| 1. |
- Abbasi, R., et al.
(författare)
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Search for neutrino-induced cascades with five years of AMANDA data
- 2011
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Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 34:6, s. 420-430
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Tidskriftsartikel (refereegranskat)abstract
- We report on the search for electromagnetic and hadronic showers ("cascades") produced by a diffuse flux of extraterrestrial neutrinos in the AMANDA neutrino telescope. Data for this analysis were recorded during 1001 days of detector livetime in the years 2000-2004. The observed event rates are consistent with the background expectation from atmospheric neutrinos and muons. An upper limit is derived for the diffuse flux of neutrinos of all flavors assuming a flavor ratio of v(e):v(mu):v(tau) = 1:1:1 at the detection site. The all-flavor flux of neutrinos with an energy spectrum Phi proportional to E-2 is less than 5.0 x 10(-7) GeV s(-1) sr(-1) cm(-2) at a 90% C.L. Here, 90% of the simulated signal would fall within the energy range 40 TeV to 9 PeV. We discuss flux limits in the context of several specific models of extraterrestrial and prompt atmospheric neutrino production.
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| 2. |
- Abbasi, R., et al.
(författare)
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First search for extremely high energy cosmogenic neutrinos with the IceCube Neutrino Observatory
- 2010
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Ingår i: Physical review. D, Particles, fields, gravitation, and cosmology. - 1550-7998. ; 82:7, s. 072003-
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Tidskriftsartikel (refereegranskat)abstract
- We report on the results of the search for extremely-high energy neutrinos with energies above 10(7) GeV obtained with the partially (similar to 30%) constructed IceCube in 2007. From the absence of signal events in the sample of 242.1 days of effective live time, we derive a 90% C.L. model independent differential upper limit based on the number of signal events per energy decade at E-2 phi(ve+v mu+v tau) similar or equal to 1.4 x 10(-6) GeV cm(-2) sec(-1) sr(-1) for neutrinos in the energy range from 3 x 10(7) to 3 x 10(9) GeV.
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| 3. |
- Abbasi, R., et al.
(författare)
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Limits on a muon flux from Kaluza-Klein dark matter annihilations in the Sun from the IceCube 22-string detector
- 2010
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Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 81:5, s. 057101-
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Tidskriftsartikel (refereegranskat)abstract
- A search for muon neutrinos from Kaluza-Klein dark matter annihilations in the Sun has been performed with the 22-string configuration of the IceCube neutrino detector using data collected in 104.3 days of live time in 2007. No excess over the expected atmospheric background has been observed. Upper limits have been obtained on the annihilation rate of captured lightest Kaluza-Klein particle (LKP) WIMPs in the Sun and converted to limits on the LKP-proton cross sections for LKP masses in the range 250-3000 GeV. These results are the most stringent limits to date on LKP annihilation in the Sun.
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| 4. |
- Feroci, M., et al.
(författare)
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The large observatory for x-ray timing
- 2014
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 9780819496126
-
Konferensbidrag (refereegranskat)abstract
- The Large Observatory For x-ray Timing (LOFT) was studied within ESA M3 Cosmic Vision framework and participated in the final downselection for a launch slot in 2022-2024. Thanks to the unprecedented combination of effective area and spectral resolution of its main instrument, LOFT will study the behaviour of matter under extreme conditions, such as the strong gravitational field in the innermost regions of accretion flows close to black holes and neutron stars, and the supranuclear densities in the interior of neutron stars. The science payload is based on a Large Area Detector (LAD, 10 m2 effective area, 2-30 keV, 240 eV spectral resolution, 1° collimated field of view) and a Wide Field Monitor (WFM, 2-50 keV, 4 steradian field of view, 1 arcmin source location accuracy, 300 eV spectral resolution). The WFM is equipped with an on-board system for bright events (e.g. GRB) localization. The trigger time and position of these events are broadcast to the ground within 30 s from discovery. In this paper we present the status of the mission at the end of its Phase A study.
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| 5. |
- Abbasi, R., et al.
