| 1. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 2. |
- 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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| 3. |
- Zhang, Yi, et al.
(författare)
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Elemene inhibits the migration and invasion of 4T1 murine breast cancer cells via heparanase
- 2017
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 16:1, s. 794-800
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Tidskriftsartikel (refereegranskat)abstract
- Elemene (ELE), a natural plant drug extracted from Curcumae Rhizoma, has been widely used for cancer treatment in China for more than 20 years. Although it is reported to be a broad-spectrum anticancer drug, the mechanism underlying the action of ELE in the treatment of breast cancer remains to be fully elucidated. Heparanase, a mammalian endo-D-glucuronidase, is involved in degradation of the extracellular matrix (ECM), and thus promotes tumor progression and metastasis. The downregulation of heparanase can effectively reduce tumor malignant behaviors. In the present study, the inhibitory effects of ELE were evaluated in breast cancer cells using a Cell Counting kit 8 assay. The migratory and invasive capabilities of cancer cells were investigated using a wound healing assay, real-time cell analysis and a Transwell assay. In addition, western blot analysis was used to assess alterations in the expression levels of key proteins. The present results confirmed the antiproliferative and antimetastatic effects of ELE, using low-molecular weight heparin (LMWH) as a positive control. In addition, ELE was demonstrated to downregulate the expression of heparanase, and decrease the phosphorylation of extracellular signal-regulated kinase and AKT. These findings suggested that ELE may be a promising agent targeting heparanase in the treatment of breast cancer.
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| 4. |
- 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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| 5. |
- Lin, Lin, et al.
(författare)
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Burst and Persistent Emission Properties during the Recent Active Episode of the Anomalous X-Ray Pulsar 1E 1841-045
- 2011
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Ingår i: Astrophysical Journal Letters. - : Institute of Physics (IOP). - 2041-8205 .- 2041-8213. ; 740:1
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Tidskriftsartikel (refereegranskat)abstract
- The Swift/Burst Alert Telescope detected the first burst from 1E 1841-045 in 2010 May with intermittent burst activity recorded through at least 2011 July. Here we present Swift and Fermi/Gamma-ray Burst Monitor observations of this burst activity and search for correlated changes to the persistent X-ray emission of the source. The T 90 durations of the bursts range between 18 and 140 ms, comparable to other magnetar burst durations, while the energy released in each burst ranges between (0.8-25) × 1038 erg, which is on the low side of soft gamma repeater bursts. We find that the bursting activity did not have a significant effect on the persistent flux level of the source. We argue that the mechanism leading to this sporadic burst activity in 1E 1841-045 might not involve large-scale restructuring (either crustal or magnetospheric) as seen in other magnetar sources.
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| 6. |
- Luo, Yifei, et al.
(författare)
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Technology Roadmap for Flexible Sensors
- 2023
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Ingår i: ACS Nano. - : American Chemical Society. - 1936-0851 .- 1936-086X. ; 17:6, s. 5211-5295
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Forskningsöversikt (refereegranskat)abstract
- Humans rely increasingly on sensors to address grand challenges and to improve quality of life in the era of digitalization and big data. For ubiquitous sensing, flexible sensors are developed to overcome the limitations of conventional rigid counterparts. Despite rapid advancement in bench-side research over the last decade, the market adoption of flexible sensors remains limited. To ease and to expedite their deployment, here, we identify bottlenecks hindering the maturation of flexible sensors and propose promising solutions. We first analyze challenges in achieving satisfactory sensing performance for real-world applications and then summarize issues in compatible sensor-biology interfaces, followed by brief discussions on powering and connecting sensor networks. Issues en route to commercialization and for sustainable growth of the sector are also analyzed, highlighting environmental concerns and emphasizing nontechnical issues such as business, regulatory, and ethical considerations. Additionally, we look at future intelligent flexible sensors. In proposing a comprehensive roadmap, we hope to steer research efforts towards common goals and to guide coordinated development strategies from disparate communities. Through such collaborative efforts, scientific breakthroughs can be made sooner and capitalized for the betterment of humanity.
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| 7. |
- Machiela, Mitchell J., et al.
(författare)
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Characterization of Large Structural Genetic Mosaicism in Human Autosomes
- 2015
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 96:3, s. 487-497
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Tidskriftsartikel (refereegranskat)abstract
- Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 3 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.
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| 8. |
- Machiela, Mitchell J, et al.
(författare)
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Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome
- 2016
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.
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| 9. |
- Sun, Jia-Qi, et al.
(författare)
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Spatholobus suberectus Column Extract Inhibits Estrogen Receptor Positive Breast Cancer via Suppressing ER MAPK PI3K/AKT Pathway
- 2016
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Ingår i: Evidence-based Complementary and Alternative Medicine. - : Hindawi Limited. - 1741-427X .- 1741-4288.
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Tidskriftsartikel (refereegranskat)abstract
- Although Chinese herbal compounds have long been alternatively applied for cancer treatment in China, their treatment effects have not been sufficiently investigated. The Chinese herb Spatholobus suberectus is commonly prescribed to cancer patients. HPLC analysis has shown that the main components of Spatholobus suberectus are flavonoids that can be classified as phytoestrogens, having a structure similar to estrogen. This study was designed to investigate the effects of Spatholobus suberectus column extract (SSCE) on the estrogen receptor-positive (ER+) breast cancer cell line MCF-7 and its possible molecular mechanism. In our study, MTT assay was performed to evaluate cell viability. The results show that SSCE (80, 160, and 320 mu g/ml) significantly decreased the viability of MCF-7 cells. SSCE also triggered apoptosis, arrested the cell cycle at the G0/G1 phase, and inhibited cell migration. A dual-luciferase reporter system showed that SSCE suppressed intranuclear p-ER activity; Western blot analysis confirmed the repressed expression of phosphorylated-ER alpha (p-ER alpha), ERK1/2, p-ERK1/2, AKT, p-AKT, p-mTOR, PI3K, and p-PI3K, indicating that SSCE suppressed the MAPK PI3K/AKT signaling pathway. Collectively, our results suggest that SSCE causes apoptosis, an arrest in the G0/G1 phase, and a decrease in migration in ER+ MCF-7 cells via hypoactivity of the ER and suppression of the MAPK PI3K/AKT pathway.
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| 10. |
- Vallejo-Vaz, Antonio J., et al.
(författare)
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Pooling and expanding registries of familial hypercholesterolaemia to assess gaps in care and improve disease management and outcomes: Rationale and design of the global EAS Familial Hypercholesterolaemia Studies Collaboration
- 2016
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Ingår i: Atherosclerosis Supplements. - : ELSEVIER IRELAND LTD. - 1567-5688 .- 1878-5050. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- Background: The potential for global collaborations to better inform public health policy regarding major non-hypercholesterolaemia (FH), a common genetic disorder associated with premature cardiovascular disease, is yet to be reliably ascertained using similar approaches. The European Atherosclerosis Society FH Studies Collaboration (EAS FHSC) is a new initiative of international stakeholders which will help establish a global FH registry to generate large-scale, robust data on the burden of FH worldwide. Methods: The EAS FHSC will maximise the potential exploitation of currently available and future FH data (retrospective and prospective) by bringing together regional/national/international data sources with access to individuals with a clinical and/or genetic diagnosis of heterozygous or homozygous FH. A novel bespoke electronic platform and FH Data Warehouse will be developed to allow secure data sharing, validation, cleaning, pooling, harmonisation and analysis irrespective of the source or format. Standard statistical procedures will allow us to investigate cross-sectional associations, patterns of real-world practice, trends over time, and analyse risk and outcomes (e.g. cardiovascular outcomes, all-cause death), accounting for potential confounders and subgroup effects. Conclusions: The EAS FHSC represents an excellent opportunity to integrate individual efforts across the world to tackle the global burden of FH. The information garnered from the registry will help reduce gaps in knowledge, inform best practices, assist in clinical trials design, support clinical guidelines and policies development, and ultimately improve the care of FH patients. (C) 2016 Elsevier Ireland Ltd.
