1,018 research outputs found
Calculation of nonzero-temperature Casimir forces in the time domain
We show how to compute Casimir forces at nonzero temperatures with
time-domain electromagnetic simulations, for example using a finite-difference
time-domain (FDTD) method. Compared to our previous zero-temperature
time-domain method, only a small modification is required, but we explain that
some care is required to properly capture the zero-frequency contribution. We
validate the method against analytical and numerical frequency-domain
calculations, and show a surprising high-temperature disappearance of a
non-monotonic behavior previously demonstrated in a piston-like geometry.Comment: 5 pages, 2 figures, submitted to Physical Review A Rapid
Communicatio
SNPs in Multi-Species Conserved Sequences (MCS) as useful markers in association studies: a practical approach
<p>Abstract</p> <p>Background</p> <p>Although genes play a key role in many complex diseases, the specific genes involved in most complex diseases remain largely unidentified. Their discovery will hinge on the identification of key sequence variants that are conclusively associated with disease. While much attention has been focused on variants in protein-coding DNA, variants in noncoding regions may also play many important roles in complex disease by altering gene regulation. Since the vast majority of noncoding genomic sequence is of unknown function, this increases the challenge of identifying "functional" variants that cause disease. However, evolutionary conservation can be used as a guide to indicate regions of noncoding or coding DNA that are likely to have biological function, and thus may be more likely to harbor SNP variants with functional consequences. To help bias marker selection in favor of such variants, we devised a process that prioritizes annotated SNPs for genotyping studies based on their location within Multi-species Conserved Sequences (MCSs) and used this process to select SNPs in a region of linkage to a complex disease. This allowed us to evaluate the utility of the chosen SNPs for further association studies. Previously, a region of chromosome 1q43 was linked to Multiple Sclerosis (MS) in a genome-wide screen. We chose annotated SNPs in the region based on location within MCSs (termed MCS-SNPs). We then obtained genotypes for 478 MCS-SNPs in 989 individuals from MS families.</p> <p>Results</p> <p>Analysis of our MCS-SNP genotypes from the 1q43 region and comparison to HapMap data confirmed that annotated SNPs in MCS regions are frequently polymorphic and show subtle signatures of selective pressure, consistent with previous reports of genome-wide variation in conserved regions. We also present an online tool that allows MCS data to be directly exported to the UCSC genome browser so that MCS-SNPs can be easily identified within genomic regions of interest.</p> <p>Conclusion</p> <p>Our results showed that MCS can easily be used to prioritize markers for follow-up and candidate gene association studies. We believe that this novel approach demonstrates a paradigm for expediting the search for genes contributing to complex diseases.</p
Mendelian Randomization with Incomplete Exposure Data: a Bayesian Approach
We expand Mendelian Randomization (MR) methodology to deal with randomly
missing data on either the exposure or the outcome variable, and furthermore
with data from nonindependent individuals (eg components of a family). Our
method rests on the Bayesian MR framework proposed by Berzuini et al (2018),
which we apply in a study of multiplex Multiple Sclerosis (MS) Sardinian
families to characterise the role of certain plasma proteins in MS causation.
The method is robust to presence of pleiotropic effects in an unknown number of
instruments, and is able to incorporate inter-individual kinship information.
Introduction of missing data allows us to overcome the bias introduced by the
(reverse) effect of treatment (in MS cases) on level of protein. From a
substantive point of view, our study results confirm recent suspicion that an
increase in circulating IL12A and STAT4 protein levels does not cause an
increase in MS risk, as originally believed, suggesting that these two proteins
may not be suitable drug targets for MS
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The Arctic Research of the Composition of the Troposphere from Aircraft and Satellites (ARCTAS) Mission: Design, Execution, and First Results
The NASA Arctic Research of the Composition of the Troposphere from Aircraft and Satellites (ARCTAS) mission was conducted in two 3-week deployments based in Alaska (April 2008) and western Canada (June–July 2008). Its goal was to better understand the factors driving current changes in Arctic atmospheric composition and climate, including (1) influx of mid-latitude pollution, (2) boreal forest fires, (3) aerosol radiative forcing, and (4) chemical processes. The June–July deployment was preceded by one week of flights over California (ARCTAS-CARB) focused on (1) improving state emission inventories for greenhouse gases and aerosols, (2) providing observations to test and improve models of ozone and aerosol pollution. ARCTAS involved three aircraft: a DC-8 with a detailed chemical payload, a P-3 with an extensive aerosol and radiometric payload, and a B-200 with aerosol remote sensing instrumentation. The aircraft data augmented satellite