(författare)
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Calibration and characterization of the IceCube photomultiplier tube
- 2010
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 618:1-3, s. 139-152
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Tidskriftsartikel (refereegranskat)abstract
- Over 5000 PMTs are being deployed at the South Pole to compose the IceCube neutrino observatory. Many are placed deep in the ice to detect Cherenkov light emitted by the products of high-energy neutrino interactions, and others are frozen into tanks on the surface to detect particles from atmospheric cosmic ray showers. IceCube is using the 10-in. diameter R7081-02 made by Hamamatsu Photonics. This paper describes the laboratory characterization and calibration of these PMTs before deployment. PMTs were illuminated with pulses ranging from single photons to saturation level. Parameterizations are given for the single photoelectron charge spectrum and the saturation behavior. Time resolution, late pulses and afterpulses are characterized. Because the PMTs are relatively large, the cathode sensitivity uniformity was measured. The absolute photon detection efficiency was calibrated using Rayleigh-scattered photons from a nitrogen laser. Measured characteristics are discussed in the context of their relevance to IceCube event reconstruction and simulation efforts. (C) 2010 Elsevier B.V. All rights reserved.
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| 6. |
- Abbasi, R., et al.
(författare)
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Measurement of acoustic attenuation in South Pole ice
- 2011
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Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 34:6, s. 382-393
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Tidskriftsartikel (refereegranskat)abstract
- Using the South Pole Acoustic Test Setup (SPATS) and a retrievable transmitter deployed in holes drilled for the IceCube experiment, we have measured the attenuation of acoustic signals by South Pole ice at depths between 190 m and 500 m. Three data sets, using different acoustic sources, have been analyzed and give consistent results. The method with the smallest systematic uncertainties yields an amplitude attenuation coefficient alpha = 3.20 +/- 0.57 km(-1) between 10 and 30 kHz, considerably larger than previous theoretical estimates. Expressed as an attenuation length, the analyses give a consistent result for lambda equivalent to 1/alpha of similar to 300 m with 20% uncertainty. No significant depth or frequency dependence has been found.
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| 7. |
- Abbasi, R., et al.
(författare)
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Measurement of the anisotropy of cosmic-ray arrival directions with icecube
- 2010
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Ingår i: The Astrophysical Journal Letters. - 2041-8205. ; 718, s. L194-L198
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Tidskriftsartikel (refereegranskat)abstract
- We report the first observation of an anisotropy in the arrival direction of cosmic rays with energies in the multi-TeV region in the Southern sky using data from the IceCube detector. Between 2007 June and 2008 March, the partially deployed IceCube detector was operated in a configuration with 1320 digital optical sensors distributed over 22 strings at depths between 1450 and 2450 m inside the Antarctic ice. IceCube is a neutrino detector, but the data are dominated by a large background of cosmic-ray muons. Therefore, the background data are suitable for high-statistics studies of cosmic rays in the southern sky. The data include 4.3 billion muons produced by downward-going cosmic-ray interactions in the atmosphere; these events were reconstructed with a median angular resolution of 3 degrees and a median energy of similar to 20 TeV. Their arrival direction distribution exhibits an anisotropy in right ascension with a first-harmonic amplitude of (6.4 +/- 0.2 stat. +/- 0.8 syst.) x 10(-4).
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| 8. |
- Abbasi, R., et al.
(författare)
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Search for muon neutrinos from gamma-ray bursts with the IceCube neutrino telescope
- 2010
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 710:1, s. 346-359
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of searches for high-energy muon neutrinos from 41 gamma-ray bursts (GRBs) in the northern sky with the IceCube detector in its 22 string configuration active in 2007/2008. The searches cover both the prompt and a possible precursor emission as well as a model-independent, wide time window of -1 hr to + 3 hr around each GRB. In contrast to previous searches with a large GRB population, we do not utilize a standard Waxman-Bahcall GRB flux for the prompt emission but calculate individual neutrino spectra for all 41 GRBs from the burst parameters measured by satellites. For all of the three time windows, the best estimate for the number of signal events is zero. Therefore, we place 90% CL upper limits on the fluence from the prompt phase of 3.7 x 10(-3) erg cm(-2) (72 TeV-6.5 PeV) and on the fluence from the precursor phase of 2.3 x 10(-3) erg cm(-2) (2.2-55 TeV), where the quoted energy ranges contain 90% of the expected signal events in the detector. The 90% CL upper limit for the wide time window is 2.7 x 10(-3) erg cm(-2) (3 TeV-2.8 PeV) assuming an E-2 flux.
