| 1. |
- Ederle, Joerg, et al.
(author)
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Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial
- 2010
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In: The Lancet. - 1474-547X. ; 375:9719, s. 985-997
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Journal article (peer-reviewed)abstract
- Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006), Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
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| 2. |
- Adrian-Martinez, S., et al.
(author)
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The First Combined Search For Neutrino Point-Sources In The Southern Hemisphere With The Antares And Icecube Neutrino Telescopes
- 2016
-
In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 823:1
-
Journal article (peer-reviewed)abstract
- We present the results of searches for point-like sources of neutrinos based on the first combined analysis of data from both the ANTARES and IceCube neutrino telescopes. The combination of both detectors, which differ in size and location, forms a window in the southern sky where the sensitivity to point sources improves by up to a factor of 2 compared with individual analyses. Using data recorded by ANTARES from 2007 to 2012, and by IceCube from 2008 to 2011, we search for sources of neutrino emission both across the southern sky and from a preselected list of candidate objects. No significant excess over background has been found in these searches, and flux upper limits for the candidate sources are presented for E-2.5 and E-2 power-law spectra with different energy cut-offs.
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| 3. |
- Petroff, E., et al.
(author)
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A polarized fast radio burst at low Galactic latitude
- 2017
-
In: Monthly notices of the Royal Astronomical Society. - : Oxford Academic. - 0035-8711 .- 1365-2966. ; 469:4, s. 4465-4482
-
Journal article (peer-reviewed)abstract
- We report on the discovery of a new fast radio burst (FRB), FRB 150215, with the Parkes radio telescope on 2015 February 15. The burst was detected in real time with a dispersion measure (DM) of 1105.6 +/- 0.8 pc cm(-3), a pulse duration of 2.8(-0.5)(+1.2) ms, and a measured peak flux density assuming that the burst was at beam centre of 0.7(-0.1)(+0.2) Jy. The FRB originated at a Galactic longitude and latitude of 24.66 degrees, 5.28 degrees and 25 degrees away from the Galactic Center. The burst was found to be 43 +/- 5 per cent linearly polarized with a rotation measure (RM) in the range -9 < RM < 12 rad m(-2) (95 per cent confidence level), consistent with zero. The burst was followed up with 11 telescopes to search for radio, optical, X-ray, gamma-ray and neutrino emission. Neither transient nor variable emission was found to be associated with the burst and no repeat pulses have been observed in 17.25 h of observing. The sightline to the burst is close to the Galactic plane and the observed physical properties of FRB 150215 demonstrate the existence of sight lines of anomalously low RM for a given electron column density. The Galactic RM foreground may approach a null value due to magnetic field reversals along the line of sight, a decreased total electron column density from the Milky Way, or some combination of these effects. A lower Galactic DM contribution might explain why this burst was detectable whereas previous searches at low latitude have had lower detection rates than those out of the plane.
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| 4. |
- Aartsen, M. G., et al.
(author)
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Search for non-relativistic magnetic monopoles with IceCube
- 2014
-
In: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 74:7, s. 2938-
-
Journal article (peer-reviewed)abstract
- The IceCube Neutrino Observatory is a large Cherenkov detector instrumenting of Antarctic ice. The detector can be used to search for signatures of particle physics beyond the Standard Model. Here, we describe the search for non-relativistic, magnetic monopoles as remnants of the Grand Unified Theory (GUT) era shortly after the Big Bang. Depending on the underlying gauge group these monopoles may catalyze the decay of nucleons via the Rubakov-Callan effect with a cross section suggested to be in the range of to . In IceCube, the Cherenkov light from nucleon decays along the monopole trajectory would produce a characteristic hit pattern. This paper presents the results of an analysis of first data taken from May 2011 until May 2012 with a dedicated slow-particle trigger for DeepCore, a subdetector of IceCube. A second analysis provides better sensitivity for the brightest non-relativistic monopoles using data taken from May 2009 until May 2010. In both analyses no monopole signal was observed. For catalysis cross sections of the flux of non-relativistic GUT monopoles is constrained up to a level of at a 90 % confidence level, which is three orders of magnitude below the Parker bound. The limits assume a dominant decay of the proton into a positron and a neutral pion. These results improve the current best experimental limits by one to two orders of magnitude, for a wide range of assumed speeds and catalysis cross sections.
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| 5. |
- Aartsen, M. G., et al.
(author)
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South Pole glacial climate reconstruction from multi-borehole laser particulate stratigraphy
- 2013
-
In: Journal of Glaciology. - 0022-1430 .- 1727-5652. ; 59:218, s. 1117-1128
-
Journal article (peer-reviewed)abstract
- The IceCube Neutrino Observatory and its prototype, AMANDA, were built in South Pole ice, using powerful hot-water drills to cleanly bore >100 holes to depths up to 2500 m. The construction of these particle physics detectors provided a unique opportunity to examine the deep ice sheet using a variety of novel techniques. We made high-resolution particulate profiles with a laser dust logger in eight of the boreholes during detector commissioning between 2004 and 2010. The South Pole laser logs are among the most clearly resolved measurements of Antarctic dust strata during the last glacial period and can be used to reconstruct paleoclimate records in exceptional detail. Here we use manual and algorithmic matching to synthesize our South Pole measurements with ice-core and logging data from Dome C, East Antarctica. We derive impurity concentration, precision chronology, annual-layer thickness, local spatial variability, and identify several widespread volcanic ash depositions useful for dating. We also examine the interval around similar to 74 ka recently isolated with radiometric dating to bracket the Toba (Sumatra) supereruption.
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| 6. |
- Aartsen, M. G., et al.
(author)
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First Observation of PeV-Energy Neutrinos with IceCube
- 2013
-
In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 111:2, s. 021103-
-
Journal article (peer-reviewed)abstract
- We report on the observation of two neutrino-induced events which have an estimated deposited energy in the IceCube detector of 1.04 +/- 0.16 and 1.14 +/- 0.17 PeV, respectively, the highest neutrino energies observed so far. These events are consistent with fully contained particle showers induced by neutral-current nu(e,mu,tau) ((nu) over bar (e,mu,tau)) or charged-current nu(e) ((nu) over bar (e)) interactions within the IceCube detector. The events were discovered in a search for ultrahigh energy neutrinos using data corresponding to 615.9 days effective live time. The expected number of atmospheric background is 0.082 +/- 0.004(stat)(-0.057)(+0.041)(syst). The probability of observing two or more candidate events under the atmospheric background-only hypothesis is 2.9 x 10(-3) (2.8 sigma) taking into account the uncertainty on the expected number of background events. These two events could be a first indication of an astrophysical neutrino flux; the moderate significance, however, does not permit a definitive conclusion at this time.
