120,194 research outputs found
Hundreds of variants clustered in genomic loci and biological pathways affect human height
No full textMost common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits(1), but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait(2,3). The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways
Memorandum from A. E. Demaray to E. C. Finney
No full textFour letters of correspondence about the purchase of Bright Angel Trail between A. E. Demaray, Acting Director of the Grand Canyon National Park; E. C. Finney, Department of the Interior First Assistant Secretary; Carl T. Hayden, Representative (AZ); and Stephen T. Mather, Director of the National Park Service
Coarse-grained, density dependent implicit solvent model reliably reproduces behavior of a model surfactant system
No full textDensity dependent, implicit solvent (DDIS) potentials, the generation of which has been described previously [ E. C. Allen and G. C. Rutledge, J. Chem. Phys. 128, 154115 (2008) ; E. C. Allen and G. C. Rutledge, J. Chem. Phys. 130, 034904 (2009) ], are used in this work to examine the self-assembly of a model surfactant system. While the measurement of thermodynamic properties in simulations of solvated micelles requires large computational resources or specialized free energy calculations, the high degree of coarse-graining enabled by the DDIS algorithm allows for the measurement of critical micelle concentration and aggregation number distribution using single processor NVT simulations. In order to evaluate the transferability of potentials derived from the DDIS methodology, the potentials are derived from simulations of simple monomeric solutes and used in the surfactant system without modification. Despite the high degree of coarse graining and the simplicity of the fitting simulations, we demonstrate that the coarse-grained DDIS potentials generated by this method reliably reproduce key properties of the underlying surfactant system: the critical micelle concentration, and the average aggregation number. The success of the DDIS algorithm suggests its utility for more realistic surfactant models.United States. Dept. of Energy (Office of Science, Computational Science Graduate Fellowship Program)United States. Dept. of Energy (National Nuclear Security Administration, Contract No. DEFG02- 97ER25308
A cryo-enzymological study of the catalytic mechanism of carboxypeptidase A using ����C NMR
No full textTypescript (photocopy).Carboxypeptidase A is classified as an exopeptidase enzyme because it is able to remove single hydrophobic amino acid residue from peptide substrates. The proposed mechanisms for the catalytic hydrolysis are still very controversial, although recent findings strongly suggest a noncovalent process. Several cryo-enzyme studies have shown that at lower temperatures, a single intermediate does appear to accumulate to reasonably high levels. Data collected on this intermediate has not been able to establish its identify. In an attempt to obtain unambiguous information on this species, ('13)C NMR was used to study chemical changes taking place at the reactive site on the substrate. Methods were developed to synthesize milligram quantities of specifically labeled substrates and inhibitors from readily available ('13)C-enriched precursors. Cryo-solvent systems were then tested for their ability to (1) lower freezing points (2) dissolve the enzyme (3) maintain the enzyme's native conformation (4) dissolve several turnovers of substrate (5) minimize the solvent viscosity. Three separate cryo-solvent systems were produced which were able to fulfill most of these requirements. An enzyme-substrate experiment using a methanol/ethylene glycol cryo-solvent was performed at -61 (+OR-) 3(DEGREES)C in an NMR spectrometer. The rate of hydrolysis, as determined from the NMR signals, was about two turnovers per day at this temperature. Although adequate signal-to-noise could be obtained, the only signals found during the course of the reaction were product and substrate peaks. No ('13)C signals were found for any metastable product, any enzyme-bound intermediate or any of the enzyme's own natural abundance resonances. Subsequent studies with an enzyme-bound inhibitor species confirmed earlier suspicions that an enzyme-bound nuclei would not give a detectable ('13)C signal under useful cryo-conditions. Further studies showed that the source of the unfavorable relaxation parameters was both the solvent viscosity and protein aggregation. Strategies for dealing with these problems are discussed
Letter from Audrey C. Broadnax to James E. Allen, June 19, 1963
No full textLetter regarding a visit by James E. Allen
C. E. F. Allen
No full textC. E. F. Allen in a horse-drawn cutter. He was appointed Curator of the Gardens in 1913 and retired in Darwin on 17 June 1936. He was a member of the first official Darwin AIF contingent which left in April 1915; he served on the Gallipoli Peninsula and later in France and Belgium. He rose to the rank of Lieutenant in the 25th Battalion in which he served throughout the war. He died in England in 1938. Annual agricultural and botany reports prepared by Allen for the Administrator during Allen's service are an enlightening and interesting legacy for researchers in that field. His contribution to Darwin is recognised by Allen Street, Fannie Bay and Allen Park, Fannie Bay (information courtesy Frank Geddes, Darwin, 22 November 1989). Photo shows Allen cutting Para grass in the Botanic Gardens.Geddes, Frank.Date:192
[Major A. C. Allen, Confederate States Army]
No full textPortrait of Major A. C. Allen, 19th Texas Infantry, Confederate States Army, taken while prisoner of war in New Orleans, Louisiana.Recto: [handwritten] Major A. C. Allen, Texas. Verso: [handwritten] Major A. C. Allen, 19th Texas Infantry Taken while a prisoner of war - at N.O. La
The duration derby: a comparison of duration based strategies in asset liability management
No full textMacaulay duration matched strategy is a key tool in bond portfolio immunization. It is well known that if term structures are not at or changes are not parallel, then Macaulay duration matched portfolio can not guarantee adequate immunization. In this paper the approximate duration is proposed to measure the bond price sensitivity to changes of interest rates of non- at term structures. Its performance in immunization is compared with those of Macaulay, partial and key rate durations using the US Treasury STRIPS and Bond data. Approximate duration turns out to be a possible contender in asset liability management: it does not assume any particular structures or patterns of changes of interest rates, it does not need short selling of bonds, and it is easy to set up and rebalance the optimal portfolio with linear programming
Author, publisher and bookseller : a tripartite synergy in Nigerian book industry
No full textThis work is about the roles of Author, Publisher and Bookseller in Book development in
Nigeria. The paper started by delving into the history of Book Publishing in Nigeria after
which it proceeded by defining who an author, a publisher, and a bookseller is and
expatiated on the indispensable roles of these key actors in Nigerian Book Industry and in
the emerging Information Society. Furthermore, the various constraints to book
development were identified while the paper advised on how the Book Industry can be
further promoted in Nigeria. However, the paper concluded and made recommendations
on how the Book sector can help in enhancing scholarship in the country
Harnessing science for a sustainable future: narrowing the policy, research and community divide
No full textAllen, C., Espey, J., Marks, A., & Skipper, M. (2021, May 1). Harnessing Science for a Sustainable Future: Narrowing the Policy, Research and Community Divide. https://media.springernature.com/full/springer-cms/rest/v1/content/19094276/data/v2<br/
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