| 1. |
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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 3. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 5. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 6. |
- 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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| 7. |
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| 8. |
- Aad, G, et al.
(författare)
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- 2015
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swepub:Mat__t
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| 9. |
- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 10. |
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| 11. |
- Mahajan, Anubha, et al.
(författare)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 12. |
- Meng, Long, et al.
(författare)
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Dynamic Response of 6MW Spar Type Floating Offshore Wind Turbine by Experiment and Numerical Analyses
- 2020
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Ingår i: China Ocean Engineering. - : Springer Science and Business Media LLC. - 0890-5487 .- 2191-8945. ; 34:5, s. 608-620
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Tidskriftsartikel (refereegranskat)abstract
- The floating offshore wind turbine (FOWT) is widely used for harvesting marine wind energy. Its dynamic responses under offshore wind and wave environment provide essential reference for the design and installation. In this study, the dynamic responses of a 6MW Spar type FOWT designed for the water depth of 100 m are investigated by means of the wave tank experiment and numerical analysis. A scaled model is manufactured for the experiment at a ratio of 65.3, while the numerical model is constructed on the open-source platform FAST (Fatigue, Aerodynamics, Structures, and Turbulence). Still water tests, wind-induced only tests, wave-induced only tests and combined wind-wave-current tests are all conducted experimentally and numerically. The accuracy of the experimental set-up as well as the loading generation has been verified. Surge, pitch and heave motions are selected to analyze and the numerical results agree well with the experimental values. Even though results obtained by using the FOWT calculation model established in FAST software show some deviations from the test results, the trends are always consistent. Both experimental and numerical studies demonstrate that they are reliable for the designed 6MW Spar type FOWT.
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| 13. |
- Takeuchi, Fumihiko, et al.
(författare)
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Interethnic analyses of blood pressure loci in populations of East Asian and European descent
- 2018
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, we perform a multi-stage genome-wide association study for BP (max N = 289,038) principally in East Asians and meta-analysis in East Asians and Europeans. We report 19 new genetic loci and ancestry-specific BP variants, conforming to a common ancestry-specific variant association model. At 10 unique loci, distinct non-rare ancestry-specific variants colocalize within the same linkage disequilibrium block despite the significantly discordant effects for the proxy shared variants between the ethnic groups. The genome-wide transethnic correlation of causal-variant effect-sizes is 0.898 and 0.851 for systolic and diastolic BP, respectively. Some of the ancestry-specific association signals are also influenced by a selective sweep. Our results provide new evidence for the role of common ancestry-specific variants and natural selection in ethnic differences in complex traits such as BP.
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| 14. |
- Ablikim, M., et al.
(författare)
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Branching fraction measurement of J/ψ→KSKL and search for J/ψ→KSKS
- 2017
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Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:11
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Tidskriftsartikel (refereegranskat)abstract
- Using a sample of 1.31 x 10(9) J/Psi events collected with the BESIII detector at the BEPCII collider, we study the decays of J/Psi -> KSKL and KSKS. The branching fraction of J/Psi -> KSKL is determined to be B(J/Psi -> KSKL) = (1.93 +/- 0.01 (stat) +/- 0.05 (syst)) x 10(-4), which significantly improves on previous measurements. No clear signal is observed for the J/Psi -> KSKS process, and the upper limit at the 95% confidence level for its branching fraction is determined to be B(J/Psi -> KSKS) < 1.4 x 10(-8), which improves on the previous searches by 2 orders in magnitude and reaches the order of the Einstein-Podolsky-Rosen expectation.
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| 15. |
- Ablikim, M., et al.
(författare)
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Evidence for e+e−→γηc(1S) at center-of-mass energies between 4.01 and 4.60 GeV
- 2017
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Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:5
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Tidskriftsartikel (refereegranskat)abstract
- We present first evidence for the process e(+)e(-) -> gamma eta(c)(1S) at six center-of-mass energies between 4.01 and 4.60 GeV using data collected by the BESIII experiment operating at BEPCII. We measure the Born cross section at each energy using a combination of twelve eta(c)(1S) decay channels. We also combine all six energies under various assumptions for the energy-dependence of the cross section. If the process is assumed to proceed via the Y(4260), we measure a peak Born cross section sigma(peak)(e(+)e(-) -> gamma eta(c)(1S)) = 2.11 +/- 0.49 (stat.) +/- 0.36 (syst.) pb with a statistical significance of 4.2 sigma.
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| 16. |
- Ablikim, M., et al.
(författare)
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Improved measurements of X-cJ -> Sigma(+) (Sigma)over-bar(-) and Sigma(0)(Sigma)over-bar(0) decays
- 2018
-
Ingår i: Physical Review D. - : American Physical Society. - 2470-0010 .- 2470-0029. ; 97:5
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Tidskriftsartikel (refereegranskat)abstract
- Using a data sample of (448.1 +/- 2.9) x 10(6) psi (3686) events collected with the BESIII detector at the BEPCII collider, we present measurements of branching fractions for the decays X-cJ -> Sigma(+) (Sigma) over bar (-) and Sigma(0) (Sigma) over bar (0) The decays X-c1.2 -> Sigma(+) (Sigma) over bar (-) and Sigma (Sigma) over bar (0) are observed for the first time, and the branching fractions for X-c0 -> Sigma(+) (Sigma) over bar (-) and Sigma(0) (Sigma) over bar (0) decays are measured with improved precision. The branching fraction ratios between the charged and neutral modes are consistent with the prediction of isospin symmetry.
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| 17. |
- Ablikim, M., et al.