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| 7. |
- Aartsen, M. G., et al.
(author)
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Measurement of Atmospheric Neutrino Oscillations with IceCube
- 2013
-
In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 111:8, s. 081801-
-
Journal article (peer-reviewed)abstract
- We present the first statistically significant detection of neutrino oscillations in the high-energy regime (> 20 GeV) from an analysis of IceCube Neutrino Observatory data collected in 2010 and 2011. This measurement is made possible by the low-energy threshold of the DeepCore detector (similar to 20 GeV) and benefits from the use of the IceCube detector as a veto against cosmic-ray-induced muon background. The oscillation signal was detected within a low-energy muon neutrino sample (20-100 GeV) extracted from data collected by DeepCore. A high-energy muon neutrino sample (100 GeV-10 TeV) was extracted from IceCube data to constrain systematic uncertainties. The disappearance of low-energy upward-going muon neutrinos was observed, and the nonoscillation hypothesis is rejected with more than 5 sigma significance. In a two-neutrino flavor formalism, our data are best described by the atmospheric neutrino oscillation parameters vertical bar Delta m(32)(2)vertical bar = (2.3(-0.5)(+0.6)) x 10(-3) eV(2) and sin(2) (2 theta(23)) > 0.93, and maximum mixing is favored.
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| 8. |
- Aartsen, M. G., et al.
(author)
-
Measurement of the Atmospheric nu(e) Flux in IceCube
- 2013
-
In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 110:15, s. 151105-
-
Journal article (peer-reviewed)abstract
- We report the first measurement of the atmospheric electron neutrino flux in the energy range between approximately 80 GeV and 6 TeV, using data recorded during the first year of operation of IceCube's DeepCore low-energy extension. Techniques to identify neutrinos interacting within the DeepCore volume and veto muons originating outside the detector are demonstrated. A sample of 1029 events is observed in 281 days of data, of which 496 +/- 66(stat) +/- 88(syst) are estimated to be cascade events, including both electron neutrino and neutral current events. The rest of the sample includes residual backgrounds due to atmospheric muons and charged current interactions of atmospheric muon neutrinos. The flux of the atmospheric electron neutrinos is consistent with models of atmospheric neutrinos in this energy range. This constitutes the first observation of electron neutrinos and neutral current interactions in a very large volume neutrino telescope optimized for the TeV energy range.
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| 9. |
- Aartsen, M. G., et al.
(author)
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Observation of the cosmic-ray shadow of the Moon with IceCube
- 2014
-
In: Physical Review D. - 1550-7998 .- 1550-2368. ; 89:10, s. 102004-
-
Journal article (peer-reviewed)abstract
- We report on the observation of a significant deficit of cosmic rays from the direction of the Moon with the IceCube detector. The study of this "Moon shadow" is used to characterize the angular resolution and absolute pointing capabilities of the detector. The detection is based on data taken in two periods before the completion of the detector: between April 2008 and May 2009, when IceCube operated in a partial configuration with 40 detector strings deployed in the South Pole ice, and between May 2009 and May 2010 when the detector operated with 59 strings. Using two independent analysis methods, the Moon shadow has been observed to high significance (> 6 sigma) in both detector configurations. The observed location of the shadow center is within 0.2 degrees of its expected position when geomagnetic deflection effects are taken into account. This measurement validates the directional reconstruction capabilities of IceCube.
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| 10. |
- Aartsen, M. G., et al.
(author)
-
Search for a diffuse flux of astrophysical muon neutrinos with the IceCube 59-string configuration
- 2014
-
In: Physical Review D. - 1550-7998 .- 1550-2368. ; 89:6, s. 062007-
-
Journal article (peer-reviewed)abstract
- A search for high-energy neutrinos was performed using data collected by the IceCube Neutrino Observatory from May 2009 to May 2010, when the array was running in its 59-string configuration. The data sample was optimized to contain muon neutrino induced events with a background contamination of atmospheric muons of less than 1%. These data, which are dominated by atmospheric neutrinos, are analyzed with a global likelihood fit to search for possible contributions of prompt atmospheric and astrophysical neutrinos, neither of which have yet been identified. Such signals are expected to follow a harder energy spectrum than conventional atmospheric neutrinos. In addition, the zenith angle distribution differs for astrophysical and atmospheric signals. A global fit of the reconstructed energies and directions of observed events is performed, including possible neutrino flux contributions for an astrophysical signal and atmospheric backgrounds as well as systematic uncertainties of the experiment and theoretical predictions. The best fit yields an astrophysical signal flux for nu(mu) + (nu) over bar (mu) of E-2. Phi(E) = 0.25 x 10(-8) GeV cm(-2) s(-1) sr(-1), and a zero prompt component. Although the sensitivity of this analysis for astrophysical neutrinos surpasses the Waxman and Bahcall upper bound, the experimental limit at 90% confidence level is a factor of 1.5 above at a flux of E-2 . Phi(E) = 1.44 x 10(-8) GeV cm(-2) s(-1) sr(-1).
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| 11. |
- Aartsen, M. G., et al.
(author)
-
Search for Dark Matter Annihilations in the Sun with the 79-String IceCube Detector
- 2013
-
In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 110:13, s. 131302-
-
Journal article (peer-reviewed)abstract
- We have performed a search for muon neutrinos from dark matter annihilation in the center of the Sun with the 79-string configuration of the IceCube neutrino telescope. For the first time, the DeepCore subarray is included in the analysis, lowering the energy threshold and extending the search to the austral summer. The 317 days of data collected between June 2010 and May 2011 are consistent with the expected background from atmospheric muons and neutrinos. Upper limits are set on the dark matter annihilation rate, with conversions to limits on spin-dependent and spin-independent scattering cross sections of weakly interacting massive particles (WIMPs) on protons, for WIMP masses in the range 20-5000 GeV=c(2). These are the most stringent spin-dependent WIMP-proton cross section limits to date above 35 GeV=c(2) for most WIMP models.
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| 12. |
- Aartsen, M. G., et al.
