| 1. |
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| 2. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 4. |
- 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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| 5. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 6. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 7. |
- Jin, Ying-Hui, et al.
(författare)
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Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19 : An evidence-based clinical practice guideline (updated version)
- 2020
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Ingår i: Military Medical Research. - : Springer Science and Business Media LLC. - 2054-9369. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.
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| 8. |
- Lensink, Marc F., et al.
(författare)
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Impact of AlphaFold on structure prediction of protein complexes: The CASP15-CAPRI experiment
- 2023
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Ingår i: Proteins. - : WILEY. - 0887-3585 .- 1097-0134.
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Tidskriftsartikel (refereegranskat)abstract
- We present the results for CAPRI Round 54, the 5th joint CASP-CAPRI protein assembly prediction challenge. The Round offered 37 targets, including 14 homodimers, 3 homo-trimers, 13 heterodimers including 3 antibody-antigen complexes, and 7 large assemblies. On average similar to 70 CASP and CAPRI predictor groups, including more than 20 automatics servers, submitted models for each target. A total of 21 941 models submitted by these groups and by 15 CAPRI scorer groups were evaluated using the CAPRI model quality measures and the DockQ score consolidating these measures. The prediction performance was quantified by a weighted score based on the number of models of acceptable quality or higher submitted by each group among their five best models. Results show substantial progress achieved across a significant fraction of the 60+ participating groups. High-quality models were produced for about 40% of the targets compared to 8% two years earlier. This remarkable improvement is due to the wide use of the AlphaFold2 and AlphaFold2-Multimer software and the confidence metrics they provide. Notably, expanded sampling of candidate solutions by manipulating these deep learning inference engines, enriching multiple sequence alignments, or integration of advanced modeling tools, enabled top performing groups to exceed the performance of a standard AlphaFold2-Multimer version used as a yard stick. This notwithstanding, performance remained poor for complexes with antibodies and nanobodies, where evolutionary relationships between the binding partners are lacking, and for complexes featuring conformational flexibility, clearly indicating that the prediction of protein complexes remains a challenging problem.
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| 9. |
- Ma, Tao, et al.
(författare)
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Genomic insights into salt adaptation in a desert poplar
- 2013
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 4, s. 2797-
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Tidskriftsartikel (refereegranskat)abstract
- Despite the high economic and ecological importance of forests, our knowledge of the genomic evolution of trees under salt stress remains very limited. Here we report the genome sequence of the desert poplar, Populus euphratica, which exhibits high tolerance to salt stress. Its genome is very similar and collinear to that of the closely related mesophytic congener, P. trichocarpa. However, we find that several gene families likely to be involved in tolerance to salt stress contain significantly more gene copies within the P. euphratica lineage. Furthermore, genes showing evidence of positive selection are significantly enriched in functional categories related to salt stress. Some of these genes, and others within the same categories, are significantly upregulated under salt stress relative to their expression in another salt-sensitive poplar. Our results provide an important background for understanding tree adaptation to salt stress and facilitating the genetic improvement of cultivated poplars for saline soils.
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| 10. |
- Okada, Yukinori, et al.
(författare)
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Genetics of rheumatoid arthritis contributes to biology and drug discovery
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 506:7488, s. 376-381
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)(1). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating similar to 10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2-4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation(5), cis-acting expression quantitative trait loci(6) and pathway analyses(7-9)-as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes-to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.
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| 11. |
- Qin, Changliang, et al.
(författare)
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Process optimizations to recessed e-SiGe source/drain for performance enhancement in 22 nm all-last high-k/metal-gate pMOSFETs
- 2016
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Ingår i: Solid-State Electronics. - : Elsevier. - 0038-1101 .- 1879-2405. ; 123, s. 38-43
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, the technology of recessed embedded SiGe (e-SiGe) source/drain (S/D) module is optimized for the performance enhancement in 22 nm all-last high-k/metal-gate (HK/MG) pMOSFETs. Different Si recess-etch techniques were applied in S/D regions to increase the strain in the channel and subsequently, improve the performance of transistors. A new recess-etch method consists of a two-step etch method is proposed. This process is an initial anisotropic etch for the formation of shallow trench followed by a final isotropic etch. By introducing the definition of the upper edge distance (D) between the recessed S/D region and the channel region, the process advantage of the new approach is clearly presented. It decreases the value of D than those by conventional one-step isotropic or anisotropic etch of Si. Therefore, the series resistance is reduced and the channel strain is increased, which confirmed by the simulation results. The physical reason of D reducing is analyzed in brief. Applying this recess design, the implant conditions for S/D extension (SDE) are also optimized by using a two-step implantation of BF2 in SiGe layers. The overlap space between doping junction and channel region has great effect on the device's performance. The designed implantation profile decreases the overlap space while keeps a shallow junction depth for a controllable short channel effect. The channel resistance as well as the transfer ID-VG curves varying with different process conditions are demonstrated. It shows the drive current of the device with the optimized SDE implant condition and Si recess-etch process is obviously improved. The change trend of on-off current distributions extracted from a series of devices confirmed the conclusions. This study provides a useful guideline for developing high performance strained PMOS SiGe technology.
