Purifying Selection in Deeply Conserved Human Enhancers Is More Consistent than in Coding Sequences

(c) 2014 De Silva et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

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

Spinning 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 signalto- 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

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

First measurement of the Hubble Constant from a Dark Standard Siren using the Dark Energy Survey Galaxies and the LIGO/Virgo Binary–Black-hole Merger GW170814

International audienceWe present a multi-messenger measurement of the Hubble constant H 0 using the binary–black-hole merger GW170814 as a standard siren, combined with a photometric redshift catalog from the Dark Energy Survey (DES). The luminosity distance is obtained from the gravitational wave signal detected by the Laser Interferometer Gravitational-Wave Observatory (LIGO)/Virgo Collaboration (LVC) on 2017 August 14, and the redshift information is provided by the DES Year 3 data. Black hole mergers such as GW170814 are expected to lack bright electromagnetic emission to uniquely identify their host galaxies and build an object-by-object Hubble diagram. However, they are suitable for a statistical measurement, provided that a galaxy catalog of adequate depth and redshift completion is available. Here we present the first Hubble parameter measurement using a black hole merger. Our analysis results in , which is consistent with both SN Ia and cosmic microwave background measurements of the Hubble constant. The quoted 68% credible region comprises 60% of the uniform prior range [20, 140] km s−1 Mpc−1, and it depends on the assumed prior range. If we take a broader prior of [10, 220] km s−1 Mpc−1, we find (57% of the prior range). Although a weak constraint on the Hubble constant from a single event is expected using the dark siren method, a multifold increase in the LVC event rate is anticipated in the coming years and combinations of many sirens will lead to improved constraints on H 0

GW170104: Observation of a 50-Solar-Mass Binary Black Hole Coalescence at Redshift 0.2

We describe the observation of GW170104, a gravitational-wave signal produced by the coalescence of a pair of stellar-mass black holes. The signal was measured on January 4, 2017 at 10: 11: 58.6 UTC by the twin advanced detectors of the Laser Interferometer Gravitational-Wave Observatory during their second observing run, with a network signal-to-noise ratio of 13 and a false alarm rate less than 1 in 70 000 years. The inferred component black hole masses are 31.2(-6.0)(+8.4)M-circle dot and 19.4(-5.9)(+5.3)M(circle dot) (at the 90% credible level). The black hole spins are best constrained through measurement of the effective inspiral spin parameter, a mass-weighted combination of the spin components perpendicular to the orbital plane, chi(eff) = -0.12(-0.30)(+0.21) . This result implies that spin configurations with both component spins positively aligned with the orbital angular momentum are disfavored. The source luminosity distance is 880(-390)(+450) Mpc corresponding to a redshift of z = 0.18(-0.07)(+0.08) . We constrain the magnitude of modifications to the gravitational-wave dispersion relation and perform null tests of general relativity. Assuming that gravitons are dispersed in vacuum like massive particles, we bound the graviton mass to m(g) <= 7.7 x 10(-23) eV/c(2). In all cases, we find that GW170104 is consistent with general relativity

Localization and Broadband Follow-Up of the Gravitational-Wave Transient GW150914

A gravitational-wave (GW) transient was identified in data recorded by the Advanced Laser InterferometerGravitational-wave Observatory (LIGO) detectors on 2015 September 14. The event, initially designated G184098and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimatesof the time, significance, and sky location of the event were shared with 63 teams of observers covering radio,optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter wedescribe the low-latency analysis of the GW data and present the sky localization of the first observed compactbinary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-rayCoordinates Network circulars, giving an overview of the participating facilities, the GW sky localizationcoverage, the timeline, and depth of the observations. As this event turned out to be a binary black hole merger,there is little expectation of a detectable electromagnetic (EM) signature. Nevertheless, this first broadbandcampaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broadcapabilities of the transient astronomy community and the observing strategies that have been developed to pursueneutron star binary merger events. Detailed investigations of the EM data and results of the EM follow-upcampaign are being disseminated in papers by the individual teams