(författare)
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Measurement of branching fractions for psi(3686) -> gamma eta ', gamma eta, and gamma pi(0)
- 2017
-
Ingår i: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 96:5
-
Tidskriftsartikel (refereegranskat)abstract
- Using a data sample of 448 x 10(6) psi(3686) events collected with the BESIII detector operating at the BEPCII storage ring, the decays psi(3686) -> gamma eta and psi(3686) -> gamma pi(0) are observed with a statistical significance of 7.3 sigma and 6.7 sigma, respectively. The branching fractions are measured to be B(psi(3686) -> gamma eta) = (0.85 +/- 0.18 +/- 0.05) x 10(-6) and B(psi(3686) ->gamma pi(0)) = (0.95 +/- 0.16 +/- 0.05) x 10(-6). In addition, we measure the branching fraction of psi(3686) -> gamma eta' to be B(psi(3686) -> gamma eta') = (125.1 +/- 2.2 +/- 6.2)x10(-6), which represents an improvement of precision over previous results.
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| 18. |
- Ablikim, M., et al.
(författare)
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Measurement of the matrix elements for the decays eta' -> eta pi(+) pi(-) and eta' -> eta pi(0)pi(0)
- 2018
-
Ingår i: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 97:1
-
Tidskriftsartikel (refereegranskat)abstract
- Based on a sample of 1.31 x 10(9) J/psi events collected with the BESIII detector, the matrix elements for the decays eta' -> eta pi(+) pi(-) and eta' -> eta pi(0)pi(0) are determined using 351,016 eta' -> (eta -> gamma gamma)pi' pi(-) and 56,249 eta' -> (eta -> gamma gamma)pi(0) pi(0) events with background levels less than 1%. Two commonly used representations are used to describe the Dalitz plot density. We find that an assumption of a linear amplitude does not describe the data well. A small deviation of the obtained matrix elements between eta' -> eta pi(+) pi(-) and eta' -> eta pi(0)pi(0) is probably caused by the mass difference between charged and neutral pions or radiative corrections. No cusp structure in eta' -> eta pi(0)pi(0) is observed.
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| 19. |
- Ablikim, M., et al.
(författare)
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Measurements of absolute branching fractions for D mesons decays into two pseudoscalar mesons
- 2018
-
Ingår i: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 97:7
-
Tidskriftsartikel (refereegranskat)abstract
- Using a data sample of e(+)e(-) collision data with an integrated luminosity of 2.93 fb(-1) taken at the center-of-mass energy root s = 3.773 GeV with the BESIII detector operating at the BEPCII storage rings, we measure the absolute branching fractions of the two-body hadronic decays D+ -> pi(+)pi(0), K+pi(0), pi(+)eta., K+eta., pi(+)eta', K+eta', K-S(0)pi(+), (KSK+)-K-0, and D-0 -> pi(+)pi(-), K+ K-, K--/+pi(+/-), K-S(0)pi(0), K-S(0)eta, K-S(0)eta' Our results are consistent with previous measurements within uncertainties. Among them, the branching fractions for D+-> pi(+)pi(0), K+pi(0), pi(+)eta, pi(+)eta', (KSK+)-K-0, (KSK+)-K-0 and D-0 -> K-S(0)pi(0), K-S(0)eta, K-S(0)eta' are determined with improved precision compared to the world average values.
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| 20. |
- Ablikim, M., et al.
(författare)
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Measurements of the branching fractions for the semileptonic decays D-s(+) -> phi e(+)v(e), phi mu(+)v(mu), eta mu(+)v(mu) and eta 'mu(+)v(mu)
- 2018
-
Ingår i: Physical Review D. - : American Physical Society. - 2470-0010 .- 2470-0029. ; 97:1
-
Tidskriftsartikel (refereegranskat)abstract
- By analyzing 482 pb(-1) of e(+) e(-) collision data collected at the center-of-mass energy root s = 4.009 GeV with the BESIII detector, we measure the branching fractions for the semi-leptonic decays D-s(+) -> phi e(+)v(e), phi mu(+)v(mu), eta mu(+)v(mu) and eta'mu(+)v(mu) to be B(D-s(+) -> phi e(+)v(e)) = (2.26 +/- 0.45 +/- 0.09)%, B(D-s(+) -> phi mu+v(mu)) = (1.94 +/- 0.53 +/- 0.09)%, B(D-s(+) -> eta mu(+)v(mu)) = (2.42 +/- 0.46 +/- 011)% and B(D-s(+) -> eta'mu(+)v(mu)) = (1.06 +/- 0.54 +/- 0.07)%, where the first and second uncertainties are statistical and systematic, respectively. The branching fractions for the three semi-muonic decays D-s(+) -> phi mu(+)v(mu), eta mu(+)v(mu) and eta'mu(+)v(mu) are determined for the first time and that of D-s(+) -> phi e(+)v(e) is consistent with the world average value within uncertainties.
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| 21. |
- Ablikim, M., et al.
(författare)
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Observation of a(0)(0)(980)-f(0)(980) Mixing
- 2018
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Ingår i: Physical Review Letters. - : AMER PHYSICAL SOC. - 0031-9007 .- 1079-7114. ; 121:2
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Tidskriftsartikel (refereegranskat)abstract
- We report the first observation of a(0)(0)(980)-f(0)(980) mixing in the decays of J/psi -> phi f(0)(980) -> phi a(0)(0)(980) -> phi eta pi(0) and chi(c1) -> a(0)(0)(980)pi(0) -> f(0)(980)pi(0)->pi(+)pi(-)pi(0), using data samples of 1.31 x 10(9) J/psi events and 4.48 x 10(8) psi (3686) events accumulated with the BESIII detector. The signals of f(0)(980) -> a(0)(0)(980) and a(0)(0)(980) -> f(0)(980) mixing are observed at levels of statistical significance of 7.4 sigma and 5.5 sigma, respectively. The corresponding branching fractions and mixing intensities are measured and the constraint regions on the coupling constants, g(a0K+K-) and g(f0K+K-), are estimated. The results improve the understanding of the nature of a(0)(0)(980) and f(0)(980).
