4,041 research outputs found

    A diagnosis of the development of a winter anticyclone over North America

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    This paper examines the 48-h life cycle of a winter anticyclone occurring over North America from 18 to 20 January 1979 using Goddard Laboratory for Atmospheres FGGE level 3b (SOP 1) global analyses on a 4 deg latitude by 5 deg longitude grid. Applying the relatively new methodology of the Zwack-Okossi equation, results show that anticyclonic vorticity advection and cold-air advection acted to develop the anticyclone, while adiabatic warming in the descending air opposed development. Other forcing processes made only small contributions to anticyclone changes. Vertical profiles of the development quantities reveal that vorticity and temperature advections, as well as the adiabatic warming, maximized in the 200-300-mb layer

    Dissecting Complex Traits Using the Drosophila Synthetic Population Resource

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    For most complex traits we have a poor understanding of the positions, phenotypic effects, and population frequencies of the underlying genetic variants contributing to their variation. Recently, several groups have developed multi-parent advanced intercross mapping panels in different model organisms in an attempt to improve our ability to characterize causative genetic variants. These panels are powerful and are particularly well suited to the dissection of phenotypic variation generated by rare alleles and loci segregating multiple functional alleles. We describe studies using one such panel, the Drosophila Synthetic Population Resource, and the implications for our understanding of the genetic basis of complex traits. In particular, we note that many loci of large effect appear to be multiallelic. If multiallelism is a general rule, analytical approaches designed to identify multiallelic variants should be a priority for both genome wide association studies and multi-parental panels

    Genetic Dissection of the Drosophila melanogaster Female Head Transcriptome Reveals Widespread Allelic Heterogeneity

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    Modern genetic mapping is plagued by the “missing heritability” problem, which refers to the discordance between the estimated heritabilities of quantitative traits and the variance accounted for by mapped causative variants. One major potential explanation for the missing heritability is allelic heterogeneity, in which there are multiple causative variants at each causative gene with only a fraction having been identified. The majority of genome-wide association studies (GWAS) implicitly assume that a single SNP can explain all the variance for a causative locus. However, if allelic heterogeneity is prevalent, a substantial amount of genetic variance will remain unexplained. In this paper, we take a haplotype-based mapping approach and quantify the number of alleles segregating at each locus using a large set of 7922 eQTL contributing to regulatory variation in the Drosophila melanogaster female head. Not only does this study provide a comprehensive eQTL map for a major community genetic resource, the Drosophila Synthetic Population Resource, but it also provides a direct test of the allelic heterogeneity hypothesis. We find that 95% of cis-eQTLs and 78% of trans-eQTLs are due to multiple alleles, demonstrating that allelic heterogeneity is widespread in Drosophila eQTL. Allelic heterogeneity likely contributes significantly to the missing heritability problem common in GWAS studies.This work was supported by NIH R01 RR024862/OD010974 to SJM and ADL, an American Recovery and Reinvestment Act (ARRA) administrative supplement to this award, and F32 GM099382 to EGK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

    Molecular evidence for gender differences in the migratory behaviour of a small seabird

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    Molecular sexing revealed an unexpectedly strong female bias in the sex ratio of pre-breeding European Storm Petrels (Hydrobates pelagicus), attracted to playback of conspecific calls during their northwards migration past SW Europe. This bias was consistent across seven years, ranging from 80.8% to 89.7% female (mean annual sex ratio ± SD = 85.5% female ±4.1%). The sex ratio did not differ significantly from unity (i.e., 50% female) among (i) Storm Petrel chicks at a breeding colony in NW France, (ii) adults found dead on beaches in Southern Portugal, (iii) breeding birds attending nest burrows in the UK, captured by hand, and (iv) adults captured near a breeding colony in the UK using copies of the same sound recordings as used in Southern Europe, indicating that females are not inherently more strongly attracted to playback calls than males. A morphological discriminant function analysis failed to provide a good separation of the sexes, showing the importance of molecular sexing for this species. We found no sex difference in the seasonal or nocturnal timing of migration past Southern Europe, but there was a significant tendency for birds to be caught in sex-specific aggregations. The preponderance of females captured in Southern Europe suggests that the sexes may differ in migration route or in their colony-prospecting behaviour during migration, at sites far away from their natal colonies. Such differences in migration behaviour between males and females are poorly understood but have implications for the vulnerability of seabirds to pollution and environmental change at sea during the non-breeding season

    Molecule Microscopy

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    Contains research objectives and reports on seven research projects.Whitaker Health Sciences FundFrancis L. Friedman ChairNational Institutes of Health (Grant AM-31546)National Institutes of Health (Grant AM-25535)International Business Machines, Inc

    Molecular Physics

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    Contains reports on two research projects.F.L. Freidman ChairNational Institutes of Health (Grant AM 25535)Whitaker FoundationInternational Business Machines, Inc

    The Genetic Architecture of Methotrexate Toxicity Is Similar in Drosophila melanogaster and Humans

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    The severity of the toxic side effects of chemotherapy varies among patients, and much of this variation is likely genetically based. Here, we use the model system Drosophila melanogaster to genetically dissect the toxicity of methotrexate (MTX), a drug used primarily to treat childhood acute lymphoblastic leukemia and rheumatoid arthritis. We use the Drosophila Synthetic Population Resource, a panel of recombinant inbred lines derived from a multiparent advanced intercross, and quantify MTX toxicity as a reduction in female fecundity. We identify three quantitative trait loci (QTL) affecting MTX toxicity; two colocalize with the fly orthologs of human genes believed to mediate MTX toxicity and one is a novel MTX toxicity gene with a human ortholog. A fourth suggestive QTL spans a centromere. Local single-marker association scans of candidate gene exons fail to implicate amino acid variants as the causative single-nucleotide polymorphisms, and we therefore hypothesize the causative variation is regulatory. In addition, the effects at our mapped QTL do not conform to a simple biallelic pattern, suggesting multiple causative factors underlie the QTL mapping results. Consistent with this observation, no single single-nucleotide polymorphism located in or near a candidate gene can explain the QTL mapping signal. Overall, our results validate D. melanogaster as a model for uncovering the genetic basis of chemotoxicity and suggest the genetic basis of MTX toxicity is due to a handful of genes each harboring multiple segregating regulatory factors

