| 1. |
- 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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| 2. |
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| 3. |
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| 4. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 5. |
- 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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| 6. |
- Kristanl, Matej, et al.
(författare)
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The Seventh Visual Object Tracking VOT2019 Challenge Results
- 2019
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Ingår i: 2019 IEEE/CVF INTERNATIONAL CONFERENCE ON COMPUTER VISION WORKSHOPS (ICCVW). - : IEEE COMPUTER SOC. - 9781728150239 ; , s. 2206-2241
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Konferensbidrag (refereegranskat)abstract
- The Visual Object Tracking challenge VOT2019 is the seventh annual tracker benchmarking activity organized by the VOT initiative. Results of 81 trackers are presented; many are state-of-the-art trackers published at major computer vision conferences or in journals in the recent years. The evaluation included the standard VOT and other popular methodologies for short-term tracking analysis as well as the standard VOT methodology for long-term tracking analysis. The VOT2019 challenge was composed of five challenges focusing on different tracking domains: (i) VOT-ST2019 challenge focused on short-term tracking in RGB, (ii) VOT-RT2019 challenge focused on "real-time" short-term tracking in RGB, (iii) VOT-LT2019 focused on long-term tracking namely coping with target disappearance and reappearance. Two new challenges have been introduced: (iv) VOT-RGBT2019 challenge focused on short-term tracking in RGB and thermal imagery and (v) VOT-RGBD2019 challenge focused on long-term tracking in RGB and depth imagery. The VOT-ST2019, VOT-RT2019 and VOT-LT2019 datasets were refreshed while new datasets were introduced for VOT-RGBT2019 and VOT-RGBD2019. The VOT toolkit has been updated to support both standard short-term, long-term tracking and tracking with multi-channel imagery. Performance of the tested trackers typically by far exceeds standard baselines. The source code for most of the trackers is publicly available from the VOT page. The dataset, the evaluation kit and the results are publicly available at the challenge website(1).
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| 7. |
- 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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| 8. |
- Jin, Ying-Hui, et al.
(författare)
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Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19 : An evidence-based clinical practice guideline (updated version)
- 2020
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Ingår i: Military Medical Research. - : Springer Science and Business Media LLC. - 2054-9369. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.
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| 9. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 10. |
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| 11. |
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| 12. |
- 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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| 13. |
- Aaltonen, T., et al.
(författare)
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Tevatron Run II combination of the effective leptonic electroweak mixing angle
- 2018
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Ingår i: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 97:11
-
Tidskriftsartikel (refereegranskat)abstract
- Drell-Yan lepton pairs produced in the process p (p) over bar -> l(+)l(-) + X through an intermediate gamma*/Z boson have an asymmetry in their angular distribution related to the spontaneous symmetry breaking of the electroweak force and the associated mixing of its neutral gauge bosons. The CDF and D0 experiments have measured the effective-leptonic electroweak mixing parameter sin(2) theta(lept)(eff) using electron and muon pairs selected from the full Tevatron proton-antiproton data sets collected in 2001-2011, corresponding to 9-10 fb(-1) of integrated luminosity. The combination of these measurements yields the most precise result from hadron colliders, sin(2)theta(lept)(eff) = 0.23148 +/- 0.00033. This result is consistent with, and approaches in precision, the best measurements from electron-positron colliders. The standard model inference of the on-shell electroweak mixing parameter sin(2) theta(W), or equivalently the W-boson mass M-W, using the ZFITTER software package yields sin(2) theta(W) = 0.22324 +/- 0.00033 or equivalently, M-W = 80.367 +/- 0.017 GeV/c(2).
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| 14. |
- 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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| 15. |
- Kristan, Matej, et al.
(författare)
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The Ninth Visual Object Tracking VOT2021 Challenge Results
- 2021
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Ingår i: 2021 IEEE/CVF INTERNATIONAL CONFERENCE ON COMPUTER VISION WORKSHOPS (ICCVW 2021). - : IEEE COMPUTER SOC. - 9781665401913 ; , s. 2711-2738
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Konferensbidrag (refereegranskat)abstract
- The Visual Object Tracking challenge VOT2021 is the ninth annual tracker benchmarking activity organized by the VOT initiative. Results of 71 trackers are presented; many are state-of-the-art trackers published at major computer vision conferences or in journals in recent years. The VOT2021 challenge was composed of four sub-challenges focusing on different tracking domains: (i) VOT-ST2021 challenge focused on short-term tracking in RGB, (ii) VOT-RT2021 challenge focused on "real-time" short-term tracking in RGB, (iii) VOT-LT2021 focused on long-term tracking, namely coping with target disappearance and reappearance and (iv) VOT-RGBD2021 challenge focused on long-term tracking in RGB and depth imagery. The VOT-ST2021 dataset was refreshed, while VOT-RGBD2021 introduces a training dataset and sequestered dataset for winner identification. The source code for most of the trackers, the datasets, the evaluation kit and the results along with the source code for most trackers are publicly available at the challenge website(1).