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| 9. |
- Abbasi, R., et al.
(författare)
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Search for relativistic magnetic monopoles with the AMANDA-II neutrino telescope
- 2010
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 69:3-4, s. 361-378
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Tidskriftsartikel (refereegranskat)abstract
- We present the search for Cherenkov signatures from relativistic magnetic monopoles in data taken with the AMANDA-II detector, a neutrino telescope deployed in the Antarctic ice cap at the Geographic South Pole. The non-observation of a monopole signal in data collected during the year 2000 improves present experimental limits on the flux of relativistic magnetic monopoles: Our flux limit varies between 3.8x10(-17) cm(-2) s(-1) sr(-1) (for monopoles moving at the vacuum speed of light) and 8.8x10(-16) cm(-2) s(-1) sr(-1) (for monopoles moving at a speed beta=v/c=0.76, just above the Cherenkov threshold in ice). These limits apply to monopoles that are energetic enough to penetrate the Earth and enter the detector from below the horizon. The limit obtained for monopoles reaching the detector from above the horizon is less stringent by roughly an order of magnitude, due to the much larger background from down-going atmospheric muons. This looser limit is however valid for a larger class of magnetic monopoles, since the monopoles are not required to pass through the Earth.
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| 10. |
- Abbasi, R., et al.
(författare)
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The energy spectrum of atmospheric neutrinos between 2 and 200 TeV with the AMANDA-II detector
- 2010
-
Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 34:1, s. 48-58
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Tidskriftsartikel (refereegranskat)abstract
- The muon and anti-muon neutrino energy spectrum is determined from 2000-2003 AMANDA telescope data using regularised unfolding. This is the first measurement of atmospheric neutrinos in the energy range 2-200 TeV. The result is compared to different atmospheric neutrino models and it is compatible with the atmospheric neutrinos from pion and kaon decays. No significant contribution from charm had-ron decays or extraterrestrial neutrinos is detected. The capabilities to improve the measurement of the neutrino spectrum with the successor experiment IceCube are discussed.
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| 11. |
- Abbasi, R., et al.
(författare)
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Measurement of sound speed vs. depth in South Pole ice for neutrino astronomy
- 2010
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Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 33:5-6, s. 277-286
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Tidskriftsartikel (refereegranskat)abstract
- We have measured the speed of both pressure waves and shear waves as a function of depth between 80 and 500 m depth in South Pole ice with better than 1% precision. The measurements were made using the South Pole Acoustic Test Setup (SPATS), an array of transmitters and sensors deployed in the ice at the South Pole in order to measure the acoustic properties relevant to acoustic detection of astrophysical neutrinos. The transmitters and sensors use piezoceramics operating at similar to 5-25 kHz. Between 200 m and 500 m depth, the measured profile is consistent with zero variation of the sound speed with depth, resulting in zero refraction, for both pressure and shear waves. We also performed a complementary study featuring an explosive signal propagating vertically from 50 to 2250 m depth, from which we determined a value for the pressure wave speed consistent with that determined for shallower depths, higher frequencies, and horizontal propagation with the SPATS sensors. The sound speed profile presented here can be used to achieve good acoustic source position and emission time reconstruction in general, and neutrino direction and energy reconstruction in particular. The reconstructed quantities could also help separate neutrino signals from background. (C) 2010 Elsevier B.V. All rights reserved.
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| 12. |
- Blunden, Jessica, et al.