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| 22. |
- Ablikim, M., et al.
(författare)
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Observation of χc2→η′η′ and χc0,2→ηη′
- 2017
-
Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:11
-
Tidskriftsartikel (refereegranskat)abstract
- Using a sample of 448.1×106 ψ(3686) events collected with the BESIII detector in 2009 and 2012, we study the decays χc0,2→η′η′ and ηη′. The decays χc2→η′η′, χc0→ηη′ and χc2→ηη′ are observed for the first time with statistical significances of 9.6σ, 13.4σ and 7.5σ, respectively. The branching fractions are determined to be B(χc0→η′η′)=(2.19±0.03±0.14)×10−3, B(χc2→η′η′)=(4.76±0.56±0.38)×10−5, B(χc0→ηη′)=(8.92±0.84±0.65)×10−5 and B(χc2→ηη′)=(2.27±0.43±0.25)×10−5, where the first uncertainties are statistical and the second are systematic. The precision for the measurement of B(χc0→η′η′) is significantly improved compared to previous measurements. Based on the measured branching fractions, the role played by the doubly and singly Okubo-Zweig-Iizuka disconnected transition amplitudes for χc0,2 decays into pseudoscalar meson pairs can be clarified.
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| 23. |
- Ablikim, M., et al.
(författare)
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Precision Measurement of the e(+)e(-) -> Lambda(+)(c)(Lambda)over-bar(c)(-) Cross Section Near Threshold
- 2018
-
Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 120:13
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Tidskriftsartikel (refereegranskat)abstract
- The cross section of the e(+)e(-) -> Lambda(+)(c)(Lambda) over bar (-)(c) process is measured with unprecedented precision using data collected with the BESIII detector at root s = 4574.5, 4580.0, 4590.0 and 4599.5 MeV. The nonzero cross section near the Lambda(+)(c)(Lambda) over bar (-)(c) production threshold is cleared. At center-of-mass energies root s = 4574.5 and 4599.5 MeV, the higher statistics data enable us to measure the Lambda(c) polar angle distributions. From these, the.c electric over magnetic form-factor ratios (vertical bar G(E)/G(M)vertical bar) are measured for the first time. They are found to be 1.14 +/- 0.14 +/- 0.07 and 1.23 +/- 0.05 +/- 0.03, respectively, where the first uncertainties are statistical and the second are systematic.
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| 24. |
- Ablikim, M., et al.
(författare)
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Search for the rare decays J/ψ→D0e+e−+c.c. and ψ(3686)→D0e+e−+c.c.
- 2017
-
Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:11
-
Tidskriftsartikel (refereegranskat)abstract
- Using the data samples of (1310.6 +/- 7.2) x 10(6) J/psi events and (448.1 +/- 2.9) x 10(6) psi(3686) events collected with the BESIII detector, we search for the rare decays J/psi -> D(0)e(+) e(-) + c.c. and psi(3686) -> D(0)e(+) e(-) + c.c. No significant signals are observed and the corresponding upper limits on the branching fractions at the 90% confidence level are determined to be B(J/psi -> D(0)e(+) e(-) + c.c.) < 8.5 x 10(-8) and B(psi(3686) -> D(0)e(+) e(-) + c.c.) < 1.4 x 10(-7), respectively. Our limit on B(J/psi -> D(0)e(+) e(-) + c.c.) is more stringent by 2 orders of magnitude than the previous results, and B(psi(3686) -> D(0)e(+) e(-) + c.c.) is measured for the first time.
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| 25. |
- Ablikim, M., et al.
(författare)
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Search for ψ(3686)→γηc(η(1405))→γπ+π−π0
- 2017
-
Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:11
-
Tidskriftsartikel (refereegranskat)abstract
- Using a sample of 448.1×106 ψ(3686) events collected with the BESIII detector, a search for the isospin violating decay ηc→π+π−π0 via ψ(3686)→γηc is presented. No signal is observed, and the upper limit on B(ψ(3686)→γηc)×B(ηc→π+π−π0) is determined to be 1.6×10−6 at the 90% confidence level. In addition, a search for η(1405)→f0(980)π0 in ψ(3686) radiative decays is performed. No signal is observed, and the branching fraction B(ψ(3686)→γη(1405))×B(η(1405)→f0(980)π0)×B(f0(980)→π+π−) is calculated to be less than 5.0×10−7 at the 90% confidence level.
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| 26. |
- Ablikim, M., et al.
(författare)
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Study of J/ψ and ψ(3686) decays to π+π−η′
- 2017
-
Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:11
-
Tidskriftsartikel (refereegranskat)abstract
- Using the data samples of 1.31×109 J/ψ events and 4.48×108 ψ(3686) events collected with the BESIII detector, partial wave analyses on the decays J/ψ and ψ(3686)→π+π−η′ are performed with a relativistic covariant tensor amplitude approach. The dominant contribution is found to be J/ψ and ψ(3686) decays to ρη′. In the J/ψ decay, the branching fraction B(J/ψ→ρη′) is determined to be (7.90±0.19(stat)±0.49(sys))×10−5. Two solutions are found in the ψ(3686) decay, and the corresponding branching fraction B(ψ(3686)→ρη′) is (1.02±0.11(stat)±0.24(sys))×10−5 for the case of destructive interference, and (5.69±1.28(stat)±2.36(sys))×10−6 for constructive interference. As a consequence, the ratios of branching fractions between ψ(3686) and J/ψ decays to ρη′ are calculated to be (12.9±1.4(stat)±3.1(sys))% and (7.2±1.6(stat)±3.0(sys))%, respectively. We also determine the inclusive branching fractions of J/ψ and ψ(3686) decays to π+π−η′ to be (1.36±0.02(stat)±0.08(sys))×10−4 and (1.51±0.14(stat)±0.23(sys))×10−5, respectively
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| 27. |
- Ariyawansa, Hiran A., et al.