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| 11. |
- Zhang, Yi, et al.
(författare)
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Gubenyiliu II Inhibits Breast Tumor Growth and Metastasis Associated with Decreased Heparanase Expression and Phosphorylation of ERK and AKT Pathways
- 2017
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Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 22:5
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Tidskriftsartikel (refereegranskat)abstract
- Gubenyiliu II (GYII), a Traditional Chinese Medicine (TCM) formula used in our hospital, has shown beneficial effects in cancer patients. In this study, we investigated the molecular mechanisms underlying the beneficial effects of GYII on murine breast cancer models. GYII showed significant inhibitory effects on tumor growth and metastasis in the murine breast cancer model. Additionally, GYII suppressed the proliferation of 4T1 and MCF-7 cells in a dose-dependent manner. A better inhibitory effect on 4T1 cell proliferation and migration was found in the decomposed recipes (DR) of GYII. Moreover, heparanase expression and the degree of angiogenesis were reduced in tumor tissues. Western blot analysis showed decreased expression of heparanase and growth factors in the cells treated with GYII and its decomposed recipes (DR2 and DR3), and thereby a reduction in the phosphorylation of extracellular signal-regulated kinase (ERK) and serine-threonine kinase (AKT). These results suggest that GYII exerts anti-tumor growth and anti-metastatic effects in the murine breast cancer model. The anti-tumor activity of GYII and its decomposed recipes is, at least partly, associated with decreased heparanase and growth factor expression, which subsequently suppressed the activation of the ERK and AKT pathways.
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| 12. |
- Aglago, Elom K., et al.
(författare)
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A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk
- 2023
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Ingår i: Cancer Research. - : American Association For Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 83:15, s. 2572-2583
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Gene-environment interactions (G × E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G × E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G × E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G × E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant G×BMI interaction located within the Formin 1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the FMN1/GREM1 gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer.SIGNIFICANCE: This gene-environment interaction analysis revealed a genetic locus in FMN1/GREM1 that interacts with body mass index in colorectal cancer risk, suggesting potential implications for precision prevention strategies.
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| 13. |
- Akbari, Parsa, et al.
(författare)
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Sequencing of 640,000 exomes identifies GPR75 variants associated with protection from obesity
- 2021
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 373:6550
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Tidskriftsartikel (refereegranskat)abstract
- Large-scale human exome sequencing can identify rare protein-coding variants with a large impact on complex traits such as body adiposity. We sequenced the exomes of 645,626 individuals from the United Kingdom, the United States, and Mexico and estimated associations of rare coding variants with body mass index (BMI). We identified 16 genes with an exome-wide significant association with BMI, including those encoding five brain-expressed G protein-coupled receptors (CALCR, MC4R, GIPR, GPR151, and GPR75). Protein-truncating variants in GPR75 were observed in ∼4/10,000 sequenced individuals and were associated with 1.8 kilograms per square meter lower BMI and 54% lower odds of obesity in the heterozygous state. Knock out of Gpr75 in mice resulted in resistance to weight gain and improved glycemic control in a high-fat diet model. Inhibition of GPR75 may provide a therapeutic strategy for obesity.
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| 14. |
- Anderson, Cynthia M., et al.
(författare)
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Permanent Genetic Resources added to Molecular Ecology Resources Database 1 December 2009-31 January 2010
- 2010
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Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:3, s. 576-579
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Tidskriftsartikel (refereegranskat)abstract
- This article documents the addition of 220 microsatellite marker loci to the Molecular Ecology Resources Database. Loci were developed for the following species: Allanblackia floribunda, Amblyraja radiata, Bactrocera cucurbitae, Brachycaudus helichrysi, Calopogonium mucunoides, Dissodactylus primitivus, Elodea canadensis, Ephydatia fluviatilis, Galapaganus howdenae howdenae, Hoplostethus atlanticus, Ischnura elegans, Larimichthys polyactis, Opheodrys vernalis, Pelteobagrus fulvidraco, Phragmidium violaceum, Pistacia vera, and Thunnus thynnus. These loci were cross-tested on the following species: Allanblackia gabonensis, Allanblackia stanerana, Neoceratitis cyanescens, Dacus ciliatus, Dacus demmerezi, Bactrocera zonata, Ceratitis capitata, Ceratitis rosa, Ceratits catoirii, Dacus punctatifrons, Ephydatia mulleri, Spongilla lacustris, Geodia cydonium, Axinella sp., Ischnura graellsii, Ischnura ramburii, Ischnura pumilio, Pistacia integerrima and Pistacia terebinthus.
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| 15. |
- Carreras-Torres, Robert, et al.
(författare)
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Genome-wide interaction study with smoking for colorectal cancer risk identifies novel genetic loci related to tumor suppression, inflammation, and immune response
- 2023
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American association for cancer research. - 1055-9965 .- 1538-7755. ; 32:3, s. 315-328
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Tobacco smoking is an established risk factor for colorectal cancer. However, genetically defined population subgroups may have increased susceptibility to smoking-related effects on colorectal cancer.METHODS: A genome-wide interaction scan was performed including 33,756 colorectal cancer cases and 44,346 controls from three genetic consortia.RESULTS: Evidence of an interaction was observed between smoking status (ever vs. never smokers) and a locus on 3p12.1 (rs9880919, P = 4.58 × 10-8), with higher associated risk in subjects carrying the GG genotype [OR, 1.25; 95% confidence interval (CI), 1.20-1.30] compared with the other genotypes (OR <1.17 for GA and AA). Among ever smokers, we observed interactions between smoking intensity (increase in 10 cigarettes smoked per day) and two loci on 6p21.33 (rs4151657, P = 1.72 × 10-8) and 8q24.23 (rs7005722, P = 2.88 × 10-8). Subjects carrying the rs4151657 TT genotype showed higher risk (OR, 1.12; 95% CI, 1.09-1.16) compared with the other genotypes (OR <1.06 for TC and CC). Similarly, higher risk was observed among subjects carrying the rs7005722 AA genotype (OR, 1.17; 95% CI, 1.07-1.28) compared with the other genotypes (OR <1.13 for AC and CC). Functional annotation revealed that SNPs in 3p12.1 and 6p21.33 loci were located in regulatory regions, and were associated with expression levels of nearby genes. Genetic models predicting gene expression revealed that smoking parameters were associated with lower colorectal cancer risk with higher expression levels of CADM2 (3p12.1) and ATF6B (6p21.33).CONCLUSIONS: Our study identified novel genetic loci that may modulate the risk for colorectal cancer of smoking status and intensity, linked to tumor suppression and immune response.IMPACT: These findings can guide potential prevention treatments.
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| 16. |
- Chi, Xiaoming, et al.
