553 research outputs found
Detection of Anisotropies in the Gravitational-Wave Stochastic Background
By correlating the signals from a pair of gravitational-wave detectors, one
can undertake sensitive searches for a stochastic background of gravitational
radiation. If the stochastic background is anisotropic, then this correlated
signal varies harmonically with the earth's rotation. We calculate how the
harmonics of this varying signal are related to the multipole moments which
characterize the anisotropy, and give a formula for the signal-to-noise ratio
of a given harmonic. The specific case of the two LIGO (Laser Interferometric
Gravitational Observatory) detectors, which will begin operation around the
year 2000, is analyzed in detail. We consider two possible examples of
anisotropy. If the gravitational-wave stochastic background contains a dipole
intensity anisotropy whose origin (like that of the Cosmic Background
Radiation) is motion of our local system, then that anisotropy will be
observable by the advanced LIGO detector (with 90% confidence in one year of
observation) if \Omega_{gw} > 5.3 \times 10^{-8} h_{100}^{-2}. We also study
the signal produced by stochastic sources distributed in the same way as the
luminous matter in the galactic disk, and in the same way as the galactic halo.
The anisotropy due to sources distributed as the galactic disk or as the
galactic halo will be observable by the advanced LIGO detector (with 90%
confidence in one year of observation) if \Omega_{gw} > 1.8 \times 10^{-10}
h_{100}^{-2} or \Omega_{gw} > 6.7 \times 10^{-8} h_{100}^{-2}, respectively.Comment: 25 pages, Latex with RevTeX and epsfig, now includes S/N ratio
calculations, expected response from anisotropy due to local motion & sources
in galax
Orthostatic hypotension and novel blood pressure-associated gene variants: Genetics of Postural Hemodynamics (GPH) Consortium
Aims: Orthostatic hypotension (OH), an independent predictor of mortality and cardiovascular events, strongly correlates with hypertension. Recent genome-wide studies have identified new loci influencing blood pressure (BP) in populations, but their impact on OH remains unknown. Methods and Results: A total of 38 970 men and women of European ancestry from five population-based cohorts were included, of whom 2656 (6.8%) met the diagnostic criteria for OH (systolic/diastolic BP drop ≥20/10 mmHg within 3 min of standing). Thirty-one recently discovered BP-associated single nucleotide polymorphisms (SNPs) were examined using an additive genetic model and the major allele as referent. Relations between OH, orthostatic systolic BP response, and genetic variants were assessed by inverse variance-weighted meta-analysis. We found Bonferroni adjusted (P < 0.0016) significant evidence for association between OH and the EBF1 locus (rs11953630, per-minor-allele odds ratio, 95% confidence interval: 0.90, 0.85–0.96; P = 0.001), and nominal evidence (P < 0.05) for CYP17A1 (rs11191548: 0.85, 0.75–0.95; P = 0.005), and NPR3-C5orf23 (rs1173771: 0.92, 0.87–0.98; P= 0.009) loci. Among subjects not taking BP-lowering drugs, three SNPs within the NPPA/NPPB locus were nominally associated with increased risk of OH (rs17367504: 1.13, 1.02–1.24; P = 0.02, rs198358: 1.10, 1.01–1.20; P = 0.04, and rs5068: 1.22, 1.04–1.43; P = 0.01). Moreover, an ADM variant was nominally associated with continuous orthostatic systolic BP response in the adjusted model (P= 0.04). Conclusion: The overall association between common gene variants in BP loci and OH was generally weak and the direction of effect inconsistent with resting BP findings. These results suggest that OH and resting BP share few genetic components
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Biological, clinical and population relevance of 95 loci for blood lipids.
Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD
Oncostatin M Protects Rod and Cone Photoreceptors and Promotes Regeneration of Cone Outer Segment in a Rat Model of Retinal Degeneration
Retinitis pigmentosa (RP) is a group of photoreceptor degenerative disorders that lead to loss of vision. Typically, rod photoreceptors degenerate first, resulting in loss of night and peripheral vision. Secondary cone degeneration eventually affects central vision, leading to total blindness. Previous studies have shown that photoreceptors could be protected from degeneration by exogenous neurotrophic factors, including ciliary neurotrophic factor (CNTF), a member of the IL-6 family of cytokines. Using a transgenic rat model of retinal degeneration (the S334-ter rat), we investigated the effects of Oncostatin M (OSM), another member of the IL-6 family of cytokines, on photoreceptor protection. We found that exogenous OSM protects both rod and cone photoreceptors. In addition, OSM promotes regeneration of cone outer segments in early stages of cone degeneration. Further investigation showed that OSM treatment induces STAT3 phosphorylation in Müller cells but not in photoreceptors, suggesting that OSM not directly acts on photoreceptors and that the protective effects of OSM on photoreceptors are mediated by Müller cells. These findings support the therapeutic strategy using members of IL-6 family of cytokines for retinal degenerative disorders. They also provide evidence that activation of the STAT3 pathway in Müller cells promotes photoreceptor survival. Our work highlights the importance of Müller cell-photoreceptor interaction in the retina, which may serve as a model of glia-neuron interaction in general
Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.
Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition
Improving the sensitivity to gravitational-wave sources by modifying the input-output optics of advanced interferometers
We study frequency dependent (FD) input-output schemes for signal-recycling
interferometers, the baseline design of Advanced LIGO and the current
configuration of GEO 600. Complementary to a recent proposal by Harms et al. to
use FD input squeezing and ordinary homodyne detection, we explore a scheme
which uses ordinary squeezed vacuum, but FD readout. Both schemes, which are
sub-optimal among all possible input-output schemes, provide a global noise
suppression by the power squeeze factor, while being realizable by using
detuned Fabry-Perot cavities as input/output filters. At high frequencies, the
two schemes are shown to be equivalent, while at low frequencies our scheme
gives better performance than that of Harms et al., and is nearly fully
optimal. We then study the sensitivity improvement achievable by these schemes
in Advanced LIGO era (with 30-m filter cavities and current estimates of
filter-mirror losses and thermal noise), for neutron star binary inspirals, and
for narrowband GW sources such as low-mass X-ray binaries and known radio
pulsars. Optical losses are shown to be a major obstacle for the actual
implementation of these techniques in Advanced LIGO. On time scales of
third-generation interferometers, like EURO/LIGO-III (~2012), with
kilometer-scale filter cavities, a signal-recycling interferometer with the FD
readout scheme explored in this paper can have performances comparable to
existing proposals. [abridged]Comment: Figs. 9 and 12 corrected; Appendix added for narrowband data analysi
Upper limits on the strength of periodic gravitational waves from PSR J1939+2134
The first science run of the LIGO and GEO gravitational wave detectors
presented the opportunity to test methods of searching for gravitational waves
from known pulsars. Here we present new direct upper limits on the strength of
waves from the pulsar PSR J1939+2134 using two independent analysis methods,
one in the frequency domain using frequentist statistics and one in the time
domain using Bayesian inference. Both methods show that the strain amplitude at
Earth from this pulsar is less than a few times .Comment: 7 pages, 1 figure, to appear in the Proceedings of the 5th Edoardo
Amaldi Conference on Gravitational Waves, Tirrenia, Pisa, Italy, 6-11 July
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Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas
This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing
molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin
Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context
Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts
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