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| 12. |
- 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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| 13. |
- An, Pengcheng, et al.
(författare)
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EmoWear: Exploring Emotional Teasers for Voice Message Interaction on Smartwatches
- 2024
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Ingår i: Conference on Human Factors in Computing Systems - Proceedings.
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Konferensbidrag (refereegranskat)abstract
- Voice messages, by nature, prevent users from gauging the emotional tone without fully diving into the audio content. This hinders the shared emotional experience at the pre-retrieval stage. Research scarcely explored “Emotional Teasers”-pre-retrieval cues offering a glimpse into an awaiting message's emotional tone without disclosing its content. We introduce EmoWear, a smartwatch voice messaging system enabling users to apply 30 animation teasers on message bubbles to reflect emotions. EmoWear eases senders' choice by prioritizing emotions based on semantic and acoustic processing. EmoWear was evaluated in comparison with a mirroring system using color-coded message bubbles as emotional cues (N=24). Results showed EmoWear significantly enhanced emotional communication experience in both receiving and sending messages. The animated teasers were considered intuitive and valued for diverse expressions. Desirable interaction qualities and practical implications are distilled for future design. We thereby contribute both a novel system and empirical knowledge concerning emotional teasers for voice messaging.
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| 14. |
- An, Xiaojin, et al.
(författare)
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Response gene to complement 32, a novel hypoxia-regulated angiogenic inhibitor.
- 2009
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 120:7, s. 617-27
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Response gene to complement 32 (RGC-32) is induced by activation of complement and regulates cell proliferation. To determine the mechanism of RGC-32 in angiogenesis, we examined the role of RGC-32 in hypoxia-related endothelial cell function.METHODS AND RESULTS: Hypoxia/ischemia is able to stimulate both angiogenesis and apoptosis. Hypoxia-inducible factor-1/vascular endothelial growth factor is a key transcriptional regulatory pathway for angiogenesis during hypoxia. We demonstrated that the increased RGC-32 expression by hypoxia was via hypoxia-inducible factor-1/vascular endothelial growth factor induction in cultured endothelial cells. However, overexpression of RGC-32 reduced the proliferation and migration and destabilized vascular structure formation in vitro and inhibited angiogenesis in Matrigel assays in vivo. Silencing RGC-32 had an opposing, stimulatory effect. RGC-32 also stimulated apoptosis as shown by the increased apoptotic cells and caspase-3 cleavage. Mechanistic studies revealed that the effect of RGC-32 on the antiangiogenic response was via attenuating fibroblast growth factor 2 expression and further inhibiting expression of cyclin E without affecting vascular endothelial growth factor and fibroblast growth factor 2 signaling in endothelial cells. In the mouse hind-limb ischemia model, RGC-32 inhibited capillary density with a significant attenuation in blood flow. Additionally, treatment with RGC-32 in the xenograft tumor model resulted in reduced growth of blood vessels that is consistent with reduced colon tumor size.CONCLUSIONS: We provide the first direct evidence for RGC-32 as a hypoxia-inducible gene and antiangiogenic factor in endothelial cells. These data suggest that RGC-32 plays an important homeostatic role in that it contributes to differentiating the pathways for vascular endothelial growth factor and fibroblast growth factor 2 in angiogenesis and provides a new target for ischemic disorder and tumor therapies.
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| 15. |
- Chen, W., et al.
