| 1. |
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| 2. |
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| 3. |
- 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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| 4. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 6. |
- Feitosa, Mary F., et al.
(författare)
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Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
- 2018
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Ingår i: PLOS ONE. - : Public library science. - 1932-6203. ; 13:6
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Tidskriftsartikel (refereegranskat)abstract
- Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in approximate to 131 K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P <1.0 x 10(-5)). In Stage 2, these SNVs were tested for independent external replication in individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10(-8)). For African ancestry samples, we detected 18 potentially novel BP loci (P< 5.0 x 10(-8)) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2 have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
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| 7. |
- Feng, Yue Hua, et al.
(författare)
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Increased apolipoprotein M induced by lack of scavenger receptor BI is not activated via HDL-mediated cholesterol uptake in hepatocytes
- 2018
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Ingår i: Lipids in Health and Disease. - : Springer Science and Business Media LLC. - 1476-511X. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Scavenger receptor BI (SR-BI) is a classic high-density lipoprotein (HDL) receptor, which mediates selective lipid uptake from HDL cholesterol esters (HDL-C). Apolipoprotein M (ApoM), as a component of HDL particles, could influence preβ-HDL formation and cholesterol efflux. The aim of this study was to determine whether SR-BI deficiency influenced the expression of ApoM. Methods: Blood samples and liver tissues were collected from SR-BI gene knockout mice, and serum lipid parameters, including total cholesterol (TC), triglyceride (TG), high and low-density lipoprotein cholesterol (HDL-C and LDL-C) and ApoM were measured. Hepatic ApoM and ApoAI mRNA levels were also determined. In addition, BLT-1, an inhibitor of SR-BI, was added to HepG2 cells cultured with cholesterol and HDL, under serum or serum-free conditions. The mRNA and protein expression levels of ApoM were detected by RT-PCR and western blot. Results: We found that increased serum ApoM protein levels corresponded with high hepatic ApoM mRNA levels in both male and female SR-BI-/- mice. Besides, serum TC and HDL-C were also significantly increased. Treatment of HepG2 hepatoma cells with SR-BI specific inhibitor, BLT-1, could up-regulate ApoM expression in serum-containing medium but not in serum-free medium, even in the presence of HDL-C and cholesterol. Conclusions: Results suggested that SR-BI deficiency promoted ApoM expression, but the increased ApoM might be independent from HDL-mediated cholesterol uptake in hepatocytes.
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| 8. |
- 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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| 9. |
- Kristan, Matej, et al.
(författare)
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The Sixth Visual Object Tracking VOT2018 Challenge Results
- 2019
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Ingår i: Computer Vision – ECCV 2018 Workshops. - Cham : Springer Publishing Company. - 9783030110086 - 9783030110093 ; , s. 3-53
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Konferensbidrag (refereegranskat)abstract
- The Visual Object Tracking challenge VOT2018 is the sixth annual tracker benchmarking activity organized by the VOT initiative. Results of over eighty 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 and a “real-time” experiment simulating a situation where a tracker processes images as if provided by a continuously running sensor. A long-term tracking subchallenge has been introduced to the set of standard VOT sub-challenges. The new subchallenge focuses on long-term tracking properties, namely coping with target disappearance and reappearance. A new dataset has been compiled and a performance evaluation methodology that focuses on long-term tracking capabilities has been adopted. The VOT toolkit has been updated to support both standard short-term and the new long-term tracking subchallenges. 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 (http://votchallenge.net).
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| 10. |
- 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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| 11. |
- Su, Yu-Ru, et al.
(författare)
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Validation of a genetic-enhanced risk prediction model for colorectal cancer in a large community-based cohort
- 2023
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American association for cancer research. - 1055-9965 .- 1538-7755. ; 32:3, s. 353-362
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Polygenic risk scores (PRS) which summarize individuals' genetic risk profile may enhance targeted colorectal cancer screening. A critical step towards clinical implementation is rigorous external validations in large community-based cohorts. This study externally validated a PRS-enhanced colorectal cancer risk model comprising 140 known colorectal cancer loci to provide a comprehensive assessment on prediction performance.METHODS: The model was developed using 20,338 individuals and externally validated in a community-based cohort (n = 85,221). We validated predicted 5-year absolute colorectal cancer risk, including calibration using expected-to-observed case ratios (E/O) and calibration plots, and discriminatory accuracy using time-dependent AUC. The PRS-related improvement in AUC, sensitivity and specificity were assessed in individuals of age 45 to 74 years (screening-eligible age group) and 40 to 49 years with no endoscopy history (younger-age group).RESULTS: In European-ancestral individuals, the predicted 5-year risk calibrated well [E/O = 1.01; 95% confidence interval (CI), 0.91-1.13] and had high discriminatory accuracy (AUC = 0.73; 95% CI, 0.71-0.76). Adding the PRS to a model with age, sex, family and endoscopy history improved the 5-year AUC by 0.06 (P < 0.001) and 0.14 (P = 0.05) in the screening-eligible age and younger-age groups, respectively. Using a risk-threshold of 5-year SEER colorectal cancer incidence rate at age 50 years, adding the PRS had a similar sensitivity but improved the specificity by 11% (P < 0.001) in the screening-eligible age group. In the younger-age group it improved the sensitivity by 27% (P = 0.04) with similar specificity.CONCLUSIONS: The proposed PRS-enhanced model provides a well-calibrated 5-year colorectal cancer risk prediction and improves discriminatory accuracy in the external cohort.IMPACT: The proposed model has potential utility in risk-stratified colorectal cancer prevention.