(författare)
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Fractal superconducting nanowire single-photon detectors with reduced polarization sensitivity
- 2018
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Ingår i: Optics Letters. - : OPTICAL SOC AMER. - 0146-9592 .- 1539-4794. ; 43:20, s. 5017-5020
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate superconducting nanowire single-photon detectors (SNSPDs) based on a fractal design of the nanowires to reduce the polarization sensitivity of detection efficiency. We patterned niobium titanium nitride thin films into Peano curves with a linewidth of 100 nm and integrated the nanowires with optical microcavities to enhance their optical absorption. At a base temperature of 2.6 K, the fractal SNSPD exhibited a polarization-maximum device efficiency of 67% and a polarization-minimum device efficiency of 61% at a wavelength of 1550 nm. Therefore, the polarization sensitivity, defined as their ratio, was 1.1, lower than the polarization sensitivity of the SNSPDs in the meander design. The reduced polarization sensitivity of the detector could be maintained for higher-order spatial modes in multimode optical fibers and could tolerate misalignment between the optical mode and the detector. This fractal design is applicable to both amorphous and polycrystalline materials that are commonly used for making SNSPDs.
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| 17. |
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| 18. |
- Haas, CB, et al.
(författare)
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Interactions between folate intake and genetic predictors of gene expression levels associated with colorectal cancer risk
- 2022
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1, s. 18852-
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Tidskriftsartikel (refereegranskat)abstract
- Observational studies have shown higher folate consumption to be associated with lower risk of colorectal cancer (CRC). Understanding whether and how genetic risk factors interact with folate could further elucidate the underlying mechanism. Aggregating functionally relevant genetic variants in set-based variant testing has higher power to detect gene–environment (G × E) interactions and may provide information on the underlying biological pathway. We investigated interactions between folate consumption and predicted gene expression on colorectal cancer risk across the genome. We used variant weights from the PrediXcan models of colon tissue-specific gene expression as a priori variant information for a set-based G × E approach. We harmonized total folate intake (mcg/day) based on dietary intake and supplemental use across cohort and case–control studies and calculated sex and study specific quantiles. Analyses were performed using a mixed effects score tests for interactions between folate and genetically predicted expression of 4839 genes with available genetically predicted expression. We pooled results across 23 studies for a total of 13,498 cases with colorectal tumors and 13,918 controls of European ancestry. We used a false discovery rate of 0.2 to identify genes with suggestive evidence of an interaction. We found suggestive evidence of interaction with folate intake on CRC risk for genes including glutathione S-Transferase Alpha 1 (GSTA1; p = 4.3E−4), Tonsuko Like, DNA Repair Protein (TONSL; p = 4.3E−4), and Aspartylglucosaminidase (AGA: p = 4.5E−4). We identified three genes involved in preventing or repairing DNA damage that may interact with folate consumption to alter CRC risk. Glutathione is an antioxidant, preventing cellular damage and is a downstream metabolite of homocysteine and metabolized by GSTA1. TONSL is part of a complex that functions in the recovery of double strand breaks and AGA plays a role in lysosomal breakdown of glycoprotein.
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| 19. |
- Hong, Nan-Sook, et al.
(författare)
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The evolution of multiple active site configurations in a designed enzyme
- 2018
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Developments in computational chemistry, bioinformatics, and laboratory evolution have facilitated the de novo design and catalytic optimization of enzymes. Besides creating useful catalysts, the generation and iterative improvement of designed enzymes can provide valuable insight into the interplay between the many phenomena that have been suggested to contribute to catalysis. In this work, we follow changes in conformational sampling, electrostatic preorganization, and quantum tunneling along the evolutionary trajectory of a designed Kemp eliminase. We observe that in the Kemp Eliminase KE07, instability of the designed active site leads to the emergence of two additional active site configurations. Evolutionary conformational selection then gradually stabilizes the most efficient configuration, leading to an improved enzyme. This work exemplifies the link between conformational plasticity and evolvability and demonstrates that residues remote from the active sites of enzymes play crucial roles in controlling and shaping the active site for efficient catalysis.
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| 20. |
- 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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| 21. |
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| 22. |
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| 23. |
- Jiang, Qing-Hui, et al.
(författare)
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Ferroic properties of highly dense multiferroic Bi1-xLa0.05TbxFeO3 ceramics via sheltered spark plasma sintering
- 2008
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Ingår i: Journal of The American Ceramic Society. - : Wiley. - 0002-7820 .- 1551-2916. ; 91:7, s. 2189-2194
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Tidskriftsartikel (refereegranskat)abstract
- Multiferroic Bi0.95-xLa0.05TbxFeO3 (BLTFO) ceramics were prepared by spark plasma sintering. The protection of CeO2 powders in the spark plasma sintering process can effectively restrain the valence fluctuation of iron ions and high-dense BLTFO ceramics with good dielectric and ferroelectric properties are fabricated. The BLTFO ceramics have low loss (tan delta similar to 5%) between 10(2) and 10(6) Hz. The doping of Tb can increase the dielectric and ferromagnetic properties, but decrease the ferroelectricity of BLTFO ceramics.
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| 24. |
- Jiang, Q. H., et al.
(författare)
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High-temperature ferroelectric phase transition observed in multiferroic Bi0.91La0.05Tb0.04FeO3
- 2009
-
Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 95:1, s. 12909-
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Tidskriftsartikel (refereegranskat)abstract
- A single-phase Bi0.91La0.05Tb0.04FeO3 polycrystalline ceramic was fabricated by spark-plasma-sintering the precursor powder prepared by a sol-gel method. Temperature-dependent properties of polycrystalline Bi0.91La0.05Tb0.04FeO3 were characterized by x-ray diffraction, dielectric, and piezoelectric measurement. The x-ray diffraction results revealed a phase transition near 700 degrees C. Especially, temperature-dependent dielectric behavior demonstrated that there was a dielectric abnormal peak at about 697 degrees C, in addition to those two well-known dielectric abnormal peaks at 337 degrees C (Neel temperature) and 831 degrees C (Curie temperature). The observations, together with thermal depoled behavior, suggest a ferroelectric-ferroelectric phase transition from R(3)c to Pbnm at around 700 degrees C.
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| 25. |
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| 26. |
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| 27. |
- Li, Junhao, et al.
(författare)
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Full-color enhanced second harmonic generation using rainbow trapping in ultrathin hyperbolic metamaterials
- 2021
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Though metamaterials enhance nonlinear light-matter interactions due to their resonant features, these materials typically show a narrow spectral bandwidth. Here, the authors report broadband enhanced second-harmonic generation in patterned multilayer hyperbolic metamaterial arrays. Metasurfaces have provided a promising approach to enhance the nonlinearity at subwavelength scale, but usually suffer from a narrow bandwidth as imposed by sharp resonant features. Here, we counterintuitively report a broadband, enhanced second-harmonic generation, in nanopatterned hyperbolic metamaterials. The nanopatterning allows the direct access of the mode with large momentum, rendering the rainbow light trapping, i.e. slow light in a broad frequency, and thus enhancing the local field intensity for boosted nonlinear light-matter interactions. For a proof-of-concept demonstration, we fabricated a nanostructured Au/ZnO multilayer, and enhanced second harmonic generation can be observed within the visible wavelength range (400-650 nm). The enhancement factor is over 50 within the wavelength range of 470-650 nm, and a maximum conversion efficiency of 1.13x10(-6) is obtained with a pump power of only 8.80 mW. Our results herein offer an effective and robust approach towards the broadband metasurface-based nonlinear devices for various important technologies.