Hypermutable Non-Synonymous Sites Are under Stronger Negative Selection

Mutation rate varies greatly between nucleotide sites of the human genome and depends both on the global genomic location and the local sequence context of a site. In particular, CpG context elevates the mutation rate by an order of magnitude. Mutations also vary widely in their effect on the molecular function, phenotype, and fitness. Independence of the probability of occurrence of a new mutation's effect has been a fundamental premise in genetics. However, highly mutable contexts may be preserved by negative selection at important sites but destroyed by mutation at sites under no selection. Thus, there may be a positive correlation between the rate of mutations at a nucleotide site and the magnitude of their effect on fitness. We studied the impact of CpG context on the rate of human–chimpanzee divergence and on intrahuman nucleotide diversity at non-synonymous coding sites. We compared nucleotides that occupy identical positions within codons of identical amino acids and only differ by being within versus outside CpG context. Nucleotides within CpG context are under a stronger negative selection, as revealed by their lower, proportionally to the mutation rate, rate of evolution and nucleotide diversity. In particular, the probability of fixation of a non-synonymous transition at a CpG site is two times lower than at a CpG site. Thus, sites with different mutation rates are not necessarily selectively equivalent. This suggests that the mutation rate may complement sequence conservation as a characteristic predictive of functional importance of nucleotide sites

The validation of the standard Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30) in pre-operative patients with brain tumor in China

<p>Abstract</p> <p>Background</p> <p>Health related quality of life (HRQOL) has increasingly emphasized on cancer patients. The psychometric properties of the standard Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30, version 3.0) in brain tumor patients wasn't proven, and there was no baseline HRQOL in brain tumor patients prior to surgery.</p> <p>Methods</p> <p>The questionnaire EORTC QLQ-C30 (version 3.0) was administered at three time points: T1, the first or the second day that patients were hospitalized after the brain tumor suspected or diagnosed by MRI or CT; T2, 1 to 2 days after T1, (T1 and T2 were both before surgery); T3, the day before discharge. Clinical variables included disease histologic types, cognitive function, and Karnofsky Performance Status.</p> <p>Results</p> <p>Cronbach's alpha coefficients for multi-item scales were greater than .70 and multitrait scaling analysis showed that most of the item-scale correlation coefficients met the standards of convergent and discriminant validity, except for the cognitive functioning scale. All scales and items exhibited construct validity. Score changes over peri-operation were observed in physical and role functioning scales. Compared with mixed cancer patients assessed after surgery but before adjuvant treatment, brain tumor patients assessed pre-surgery presented better function and fewer symptoms.</p> <p>Conclusions</p> <p>The standard Chinese version of the EORTC QLQ-C30 was overall a valid instrument to assess HRQOL in brain tumor patients in China. The baseline HRQOL in brain tumor patients pre-surgery was better than that in mixed cancer patients post-surgery. Future study should modify cognitive functioning scale and examine test-retest reliability and response validity.</p

A Wide and Deep Neural Network for Survival Analysis from Anatomical Shape and Tabular Clinical Data

We introduce a wide and deep neural network for prediction of progression from patients with mild cognitive impairment to Alzheimer's disease. Information from anatomical shape and tabular clinical data (demographics, biomarkers) are fused in a single neural network. The network is invariant to shape transformations and avoids the need to identify point correspondences between shapes. To account for right censored time-to-event data, i.e., when it is only known that a patient did not develop Alzheimer's disease up to a particular time point, we employ a loss commonly used in survival analysis. Our network is trained end-to-end to combine information from a patient's hippocampus shape and clinical biomarkers. Our experiments on data from the Alzheimer's Disease Neuroimaging Initiative demonstrate that our proposed model is able to learn a shape descriptor that augments clinical biomarkers and outperforms a deep neural network on shape alone and a linear model on common clinical biomarkers.Comment: Data and Machine Learning Advances with Multiple Views Workshop, ECML-PKDD 201

Hypermutable Non-Synonymous Sites Are under Stronger Negative Selection

Mutation rate varies greatly between nucleotide sites of the human genome and depends both on the global genomic location and the local sequence context of a site. In particular, CpG context elevates the mutation rate by an order of magnitude. Mutations also vary widely in their effect on the molecular function, phenotype, and fitness. Independence of the probability of occurrence of a new mutation's effect has been a fundamental premise in genetics. However, highly mutable contexts may be preserved by negative selection at important sites but destroyed by mutation at sites under no selection. Thus, there may be a positive correlation between the rate of mutations at a nucleotide site and the magnitude of their effect on fitness. We studied the impact of CpG context on the rate of human–chimpanzee divergence and on intrahuman nucleotide diversity at non-synonymous coding sites. We compared nucleotides that occupy identical positions within codons of identical amino acids and only differ by being within versus outside CpG context. Nucleotides within CpG context are under a stronger negative selection, as revealed by their lower, proportionally to the mutation rate, rate of evolution and nucleotide diversity. In particular, the probability of fixation of a non-synonymous transition at a CpG site is two times lower than at a CpG site. Thus, sites with different mutation rates are not necessarily selectively equivalent. This suggests that the mutation rate may complement sequence conservation as a characteristic predictive of functional importance of nucleotide sites