(author)
-
Search for neutrino-induced particle showers with IceCube-40
- 2014
-
In: Physical Review D. - 1550-7998 .- 1550-2368. ; 89:10, s. 102001-
-
Journal article (peer-reviewed)abstract
- We report on the search for neutrino-induced particle showers, so-called cascades, in the IceCube-40 detector. The data for this search were collected between April 2008 and May 2009 when the first 40 IceCube strings were deployed and operational. Three complementary searches were performed, each optimized for different energy regimes. The analysis with the lowest energy threshold (2 TeV) targeted atmospheric neutrinos. A total of 67 events were found, consistent with the expectation of 41 atmospheric muons and 30 atmospheric neutrino events. The two other analyses targeted a harder, astrophysical neutrino flux. The analysis with an intermediate threshold of 25 TeV leads to the observation of 14 cascadelike events, again consistent with the prediction of 3.0 atmospheric neutrino and 7.7 atmospheric muon events. We hence set an upper limit of E-2 Phi(lim) <= 7.46 x 10(-8) GeV sr(-1) s(-1) cm(-2) (90% C.L.) on the diffuse flux from astrophysical neutrinos of all neutrino flavors, applicable to the energy range 25 TeV to 5 PeV, assuming an E-nu(-2) spectrum and a neutrino flavor ratio of 1: 1: 1 at the Earth. The third analysis utilized a larger and optimized sample of atmospheric muon background simulation, leading to a higher energy threshold of 100 TeV. Three events were found over a background prediction of 0.04 atmospheric muon events and 0.21 events from the flux of conventional and prompt atmospheric neutrinos. Including systematic errors this corresponds to a 2.7 sigma excess with respect to the background-only hypothesis. Our observation of neutrino event candidates above 100 TeV complements IceCube's recently observed evidence for high-energy astrophysical neutrinos.
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| 13. |
- Abbasi, R., et al.
(author)
-
IceTop : The surface component of IceCube
- 2013
-
In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 700, s. 188-220
-
Journal article (peer-reviewed)abstract
- IceTop, the surface component of the IceCube Neutrino Observatory at the South Pole, is an air shower array with an area of 1 km(2). The detector allows a detailed exploration of the mass composition of primary cosmic rays in the energy range from about 100 TeV to 1 EeV by exploiting the correlation between the shower energy measured in IceTop and the energy deposited by muons in the deep ice. In this paper we report on the technical design, construction and installation, the trigger and data acquisition systems as well as the software framework for calibration, reconstruction and simulation. Finally the first experience from commissioning and operating the detector and the performance as an air shower detector will be discussed.
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| 14. |
- Aartsen, M. G., et al.
(author)
-
Energy reconstruction methods in the IceCube neutrino telescope
- 2014
-
In: Journal of Instrumentation. - 1748-0221. ; 9, s. P03009-
-
Journal article (peer-reviewed)abstract
- Accurate measurement of neutrino energies is essential to many of the scientific goals of large-volume neutrino telescopes. The fundamental observable in such detectors is the Cherenkov light produced by the transit through a medium of charged particles created in neutrino interactions. The amount of light emitted is proportional to the deposited energy, which is approximately equal to the neutrino energy for v(e) and v(mu) charged-current interactions and can be used to set a lower bound on neutrino energies and to measure neutrino spectra statistically in other channels. Here we describe methods and performance of reconstructing charged-particle energies and topologies from the observed Cherenkov light yield, including techniques to measure the energies of uncontained muon tracks, achieving average uncertainties in electromagnetic-equivalent deposited energy of similar to 15% above 10 TeV.
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| 15. |
- Aartsen, M. G., et al.
(author)
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Evidence for High-Energy Extraterrestrial Neutrinos at the IceCube Detector
- 2013
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 342:6161, s. 947-
-
Journal article (peer-reviewed)abstract
- We report on results of an all-sky search for high-energy neutrino events interacting within the IceCube neutrino detector conducted between May 2010 and May 2012. The search follows up on the previous detection of two PeV neutrino events, with improved sensitivity and extended energy coverage down to about 30 TeV. Twenty-six additional events were observed, substantially more than expected from atmospheric backgrounds. Combined, both searches reject a purely atmospheric origin for the 28 events at the 4 sigma level. These 28 events, which include the highest energy neutrinos ever observed, have flavors, directions, and energies inconsistent with those expected from the atmospheric muon and neutrino backgrounds. These properties are, however, consistent with generic predictions for an additional component of extraterrestrial origin.
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| 16. |
- Aartsen, M. G., et al.
(author)
-
IceCube search for dark matter annihilation in nearby galaxies and galaxy clusters
- 2013
-
In: Physical Review D. - 1550-7998 .- 1550-2368. ; 88:12
-
Journal article (peer-reviewed)abstract
- We present the results of a first search for self-annihilating dark matter in nearby galaxies and galaxy clusters using a sample of high-energy neutrinos acquired in 339.8 days of live time during 2009/10 with the IceCube neutrino observatory in its 59-string configuration. The targets of interest include the Virgo and Coma galaxy clusters, the Andromeda galaxy, and several dwarf galaxies. We obtain upper limits on the cross section as a function of the weakly interacting massive particle mass between 300 GeV and 100 TeV for the annihilation into b (b) over bar, W+(W) over bar (-), tau(+)tau(-), mu(+)mu(-) , and nu(nu) over bar. A limit derived for the Virgo cluster, when assuming a large effect from subhalos, challenges the weakly interacting massive particle interpretation of a recently observed GeV positron excess in cosmic rays.
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| 17. |
- Aartsen, M. G., et al.
(author)
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Improvement in fast particle track reconstruction with robust statistics
- 2014
-
In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 736, s. 143-149
-
Journal article (peer-reviewed)abstract
- The IceCube project has transformed 1 km(3) of deep natural Antarctic ice into a Cherenkov detector Muon neutrinos are detected and their direction is inferred by mapping the light produced by the secondary muon track inside the volume instrumented with photomultipliers. Reconstructing the muon track from the observed light is challenging due to noise, light scattering in the ice medium, and the possibility of simultaneously having multiple muons inside the detector, resulting from the large flux of cosmic ray muons. This paper describes work on two problems: (1) the truck reconstruction problem, in which, given a set of observations, the goal is to recover the track of a muon; and (2) the coincident event problem, which is to determine how many muons are active in the detector during a time window. Rather than solving these problems by developing more complex physical models that are applied at later stages of the analysis, our approach is to augment the detector's early reconstruction with data filters and robust statistical techniques. These can be implemented at the level of on-line reconstruction and, therefore, improve all subsequent reconstructions. Using the metric of median angular resolution, a standard metric for track reconstruction, we improve the accuracy in the initial reconstruction direction by 13%. We also present improvements in measuring the number of muons in coincident events: we can accurately determine the number of muons 98% of the time.
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| 18. |
- Aartsen, M. G., et al.