(författare)
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State of the Climate in 2012
- 2013
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 94:8, s. S1-S258
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Tidskriftsartikel (refereegranskat)abstract
- For the first time in serveral years, the El Nino-Southern Oscillation did not dominate regional climate conditions around the globe. A weak La Ni a dissipated to ENSOneutral conditions by spring, and while El Nino appeared to be emerging during summer, this phase never fully developed as sea surface temperatures in the eastern conditions. Nevertheless, other large-scale climate patterns and extreme weather events impacted various regions during the year. A negative phase of the Arctic Oscillation from mid-January to early February contributed to frigid conditions in parts of northern Africa, eastern Europe, and western Asia. A lack of rain during the 2012 wet season led to the worst drought in at least the past three decades for northeastern Brazil. Central North America also experienced one of its most severe droughts on record. The Caribbean observed a very wet dry season and it was the Sahel's wettest rainy season in 50 years. Overall, the 2012 average temperature across global land and ocean surfaces ranked among the 10 warmest years on record. The global land surface temperature alone was also among the 10 warmest on record. In the upper atmosphere, the average stratospheric temperature was record or near-record cold, depending on the dataset. After a 30-year warming trend from 1970 to 1999 for global sea surface temperatures, the period 2000-12 had little further trend. This may be linked to the prevalence of La Ni a-like conditions during the 21st century. Heat content in the upper 700 m of the ocean remained near record high levels in 2012. Net increases from 2011 to 2012 were observed at 700-m to 2000-m depth and even in the abyssal ocean below. Following sharp decreases in to the effects of La Ni a, sea levels rebounded to reach records highs in 2012. The increased hydrological cycle seen in recent years continued, with more evaporation in drier locations and more precipitation in rainy areas. In a pattern that has held since 2004, salty areas of the ocean surfaces and subsurfaces were anomalously salty on average, while fresher areas were anomalously fresh. Global tropical cyclone activity during 2012 was near average, with a total of 84 storms compared with the 1981-2010 average of 89. Similar to 2010 and 2011, the North Atlantic was the only hurricane basin that experienced above-normal activity. In this basin, Sandy brought devastation to Cuba and parts of the eastern North American seaboard. All other basins experienced either near-or below-normal tropical cyclone activity. Only three tropical cyclones reached Category 5 intensity-all in Bopha became the only storm in the historical record to produce winds greater than 130 kt south of 7 N. It was also the costliest storm to affect the Philippines and killed more than 1000 residents. Minimum Arctic sea ice extent in September and Northern Hemisphere snow cover extent in June both reached new record lows. June snow cover extent is now declining at a faster rate (-17.6% per decade) than September sea ice extent (-13.0% per decade). Permafrost temperatures reached record high values in northernmost Alaska. A new melt extent record occurred on 11-12 July on the Greenland ice sheet; 97% of the ice sheet showed some form of melt, four times greater than the average melt for this time of year. The climate in Antarctica was relatively stable overall. The largest maximum sea ice extent since records begain in 1978 was observed in September 2012. In the stratosphere, warm air led to the second smallest ozone hole in the past two decades. Even so, the springtime ozone layer above Antarctica likely will not return to its early 1980s state until about 2060. Following a slight decline associated with the global 2 emissions from fossil fuel combustion and cement production reached a record 9.5 +/- 0.5 Pg C in 2011 and a new record of 9.7 +/- 0.5 Pg C is estimated for 2012. Atmospheric CO2 concentrations increased by 2.1 ppm in 2012, to 392.6 ppm. In spring 2012, 2 concentration exceeded 400 ppm at 7 of the 13 Arctic observation sites. Globally, other greenhouse gases including methane and nitrous oxide also continued to rise in concentration and the combined effect now represents a 32% increase in radiative forcing over a 1990 baseline. Concentrations of most ozone depleting substances continued to fall.
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| 13. |
- Meyer, H., et al.