(författare)
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Directional dual-band slotted semi-circular inverted-F antenna for WLAN applications
- 2015
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Ingår i: Electronics Letters. - : Institution of Engineering and Technology (IET). - 1350-911X .- 0013-5194. ; 51:24, s. 1960-1961
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Tidskriftsartikel (refereegranskat)abstract
- A simple and compact directional dual-band semi-circular inverted-F antenna for wireless local area network applications is reported. Two pairs of semi-circular slots as well as a pair of arms are employed to generate the dual resonances in the 2.4-2.48 and 5.2-5.8 GHz bands. The measured results show that the proposed antenna can provide two 10 dB impedance bandwidths of 160 MHz (2.40-2.56 GHz) and 900 MHz (4.95-5.85 GHz). Nearly constant directivities (about 4.7 dBi) are observed in the lower band, while directivities in the upper band vary between 6.3 and 8.6 dBi.
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| 16. |
- Cho, Chang-woo, et al.
(författare)
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Evidence for the Fulde-Ferrell-Larkin-Ovchinnikov state in bulk NbS2
- 2021
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- We present measurements of the magnetic torque, specific heat and thermal expansion of the bulk transition metal dichalcogenide (TMD) superconductor NbS2 in high magnetic fields, with its layer structure aligned strictly parallel to the field using a piezo rotary positioner. The upper critical field of superconducting TMDs in the 2D form is known to be dramatically enhanced by a special form of Ising spin orbit coupling. This Ising superconductivity is very robust to the Pauli paramagnetic effect and can therefore exist beyond the Pauli limit for superconductivity. We find that superconductivity beyond the Pauli limit still exists in bulk single crystals of NbS2 for a precisely parallel field alignment. However, the comparison of our upper critical field transition line with numerical simulations rather points to the development of a Fulde-Ferrell-Larkin-Ovchinnikov state above the Pauli limit as a cause. This is also consistent with the observation of a magnetic field driven phase transition in the thermodynamic quantities within the superconducting state near the Pauli limit. Superconductivity is often destroyed under magnetic field larger than a critical value called Pauli limit. Here, the authors report superconductivity beyond the Pauli limit in bulk single crystals of NbS2, suggesting the development of a Fulde-Ferrell-Larkin-Ovchinnikov state.
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| 17. |
- Cho, Yoon Shin, et al.
(författare)
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Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians.
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:1
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression, is known for its association with fasting glucose levels. The evidence of an association with T2D for PEPD and HNF4A has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D.
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| 18. |
- de las Fuentes, Lisa, et al.
(författare)
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Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26:6, s. 2111-2125
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Tidskriftsartikel (refereegranskat)abstract
- Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, “Some College” (yes/no) and “Graduated College” (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
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| 19. |
- 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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| 20. |
- Deng, Tingzhi, et al.
(författare)
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Hippocampal Transcriptome-Wide Association Study Reveals Correlations Between Impaired Glutamatergic Synapse Pathway and Age-Related Hearing Loss in BXD-Recombinant Inbred Mice
- 2021
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Ingår i: Frontiers in Neuroscience. - : Frontiers Media S.A.. - 1662-4548 .- 1662-453X. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Age-related hearing loss (ARHL) is associated with cognitive dysfunction; however, the detailed underlying mechanisms remain unclear. The aim of this study is to investigate the potential underlying mechanism with a system genetics approach. A transcriptome-wide association study was performed on aged (12-32 months old) BXD mice strains. The hippocampus gene expression was obtained from 56 BXD strains, and the hearing acuity was assessed from 54 BXD strains. Further correlation analysis identified a total of 1,435 hearing-related genes in the hippocampus (p < 0.05). Pathway analysis of these genes indicated that the impaired glutamatergic synapse pathway is involved in ARHL (p = 0.0038). Further gene co-expression analysis showed that the expression level of glutamine synthetase (Gls), which is significantly correlated with ARHL (n = 26, r = -0.46, p = 0.0193), is a crucial regulator in glutamatergic synapse pathway and associated with learning and memory behavior. In this study, we present the first systematic evaluation of hippocampus gene expression pattern associated with ARHL, learning, and memory behavior. Our results provide novel potential molecular mechanisms involved in ARHL and cognitive dysfunction association.
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| 21. |
- Duan, Yu Xia, et al.