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| 16. |
- 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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| 17. |
- 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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| 18. |
- Takeuchi, Fumihiko, et al.
(författare)
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Interethnic analyses of blood pressure loci in populations of East Asian and European descent
- 2018
-
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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| 19. |
- 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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| 20. |
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| 21. |
- Abazov, V. M., et al.
(författare)
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Measurement of the Effective Weak Mixing Angle in p¯p→Z/γ∗→ℓ+ℓ− Events
- 2018
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 120:24
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Tidskriftsartikel (refereegranskat)abstract
- We present a measurement of the effective weak mixing angle parameter sin(2)theta(l)(eff) in p (p) over bar -> Z/gamma* -> mu(+)mu(-) events at a center-of-mass energy of 1.96 TeV, collected by the D0 detector at the Fermilab Tevatron Collider and corresponding to 8.6 fb(-1) of integrated luminosity. The measured value of sin(2)theta(l)(eff)[mu mu] = 0.23016 +/- 0.00064 is further combined with the result from the D0 measurement in p (p) over bar -> Z/gamma* -> e(+)e(-) events, resulting in sin(2)theta(l)(eff)[comb] = 0.23095 +/- 0.00040. This combined result is the most precise measurement from a single experiment at a hadron collider and is the most precise determination using the coupling of the Z/gamma* to light quarks.
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| 22. |
- Kato, Norihiro, et al.
(författare)
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Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
- 2015
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
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Tidskriftsartikel (refereegranskat)abstract
- We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
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| 23. |
- Liu, Wei, et al.
(författare)
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Coherent dynamics of multi-spin V-B(-) center in hexagonal boron nitride
- 2022
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Ingår i: Nature Communications. - : Nature Portfolio. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Hexagonal boron nitride (hBN) has recently been demonstrated to contain optically polarized and detected electron spins that can be utilized for implementing qubits and quantum sensors in nanolayered-devices. Understanding the coherent dynamics ofmicrowave driven spins in hBN is of crucial importance for advancing these emerging new technologies. Here, we demonstrate and study the Rabi oscillation and related phenomena of a negatively charged boron vacancy (V-B(-)) spin ensemble in hBN. We report on different dynamics of the V-B(-) spins at weak and strong magnetic fields. In the former case the defect behaves like a single electron spin system, while in the latter case it behaves like a multi-spin system exhibiting multiple-frequency dynamical oscillation as beat in the Ramsey fringes. We also carry out theoretical simulations for the spin dynamics of V-B(-) and reveal that the nuclear spins can be driven via the strong electron nuclear coupling existing in V-B(-) center, which can be modulated by the magnetic field and microwave field.
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| 24. |
- Wang, Fang, et al.
(författare)
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Emerging contaminants: A One Health perspective
- 2024
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Ingår i: Innovation. - 2666-6758. ; 5
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Forskningsöversikt (refereegranskat)abstract
- Environmental pollution is escalating due to rapid global development that often prioritizes human needs over planetary health. Despite global efforts to mitigate legacy pollutants, the continuous introduction of new substances remains a major threat to both people and the planet. In response, global initiatives are focusing on risk assessment and regulation of emerging contaminants, as demonstrated by the ongoing efforts to establish the UN's Intergovernmental Science-Policy Panel on Chemicals, Waste, and Pollution Prevention. This review identifies the sources and impacts of emerging contaminants on planetary health, emphasizing the importance of adopting a One Health approach. Strategies for monitoring and addressing these pollutants are discussed, underscoring the need for robust and socially equitable environmental policies at both regional and international levels. Urgent actions are needed to transition toward sustainable pollution management practices to safeguard our planet for future generations.
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| 25. |
- Algaba, Juan-Carlos, et al.
(författare)
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Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign
- 2021
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 911:1
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Forskningsöversikt (refereegranskat)abstract
- In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M o˙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87's spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded.
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| 26. |
- Faber, Zachary J, et al.