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| 28. |
- Liang, Xiaoyan, et al.
(författare)
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Association and interaction of TOMM40 and PVRL2 with plasma amyloid-β and Alzheimer's disease among Chinese older adults : a population-based study
- 2022
-
Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 113, s. 143-151
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Tidskriftsartikel (refereegranskat)abstract
- Genetic studies have identified Alzheimer's disease (AD)-associated SNPs in TOMM40 and PVRL2 genes, but the underlying mechanisms remain unknown. We examined their associations and interactions with AD risk and plasma biomarkers among Chinese older adults. This population-based study included 4876 participants. TOMM40(rs2075650) and PVRL2(rs6859) polymorphisms were detected using multiple-polymerase chain reaction amplification. Plasma Aβ40, Aβ42, and t-tau concentrations were measured using SIMOA in a subsample (n = 1257). AD was diagnosed following the international criteria. Data were analyzed using multiple logistic and general linear models. AD was diagnosed in 182 participants. The multiadjusted odds ratio of AD was 6.24 (95% CI 1.73–22.48) for TOMM40GG, 1.47 (0.89–2.42) for PVRL2AA, and 12.87 (3.97–41.73) for having both risk alleles (Pinteraction = 0.0003). Among APOEε3/ε3 carriers, the multiadjusted odds ratio of AD associated with TOMM40AG was 2.90(1.15–7.31). In biomarker subsample, TOMM40GG was significantly associated with lower plasma Aβ42 and the Aβ42-to-Aβ40 ratio (p < 0.05). TOMM40 genotype is differentially associated with AD risk depending on APOE genotype. TOMM40 and PVRL2 genes could interact to substantially increase AD risk, possibly through influencing Aβ metabolism.
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| 29. |
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| 30. |
- Lin, Yuan-Hua, et al.
(författare)
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Electrical transport properties of La2CuO4 ceramics processed by the spark plasma sintering
- 2007
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Ingår i: Journal of The American Ceramic Society. - : Wiley. - 0002-7820 .- 1551-2916. ; 90:12, s. 4005-4008
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Tidskriftsartikel (refereegranskat)abstract
- Highly dense La2CuO4 ceramics have been prepared by the spark plasma sintering technique. Temperature dependence of electrical conductivity indicates that La2CuO4 ceramics sintered at over 875 degrees C exhibit a metal-like behavior, which should be ascribed to the special La2CuO4 crystal structure and its correlation splitting of the half-filled d(x2-y2) band. Our experimental data indicate that all of the La2CuO4 samples exhibit positive thermoelectric power in the whole measuring temperature range, indicating that the majority of charge carriers are holes. It is desirable to obtain good thermoelectric performance for this system by optimizing the electrical properties and reducing the thermal conductivity.
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| 31. |
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| 32. |
- Liu, Bo, et al.
(författare)
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Zircon U-Pb-Hf Isotopes and Whole-Rock Geochemistry of the “Kulumudi Formation” from the Laofengkou Area (West Junggar) : Implications of the Construction of a Juvenile Arc in the Junggar–Balkhash Ocean
- 2024
-
Ingår i: Minerals. - 2075-163X. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- The properties of ancient magmatic arcs are crucial for understanding the tectonic evolution of the Central Asian Orogenic Belt. The Middle Devonian Kulumudi Formation in the Laofengkou area of West Junggar lacks accurate chronological data constraints, which hampers the knowledge of the nature of the Late Paleozoic magmatic arcs in the West Junggar and circum-Balkhash areas. In this contribution, samples of pyroclastic rocks and sedimentary rocks were collected from the volcano–sedimentary strata of the Kulumudi Formation. Petrography, zircon U-Pb-Hf isotopic analysis and whole-rock geochemistry were carried out to constrain the age and the tectonic setting of the Kulumudi Formation. The zircon U-Pb age of the lithic crystal tuff from the Kulumudi Formation on the northeast side of the Alemale Mountains was 386 ± 2 Ma, accurately indicating that this rock unit formed during the Middle Devonian. However, the fine sandstone near the Huojierte Mongolian Township, originally assigned as the “Kulumudi Formation”, yielded a maximum depositional age of 341 ± 3 Ma. Combined with the stratigraphic contact, this rock unit was redefined to belong to the Lower Carboniferous Jiangbasitao Formation. According to the whole-rock geochemistry study, the lithic crystal tuff of the Kulumudi Formation was characterized as medium potassium–calc–alkaline series rock, which is relatively enriched in light rare earth elements and large ion lithophile elements (i.e., Rb, Ba, K) and depleted in high-field-strength elements (i.e., Nb, Ta, Ti), showing similar geochemical characteristics to the volcanic arc rocks. By contrast, the fine sandstone from the Jiangbasitao Formation had Al2O3/SiO2 (0.25–0.29) and K2O/Na2O (1.29–1.72) ratios close to those derived from the continental arc and active continental margin and was characterized as part of the continental arc field in the La-Th-Sc and Th-Sc-Zr/10 tectonic discrimination diagrams. Zircon Hf isotope analysis showed that the εHf(t) values of the Kulumudi Formation were +5.6–+12.8, and those of the Jiangbasitao Formation were +11.43–+15.48, both of which show highly positive juvenile characteristics. The above data indicate that the Kulumudi Formation and Jiangbasitao Formation both formed in a juvenile arc setting with ocean–continent subduction. Combined with the previous work, it was concluded that the southward subduction of the ocean basin represented by the Darbut–Karamay ophiolitic mélanges beneath the newly accreted arc crustal segments produced a juvenile arc with positive Hf isotope characteristics.
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| 33. |
- Liu, Jun, et al.
(författare)
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Microbial community structure and function in sediments from e-waste contaminated rivers at Guiyu area of China
- 2018
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Ingår i: Environmental Pollution. - : Elsevier BV. - 0269-7491. ; 235, s. 171-179
-
Tidskriftsartikel (refereegranskat)abstract
- The release of toxic organic pollutants and heavy metals by primitive electronic waste (e-waste) processing to waterways has raised significant concerns, but little is known about their potential ecological effects on aquatic biota especially microorganisms. We characterized the microbial community composition and diversity in sediments sampled along two rivers consistently polluted by e-waste, and explored how community functions may respond to the complex combined pollution. High-throughput 16S rRNA gene sequencing showed that Proteobacteria (particularly Deltaproteobacteria) dominated the sediment microbial assemblages followed by Bacteroidetes, Acidobacteria, Chloroflexi and Firmicutes. PICRUSt metagenome inference provided an initial insight into the metabolic potentials of these e-waste affected communities, speculating that organic pollutants degradation in the sediment might be mainly performed by some of the dominant genera (such as Sulfuricurvum, Thiobacillus and Burkholderia) detected in situ. Statistical analyses revealed that toxic organic compounds contributed more to the observed variations in sediment microbial community structure and predicted functions (24.68% and 8.89%, respectively) than heavy metals (12.18% and 4.68%), and Benzo(a)pyrene, bioavailable lead and electrical conductivity were the key contributors. These results have shed light on the microbial assemblages in e-waste contaminated river sediments, indicating a potential influence of e-waste pollution on the microbial community structure and function in aquatic ecosystems.
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| 34. |
- Manschwetus, Bastian, et al.