(författare)
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Overview of physics results from MAST towards ITER/DEMO and the MAST Upgrade
- 2013
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 53:10, s. 104008-
-
Tidskriftsartikel (refereegranskat)abstract
- New diagnostic, modelling and plant capability on the Mega Ampere Spherical Tokamak (MAST) have delivered important results in key areas for ITER/DEMO and the upcoming MAST Upgrade, a step towards future ST devices on the path to fusion currently under procurement. Micro-stability analysis of the pedestal highlights the potential roles of micro-tearing modes and kinetic ballooning modes for the pedestal formation. Mitigation of edge localized modes (ELM) using resonant magnetic perturbation has been demonstrated for toroidal mode numbers n = 3, 4, 6 with an ELM frequency increase by up to a factor of 9, compatible with pellet fuelling. The peak heat flux of mitigated and natural ELMs follows the same linear trend with ELM energy loss and the first ELM-resolved T-i measurements in the divertor region are shown. Measurements of flow shear and turbulence dynamics during L-H transitions show filaments erupting from the plasma edge whilst the full flow shear is still present. Off-axis neutral beam injection helps to strongly reduce the redistribution of fast-ions due to fishbone modes when compared to on-axis injection. Low-k ion-scale turbulence has been measured in L-mode and compared to global gyro-kinetic simulations. A statistical analysis of principal turbulence time scales shows them to be of comparable magnitude and reasonably correlated with turbulence decorrelation time. T-e inside the island of a neoclassical tearing mode allow the analysis of the island evolution without assuming specific models for the heat flux. Other results include the discrepancy of the current profile evolution during the current ramp-up with solutions of the poloidal field diffusion equation, studies of the anomalous Doppler resonance compressional Alfven eigenmodes, disruption mitigation studies and modelling of the new divertor design for MAST Upgrade. The novel 3D electron Bernstein synthetic imaging shows promising first data sensitive to the edge current profile and flows.
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| 14. |
- Weinstein, John N., et al.
(författare)
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The cancer genome atlas pan-cancer analysis project
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
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Forskningsöversikt (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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| 15. |
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| 16. |
- Johnston, Jennifer J., et al.
(författare)
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Molecular Analysis Expands the Spectrum of Phenotypes Associated with GLI3 Mutations
- 2010
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794. ; 31:10, s. 1142-1154
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Tidskriftsartikel (refereegranskat)abstract
- A range of phenotypes including Greig cephalopolysyndactyly and Pallister-Hall syndromes (GCPS, PHS) are caused by pathogenic mutation of the GLI3 gene. To characterize the clinical variability of GLI3 mutations, we present a subset of a cohort of 174 probands referred for GLI3 analysis. Eighty-one probands with typical GCPS or PHS were previously reported, and we report the remaining 93 probands here. This includes 19 probands (12 mutations) who fulfilled clinical criteria for GCPS or PHS, 48 probands (16 mutations) with features of GCPS or PHS but who did not meet the clinical criteria (sub-GCPS and sub-PHS), 21 probands (6 mutations) with features of PHS or GCPS and oral-facial- digital syndrome, and 5 probands (1 mutation) with nonsyndromic polydactyly. These data support previously identified genotype-phenotype correlations and demonstrate a more variable degree of severity than previously recognized. The finding of GLI3 mutations in patients with features of oral-facial-digital syndrome supports the observation that GLI3 interacts with cilia. We conclude that the phenotypic spectrum of GLI3 mutations is broader than that encompassed by the clinical diagnostic criteria, but the genotype-phenotype correlation persists. Individuals with features of either GCPS or PHS should be screened for mutations in GLI3 even if they do not fulfill clinical criteria. Hum Mutat 31:1142-1154, 2010. (C) 2010 Wiley-Liss, Inc.
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| 17. |
- Cavieres, Lohengrin A., et al.
(författare)
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Facilitative plant interactions and climate simultaneously drive alpine plant diversity
- 2014
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Ingår i: Ecology Letters. - : Wiley. - 1461-0248 .- 1461-023X. ; 17:2, s. 193-202
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Tidskriftsartikel (refereegranskat)abstract
- Interactions among species determine local-scale diversity, but local interactions are thought to have minor effects at larger scales. However, quantitative comparisons of the importance of biotic interactions relative to other drivers are rarely made at larger scales. Using a data set spanning 78 sites and five continents, we assessed the relative importance of biotic interactions and climate in determining plant diversity in alpine ecosystems dominated by nurse-plant cushion species. Climate variables related with water balance showed the highest correlation with richness at the global scale. Strikingly, although the effect of cushion species on diversity was lower than that of climate, its contribution was still substantial. In particular, cushion species enhanced species richness more in systems with inherently impoverished local diversity. Nurse species appear to act as a ‘safety net’ sustaining diversity under harsh conditions, demonstrating that climate and species interactions should be integrated when predicting future biodiversity effects of climate change.
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| 18. |
- Ho, Joshua W. K., et al.
