| 1. |
- 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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| 2. |
- 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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| 3. |
- 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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| 4. |
- 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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| 5. |
- 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
-
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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| 6. |
- 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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| 7. |
- 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
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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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| 8. |
- 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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| 9. |
- 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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| 10. |
- 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
-
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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| 11. |
- Abbasi, R., et al.
(författare)
-
First search for extremely high energy cosmogenic neutrinos with the IceCube Neutrino Observatory
- 2010
-
Ingår i: Physical review. D, Particles, fields, gravitation, and cosmology. - 1550-7998. ; 82:7, s. 072003-
-
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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| 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. |
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| 15. |
- 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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| 16. |
- Yusuf, D, et al.
(författare)
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The transcription factor encyclopedia
- 2012
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906. ; 13:3, s. R24-
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Tidskriftsartikel (refereegranskat)
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| 17. |
- 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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| 18. |
- Blunden, Jessica, et al.
(författare)
-
State of the climate in 2013
- 2014
-
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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| 19. |
- Ferrari, Raffaele, et al.
(författare)
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Frontotemporal dementia and its subtypes: a genome-wide association study.
- 2014
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Ingår i: Lancet Neurology. - 1474-4465. ; 13:7, s. 686-699
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder.
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| 20. |
- Mattsson, Niklas, 1979, et al.
(författare)
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The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers.
- 2011
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer's disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer's Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program.
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| 21. |
- Cavieres, Lohengrin A., et al.
(författare)
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Facilitative plant interactions and climate simultaneously drive alpine plant diversity
- 2014
-
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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| 22. |
- 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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| 23. |
- 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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| 24. |
- Smith, Bradley N., et al.
(författare)
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The C9ORF72 expansion mutation is a common cause of ALS+/-FTD in Europe and has a single founder
- 2013
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Ingår i: European Journal of Human Genetics. - London : Nature Publishing Group. - 1018-4813 .- 1476-5438. ; 21:1, s. 102-108
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Tidskriftsartikel (refereegranskat)abstract
- A massive hexanucleotide repeat expansion mutation (HREM) in C9ORF72 has recently been linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we describe the frequency, origin and stability of this mutation in ALS+/-FTD from five European cohorts (total n = 1347). Single-nucleotide polymorphisms defining the risk haplotype in linked kindreds were genotyped in cases (n = 434) and controls (n = 856). Haplotypes were analysed using PLINK and aged using DMLE+. In a London clinic cohort, the HREM was the most common mutation in familial ALS+/-FTD: C9ORF72 29/112 (26%), SOD1 27/112 (24%), TARDBP 1/112 (1%) and FUS 4/112 (4%) and detected in 13/216 (6%) of unselected sporadic ALS cases but was rare in controls (3/856, 0.3%). HREM prevalence was high for familial ALS+/-FTD throughout Europe: Belgium 19/22 (86%), Sweden 30/41 (73%), the Netherlands 10/27 (37%) and Italy 4/20 (20%). The HREM did not affect the age at onset or survival of ALS patients. Haplotype analysis identified a common founder in all 137 HREM carriers that arose around 6300 years ago. The haplotype from which the HREM arose is intrinsically unstable with an increased number of repeats (average 8, compared with 2 for controls, P<10(-8)). We conclude that the HREM has a single founder and is the most common mutation in familial and sporadic ALS in Europe.
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| 25. |
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| 26. |
- Vreeswijk, Paul M., et al.
