| 1. |
- Escott-Price, Valentina, et al.
(författare)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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| 2. |
- de Boer, G., et al.
(författare)
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Near-surface meteorology during the Arctic Summer Cloud Ocean Study (ASCOS) : evaluation of reanalyses and global climate models
- 2014
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 14:1, s. 427-445
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Tidskriftsartikel (refereegranskat)abstract
- Atmospheric measurements from the Arctic Summer Cloud Ocean Study (ASCOS) are used to evaluate the performance of three atmospheric reanalyses (European Centre for Medium Range Weather Forecasting (ECMWF)-Interim reanalysis, National Center for Environmental Prediction (NCEP)-National Center for Atmospheric Research (NCAR) reanalysis, and NCEP-DOE (Department of Energy) reanalysis) and two global climate models (CAM5 (Community Atmosphere Model 5) and NASA GISS (Goddard Institute for Space Studies) ModelE2) in simulation of the high Arctic environment. Quantities analyzed include near surface meteorological variables such as temperature, pressure, humidity and winds, surface-based estimates of cloud and precipitation properties, the surface energy budget, and lower atmospheric temperature structure. In general, the models perform well in simulating large-scale dynamical quantities such as pressure and winds. Near-surface temperature and lower atmospheric stability, along with surface energy budget terms, are not as well represented due largely to errors in simulation of cloud occurrence, phase and altitude. Additionally, a development version of CAMS, which features improved handling of cloud macro physics, has demonstrated to improve simulation of cloud properties and liquid water amount. The ASCOS period additionally provides an excellent example of the benefits gained by evaluating individual budget terms, rather than simply evaluating the net end product, with large compensating errors between individual surface energy budget terms that result in the best net energy budget.
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| 3. |
- Davidsson, Björn J. R., et al.
(författare)
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Thermal inertia and surface roughness of Comet 9P/Tempel 1
- 2013
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Ingår i: Icarus. - : Elsevier BV. - 0019-1035 .- 1090-2643. ; 224:1, s. 154-171
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Tidskriftsartikel (refereegranskat)abstract
- Re-calibrated near-infrared spectroscopy of the resolved nucleus of Comet 9P/Tempel 1 acquired by the Deep Impact spacecraft has been analyzed by utilizing the post-Stardust-NExT nucleus shape model and spin pole solution, as well as a novel thermophysical model that explicitly accounts for small-scale surface roughness and thermal inertia. We find that the thermal inertia varies measurably across the surface, and that thermal emission from certain regions only can be reproduced satisfactory if surface roughness is accounted for. Particularly, a scarped/pitted terrain that experienced morning sunrise during the flyby is measurably rough (Hapke mean slope angle similar to 45 degrees) and has a thermal inertia of at most 50J m(-2) K-1 s(-1/2), but probably much lower. However, thick layered terrain and thin layered terrain experiencing local noon during the flyby have a substantially larger thermal inertia, reaching 150J m(-2) K-1 s(-1/2) if the surface is as rough as the scarped/pitted terrain, but 200J m(-2) K-1 s(-1/2) if the terrain is considered locally flat. Furthermore, the reddening of the nucleus near-infrared 1.5-2.2 gm spectrum varies between morphological units, being reddest for thick layered terrain (median value 3.4% k angstrom(-1)) and most neutral for the smooth terrain known to contain surface water ice (median value 3.1% k angstrom(-1)). Thus, Comet 9P/Tempel 1 is heterogeneous in terms of both thermophysical and optical properties, due to formation conditions and/or post-formation processing.
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| 4. |
- Zabriskie, Matthew S., et al.
(författare)
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BCR-ABL1 Compound Mutations Combining Key Kinase Domain Positions Confer Clinical Resistance to Ponatinib in Ph Chromosome-Positive Leukemia
- 2014
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Ingår i: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 26:3, s. 428-442
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Tidskriftsartikel (refereegranskat)abstract
- Ponatinib is the only currently approved tyrosine kinase inhibitor (TKI) that suppresses all BCR-ABL1 single mutants in Philadelphia chromosome-positive (Ph+) leukemia, including the recalcitrant BCR-ABL1(T315I) mutant. However, emergence of compound mutations in a BCR-ABL1 allele may confer ponatinib resistance. We found that clinically reported BCR-ABL1 compound mutants center on 12 key positions and confer varying resistance to imatinib, nilotinib, dasatinib, ponatinib, rebastinib, and bosutinib. T315I-inclusive compound mutants confer high-level resistance to TKIs, including ponatinib. In vitro resistance profiling was predictive of treatment outcomes in Ph+ leukemia patients. Structural explanations for compound mutation-based resistance were obtained through molecular dynamics simulations. Our findings demonstrate that BCR-ABL1 compound mutants confer different levels of TKI resistance, necessitating rational treatment selection to optimize clinical outcome.
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