(författare)
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The genomic landscape of core-binding factor acute myeloid leukemias
- 2016
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 48, s. 1551-1556
-
Tidskriftsartikel (refereegranskat)abstract
- Acute myeloid leukemia (AML) comprises a heterogeneous group of leukemias frequently defined by recurrent cytogenetic abnormalities, including rearrangements involving the core-binding factor (CBF) transcriptional complex. To better understand the genomic landscape of CBF-AMLs, we analyzed both pediatric (n = 87) and adult (n = 78) samples, including cases with RUNX1-RUNX1T1 (n = 85) or CBFB-MYH11 (n = 80) rearrangements, by whole-genome or whole-exome sequencing. In addition to known mutations in the Ras pathway, we identified recurrent stabilizing mutations in CCND2, suggesting a previously unappreciated cooperating pathway in CBF-AML. Outside of signaling alterations, RUNX1-RUNX1T1 and CBFB-MYH11 AMLs demonstrated remarkably different spectra of cooperating mutations, as RUNX1-RUNX1T1 cases harbored recurrent mutations in DHX15 and ZBTB7A, as well as an enrichment of mutations in epigenetic regulators, including ASXL2 and the cohesin complex. This detailed analysis provides insights into the pathogenesis and development of CBF-AML, while highlighting dramatic differences in the landscapes of cooperating mutations for these related AML subtypes.
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| 27. |
- He, Mao Qiang, et al.
(författare)
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Phylogenomics, divergence times and notes of orders in Basidiomycota
- 2024
-
Ingår i: Fungal Diversity. - 1560-2745 .- 1878-9129. ; 126, s. 127-406
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Tidskriftsartikel (refereegranskat)abstract
- Basidiomycota is one of the major phyla in the fungal tree of life. The outline of Basidiomycota provides essential taxonomic information for researchers and workers in mycology. In this study, we present a time-framed phylogenomic tree with 487 species of Basidiomycota from 127 families, 47 orders, 14 classes and four subphyla; we update the outline of Basidiomycota based on the phylogenomic relationships and the taxonomic studies since 2019; and we provide notes for each order and discuss the history, defining characteristics, evolution, justification of orders, problems, significance, and plates. Our phylogenomic analysis suggests that the subphyla diverged in a time range of 443–490 Myr (million years), classes in a time range of 312–412 Myr, and orders in a time range of 102–361 Myr. Families diverged in a time range of 50–289 Myr, 76–224 Myr, and 62–156 Myr in Agaricomycotina, Pucciniomycotina, and Ustilaginomycotina, respectively. Based on the phylogenomic relationships and divergence times, we propose a new suborder Mycenineae in Agaricales to accommodate Mycenaceae. In the current outline of Basidiomycota, there are four subphyla, 20 classes, 77 orders, 297 families, and 2134 genera accepted. When building a robust taxonomy of Basidiomycota in the genomic era, the generation of molecular phylogenetic data has become relatively easier. Finding phenotypical characters, especially those that can be applied for identification and classification, however, has become increasingly challenging.
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| 28. |
- Li, Xiang-Yung, et al.
(författare)
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Cloud-droplet growth due to supersaturation fluctuations in stratiform clouds
- 2019
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 19:1, s. 639-648
-
Tidskriftsartikel (refereegranskat)abstract
- Condensational growth of cloud droplets due to supersaturation fluctuations is investigated by solving the hydrodynamic and thermodynamic equations using direct numerical simulations (DNS) with droplets being modeled as Lagrangian particles. The supersaturation field is calculated directly by simulating the temperature and water vapor fields instead of being treated as a passive scalar. Thermodynamic feedbacks to the fields due to condensation are also included for completeness. We find that the width of droplet size distributions increases with time, which is contrary to the classical theory without supersaturation fluctuations, where condensational growth leads to progressively narrower size distributions. Nevertheless, in agreement with earlier Lagrangian stochastic models of the condensational growth, the standard deviation of the surface area of droplets increases as t 1/2 . Also, for the first time, we explicitly demonstrate that the time evolution of the size distribution is sensitive to the Reynolds number, but insensitive to the mean energy dissipation rate. This is shown to be due to the fact that temperature fluctuations and water vapor mixing ratio fluctuations increase with increasing Reynolds number; therefore the resulting supersaturation fluctuations are enhanced with increasing Reynolds number. Our simulations may explain the broadening of the size distribution in stratiform clouds qualitatively, where the mean updraft velocity is almost zero.
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| 29. |
- Li, Xiang-Yu, et al.