(författare)
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THE HYDROGEN-POOR SUPERLUMINOUS SUPERNOVA iPTF 13ajg AND ITS HOST GALAXY IN ABSORPTION AND EMISSION
- 2014
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 797:1, s. 24-
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Tidskriftsartikel (refereegranskat)abstract
- We present imaging and spectroscopy of a hydrogen-poor superluminous supernova (SLSN) discovered by the intermediate Palomar Transient Factory, iPTF 13ajg. At a redshift of z = 0.7403, derived from narrow absorption lines, iPTF 13ajg peaked at an absolute magnitude of M-u,M-AB = -22.5, one of the most luminous supernovae to date. The observed bolometric peak luminosity of iPTF 13ajg is 3.2 x 10(44) erg s(-1), while the estimated total radiated energy is 1.3 x 10(51) erg. We detect narrow absorption lines of Mg I, Mg II, and Fe II, associated with the cold interstellar medium in the host galaxy, at two different epochs with X-shooter at the Very Large Telescope. From Voigt profile fitting, we derive the column densities log N(Mg I) = 11.94 +/- 0.06, log N(Mg II) = 14.7 +/- 0.3, and log N(Fe II) = 14.25 +/- 0.10. These column densities, as well as the Mg I and Mg II equivalent widths of a sample of hydrogen-poor SLSNe taken from the literature, are at the low end of those derived for gamma-ray bursts (GRBs) whose progenitors are also thought to be massive stars. This suggests that the environments of hydrogen-poor SLSNe and GRBs are different. From the nondetection of Fe II fine-structure absorption lines, we derive a lower limit on the distance between the supernova and the narrow-line absorbing gas of 50 pc. The neutral gas responsible for the absorption in iPTF 13ajg exhibits a single narrow component with a low velocity width, Delta V = 76 km s(-1), indicating a low-mass host galaxy. No host galaxy emission lines are detected, leading to an upper limit on the unobscured star formation rate (SFR) of SFR[O II] < 0.07 M-circle dot yr(-1). Late-time imaging shows the iPTF 13ajg host galaxy to be faint, with g(AB) approximate to 27.0 and R-AB >= 26.0 mag, corresponding to M-B,M-Vega greater than or similar to -17.7 mag.
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| 27. |
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| 28. |
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| 29. |
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| 30. |
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| 31. |
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| 32. |
- Callaghan, Terry V., et al.
(författare)
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Changing snow cover and its impacts
- 2011
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Ingår i: Snow, Water, Ice and Permafrost in the Arctic (SWIPA). - Oslo : Arctic Monitoring and Assessment Programme. - 9788279710714 ; , s. 4:1-4:58
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Bokkapitel (refereegranskat)
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| 33. |
- de Lemos, Rogerio, et al.
(författare)
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Software Engineering for Self-Adaptive Systems : A Second Research Roadmap
- 2013
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Ingår i: Software Engineering for Self-Adaptive Systems II. - Berlin, Heidelberg : Springer. - 9783642358128 ; , s. 1-32
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The goal of this roadmap paper is to summarize the state-of-the-art and identify research challenges when developing, deploying and managing self-adaptive software systems. Instead of dealing with a wide range of topics associated with the field, we focus on four essential topics of self-adaptation: design space for self-adaptive solutions, software engineering processes for self-adaptive systems, from centralized to decentralized control, and practical run-time verification & validation for self-adaptive systems. For each topic, we present an overview, suggest future directions, and focus on selected challenges. This paper complements and extends a previous roadmap on software engineering for self-adaptive systems published in 2009 covering a different set of topics, and reflecting in part on the previous paper. This roadmap is one of the many results of the Dagstuhl Seminar 10431 on Software Engineering for Self-Adaptive Systems, which took place in October 2010.
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| 34. |
- Fukumoto, Noriko, et al.
(författare)
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Sexually dimorphic effect of the Val66Met polymorphism of BDNF on susceptibility to Alzheimer's disease : New data and meta-analysis
- 2010
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Ingår i: American journal of medical genetics. Part B, Neuropsychiatric genetics. - : Wiley. - 1552-4841 .- 1552-485X. ; 153B:1, s. 235-242
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Tidskriftsartikel (refereegranskat)abstract
- Conflicting results have been reported as to whether genetic variations (Val66Met and C270T) of the brain-derived neurotrophic factor gene (BDNF) confer susceptibility to Alzheimer's disease (AD). We genotyped these polymorphisms in a Japanese sample of 657 patients with AD and 525 controls, and obtained weak evidence of association for Val66Met (P = 0.063), but not for C270T. After stratification by sex, we found a significant allelic association between Val66Met and AD in women (P = 0.017), but not in men. To confirm these observations, we collected genotyping data for each sex from 16 research centers worldwide (4,711 patients and 4,537 controls in total). The meta-analysis revealed that there was a clear sex difference in the allelic association; the Met66 allele confers susceptibility to AD in women (odds ratio = 1.14, 95% CI 1.05-1.24, P = 0.002), but not in men. Our results provide evidence that the Met66 allele of BDNF has a sexually dimorphic effect on susceptibility to AD.
