112 research outputs found
Electrochemical determination of the corrosion behavior of candidate alloys proposed for containment of high level nuclear waste in tuff
Long-term geological disposal of nuclear waste requires corrosion-resistant canister materials for encapsulation. Several austenitic stainless steels are under consideration for such purposes for the disposal of high-level waste at the candidate repository site located at Yucca Mountain, Nevada. With regard to corrosion considerations, a worst case scenario at this prospective repository location would result from the intrusion of vadose water. This preliminary study focuses on the electrochemical and corrosion behavior of the candidate canister materials under worst-case repository environments. Electrochemical parameters related to localized attack (e.g., pitting potentials) and the electrochemical corrosion rates have been examined. 15 references, 15 figures, 4 tables
An integrated map of structural variation in 2,504 human genomes
Structural variants are implicated in numerous diseases and make up the majority of varying nucleotides among human genomes. Here we describe an integrated set of eight structural variant classes comprising both balanced and unbalanced variants, which we constructed using short-read DNA sequencing data and statistically phased onto haplotype blocks in 26 human populations. Analysing this set, we identify numerous gene-intersecting structural variants exhibiting population stratification and describe naturally occurring homozygous gene knockouts that suggest the dispensability of a variety of human genes. We demonstrate that structural variants are enriched on haplotypes identified by genome-wide association studies and exhibit enrichment for expression quantitative trait loci. Additionally, we uncover appreciable levels of structural variant complexity at different scales, including genic loci subject to clusters of repeated rearrangement and complex structural variants with multiple breakpoints likely to have formed through individual mutational events. Our catalogue will enhance future studies into structural variant demography, functional impact and disease association. © 2015 Macmillan Publishers Limited. All rights reserved
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
A draft human pangenome reference
Here the Human Pangenome Reference Consortium presents a first draft of the human pangenome reference. The pangenome contains 47 phased, diploid assemblies from a cohort of genetically diverse individuals. These assemblies cover more than 99% of the expected sequence in each genome and are more than 99% accurate at the structural and base pair levels. Based on alignments of the assemblies, we generate a draft pangenome that captures known variants and haplotypes and reveals new alleles at structurally complex loci. We also add 119 million base pairs of euchromatic polymorphic sequences and 1,115 gene duplications relative to the existing reference GRCh38. Roughly 90 million of the additional base pairs are derived from structural variation. Using our draft pangenome to analyse short-read data reduced small variant discovery errors by 34% and increased the number of structural variants detected per haplotype by 104% compared with GRCh38-based workflows, which enabled the typing of the vast majority of structural variant alleles per sample
Semi-automated assembly of high-quality diploid human reference genomes
The current human reference genome, GRCh38, represents over 20 years of effort to generate a high-quality assembly, which has benefitted society. However, it still has many gaps and errors, and does not represent a biological genome as it is a blend of multiple individuals. Recently, a high-quality telomere-to-telomere reference, CHM13, was generated with the latest long-read technologies, but it was derived from a hydatidiform mole cell line with a nearly homozygous genome. To address these limitations, the Human Pangenome Reference Consortium formed with the goal of creating high-quality, cost-effective, diploid genome assemblies for a pangenome reference that represents human genetic diversity. Here, in our first scientific report, we determined which combination of current genome sequencing and assembly approaches yield the most complete and accurate diploid genome assembly with minimal manual curation. Approaches that used highly accurate long reads and parent-child data with graph-based haplotype phasing during assembly outperformed those that did not. Developing a combination of the top-performing methods, we generated our first high-quality diploid reference assembly, containing only approximately four gaps per chromosome on average, with most chromosomes within ±1% of the length of CHM13. Nearly 48% of protein-coding genes have non-synonymous amino acid changes between haplotypes, and centromeric regions showed the highest diversity. Our findings serve as a foundation for assembling near-complete diploid human genomes at scale for a pangenome reference to capture global genetic variation from single nucleotides to structural rearrangements
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Materials evaluation for geothermal applications: turbine materials
A number of candidate turbine materials are being evaluated for their resistance to erosion, corrosion, and stress corrosion cracking (SCC) in geothermal brines. These materials include Fe-, Ni-, Co and Ti-base alloys, coatings and ceramics. Tapered wearblades, simulating the leading edge of a turbine blade, are exposed to the direct impact of a two-phase nozzle exhaust. Bent beam SCC specimens, which are constrained in fixtures attached to the wearblade holders, are also exposed to this exhaust. Results of a test series are reported in which acidified liquid brine was expanded to atmospheric pressure are reported. The tests were performed at the LLL Field Test Station near Niland in the Salton Sea Geothermal Field. Evaluation of the exposed materials indicates that Ti-base alloys show the most promise for turbine wheel components in the high salinity geothermal environments
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Behavior of stressed and unstressed 304L specimens in tuff repository environmental conditions
This paper presents preliminary results of an investigation of the behavior of candidate barrier material for high-level nuclear waste storage, Type 304L stainless steel, in tuff repository environmental conditions. Tuff is a densely welded, devitrified, igneous rock common to the proposed repository site at Yucca Mountain, Nevada. The results discussed include: irradiation corrosion tests, U-bend irradiation corrosion tests, slow strain rate tests, and bent beam stress corrosion tests. Results indicate that Type 304L stainless steel shows excellent resistance to general, localized, and stress corrosion under the environmental and microstructural conditions tested so far. The environmental test conditions are 50 to 100{sup 0}C J-13 well water (non-saline, near neutral pH, and oxic in nature) and saturated steam at 100{sup 0}C. Microstructural conditions include solution annealed and long furnace heat treatments to provoke a sensitized structure. However, this particular type of stainless steel may be susceptible to long-term, low-temperature sensitization because of the combination of expected time at elevated temperature and residual stress in the container after emplacement in the repository. Other grades of austenitic stainless steels are reported to be more resistant to low-temperature sensitization. Future work will therefore include more extensive testing of these grades. 15 references, 5 figures, 7 tables
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