(author)
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Measurement of South Pole ice transparency with the IceCube LED calibration system
- 2013
-
In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 711, s. 73-89
-
Journal article (peer-reviewed)abstract
- The IceCube Neutrino Observatory, approximately 1 km(3) in size, is now complete with 86 strings deployed in the Antarctic ice. IceCube detects the Cherenkov radiation emitted by charged particles passing through or created in the ice. To realize the full potential of the detector, the properties of light propagation in the ice in and around the detector must be well understood. This report presents a new method of fitting the model of light propagation in the ice to a data set of in situ light source events collected with IceCube. The resulting set of derived parameters, namely the measured values of scattering and absorption coefficients vs. depth, is presented and a comparison of IceCube data with simulations based on the new model is shown.
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| 19. |
- Aartsen, M. G., et al.
(author)
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Measurement of the cosmic ray energy spectrum with IceTop-73
- 2013
-
In: Physical Review D. - 1550-7998 .- 1550-2368. ; 88:4, s. 042004-
-
Journal article (peer-reviewed)abstract
- We report on the measurement of the all-particle cosmic ray energy spectrum with the IceTop air shower array in the energy range from 1.58 PeV to 1.26 EeV. The IceTop air shower array is the surface component of the IceCube Neutrino Observatory at the geographical South Pole. The analysis was performed using only information from IceTop. The data used in this work were taken from June 1, 2010 to May 13, 2011. During that period the IceTop array consisted of 73 stations, compared to 81 in its final configuration. The measured spectrum exhibits a clear deviation from a single power law above the knee around 4 PeV and below 1 EeV. We observe spectral hardening around 18 PeV and steepening around 130 PeV.
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| 20. |
- Aartsen, M. G., et al.
(author)
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Observation of Cosmic-Ray Anisotropy with the Icetop Air Shower Array
- 2013
-
In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 765:1, s. 55-
-
Journal article (peer-reviewed)abstract
- We report on the observation of anisotropy in the arrival direction distribution of cosmic rays at PeV energies. The analysis is based on data taken between 2009 and 2012 with the IceTop air shower array at the south pole. IceTop, an integral part of the IceCube detector, is sensitive to cosmic rays between 100 TeV and 1 EeV. With the current size of the IceTop data set, searches for anisotropy at the 10(-3) level can, for the first time, be extended to PeV energies. We divide the data set into two parts with median energies of 400 TeV and 2 PeV, respectively. In the low energy band, we observe a strong deficit with an angular size of about 30 degrees and an amplitude of (-1.58 +/- 0.46(stat) +/- 0.52(sys)) x 10(-3) at a location consistent with previous observations of cosmic rays with the IceCube neutrino detector. The study of the high energy band shows that the anisotropy persists to PeV energies and increases in amplitude to (-3.11 +/- 0.38(stat) +/- 0.96(sys)) x 10(-3).
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| 21. |
- Aartsen, M. G., et al.
(author)
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Probing the origin of cosmic rays with extremely high energy neutrinos using the IceCube Observatory
- 2013
-
In: Physical Review D. - 1550-7998 .- 1550-2368. ; 88:11
-
Journal article (peer-reviewed)abstract
- We have searched for extremely high energy neutrinos using data taken with the IceCube detector between May 2010 and May 2012. Two neutrino-induced particle shower events with energies around 1 PeV were observed, as reported previously. In this work, we investigate whether these events could originate from cosmogenic neutrinos produced in the interactions of ultrahigh energy cosmic rays with ambient photons while propagating through intergalactic space. Exploiting IceCube's large exposure for extremely high energy neutrinos and the lack of observed events above 100 PeV, we can rule out the corresponding models at more than 90% confidence level. The model-independent quasidifferential 90% C. L. upper limit, which amounts to E-2 phi(nu e)+(nu mu)+(nu tau) = 1.2 x 10(-7) GeV cm(-2) s(-1) sr(-1) at 1 EeV, provides the most stringent constraint in the energy range from 10 PeV to 10 EeV. Our observation disfavors strong cosmological evolution of the highest energy cosmic-ray sources such as the Fanaroff-Riley type II class of radio galaxies.
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| 22. |
- Aartsen, M. G., et al.
(author)
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Search for Galactic PeV gamma rays with the IceCube Neutrino Observatory
- 2013
-
In: Physical Review D. - 1550-7998 .- 1550-2368. ; 87:6, s. 062002-
-
Journal article (peer-reviewed)abstract
- Gamma-ray induced air showers are notable for their lack of muons, compared to hadronic showers. Hence, air shower arrays with large underground muon detectors can select a sample greatly enriched in photon showers by rejecting showers containing muons. IceCube is sensitive to muons with energies above similar to 500 GeV at the surface, which provides an efficient veto system for hadronic air showers with energies above 1 PeV. One year of data from the 40-string IceCube configuration was used to perform a search for point sources and a Galactic diffuse signal. No sources were found, resulting in a 90% C.L. upper limit on the ratio of gamma rays to cosmic rays of 1.2 x 10(-3) for the flux coming from the Galactic plane region (-80 degrees less than or similar to l less than or similar to -30 degrees; -10 degrees less than or similar to b less than or similar to 5 degrees) in the energy range 1.2-6.0 PeV. In the same energy range, point source fluxes with E-2 spectra have been excluded at a level of (E/TeV)(2)d Phi/dE similar to 10(-12)-10(-11) cm(-2) s(-1) TeV-1 depending on source declination. The complete IceCube detector will have a better sensitivity (due to the larger detector size), improved reconstruction, and vetoing techniques. Preliminary data from the nearly final IceCube detector configuration have been used to estimate the 5-yr sensitivity of the full detector. It is found to be more than an order of magnitude better, allowing the search for PeV extensions of known TeV gamma-ray emitters.
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| 23. |
- Aartsen, M. G., et al.