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| 35. |
- Fuqua, Joshua L, et al.
(författare)
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Dynamic changes in dopamine neuron function after DNSP-11 treatment: Effects in vivo and increased ERK 1/2 phosphorylation in vitro.
- 2014
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Ingår i: Peptides. - : Elsevier BV. - 1873-5169 .- 0196-9781. ; 54:Jan 7, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Glial cell-line derived neurotrophic factor (GDNF) has demonstrated robust effects on dopamine (DA) neuron function and survival. A post-translational processing model of the human GDNF proprotein theorizes the formation of smaller, amidated peptide(s) from the proregion that exhibit neurobiological function, including an 11-amino-acid peptide named dopamine neuron stimulating peptide-11 (DNSP-11). A single treatment of DNSP-11 was delivered to the substantia nigra in the rat to investigate effects on DA-neuron function. Four weeks after treatment, potassium (K+) and d-amphetamine evoked DA release were studied in the striatum using microdialysis. There were no significant changes in DA-release after DNSP-11 treatment determined by microdialysis. Dopamine release was further examined in discrete regions of the striatum using high-speed chronoamperometry at 1-, 2-, and 4-weeks after DNSP-11 treatment. Two weeks after DNSP-11 treatment, potassium-evoked DA release was increased in specific subregions of the striatum. However, spontaneous locomotor activity was unchanged by DNSP-11 treatment. In addition, we show that a single treatment of DNSP-11 in the MN9D dopaminergic neuronal cell line results in phosphorylation of ERK1/2, which suggests a novel cellular mechanism responsible for increases in DA function.
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| 36. |
- Goodfellow, Bradley W., et al.
(författare)
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Arctic-alpine blockfields in the northern Swedish Scandes : late Quaternary - not Neogene
- 2014
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Ingår i: Earth Surface Dynamics. - : Copernicus GmbH. - 2196-6311 .- 2196-632X. ; 2:2, s. 383-401
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Tidskriftsartikel (refereegranskat)abstract
- Autochthonous blockfield mantles may indicate alpine surfaces that have not been glacially eroded. These surfaces may therefore serve as markers against which to determine Quaternary erosion volumes in adjacent glacially eroded sectors. To explore these potential utilities, chemical weathering features, erosion rates, and regolith residence durations of mountain blockfields are investigated in the northern Swedish Scandes. This is done, firstly, by assessing the intensity of regolith chemical weathering along altitudinal transects descending from three blockfield-mantled summits. Clay / silt ratios, secondary mineral assemblages, and imaging of chemical etching of primary mineral grains in fine matrix are each used for this purpose. Secondly, erosion rates and regolith residence durations of two of the summits are inferred from concentrations of in situ-produced cosmogenic Be-10 and Al-26 in quartz at the blockfield surfaces. An interpretative model is adopted that includes temporal variations in nuclide production rates through surface burial by glacial ice and glacial isostasy-induced elevation changes of the blockfield surfaces. Together, our data indicate that these blockfields are not derived from remnants of intensely weathered Neogene weathering profiles, as is commonly considered. Evidence for this interpretation includes minor chemical weathering in each of the three examined blockfields, despite consistent variability according to slope position. In addition, average erosion rates of similar to 16.2 and similar to 6.7 mm ka(-1), calculated for the two blockfield-mantled summits, are low but of sufficient magnitude to remove present blockfield mantles, of up to a few metres in thickness, within a late Quaternary time frame. Hence, blockfield mantles appear to be replenished by regolith formation through, primarily physical, weathering processes that have operated during the Quaternary. The persistence of autochthonous blockfields over multiple glacial-interglacial cycles confirms their importance as key markers of surfaces that were not glacially eroded through, at least, the late Quaternary. However, presently blockfield-mantled surfaces may potentially be subjected to large spatial variations in erosion rates, and their Neogene regolith mantles may have been comprehensively eroded during the late Pliocene and early Pleistocene. Their role as markers by which to estimate glacial erosion volumes in surrounding landscape elements therefore remains uncertain.
