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- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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2. |
- Gleisner, Magdalena, et al.
(författare)
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Pyrite oxidation by Acidithiobacillus ferrooxidans at various concentrations of dissolved oxygen.
- 2006
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Ingår i: Chemical Geology. - : Elsevier BV. - 0009-2541 .- 1872-6836. ; 225:1-2, s. 16-29
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Tidskriftsartikel (refereegranskat)abstract
- Pyrite oxidation rates were examined at various concentrations of dissolved oxygen (DO) in the presence of the sulfur and iron oxidizer Acidithiobacillus ferrooxidans. Five different batch experiments were performed at room temperature for 75 days under various DO levels (273, 129, 64.8, 13.2, and ≤ 0.006 μM), containing pyrite grains (particle size 63–250 μm) and a modified 9K nutrient medium at pH 3. The reactors were inoculated with A. ferrooxidans. In all experiments, pH decreased with time and sulfur and iron were released to the solution, indicating pyrite oxidation at all DO levels. Pyrite oxidation rates (ca. 5 × 10− 10 mol m− 2 s− 1 at 273 μM DO) from all experiments showed positive correlation with DO, Fe(III), and bacterial concentration. These rates were significantly slower than rates presented in other published studies, but this is probably due to the significantly greater Fe(III) concentration at lower pH in these previous studies. The results obtained in this study suggest that ferric iron reduction at the pyrite surface is the primarily mechanism for microbial pyrite oxidation in the presence of DO. The results from our study support the indirect mechanism of sulfide oxidation, where A. ferrooxidans oxidizes ferrous iron in the presence of DO, which then oxidizes pyrite.
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4. |
- Hylander, Lars Daniel, 1954-, et al.
(författare)
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Mercury By-Production and Emissions at Pyrometallurgical Extraction of Nonferrous Sulfide Ores Globally
- 2009
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Ingår i: Proceedings of the 9th International Conference on Mercury as a Global Pollutant. ; , s. 42-
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Pyrometallurgical extraction of nonferrous sulfide ores may be a significant source of mercury (Hg) emissions and Hg by-production globally. In this study, we estimate Hg emissions from the pyrometallurgical treatment of Cu, Pb, and Zn sulfide ores. We base our calculations on quantities processed and Hg content in the concentrates, derived from unique global databases on smelter feed and production. In 2005, about 275 tons of Hg were emitted globally to the atmosphere from Cu, Pb, and Zn smelters. Nearly one-half was emitted from Zn smelters and the other half equally divided between Cu and Pb smelters. Most Hg was emitted in China, followed by the Russian Federation, India, and South Korea. Calculations indicate that Hg abatementtechnologies applied to flue gases may have recovered 8.8 tons and 228 tons Hg from Pb and Zn smelters, respectively, most of which was probably sold as a byproduct. In conclusion, Hg emitted from processing copper, lead, and zinc ores has been largely underestimated in Hg emission inventories, amounting to rougly the same amounts of Hg by-production and Hg emissions as industrial gold mining. Reducing these emissions may be one of the most economical measures to reduce global Hg emissions.
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5. |
- Jacobs, Kevin B, et al.
(författare)
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Detectable clonal mosaicism and its relationship to aging and cancer.
- 2012
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Ingår i: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:6, s. 651-658
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Tidskriftsartikel (refereegranskat)abstract
- In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
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6. |
- Schippers, Axel, et al.
(författare)
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Geomicrobiological and geochemical investigation of pyrite – containing tailings from Kristineberg, Northern Sweden
- 2005
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Ingår i: Proceedings, Securing the Future. Skellefteå, Sweden. ; , s. 866-875
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Konferensbidrag (populärvet., debatt m.m.)abstract
- Pyrite - containing tailings in Impoundment 1 in Kristineberg, northern Sweden were covered in 1996 with a soil cover consisting of 0.3 m compacted till and 1.5 m unspecified till. From the 1940s until 1996, the impoundment was unremediated and sulfide oxidation occurred to depths of 1 m in the tailings. This study focuses on the importance of microorganisms for pyrite oxidation and the release of oxidation products in the remediated tailings. Three cores containing material from the sealing layer and the zones of oxidized and unoxidized tailings were taken in September 2003 and geomicrobiologically and geochemically analyzed. Most-probable-number (MPN) numbers of pyrite-oxidizing, acidophilic Fe(II)-oxidizing microorganisms of the type Acidithiobacillus ferrooxidans were highest with up to 106 cells g-1 dw at the interface between the oxidized and unoxidized tailings, which correlates with maximum metal and sulfate pore water concentrations, a shift of pH and pe, as well as with high potential biological pyrite oxidation rates measured by microcalorimetry at atmospheric oxygen content. The mean proportion of biological pyrite oxidation was 80 % for the oxidized tailings. The potential pyrite oxidation rate for an assumed 0.3 m thick oxidation zone within the oxidized tailings was 4.7 x10-6 mol m-2 s-1 tailings surface (18 kg FeS2 m-2 year-1). The potential chemical pyrite oxidation rate was highest for the unoxidized tailings where Fe(II)-oxidizing microorganisms could not be detected and where the pyrite content was much higher than in the oxidized tailings. The results show that pyrite is biologically oxidized in particular zones of the mine tailings.
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