observations of Arctic atmospheric composition, in particular from the NASA A-Train. The spring phase (ARCTAS-A) revealed pervasive Asian pollution throughout the Arctic as well as significant European pollution below 2 km. Unusually large Siberian fires in April 2008 caused high concentrations of carbonaceous aerosols and also affected ozone. Satellite observations of BrO column hotspots were found not to be related to Arctic boundary layer events but instead to tropopause depressions, suggesting the presence of elevated inorganic bromine (5–10 pptv) in the lower stratosphere. Fresh fire plumes from Canada and California sampled during the summer phase (ARCTAS-B) indicated low emission factors from the fires, rapid conversion of to PAN, no significant secondary aerosol production, and no significant ozone enhancements except when mixed with urban pollution.Engineering and Applied Science
Reconstructing the Population Genetic History of the Caribbean
The Caribbean basin is home to some of the most complex interactions in
recent history among previously diverged human populations. Here, by making use
of genome-wide SNP array data, we characterize ancestral components of
Caribbean populations on a sub-continental level and unveil fine-scale patterns
of population structure distinguishing insular from mainland Caribbean
populations as well as from other Hispanic/Latino groups. We provide genetic
evidence for an inland South American origin of the Native American component
in island populations and for extensive pre-Columbian gene flow across the
Caribbean basin. The Caribbean-derived European component shows significant
differentiation from parental Iberian populations, presumably as a result of
founder effects during the colonization of the New World. Based on demographic
models, we reconstruct the complex population history of the Caribbean since
the onset of continental admixture. We find that insular populations are best
modeled as mixtures absorbing two pulses of African migrants, coinciding with
early and maximum activity stages of the transatlantic slave trade. These two
pulses appear to have originated in different regions within West Africa,
imprinting two distinguishable signatures in present day Afro-Caribbean genomes
and shedding light on the genetic impact of the dynamics occurring during the
slave trade in the Caribbean.Comment: 26 pages, 6 figures, and supporting informatio
Search for short baseline nu(e) disappearance with the T2K near detector
8 pages, 6 figures, submitted to PRD rapid communication8 pages, 6 figures, submitted to PRD rapid communicationWe thank the J-PARC staff for superb accelerator performance and the CERN NA61 collaboration for providing valuable particle production data. We acknowledge the support of MEXT, Japan; NSERC, NRC and CFI, Canada; Commissariat `a l’Energie Atomique and Centre National de la Recherche Scientifique–Institut National de Physique Nucle´aire et de Physique des Particules, France; DFG, Germany; INFN, Italy; National Science Centre (NCN), Poland; Russian Science Foundation, RFBR and Ministry of Education and Science, Russia; MINECO and European Regional Development Fund, Spain; Swiss National Science Foundation and State Secretariat for Education, Research and Innovation, Switzerland; STFC, UK; and DOE, USA. We also thank CERN for the UA1/NOMAD magnet, DESY for the HERA-B magnet mover system, NII for SINET4, the WestGrid and SciNet consortia in Compute Canada, GridPP, UK. In addition participation of individual researchers and institutions has been further supported by funds from ERC (FP7), EU; JSPS, Japan; Royal Society, UK; DOE Early Career program, USA
Measurements of neutrino oscillation in appearance and disappearance channels by the T2K experiment with 6.6 x 10(20) protons on target
111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee comments111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee comments111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee commentsWe thank the J-PARC staff for superb accelerator performance and the CERN NA61/SHINE Collaboration for providing valuable particle production data. We acknowledge the support of MEXT, Japan; NSERC, NRC, and CFI, Canada; CEA and CNRS/IN2P3, France; DFG, Germany; INFN, Italy; National Science Centre (NCN), Poland; RSF, RFBR and MES, Russia; MINECO and ERDF funds, Spain; SNSF and SER, Switzerland; STFC, UK; and the U. S. Deparment of Energy, USA. We also thank CERN for the UA1/NOMAD magnet, DESY for the HERA-B magnet mover system, NII for SINET4, the WestGrid and SciNet consortia in Compute Canada, GridPP, UK, and the Emerald High Performance Computing facility in the Centre for Innovation, UK. In addition, participation of individual researchers and institutions has been further supported by funds from ERC (FP7), EU; JSPS, Japan; Royal Society, UK; and DOE Early Career program, USA
Measurement of the electron neutrino charged-current interaction rate on water with the T2K ND280 pi(0) detector
10 pages, 6 figures, Submitted to PRDhttp://journals.aps.org/prd/abstract/10.1103/PhysRevD.91.112010© 2015 American Physical Society11 pages, 6 figures, as accepted to PRD11 pages, 6 figures, as accepted to PRD11 pages, 6 figures, as accepted to PR
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.
Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis
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