| 1. |
- Fresard, Laure, et al.
(författare)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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| 2. |
- Aartsen, M. G., et al.
(författare)
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An All-Sky Search For Three Flavors Of Neutrinos From Gamma-Ray Bursts With The Icecube Neutrino Observatory
- 2016
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 824:2
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Tidskriftsartikel (refereegranskat)abstract
- We present the results and methodology of a search for neutrinos produced in the decay of charged pions created in interactions between protons and gamma-rays during the prompt emission of 807 gamma-ray bursts (GRBs) over the entire sky. This three-year search is the first in IceCube for shower-like Cherenkov light patterns from electron, muon, and tau neutrinos correlated with GRBs. We detect five low-significance events correlated with five GRBs. These events are consistent with the background expectation from atmospheric muons and neutrinos. The results of this search in combination with those of IceCube's four years of searches for track-like Cherenkov light patterns from muon neutrinos correlated with Northern-Hemisphere GRBs produce limits that tightly constrain current models of neutrino and ultra high energy cosmic ray production in GRB fireballs.
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| 3. |
- Aartsen, M. G., et al.
(författare)
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Anisotropy In Cosmic-Ray Arrival Directions In The Southern Hemisphere Based On Six Years Of Data From The Icecube Detector
- 2016
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 826:2
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Tidskriftsartikel (refereegranskat)abstract
- The IceCube Neutrino Observatory accumulated a total of 318 billion cosmic-ray-induced muon events between 2009 May and 2015 May. This data set was used for a detailed analysis of the sidereal anisotropy in the arrival directions of cosmic rays in the TeV to PeV energy range. The observed global sidereal anisotropy features large regions of relative excess and deficit, with amplitudes of the order of 10(-3) up to about 100 TeV. A decomposition of the arrival direction distribution into spherical harmonics shows that most of the power is contained in the low-multipole (l <= 4) moments. However, higher multipole components are found to be statistically significant down to an angular scale of less than 10 degrees, approaching the angular resolution of the detector. Above 100 TeV, a change in the morphology of the arrival direction distribution is observed, and the anisotropy is characterized by a wide relative deficit whose amplitude increases with primary energy up to at least 5 PeV, the highest energies currently accessible to IceCube. No time dependence of the large-and small-scale structures is observed in the period of six years covered by this analysis. The high-statistics data set reveals more details of the properties of the anisotropy and is potentially able to shed light on the various physical processes that are responsible for the complex angular structure and energy evolution.
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| 4. |
- Aartsen, M. G., et al.
(författare)
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Characterization of the atmospheric muon flux in IceCube
- 2016
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Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 78, s. 1-27
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Tidskriftsartikel (refereegranskat)abstract
- Muons produced in atmospheric cosmic ray showers account for the by far dominant part of the event yield in large-volume underground particle detectors. The IceCube detector, with an instrumented volume of about a cubic kilometer, has the potential to conduct unique investigations on atmospheric muons by exploiting the large collection area and the possibility to track particles over a long distance. Through detailed reconstruction of energy deposition along the tracks, the characteristics of muon bundles can be quantified, and individual particles of exceptionally high energy identified. The data can then be used to constrain the cosmic ray primary flux and the contribution to atmospheric lepton fluxes from prompt decays of short-lived hadrons. In this paper, techniques for the extraction of physical measurements from atmospheric muon events are described and first results are presented. The multiplicity spectrum of TeV muons in cosmic ray air showers for primaries in the energy range from the knee to the ankle is derived and found to be consistent with recent results from surface detectors. The single muon energy spectrum is determined up to PeV energies and shows a clear indication for the emergence of a distinct spectral component from prompt decays of short-lived hadrons. The magnitude of the prompt flux, which should include a substantial contribution from light vector meson di-muon decays, is consistent with current theoretical predictions. The variety of measurements and high event statistics can also be exploited for the evaluation of systematic effects. In the course of this study, internal inconsistencies in the zenith angle distribution of events were found which indicate the presence of an unexplained effect outside the currently applied range of detector systematics. The underlying cause could be related to the hadronic interaction models used to describe muon production in air showers.
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| 5. |
- Aartsen, M. G., et al.