(författare)
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Fungal diversity notes 111–252—taxonomic and phylogenetic contributions to fungal taxa
- 2015
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Ingår i: Fungal diversity. - : Springer Science and Business Media LLC. - 1560-2745 .- 1878-9129. ; 75, s. 27-274
-
Tidskriftsartikel (refereegranskat)abstract
- This paper is a compilation of notes on 142 fungal taxa, including five new families, 20 new genera, and 100 new species, representing a wide taxonomic and geographic range. The new families, Ascocylindricaceae, Caryosporaceae and Wicklowiaceae (Ascomycota) are introduced based on their distinct lineages and unique morphology. The new Dothideomycete genera Pseudomassariosphaeria (Amniculicolaceae), Heracleicola, Neodidymella and P s e u d o m i c ros p h a e r i o p s i s ( D id y m e l l a c e a e ) , P s e u d o p i t h o m y c e s ( D i d y m o s p h a e r i a c e a e ) , Brunneoclavispora, Neolophiostoma and Sulcosporium (Halotthiaceae), Lophiohelichrysum (Lophiostomataceae), G a l l i i c o l a , Popul o c re s c e n t i a a nd Va g i c o l a (Phaeosphaeriaceae), Ascocylindrica (Ascocylindricaceae), E l o n g a t o p e d i c e l l a t a ( R o u s s o e l l a c e a e ) , Pseudoasteromassaria (Latoruaceae) and Pseudomonodictys (Macrodiplodiopsidaceae) are introduced. The newly described species of Dothideomycetes (Ascomycota) are Pseudomassariosphaeria bromicola (Amniculicolaceae), Flammeascoma lignicola (Anteagloniaceae), Ascocylindrica marina (Ascocylindricaceae) , Lembosia xyliae (Asterinaceae), Diplodia crataegicola and Diplodia galiicola ( B o t r yosphae r i a cea e ) , Caryospor a aquat i c a (Caryosporaceae), Heracleicola premilcurensis and Neodi dymell a thai landi cum (Didymellaceae) , Pseudopithomyces palmicola (Didymosphaeriaceae), Floricola viticola (Floricolaceae), Brunneoclavispora bambusae, Neolophiostoma pigmentatum and Sulcosporium thailandica (Halotthiaceae), Pseudoasteromassaria fagi (Latoruaceae), Keissleriella dactylidicola (Lentitheciaceae), Lophiohelichrysum helichrysi (Lophiostomataceae), Aquasubmersa japonica (Lophiotremataceae) , Pseudomonodictys tectonae (Macrodiplodiopsidaceae), Microthyrium buxicola and Tumidispora shoreae (Microthyriaceae), Alloleptosphaeria clematidis, Allophaeosphaer i a c y t i s i , Allophaeosphae r i a subcylindrospora, Dematiopleospora luzulae, Entodesmium artemisiae, Galiicola pseudophaeosphaeria, Loratospora(Basidiomycota) are introduced together with a new genus Neoantrodiella (Neoantrodiellaceae), here based on both morphology coupled with molecular data. In the class Agaricomycetes, Agaricus pseudolangei, Agaricus haematinus, Agaricus atrodiscus and Agaricus exilissimus (Agaricaceae) , Amanita m e l l e i a l b a , Amanita pseudosychnopyramis and Amanita subparvipantherina (Amanitaceae), Entoloma calabrum, Cora barbulata, Dictyonema gomezianum and Inocybe granulosa (Inocybaceae), Xerocomellus sarnarii (Boletaceae), Cantharellus eucalyptorum, Cantharellus nigrescens, Cantharellus tricolor and Cantharellus variabilicolor (Cantharellaceae), Cortinarius alboamarescens, Cortinarius brunneoalbus, Cortinarius ochroamarus, Cortinarius putorius and Cortinarius seidlii (Cortinariaceae), Hymenochaete micropora and Hymenochaete subporioides (Hymenochaetaceae), Xylodon ramicida (Schizoporaceae), Colospora andalasii (Polyporaceae), Russula guangxiensis and Russula hakkae (Russulaceae), Tremella dirinariae, Tremella graphidis and Tremella pyrenulae (Tremellaceae) are introduced. Four new combinations Neoantrodiella gypsea, Neoantrodiella thujae (Neoantrodiellaceae), Punctulariopsis cremeoalbida, Punctulariopsis efibulata (Punctulariaceae) are also introduced here for the division Basidiomycota. Furthermore Absidia caatinguensis, Absidia koreana and Gongronella koreana (Cunninghamellaceae), Mortierella pisiformis and Mortierella formosana (Mortierellaceae) are newly introduced in the Zygomycota, while Neocallimastix cameroonii and Piromyces irregularis (Neocallimastigaceae) ar e i n t roduced i n the Neocallimastigomycota. Reference specimens or changes in classification and notes are provided for Alternaria ethzedia, Cucurbitaria ephedricola, Austropleospora, Austropleospora archidendri, Byssosphaeria rhodomphala, Lophiostoma caulium, Pseudopithomyces maydicus, Massariosphaeria, Neomassariosphaeria and Pestalotiopsis montellica.
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| 28. |
- Chen, Zhishan, et al.
(författare)
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Fine-mapping analysis including over 254 000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
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| 29. |
- Chen, Zhi, et al.