(author)
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SEARCH FOR TIME-INDEPENDENT NEUTRINO EMISSION FROM ASTROPHYSICAL SOURCES WITH 3 yr OF IceCube DATASearch for time-independent neutrino emission from astrophysical sources with 3 yr of icecube data
- 2013
-
In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 779:2, s. 132-
-
Journal article (peer-reviewed)abstract
- We present the results of a search for neutrino point sources using the IceCube data collected between 2008 April and 2011 May with three partially completed configurations of the detector: the 40-, 59-, and 79-string configurations. The live-time of this data set is 1040 days. An unbinned maximum likelihood ratio test was used to search for an excess of neutrinos above the atmospheric background at any given direction in the sky. By adding two more years of data with improved event selection and reconstruction techniques, the sensitivity was improved by a factor of 3.5 or more with respect to the previously published results obtained with the 40-string configuration of IceCube. We performed an all-sky survey and a dedicated search using a catalog of a priori selected objects observed by other telescopes. In both searches, the data are compatible with the background-only hypothesis. In the absence of evidence for a signal, we set upper limits on the flux of muon neutrinos. For an E-2 neutrino spectrum, the observed limits are (0.9-5) x 10(-12) TeV-1 cm(-2) s(-1) for energies between 1 TeV and 1 PeV in the northern sky and (0.9-23.2) x 10(-12) TeV-1 cm(-2) s(-1) for energies between 10(2) TeV and 10(2) PeV in the southern sky. We also report upper limits for neutrino emission from groups of sources that were selected according to theoretical models or observational parameters and analyzed with a stacking approach. Some of the limits presented already reach the level necessary to quantitatively test current models of neutrino emission.
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| 24. |
- Aartsen, M. G., et al.
(author)
-
The IceProd framework : Distributed data processing for the IceCube neutrino observatory
- 2015
-
In: Journal of Parallel and Distributed Computing. - : Elsevier BV. - 0743-7315 .- 1096-0848. ; 75, s. 198-211
-
Journal article (peer-reviewed)abstract
- IceCube is a one-gigaton instrument located at the geographic South Pole, designed to detect cosmic neutrinos, identify the particle nature of dark matter, and study high-energy neutrinos themselves. Simulation of the IceCube detector and processing of data require a significant amount of computational resources. This paper presents the first detailed description of IceProd, a lightweight distributed management system designed to meet these requirements. It is driven by a central database in order to manage mass production of simulations and analysis of data produced by the IceCube detector. IceProd runs as a separate layer on top of other middleware and can take advantage of a variety of computing resources, including grids and batch systems such as CREAM, HTCondor, and PBS. This is accomplished by a set of dedicated daemons that process job submission in a coordinated fashion through the use of middleware plugins that serve to abstract the details of job submission and job management from the framework. (C) 2014 Elsevier Inc. All rights reserved.
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| 25. |
- Abbasi, R., et al.
(author)
-
An improved method for measuring muon energy using the truncated mean of dE/dx
- 2013
-
In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 703, s. 190-198
-
Journal article (peer-reviewed)abstract
- The measurement of muon energy is critical for many analyses in large Cherenkov detectors, particularly those that involve separating extraterrestrial neutrinos from the atmospheric neutrino background. Muon energy has traditionally been determined by measuring the specific energy loss (dE/dx) along the muon's path and relating the dE/dx to the muon energy. Because high-energy muons (Eμ>1TeV) lose energy randomly, the spread in dE/dx values is quite large, leading to a typical energy resolution of 0.29 in log10(Eμ) for a muon observed over a 1 km path length in the IceCube detector. In this paper, we present an improved method that uses a truncated mean and other techniques to determine the muon energy. The muon track is divided into separate segments with individual dE/dx values. The elimination of segments with the highest dE/dx results in an overall dE/dx that is more closely correlated to the muon energy. This method results in an energy resolution of 0.22 in log10(Eμ), which gives a 26% improvement. This technique is applicable to any large water or ice detector and potentially to large scintillator or liquid argon detectors.
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| 26. |
- Abbasi, R., et al.
(author)
-
Cosmic ray composition and energy spectrum from 1-30 PeV using the 40-string configuration of IceTop and IceCube
- 2013
-
In: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 42, s. 15-32
-
Journal article (peer-reviewed)abstract
- The mass composition of high energy cosmic rays depends on their production, acceleration, and propagation. The study of cosmic ray composition can therefore reveal hints of the origin of these particles. At the South Pole, the IceCube Neutrino Observatory is capable of measuring two components of cosmic ray air showers in coincidence: the electromagnetic component at high altitude (2835 m) using the IceTop surface array, and the muonic component above ∼1 TeV using the IceCube array. This unique detector arrangement provides an opportunity for precision measurements of the cosmic ray energy spectrum and composition in the region of the knee and beyond. We present the results of a neural network analysis technique to study the cosmic ray composition and the energy spectrum from 1 PeV to 30 PeV using data recorded using the 40-string/40-station configuration of the IceCube Neutrino Observatory.
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| 27. |
- Abbasi, R., et al.
(author)
-
Lateral distribution of muons in IceCube cosmic ray events
- 2013
-
In: Physical Review D. - 1550-7998 .- 1550-2368. ; 87:1, s. 012005-
-
Journal article (peer-reviewed)abstract
- In cosmic ray air showers, the muon lateral separation from the center of the shower is a measure of the transverse momentum that the muon parent acquired in the cosmic ray interaction. IceCube has observed cosmic ray interactions that produce muons laterally separated by up to 400 m from the shower core, a factor of 6 larger distance than previous measurements. These muons originate in high p(T) (> 2 GeV/c) interactions from the incident cosmic ray, or high-energy secondary interactions. The separation distribution shows a transition to a power law at large values, indicating the presence of a hard p(T) component that can be described by perturbative quantum chromodynamics. However, the rates and the zenith angle distributions of these events are not well reproduced with the cosmic ray models tested here, even those that include charm interactions. This discrepancy may be explained by a larger fraction of kaons and charmed particles than is currently incorporated in the simulations. DOI: 10.1103/PhysRevD.87.012005
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| 28. |
- Abbasi, R., et al.
(author)
-
Search for relativistic magnetic monopoles with IceCube
- 2013
-
In: Physical Review D. - 1550-7998 .- 1550-2368. ; 87:2, s. 022001-
-
Journal article (peer-reviewed)abstract
- We present the first results in the search for relativistic magnetic monopoles with the IceCube detector, a subsurface neutrino telescope located in the South Polar ice cap containing a volume of 1 km(3). This analysis searches data taken on the partially completed detector during 2007 when roughly 0.2 km(3) of ice was instrumented. The lack of candidate events leads to an upper limit on the flux of relativistic magnetic monopoles of Phi(90%C.L.) similar to 3 x 10(-18) cm(-2) sr(-1) s(-1) for beta >= 0.8. This is a factor of 4 improvement over the previous best experimental flux limits up to a Lorentz boost gamma below 10(7). This result is then interpreted for a wide range of mass and kinetic energy values.
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| 29. |
- Abbasi, R., et al.