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| 12. |
- Thomas, Minta, et al.
(författare)
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Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values < 0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice.
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| 13. |
- Yi, Huan, et al.
(författare)
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Association of Levonorgestrel-Releasing Intrauterine Device with Gynecologic and Breast Cancers: National Cohort Study in Sweden
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Ingår i: American Journal of Obstetrics and Gynecology. - 1097-6868.
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe levonorgestrel-releasing intrauterine device (LNG-IUD) is widely used for the treatment of menorrhagia, dysmenorrhea, and for contraception. However, the association between the use of LNG-IUD and the risk of site-specific gynecologic and breast cancers remains inconclusive.ObjectiveWe aim to address this knowledge gap by investigating whether the use of LNG-IUD is associated with a significant risk of site-specific gynecologic and breast cancers. This will be achieved by accessing the nationwide Swedish Registers, with consideration given to the influence and potential interaction of family history of cancer.Study DesignA total of 514719 women aged 18 to 50 years who have used LNG-IUD between July 2005 and December 2018 were identified from the Swedish Prescribed Drug Register and randomly matched with 1544157 comparisons who did not use LNG-IUD at a ratio of 1:3. The propensity score was calculated and matched among women who used LNG-IUD and the matched comparisons. The follow-up period started from the date of the first prescription of LNG-IUD for users as well as for their matched comparisons and ended at the date of diagnosis of gynecologic and breast cancers, date of death from any cause, and the end of the study period, whichever came first. The Cox proportional hazard model with a competing risk analysis was used to calculate hazard ratios and 95% confidence intervals. Additive interaction was calculated as the relative excess risk for interaction, while multiplicative interaction was calculated by including a product term in the regression model.ResultsThe use of LNG-IUD was associated with a 13% higher risk of breast cancer (adjusted HR, 1.13; 95% CI, 1.10-1.17), a 33% lower risk of endometrial cancer (adjusted HR, 0.67; 95% CI, 0.56-0.80), a 14% lower risk of ovarian cancer (adjusted HR, 0.86; 95% CI, 0.75-0.99) and a 9% reduced risk of cervical cancer (adjusted HR, 0.91; 95% CI, 0.84-0.99) compared to women who did not use LNG-IUD. A significant additive interaction between LNG-IUD use and family history of cancer was observed in breast cancer, indicating a relative 19% excess risk for interaction (P < 0.002), and 1.63 additional cases per 10,000 person-years.ConclusionsThe risk of gynecologic and breast cancers exhibits a site-specific effect among LNG-IUD users. It's important to note that the observed effect is small for breast cancer and the results are limited by the observational study design. Clinical recommendations regarding the use of LNG-IUD should carefully weigh its potential benefits and risks. Close monitoring is advisable for the potential development of breast cancer, particularly among women with a family history of breast cancer.
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| 14. |
- Bond, Alexander E., et al.
(författare)
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A synthesis of approaches for modelling coupled thermal-hydraulic-mechanical-chemical processes in a single novaculite fracture experiment
- 2017
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Ingår i: Environmental Earth Sciences. - : Springer. - 1866-6280 .- 1866-6299. ; 76:1
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Tidskriftsartikel (refereegranskat)abstract
- The geological formation immediately surrounding a nuclear waste disposal facility has the potential to undergo a complex set of physical and chemical processes starting from construction and continuing many years after closure. The DECOVALEX project (DEvelopment of COupled models and their VALidation against EXperiments) was established and maintained by a variety of waste management organisations, regulators and research organisations to help improve capabilities in experimental interpretation, numerical modelling and blind prediction of complex coupled systems. In the present round of DECOVALEX (D-2015), one component of Task C1 has considered the detailed experimental work of Yasuhara et al. (Earth Planet Sci Lett 244: 186-200, 2006), wherein a single artificial fracture in novaculite (micro-or crypto-crystalline quartz) is subject to variable fluid flows, mechanical confining pressure and different applied temperatures. This paper presents a synthesis of the completed work of six separate research teams. A range of approaches are presented including 2D and 3D high-resolution coupled thermo-hydro-mechanical-chemical models. The results of the work show that while good, physically plausible representations of the experiment can be obtained using a range of approaches, there is considerable uncertainty in the relative importance of the various processes, and that the parameterisation of these processes can be closely linked to the interpretation of the fracture surface topography at different spatial scales.
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| 15. |
- Bratman, Gregory N., et al.
(författare)
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Nature and mental health : An ecosystem service perspective
- 2019
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 5:7
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Forskningsöversikt (refereegranskat)abstract
- A growing body of empirical evidence is revealing the value of nature experience for mental health. With rapid urbanization and declines in human contact with nature globally, crucial decisions must be made about how to preserve and enhance opportunities for nature experience. Here, we first provide points of consensus across the natural, social, and health sciences on the impacts of nature experience on cognitive functioning, emotional well-being, and other dimensions of mental health. We then show how ecosystem service assessments can be expanded to include mental health, and provide a heuristic, conceptual model for doing so.
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| 16. |
- 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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| 17. |
- Chen, I-Hua, et al.