(författare)
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Condensational and Collisional Growth of Cloud Droplets in a Turbulent Environment
- 2020
-
Ingår i: Journal of the Atmospheric Sciences. - : AMER METEOROLOGICAL SOC. - 0022-4928 .- 1520-0469. ; 77:1, s. 337-353
-
Tidskriftsartikel (refereegranskat)abstract
- We investigate the effect of turbulence on the combined condensational and collisional growth of cloud droplets by means of high-resolution direct numerical simulations of turbulence and a superparticle approximation for droplet dynamics and collisions. The droplets are subject to turbulence as well as gravity, and their collision and coalescence efficiencies are taken to be unity. We solve the thermodynamic equations governing temperature, water vapor mixing ratio, and the resulting supersaturation fields together with the Navier-Stokes equation. We find that the droplet size distribution broadens with increasing Reynolds number and/or mean energy dissipation rate. Turbulence affects the condensational growth directly through supersaturation fluctuations, and it influences collisional growth indirectly through condensation. Our simulations show for the first time that, in the absence of the mean updraft cooling, supersaturation-fluctuation-induced broadening of droplet size distributions enhances the collisional growth. This is contrary to classical (nonturbulent) condensational growth, which leads to a growing mean droplet size, but a narrower droplet size distribution. Our findings, instead, show that condensational growth facilitates collisional growth by broadening the size distribution in the tails at an early stage of rain formation. With increasing Reynolds numbers, evaporation becomes stronger. This counteracts the broadening effect due to condensation at late stages of rain formation. Our conclusions are consistent with results of laboratory experiments and field observations, and show that supersaturation fluctuations are important for precipitation.
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| 30. |
- Li, Xiang-Yung, et al.
(författare)
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Dust Growth by Accretion of Molecules in Supersonic Interstellar Turbulence
- 2020
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 903:2
-
Tidskriftsartikel (refereegranskat)abstract
- We show that the growth rate of dust grains in cold molecular clouds is enhanced by the high degree of compressibility of a turbulent, dilute gas. By means of high-resolution (1024(3)) numerical simulations, we confirm the theory that the spatial mean growth rate is proportional to the gas-density variance. This also results in broadening of the grain-size distribution (GSD) due to turbulence-induced variation of the grain-growth rate. We show, for the first time in a detailed numerical simulation of hydrodynamic turbulence, that the GSD evolves toward a shape that is a reflection of the gas-density distribution, regardless of the initial distribution. That is, in case of isothermal, rotationally forced turbulence, the GSD tends to be a lognormal distribution. We also show that in hypersonic turbulence, decoupling of gas and dust becomes important and that this leads to an even further accelerated grain growth.
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| 31. |
- Li, Xiang-Yung, et al.
(författare)
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Effect of turbulence on collisional growth of cloud droplets
- 2018
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Ingår i: Journal of the Atmospheric Sciences. - : American Meteorological Society. - 0022-4928 .- 1520-0469. ; 75:10, s. 3469-3487
-
Tidskriftsartikel (refereegranskat)abstract
- Weinvestigate the effect of turbulence on the collisional growth of micrometer-sized droplets through highresolution numerical simulations with well-resolved Kolmogorov scales, assuming a collision and coalescence efficiency of unity. The droplet dynamics and collisions are approximated using a superparticle approach. In the absence of gravity, we show that the time evolution of the shape of the droplet-size distribution due to turbulence-induced collisions depends strongly on the turbulent energy-dissipation rate ε, but only weakly on the Reynolds number. This can be explained through the « dependence of the mean collision rate described by the Saffman-Turner collision model. Consistent with the Saffman-Turner collision model and its extensions, the collision rate increases as ε1/2 even when coalescence is invoked. The size distribution exhibits power-law behavior with a slope of 23.7 from a maximum at approximately 10 up to about 40 mm. When gravity is invoked, turbulence is found to dominate the time evolution of an initially monodisperse droplet distribution at early times. At later times, however, gravity takes over and dominates the collisional growth. We find that the formation of large droplets is very sensitive to the turbulent energy dissipation rate. This is because turbulence enhances the collisional growth between similar-sized droplets at the early stage of raindrop formation. The mean collision rate grows exponentially, which is consistent with the theoretical prediction of the continuous collisional growth even when turbulence-generated collisions are invoked. This consistency only reflects the mean effect of turbulence on collisional growth.
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| 32. |
- 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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| 33. |
- Ren, Luyao, et al.