(författare)
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Crystal electric field splitting and f -electron hybridization in heavy-fermion CePt2In7
- 2019
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Ingår i: Physical Review B. - : AMER PHYSICAL SOC. - 2469-9969 .- 2469-9950. ; 100:8
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Tidskriftsartikel (refereegranskat)abstract
- We use high-resolution angle-resolved photoemission spectroscopy to investigate the electronic structure of the antiferromagnetic heavy fermion compound CePt2In7, which is a member of the CeIn3-derived heavy fermion material family. Weak hybridization among 4f electron states and conduction bands was identified in CePt2In7 at low temperature much weaker than that in the other heavy fermion compounds like CeIrIn5 and CeRhIn5. The Ce 4f spectrum shows fine structures near the Fermi energy, reflecting the crystal electric field splitting of the 4f5/21 and 4f7/21 states. Also, we find that the Fermi surface has a strongly three-dimensional topology, in agreement with density-functional theory calculations. © 2019 American Physical Society.
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| 22. |
- 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
-
Ingår i: PLOS ONE. - : Public library science. - 1932-6203. ; 13:6
-
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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| 23. |
- Gao, Chao, et al.
(författare)
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Isostructural Three-Dimensional Covalent Organic Frameworks
- 2019
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Ingår i: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 58:29, s. 9770-9775
-
Tidskriftsartikel (refereegranskat)abstract
- Herein, we reported the designed synthesis of three isostructural three-dimensional covalent organic frameworks (3D COFs) with -H, -Me, or -F substituents, which have similar crystallinity and topology. Their crystal structures were determined by continuous rotation electron diffraction (cRED), and all three 3D COFs were found to adopt a fivefold interpenetrated pts topology. More importantly, the resolution of these cRED datasets reached up to 0.9-1.0 angstrom, enabling the localization of all non-hydrogen atomic positions in a COF framework directly by 3D ED techniques for the first time. In addition, the precise control of the pore environments through the use of different functional groups led to different selectivities for CO2 over N-2. We have thus confirmed that polycrystalline COFs can be definitely studied to the atomic level as other materials, and this study should also inspire the design and synthesis of 3D COFs with tailored pore environments for interesting applications.
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| 24. |
- Gao, Chao, et al.
(författare)
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Redox-triggered switching in three-dimensional covalent organic frameworks
- 2020
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- The tuning of molecular switches in solid state toward stimuli-responsive materials has attracted more and more attention in recent years. Herein, we report a switchable three-dimensional covalent organic framework (3D COF), which can undergo a reversible transformation through a hydroquinone/quinone redox reaction while retaining the crystallinity and porosity. Our results clearly show that the switching process gradually happened through the COF framework, with an almost quantitative conversion yield. In addition, the redox-triggered transformation will form different functional groups on the pore surface and modify the shape of pore channel, which can result in tunable gas separation property. This study strongly demonstrates 3D COFs can provide robust platforms for efficient tuning of molecular switches in solid state. More importantly, switching of these moieties in 3D COFs can remarkably modify the internal pore environment, which will thus enable the resulting materials with interesting stimuli-responsive properties. Tuning of molecular switches in solid state toward stimuli-responsive materials attracted attention in recent years but has not yet been realized in three-dimensional (3D) covalent organic frameworks (COFs). Herein, the authors demonstrate a stable and switchable 3D COF which undergoes reversible transformation through a hydroquinone/quinone redox reaction.
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| 25. |
- Gao, Chao, et al.
(författare)
-
Twist Building Blocks from Planar to Tetrahedral for the Synthesis of Covalent Organic Frameworks
- 2020
-
Ingår i: Journal of the American Chemical Society. - 0002-7863 .- 1520-5126. ; 142:8, s. 3718-3723
-
Tidskriftsartikel (refereegranskat)abstract
- Rational construction of covalent organic frameworks (COFs) with novel structures still remains a challenge. Herein, we report the designed synthesis of two COFs, 2D-BPTA-COF and 3D-BMTA-COF, starting from biphenyl-based precursors but with different groups at the ortho positions. Both COFs exhibited high crystallinity and large surface area, and interestingly, 2D-BPTA-COF crystallizes into 2D sheets with AB stacking mode while 3D-BMTA-COF adopts a 7-fold interpenetrated structure with pts topology. This structural difference could be ascribed to the introduction of methyl groups in the building blocks, as the dihedral angle of biphenyl rings in 2D-BPTA-COF is similar to 0 degrees while in 3D-BMTA-COF it is similar to 60 degrees. Therefore, it is possible to synthesize COFs with different structures by twisting building blocks from planar to tetrahedral with steric hindrance. We believe this result represents a general and straightforward way to expand the diversity of tetrahedral nodes for constructing 3D COFs in the future, and moreover, a new tetrahedral node for constructing 3D COFs is now available.