(författare)
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Psychometric properties of the Depression, Anxiety, and Stress Scale (DASS-21) among different Chinese populations : A cross-sectional and longitudinal analysis
- 2023
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Ingår i: Acta Psychologica. - : Elsevier. - 0001-6918 .- 1873-6297. ; 240
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Tidskriftsartikel (refereegranskat)abstract
- Given that there is limited evidence concerning the psychometric properties of DASS-21 when applied to primary school students, the present study undertook a comprehensive exploration of the psychometric evidence supporting the use of the DASS-21 within this demographic. The research comprised three studies. In Study 1, the basic psychometric properties of internal consistency and construct validity were examined. A total of 3138 primary school students from three provinces in mainland China participated. The internal reliability of the overall scale was 0.93, and for all the subscales, it was higher than 0.80. Construct validity was partially supported. Both exploratory and confirmatory factor analyses upheld the factorial validity of the original three-factor structure. While convergent validity was established, the results showed unsatisfactory discriminant validity. The bifactor model showed that DASS-21 raw scores predominantly indicated the general factor, evidenced by the high explained common variance and omega-hierarchical values. However, the contributions from the three specific factors were minimal, with their omega hierarchical values all below 0.15. In Study 2, a longitudinal design was adopted, tracking 1366 primary school students from Southwest China over a three-month interval. The results further confirmed that the DASS-21 exhibited scalar time-invariance. The latent mean analysis showed that there were no statistically significant differences in the latent means of depression, anxiety, and stress between Time 1 and Time 2. In Study 3, which included 364 college students and 483 enterprise workers, the results demonstrated that the DASS-21 had measurement invariance across different populations. The latent mean analysis further confirmed that, in terms of the latent mean of all three subscales, both college students and enterprise workers had significantly higher scores than primary school students. Overall, the findings indicated that the DASS-21 is a suitable tool for screening schoolchildren for general psychological distress, but it is not suitable for discerning distinct negative mood state disorders.
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| 18. |
- Chen, Yujie, et al.
(författare)
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Shape-Memory Polymeric Artificial Muscles : Mechanisms, Applications and Challenges
- 2020
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Ingår i: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 25:18
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Forskningsöversikt (refereegranskat)abstract
- Shape-memory materials are smart materials that can remember an original shape and return to their unique state from a deformed secondary shape in the presence of an appropriate stimulus. This property allows these materials to be used as shape-memory artificial muscles, which form a subclass of artificial muscles. The shape-memory artificial muscles are fabricated from shape-memory polymers (SMPs) by twist insertion, shape fixation via T(m)or T-g, or by liquid crystal elastomers (LCEs). The prepared SMP artificial muscles can be used in a wide range of applications, from biomimetic and soft robotics to actuators, because they can be operated without sophisticated linkage design and can achieve complex final shapes. Recently, significant achievements have been made in fabrication, modelling, and manipulation of SMP-based artificial muscles. This paper presents a review of the recent progress in shape-memory polymer-based artificial muscles. Here we focus on the mechanisms of SMPs, applications of SMPs as artificial muscles, and the challenges they face concerning actuation. While shape-memory behavior has been demonstrated in several stimulated environments, our focus is on thermal-, photo-, and electrical-actuated SMP artificial muscles.
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| 19. |
- 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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| 20. |
- Cheng, Shi-Ping, et al.
(författare)
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Haplotype-resolved genome assembly and allele-specific gene expression in cultivated ginger
- 2021
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Ingår i: Horticulture Research. - : Springer Nature. - 2052-7276. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Ginger (Zingiber officinale) is one of the most valued spice plants worldwide; it is prized for its culinary and folk medicinal applications and is therefore of high economic and cultural importance. Here, we present a haplotype-resolved, chromosome-scale assembly for diploid ginger anchored to 11 pseudochromosome pairs with a total length of 3.1 Gb. Remarkable structural variation was identified between haplotypes, and two inversions larger than 15 Mb on chromosome 4 may be associated with ginger infertility. We performed a comprehensive, spatiotemporal, genome-wide analysis of allelic expression patterns, revealing that most alleles are coordinately expressed. The alleles that exhibited the largest differences in expression showed closer proximity to transposable elements, greater coding sequence divergence, more relaxed selection pressure, and more transcription factor binding site differences. We also predicted the transcription factors potentially regulating 6-gingerol biosynthesis. Our allele-aware assembly provides a powerful platform for future functional genomics, molecular breeding, and genome editing in ginger.
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| 21. |
- de Vries, Paul S., et al.
(författare)
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Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
- 2019
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Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1033-1054
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Tidskriftsartikel (refereegranskat)abstract
- A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
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| 22. |
- Du, Chenqiu, et al.
(författare)
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Home dampness/mold(D/M) improvement in children's residences over the past decade in China-a comparison of repeated surveys in 2010 and 2019
- 2021
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Ingår i: Building and Environment. - : Elsevier. - 0360-1323 .- 1873-684X. ; 205
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Tidskriftsartikel (refereegranskat)abstract
- There is mounting evidence that exposure to household dampness/mold (D/M) is the cause of respiratory, allergic diseases for children. While few research focuses on the effects caused by building environment changes, from a longitudinal investigation perspective, especially for China experiencing a rapid development in recent years. This study aimed to explore the changes of D/M in Chinese homes over the past 10 years and identify the impacts of climate, building energy efficiency and residents' behaviors. The cross-sectional surveys were repeatedly conducted in children' residences in 2010 (Period I) and 2019 (Period II), among Taiyuan, Urumqi in northern China, and Nanjing, Shanghai, Wuhan, Changsha, Chongqing in southern China. Finally, 23465 children in Period I and 34720 children in Period II were involved, with no changes of residences since birth. The results showed that the proportions for reported D/M indicators were significantly reduced in Period II: e.g., 93.8% and 84.1% residents respectively answered no visible mold spots and damp stains in current residences, compared to only 78.3% and 62.2% in Period I. Southern homes accounted for high proportions for D/M indicator occurrences; warm-humid climate, annual higher precipitation and lower sunshine hours, etc., exacerbated the indoor D/M exposure risks. While residents' behaviors like ventilation, airing quilt/beddings, regular cleaning ameliorated the reported D/M significantly. The findings, from a temporal and spacious dimension perspective, advance our understanding of indoor D/M changes, precisely improvement in children' homes over the past 10 years, benefiting to promote indoor air quality standards in China.