(author)
-
Searches for high-energy neutrino emission in the galaxy with the combined icecube-amanda detector
- 2013
-
In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 763:1, s. 33-
-
Journal article (peer-reviewed)abstract
- We report on searches for neutrino sources at energies above 200 GeV in the Northern sky of the Galactic plane, using the data collected by the South Pole neutrino telescope, IceCube, and AMANDA. The Galactic region considered in this work includes the local arm toward the Cygnus region and our closest approach to the Perseus Arm. The searches are based on the data collected between 2007 and 2009. During this time AMANDA was an integrated part of IceCube, which was still under construction and operated with 22 strings (2007-2008) and 40 strings (2008-2009) of optical modules deployed in the ice. By combining the advantages of the larger IceCube detector with the lower energy threshold of the more compact AMANDA detector, we obtain an improved sensitivity at energies below ∼10 TeV with respect to previous searches. The analyses presented here are a scan for point sources within the Galactic plane, a search optimized for multiple and extended sources in the Cygnus region, which might be below the sensitivity of the point source scan, and studies of seven pre-selected neutrino source candidates. For one of them, Cygnus X-3, a time-dependent search for neutrino emission in coincidence with observed radio and X-ray flares has been performed. No evidence of a signal is found, and upper limits are reported for each of the searches. We investigate neutrino spectra proportional to E -2 and E -3 in order to cover the entire range of possible neutrino spectra. The steeply falling E -3 neutrino spectrum can also be used to approximate neutrino energy spectra with energy cutoffs below 50 TeV since these result in a similar energy distribution of events in the detector. For the region of the Galactic plane visible in the Northern sky, the 90% confidence level muon neutrino flux upper limits are in the range E 3 dN/dE ∼ 5.4-19.5 × 10-11 TeV2 cm-2 s-1 for point-like neutrino sources in the energy region [180.0 GeV-20.5 TeV]. These represent the most stringent upper limits for soft-spectra neutrino sources within the Galaxy reported to date.
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| 30. |
- Scott, P., et al.
(author)
-
Use of event-level neutrino telescope data in global fits for theories of new physics
- 2012
-
In: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :11, s. 057-
-
Journal article (peer-reviewed)abstract
- We present a fast likelihood method for including event-level neutrino telescope data in parameter explorations of theories for new physics, and announce its public release as part of DarkSUSY 5.0.6. Our construction includes both angular and spectral information about neutrino events, as well as their total number. We also present a corresponding measure for simple model exclusion, which can be used for single models without reference to the rest of a parameter space. We perform a number of supersymmetric parameter scans with IceCube data to illustrate the utility of the method: example global fits and a signal recovery in the constrained minimal supersymmetric standard model (CMSSM), and a model exclusion exercise in a 7-parameter phenomenological version of the MSSM. The final IceCube detector con figuration will probe almost the entire focus-point region of the CMSSM, as well as a number of MSSM-7 models that will not otherwise be accessible to e. g. direct detection. Our method accurately recovers the mock signal, and provides tight constraints on model parameters and derived quantities. We show that the inclusion of spectral information significantly improves the accuracy of the recovery, providing motivation for its use in future IceCube analyses.
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| 31. |
- Aguilar, J A, et al.
(author)
-
Transmission of light in deep sea water at the site of the ANTARES neutrino telescope
- 2005
-
In: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 23:1, s. 131-155
-
Journal article (peer-reviewed)abstract
- The ANTARES neutrino telescope is a large photomultiplier array designed to detect neutrino-induced upward-going muons by their Cherenkov radiation. Understanding the absorption and scattering of light in the deep Mediterranean is fundamental to optimising the design and performance of the detector. This paper presents measurements of blue and UV light transmission at the ANTARES site taken between 1997 and 2000. The derived values for the scattering length and the angular distribution of particulate scattering were found to be highly correlated, and results are therefore presented in terms of an absorption length;,ab, and an effective scattering length lambda(sct)(eff). The values for blue (UV) light are found to be lambda(abs) similar or equal to 60(26) m, lambda(sct)(eff similar or equal to) 265(122) m, with significant (similar to15%) time variability. Finally, the results of ANTARES simulations showing the effect of these water properties on the anticipated performance of the detector are presented. (C) 2004 Elsevier B.V. All rights reserved.
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| 32. |
- Ageron, M., et al.
(author)
-
Studies of a full-scale mechanical prototype line for the ANTARES neutrino telescope and tests of a prototype instrument for deep-sea acoustic measurements
- 2007
-
In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 581:3, s. 695-708
-
Journal article (peer-reviewed)abstract
- full-scale mechanical prototype line was deployed to a depth of 2500 m to test the leak tightness of the electronics containers and the pressure-resistant properties of an electromechanical cable under evaluation for use in the ANTARES deep-sea neutrino telescope. During a month-long immersion study, line parameter data were taken using miniature autonomous data loggers and shore-based optical time domain reflectometry. Details of the mechanical prototype line, the electromechanical cable and data acquisition are presented. Data taken during the immersion study revealed deficiencies in the pressure resistance of the electromechanical cable terminations at the entry points to the electronics containers. The improvements to the termination, which have been integrated into subsequent detection lines, are discussed. The line also allowed deep-sea acoustic measurements with a prototype hydrophone system. The technical setup of this system is described, and the first results of the data analysis are presented. (c) 2007 Elsevier B.V. All rights reserved.
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| 33. |
- Aguilar, J A, et al.
(author)
-
Study of large hemispherical photomultiplier tubes for the ANTARES neutrino telescope
- 2005
-
In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 555:1-2, s. 132-141
-
Journal article (peer-reviewed)abstract
- The ANTARES neutrino telescope, to be immersed depth in the Mediterranean Sea, will consist of a three-dimensional matrix of 900 large area photomultiplier tubes housed in pressure-resistant glass spheres. The selection of the optimal photomultiplier was a critical step for the project and required an intensive phase of tests and developments carried out in close collaboration with the main manufacturers worldwide. This paper provides an overview of the tests performed by the collaboration and describes in detail the features of the photomultiplier tube chosen for ANTARES. (c) 2005 Elsevier B.V. All rights reserved.
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| 34. |
- Ageron, M., et al.