(författare)
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Self-Probing Spectroscopy of the SF6 Molecule: A Study of the Spectral Amplitude and Phase of the High Harmonic Emission
- 2015
-
Ingår i: The Journal of Physical Chemistry Part A: Molecules, Spectroscopy, Kinetics, Environment and General Theory. - : American Chemical Society (ACS). - 1520-5215. ; 119:23, s. 6111-6122
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Tidskriftsartikel (refereegranskat)abstract
- We present characterizations of the attosecond pulse train produced in the high harmonic generation (HHG) from SF6 molecules irradiated by a strong pulsed laser field at 800 nm. At harmonic order 17, we observe a minimum in the amplitude of the emitted spectrum and a corresponding distortion in the phase. Our experimental results are compared to two models: a multicenter interference model focused on the effect of the structure of the SF6 molecule in HHG and a model focused on the interferences between multiple ionization channels in HHG. We find that the experimental results agree very well with the multiple ionization channels model, illustrating that HHG in molecules can be very complex and that it provides insights of the intramolecular electron dynamics during the interaction process.
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| 35. |
- McNabb, Sarah, et al.
(författare)
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Meta-analysis of 16 studies of the association of alcohol with colorectal cancer
- 2020
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 146:3, s. 861-873
-
Tidskriftsartikel (refereegranskat)abstract
- Alcohol consumption is an established risk factor for colorectal cancer (CRC). However, while studies have consistently reported elevated risk of CRC among heavy drinkers, associations at moderate levels of alcohol consumption are less clear. We conducted a combined analysis of 16 studies of CRC to examine the shape of the alcohol-CRC association, investigate potential effect modifiers of the association, and examine differential effects of alcohol consumption by cancer anatomic site and stage. We collected information on alcohol consumption for 14,276 CRC cases and 15,802 controls from 5 case-control and 11 nested case-control studies of CRC. We compared adjusted logistic regression models with linear and restricted cubic splines to select a model that best fit the association between alcohol consumption and CRC. Study-specific results were pooled using fixed-effects meta-analysis. Compared to non-/occasional drinking (<= 1 g/day), light/moderate drinking (up to 2 drinks/day) was associated with a decreased risk of CRC (odds ratio [OR]: 0.92, 95% confidence interval [CI]: 0.88-0.98, p = 0.005), heavy drinking (2-3 drinks/day) was not significantly associated with CRC risk (OR: 1.11, 95% CI: 0.99-1.24, p = 0.08) and very heavy drinking (more than 3 drinks/day) was associated with a significant increased risk (OR: 1.25, 95% CI: 1.11-1.40, p < 0.001). We observed no evidence of interactions with lifestyle risk factors or of differences by cancer site or stage. These results provide further evidence that there is a J-shaped association between alcohol consumption and CRC risk. This overall pattern was not significantly modified by other CRC risk factors and there was no effect heterogeneity by tumor site or stage.
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| 36. |
- Piao, Shilong, et al.
(författare)
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Evaluation of terrestrial carbon cycle models for their response to climate variability and to CO2 trends
- 2013
-
Ingår i: Global Change Biology. - : Wiley. - 1354-1013. ; 19:7, s. 2117-2132
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to evaluate 10 process-based terrestrial biosphere models that were used for the IPCC fifth Assessment Report. The simulated gross primary productivity (GPP) is compared with flux-tower-based estimates by Jung etal. [Journal of Geophysical Research 116 (2011) G00J07] (JU11). The net primary productivity (NPP) apparent sensitivity to climate variability and atmospheric CO2 trends is diagnosed from each model output, using statistical functions. The temperature sensitivity is compared against ecosystem field warming experiments results. The CO2 sensitivity of NPP is compared to the results from four Free-Air CO2 Enrichment (FACE) experiments. The simulated global net biome productivity (NBP) is compared with the residual land sink (RLS) of the global carbon budget from Friedlingstein etal. [Nature Geoscience 3 (2010) 811] (FR10). We found that models produce a higher GPP (133 +/- 15Pg Cyr-1) than JU11 (118 +/- 6Pg Cyr-1). In response to rising atmospheric CO2 concentration, modeled NPP increases on average by 16% (5-20%) per 100ppm, a slightly larger apparent sensitivity of NPP to CO2 than that measured at the FACE experiment locations (13% per 100ppm). Global NBP differs markedly among individual models, although the mean value of 2.0 +/- 0.8Pg Cyr-1 is remarkably close to the mean value of RLS (2.1 +/- 1.2 Pg Cyr-1). The interannual variability in modeled NBP is significantly correlated with that of RLS for the period 1980-2009. Both model-to-model and interannual variation in model GPP is larger than that in model NBP due to the strong coupling causing a positive correlation between ecosystem respiration and GPP in the model. The average linear regression slope of global NBP vs. temperature across the 10 models is -3.0 +/- 1.5Pg Cyr-1 degrees C-1, within the uncertainty of what derived from RLS (-3.9 +/- 1.1Pg Cyr-1 degrees C-1). However, 9 of 10 models overestimate the regression slope of NBP vs. precipitation, compared with the slope of the observed RLS vs. precipitation. With most models lacking processes that control GPP and NBP in addition to CO2 and climate, the agreement between modeled and observation-based GPP and NBP can be fortuitous. Carbon-nitrogen interactions (only separable in one model) significantly influence the simulated response of carbon cycle to temperature and atmospheric CO2 concentration, suggesting that nutrients limitations should be included in the next generation of terrestrial biosphere models.
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| 37. |
- Qi, Nan, et al.
(författare)
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Efficient Coded Cooperative Networks With Energy Harvesting and Transferring
- 2017
-
Ingår i: IEEE Transactions on Wireless Communications. - : Institute of Electrical and Electronics Engineers (IEEE). - 1536-1276 .- 1558-2248. ; 16:10, s. 6335-6349
-
Tidskriftsartikel (refereegranskat)abstract
- In this paper, a multi-user multi-relay network with integrated energy harvesting and transferring (IEHT) strategy is studied. In our system, a simultaneous two-level cooperation, i.e., information-and energy-level cooperation is conducted for uplink data transmissions (from the users to a destination). Specifically, network coding is employed at the relays to facilitate the information-level cooperation; meanwhile, ET is adopted to share the harvested energy among the users for the energy-level cooperation. For generality purposes, the Nakagami-m fading channels that are independent but not necessarily identically distributed (i.n.i.d.)are considered. The problem of energy efficiency maximization under constraints of the energy causality and a predefined outage probability threshold is formulated and shown to be non-convex. By exploiting fractional and geometric programming, a convex form-based iterative algorithm is developed to solve the problem efficiently. Close-to-optimal power allocation and energy cooperation policies across consecutive transmissions are found. Moreover, the effects of relay locations, wireless energy transmission efficiency, battery capacity as well as the existence of direct links are investigated. The performance comparison with the current state of solutions demonstrates that the proposed policies can manage the harvested energy more efficiently.
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| 38. |
- Qie, Zhiwei, et al.