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| 23. |
- Elsayed, Mohamed Hammad, et al.
(författare)
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Visible-light-driven hydrogen evolution using nitrogen-doped carbon quantum dot-implanted polymer dots as metal-free photocatalysts
- 2021
-
Ingår i: Applied Catalysis B: Environmental. - : Elsevier BV. - 0926-3373. ; 283
-
Tidskriftsartikel (refereegranskat)abstract
- Given the photocatalytic properties of semiconducting polymers and carbon quantum dots (CQDs), we report a new structure for a metal-free photocatalytic system with a promising efficiency for hydrogen production through the combination of an organic semiconducting polymer (PFTBTA) and N-doped carbon quantum dots (NCQDs) covered by PS-PEGCOOH to produce heterostructured photocatalysts in the form of polymer dots (Pdots). This design could provide strong interactions between the two materials owing to the space confinement effect in nanometer-sized Pdots. Small particle size NCQDs are easy to insert inside the Pdot, which leads to an increase in the stability of the Pdot structure and enhances the hydrogen evolution rate by approximately 5-fold over that of pure PFTBTA Pdots. The photophysics and the mechanism behind the catalytic activity of our design are investigated by transient absorption measurement, demonstrating the role of NCQDs to enhance the charge separation and the photocatalytic efficiency of the PFTBTA Pdot.
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| 24. |
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| 25. |
- Eme, Laura, et al.
(författare)
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Inference and reconstruction of the heimdallarchaeial ancestry of eukaryotes
- 2023
-
Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 618:7967, s. 992-
-
Tidskriftsartikel (refereegranskat)abstract
- In the ongoing debates about eukaryogenesis-the series of evolutionary events leading to the emergence of the eukaryotic cell from prokaryotic ancestors-members of the Asgard archaea play a key part as the closest archaeal relatives of eukaryotes(1). However, the nature and phylogenetic identity of the last common ancestor of Asgard archaea and eukaryotes remain unresolved(2-4). Here we analyse distinct phylogenetic marker datasets of an expanded genomic sampling of Asgard archaea and evaluate competing evolutionary scenarios using state-of-the-art phylogenomic approaches. We find that eukaryotes are placed, with high confidence, as a well-nested clade within Asgard archaea and as a sister lineage to Hodarchaeales, a newly proposed order within Heimdallarchaeia. Using sophisticated gene tree and species tree reconciliation approaches, we show that analogous to the evolution of eukaryotic genomes, genome evolution in Asgard archaea involved significantly more gene duplication and fewer gene loss events compared with other archaea. Finally, we infer that the last common ancestor of Asgard archaea was probably a thermophilic chemolithotroph and that the lineage from which eukaryotes evolved adapted to mesophilic conditions and acquired the genetic potential to support a heterotrophic lifestyle. Our work provides key insights into the prokaryote-to-eukaryote transition and a platform for better understanding the emergence of cellular complexity in eukaryotic cells.
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| 26. |
- Fan, Mei-Cen, et al.
(författare)
-
Room-temperature extraction of individual elements from charged spent LiFePO4 batteries
- 2022
-
Ingår i: Rare Metals. - : Springer. - 1001-0521 .- 1867-7185.
-
Tidskriftsartikel (refereegranskat)abstract
- Recycling millions of metric tons of spent LiFePO4 batteries would benefit human health while reducing resource depletion and environmental pollution. However, recovering individual elements from the spent batteries without generating waste is challenging. Here, we present a distinctive approach for recycling spent LiFePO4 batteries at room temperature, where water is the only leaching agent consumed. FePO4 and lithium intercalated graphite act as a precursor material for selectively extracting lithium, iron, and phosphorus through charging the LiFePO4 batteries to the delithiated state. NaOH solution extracted Fe from FePO4 within 30 min and regenerated without consumption, similar to a catalyst. Under the optimal leaching conditions (1 mol·L−1 NaOH, 0.5 h, NaOH/Fe molar ratio of 4.5), Fe and P leaching efficiencies achieved 89.1% and 99.2%, respectively. The methodology reflected in this research reduced the material cost per kg cathode material to a fraction of previously published reports, only occupies 6.13% of previous reports. In addition, the method improved the battery recycling revenue calculated by the EverBatt model by 2.31 times and 1.94 times over pyrometallurgical and hydrometallurgical methods. The proposed method allows for the convenient recovery of the elemental components of spent LiFePO4 batteries.
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| 27. |
- 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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| 28. |
- Guo, Hua, et al.