(author)
-
The ANTARES optical beacon system
- 2007
-
In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 578:3, s. 498-509
-
Journal article (peer-reviewed)abstract
- ANTARES is a neutrino telescope being deployed in the Mediterranean Sea. It consists of a three-dimensional array of photomultiplier tubes that can detect the Cherenkov light induced by charged particles produced in the interactions of neutrinos with the surrounding medium. High angular resolution can be achieved, in particular, when a muon is produced, provided that the Cherenkov photons are detected with sufficient timing precision. Considerations of the intrinsic time uncertainties stemming from the transit time spread in the photomultiplier tubes and the mechanism of transmission of light in sea water lead to the conclusion that a relative time accuracy of the order of 0.5 ns is desirable. Accordingly, different time calibration systems have been developed for the ANTARES telescope. In this article, a system based on Optical Beacons, a set of external and well-controlled pulsed light sources located throughout the detector, is described. This calibration system takes into account the optical properties of sea water, which is used as the detection volume of the ANTARES telescope. The design, tests, construction and first results of the two types of beacons, LED and laser-based, are presented. (C) 2007 Elsevier B.V. All rights reserved.
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| 35. |
- Aguilar, J. A., et al.
(author)
-
First results of the instrumentation line for the deep-sea ANTARES neutrino telescope
- 2006
-
In: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 26:4-5, s. 314-324
-
Journal article (peer-reviewed)abstract
- In 2005, the ANTARES Collaboration deployed and operated at a depth of 2500 m a so-called Mini Instrumentation Line equipped with Optical Modules (MILOM) at the ANTARES site. The various data acquired during the continuous operation from April to December 2005 of the MILOM confirm the satisfactory performance of the Optical Modules, their front-end electronics and readout system. as well as the calibration devices of the detector. The in situ measurement of the Optical Module time response yields a resolution better than 0.5 ns. The performance of the acoustic positioning system, which enables the spatial reconstruction of the ANTARES detector with a precision of about 10 cm, is verified. These results demonstrate that with the full ANTARES neutrino telescope the design angular resolution of better than 0.3 degrees can be realistically achieved.
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| 36. |
- Aguilar, J. A., et al.
(author)
-
The data acquisition system for the ANTARES neutrino telescope
- 2007
-
In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 570:1, s. 107-116
-
Journal article (peer-reviewed)abstract
- The ANTARES neutrino telescope is being constructed in the Mediterranean Sea. It consists of a large three-dimensional array of photo-multiplier tubes. The data acquisition system of the detector takes care of the digitisation of the photo-multiplier tube signals, data transport, data filtering, and data storage. The detector is operated using a control program interfaced with all elements. The design and the implementation of the data acquisition system are described. (c) 2006 Elsevier B.V. All rights reserved.
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| 37. |
- Medema, M. H., et al.
(author)
-
Minimum Information about a Biosynthetic Gene cluster
- 2015
-
In: Nature Chemical Biology. - : Springer Science and Business Media LLC. - 1552-4450 .- 1552-4469. ; 11:9, s. 625-631
-
Research review (peer-reviewed)abstract
- A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.
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| 38. |
- Ageron, M., et al.
(author)
-
Performance of the first ANTARES detector line
- 2009
-
In: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 31:4, s. 277-283
-
Journal article (peer-reviewed)abstract
- In this paper we report on the data recorded with the first Antares detector line. The line was deployed on the 14th of February 2006 and was connected to the readout 2 weeks later. Environmental data for one and a half years of running are shown. Measurements of atmospheric muons from data taken from selected runs during the first 6 months of operation are presented. Performance figures in terms of time residuals and angular resolution are given. Finally the angular distribution of atmospheric muons is presented and from this the depth profile of the muon intensity is derived. (C) 2009 Elsevier B.V. All rights reserved.
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| 39. |
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| 40. |
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| 41. |
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| 42. |
- Fall, Tove, et al.
(author)
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The Role of Adiposity in Cardiometabolic Traits : A Mendelian Randomization Analysis
- 2013
-
In: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 10:6, s. e1001474-
-
Journal article (peer-reviewed)abstract
- Background: The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach. Methods and Findings: We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses. Age-and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p<0.05). For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p<0.05). The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimate (p = 0.001). Conclusions: We provide novel evidence for a causal relationship between adiposity and heart failure as well as between adiposity and increased liver enzymes.
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| 43. |
- Freitag, Daniel F., et al.
(author)
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Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis
- 2015
-
In: The Lancet Diabetes & Endocrinology. - 2213-8595. ; 3:4, s. 243-253
-
Journal article (peer-reviewed)abstract
- Background To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods We created a genetic score combining the effects of alleles of two common variants (rs6743376 and rs1542176) that are located upstream of IL1RN, the gene encoding the IL-1 receptor antagonist (IL-1Ra; an endogenous inhibitor of both IL-1 alpha and IL-1 beta); both alleles increase soluble IL-1Ra protein concentration. We compared effects on inflammation biomarkers of this genetic score with those of anakinra, the recombinant form of IL-1Ra, which has previously been studied in randomised trials of rheumatoid arthritis and other inflammatory disorders. In primary analyses, we investigated the score in relation to rheumatoid arthritis and four cardiometabolic diseases (type 2 diabetes, coronary heart disease, ischaemic stroke, and abdominal aortic aneurysm; 453 411 total participants). In exploratory analyses, we studied the relation of the score to many disease traits and to 24 other disorders of proposed relevance to IL-1 signalling (746 171 total participants). Findings For each IL1RN minor allele inherited, serum concentrations of IL-1Ra increased by 0.22 SD (95% CI 0.18-0.25; 12.5%; p=9.3 x 10(-33)), concentrations of interleukin 6 decreased by 0.02 SD (-0.04 to -0.01; -1,7%; p=3.5 x 10(-3)), and concentrations of C-reactive protein decreased by 0.03 SD (-0.04 to -0.02; -3.4%; p=7.7 x 10(-14)). We noted the effects of the genetic score on these inflammation biomarkers to be directionally concordant with those of anakinra. The allele count of the genetic score had roughly log-linear, dose-dependent associations with both IL-1Ra concentration and risk of coronary heart disease. For people who carried four IL-1Ra-raising alleles, the odds ratio for coronary heart disease was 1.15 (1.08-1.22; p=1.8 x 10(-6)) compared with people who carried no IL-1Ra-raising alleles; the per-allele odds ratio for coronary heart disease was 1.03 (1.02-1.04; p=3.9 x 10(-10)). Perallele odds ratios were 0.97 (0.95-0.99; p=9.9 x 10(-4)) for rheumatoid arthritis, 0.99 (0.97-1.01; p=0.47) for type 2 diabetes, 1.00 (0.98-1.02; p=0.92) for ischaemic stroke, and 1.08 (1.04-1.12; p=1.8 x 10(-5)) for abdominal aortic aneurysm. In exploratory analyses, we observed per-allele increases in concentrations of proatherogenic lipids, including LDL-cholesterol, but no clear evidence of association for blood pressure, glycaemic traits, or any of the 24 other disorders studied. Modelling suggested that the observed increase in LDL-cholesterol could account for about a third of the association observed between the genetic score and increased coronary risk. Interpretation Human genetic data suggest that long-term dual IL-1 alpha/beta inhibition could increase cardiovascular risk and, conversely, reduce the risk of development of rheumatoid arthritis. The cardiovascular risk might, in part, be mediated through an increase in proatherogenic lipid concentrations. Copyright (C) The Interleukin 1 Genetics Consortium. Open Access article distributed under the terms of CC-BY-NC-ND.