(författare)
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Sensitive detection of atrazine in tap water using TELISA
- 2015
-
Ingår i: Analyst. - : Royal Society of Chemistry (RSC). - 1364-5528. ; 140:15, s. 5220-5226
-
Tidskriftsartikel (refereegranskat)abstract
- A highly sensitive flow injection analysis (FIA)-based thermal enzyme-linked immunoassay, TELISA, was developed for the rapid detection of atrazine (ATZ) in tap water. ATZ and beta-lactamase-labeled ATZ were employed in a competitive immunoassay using a monoclonal antibody (mAb). After the off-column liquid-phase competition, the mAb was captured on the Protein G Sepharose (TM) 4 Fast Flow (PGSFF) column support material. Injected beta-lactamase substrate ampicillin was degraded by the column-bound ATZ-beta-lactamase, generating a detectable heat signal. Several assay parameters were optimized, including substrate concentration, flow rates and regeneration conditions, as well as the mAb and ATZ-beta dilution ratios and concentrations. The assay linear range was 0.73-4.83 ng mL(-1) with a detection limit of 0.66 ng mL(-1). An entire heat signal requires 10 min for generation, and the cycle time is less than 40 min. The results were reproducible and stable. ATZ-spiked tap water samples exhibited a recovery rate of 103%-116%, which correlated with the UHPLC-MS/MS measurements. We attributed this significant increase in sensitivity over our previously published work to the following factors: (i) the capture of already-formed immune complexes on the column via immobilized Protein G, which eliminated chemical immobilization of the antibody; (ii) off-column preincubation allows the formation of immune complexes under nearly ideal conditions; and (iii) multiple buffers can be used to, in one case, enhance immune-complex formation and in the other to maximize enzymatic activity. Furthermore, the scheme creates a universal assay platform in which sensing is performed in the off-column incubation and detection after capture in the enzyme thermistor (ET) detector, which opens up the possibility of detecting any antigen for which antibodies were available.
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| 39. |
- Qin, Shuang-Jian, et al.
(författare)
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Neurotoxicity of fine and ultrafine particulate matter : a comprehensive review using a toxicity pathway-oriented adverse outcome pathway framework
- 2024
-
Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 947
-
Forskningsöversikt (refereegranskat)abstract
- Fine particulate matter (PM2.5) can cause brain damage and diseases. Of note, ultrafine particles (UFPs) with an aerodynamic diameter less than or equal to 100 nm are a growing concern. Evidence has suggested toxic effects of PM2.5 and UFPs on the brain and links to neurological diseases. However, the underlying mechanism has not yet been fully illustrated due to the variety of the study models, different endpoints, etc. The adverse outcome pathway (AOP) framework is a pathway-based approach that could systematize mechanistic knowledge to assist health risk assessment of pollutants. Here, we constructed AOPs by collecting molecular mechanisms in PM-induced neurotoxicity assessments. We chose particulate matter (PM) as a stressor in the Comparative Toxicogenomics Database (CTD) and identified the critical toxicity pathways based on Ingenuity Pathway Analysis (IPA). We found 65 studies investigating the potential mechanisms linking PM2.5 and UFPs to neurotoxicity, which contained 2, 675 genes in all. IPA analysis showed that neuroinflammation signaling and glucocorticoid receptor signaling were the common toxicity pathways. The upstream regulator analysis (URA) of PM2.5 and UFPs demonstrated that the neuroinflammation signaling was the most initially triggered upstream event. Therefore, neuroinflammation was recognized as the MIE. Strikingly, there is a clear sequence of activation of downstream signaling pathways with UFPs, but not with PM2.5. Moreover, we found that inflammation response and homeostasis imbalance were key cellular events in PM2.5 and emphasized lipid metabolism and mitochondrial dysfunction, and blood-brain barrier (BBB) impairment in UFPs. Previous AOPs, which only focused on phenotypic changes in neurotoxicity upon PM exposure, we for the first time propose AOP framework in which PM2.5 and UFPs may activate pathway cascade reactions, resulting in adverse outcomes associated with neurotoxicity. Our toxicity pathway-based approach not only advances risk assessment for PM-induced neurotoxicity but shines a spotlight on constructing AOP frameworks for new chemicals.
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| 40. |
- Shang, Nan, et al.
(författare)
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Nodal market power assessment of flexible demand resources
- 2019
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Ingår i: Applied Energy. - : ELSEVIER SCI LTD. - 0306-2619 .- 1872-9118. ; 235, s. 564-577
-
Tidskriftsartikel (refereegranskat)abstract
- With the incorporation of higher shares of intermittent renewable energies (RES), more flexible resources are required in power systems to keep load balance. Under some extreme circumstances, the flexible demand resources (FDRs) may have the potential to dominate and obtain excess benefits, preventing other FDRs from participating in the electricity markets. Therefore, it is of great significance to identify the key FDR market power locations and implement some corresponding regulations. However, the relevant researches in power systems focused on the supply side, rather than the demand side. In this paper, a novel nodal market power analysis method is proposed to evaluate the potential influence of FDRs on electricity markets. Firstly, a multi-state model is established to present the multiple power system operation states including the random failures of system components. Then, the nodal market power assessment model is established under each specific state and new indices are proposed to evaluate the nodal market power of FDRs quantitatively. Furthermore, the key FDR nodes in demand side with stronger power in capturing excess revenue are identified. The 24-bus IEEE Reliability Test System is modified to demonstrate the feasibility of the proposed method. The numerical results of the proposed method are capable to display the existence of market power in demand side, and provide some valuable guidance for classification and operation of electricity markets.
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| 41. |
- Shang, Naigui, et al.
(författare)
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Self-Assembled Growth, Microstructure, and Field-Emission High-Performance of Ultrathin Diamond Nanorods
- 2009
-
Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-086X .- 1936-0851. ; 3:4, s. 1032-1038
-
Tidskriftsartikel (refereegranskat)abstract
- We report the growth of ultrathin diamond nanorods (DNRs) by a microwave plasma assisted chemical vapor deposition method using a mixture gas of nitrogen and methane. DNRs have a diameter as thin as 2.1 nm, which is not only smaller than reported one-dimensional diamond nanostructures (4-300 nm) but also smaller than the theoretical value for energetically stable DNRs. The ultrathin DNR is encapsulated in tapered carbon nanotubes (CNTs) with an orientation relation of (111)(diamond)//(0002)(graphite). Together with diamond nanoclusters and multilayer graphene nanowires/nano-onions, DNRs are self-assembled into isolated electron-emitting spherules and exhibit a low-threshold, high current-density (flat panel display threshold: 10 mA/cm(2) at 2.9 V/mu m) field emission performance, better than that of all other conventional (Mo and Si tips, etc.) and popular nanostructural (ZnO nanostructure and nanodiamond, etc.) field emitters except for oriented CNTs. The forming mechanism of DNRs is suggested based on a heterogeneous self-catalytic vapor-solid process. This novel DNRs-based integrated nanostructure has not only a theoretical significance but also has a potential for use as low-power cold cathodes.
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| 42. |
- Tian, Jiahan, et al.
(författare)
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Wide-field-of-view auto-coupling optical antenna system for high-speed bidirectional optical wireless communications in C band
- 2023
-
Ingår i: Optics Express. - : Optica Publishing Group. - 1094-4087. ; 31:20, s. 33435-33448
-
Tidskriftsartikel (refereegranskat)abstract
- Due to a great many superior features of infrared light communication (ILC), like high capacity and strong privacy, ILC is considered a potential candidate for serving the high demands of beyond fifth-generation/sixth-generation (B5G/6 G) communication systems. However, the terminal's limited field-of-view (FOV) induces great difficulty in establishing line-of-sight (LoS) link between the transceiver and the terminal. In this paper, we propose a wide-FOV auto-coupling optical antenna system that utilizes a wide-FOV telecentric lens to collect incident infrared beams and automatically couple them into a specific single-mode-fiber (SMF) channel of fiber array and optical switch. The performance of this optical antenna system is assessed through simulation and manual alignment operation, and validated by automatic alignment results. A coupling loss of less than 10.6 dB within a FOV of 100(degrees )for both downstream and upstream beams in C band is demonstrated by the designed system. Furthermore, we establish a bidirectional optical wireless communications (OWC) system employing this antenna and a fiber-type modulating retro-reflector (MRR) system in the terminal. Both 10-Gbps on-off keying (OOK) downstream and upstream transmissions are successfully realized with the FOV of up to 100(degrees) in C band where the measured bit-error-rate (BER) is lower than 3.8 x 10-3. To the best of our knowledge, this is a brand-new auto-coupling optical antenna system with the largest FOV in ILC automatic alignment works in terminals that have ever been reported.