(författare)
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Comparative analysis of metazoan chromatin organization
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 512:7515, s. 449-U507
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Tidskriftsartikel (refereegranskat)abstract
- Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms(1-3). Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal 'arms', and centromeres distributed along their lengths(4,5). To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function.
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| 19. |
- Hov, J. R., et al.
(författare)
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Electrostatic Modifications of the Human Leukocyte Antigen-DR P9 Peptide-Binding Pocket and Susceptibility to Primary Sclerosing Cholangitis
- 2011
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Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 53:6, s. 1967-1976
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Tidskriftsartikel (refereegranskat)abstract
- The strongest genetic risk factors for primary sclerosing cholangitis (PSC) are found in the human leukocyte antigen (HLA) complex at chromosome 6p21. Genes in the HLA class II region encode molecules that present antigen to T lymphocytes. Polymorphisms in these genes are associated with most autoimmune diseases, most likely because they contribute to the specificity of immune responses. The aim of this study was to analyze the structure and electrostatic properties of the peptide-binding groove of HLA-DR in relation to PSC. Thus, four-digit resolution HLA-DRB1 genotyping was performed in 356 PSC patients and 366 healthy controls. Sequence information was used to assign which amino acids were encoded at all polymorphic positions. In stepwise logistic regressions, variations at residues 37 and 86 were independently associated with PSC (P = 1.2 x 10(-32) and P = 1.8 x 10(-22) in single-residue models, respectively). Three-dimensional modeling was performed to explore the effect of these key residues on the HLA-DR molecule. This analysis indicated that residue 37 was a major determinant of the electrostatic properties of pocket P9 of the peptide-binding groove. Asparagine at residue 37, which was associated with PSC, induced a positive charge in pocket P9. Tyrosine, which protected against PSC, induced a negative charge in this pocket. Consistent with the statistical observations, variation at residue 86 also indirectly influenced the electrostatic properties of this pocket. DRB1*13:01, which was PSC-associated, had a positive P9 pocket and DRB1*13:02, protective against PSC, had a negative P9 pocket. Conclusion: The results suggest that in patients with PSC, residues 37 and 86 of the HLA-DR beta chain critically influence the electrostatic properties of pocket P9 and thereby the range of peptides presented. (HEPATOLOGY 2011;53:1967-1976)
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| 20. |
- Van Deerlin, Vivian M, et al.
(författare)
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Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:3, s. 234-239
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal lobar degeneration (FTLD) is the second most common cause of presenile dementia. The predominant neuropathology is FTLD with TAR DNA-binding protein (TDP-43) inclusions (FTLD-TDP). FTLD-TDP is frequently familial, resulting from mutations in GRN (which encodes progranulin). We assembled an international collaboration to identify susceptibility loci for FTLD-TDP through a genome-wide association study of 515 individuals with FTLD-TDP. We found that FTLD-TDP associates with multiple SNPs mapping to a single linkage disequilibrium block on 7p21 that contains TMEM106B. Three SNPs retained genome-wide significance following Bonferroni correction (top SNP rs1990622, P = 1.08 x 10(-11); odds ratio, minor allele (C) 0.61, 95% CI 0.53-0.71). The association replicated in 89 FTLD-TDP cases (rs1990622; P = 2 x 10(-4)). TMEM106B variants may confer risk of FTLD-TDP by increasing TMEM106B expression. TMEM106B variants also contribute to genetic risk for FTLD-TDP in individuals with mutations in GRN. Our data implicate variants in TMEM106B as a strong risk factor for FTLD-TDP, suggesting an underlying pathogenic mechanism.
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| 21. |
- van der Schaaf, Rene J., et al.