(författare)
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Quartet DNA reference materials and datasets for comprehensively evaluating germline variant calling performance
- 2023
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Ingår i: Genome Biology. - : BioMed Central (BMC). - 1465-6906 .- 1474-760X. ; 24:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Genomic DNA reference materials are widely recognized as essential for ensuring data quality in omics research. However, relying solely on reference datasets to evaluate the accuracy of variant calling results is incomplete, as they are limited to benchmark regions. Therefore, it is important to develop DNA reference materials that enable the assessment of variant detection performance across the entire genome.RESULTS: We established a DNA reference material suite from four immortalized cell lines derived from a family of parents and monozygotic twins. Comprehensive reference datasets of 4.2 million small variants and 15,000 structural variants were integrated and certified for evaluating the reliability of germline variant calls inside the benchmark regions. Importantly, the genetic built-in-truth of the Quartet family design enables estimation of the precision of variant calls outside the benchmark regions. Using the Quartet reference materials along with study samples, batch effects are objectively monitored and alleviated by training a machine learning model with the Quartet reference datasets to remove potential artifact calls. Moreover, the matched RNA and protein reference materials and datasets from the Quartet project enables cross-omics validation of variant calls from multiomics data.CONCLUSIONS: The Quartet DNA reference materials and reference datasets provide a unique resource for objectively assessing the quality of germline variant calls throughout the whole-genome regions and improving the reliability of large-scale genomic profiling.
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| 34. |
- Sung, Yun Ju, et al.
(författare)
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A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure
- 2019
-
Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 28:15, s. 2615-2633
-
Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
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| 35. |
- Wang, H. Y., et al.
(författare)
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Cellular Analysis and Comparative Transcriptomics Reveal the Tolerance Mechanisms of Candida tropicalis Toward Phenol
- 2020
-
Ingår i: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Phenol is a ubiquitous pollutant and can contaminate natural water resources. Hence, the removal of phenol from wastewater is of significant importance. A series of biological methods were used to remove phenol based on the natural ability of microorganisms to degrade phenol, but the tolerance mechanism of phenol-degraded strains to phenol are not very clear. Morphological observation on Candida tropicalis showed that phenol caused the reactive oxygen species (ROS) accumulation, damaging the mitochondrial and the endoplasmic reticulum. On the basis of transcriptome data and cell wall susceptibility analysis, it was found that C. tropicalis prevented phenol-caused cell damage through improvement of cell wall resistance, maintenance of high-fidelity DNA replication, intracellular protein homeostasis, organelle integrity, and kept the intracellular phenol concentration at a low level through cell-wall remodeling and removal of excess phenol via MDR/MXR transporters. The knowledge obtained will promote the genetic modification of yeast strains in general to tolerate the high concentrations of phenol and improve their efficiency of phenol degradation.
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| 36. |
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| 37. |
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| 38. |
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| 39. |
- Chen, Zhibin, et al.
(författare)
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Summary of the 3rd International Workshop on Gas-Dynamic Trap based Fusion Neutron Source (GDT-FNS)
- 2022
-
Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:6
-
Tidskriftsartikel (refereegranskat)abstract
- The 3rd International Workshop on Gas-Dynamic Trap-based Fusion Neutron Source (GDT-FNS) was held through the hybrid mode on 13-14 September 2021 in Hefei, China, jointly organized by the Hefei Institutes of Physical Science (HFIPS), Chinese Academy of Sciences (CAS), and the Budker Institute of Nuclear Physics (BINP), Russian Academy of Sciences (RAS). It followed the 1st GDT-FNS Workshop held in November 2018 in Hefei, China, and the 2nd taking place in November 2019 in Novosibirsk, Russian Federation. With the financial support from CAS and China Association for Science and Technology (CAST), this workshop was attended by more than 80 participants representing 20 institutes and universities from seven countries, with oral presentations broadcast via the Zoom conferencing system. Twenty-two presentations were made with topics covering design and key technologies, simulation and experiments, steady-state operation, status of the ALIANCE project, multi applications of neutron sources, and other concepts (Tokamaks, Mirrors, FRC, Plasma Focus, etc). The workshop consensus was made including the establishment of the ALIANCE International Working Group. The next GDT-FNS workshop is planned to be held in May 2022 in Novosibirsk.
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| 40. |
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| 41. |
- Ding, Jun-Li, et al.