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| 43. |
- Tian, Yu, et al.
(författare)
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Genetic risk impacts the association of menopausal hormone therapy with colorectal cancer risk
- 2024
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Ingår i: British Journal of Cancer. - : Springer Nature. - 0007-0920 .- 1532-1827. ; 130:10, s. 1687-1696
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Tidskriftsartikel (refereegranskat)abstract
- Background: Menopausal hormone therapy (MHT), a common treatment to relieve symptoms of menopause, is associated with a lower risk of colorectal cancer (CRC). To inform CRC risk prediction and MHT risk-benefit assessment, we aimed to evaluate the joint association of a polygenic risk score (PRS) for CRC and MHT on CRC risk.Methods: We used data from 28,486 postmenopausal women (11,519 cases and 16,967 controls) of European descent. A PRS based on 141 CRC-associated genetic variants was modeled as a categorical variable in quartiles. Multiplicative interaction between PRS and MHT use was evaluated using logistic regression. Additive interaction was measured using the relative excess risk due to interaction (RERI). 30-year cumulative risks of CRC for 50-year-old women according to MHT use and PRS were calculated.Results: The reduction in odds ratios by MHT use was larger in women within the highest quartile of PRS compared to that in women within the lowest quartile of PRS (p-value = 2.7 × 10−8). At the highest quartile of PRS, the 30-year CRC risk was statistically significantly lower for women taking any MHT than for women not taking any MHT, 3.7% (3.3%–4.0%) vs 6.1% (5.7%–6.5%) (difference 2.4%, P-value = 1.83 × 10−14); these differences were also statistically significant but smaller in magnitude in the lowest PRS quartile, 1.6% (1.4%–1.8%) vs 2.2% (1.9%–2.4%) (difference 0.6%, P-value = 1.01 × 10−3), indicating 4 times greater reduction in absolute risk associated with any MHT use in the highest compared to the lowest quartile of genetic CRC risk.Conclusions: MHT use has a greater impact on the reduction of CRC risk for women at higher genetic risk. These findings have implications for the development of risk prediction models for CRC and potentially for the consideration of genetic information in the risk-benefit assessment of MHT use.
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| 44. |
- Tian, Yu, et al.
(författare)
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Genome-Wide Interaction Analysis of Genetic Variants With Menopausal Hormone Therapy for Colorectal Cancer Risk
- 2022
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 114:8, s. 1135-1148
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The use of menopausal hormone therapy (MHT) may interact with genetic variants to influence colorectal cancer (CRC) risk. METHODS: We conducted a genome-wide, gene-environment interaction between single nucleotide polymorphisms and the use of any MHT, estrogen only, and combined estrogen-progestogen therapy with CRC risk, among 28 486 postmenopausal women (11 519 CRC patients and 16 967 participants without CRC) from 38 studies, using logistic regression, 2-step method, and 2- or 3-degree-of-freedom joint test. A set-based score test was applied for rare genetic variants. RESULTS: The use of any MHT, estrogen only and estrogen-progestogen were associated with a reduced CRC risk (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.64 to 0.78; OR = 0.65, 95% CI = 0.53 to 0.79; and OR = 0.73, 95% CI = 0.59 to 0.90, respectively). The 2-step method identified a statistically significant interaction between a GRIN2B variant rs117868593 and MHT use, whereby MHT-associated CRC risk was statistically significantly reduced in women with the GG genotype (OR = 0.68, 95% CI = 0.64 to 0.72) but not within strata of GC or CC genotypes. A statistically significant interaction between a DCBLD1 intronic variant at 6q22.1 (rs10782186) and MHT use was identified by the 2-degree-of-freedom joint test. The MHT-associated CRC risk was reduced with increasing number of rs10782186-C alleles, showing odds ratios of 0.78 (95% CI = 0.70 to 0.87) for TT, 0.68 (95% CI = 0.63 to 0.73) for TC, and 0.66 (95% CI = 0.60 to 0.74) for CC genotypes. In addition, 5 genes in rare variant analysis showed suggestive interactions with MHT (2-sided P < 1.2 × 10-4). CONCLUSION: Genetic variants that modify the association between MHT and CRC risk were identified, offering new insights into pathways of CRC carcinogenesis and potential mechanisms involved.
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| 45. |
- Wang, Lina, et al.
(författare)
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Tailoring Alkane Uniaxial Self-Assembly via Polymer Modified Step Edges
- 2019
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Ingår i: The Journal of Physical Chemistry C. - : AMER CHEMICAL SOC. - 1932-7447 .- 1932-7455. ; 123:47, s. 28811-28815
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Tidskriftsartikel (refereegranskat)abstract
- Controlling the orientations of molecules in self-assembled monolayers on surfaces is an effective means to construct high quality organic devices. Herein, we utilize linear polymer-modified step edges as a simple and peculiar template for regulating the subsequent self-assembly of alkane molecules (n-C32H66). With this strategy, all the alkane molecules orientate along the step edge ([011] directions). Combining with systematical DFT calculations, we demonstrated that it is the van der Waals interactions between the molecules that leads to (1) the initially adsorbed alkane monomers lie parallel to the polymers; (2) the adjacent alkane molecules show a parallel configuration. Since the polymers anchor on the surface along an exclusive [011] direction, all the adsorbed molecules in the self-assembly islands are regulated along the [011] directions as well.
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| 46. |
- Wang, Yanan, et al.
(författare)
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Rapid Dimming Followed by a State Transition: A Study of the Highly Variable Nuclear Transient AT 2019avd over 1000+ Days
- 2024
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Ingår i: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 962:1
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Tidskriftsartikel (refereegranskat)abstract
- The tidal disruption of a star around a supermassive black hole (SMBH) offers a unique opportunity to study accretion onto an SMBH on a human timescale. We present results from our 1000+ days monitoring campaign of AT 2019avd, a nuclear transient with tidal-disruption-event-like properties, with NICER, Swift, and Chandra. Our primary finding is that approximately 225 days following the peak of the X-ray emission, there is a rapid drop in luminosity exceeding 2 orders of magnitude. This X-ray dropoff is accompanied by X-ray spectral hardening, followed by a plateau phase of 740 days. During this phase, the spectral index decreases from 6.2 ± 1.1 to 2.3 ± 0.4, while the disk temperature remains constant. Additionally, we detect pronounced X-ray variability, with an average fractional rms amplitude of 47%, manifesting over timescales of a few dozen minutes. We propose that this phenomenon may be attributed to intervening clumpy outflows. The overall properties of AT 2019avd suggest that the accretion disk evolves from a super-Eddington to a sub-Eddington luminosity state, possibly associated with a compact jet. This evolution follows a pattern in the hardness-intensity diagram similar to that observed in stellar-mass BHs, supporting the mass invariance of accretion-ejection processes around BHs
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| 47. |
- Wu, Mingxing, et al.
