Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved

Bulk and surface thermal stability of ultra nanocrystalline diamond films with 10-30 nm grain size prepared by chemical vapor deposition

The thermal stability of nanocrystalline diamond films with 10-30 nm grain size deposited by microwave enhanced chemical vapor deposition on silicon substrate was investigated as a function of annealing temperature up to 1200&deg;C. The thermal stability of the surface-upper atomic layers was studied with near edge x-ray absorption fine structure (NEXAFS) spectroscopy recorded in the partial electron yield mode. This technique indicated substantial thermally induced graphitization of the film within a close proximity to the surface. While in the bulk region of the film no graphitization was observed with either Raman spectroscopy or NEXAFS spectroscopy recorded in total electron yield mode, even after annealing to 1200&deg;C. Raman spectroscopy did detect the complete disappearance of transpolyacetylene (t-PA)-like 1 and 3 modes following annealing at 1000&deg;C. Secondary ion mass spectroscopy, applied to investigate this relative decrease in hydrogen atom concentration detected only a &sim;30% decrease in the bulk content of hydrogen atoms. This enhanced stability of sp3 hybridized atoms within the bulk region with respect to graphitization is discussed in terms of carbon bond rearrangement due to the thermal decomposition of t-PA-like fragments. <br /

Surface magnetism in iron, cobalt, and nickel

We have calculated magnetic moments, work functions, and surface energies for several of the most closely packed surfaces of iron, cobalt, and nickel by means of a spin-polarized Green’s-function technique based on the linear muffin-tin orbitals method within the tight-binding and atomic sphere approximations. We find enhanced spin moments at all the surfaces considered except for Ni fcc(111), where the moment at the surface reverts to its bulk value. This is in close agreement with earlier slab calculations. In addition, we find that the calculated work functions and surface energies agree with experimental values to within 10%, which may be considered most satisfactory in view of the computational efficiency of the Green’s function technique. Exchange and correlation have been treated wihtin the local spin-density approximation and we have considered three different parametrizations of the original many-body data. We find that the calculated work functions depend as much on the choice of this parametrization as on the effect of spin polarization

Differential inhibition of the release of endogenous and newly synthesized acetylcholine from Torpedo synaptosomes by presynaptic muscarinic receptors

AbstractActivation of Torpedo presynaptic muscarinic acetylcholine (ACh) receptors with the agonist oxotremorine (20 μM) results in the inhibition of Ca2+-dependent release of endogenous ACh from Torpedo synaptosomes. This effect is reversed by the muscarinic antagonist atropine (1 μM) which, by itself, has no effect. In contrast, under the same conditions the amount of newly synthesized radiolabeled [3H]ACh released is not affected by muscarinic ligands. These findings suggest that presynaptic muscarinic inhibition in the Torpedo is due to interference with the mobilization of ACh from a storage pool