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| 37. |
- Helsmoortel, Celine, et al.
(författare)
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A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP
- 2014
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:4, s. 380-
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Tidskriftsartikel (refereegranskat)abstract
- Despite the high heritability of autism spectrum disorders (ASD), characterized by persistent deficits in social communication and interaction and restricted, repetitive patterns of behavior, interests or activities(1), a genetic diagnosis can be established in only a minority of patients. Known genetic causes include chromosomal aberrations, such as the duplication of the 15q11-13 region, and monogenic causes, as in Rett and fragile- X syndromes. The genetic heterogeneity within ASD is striking, with even the most frequent causes responsible for only 1% of cases at the most. Even with the recent developments in nextgeneration sequencing, for the large majority of cases no molecular diagnosis can be established(2-7). Here, we report ten patients with ASD and other shared clinical characteristics, including intellectual disability and facial dysmorphisms caused by a mutation in ADNP, a transcription factor involved in the SWI/ SNF remodeling complex. We estimate this gene to be mutated in at least 0.17% of ASD cases, making it one of the most frequent ASD- associated genes known to date.
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| 38. |
- Honkalampi-Hämäläinen, U., et al.
(författare)
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Safety evaluation of food contact paper and board using chemical tests and in vitro bioassays : Role of known and unknown substances
- 2010
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Ingår i: Food Additives and Contaminants. - : Informa UK Limited. - 0265-203X .- 1464-5122. ; 27:3, s. 406-115
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Tidskriftsartikel (refereegranskat)abstract
- In vitro toxicological tests have been proposed as an approach to complement the chemical safety assessment of food contact materials, particularly those with a complex or unknown chemical composition such as paper and board. Among the concerns raised regarding the applicability of in vitro tests are the effects of interference of the extractables on the outcome of the cytotoxicity and genotoxicity tests applied and the role of known compounds present in chemically complex materials, such as paper and board, either as constituents or contaminants. To answer these questions, a series of experiments were performed to assess the role of natural substances (wood extracts, resin acids), some additives (diisopropylnaphthalene, phthalates, acrylamide, fluorescent whitening agents) and contaminants (2,4-diaminotoluene, benzo[a]pyrene) in the toxicological profile of paper and board. These substances were individually tested or used to spike actual paper and board extracts. The toxic concentrations of diisopropylnaphthalenes and phthalates were compared with those actually detected in paper and board extracts showing conspicuous toxicity. According to the results of the spiking experiments, the extracts did not affect the toxicity of tested chemicals nor was there any significant metabolic interference in the cases where two compounds were used in tests involving xenobiotic metabolism by the target cells. While the identified substances apparently have a role in the cytotoxicity of some of the project samples, their presence does not explain the total toxicological profile of the extracts. In conclusion, in vitro toxicological testing can have a role in the safety assessment of chemically complex materials in detecting potentially harmful activities not predictable by chemical analysis alone.
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| 39. |
- Nelson, Peter T., et al.