(författare)
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Highly effective Pt/MoSi2 composite counter electrode catalyst for dye-sensitized solar cell
- 2014
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Ingår i: Journal of Power Sources. - : Elsevier BV. - 0378-7753 .- 1873-2755. ; 263, s. 154-157
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Tidskriftsartikel (refereegranskat)abstract
- MoSi2 is introduced into dye-sensitized solar cell (DSC) as counter electrode (CE) catalyst for the first time, and the DSC produces power conversion efficiency (PCE) of 4.87%. To improve the catalytic activity, Pt/MoSi2 composite catalyst is synthesized and it is found that 1.13 wt% of Pt loading is enough for achieving high catalytic activity. After optimization, the DSC using the Pt/MoSi2 composite CE shows high PCE of 7.68%, close to the Pt CE based DSC (7.94%).
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| 48. |
- Wu, Mingxing, et al.
(författare)
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Synthesis of Highly Effective Vanadium Nitride (VN) Peas as a Counter Electrode Catalyst in Dye-Sensitized Solar Cells
- 2014
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Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 118:24, s. 12625-12631
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Tidskriftsartikel (refereegranskat)abstract
- Vanadium nitride (VN) peas and cubes were synthesized by regulating the molar ratio of the starting materials (urea/VOCl3) via the urea-metal chloride route. The as-prepared VN compounds were subsequently introduced into dye-sensitized solar cells (DSCs) as counter electrode (CE) catalysts for the regeneration of novel organic thiolate/disulfide (T-/T-2) and traditional iodide/triiodide (I-/I-3(-))redox couples. The cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and Tafel polarization curve results proved that the catalytic activity of the prepared VN was significantly affected by particle shape and particle size. The VN peas showed the highest catalytic activity, followed by the small VN cubes and large VN cubes. The I-/I-3(-)-electrolyte-based DSCs yielded a high power conversion efficiency (PCE) of 7.29%. The Pt-free VN CE catalysts are more suitable for the new organic redox couples of T-/T-2. The DSCs based on VN peas CE showed a PCE of 5.57%, an enhancement of 40.7% relative to the Pt-CE-based DSCs (3.96%).
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| 49. |
- Xia, Zhiyu, et al.
(författare)
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Functional informed genome-wide interaction analysis of body mass index, diabetes and colorectal cancer risk.
- 2020
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Ingår i: Cancer Medicine. - : Wiley. - 2045-7634. ; 9:10, s. 3563-3573
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Body mass index (BMI) and diabetes are established risk factors for colorectal cancer (CRC), likely through perturbations in metabolic traits (e.g. insulin resistance and glucose homeostasis). Identification of interactions between variation in genes and these metabolic risk factors may identify novel biologic insights into CRC etiology.METHODS: To improve statistical power and interpretation for gene-environment interaction (G × E) testing, we tested genetic variants that regulate expression of a gene together for interaction with BMI (kg/m2 ) and diabetes on CRC risk among 26 017 cases and 20 692 controls. Each variant was weighted based on PrediXcan analysis of gene expression data from colon tissue generated in the Genotype-Tissue Expression Project for all genes with heritability ≥1%. We used a mixed-effects model to jointly measure the G × E interaction in a gene by partitioning the interactions into the predicted gene expression levels (fixed effects), and residual G × E effects (random effects). G × BMI analyses were stratified by sex as BMI-CRC associations differ by sex. We used false discovery rates to account for multiple comparisons and reported all results with FDR <0.2.RESULTS: Among 4839 genes tested, genetically predicted expressions of FOXA1 (P = 3.15 × 10-5 ), PSMC5 (P = 4.51 × 10-4 ) and CD33 (P = 2.71 × 10-4 ) modified the association of BMI on CRC risk for men; KIAA0753 (P = 2.29 × 10-5 ) and SCN1B (P = 2.76 × 10-4 ) modified the association of BMI on CRC risk for women; and PTPN2 modified the association between diabetes and CRC risk in both sexes (P = 2.31 × 10-5 ).CONCLUSIONS: Aggregating G × E interactions and incorporating functional information, we discovered novel genes that may interact with BMI and diabetes on CRC risk.
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| 50. |
- Xiang, Dunfeng, et al.
(författare)
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Cenozoic Pulsed Rise and Growth of the Chinese South Tianshan Revealed by Zircon and Apatite Provenance Analyses: Implications for Stepwise Aridification in the Tarim Basin
- 2024
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Ingår i: TECTONICS. - 0278-7407 .- 1944-9194. ; 43:8
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Tidskriftsartikel (refereegranskat)abstract
- Cenozoic uplift in the Tianshan played an important role in driving Proto-Paratethys Sea retreat and Asian aridification. However, most paleoclimate studies have focused on the Pamir-Tianshan corridor, and frequently overlook the role of the entire Tianshan range in modifying the Central Asian climate during Cenozoic uplift. When and how Cenozoic deformation of Tianshan was initiated and propagated are intensively debated which makes its role in contributing to climate change in Central Asia more ambiguous. To address this issue, this study presents new detrital zircon U-Pb and detrital apatite U-Pb and fission track age data from Cenozoic sedimentary successions (54-0 Ma) in the northern margin of the Tarim Basin and integrates these data with published provenance data from adjacent regions. Our results show that deformation/uplift of the Baicheng-Kuqa Depression and the South Tianshan occurred at similar to 41-37 Ma and similar to 24 Ma, when topographic growth of South Tianshan began to block the flow of sediment from the north. Continued uplift of the South Tianshan completely blocked fluvial transport from the Central Tianshan-Yili Block by similar to 10 Ma, as shown by the paucity of 380-310 Ma detrital zircons/apatites. Far-field, north-directed compressive stress resulting from the India-Asia collision began to propagate toward the South Tianshan and its foreland during the Late Eocene, and continued to propagate into the South Tianshan and northward at the similar to 24 Ma and 10 Ma. Finally, we suggest a two-stage of aridification in the Tarim Basin which can be linked to two stages (similar to 24 and 10 Ma) of growth of the Tianshan. The Tarim Basin and the Taklimakan Desert are located in Central Asia, between the Tibetan Plateau to the south and the Tianshan orogenic belt to the north. This region is a crucial area for exploring the primary drivers of Cenozoic desertification. We performed a systematic zircon and apatite provenance study (including detrital apatite and zircon U-Pb dating, and detrital apatite fission track analysis) in Cenozoic strata from the northern margin of the Tarim Basin. Our results reveal pulsed deformation of the South Tianshan that initiated at similar to 41-37 Ma with two subsequent pulses at similar to 24 Ma and similar to 10 Ma, the timing of which suggests a close link to the two-step aridification (similar to 24 and 10 Ma) of the Tarim Basin. We suggest that the pulsed Cenozoic rise and growth of the South Tianshan played a crucial role in blocking westerly winds, restricting moisture from reaching the Tarim Basin, and driving Cenozoic aridification of the Tarim Basin. Initiation of the Cenozoic uplift of the South Tianshan occurred in the Late Eocene Further uplift of the South Tianshan completely blocked fluvial transport from the north by similar to 10 Ma Pulsed growth of Tianshan play a dominant role in the two-step aridification of the Tarim Basin
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