| 1. |
- Aartsen, M. G., et al.
(författare)
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Improvement in fast particle track reconstruction with robust statistics
- 2014
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 736, s. 143-149
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Tidskriftsartikel (refereegranskat)abstract
- The IceCube project has transformed 1 km(3) of deep natural Antarctic ice into a Cherenkov detector Muon neutrinos are detected and their direction is inferred by mapping the light produced by the secondary muon track inside the volume instrumented with photomultipliers. Reconstructing the muon track from the observed light is challenging due to noise, light scattering in the ice medium, and the possibility of simultaneously having multiple muons inside the detector, resulting from the large flux of cosmic ray muons. This paper describes work on two problems: (1) the truck reconstruction problem, in which, given a set of observations, the goal is to recover the track of a muon; and (2) the coincident event problem, which is to determine how many muons are active in the detector during a time window. Rather than solving these problems by developing more complex physical models that are applied at later stages of the analysis, our approach is to augment the detector's early reconstruction with data filters and robust statistical techniques. These can be implemented at the level of on-line reconstruction and, therefore, improve all subsequent reconstructions. Using the metric of median angular resolution, a standard metric for track reconstruction, we improve the accuracy in the initial reconstruction direction by 13%. We also present improvements in measuring the number of muons in coincident events: we can accurately determine the number of muons 98% of the time.
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| 2. |
- 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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| 3. |
- 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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