(författare)
-
Barium Titanium Oxynitride from Ammonia-Free Nitridation of Reduced BaTiO3
- 2021
-
Ingår i: Inorganics. - : MDPI AG. - 2304-6740. ; 9:8
-
Tidskriftsartikel (refereegranskat)abstract
- We investigated the nitridation of reduced BaTiO3, BaTiO2.60H0.08, corresponding to an oxyhydride with a large concentration of O defects (>10%). The material is readily nitrided under flowing N2 gas at temperatures between 400 and 450 °C to yield oxynitrides BaTiO2.6Nx (x = 0.2−0.22) with a slightly tetragonally distorted perovskite structure, a ≈ 4.01 and c ≈ 4.02 Å, and Ti partially remaining in the oxidation state III. The tetragonal structure was confirmed from Raman spectroscopy. 14N MAS NMR spectroscopy shows a single resonance at 270 ppm, which is typical for perovskite transition metal oxynitrides. However, largely different signal intensity for materials with very similar N content suggests N/O/vacancy ordering when prolonging nitridation times to hours. Diffuse reflectance UV-VIS spectroscopy shows a reduction of the intrinsic band gap to 2.4–2.45 eV compared to BaTiO3 (~3.2 eV). Mott-Schottky measurements confirm n-type conductivity and reveal a slight negative shift of the conduction band edge from –0.59 V (BaTiO3) to ~–0.65 eV.
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| 29. |
- Guo, Hua, et al.
(författare)
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Controllable synthesis of LiFePO4 in different polymorphs and study of the reaction mechanism
- 2017
-
Ingår i: Journal of Materials Chemistry A. - : Royal Society of Chemistry (RSC). - 2050-7488 .- 2050-7496. ; 5:27, s. 14294-14300
-
Tidskriftsartikel (refereegranskat)abstract
- Lithium iron phosphate, a widely used cathode material in Lithium Ion Batteries (LIBs), crystallizes typically in an olivine-type phase, alpha-LiFePO4 (aLFP). However, the new phase beta-LiFePO4 (bLFP), which can be transformed from aLFP at high temperature with high pressure, can be produced through a simple liquid-phase reaction. The mechanism of controllable synthesis of the two polymorphs of lithium iron phosphate has not been studied thoroughly. In this paper, with thorough experiments, we demonstrate that controllable synthesis of LFP with different crystal polymorphs can be obtained by controlling certain conditions. The phosphoric acid ratio in the reactants and the reaction time play key roles in the controllable syntheses. Higher phosphoric acid ratios and shorter reaction times would result in a higher bLFP content, while a lower amount of phosphoric acid and a longer reaction time would be beneficial to aLFP formation. To illustrate the mechanism for this phenomenon, the detailed reaction process was researched via X-ray diffraction, from which a possible mechanism associated with the evolution of crystal structures was demonstrated. The solvent content is also important for the process: some water content would lead to nanoplate-shaped aLFP particles appearing. Their influence on the reaction could be attributed to the change of thermodynamics and kinetics, which leads to different crystal nucleation, growth and phase-change processes.
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| 30. |
- Guo, Peng Fei, et al.
(författare)
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Iron-chelated thermoresponsive polymer brushes on bismuth titanate nanosheets for metal affinity separation of phosphoproteins
- 2020
-
Ingår i: Colloids and Surfaces B: Biointerfaces. - : Elsevier BV. - 0927-7765. ; 196
-
Tidskriftsartikel (refereegranskat)abstract
- Separation of phosphoproteins plays an important role for identification of biomarkers in life science. In this work, bismuth titanate supported, iron-chelated thermoresponsive polymer brushes were prepared for selective separation of phosphoproteins. The iron-chelated thermoresponsive polymer brushes were synthesized by surface-initiated atom transfer radical polymerization of N-isopropylacrylamide and glycidyl methacrylate, followed by a ring opening reaction of epoxy group, and chelation of the obtained cis-diols with Fe3+ ions. The composite material was characterized to determine the size and thickness, the content of the organic polymer and the metal loading. The bismuth titanate supported, iron-chelated thermoresponsive polymer brushes showed selective binding for phosphoproteins in the presence of abundant interfering proteins, and a high binding capacity for phosphoproteins by virtue of the metal affinity between the metal ions on the polymer brushes and the phosphate groups in the phosphoproteins (664 mg β-Casein per g sorbent). The thermoresponsive property of the polymer brushes made it possible to adjust phosphoprotein binding by changing temperature. Finally, separation of phosphoproteins from a complex biological sample (i.e. milk) was demonstrated using the nanosheet-supported thermoresponsive polymer brushes.
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| 31. |
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| 32. |
- Hansen, Kjetil Falkenberg, 1972-, et al.
(författare)
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A music puzzle game application for engaging in active listening
- 2012
-
Ingår i: Proceedings of 97th Information Science and Music (SIGMUS) Research Conference. - Tokyo : Information Processing Society of Japan. ; , s. 1-4
-
Konferensbidrag (refereegranskat)abstract
- In this paper we introduce an application for tablet devices with Android operating system called The Music Puzzle.This work is part of an ongoing projectcalled The Soundparkï¿œUsing modern smartphones to create interactive listening experiences for hearing impaired. In the Soundpark, we intend to provide different experimental applications for interacting with sound. The aim of the presented study was to create interactive and game-inspired listening experiences for persons with hearing impairmens (and possibly using hearing aids or having cochlea implants). Audio-based programs constitute a significant part of the Android market, but the scopes of existing applications are limited. Modern smart devices open up new possibilities both in terms of usingexternal information as input and providing real-time audio feedback to the user, and the Music Puzzle has a novel approach that explores the new possibilities.
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| 33. |
- Hansen, Kjetil Falkenberg, 1972-, et al.