(författare)
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Attenuation of Acute Pancreatitis by Peroxisome Proliferator-Activated Receptor-α in Rats: The Effect on Toll-Like Receptor Signaling Pathways
- 2013
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Ingår i: Pancreas. - : Lippincott, Williams and Wilkins. - 0885-3177 .- 1536-4828. ; 42:1, s. 114-122
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The peroxisome proliferator-activated receptor-α (PPAR-α) has attracted considerable attention for its anti-inflammatory properties; however, Toll-like receptor (TLR) pathways have an essential proinflammatory role in acute pancreatitis (AP). This study aimed to evaluate the attenuation of inflammation by PPAR-α and to investigate the interaction between PPAR-α and TLR pathways in AP.Methods: Acute pancreatitis was induced in rats by administration of cerulein. The PPAR-α agonist WY14643 and/or antagonist MK886 was administered. The severity of AP was determined by measuring serum amylase, lipase, Ca2+, pathological changes, myeloperoxidase activity, serum levels of interleukin (IL)-6, and intercellular adhesion molecule-1 (ICAM-1). The TLR2 and TLR4 messenger RNA (mRNA) and proteins were determined by real-time reverse transcriptase polymerase chain reaction and Western blotting, respectively. The mRNA expressions of target molecules of TLR pathways, including IL-6, IL-10, ICAM-1, and tumor necrosis factor α were also measured.Results: Treatment with WY14643 significantly decreased amylase, lipase, myeloperoxidase activity, pathological scores, IL-6, and ICAM-1 levels. The TLR2 and TLR4 mRNA and proteins were markedly decreased after treatment with WY14643, along with IL-6, ICAM-1, and tumor necrosis factor α mRNA levels. However, these effects were completely reversed by the coadministration of MK886.Conclusions: Activation of PPAR-α played a protective role in AP, partially mediated by modulation of TLR pathways.
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| 42. |
- Fu, Jinrong, et al.
(författare)
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Anti-ischemia/reperfusion of C1 inhibitor in myocardial cell injury via regulation of local myocardial C3 activity.
- 2006
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 350:1, s. 162-8
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Tidskriftsartikel (refereegranskat)abstract
- C3 is common to all pathways of complement activation augmenting ischemia/reperfusion (I/R)-induced myocardial injury and cardiac dysfunction. Complement inhibition with the complement regulatory protein, C1 inhibitor (C1INH), obviously exerts cardioprotective effects. Here, we examine whether C1INH regulates C3 activity in the ischemic myocardial tissue. C1INH markedly suppressed C3 mRNA expression and protein synthesis in both a model of I/R-induced rat acute myocardial infarction (AMI) and the cultured rat H9c2 heart myocytes. At least, this regulation was at the transcriptional level in response to oxygen tension. In vitro, C3 deposition on, and binding to, the surface of rat myocardial cells were significantly blocked by C1INH treatment. C1INH could inhibit classical complement-mediated cell lysis via suppressing the biological activity of C3. Therefore, C1INH, in addition to inhibition of the systemic complement activation, prevents myocardial cell injury via a direct inhibitory role in the local myocardial C3 activity.
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| 43. |
- Huang, Xiao-Yu, et al.
(författare)
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Matrix Factorization for Evolution Data
- 2014
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Ingår i: Mathematical problems in engineering (Print). - : Hindawi Limited. - 1024-123X .- 1563-5147. ; , s. 525398-
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Tidskriftsartikel (refereegranskat)abstract
- We study a matrix factorization problem, that is, to find two factor matrices U and V such that R approximate to U-T x V, where R is a matrix composed of the values of the objects O-1, O-2, ... , O-n at consecutive time points T-1, T-2, ... , T-t. We first present MAFED, a constrained optimization model for this problem, which straightforwardly performs factorization on R. Then based on the interplay of the data in U,V, and R, a probabilistic graphical model using the same optimization objects is constructed, in which structural dependencies of the data in these matrices are revealed. Finally, we present a fitting algorithm to solve the proposed MAFED model, which produces the desired factorization. Empirical studies on real-world datasets demonstrate that our approach outperforms the state-of-the-art comparison algorithms.
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| 44. |
- Huang, Xiao-Yu, et al.
