rate to be between 10 Gpc3yr1\rm{Gpc^{-3} yr^{-1}} and 1700 Gpc3yr1\rm{Gpc^{-3} yr^{-1}} and the NSBH merger rate to be between 7.8 Gpc3yr1\rm{Gpc^{-3}\, yr^{-1}} and 140 Gpc3yr1\rm{Gpc^{-3} yr^{-1}} , assuming a constant rate density versus comoving volume and taking the union of 90% credible intervals for methods used in this work. Accounting for the BBH merger rate to evolve with redshift, we find the BBH merger rate to be between 17.9 Gpc3yr1\rm{Gpc^{-3}\, yr^{-1}} and 44 Gpc3yr1\rm{Gpc^{-3}\, yr^{-1}} at a fiducial redshift (z=0.2). We obtain a broad neutron star mass distribution extending from 1.20.2+0.1M1.2^{+0.1}_{-0.2} M_\odot to 2.00.3+0.3M2.0^{+0.3}_{-0.3} M_\odot. We can confidently identify a rapid decrease in merger rate versus component mass between neutron star-like masses and black-hole-like masses, but there is no evidence that the merger rate increases again before 10 MM_\odot. We also find the BBH mass distribution has localized over- and under-densities relative to a power law distribution. While we continue to find the mass distribution of a binary's more massive component strongly decreases as a function of primary mass, we observe no evidence of a strongly suppressed merger rate above 60M\sim 60 M_\odot. The rate of BBH mergers is observed to increase with redshift at a rate proportional to (1+z)κ(1+z)^{\kappa} with κ=2.91.8+1.7\kappa = 2.9^{+1.7}_{-1.8} for z1z\lesssim 1. Observed black hole spins are small, with half of spin magnitudes below χi0.25\chi_i \simeq 0.25. We observe evidence of negative aligned spins in the population, and an increase in spin magnitude for systems with more unequal mass ratio

    All-sky search in early O3 LIGO data for continuous gravitational-wave signals from unknown neutron stars in binary systems

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    Rapidly spinning neutron stars are promising sources of continuous gravitational waves. Detecting such a signal would allow probing of the physical properties of matter under extreme conditions. A significant fraction of the known pulsar population belongs to binary systems. Searching for unknown neutron stars in binary systems requires specialized algorithms to address unknown orbital frequency modulations. We present a search for continuous gravitational waves emitted by neutron stars in binary systems in early data from the third observing run of the Advanced LIGO and Advanced Virgo detectors using the semicoherent, GPU-accelerated, binaryskyhough pipeline. The search analyzes the most sensitive frequency band of the LIGO detectors, 50-300 Hz. Binary orbital parameters are split into four regions, comprising orbital periods of three to 45 days and projected semimajor axes of two to 40 light seconds. No detections are reported. We estimate the sensitivity of the search using simulated continuous wave signals, achieving the most sensitive results to date across the analyzed parameter space
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