(författare)
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Music Puzzle : An audio-based computer game that inspires to train listening abilities
- 2013
-
Ingår i: Advances in Computer Entertainment. - Cham : Springer. - 9783319031606 - 9783319031613 ; , s. 540-543
-
Konferensbidrag (refereegranskat)abstract
- The Music Puzzle is a computer game for tablets and smartphones using sounds for the gameplay. Just like an original picture is reconstructed from pieces with jigsaw puzzle, an original sound is reconstructed from musical segments with Music Puzzle. Each segment is distorted by shifting the pitch and equalization. To finish the game, the user listens to each segment visualized as pieces on the screen, reorders them, and corrects their pitch and equalization. The game has a possibility for deaf and hard of hearing people to improve their residual hearing ability since the observation shows their concentrating the game with sounds and preference for music.
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| 34. |
- Hua, Wei, et al.
(författare)
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A Germanosilicate Structure with 11 x 11 x 12-Ring Channels Solved by Electron Crystallography
- 2014
-
Ingår i: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 53:23, s. 5868-5871
-
Tidskriftsartikel (refereegranskat)abstract
- Zeolites have been widely used in industry owing to their ordered micropores and stable frameworks. The pore sizes and shapes are the key parameters that affect the selectivity and efficiency in their applications in catalysis, sorption, and separation. Zeolites with pores defined by 10 and 12 TO4 tetrahedra are often used for various catalytic processes. To optimize the performance of zeolites, it is extremely desirable to fine-tune the pore sizes/shapes. The first germanosilicate zeolite with a three-dimensional 11 x 11 x 12-ring channel system, PKU-16 (PKU, Peking University) is presented. Nanosized PKU-16 was structurally characterized by the new three-dimensional rotation electron diffraction (RED) technique. PKU-16 is structurally related to the zeolite beta polymorph C (BEC, 12 x 12 x 12-ring channels) by rotating half of the four-rings in double mtw units.
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| 35. |
- Huyghe, Jeroen R., et al.
(författare)
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Discovery of common and rare genetic risk variants for colorectal cancer
- 2019
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:1, s. 76-
-
Tidskriftsartikel (refereegranskat)abstract
- To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 x 10(-8), bringing the number of known independent signals for CRC to similar to 100. New signals implicate lower-frequency variants, Kruppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.
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| 36. |
- Jiang, Ziyu, et al.
(författare)
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HLA class I genes modulate disease risk and age at onset together with DR-DQ in Chinese patients with insulin-requiring type 1 diabetes
- 2021
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 64:9, s. 2026-2036
-
Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: The study aimed to investigate the effects of HLA class I genes on susceptibility to type 1 diabetes with different onset ages, in addition to the well-established effects of HLA class II genes. Methods: A total of 361 patients with type 1 diabetes (192 patients with onset <18 years and 169 patients with onset ≥18 years) and 500 healthy control participants from China were enrolled and genotyped for the HLA-A, -B, -C, -DQA1, -DQB1 and -DRB1 genes using next-generation sequencing. Results: The susceptible DR3 (β = −0.09, p = 0.0009) and DR4-DQ8 (β = −0.13, p = 0.0059) haplotypes were negatively associated with onset age, while the protective DR11 (β = 0.21, p = 0.0314) and DR12 (β = 0.27, p < 0.0001) haplotypes were positively associated with onset age. After adjustment for linkage disequilibrium with DR-DQ haplotypes, A*11:01:01 was positively associated with onset age (β = 0.06, p = 0.0370), while the susceptible C*15:02:01 was negatively associated with onset age (β = −0.21, p = 0.0050). The unit for β was double square-root (fourth root) transformed years of change in onset age associated with per copy of the HLA haplotype/allele. In addition, B*46:01:01 was protective (OR 0.41, 0.46; pc [corrected for multiple comparisons] = 0.0044, 0.0040), whereas A*24:02:01 (OR 2.71, 2.25; pc = 0.0003, 0.0002) and B*54:01:01 (OR 3.96, 3.79; pc = 0.0018, 0.0004) were predisposing in both the <18 group and the ≥18 group compared with healthy control participants. In the context of DR4-DQ4, A*11:01:01 (61.29% vs 28.26%, pc = 0.0144) was increased while the predisposing A*24:02:01 (19.35% vs 47.83%, pc = 0.0403) was decreased in patients with onset ≥18 years when compared with patients with onset <18 years. Conclusions/interpretation: In addition to DR-DQ haplotypes, novel HLA class I alleles were detected to play a role in susceptibility to type 1 diabetes with different onset ages, which could improve the understanding of disease heterogeneity and has implications for the design of future studies. Graphical abstract: [Figure not available: see fulltext.].
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| 37. |
- Justice, Anne E., et al.
(författare)
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Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
- 2019
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
-
Tidskriftsartikel (refereegranskat)abstract
- Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
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| 38. |
- Lee, James J, et al.
(författare)
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Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals.
- 2018
-
Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 50:8, s. 1112-1121
-
Tidskriftsartikel (refereegranskat)abstract
- Here we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1million individuals and identify 1,271independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development processes and neuron-to-neuron communication. In a separate analysis of the X chromosome, we identify 10independent genome-wide-significant SNPs and estimate a SNP heritability of around 0.3% in both men and women, consistent with partial dosage compensation. A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11-13% of the variance in educational attainment and 7-10% of the variance in cognitive performance. This prediction accuracy substantially increases the utility of polygenic scores as tools in research.
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| 39. |
- Li, Cong, et al.