(författare)
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Differential limit on the extremely-high-energy cosmic neutrino flux in the presence of astrophysical background from nine years of IceCube data
- 2018
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Ingår i: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 98:6
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Tidskriftsartikel (refereegranskat)abstract
- We report a quasidifferential upper limit on the extremely-high-energy (EHE) neutrino flux above 5 x 10(6) GeV based on an analysis of nine years of IceCube data. The astrophysical neutrino flux measured by IceCube extends to PeV energies, and it is a background flux when searching for an independent signal flux at higher energies, such as the cosmogenic neutrino signal. We have developed a new method to place robust limits on the EHE neutrino flux in the presence of an astrophysical background, whose spectrum has yet to be understood with high precision at PeV energies. A distinct event with a deposited energy above 10(6) GeV was found in the new two-year sample, in addition to the one event previously found in the seven-year EHE neutrino search. These two events represent a neutrino flux that is incompatible with predictions for a cosmogenic neutrino flux and are considered to be an astrophysical background in the current study. The obtained limit is the most stringent to date in the energy range between 5 x 10(6) and 2 x 10(10) GeV. This result constrains neutrino models predicting a three-flavor neutrino flux of E-nu(2)phi(nu e+nu mu+nu tau) similar or equal to 2 x 10(-8) GeV/cm(2) sec sr at 10(9) GeV. A significant part of the parameter space for EHE neutrino production scenarios assuming a proton-dominated composition of ultra-high-energy cosmic rays is disfavored independently of uncertain models of the extragalactic background light which previous IceCube constraints partially relied on.
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| 6. |
- Aartsen, M. G., et al.
(författare)
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Lowering Icecube'S Energy Threshold For Point Source Searches In The Southern Sky
- 2016
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Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 824:2
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Tidskriftsartikel (refereegranskat)abstract
- Observation of a point source of astrophysical neutrinos would be a "smoking gun" signature of a cosmic-ray accelerator. While IceCube has recently discovered a diffuse flux of astrophysical neutrinos, no localized point source has been observed. Previous IceCube searches for point sources in the southern sky were restricted by either an energy threshold above a few hundred TeV or poor neutrino angular resolution. Here we present a search for southern sky point sources with greatly improved sensitivities to neutrinos with energies below 100 TeV. By selecting charged-current nu(mu) interacting inside the detector, we reduce the atmospheric background while retaining efficiency for astrophysical neutrino-induced events reconstructed with sub-degree angular resolution. The new event sample covers three years of detector data and leads to a factor of 10 improvement in sensitivity to point sources emitting below 100 TeV in the southern sky. No statistically significant evidence of point sources was found, and upper limits are set on neutrino emission from individual sources. A posteriori analysis of the highest-energy (similar to 100 TeV) starting event in the sample found that this event alone represents a 2.8 sigma deviation from the hypothesis that the data consists only of atmospheric background.
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| 7. |
- Aartsen, M. G., et al.
(författare)
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Measurement of atmospheric tau neutrino appearance with IceCube DeepCore
- 2019
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Ingår i: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 99:3
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Tidskriftsartikel (refereegranskat)abstract
- We present a measurement of atmospheric tau neutrino appearance from oscillations with three years of data from the DeepCore subarray of the IceCube Neutrino Observatory. This analysis uses atmospheric neutrinos from the full sky with reconstructed energies between 5.6 and 56 GeV to search for a statistical excess of cascadelike neutrino events which are the signature of nu(tau) interactions. For CC thorn NC (CC-only) interactions, we measure the tau neutrino normalization to be 0.73(-0.24)(+0.30) (0.57(-0.30)(+0.36)) and exclude the absence of tau neutrino oscillations at a significance of 3.2 sigma (2.0 sigma) These results are consistent with, and of similar precision to, a confirmatory IceCube analysis also presented, as well as measurements performed by other experiments.
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| 8. |
- Aartsen, M. G., et al.