    The effects of sulphur poisoning on the microstructure, composition and oxygen transport properties of perovskite membranes coated with nanoscale alumina layers

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    Perovskite oxides displaying mixed ionic and electronic conductivity have attracted a lot of interest for application in oxygen separation membranes. Such membranes could be used for a range of processes, including the conversion of natural gas to hydrogen or syngas. A major limitation of these materials is their tendency to segregate into simpler oxides under operating conditions, reacting with sulphur-based species often found in natural gas and leading to irreversible membrane degradation over time. Here we aim to delay or prevent this process by coating La0.6Sr0.4Co0.2Fe0.8O3-δ membranes with Alumina (Al2O3) layers of 1–100 nm thickness by using atomic layer deposition. We show that coatings of about 30 nm have negligible negative effect on O2 transport flux across the membrane and display good flux recovery when H2S is removed from the stream. Coatings thinner than this critical value provide little protection against irreversible poisoning while thicker coatings dramatically decrease overall O2 permeation fluxes. We also show that the irreversible sulphur poisoning under O2 permeation conditions is linked to microstructural and composition changes at the membrane surface caused predominantly by the formation of SrSO4 particles at the perovskite grain boundaries

    Lithium in the Intermediate-Age Open Cluster, NGC 3680

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    High-dispersion spectra centered on the Li 6708 A line have been obtained for 70 potential members of the open cluster NGC 3680, with an emphasis on stars in the turnoff region. A measurable Li abundance has been derived for 53 stars, 39 of which have radial velocities and proper motions consistent with cluster membership. After being transferred to common temperature and abundance scales, previous Li estimates have been combined to generate a sample of 49 members, 40 of which bracket the cluster Li-dip. Spectroscopic elemental analysis of 8 giants and 5 turnoff stars produces [Fe/H] = -0.17 +/- 0.07 (sd) and -0.07 +/- 0.02 (sd), respectively. We also report measurements of Ca, Si and Ni which are consistent with scaled-solar ratios within the errors. Adopting [Fe/H] = -0.08 (Sect. 3.6), Y^2 isochrone comparisons lead to an age of 1.75 +/- 0.10 Gyr and an apparent modulus of (m-M) = 10.30 +/- 0.15 for the cluster, placing the center of the Li-dip at 1.35 +/- 0.03 solar masses. Among the giants, 5 of 9 cluster members are now known to have measurable Li with A(Li) near 1.0. A combined sample of dwarfs in the Hyades and Praesepe is used to delineate the Li-dip profile at 0.7 Gyr and [Fe/H] = +0.15, establishing its center at 1.42 +/- 0.02 solar masses and noting the possible existence of secondary dip on its red boundary. When evolved to the typical age of the clusters NGC 752, IC 4651 and NGC 3680, the Hyades/Praesepe Li-dip profile reproduces the observed morphology of the combined Li-dip within the CMD's of the intermediate-age clusters while implying a metallicity dependence for the central mass of the Li-dip given by Mass = (1.38 +/-0.04) + (0.4 +/- 0.2)[Fe/H]. The implications of the similarity of the Li-dichotomy among giants in NGC 752 and IC 4651 and the disagreement with the pattern among NGC 3680 giants are discussed.Comment: Latex ms. is 56 pages, including 10 figures and 4 tables. Accepted for the Astronomical Journa

    Shorter constant work rate cycling tests as proxies for longer tests in highly trained cyclists

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    Severe-intensity constant work rate (CWR) cycling tests simulate the high-intensity competition environment and are useful for monitoring training progression and adaptation, yet impose significant physiological and psychological strain, require substantial recovery, and may disrupt athlete training or competition preparation. A brief, minimally fatiguing test providing comparable information is desirable. Purpose To determine whether physiological variables measured during, and functional decline in maximal power output immediately after, a 2-min CWR test can act as a proxy for 4-min test outcomes. Methods Physiological stress (VO _2 kinetics, heart rate, blood lactate concentrations ([La-]b)) was monitored and performance fatigability was estimated (as pre-to-post-CWR changes in 10-s sprint power) during 2- and 4-min CWR tests in 16 high-level cyclists (VO _2peak ¼ 64:4 ± 6:0 ml·kg-1·min-1). The relationship between the 2- and 4-min CWR tests and the physiological variables that best relate to the performance fatigability were investigated. Results The 2-min CWR test evoked a smaller decline in sprint mechanical power (32% vs. 47%, p \u3c 0.001). Both the physiological variables (r = 0.66–0.96) and sprint mechanical power (r = 0.67–0.92) were independently and strongly correlated between 2- and 4-min tests. Differences in VO _2peak and [La-]b in both CWR tests were strongly associated with the decline in sprint mechanical power. Conclusion Strong correlations between 2- and 4-min severe-intensity CWR test outcomes indicated that the shorter test can be used as a proxy for the longer test. A shorter test may be more practical within the elite performance environment due to lower physiological stress and performance fatigability and should have less impact on subsequent training and competition preparation
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