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| 26. |
- Gravgaard Askjær, Thomas, et al.
(författare)
-
Multi-centennial Holocene climate variability in proxy records and transient model simulations
- 2022
-
Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 296
-
Tidskriftsartikel (refereegranskat)abstract
- Variability on centennial to multi-centennial timescales is mentioned as a feature in reconstructions of the Holocene climate. As more long transient model simulations with complex climate models become available and efforts have been made to compile large proxy databases, there is now a unique opportunity to study multi-centennial variability with greater detail and a large amount of data than earlier. This paper presents a spectral analysis of transient Holocene simulations from 9 models and 120 proxy records to find the common signals related to oscillation periods and geographic dependencies and discuss the implications for the potential driving mechanisms. Multi-centennial variability is significant in most proxy records, with the dominant oscillation periods around 120–130 years and an average of 240 years. Spectra of model-based global mean temperature (GMT) agree well with proxy evidence with significant multi-centennial variability in all simulations with the dominant oscillation periods around 120–150 years. It indicates a comparatively good agreement between model and proxy data. A lack of latitudinal dependencies in terms of oscillation period is found in both the model and proxy data. However, all model simulations have the highest spectral density distributed over the Northern hemisphere high latitudes, which could indicate a particular variability sensitivity or potential driving mechanisms in this region. Five models also have differentiated forcings simulations with various combinations of forcing agents. Significant multi-centennial variability with oscillation periods between 100 and 200 years is found in all forcing scenarios, including those with only orbital forcing. The different forcings induce some variability in the system. Yet, none appear to be the predominant driver based on the spectral analysis. Solar irradiance has long been hypothesized to be a primary driver of multi-centennial variability. However, all the simulations without this forcing have shown significant multi-centennial variability. The results then indicate that internal mechanisms operate on multi-centennial timescales, and the North Atlantic-Arctic is a region of interest for this aspect.
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| 27. |
- Iwamoto, Hideki, et al.
(författare)
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PlGF-induced VEGFR1-dependent vascular remodeling determines opposing antitumor effects and drug resistance to Dll4-Notch inhibitors
- 2015
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Ingår i: Science Advances. - : AMER ASSOC ADVANCEMENT SCIENCE. - 2375-2548. ; 1:3
-
Tidskriftsartikel (refereegranskat)abstract
- Inhibition of Dll4 (delta-like ligand 4)-Notch signaling-mediated tumor angiogenesis is an attractive approach in cancer therapy. However, inhibition of Dll4-Notch signaling has produced different effects in various tumors, and no biomarkers are available for predicting the anti-Dll4-Notch-associated antitumor activity. We show that human and mouse tumor cell-derived placental growth factor (PlGF) is a key determinant of the Dll4-Notch-induced vascular remodeling and tumor growth. In natural PlGF-expressing human tumors, inhibition of Dll4-Notch signaling markedly accelerated tumor growth by increasing blood perfusion in nonleaking tumor vasculatures. Conversely, in PlGF-negative tumors, Dll4 inhibition suppressed tumor growth by the formation of nonproductive and leaky vessels. Surprisingly, genetic inactivation of vascular endothelial growth factor receptor 1 (VEGFR1) completely abrogated the PlGF-modulated vascular remodeling and tumor growth, indicating a crucial role for VEGFR1-mediated signals in modulating Dll4-Notch functions. These findings provide mechanistic insights on PlGF-VEGFR1 signaling in the modulation of the Dll4-Notch pathway in angiogenesis and tumor growth, and have therapeutic implications of PlGF as a biomarker for predicting the antitumor benefits of Dll4 and Notch inhibitors.
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| 28. |
- Ji, Hong, et al.