(författare)
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Impacts of conservation and human development policy across stakeholders and scales
- 2015
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:24, s. 7396-7401
-
Tidskriftsartikel (refereegranskat)abstract
- Ideally, both ecosystem service and human development policies should improve human well-being through the conservation of ecosystems that provide valuable services. However, program costs and benefits to multiple stakeholders, and how they change through time, are rarely carefully analyzed. We examine one of China's new ecosystem service protection and human development policies: the Relocation and Settlement Program of Southern Shaanxi Province (RSP), which pays households who opt voluntarily to resettle from mountainous areas. The RSP aims to reduce disaster risk, restore important ecosystem services, and improve human well-being. We use household surveys and biophysical data in an integrated economic cost-benefit analysis for multiple stakeholders. We project that the RSP will result in positive net benefits to the municipal government, and to cross-region and global beneficiaries over the long run along with environment improvement, including improved water quality, soil erosion control, and carbon sequestration. However, there are significant short-run relocation costs for local residents so that poor households may have difficulty participating because they lack the resources to pay the initial costs of relocation. Greater subsidies and subsequent supports after relocation are necessary to reduce the payback period of resettled households in the long run. Compensation from downstream beneficiaries for improved water and from carbon trades could be channeled into reducing relocation costs for the poor and sharing the burden of RSP implementation. The effectiveness of the RSP could also be greatly strengthened by early investment in developing human capital and environment-friendly jobs and establishing long-term mechanisms for securing program goals. These challenges and potential solutions pervade ecosystem service efforts globally.
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| 40. |
- Li, Zheng, et al.
(författare)
-
Music Puzzle: An Application for Hearing Training on Android Smart Devices
- 2012
-
Ingår i: TMH-QPSR special issue: Proceedings of SMC Sweden 2012 Sound and Music Computing, Understanding and Practicing in Sweden. - Stockholm. - 1104-5787. ; 52:1, s. 44-45, s. 44-45
-
Tidskriftsartikel (refereegranskat)abstract
- The Music Puzzle is part of an ongoing project called Ljudparken/The Soundpark – Using modern smartphones to create interactive listening experiences for hearing impaired. The aim is to create interactive listening experiences for Deaf or Hard-of-Hearing persons (DHH). The interaction is carried out through using new sensor-based audio interfaces.
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| 41. |
- Liang, Hua, et al.
(författare)
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Recognition of maturity-onset diabetes of the young in China
- 2021
-
Ingår i: Journal of Diabetes Investigation. - : Wiley. - 2040-1116 .- 2040-1124. ; 12:4, s. 501-509
-
Tidskriftsartikel (refereegranskat)abstract
- Aims/Introduction: Given that mutations related to maturity-onset diabetes of the young (MODY) are rarely found in Chinese populations, we aim to characterize the mutation spectrum of MODY pedigrees. Materials and Methods: Maturity-onset diabetes of the young candidate gene- or exome-targeted capture sequencing was carried out in 76 probands from unrelated families fulfilling the clinical diagnostic criteria for MODY. MAF <0.01 in the GnomAD or ExAC database was used to filter significant variants. Sanger sequencing was then carried out to validate findings. Function prediction by SIFT, PolyPhen-2 and PROVEAN or CADD was carried out in missense mutations. Results: A total of 32 mutations in six genes were identified in 31 families, accounting for 40.79% of the potential MODY families. The MODY subtype detection rate was 18.42% for GCK, 15.79% for HNF1A, 2.63% for HNF4A, and 1.32% for KLF11, PAX4 and NEUROG3. Seven nonsense/frameshift mutations and four missense mutations with damaging prediction were newly identified novel mutations. The clinical features of MODY2, MODY3/1 and MODYX are similar to previous reports. Clinical phenotype of NEUROG3 p.Arg55Glufs*23 is characterized by hyperglycemia and mild intermittent abdominal pain. Conclusions: This study adds to the emerging pattern of MODY epidemiology that the proportion of MODY explained by known pathogenic genes is higher than that previously reported, and found NEUROG3 as a new causative gene for MODY.
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| 42. |
- Liu, Hui, et al.
(författare)
-
Centromere-Specific Retrotransposons and Very-Long-Chain Fatty Acid Biosynthesis in the Genome of Yellowhorn (Xanthoceras sorbifolium, Sapindaceae), an Oil-Producing Tree With Significant Drought Resistance
- 2021
-
Ingår i: Frontiers in Plant Science. - : Frontiers Media S.A.. - 1664-462X. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- In-depth genome characterization is still lacking for most of biofuel crops, especially for centromeres, which play a fundamental role during nuclear division and in the maintenance of genome stability. This study applied long-read sequencing technologies to assemble a highly contiguous genome for yellowhorn (Xanthoceras sorbifolium), an oil-producing tree, and conducted extensive comparative analyses to understand centromere structure and evolution, and fatty acid biosynthesis. We produced a reference-level genome of yellowhorn, ∼470 Mb in length with ∼95% of contigs anchored onto 15 chromosomes. Genome annotation identified 22,049 protein-coding genes and 65.7% of the genome sequence as repetitive elements. Long terminal repeat retrotransposons (LTR-RTs) account for ∼30% of the yellowhorn genome, which is maintained by a moderate birth rate and a low removal rate. We identified the centromeric regions on each chromosome and found enrichment of centromere-specific retrotransposons of LINE1 and Gypsy in these regions, which have evolved recently (∼0.7 MYA). We compared the genomes of three cultivars and found frequent inversions. We analyzed the transcriptomes from different tissues and identified the candidate genes involved in very-long-chain fatty acid biosynthesis and their expression profiles. Collinear block analysis showed that yellowhorn shared the gamma (γ) hexaploidy event with Vitis vinifera but did not undergo any further whole-genome duplication. This study provides excellent genomic resources for understanding centromere structure and evolution and for functional studies in this important oil-producing plant.