(författare)
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Multi-Matrices Factorization with Application to Missing Sensor Data Imputation
- 2013
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Ingår i: Sensors. - : MDPI AG. - 1424-8220. ; 13:11, s. 15172-15186
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Tidskriftsartikel (refereegranskat)abstract
- We formulate a multi-matrices factorization model (MMF) for the missing sensor data estimation problem. The estimation problem is adequately transformed into a matrix completion one. With MMF, an n-by-t real matrix, R, is adopted to represent the data collected by mobile sensors from n areas at the time, T-1, T-2, . . . , T-t, where the entry, R-i,R-j, is the aggregate value of the data collected in the ith area at T-j. We propose to approximate R by seeking a family of d-by-n probabilistic spatial feature matrices, U-(1), U-(2), . . . , U-(t), and a probabilistic temporal feature matrix, V epsilon R-dxt, where R-j approximate to U-(j)(T) T-j. We also present a solution algorithm to the proposed model. We evaluate MMF with synthetic data and a real-world sensor dataset extensively. Experimental results demonstrate that our approach outperforms the state-of-the-art comparison algorithms.
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| 45. |
- Kilpelainen, TO, et al.
(författare)
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Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity
- 2019
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Ingår i: Nature communications. - London : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 376-
-
Tidskriftsartikel (refereegranskat)abstract
- Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.
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| 46. |
- Leng, Xue-Li, et al.
(författare)
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Spiral Coil Inserts for Heat Transfer Enhancement in a Parallel-plate Channel
- 2014
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Ingår i: Numerical Heat Transfer Part A: Applications. - : Informa UK Limited. - 1040-7782 .- 1521-0634. ; 66:7, s. 756-772
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Tidskriftsartikel (refereegranskat)abstract
- The flow fields and heat transfer characteristics in a parallel-plate channel with a transversely placed spiral coil insert were investigated by three-dimensional numerical simulation. The structure of multi-longitudinal-vortices (MLVs) induced by the spiral coil and the effects of MLVs on velocity and temperature fields were studied. The three-dimensional spiral coil induces a series of longitudinal vortices in the channel including leading longitudinal vortex, mainstream longitudinal vortices, near-wall longitudinal vortices, and rear central longitudinal vortex. Transport by the longitudinal vortices can increase the mass exchange between the boundary layer and the mainstream, which speeds up the heat migration from the channel walls and enhances the heat diffusion in the mainstream.
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| 47. |
- Li, Fang-Yi, et al.
(författare)
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Inhibition of K-Ras4B-plasma membrane association with a membrane microdomain-targeting peptide
- 2020
-
Ingår i: Chemical Science. - : Royal Society of Chemistry. - 2041-6520 .- 2041-6539. ; 11:3, s. 826-832
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Tidskriftsartikel (refereegranskat)abstract
- The association of K-Ras4B protein with plasma membrane (PM) is required for its signaling activity. Thus, direct inhibition of K-Ras4B-PM interaction could be a potential anti-Ras therapeutic strategy. However, it remains challenging to modulate such protein-PM interaction. Based on Ras isoform-specific PM microdomain localization patterns, we have developed a potent and isoform-selective peptide inhibitor, Memrasin, for detachment of K-Ras4B from the PM. Memrasin is one of the first direct inhibitors of K-Ras4B-PM interaction, and consists of a membrane l(d) region-binding sequence derived from the C-terminal region of K-Ras4B and an endosome-escape enhancing motif that can aggregate on membrane. It forms peptide-enriched domains in the l(d) region, abrogates the tethering of K-Ras4B to the PM and accordingly impairs Ras signaling activity, thereby efficiently decreasing the viability of several human lung cancer cells in a dose-responsive and K-Ras dependent manner. Memrasin provides a useful tool for exploring the biological function of K-Ras4B on or off the PM and a potential starting point for further development into anti-Ras therapeutics.
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| 48. |
- Li, Q., et al.
(författare)
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Discovery of new strains for furfural degradation using adaptive laboratory evolution in Saccharomyces cerevisiae
- 2023
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Ingår i: Journal of Hazardous Materials. - 0304-3894. ; 459
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Tidskriftsartikel (refereegranskat)abstract
- In industrial production, the excessive discharge of furfural can pose harm to soil microorganisms, aquatic an-imals and plants, as well as humans. Therefore, it is crucial to develop efficient and cost-effective methods for degrading furfural in the environment. Currently, the use of Saccharomyces cerevisiae for furfural degradation in water has shown effectiveness, but there is a need to explore improved efficiency and tolerance in S. cerevisiae for this purpose. In this study, we isolated and evolved highly efficient furfural degradation strains, namely YBA_08 and F60C. These strains exhibited remarkable capabilities, degrading 59% and 99% furfural in the YPD medium after 72 h of incubation, significantly higher than the 31% achieved by the model strain S288C. Through analysis of the efficient degradation mechanism in the evolutionary strain F60C, we discovered a 326% increase in the total amount of NADH and NADPH. This increase likely promotes faster furfural degradation through intracel-lular aldehyde reductases. Moreover, the decrease in NADPH content led to a 406% increase in glutathione content at the background level, which protects cells from damage caused by reactive oxygen species. Mutations and differential expression related to cell cycle and cell wall synthesis were observed, enabling cell survival in the presence of furfural and facilitating rapid furfural degradation and growth recovery. Based on these findings, it is speculated that strains YBA_08 and F60C have the potential to contribute to furfural degradation in water and the production of furfuryl alcohol, ethanol, and FDCA in biorefinery processes.
