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1.
  • Arking, D. E., et al. (författare)
  • Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
  • 2014
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:8, s. 826-836
  • Tidskriftsartikel (refereegranskat)abstract
    • The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼ 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD. © 2014 Nature America, Inc.
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2.
  • Locke, Adam E, et al. (författare)
  • Genetic studies of body mass index yield new insights for obesity biology.
  • 2015
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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3.
  • Aartsen, M. G., et al. (författare)
  • Very high-energy gamma-ray follow-up program using neutrino triggers from IceCube
  • 2016
  • Ingår i: Journal of Instrumentation. - 1748-0221 .- 1748-0221. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • We describe and report the status of a neutrino-triggered program in IceCube that generates real-time alerts for gamma-ray follow-up observations by atmospheric-Cherenkov telescopes (MAGIC and VERITAS). While IceCube is capable of monitoring the whole sky continuously, high-energy gamma-ray telescopes have restricted fields of view and in general are unlikely to be observing a potential neutrino-flaring source at the time such neutrinos are recorded. The use of neutrino-triggered alerts thus aims at increasing the availability of simultaneous multi-messenger data during potential neutrino flaring activity, which can increase the discovery potential and constrain the phenomenological interpretation of the high-energy emission of selected source classes (e. g. blazars). The requirements of a fast and stable online analysis of potential neutrino signals and its operation are presented, along with first results of the program operating between 14 March 2012 and 31 December 2015.
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4.
  • Tidskriftsartikel (refereegranskat)
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5.
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6.
  • Abbasi, R., et al. (författare)
  • The IceCube data acquisition system : Signal capture, digitization, and timestamping
  • 2009
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - 0168-9002 .- 1872-9576. ; 601:3, s. 294-316
  • Tidskriftsartikel (refereegranskat)abstract
    • IceCube is a km-scale neutrino observatory under construction at the South Pole with sensors both in the deep ice (InIce) and on the surface (IceTop). The sensors, called Digital Optical Modules (DOMs). detect, digitize and timestamp the signals from optical Cherenkov-radiation photons. The DOM Main Board (MB) data acquisition subsystem is connected to the central DAQ in the IceCube Laboratory (ICL) by a single twisted copper wire-pair and transmits packetized data on demand. Time calibration is maintained throughout the array by regular transmission to the DOMs of precisely timed analog signals, synchronized to a central GPS-disciplined clock. The design goals and consequent features, functional capabilities, and initial performance of the DOM MB, and the operation of a combined array of DOMs as a system, are described here. Experience with the first InIce strings and the IceTop stations indicates that the system design and performance goals have been achieved. (c) 2009 Elsevier B.V. All rights reserved.
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7.
  • Abbasi, R., et al. (författare)
  • SEARCH FOR HIGH-ENERGY MUON NEUTRINOS FROM THE "NAKED-EYE" GRB 080319B WITH THE IceCube NEUTRINO TELESCOPE
  • 2009
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 701:2, s. 1721-1731
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on a search with the IceCube detector for high-energy muon neutrinos from GRB 080319B, one of the brightest gamma-ray bursts (GRBs) ever observed. The fireball model predicts that a mean of 0.1 events should be detected by IceCube for a bulk Lorentz boost of the jet of 300. In both the direct on-time window of 66 s and an extended window of about 300 s around the GRB, no excess was found above background. The 90% CL upper limit on the number of track-like events from the GRB is 2.7, corresponding to a muon neutrino fluence limit of 9.5 x 10(-3) erg cm(-2) in the energy range between 120 TeV and 2.2 PeV, which contains 90% of the expected events.
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8.
  • Shungin, Dmitry, et al. (författare)
  • New genetic loci link adipose and insulin biology to body fat distribution.
  • 2015
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
  • Tidskriftsartikel (refereegranskat)abstract
    • Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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9.
  • Abbasi, R., et al. (författare)
  • Extending the Search for Neutrino Point Sources with IceCube above the Horizon
  • 2009
  • Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 103:22, s. Article ID: 221102-
  • Tidskriftsartikel (refereegranskat)abstract
    • Point source searches with the IceCube neutrino telescope have been restricted to one hemisphere, due to the exclusive selection of upward going events as a way of rejecting the atmospheric muon background. We show that the region above the horizon can be included by suppressing the background through energy-sensitive cuts. This improves the sensitivity above PeV energies, previously not accessible for declinations of more than a few degrees below the horizon due to the absorption of neutrinos in Earth. We present results based on data collected with 22 strings of IceCube, extending its field of view and energy reach for point source searches. No significant excess above the atmospheric background is observed in a sky scan and in tests of source candidates. Upper limits are reported, which for the first time cover point sources in the southern sky up to EeV energies.
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10.
  • Abbasi, R., et al. (författare)
  • Determination of the atmospheric neutrino flux and searches for new physics with AMANDA-II
  • 2009
  • Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 79, s. 102005-
  • Tidskriftsartikel (refereegranskat)abstract
    • The AMANDA-II detector, operating since 2000 in the deep ice at the geographic South Pole, has accumulated a large sample of atmospheric muon neutrinos in the 100 GeV to 10 TeV energy range. The zenith angle and energy distribution of these events can be used to search for various phenomenological signatures of quantum gravity in the neutrino sector, such as violation of Lorentz invariance or quantum decoherence. Analyzing a set of 5511 candidate neutrino events collected during 1387 days of livetime from 2000 to 2006, we find no evidence for such effects and set upper limits on violation of Lorentz invariance and quantum decoherence parameters using a maximum likelihood method. Given the absence of evidence for new flavor-changing physics, we use the same methodology to determine the conventional atmospheric muon neutrino flux above 100 GeV.
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