158 research outputs found

    Induction flowmeter for dielectric fluids, experimental verification final report

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    Experimental verification of induction flow meter for use with dielectric fluid

    The AXAF technology program: The optical flats tests

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    The results of a technology program aimed at determining the limits of surface polishing for reflecting X-ray telescopes is presented. This program is part of the major task of developing the Advanced X-ray Astrophysical Facility (AXAF). By studying the optical properties of state-of-the-art polished flat surfaces, conclusions were drawn as to the potential capability of AXAF. Surface microtopography of the flats as well as their figure are studied by X-ray, visual, and mechanical techniques. These techniques and their results are described. The employed polishing techniques are more than adequate for the specifications of the AXAF mirrors

    The solution structure of a cyclic endothelin antagonist, BQ-123, based on 1Hî—¸1H and 13Hî—¸1H three bond oupling constants

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    AbstractA cyclic pentapeptide endothelin antagonist, cyclo(dTrp-dAsp-Pro-dVal-Leu), recently reported (K. Ishikawa et al., 13th Am. Pept. Symp., Cambridge MA, 1991) has been studied by NMR spectroscopy and molecular modeling. A stable structure has been determined without the use of nuclear Overhauser effects and is based primarily on homonuclear and heteronuclear three bond coupling constants. The 13C-edited TOCSY experiment is demonstrated at natural abundance and ∼30 mM peptide concentrations. Three bond 13C1H coupling constants obtained by this method are shown to reduce the ambiguity in φ angle determination which exists when only interproton coupling constants are used. Three out of four φ angles were determined uniquely by this method and the fourth was reduced to two possible values. The proline φ angle was determined to be −78° based on the 3JHzHα and 3JHzHβ coupling constants. Comparison of amide proton temperature dependence, chemical shifts and vicinal proton coupling constants in a 20% acetonitrile/80% water solvent mixture and in (CD3)2SO indicates that the structure is similar in both solvents

    Exome Chip Meta-analysis Fine Maps Causal Variants and Elucidates the Genetic Architecture of Rare Coding Variants in Smoking and Alcohol Use

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    BACKGROUND: Smoking and alcohol use have been associated with common genetic variants in multiple loci. Rare variants within these loci hold promise in the identification of biological mechanisms in substance use. Exome arrays and genotype imputation can now efficiently genotype rare nonsynonymous and loss of function variants. Such variants are expected to have deleterious functional consequences and to contribute to disease risk. METHODS: We analyzed similar to 250,000 rare variants from 16 independent studies genotyped with exome arrays and augmented this dataset with imputed data from the UK Biobank. Associations were tested for five phenotypes: cigarettes per day, pack-years, smoking initiation, age of smoking initiation, and alcoholic drinks per week. We conducted stratified heritability analyses, single-variant tests, and gene-based burden tests of nonsynonymous/loss-of-function coding variants. We performed a novel fine-mapping analysis to winnow the number of putative causal variants within associated loci. RESULTS: Meta-analytic sample sizes ranged from 152,348 to 433,216, depending on the phenotype. Rare coding variation explained 1.1% to 2.2% of phenotypic variance, reflecting 11% to 18% of the total single nucleotide polymorphism heritability of these phenotypes. We identified 171 genome-wide associated loci across all phenotypes. Fine mapping identified putative causal variants with double base-pair resolution at 24 of these loci, and between three and 10 variants for 65 loci. Twenty loci contained rare coding variants in the 95% credible intervals. CONCLUSIONS: Rare coding variation significantly contributes to the heritability of smoking and alcohol use. Fine-mapping genome-wide association study loci identifies specific variants contributing to the biological etiology of substance use behavior.Peer reviewe

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

    Patient and stakeholder engagement learnings: PREP-IT as a case study

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