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| 43. |
- Liu, Tang hong, et al.
(författare)
-
Differences in aerodynamic effects when trains with different marshalling forms and lengths enter a tunnel
- 2019
-
Ingår i: Tunnelling and Underground Space Technology. - : Elsevier BV. - 0886-7798. ; 84, s. 70-81
-
Tidskriftsartikel (refereegranskat)abstract
- Unsteady Reynolds-averaged Navier-Stokes (URANS) simulations were performed to simulate trains with different marshalling forms and lengths entering a tunnel. Three models, including a short train, a double train and a long train, were used to analyse the influence of the train configuration on the pressure variations during a train's passage. The results of the numerical predictions were validated against existing experimental data, with which they showed good agreement. The differences in the maximum pressure peak distribution and the pressure fluctuations were analysed by means of Mach diagrams. The results show that the grouping length exerts a considerable influence on the amplitude of the pressure on the train body and that the influence of the grouping length on the pressure variation on the tunnel wall varies with the location in the tunnel. The tunnel space can be divided into three and four zones with regard to the influences on the maximum positive and negative pressure values, respectively. The different marshalling forms also influence the maximum peak values and local profiles of the pressure history curves, although this influence is much slighter than that of the train's grouping length.
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| 44. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
-
Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 45. |
- 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
-
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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| 46. |
- Ma, Zhanyu, et al.
(författare)
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Decorrelation of Neutral Vector Variables : Theory and Applications
- 2018
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Ingår i: IEEE Transactions on Neural Networks and Learning Systems. - : IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. - 2162-237X .- 2162-2388. ; 29:1, s. 129-143
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we propose novel strategies for neutral vector variable decorrelation. Two fundamental invertible transformations, namely, serial nonlinear transformation and parallel nonlinear transformation, are proposed to carry out the decorrelation. For a neutral vector variable, which is not multivariate-Gaussian distributed, the conventional principal component analysis cannot yield mutually independent scalar variables. With the two proposed transformations, a highly negatively correlated neutral vector can be transformed to a set of mutually independent scalar variables with the same degrees of freedom. We also evaluate the decorrelation performances for the vectors generated from a single Dirichlet distribution and a mixture of Dirichlet distributions. The mutual independence is verified with the distance correlation measurement. The advantages of the proposed decorrelation strategies are intensively studied and demonstrated with synthesized data and practical application evaluations.
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| 47. |
- Ma, Zhanyu, 1982-, et al.
(författare)
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EEG Signal Classification with Super-Dirichlet Mixture Model
- 2012
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Ingår i: Processings of IEEE Statistical Signal Processing (SSP) Workshop 2012. - : IEEE. - 9781467301831 ; , s. 440-443
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Konferensbidrag (refereegranskat)abstract
- Classification of the Electroencephalogram (EEG) signal is a challengeable task in the brain-computer interface systems. The marginalized discrete wavelet transform (mDWT) coefficients extracted from the EEG signals have been frequently used in researches since they reveal features related to the transient nature of the signals. To improve the classification performance based on the mDWT coefficients, we propose a new classification method by utilizing the nonnegative and sum-to-one properties of the mDWT coefficients. To this end, the distribution of the mDWT coefficients is modeled by the Dirichlet distribution and the distribution of the mDWT coefficients from more than one channels is described by a super-Dirichletmixture model (SDMM). The Fisher ratio and the generalization error estimation are applied to select relevant channels, respectively. Compared to the state-of-the-art support vector machine (SVM) based classifier, the SDMM based classifier performs more stable and shows a promising improvement, with both channel selection strategies.
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| 48. |
- Ma, Zhanyu, et al.
(författare)
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Predictive Distribution of the Dirichlet Mixture Model by Local Variational Inference
- 2014
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Ingår i: Journal of Signal Processing Systems. - : Springer Science and Business Media LLC. - 1939-8018 .- 1939-8115. ; 74:3, s. 359-374
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Tidskriftsartikel (refereegranskat)abstract
- In Bayesian analysis of a statistical model, the predictive distribution is obtained by marginalizing over the parameters with their posterior distributions. Compared to the frequently used point estimate plug-in method, the predictive distribution leads to a more reliable result in calculating the predictive likelihood of the new upcoming data, especially when the amount of training data is small. The Bayesian estimation of a Dirichlet mixture model (DMM) is, in general, not analytically tractable. In our previous work, we have proposed a global variational inference-based method for approximately calculating the posterior distributions of the parameters in the DMM analytically. In this paper, we extend our previous study for the DMM and propose an algorithm to calculate the predictive distribution of the DMM with the local variational inference (LVI) method. The true predictive distribution of the DMM is analytically intractable. By considering the concave property of the multivariate inverse beta function, we introduce an upper-bound to the true predictive distribution. As the global minimum of this upper-bound exists, the problem is reduced to seek an approximation to the true predictive distribution. The approximated predictive distribution obtained by minimizing the upper-bound is analytically tractable, facilitating the computation of the predictive likelihood. With synthesized data and real data evaluations, the good performance of the proposed LVI based method is demonstrated by comparing with some conventionally used methods.
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| 49. |
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| 50. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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