(författare)
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Large-Area Crystalline Zeolitic Imidazolate Framework Thin Films
- 2021
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Ingår i: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 60:25, s. 14124-14130
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Tidskriftsartikel (refereegranskat)abstract
- We report that continuous MOF films with highly controlled thickness (from 44 to 5100 nm) can be deposited over length scales greater than 80 centimeters by a facile, fast, and cost-effective spray-coating method. Such success relies on our discovery of unprecedented perfectly dispersed colloidal solutions consisting of amorphous MOF nanoparticles, which we adopted as precursors that readily converted to the crystalline films upon low-temperature in situ heating. The colloidal solutions allow for the fabrication of compact and uniform MOF films on a great deal of substrates such as fluorine-doped tin oxide, glass, SiO2, Al2O3, Si, Cu, and even flexible polycarbonate, widening their technological applications where substrates are essential. Despite the present work focuses on the fabrication of uniform cobalt-(2-methylimidazole)2 and zinc-(2-methylimidazole)2 films, our findings mark a great possibility in producing other high-quality MOF thin films on a large scale.
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| 30. |
- Cho, Yoon Shin, et al.
(författare)
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Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians.
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:1
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression, is known for its association with fasting glucose levels. The evidence of an association with T2D for PEPD and HNF4A has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D.
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| 31. |
- Fernandez-Rozadilla, Ceres, et al.
(författare)
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Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries
- 2023
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 55, s. 89-99
-
Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high-confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Crosstissue analyses indicated that over a third of effector genes most probably act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.
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| 32. |
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| 33. |
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| 34. |
- Guo, Jia Wei, et al.
(författare)
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2D Co metal-organic framework nanosheet as an oxidase-like nanozyme for sensitive biomolecule monitoring
- 2023
-
Ingår i: Rare Metals. - : Springer Science and Business Media LLC. - 1001-0521 .- 1867-7185. ; 42:3, s. 797-805
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Nanozyme-based biomolecules sensitive and quantitative detection is an attractive strategy due to their high chemical, thermal stability and reactive activity. Here, we have synthesized a significant number of two-dimensional (2D) cobalt-metal-organic framework (Co-MOF) nanosheets with oxidase (OXD)-like activity using a facile solvothermal method in one pot for biomolecule monitoring. The synthesized Co-MOF nanosheets exhibit strong stability, higher specific surface area and more active sites due to their MOF structure. Such Co-MOF nanosheets with excellent OXD-like activity show adequate analytical performance in the quantitative determination of dopamine (DA) and glutathione (GSH) with a wider dynamic sensing range and lower detection limits (DA and GSH: 0.24 and 0.067 μmol·L−1, 3σ/slope, where σ is standard deviation of the blank). This work extends the application of 2D-MOF structures in bioassays and brings new insights into the application of OXD-like nanozymes in bioassays. Graphical abstract: [Figure not available: see fulltext.]
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| 35. |
- Lu, Yingchang, et al.
(författare)
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Identification of Novel Loci and New Risk Variant in Known Loci for Colorectal Cancer Risk in East Asians
- 2020
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 29:2, s. 477-486
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Tidskriftsartikel (refereegranskat)abstract
- Background: Risk variants identified so far for colorectal cancer explain only a small proportion of milial risk of this cancer, particularly in Asians.Methods: We performed a genome-wide association study (GWAS) of colorectal cancer in East Asians, cluding 23,572 colorectal cancer cases and 48,700 controls. To identify novel risk loci, we selected 60 omising risk variants for replication using data from 58,131 colorectal cancer cases and 67,347 controls European descent. To identify additional risk variants in known colorectal cancer loci, we performed nditional analyses in East Asians.Results: An indel variant, rs67052019 at 1p13.3, was found to be associated with colorectal cancer risk P = 3.9 x 10(-8) in Asians (OR per allele deletion = 1.13, 95% confidence interval = 1.08-1.18). This sociation was replicated in European descendants using a variant (rs2938616) in complete linkage sequilibrium with rs67052019 (P = 7.7 x 10(-3)). Of the remaining 59 variants, 12 showed an association P < 0.05 in the European-ancestry study, including rs11108175 and rs9634162 at P < 5 x 10(-8) and o variants with an association near the genome-wide significance level (rs60911071, P = 5.8 x 10(-8); 62558833, P = 7.5 x 10(-8)) in the combined analyses of Asian- and European-ancestry data. In addition, ing data from East Asians, we identified 13 new risk variants at 11 loci reported from previous GWAS.Conclusions: In this large GWAS, we identified three novel risk loci and two highly suggestive loci for lorectal cancer risk and provided evidence for potential roles of multiple genes and pathways in the iology of colorectal cancer. In addition, we showed that additional risk variants exist in many colorectal ncer risk loci identified previously.Impact: Our study provides novel data to improve the understanding of the genetic basis for colorectal ncer risk.
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| 36. |
- Machiela, Mitchell J., et al.
(författare)
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Characterization of Large Structural Genetic Mosaicism in Human Autosomes
- 2015
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 96:3, s. 487-497
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Tidskriftsartikel (refereegranskat)abstract
- Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 3 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.
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| 37. |
- Machiela, Mitchell J, et al.
(författare)
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Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome
- 2016
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.
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| 38. |
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| 39. |
- Qi, Qibin, et al.
(författare)
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FTO genetic variants, dietary intake and body mass index : insights from 177 330 individuals
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:25, s. 6961-6972
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Tidskriftsartikel (refereegranskat)abstract
- FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177 330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity.
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| 40. |
- Qian, Jin yuan, et al.
