238 research outputs found

    When do fractured media become seismically anisotropic? Some implications on quantifying fracture properties

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    Fractures are pervasive features within the Earth's crust and they have a significant influence on the multi-physical response of the subsurface. The presence of coherent fracture sets often leads to observable seismic anisotropy enabling seismic techniques to remotely locate and characterise fracture systems. In this study, we confirm the general scale-dependence of seismic anisotropy and provide new results specific to shear-wave splitting (SWS). We find that SWS develops under conditions when the ratio of wavelength to fracture size (λS/d) is greater than 3, where Rayleigh scattering from coherent fractures leads to an effective anisotropy such that effective medium model (EMM) theory is qualitatively valid. When 1<λS/d<3 there is a transition from Rayleigh to Mie scattering, where no effective anisotropy develops and hence the SWS measurements are unstable. When λS/d<1 we observe geometric scattering and begin to see behaviour similar to transverse isotropy. We find that seismic anisotropy is more sensitive to fracture density than fracture compliance ratio. More importantly, we observe that the transition from scattering to an effective anisotropic regime occurs over a propagation distance between 1 and 2 wavelengths depending on the fracture density and compliance ratio. The existence of a transition zone means that inversion of seismic anisotropy parameters based on EMM will be fundamentally biased. More importantly, we observe that linear slip EMM commonly used in inverting fracture properties is inconsistent with our results and leads to errors of approximately 400% in fracture spacing (equivalent to fracture density) and 60% in fracture compliance. Although EMM representations can yield reliable estimates of fracture orientation and spatial location, our results show that EMM representations will systematically fail in providing quantitatively accurate estimates of other physical fracture properties, such as fracture density and compliance. Thus more robust and accurate quantitative estimates of in situ fracture properties will require improvements to effective medium models as well as the incorporation of full-waveform inversion techniques

    DNA damage-induced PARP1 activation confers cardiomyocyte dysfunction through NAD(+) depletion in experimental atrial fibrillation

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    Atrial fibrillation (AF) is the most common clinical tachyarrhythmia with a strong tendency to progress in time. AF progression is driven by derailment of protein homeostasis, which ultimately causes contractile dysfunction of the atria. Here we report that tachypacing-induced functional loss of atrial cardiomyocytes is precipitated by excessive poly(ADP)-ribose polymerase 1 (PARP1) activation in response to oxidative DNA damage. PARP1-mediated synthesis of ADP-ribose chains in turn depletes nicotinamide adenine dinucleotide (NAD+), induces further DNA damage and contractile dysfunction. Accordingly, NAD+ replenishment or PARP1 depletion precludes functional loss. Moreover, inhibition of PARP1 protects against tachypacing-induced NAD+ depletion, oxidative stress, DNA damage and contractile dysfunction in atrial cardiomyocytes and Drosophila. Consistently, cardiomyocytes of persistent AF patients show significant DNA damage, which correlates with PARP1 activity. The findings uncover a mechanism by which tachypacing impairs cardiomyocyte function and implicates PARP1 as a possible therapeutic target that may preserve cardiomyocyte function in clinical AF

    The Public Repository of Xenografts enables discovery and randomized phase II-like trials in mice

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    More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional, and proteomic biomarkers in both treatment-naive and relapsed/refractory disease

    Supernova 2013fc in a circumnuclear ring of a luminous infrared galaxy: the big brother of SN 1998S

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    We present photometric and spectroscopic observations of SN 2013fc, a bright type II supernova (SN) in a circumnuclear star-forming ring in the luminous infrared galaxy ESO 154-G010, observed as part of the Public ESO Spectroscopic Survey of Transient Objects. SN 2013fc is both photometrically and spectroscopically similar to the well-studied type IIn SN 1998S and to the bright type II-L SN 1979C. It exhibits an initial linear decline, followed by a short plateau phase and a tail phase with a decline too fast for 56Co decay with full γ-ray trapping. Initially, the spectrum was blue and featureless. Later on, a strong broad (˜8000 km s-1) H α emission profile became prominent. We apply a STARLIGHT stellar population model fit to the SN location (observed when the SN had faded) to estimate a high extinction of AV = 2.9 ± 0.2 mag and an age of 10_{-2}^{+3} Myr for the underlying cluster. We compare the SN to SNe 1998S and 1979C and discuss its possible progenitor star considering the similarities to these events. With a peak brightness of B = -20.46 ± 0.21 mag, SN 2013fc is 0.9 mag brighter than SN 1998S and of comparable brightness to SN 1979C. We suggest that SN 2013fc was consistent with a massive red supergiant (RSG) progenitor. Recent mass loss probably due to a strong RSG wind created the circumstellar matter illuminated through its interaction with the SN ejecta. We also observe a near-infrared excess, possibly due to newly condensed dust.</p

    Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

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    A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

    All-sky search for long-duration gravitational wave transients with initial LIGO

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    We present the results of a search for long-duration gravitational wave transients in two sets of data collected by the LIGO Hanford and LIGO Livingston detectors between November 5, 2005 and September 30, 2007, and July 7, 2009 and October 20, 2010, with a total observational time of 283.0 days and 132.9 days, respectively. The search targets gravitational wave transients of duration 10-500 s in a frequency band of 40-1000 Hz, with minimal assumptions about the signal waveform, polarization, source direction, or time of occurrence. All candidate triggers were consistent with the expected background; as a result we set 90% confidence upper limits on the rate of long-duration gravitational wave transients for different types of gravitational wave signals. For signals from black hole accretion disk instabilities, we set upper limits on the source rate density between 3.4×10-5 and 9.4×10-4 Mpc-3 yr-1 at 90% confidence. These are the first results from an all-sky search for unmodeled long-duration transient gravitational waves. © 2016 American Physical Society

    All-sky search for long-duration gravitational wave transients with initial LIGO

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    We present the results of a search for long-duration gravitational wave transients in two sets of data collected by the LIGO Hanford and LIGO Livingston detectors between November 5, 2005 and September 30, 2007, and July 7, 2009 and October 20, 2010, with a total observational time of 283.0 days and 132.9 days, respectively. The search targets gravitational wave transients of duration 10-500 s in a frequency band of 40-1000 Hz, with minimal assumptions about the signal waveform, polarization, source direction, or time of occurrence. All candidate triggers were consistent with the expected background; as a result we set 90% confidence upper limits on the rate of long-duration gravitational wave transients for different types of gravitational wave signals. For signals from black hole accretion disk instabilities, we set upper limits on the source rate density between 3.4×10-5 and 9.4×10-4 Mpc-3 yr-1 at 90% confidence. These are the first results from an all-sky search for unmodeled long-duration transient gravitational waves. © 2016 American Physical Society

    Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

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    We present results from a semicoherent search for continuous gravitational waves from the low-mass x-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the J-statistic, and by analyzing data from Advanced LIGO's second observing run. In the frequency range searched, from 60 to 650 Hz, we find no evidence of gravitational radiation. At 194.6 Hz, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95% confidence) of h095%=3.47×10-25 when marginalizing over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering. © 2019 American Physical Society

    Search for Tensor, Vector, and Scalar Polarizations in the Stochastic Gravitational-Wave Background

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    The detection of gravitational waves with Advanced LIGO and Advanced Virgo has enabled novel tests of general relativity, including direct study of the polarization of gravitational waves. While general relativity allows for only two tensor gravitational-wave polarizations, general metric theories can additionally predict two vector and two scalar polarizations. The polarization of gravitational waves is encoded in the spectral shape of the stochastic gravitational-wave background, formed by the superposition of cosmological and individually unresolved astrophysical sources. Using data recorded by Advanced LIGO during its first observing run, we search for a stochastic background of generically polarized gravitational waves. We find no evidence for a background of any polarization, and place the first direct bounds on the contributions of vector and scalar polarizations to the stochastic background. Under log-uniform priors for the energy in each polarization, we limit the energy densities of tensor, vector, and scalar modes at 95% credibility to Ω0T<5.58×10-8, Ω0V<6.35×10-8, and Ω0S<1.08×10-7 at a reference frequency f0=25 Hz. © 2018 American Physical Society
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