(författare)
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TNFR1 mediates TNF-alpha-induced tumour lymphangiogenesis and metastasis by modulating VEGF-C-VEGFR3 signalling
- 2014
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Ingår i: Nature Communications. - : Nature Publishing Group: Nature Communications. - 2041-1723. ; 5:4944
-
Tidskriftsartikel (refereegranskat)abstract
- Inflammation and lymphangiogenesis are two cohesively coupled processes that promote tumour growth and invasion. Here we report that TNF-alpha markedly promotes tumour lymphangiogenesis and lymphatic metastasis. The TNF-alpha-TNFR1 signalling pathway directly stimulates lymphatic endothelial cell activity through a VEGFR3-independent mechanism. However, VEGFR3-induced lymphatic endothelial cell tips are a prerequisite for lymphatic vessel growth in vivo, and a VEGFR3 blockade completely ablates TNF-alpha-induced lymphangiogenesis. Moreover, TNF-alpha-TNFR1-activated inflammatory macrophages produce high levels of VEGF-C to coordinately activate VEGFR3. Genetic deletion of TNFR1 (Tnfr1(-/-)) in mice or depletion of tumour-associated macrophages (TAMs) virtually eliminates TNF-alpha-induced lymphangiogenesis and lymphatic metastasis. Gain-of-function experiments show that reconstitution of Tnfr1(+/+) macrophages in Tnfr1(+/+) mice largely restores tumour lymphangiogenesis and lymphatic metastasis. These findings shed mechanistic light on the intimate interplay between inflammation and lymphangiogenesis in cancer metastasis, and propose therapeutic intervention of lymphatic metastasis by targeting the TNF-alpha-TNFR1 pathway.
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| 29. |
- Jin, Yi, et al.
(författare)
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RTEF-1, an upstream gene of hypoxia-inducible factor-1α, accelerates recovery from ischemia.
- 2011
-
Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 286:25, s. 22699-22705
-
Tidskriftsartikel (refereegranskat)abstract
- The amount of available hypoxia-inducible factor (HIF)-1α has been considered to be largely a consequence of post-translational modification by multiple ubiquitin-proteasome pathways. However, the role of transcriptional regulation of HIF-1α is less certain, and the mechanisms of transcriptional regulation of HIF-1α require further investigation. Here we report that related transcriptional enhancer factor-1 (RTEF-1), a member of the TEF transcriptional factor family, transcriptionally regulates the HIF-1α gene under normoxic and hypoxic conditions. The expression of HIF-1α mRNA was decreased in endothelial cells in which RTEF-1 was knocked down with siRNA. Sequential deletional analysis of the HIF-1α promoter revealed that the MCAT-like element in the HIF-1α promoter was essential for HIF-1α transcription. Binding of RTEF-1 to the MCAT-like element was confirmed by ChIP. Treatment of endothelial cells with a HIF-1 inhibitor resulted in retardation of RTEF-1-induced proliferation and tube formation. Moreover, increased HIF-1α expression was observed in transgenic mice expressing RTEF-1 under the VE-cadherin promoter (VE-Cad/RTEF-1). VE-Cad/RTEF-1 mice subjected to hindlimb ischemia demonstrated increased levels of HIF-1α, accelerated recovery of blood flow, and increased capillary density compared with littermate controls. These results identify RTEF-1 as a regulator of HIF-1α transcription, which results in up-regulation of HIF-1α and acceleration of recovery from ischemia.
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| 30. |
- Kato, Norihiro, et al.
(författare)
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Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
- 2015
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
-
Tidskriftsartikel (refereegranskat)abstract
- We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
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| 31. |
- Kuang, Chaoyang, et al.
(författare)
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Critical role of additive-induced molecular interaction on the operational stability of perovskite light-emitting diodes
- 2021
-
Ingår i: Joule. - : Cell Press. - 2542-4351. ; 5:3, s. 618-630
-
Tidskriftsartikel (refereegranskat)abstract
- Despite rapid improvements in efficiency and brightness of perovskite light-emitting diodes (PeLEDs), the poor operational stability remains a critical challenge hindering their practical applications. Here, we demonstrate greatly improved operational stability of high-efficiency PeLEDs, enabled by incorporating dicarboxylic acids into the precursor for perovskite depositions. We reveal that the dicarboxylic acids efficiently eliminate reactive organic ingredients in perovskite emissive layers through an in situ amidation process, which is catalyzed by the alkaline zinc oxide substrate. The formed stable amides prohibit detrimental reactions between the perovskites and the charge injection layer underneath, stabilizing the perovskites and the interfacial contacts and ensuring the excellent operational stability of the resulting PeLEDs. Through rationally optimizing the amidation reaction in the perovskite emissive layers, we achieve efficient PeLEDs with a peak external quantum efficiency of 18.6% and a long half-life time of 682 h at 20 mA cm(-2), presenting an important breakthrough in PeLEDs.