(författare)
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Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status : A Review of the Literature
- 2012
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Ingår i: Journal of Neuropathology and Experimental Neurology. - 0022-3069 .- 1554-6578. ; 71:5, s. 362-381
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Forskningsöversikt (refereegranskat)abstract
- Clinicopathologic correlation studies are critically important for the field of Alzheimer disease (AD) research. Studies on human subjects with autopsy confirmation entail numerous potential biases that affect both their general applicability and the validity of the correlations. Many sources of data variability can weaken the apparent correlation between cognitive status and AD neuropathologic changes. Indeed, most persons in advanced old age have significant non-AD brain lesions that may alter cognition independently of AD. Worldwide research efforts have evaluated thousands of human subjects to assess the causes of cognitive impairment in the elderly, and these studies have been interpreted in different ways. We review the literature focusing on the correlation of AD neuropathologic changes (i.e. beta-amyloid plaques and neurofibrillary tangles) with cognitive impairment. We discuss the various patterns of brain changes that have been observed in elderly individuals to provide a perspective for understanding AD clinicopathologic correlation and conclude that evidence from many independent research centers strongly supports the existence of a specific disease, as defined by the presence of AA plaques and neurofibrillary tangles. Although AA plaques may play a key role in AD pathogenesis, the severity of cognitive impairment correlates best with the burden of neocortical neurofibrillary tangles.
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| 40. |
- Rademakers, Rosa, et al.
(författare)
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Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids.
- 2012
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:2, s. 200-5
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal-dominant central nervous system white-matter disease with variable clinical presentations, including personality and behavioral changes, dementia, depression, parkinsonism, seizures and other phenotypes. We combined genome-wide linkage analysis with exome sequencing and identified 14 different mutations affecting the tyrosine kinase domain of the colony stimulating factor 1 receptor (encoded by CSF1R) in 14 families with HDLS. In one kindred, we confirmed the de novo occurrence of the mutation. Follow-up sequencing identified an additional CSF1R mutation in an individual diagnosed with corticobasal syndrome. In vitro, CSF-1 stimulation resulted in rapid autophosphorylation of selected tyrosine residues in the kinase domain of wild-type but not mutant CSF1R, suggesting that HDLS may result from partial loss of CSF1R function. As CSF1R is a crucial mediator of microglial proliferation and differentiation in the brain, our findings suggest an important role for microglial dysfunction in HDLS pathogenesis.
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| 41. |
- Roy, Sushmita, et al.
(författare)
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Identification of functional elements and regulatory circuits by Drosophila modENCODE.
- 2010
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 330:6012, s. 1787-1797
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Tidskriftsartikel (refereegranskat)abstract
- To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation.
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| 42. |
- Shatunov, Aleksey, et al.
(författare)
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Chromosome 9p21 in sporadic amyotrophic lateral sclerosis in the UK and seven other countries : a genome-wide association study
- 2010
-
Ingår i: Lancet Neurology. - 1474-4422 .- 1474-4465. ; 9:10, s. 986-994
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Tidskriftsartikel (refereegranskat)abstract
- We have found strong evidence of a genetic association of two single nucleotide polymorphisms on chromosome 9 with sporadic ALS, in line with findings from previous independent GWAS of ALS and linkage studies of ALS-frontotemporal dementia. Our findings together with these earlier findings suggest that genetic variation at this locus on chromosome 9 causes sporadic ALS and familial ALS-frontotemporal dementia. Resequencing studies and then functional analysis should be done to identify the defective gene.
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| 43. |
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| 44. |
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| 45. |
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| 46. |
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| 47. |
- Akimoto, Chizuru, et al.
(författare)
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A blinded international study on the reliability of genetic testing for GGGGCC-repeat expansions in C9orf72 reveals marked differences in results among 14 laboratories
- 2014
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Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 51:6, s. 419-424
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Tidskriftsartikel (refereegranskat)abstract
- Background The GGGGCC-repeat expansion in C9orf72 is the most frequent mutation found in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Most of the studies on C9orf72 have relied on repeat-primed PCR (RP-PCR) methods for detection of the expansions. To investigate the inherent limitations of this technique, we compared methods and results of 14 laboratories. Methods The 14 laboratories genotyped DNA from 78 individuals (diagnosed with ALS or FTD) in a blinded fashion. Eleven laboratories used a combination of amplicon-length analysis and RP-PCR, whereas three laboratories used RP-PCR alone; Southern blotting techniques were used as a reference. Results Using PCR-based techniques, 5 of the 14 laboratories got results in full accordance with the Southern blotting results. Only 50 of the 78 DNA samples got the same genotype result in all 14 laboratories. There was a high degree of false positive and false negative results, and at least one sample could not be genotyped at all in 9 of the 14 laboratories. The mean sensitivity of a combination of amplicon-length analysis and RP-PCR was 95.0% (73.9-100%), and the mean specificity was 98.0% (87.5-100%). Overall, a sensitivity and specificity of more than 95% was observed in only seven laboratories. Conclusions Because of the wide range seen in genotyping results, we recommend using a combination of amplicon-length analysis and RP-PCR as a minimum in a research setting. We propose that Southern blotting techniques should be the gold standard, and be made obligatory in a clinical diagnostic setting.