(författare)
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Flow rate analysis of compressible superheated steam through pressure reducing valves
- 2017
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Ingår i: Energy. - : Elsevier BV. - 0360-5442. ; 135, s. 650-658
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Tidskriftsartikel (refereegranskat)abstract
- Steam flow is the main form for energy transfer in power plants, process industries, etc. The flow rate of the steam relates to the energy transfer amount directly. Pressure reducing valves are used for flow rate control of the compressible superheated steam in these piping systems. In this paper, a pressure reducing valve with a novel valve core is proposed. In order to analyze the internal flow characteristics of the compressible superheated steam and the flow rate adjustment performance of the proposed pressure reducing valve, a numerical model of DN80 pressure reducing valve is established. Then, the flow characteristics inside are studied numerically. Meanwhile, the flow rate adjustment performance is also carried out experimentally. Compared with the numerical and experimental results, it shows an agreement and both of them are similar to linear flow rate. Furthermore, a fitting equation for the flow rate prediction is carried out for the engineering applications under different working conditions.
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| 41. |
- Ramdas, S., et al.
(författare)
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A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
- 2022
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 109:8, s. 1366-1387
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
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| 42. |
- Shu, Xiang, et al.
(författare)
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Large-scale Integrated Analysis of Genetics and Metabolomic Data Reveals Potential Links Between Lipids and Colorectal Cancer Risk
- 2022
-
Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 31:6, s. 1216-1226
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Tidskriftsartikel (refereegranskat)abstract
- Background: The etiology of colorectal cancer is not fully understood.Methods: Using genetic variants and metabolomics data including 217 metabolites from the Framingham Heart Study (n = 1,357), we built genetic prediction models for circulating metabolites. Models with prediction R2 > 0.01 (Nmetabolite = 58) were applied to predict levels of metabolites in two large consortia with a combined sample size of approximately 46,300 cases and 59,200 controls of European and approximately 21,700 cases and 47,400 controls of East Asian (EA) descent. Genetically predicted levels of metabolites were evaluated for their associations with colorectal cancer risk in logistic regressions within each racial group, after which the results were combined by meta-analysis.Results: Of the 58 metabolites tested, 24 metabolites were significantly associated with colorectal cancer risk [Benjamini-Hochberg FDR (BH-FDR) < 0.05] in the European population (ORs ranged from 0.91 to 1.06; P values ranged from 0.02 to 6.4 × 10-8). Twenty one of the 24 associations were replicated in the EA population (ORs ranged from 0.26 to 1.69, BH-FDR < 0.05). In addition, the genetically predicted levels of C16:0 cholesteryl ester was significantly associated with colorectal cancer risk in the EA population only (OREA: 1.94, 95% CI, 1.60−2.36, P = 2.6 × 10-11; OREUR: 1.01, 95% CI, 0.99−1.04, P = 0.3). Nineteen of the 25 metabolites were glycerophospholipids and triacylglycerols (TAG). Eighteen associations exhibited significant heterogeneity between the two racial groups (PEUR-EA-Het < 0.005), which were more strongly associated in the EA population. This integrative study suggested a potential role of lipids, especially certain glycerophospholipids and TAGs, in the etiology of colorectal cancer.Conclusions: This study identified potential novel risk biomarkers for colorectal cancer by integrating genetics and circulating metabolomics data.Impact: The identified metabolites could be developed into new tools for risk assessment of colorectal cancer in both European and EA populations.
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| 43. |
- Tang, Xiang-long, et al.
(författare)
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Near-infrared light-activated red-emitting upconverting nanoplatform for T-1-weighted magnetic resonance imaging and photodynamic therapy
- 2018
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Ingår i: Acta Biomaterialia. - : ELSEVIER SCI LTD. - 1742-7061 .- 1878-7568. ; 74, s. 360-373
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Tidskriftsartikel (refereegranskat)abstract
- Photodynamic therapy (PDT) has increasingly become an efficient and attractive cancer treatment modality based on reactive oxygen species (ROS) that can induce tumor death after irradiation with ultraviolet or visible light. Herein, to overcome the limited tissue penetration in traditional PDT, a novel near-infrared (NIR) light-activated NaScF4: 40% Yb, 2% Er@CaF2 upconversion nanoparticle (rUCNP) is successfully designed and synthesized. Chlorin e6, a photosensitizer and a chelating agent for Mn2+, is loaded into human serum albumin (HSA) that further conjugates onto rUCNPs. To increase the ability to target glioma tumor, an acyclic Arg-Gly-Asp peptide (cRGDyK) is linked to rUCNPs@HSA(Ce6-Mn). This nanoplatform enables efficient adsorption and conversion of NIR light (980 nm) into bright red emission (660 nm), which can trigger the photosensitizer Ce6-Mn complex for PDT and T-1-weighted magnetic resonance imaging (T-1-weighted MRI) for glioma diagnosis. Our in vitro and in vivo experiments demonstrate that NIR light-activated and glioma tumor-targeted PDT can generate large amounts of intracellular ROS that induce U87 cell apoptosis and suppress glioma tumor growth owing to the deep tissue penetration of irradiated light and excellent tumor-targeting ability. Thus, this nanoplatform holds potential for applications in T-1-weighted MRI diagnosis and PDT of glioma for antitumor therapy. Statement of Significance A near-infrared (NIR) light-activated nanoplatform for photodynamic therapy (PDT) was designed and synthesized. The Red-to-Green (RIG) ratio of NaScF4: 40% Yb, 2% Er almost reached 9, a value that was much higher than that of a traditional Yb/Er-codoped upconversion nanoparticle (rUCNP). By depositing a CaF2 shell, the red-emission intensities of the rUCNPs were seven times strong as that of NaScF4: 40% Yb, 2% Er. The enhanced red-emitting rUCNPs could be applied in many fields such as bioimaging, controlled release, and real-time diagnosis. The nanoplatform had a strong active glioma-targeting ability, and all results achieved on subcutaneous glioma demonstrated that our NIR light-activated redemitting upconverting nanoplatform was efficient for PDT. By loading Ce6-Mn complex into rUCNPs@HSA-RGD, the nanoplatform could be used as a T-1-weighted magnetic resonance imaging agent for tumor diagnosis.