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| 32. |
- Li, Xing-Yu, et al.
(författare)
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Comparative Study of Dayside Pulsating Auroras Induced by Ultralow-Frequency Waves
- 2023
-
Ingår i: Universe. - : MDPI AG. - 2218-1997. ; 9:6
-
Tidskriftsartikel (refereegranskat)abstract
- Pulsating auroras are usually observed with ultralow-frequency (ULF) waves in the Pc 3-5 band (period 10-600 s). These auroras are thought to result from interactions between energetic electrons and chorus waves, but their relationship with ULF waves remains an open question. In this study, we investigated this question by conducting a comparative study on two ULF wave events with pulsating auroras observed near the magnetic footprints. Conjugate observations from the Magnetospheric Multiscale mission and the Chinese Yellow River Station were used. In both events, lower-band chorus waves were observed, which were suggested to be connected with the auroral pulsations by wavelet analysis. The intensity of these waves oscillates at the period of the ULF waves, but the physics laid behind them differs by events. During the event of 22 January 2019, compressional ULF waves changed the threshold for the whistler anisotropy instability periodically, affecting the emission of chorus waves. In the event on 10 January 2016, poloidal ULF waves modulated the chorus wave generation by regulating electron temperature anisotropy through drift resonance. ULF waves in these events may originate from perturbations in the solar wind. We highlight the role of ULF waves in the solar wind-magnetosphere-ionosphere coupling, which requires further study.
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| 33. |
- Liang, Akun, et al.
(författare)
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High-Pressure Synthesis of Ultra-Incompressible, Hard and Superconducting Tungsten Nitrides
- 2024
-
Ingår i: Advanced Functional Materials. - : WILEY-V C H VERLAG GMBH. - 1616-301X .- 1616-3028.
-
Tidskriftsartikel (refereegranskat)abstract
- Transition metal nitrides, particularly those of 5d metals, are known for their outstanding properties, often relevant for industrial applications. Among these metal elements, tungsten is especially attractive given its low cost. In this high-pressure investigation of the W-N system, two novel ultra-incompressible tungsten nitride superconductors, namely W2N3 and W3N5, are successfully synthesized at 35 and 56 GPa, respectively, through a direct reaction between N2 and W in laser-heated diamond anvil cells. Their crystal structure is determined using synchrotron single-crystal X-ray diffraction. While the W2N3 solid's sole constituting nitrogen species are N3- units, W3N5 features both discrete N3- as well as N24- pernitride anions. The bulk modulus of W2N3 and W3N5 is experimentally determined to be 380(3) and 406(7) GPa, and their ultra-incompressible behavior is rationalized by their constituting WN7 polyhedra and their linkages. Importantly, both W2N3 and W3N5 are recoverable to ambient conditions and stable in air. Density functional theory calculations reveal W2N3 and W3N5 to have a Vickers hardness of 30 and 34 GPa, and superconducting transition temperatures at ambient pressure (50 GPa) of 11.6 K (9.8 K) and 9.4 K (7.2 K), respectively. Additionally, transport measurements performed at 50 GPa on W2N3 corroborate with the calculations. Two recoverable tungsten nitrides, namely W2N3 and W3N5, are synthesized using laser-heated diamond anvil cells. Both compounds exhibit a high bulk modulus, hardness, and superconducting transition temperature. image
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| 34. |
- Liu, Xiaoling, et al.
(författare)
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A Crystalline Three-Dimensional Covalent Organic Framework with Flexible Building Blocks
- 2021
-
Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 143:4, s. 2123-2129
-
Tidskriftsartikel (refereegranskat)abstract
- The construction of three-dimensional covalent organic frameworks (3D COFs) has proven to be very challenging, as their synthetic driving force mainly comes from the formation of covalent bonds. To facilitate the synthesis, rigid building blocks are always the first choice for designing 3D COFs. In principle, it should be very appealing to construct 3D COFs from flexible building blocks, but there are some obstacles blocking the development of such systems, especially for the designed synthesis and structure determination. Herein, we reported a novel highly crystalline 3D COF (FCOF-5) with flexible C–O single bonds in the building block backbone. By merging 17 continuous rotation electron diffraction data sets, we successfully determined the crystal structure of FCOF-5 to be a 6-fold interpenetrated pts topology. Interestingly, FCOF-5 is flexible and can undergo reversible expansion/contraction upon vapor adsorption/desorption, indicating a breathing motion. Moreover, a smart soft polymer composite film with FCOF-5 was fabricated, which can show a reversible vapor-triggered shape transformation. Therefore, 3D COFs constructed from flexible building blocks can exhibit interesting breathing behavior, and finally, a totally new type of soft porous crystals made of pure organic framework was announced.