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| 44. |
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| 45. |
- Pennings, M., et al.
(author)
-
KIF1A variants are a frequent cause of autosomal dominant hereditary spastic paraplegia
- 2020
-
In: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 28, s. 40-49
-
Journal article (peer-reviewed)abstract
- Variants in the KIF1A gene can cause autosomal recessive spastic paraplegia 30, autosomal recessive hereditary sensory neuropathy, or autosomal (de novo) dominant mental retardation type 9. More recently, variants in KIF1A have also been described in a few cases with autosomal dominant spastic paraplegia. Here, we describe 20 KIF1A variants in 24 patients from a clinical exome sequencing cohort of 347 individuals with a mostly ‘pure’ spastic paraplegia. In these patients, spastic paraplegia was slowly progressive and mostly pure, but with a highly variable disease onset (0–57 years). Segregation analyses showed a de novo occurrence in seven cases, and a dominant inheritance pattern in 11 families. The motor domain of KIF1A is a hotspot for disease causing variants in autosomal dominant spastic paraplegia, similar to mental retardation type 9 and recessive spastic paraplegia type 30. However, unlike these allelic disorders, dominant spastic paraplegia was also caused by loss-of-function variants outside this domain in six families. Finally, three missense variants were outside the motor domain and need further characterization. In conclusion, KIF1A variants are a frequent cause of autosomal dominant spastic paraplegia in our cohort (6–7%). The identification of KIF1A loss-of-function variants suggests haploinsufficiency as a possible mechanism in autosomal dominant spastic paraplegia. © 2019, The Author(s).
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| 46. |
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| 47. |
- Calon, T. G. A., et al.
(author)
-
Minimally Invasive Ponto Surgery Versus the Linear Incision Technique With Soft Tissue Preservation for Bone Conduction Hearing Implants: A Multicenter Randomized Controlled Trial
- 2018
-
In: Otology & Neurotology. - : Ovid Technologies (Wolters Kluwer Health). - 1531-7129 .- 1537-4505. ; 39:7, s. 882-893
-
Journal article (peer-reviewed)abstract
- Objective:To compare the surgical outcomes of the Minimally Invasive Ponto Surgery (MIPS) technique with those of the linear incision technique with soft-tissue preservation for bone-anchored hearing systems (BAHS).Design:Sponsor-initiated multicenter, open, randomized, controlled clinical trial.Setting:Maastricht University Medical Centre, Ziekenhuisgroep Twente and Medisch Centrum Leeuwarden, all situated in The Netherlands.Participants:Sixty-four adult patients eligible for unilateral BAHS surgery.Interventions Single-stage BAHS surgery with 1:1 randomization to the linear incision technique with soft-tissue preservation (control) or the MIPS (test) group.Primary and Secondary Outcome Measurements:Primary objective: compare the incidence of inflammation (Holgers Index 2) during 12 weeks' follow-up after surgery. Secondary objectives: skin dehiscence, pain scores, loss of sensibility around the implant, soft-tissue overgrowth, skin sagging, implant extrusion, cosmetic results, surgical time, wound healing and Implant Stability Quotient measurements.Results:Sixty-three subjects were analyzed in the intention-to-treat population. No significant difference was found for the incidence of inflammation between groups. Loss of skin sensibility, cosmetic outcomes, skin sagging, and surgical time were significantly better in the test group. No statistically significant differences were found for dehiscence, pain, and soft-tissue overgrowth. A nonsignificant difference in extrusion was found for the test group. The Implant Stability Quotient was statistically influenced by the surgical technique, abutment length, and time.Conclusion:No significant differences between the MIPS and the linear incision techniques were observed regarding skin inflammation. MIPS results in a statistically significant reduction in the loss of skin sensibility, less skin sagging, improved cosmetic results, and reduced surgical time. Although nonsignificant, the implant extrusion rate warrants further research.
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| 48. |
- Escott-Price, Valentina, et al.
(author)
-
Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
-
Journal article (peer-reviewed)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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| 49. |
- Jiang, Rays H. Y., et al.
(author)
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Distinctive Expansion of Potential Virulence Genes in the Genome of the Oomycete Fish Pathogen Saprolegnia parasitica
- 2013
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In: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 9:6, s. e1003272-
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Journal article (peer-reviewed)abstract
- Oomycetes in the class Saprolegniomycetidae of the Eukaryotic kingdom Stramenopila have evolved as severe pathogens of amphibians, crustaceans, fish and insects, resulting in major losses in aquaculture and damage to aquatic ecosystems. We have sequenced the 63 Mb genome of the fresh water fish pathogen, Saprolegnia parasitica. Approximately 1/3 of the assembled genome exhibits loss of heterozygosity, indicating an efficient mechanism for revealing new variation. Comparison of S. parasitica with plant pathogenic oomycetes suggests that during evolution the host cellular environment has driven distinct patterns of gene expansion and loss in the genomes of plant and animal pathogens. S. parasitica possesses one of the largest repertoires of proteases (270) among eukaryotes that are deployed in waves at different points during infection as determined from RNA-Seq data. In contrast, despite being capable of living saprotrophically, parasitism has led to loss of inorganic nitrogen and sulfur assimilation pathways, strikingly similar to losses in obligate plant pathogenic oomycetes and fungi. The large gene families that are hallmarks of plant pathogenic oomycetes such as Phytophthora appear to be lacking in S. parasitica, including those encoding RXLR effectors, Crinkler's, and Necrosis Inducing-Like Proteins (NLP). S. parasitica also has a very large kinome of 543 kinases, 10% of which is induced upon infection. Moreover, S. parasitica encodes several genes typical of animals or animal-pathogens and lacking from other oomycetes, including disintegrins and galactose-binding lectins, whose expression and evolutionary origins implicate horizontal gene transfer in the evolution of animal pathogenesis in S. parasitica.
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- Jones, Lesley, et al.
(author)
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Convergent genetic and expression data implicate immunity in Alzheimer's disease
- 2015
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In: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
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Journal article (peer-reviewed)abstract
- Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
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