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| 44. |
- Wan, Lu Ming, et al.
(författare)
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Heparanase Facilitates PMA-Induced Megakaryocytic Differentiation in K562 Cells via Interleukin 6/STAT3 Pathway
- 2020
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Ingår i: Thrombosis and Haemostasis. - : GEORG THIEME VERLAG KG. - 0340-6245 .- 2567-689X. ; 120:4, s. 647-657
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Tidskriftsartikel (refereegranskat)abstract
- Heparanase (HPSE) is an endo-beta-D-glucuronidase that cleaves heparan sulfate and hence participates in remodeling of the extracellular matrix, leading to release of cytokines that are immobilized by binding to heparan sulfate proteoglycans (HSPGs), and consequently activating signaling pathways. This function of HPSE is correlated to its expression level that is normally very low in majority of the tissues. Exceptionally, human platelets express high level of HPSE, suggesting a unique physiological role in this cell. Using K562 cell line, we found a progressive increase of HPSE during the megakaryocytic differentiation. Analysis of a series of megakaryocytic differentiation-related heparin-binding proteins (HBPs) in the cell culture medium revealed an exclusive positive correlation between the level of interleukin 6 (IL-6) and HPSE expression. IL-6 modulated megakaryocytic differentiation through activation of STAT3. Further, we demonstrated that overexpression of HPSE potentiates megakaryocytic differentiation, whereas elimination of HPSE led to a delayed differentiation. This function of HPSE is associated with its activity, as overexpression of inactive HPSE had no effect on IL-6 production and megakaryocytic differentiation. The role of HPSE is further supported by the observation in an umbilical cord blood CD34+ cells megakaryocytic differentiation model. Our data propose a novel role for HPSE in platelets production by a HPSE/IL-6/STAT3 positive feedback loop that specifically regulates megakaryocytes maturation.
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| 45. |
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| 46. |
- Yan, Bao-Yong, et al.
(författare)
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Overexpression of MAC30 in the Cytoplasm of Oral Squamous Cell Carcinoma Predicts Nodal Metastasis and Poor Differentiation
- 2010
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Ingår i: Chemotherapy. - : S, Karger AG, Basel. - 0009-3157 .- 1421-9794. ; 56:6, s. 424-428
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Tidskriftsartikel (refereegranskat)abstract
- Background: Expression of the meningioma-associated protein (MAC30) was increased in several types of tumors, including esophageal, gastric and colon tumors, compared to normal tissue. MAC30 expression levels gradually increased from normal colorectal mucosa to primary colorectal cancer and colorectal cancer spreading to the lymph nodes. MAC30 expression was related to survival in patients with colorectal cancer. However, there is no study on MAC30 in oral squamous cell carcinoma (OSCC). Methods: Therefore, MAC30 expression in OSCC was investigated and possible associations of MAC30 expression with clinicopathological variables in OSCC have been analyzed. MAC30 expression was immunohistochemically examined in 20 normal oral mucosa and 43 OSCC specimens. Results: Expression levels of MAC30 in the cytoplasm markedly increased from normal oral epithelial cells to primary OSCC. Strong cytoplasmic staining was significantly higher in primary OSCC compared to normal oral mucosa samples (51 vs. 20%, p = 0.019). Furthermore, MAC30 expression levels in primary tumors of patients with lymph node metastasis exceeded levels in those without metastasis (65 vs. 35%, p = 0.048), and MAC30 expression in poorly differentiated tumors was higher than in well-differentiated ones (90 vs. 39%, p = 0.005). Conclusion: Overexpression of MAC30 in the cytoplasm of OSCC may predict nodal metastasis and poor differentiation.
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| 47. |
- Zhang, Jin-Ting, et al.
(författare)
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Nuclear to cytoplasmic shift of p33ING1b protein from normal oral mucosa to oral squamous cell carcinoma in relation to clinicopathological variables
- 2008
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Ingår i: Journal of Cancer Research and Clinical Oncology. - : Springer Science and Business Media LLC. - 0171-5216 .- 1432-1335. ; 134:3, s. 421-426
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: p33ING1b, as a candidate tumour suppressor gene, has been found to be expressed a proportion of oral squamous cell carcinomas (OSCCs), however, its clinicopathological significance is not studied yet. Our aim was to investigate association of p33ING1b expression with clinicopathological variables and particularly interesting new cysteine-histidine rich protein (PINCH) in OSCCs. Methods: p33ING1b expression was immumohistochemically examined in 20 normal oral mucosa specimens and 49 OSCCs. Results: Normal squamous cells showed only p33ING1b nuclear expression (no cytoplasmic expression), with a rate of 90% positive cases. While 24% of OSCCs appeared cytoplasmic expression (11 of them with weak nuclear staining) and the rest tumours (76%) were negative for p33 ING1b. Furthermore, the cases having lymph node metastasis showed a higher frequency of positive cytoplasmic expression than those without metastasis (P = 0.03). The p33ING1b cytoplasmic expression was positively related to PINCH expression (P = 0.04), the cases positive for both proteins had a high rate of the metastasis (P = 0.03). Conclusions: The transfer of p33ING1b protein from the nucleus to the cytoplasm may result in loss of normal cellular function of the protein, which might play a role in the tumourigenesis and metastasis of OSCCs. © 2007 Springer-Verlag.