(författare)
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Rationale and design of EXPLORE: a randomized, prospective, multicenter trial investigating the impact of recanalization of a chronic total occlusion on left ventricular function in patients after primary percutaneous coronary intervention for acute ST-elevation myocardial infarction
- 2010
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: In the setting of primary percutaneous coronary intervention, patients with a chronic total occlusion in a non-infarct related artery were recently identified as a high-risk subgroup. It is unclear whether ST-elevation myocardial infarction patients with a chronic total occlusion in a non-infarct related artery should undergo additional percutaneous coronary intervention of the chronic total occlusion on top of optimal medical therapy shortly after primary percutaneous coronary intervention. Possible beneficial effects include reduction in adverse left ventricular remodeling and preservation of global left ventricular function and improved clinical outcome during future coronary events. Methods/Design: The Evaluating Xience V and left ventricular function in Percutaneous coronary intervention on occLusiOns afteR ST-Elevation myocardial infarction ( EXPLORE) trial is a randomized, prospective, multicenter, two-arm trial with blinded evaluation of endpoints. Three hundred patients after primary percutaneous coronary intervention for ST-elevation myocardial infarction with a chronic total occlusion in a non-infarct related artery are randomized to either elective percutaneous coronary intervention of the chronic total occlusion within seven days or standard medical treatment. When assigned to the invasive arm, an everolimus-eluting coronary stent is used. Primary endpoints are left ventricular ejection fraction and left ventricular end-diastolic volume assessed by cardiac Magnetic Resonance Imaging at four months. Clinical follow-up will continue until five years. Discussion: The ongoing EXPLORE trial is the first randomized clinical trial powered to investigate whether recanalization of a chronic total occlusion in a non-infarct related artery after primary percutaneous coronary intervention for ST-elevation myocardial infarction results in a better preserved residual left ventricular ejection fraction, reduced end-diastolic volume and enhanced clinical outcome.
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| 22. |
- Wray, Selina, et al.
(författare)
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Creation of an Open-Access, Mutation-Defined Fibroblast Resource for Neurological Disease Research
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:8
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Tidskriftsartikel (refereegranskat)abstract
- Our understanding of the molecular mechanisms of many neurological disorders has been greatly enhanced by the discovery of mutations in genes linked to familial forms of these diseases. These have facilitated the generation of cell and animal models that can be used to understand the underlying molecular pathology. Recently, there has been a surge of interest in the use of patient-derived cells, due to the development of induced pluripotent stem cells and their subsequent differentiation into neurons and glia. Access to patient cell lines carrying the relevant mutations is a limiting factor for many centres wishing to pursue this research. We have therefore generated an open-access collection of fibroblast lines from patients carrying mutations linked to neurological disease. These cell lines have been deposited in the National Institute for Neurological Disorders and Stroke (NINDS) Repository at the Coriell Institute for Medical Research and can be requested by any research group for use in in vitro disease modelling. There are currently 71 mutation-defined cell lines available for request from a wide range of neurological disorders and this collection will be continually expanded. This represents a significant resource that will advance the use of patient cells as disease models by the scientific community.
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| 23. |
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| 24. |
- Blunden, Jessica, et al.
(författare)
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State of the climate in 2013
- 2014
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Ingår i: Bulletin of the American Meteorological Society. - 0003-0007. ; 95
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Tidskriftsartikel (refereegranskat)abstract
- © 2014, American Meteorological Society. All rights reserved. In 2013, the vast majority of the monitored climate variables reported here maintained trends established in recent decades. ENSO was in a neutral state during the entire year, remaining mostly on the cool side of neutral with modest impacts on regional weather patterns around the world. This follows several years dominated by the effects of either La Niña or El Niño events. According to several independent analyses, 2013 was again among the 10 warmest years on record at the global scale, both at the Earth’s surface and through the troposphere. Some regions in the Southern Hemisphere had record or near-record high temperatures for the year. Australia observed its hottest year on record, while Argentina and New Zealand reported their second and third hottest years, respectively. In Antarctica, Amundsen-Scott South Pole Station reported its highest annual