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| 48. |
- Bergstrom, Stig M., et al.
(författare)
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Revision of the position of the Ordovician-Silurian boundary in southern Ontario: regional chronostratigraphic implications of delta C-13 chemostratigraphy of the Manitoulin Formation and associated strata
- 2011
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Ingår i: Canadian Journal of Earth Sciences. - 0008-4077. ; 48:11, s. 1447-1470
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Tidskriftsartikel (refereegranskat)abstract
- delta C-13 values of 142 samples from the Manitoulin Formation and subjacent strata collected from 14 exposures and two drill-cores on Manitoulin Island, Bruce Peninsula, and the region south of Georgian Bay suggest that the Manitoulin Formation is latest Ordovician (Hirnantian) rather than earliest Silurian in age. A delta C-13 excursion identified as the Hirnantian isotope carbon excursion (HICE), which has a magnitude of nearly 2.5 parts per thousand above baseline values, is present in an interval from the upper Queenston Formation to the lower to middle part of the Manitoulin Formation in most of Bruce Peninsula and in the area south of Georgian Bay, whereas on Manitoulin Island the RICE appears to be absent. This indicates that a significant part of the Manitoulin Formation is older on the Bruce Peninsula and in its adjacent region than on Manitoulin Island. The chemostratigraphically based conclusions are consistent with biostratigraphic data from conodonts and brachiopods. The Hirnantian delta C-13 curve from Anticosti Island, Quebec is closely similar to those of southern Ontario. Traditionally, the Ordovician-Silurian boundary has been placed at the base of the Manitoulin Formation, but the new results suggest that it is more likely to be at, or near, the base of the overlying Cabot Head Formation. These new results have major implications For the interpretation of the geologic history and marine depositional patterns of the latest Ordovician of a large part of the North American Midcontinent.
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| 49. |
- Beyer, Anja-Silke, et al.
(författare)
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Engulfment adapter PTB domain containing 1 interacts with and affects processing of the amyloid-beta precursor protein
- 2010
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Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 33:4, s. 732-743
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies identified engulfment adapter phosphotyrosine binding (PTB) domain containing 1 (GULP1) as an NPXY-motif interactor of low-density lipoprotein receptor-related protein 1 (LRP1) and suggested a potential relevance in Alzheimer's disease (AD). Since AD associated proteins amyloid-beta A4 precursor protein (APP) and LRP1 were shown to interact with the PTB domain of Fe65 and several other adapters via their intracellular NPXY-motifs, we examined a possible interaction of GULP1 PTB domain with the YENPTY-motif of APP. Here we demonstrate that GULP1 is present in human hippocampal and neocortical neurons. Confocal live cell imaging revealed that coexpressed and endogenous GULP1 colocalizes with APP in the Golgi and endoplasmic reticulum. Analysis of the interacting domains by co-immunoprecipitation of point and deletion mutants revealed that the interaction depends on the PTB domain of GULP1 and the YENPTY-motif of APP. Coexpression of GULP1 affected APP cell surface localization and suppressed generation of Abeta40/42 and sAPPalpha. Taken together, these data identify GULP1 as a novel neuronal APP interacting protein that alters trafficking and processing of APP.
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| 50. |
- Bichler, Robert M., et al.
(författare)
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Sustainable development and ICTs
- 2010
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Ingår i: Information, Communication and Society. - : Informa UK Limited. - 1369-118X .- 1468-4462. ; 13:1, s. 1-5
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Tidskriftsartikel (refereegranskat)
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