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| 48. |
- Zhang, Wei, et al.
(författare)
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Geochemical evaluation of heavy metal migration in Pb-Zn tailings covered by different topsoils
- 2016
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Ingår i: Journal of Geochemical Exploration. - : Elsevier BV. - 0375-6742 .- 1879-1689. ; 165, s. 134-142
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Tidskriftsartikel (refereegranskat)abstract
- Heavy metal migration was evaluated in Pb-Zn tailings covered by different topsoil constructions. The four topsoil constructions each had different interlayers: one with direct topsoiling above the tailings (CT); the second had a limestone interlayer between the tailings and topsoil with two geotextile layers set above and below the interlayer (SLS); the third had a lime interlayer, also with two geotextile layers (SL); and the fourth had a clay interlayer with two geotextile layers (SC). The topsoils were evaluated in a 210-day laboratory column leaching experiments and in a 3-year field cover application at an abandoned Pb-Zn tailings pond (northeastern China). The contents of Pb, Zn and Cd in the soils, leachates, interlayers and leaves of Amorpha fruticosa L. were analysed by inductively coupled plasma optical emission spectroscopy (ICP-OES).Results showed that the pH values of the leachates from the columns increased with time, from 6.5 to the range of 7.5 to 8.03, and the maximum in pH in C1 (tailings), C2 (CT), C3 (SLS), C4 (SL) and C5 (SC) appeared after the 180th day, at 7.85, 7.89, 7.78, 8.03, and 7.89, respectively. The topsoil effectively reduced the concentrations of Pb, Zn and Cd in the leachate, and the addition of a limestone or lime interlayer enhanced the efficiency, especially for Zn and Cd. The Pb, Zn and Cd concentrations in the topsoil that directly cover the tailings were appreciably less than the initial concentrations, resulting from the eluviation. The presence of a limestone or lime interlayer reduced the mobility of Zn and Cd, and a clay interlayer was effective in preventing the migration of Pb and Zn but had less impact on Cd.During the 3-year field experiment, the pH values of the topsoil increased slightly with time, from 7.15 to the range of 7.67 to 8.20. At the end of the experiment, Pb, Zn and Cd concentrations in the topsoil at the SLS, SL and SC plots showed little change compared with the initial value in 2012. Acid-soluble Pb, Zn and Cd concentrations of the upper soil (0–0.1 m) at CT increased from 0.19, 1.95 and 0.11 mg kg− 1 in 2012 to 1.82, 32.87 and 0.56 mg kg− 1 in 2015, indicating that acid-soluble heavy metals migrated from tailings to topsoil. Acid-soluble Cd in topsoil and in the interlayer showed a small increase at plot SC, indicating that Cd may migrate through the clay layer to topsoil with pore water. The Pb contents in leaves at SLS and SL were 2.38 and 3.04 mg kg− 1, which were appreciably lower than at CT and SC, and the Zn and Cd contents in leaves at CT were 45.78 and 0.26 mg kg− 1, which were higher than at SLS, SL and SC. Topsoiling with an interlayer could be a reliable technique for preventing toxic elements from moving downward or upward during ecological restoration of tailings ponds.
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| 49. |
- Zhang, Wei, et al.
(författare)
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Vertical distribution and historical loss estimation of heavy metals in an abandoned tailings pond at HTM copper mine, northeastern China
- 2016
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Ingår i: Environmental Earth Sciences. - : Springer Science and Business Media LLC. - 1866-6280 .- 1866-6299. ; 75:22
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Tidskriftsartikel (refereegranskat)abstract
- In the tailings pond of the Hongtou Mountain (HTM) copper mine in northeastern China, four sampling points were set at intervals of 80 m along the discharge direction of the tailings slurry to investigate the vertical distribution characteristics of heavy metals in shallow layer (0–5 m) tailings. In addition, 18 sampling points were set by a grid method (50 m × 50 m) to estimate the historical loss amount of contaminants from the surface layer (0–1.2 m) of the HTM tailings pond. Tailings samples were taken at every 0.2 m, and the pH value, the total content and acid-soluble fraction of heavy metals and chemical compositions were determined following the standard methods. The results showed that the pH values of tailings ranged from 3.01 to 8.11, which increased with depths from 0 to 2.2 m, and varied between pH values of 7.0 and 7.5 in 2.2–5 m. Cu, Zn, Cd and S were the major contaminants in the tailings. The total Cu content was higher at the downstream sampling points near the dam. Zn and Cd were higher at the upstream sampling points near the discharge. Three distinct zones (oxidised zone, cemented layer and unoxidised zone) were found in the HTM tailings pond. The depth of the oxidised zone was 0.4 m, and the elements in the oxidised tailings were obviously lower due to the sulphides oxidation and acid mine drainage. Cu was enriched in the cemented layer, and the Cu content reached values between 1200 and 3000 mg/kg, which were 1.5–3 times higher than the average value. Zn, Cd, Ni and Fe were also slightly elevated in the cemented layer. Below the groundwater table, the acid-soluble fraction of Cu, Zn and Cd was relatively stable at a lower level and showed insignificant variations, as the cemented layer and groundwater could efficiently prevent the oxidation process. The amount of Cu, Zn and Cd leaving the tailings pond with drainage water was 8.08, 21.60 and 72.93%, respectively, of the amount released from oxidation. Most of the Cu released from oxidation was retained in the cemented layer. The total mass of S, Zn and Cd released from the tailings to surrounding ecosystems was estimated approximately 762.75 t, 6997.5 and 86.06 kg, respectively, in the last 20 years.
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| 50. |
- Kanai, M, et al.
(författare)
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- 2023
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