temperature since records began in 1957. At the opposite pole, the Arctic observed its seventh warmest year since records began in the early 20th century. At 20-m depth, record high temperatures were measured at some permafrost stations on the North Slope of Alaska and in the Brooks Range. In the Northern Hemisphere extratropics, anomalous meridional atmospheric circulation occurred throughout much of the year, leading to marked regional extremes of both temperature and precipitation. Cold temperature anomalies during winter across Eurasia were followed by warm spring temperature anomalies, which were linked to a new record low Eurasian snow cover extent in May. Minimum sea ice extent in the Arctic was the sixth lowest since satellite observations began in 1979. Including 2013, all seven lowest extents on record have occurred in the past seven years. Antarctica, on the other hand, had above-average sea ice extent throughout 2013, with 116 days of new daily high extent records, including a new daily maximum sea ice area of 19.57 million km2 reached on 1 October. ENSO-neutral conditions in the eastern central Pacific Ocean and a negative Pacific decadal oscillation pattern in the North Pacific had the largest impacts on the global sea surface temperature in 2013. The North Pacific reached a historic high temperature in 2013 and on balance the globally-averaged sea surface temperature was among the 10 highest on record. Overall, the salt content in nearsurface ocean waters increased while in intermediate waters it decreased. Global mean sea level continued to rise during 2013, on pace with a trend of 3.2 mm yr-1 over the past two decades. A portion of this trend (0.5 mm yr-1) has been attributed to natural variability associated with the Pacific decadal oscillation as well as to ongoing contributions from the melting of glaciers and ice sheets and ocean warming. Global tropical cyclone frequency during 2013 was slightly above average with a total of 94 storms, although the North Atlantic Basin had its quietest hurricane season since 1994. In the Western North Pacific Basin, Super Typhoon Haiyan, the deadliest tropical cyclone of 2013, had 1-minute sustained winds estimated to be 170 kt (87.5 m s-1) on 7 November, the highest wind speed ever assigned to a tropical cyclone. High storm surge was also associated with Haiyan as it made landfall over the central Philippines, an area where sea level is currently at historic highs, increasing by 200 mm since 1970. In the atmosphere, carbon dioxide, methane, and nitrous oxide all continued to increase in 2013. As in previous years, each of these major greenhouse gases once again reached historic high concentrations. In the Arctic, carbon dioxide and methane increased at the same rate as the global increase. These increases are likely due to export from lower latitudes rather than a consequence of increases in Arctic sources, such as thawing permafrost. At Mauna Loa, Hawaii, for the first time since measurements began in 1958, the daily average mixing ratio of carbon dioxide exceeded 400 ppm on 9 May. The state of these variables, along with dozens of others, and the 2013 climate conditions of regions around the world are discussed in further detail in this 24th edition of the State of the Climate series.
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| 25. |
- de Gonzalez, Amy Berrington, et al.
(författare)
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Body-Mass Index and Mortality among 1.46 Million White Adults.
- 2010
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Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 363:23, s. 2211-2219
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Tidskriftsartikel (refereegranskat)abstract
- Background: A high body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) is associated with increased mortality from cardiovascular disease and certain cancers, but the precise relationship between BMI and all-cause mortality remains uncertain. Methods: We used Cox regression to estimate hazard ratios and 95% confidence intervals for an association between BMI and all-cause mortality, adjusting for age, study, physical activity, alcohol consumption, education, and marital status in pooled data from 19 prospective studies encompassing 1.46 million white adults, 19 to 84 years of age (median, 58). Results: The median baseline BMI was 26.2. During a median follow-up period of 10 years (range, 5 to 28), 160,087 deaths were identified. Among healthy participants who never smoked, there was a J-shaped relationship between BMI and all-cause mortality. With a BMI of 22.5 to 24.9 as the reference category, hazard ratios among women were 1.47 (95 percent confidence interval [CI], 1.33 to 1.62) for a BMI of 15.0 to 18.4; 1.14 (95% CI, 1.07 to 1.22) for a BMI of 18.5 to 19.9; 1.00 (95% CI, 0.96 to 1.04) for a BMI of 20.0 to 22.4; 1.13 (95% CI, 1.09 to 1.17) for a BMI of 25.0 to 29.9; 1.44 (95% CI, 1.38 to 1.50) for a BMI of 30.0 to 34.9; 1.88 (95% CI, 1.77 to 2.00) for a BMI of 35.0 to 39.9; and 2.51 (95% CI, 2.30 to 2.73) for a BMI of 40.0 to 49.9. In general, the hazard ratios for the men were similar. Hazard ratios for a BMI below 20.0 were attenuated with longer-term follow-up. Conclusions: In white adults, overweight and obesity (and possibly underweight) are associated with increased all-cause mortality. All-cause mortality is generally lowest with a BMI of 20.0 to 24.9. N Engl J Med 2010;363:2211-9.
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