(författare)
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Measurements using the inelasticity distribution of multi-TeV neutrino interactions in IceCube
- 2019
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Ingår i: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 99:3
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Tidskriftsartikel (refereegranskat)abstract
- Inelasticity, the fraction of a neutrino's energy transferred to hadrons, is a quantity of interest in the study of astrophysical and atmospheric neutrino interactions at multi-TeV energies with IceCube. In this work, a sample of contained neutrino interactions in IceCube is obtained from five years of data and classified as 2650 tracks and 965 cascades. Tracks arise predominantly from charged-current nu(mu) interactions, and we demonstrate that we can reconstruct their energy and inelasticity. The inelasticity distribution is found to be consistent with the calculation of Cooper-Sarkar et al. across the energy range from similar to 1 to similar to 100 TeV. Along with cascades from neutrinos of all flavors, we also perform a fit over the energy, zenith angle, and inelasticity distribution to characterize the flux of astrophysical and atmospheric neutrinos. The energy spectrum of diffuse astrophysical neutrinos is described well by a power law in both track and cascade samples, and a best-fit index gamma = 2.62 +/- 0.07 is found in the energy range from 3.5 TeV to 2.6 PeV. Limits are set on the astrophysical flavor composition and are compatible with a ratio of (1/3 : 1/3 : 1/3)(circle plus). Exploiting the distinct inelasticity distribution of nu(mu) and (nu) over bar (mu) interactions, the atmospheric nu(mu) to (nu) over bar (mu) flux ratio in the energy range from 770 GeV to 21 TeV is found to be 0.77(-0.25)(+0.44) times the calculation by Honda et al. Lastly, the inelasticity distribution is also sensitive to neutrino charged-current charm production. The data are consistent with a leading-order calculation, with zero charm production excluded at 91% confidence level. Future analyses of inelasticity distributions may probe new physics that affects neutrino interactions both in and beyond the Standard Model.
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| 9. |
- Aartsen, M. G., et al.
(författare)
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Neutrino oscillation studies with IceCube-DeepCore
- 2016
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Ingår i: Nuclear Physics B. - : Elsevier BV. - 0550-3213 .- 1873-1562. ; 908, s. 161-177
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Tidskriftsartikel (refereegranskat)abstract
- IceCube, a gigaton-scale neutrino detector located at the South Pole, was primarily designed to search for astrophysical neutrinos with energies of PeV and higher. This goal has been achieved with the detection of the highest energy neutrinos to date. At the other end of the energy spectrum, the DeepCore extension lowers the energy threshold of the detector to approximately 10 GeV and opens the door for oscillation studies using atmospheric neutrinos. An analysis of the disappearance of these neutrinos has been completed, with the results produced being complementary with dedicated oscillation experiments. Following a review of the detector principle and performance, the method used to make these calculations, as well as the results, is detailed. Finally, the future prospects of IceCube-DeepCore and the next generation of neutrino experiments at the South Pole (IceCube-Gen2, specifically the PINGU sub-detector) are briefly discussed.
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| 10. |
- Aartsen, M. G., et al.
(författare)
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Search For Sources Of High-Energy Neutrons With Four Years Of Data From The Icetop Detector
- 2016
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Ingår i: Astrophysical Journal. - : IOP PUBLISHING LTD. - 0004-637X .- 1538-4357. ; 830:2
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Tidskriftsartikel (refereegranskat)abstract
- IceTop is an air-shower array located on the Antarctic ice sheet at the geographic South Pole. IceTop can detect an astrophysical flux of neutrons from Galactic sources as an excess of cosmic-ray air showers arriving from the source direction. Neutrons are undeflected by the Galactic magnetic field and can typically travel 10 (E/PeV) pc before decay. Two searches are performed using 4 yr of the IceTop data set to look for a statistically significant excess of events with energies above 10 PeV (10(16) eV) arriving within a small solid angle. The all-sky search method covers from -90 degrees to approximately -50 degrees in declination. No significant excess is found. A targeted search is also performed, looking for significant correlation with candidate sources in different target sets. This search uses a higher-energy cut (100 PeV) since most target objects lie beyond 1 kpc. The target sets include pulsars with confirmed TeV energy photon fluxes and high-mass X-ray binaries. No significant correlation is found for any target set. Flux upper limits are determined for both searches, which can constrain Galactic neutron sources and production scenarios.
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