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| 49. |
- Li, Xiang, et al.
(författare)
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A study on crown interception with four dominant tree species : A direct measurement
- 2016
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Ingår i: Hydrology Research. - : IWA Publishing. - 1998-9563 .- 0029-1277 .- 2224-7955. ; 47:4, s. 857-868
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Tidskriftsartikel (refereegranskat)abstract
- An experiment was conducted to concentrate on the rainfall interception process of individual trees for four common species in Beijing, China, which included needle species (Platycladus orientalis and Pinus tabulaeformis) and broadleaf species (Quercus variabilis and Acer truncatum). Two types of interception storages, the maximum (Cmax) and the minimum interception storage (Cmin), were examined at four simulated rainfall intensities (from 11.7 to 78.5 mm hr-1). Results showed that an average of 91% of Cmax for all the species was intercepted during the first 10 minutes of rainfall, while 45% of Cmax drained off after rainfall cessation. Leaf area index (LAI) and leaf area (LA) were significantly correlated (p < 0.05) with Cmax and Cmin, while such significant correlations were not found between rainfall intensity and Cmax and Cmin. Average Cmax and Cmin across all the species corresponded to 3 and 1% of gross rainfall. Mean Cmax and Cmin of the needle species were 3.0 and 1.8 times larger than that for the broadleaf ones. Results revealed that interception was a dynamic process which encompassed three phases. In addition, LAI and LA were valid predictors of interception in small trees, and deserve further test in forest stands.
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- Liu, Li, et al.
(författare)
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Cardiomyocyte-specific Loss of Diacylglycerol Acyltransferase 1 (DGAT1) Reproduces the Abnormalities in Lipids Found in Severe Heart Failure
- 2014
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 289:43, s. 29881-29891
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Tidskriftsartikel (refereegranskat)abstract
- Background: Total body DGAT1 mice have no cardiac phenotype. Results: Cardiomyocyte DGAT1 knock-out mice have increased mortality and accumulation of potentially toxic lipids, which were corrected by intestinal DGAT1 deletion and GLP-1 receptor agonists. Conclusion: Cardiomyocyte DGAT1 deletion produces heart dysfunction and lipid abnormalities. Significance: Lipotoxicity in the heart can be alleviated by changes in intestinal metabolism. Diacylglycerol acyltransferase 1 (DGAT1) catalyzes the final step in triglyceride synthesis, the conversion of diacylglycerol (DAG) to triglyceride. Dgat1(-/-) mice exhibit a number of beneficial metabolic effects including reduced obesity and improved insulin sensitivity and no known cardiac dysfunction. In contrast, failing human hearts have severely reduced DGAT1 expression associated with accumulation of DAGs and ceramides. To test whether DGAT1 loss alone affects heart function, we created cardiomyocyte-specific DGAT1 knock-out (hDgat1(-/-)) mice. hDgat1(-/-) mouse hearts had 95% increased DAG and 85% increased ceramides compared with floxed controls. 50% of these mice died by 9 months of age. The heart failure marker brain natriuretic peptide increased 5-fold in hDgat1(-/-) hearts, and fractional shortening (FS) was reduced. This was associated with increased expression of peroxisome proliferator-activated receptor and cluster of differentiation 36. We crossed hDgat1(-/-) mice with previously described enterocyte-specific Dgat1 knock-out mice (hiDgat1(-/-)). This corrected the early mortality, improved FS, and reduced cardiac ceramide and DAG content. Treatment of hDgat1(-/-) mice with the glucagon-like peptide 1 receptor agonist exenatide also improved FS and reduced heart DAG and ceramide content. Increased fatty acid uptake into hDgat1(-/-) hearts was normalized by exenatide. Reduced activation of protein kinase C (PKC), which is increased by DAG and ceramides, paralleled the reductions in these lipids. Our mouse studies show that loss of DGAT1 reproduces the lipid abnormalities seen in severe human heart failure.
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