| 1. |
- Joshi, Peter K, et al.
(author)
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Directional dominance on stature and cognition in diverse human populations
- 2015
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462
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Journal article (peer-reviewed)abstract
- Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
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| 2. |
- Kunder, Andrea, et al.
(author)
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THE RADIAL VELOCITY EXPERIMENT (RAVE) : FIFTH DATA RELEASE
- 2017
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In: The Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 153:2
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Journal article (peer-reviewed)abstract
- Data Release 5 (DR5) of the Radial Velocity Experiment (RAVE) is the fifth data release from a magnitude-limited (9 < I < 12) survey of stars randomly selected in the Southern Hemisphere. The RAVE medium-resolution spectra (R ∼ 7500) covering the Ca-triplet region (8410-8795 A) span the complete time frame from the start of RAVE observations in 2003 to their completion in 2013. Radial velocities from 520,781 spectra of 457,588 unique stars are presented, of which 255,922 stellar observations have parallaxes and proper motions from the Tycho-Gaia astrometric solution in Gaia DR1. For our main DR5 catalog, stellar parameters (effective temperature, surface gravity, and overall metallicity) are computed using the RAVE DR4 stellar pipeline, but calibrated using recent K2 Campaign 1 seismic gravities and Gaia benchmark stars, as well as results obtained from high-resolution studies. Also included are temperatures from the Infrared Flux Method, and we provide a catalog of red giant stars in the dereddened color - (J Ks) 0 interval (0.50, 0.85) for which the gravities were calibrated based only on seismology. Further data products for subsamples of the RAVE stars include individual abundances for Mg, Al, Si, Ca, Ti, Fe, and Ni, and distances found using isochrones. Each RAVE spectrum is complemented by an error spectrum, which has been used to determine uncertainties on the parameters. The data can be accessed via the RAVE Web site or the VizieR database.
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| 3. |
- Xiang, Jinbao, et al.
(author)
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Hindered dialkyl ether synthesis with electrogenerated carbocations
- 2019
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In: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 573:7774, s. 398-
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Journal article (peer-reviewed)abstract
- Hindered ethers are of high value for various applications; however, they remain an underexplored area of chemical space because they are difficult to synthesize via conventional reactions(1,2). Such motifs are highly coveted in medicinal chemistry, because extensive substitution about the ether bond prevents unwanted metabolic processes that can lead to rapid degradation in vivo. Here we report a simple route towards the synthesis of hindered ethers, in which electrochemical oxidation is used to liberate high-energy carbocations from simple carboxylic acids. These reactive carbocation intermediates, which are generated with low electrochemical potentials, capture an alcohol donor under non-acidic conditions; this enables the formation of a range of ethers (more than 80 have been prepared here) that would otherwise be difficult to access. The carbocations can also be intercepted by simple nucleophiles, leading to the formation of hindered alcohols and even alkyl fluorides. This method was evaluated for its ability to circumvent the synthetic bottlenecks encountered in the preparation of 12 chemical scaffolds, leading to higher yields of the required products, in addition to substantial reductions in the number of steps and the amount of labour required to prepare them. The use of molecular probes and the results of kinetic studies support the proposed mechanism and the role of additives under the conditions examined. The reaction manifold that we report here demonstrates the power of electrochemistry to access highly reactive intermediates under mild conditions and, in turn, the substantial improvements in efficiency that can be achieved with these otherwise-inaccessible intermediates.
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