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| 35. |
- Liu, Yuchen, et al.
(författare)
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Effect of probe pulse duration in picosecond ultrasonics
- 2022
-
Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 120:20
-
Tidskriftsartikel (refereegranskat)abstract
- Picosecond ultrasonics is a powerful tool for nanoscale metrology, giving access to dimensions and mechanical, thermal, and optical properties of nanomaterials. By monitoring the temporal evolution of the interaction of light with coherent acoustic phonons, also known as Brillouin oscillations, phonon lifetime and optical absorption can be measured. However, the extraction of these quantities can be inaccurate due to the common assumption of the infinite coherence length of probe pulses. Here, we demonstrate the effect of probe pulse duration on picosecond ultrasonic measurements numerically and experimentally. We establish a model that shows how the probe coherence length affects the measured signal loss and how we can overcome this limitation and measure an upper limit of the acoustic attenuation factor. The model is verified experimentally on a GaAs bulk substrate by varying the probe pulse duration, showing a strong effect for sub-100 fs pulses. Finally, we applied to CH3NH3PbBr3, where we reveal a high acoustic attenuation factor, which is in line with recent claims of strong anharmonicity in halide perovskites.
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| 36. |
- Luo, Yang, et al.
(författare)
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Three-dimensional and temperature-dependent electronic structure of the heavy-fermion compound CePt2In7 studied by angle-resolved photoemission spectroscopy
- 2020
-
Ingår i: Physical Review B. - : AMER PHYSICAL SOC. - 2469-9950 .- 2469-9969. ; 101:11
-
Tidskriftsartikel (refereegranskat)abstract
- The three-dimensional and temperature-dependent electronic structures of the heavy-fermion superconductor CePt2In7 are investigated. Angle-resolved photoemission spectroscopy using variable photon energy establishes the existence of quasi-two- and three-dimensional Fermi surface topologies. Temperature-dependent 4d-4f on-resonance photoemission spectroscopies data reveal that heavy quasiparticle bands begin to form at a temperature well above the characteristic (coherence) temperature T+. The emergence of low-lying crystal electric field excitation may be responsible for the "relocalization" or the precursor to the establishment of heavy electrons coherence in heavy-fermion compounds. These findings provide critical insight into understanding the hybridization in heavy-fermion systems.
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| 37. |
- Mahajan, Anubha, et al.
(författare)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
-
Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
-
Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 38. |
- Pang, F., et al.
(författare)
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A dual-band slotted trapezoidal inverted-F antenna for indoor WLAN communications
- 2016
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Ingår i: Progress In Electromagnetics Research Letters. - 1937-6480. ; 64, s. 57-63
-
Tidskriftsartikel (refereegranskat)abstract
- This letter presents a new directional dual-band slotted trapezoidal inverted-F antenna (IFA) for indoor Wireless Local Area Network (WLAN) applications. The dual-band performance can be obtained by tuning the lengths of the inner symmetrical trapezoidal slots and the outer trapezoidal arms in a nearly independent manner. The measured results show that the proposed antenna can provide two separate impedance bandwidths (return loss better than 10 dB) around 180MHz and 750MHz for 2.4/5.1-5.8 GHz WLAN bands, respectively. Good radiation performance and roughly constant in-band antenna directivities are also observed.
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| 39. |
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| 40. |
- Ruilope, LM, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
-
Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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| 41. |
- Satizabal, Claudia L., et al.
(författare)
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Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
-
Tidskriftsartikel (refereegranskat)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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| 42. |
- Song, Jiao-Jiao, et al.
(författare)
-
Relocalization of uranium 5f electrons in the antiferromagnetic heavy-fermion superconductor UPd2Al3 : Insights from angle-resolved photoemission spectroscopy
- 2024
-
Ingår i: Physical Review B. - : American Physical Society. - 2469-9950 .- 2469-9969. ; 109:20
-
Tidskriftsartikel (refereegranskat)abstract
- We investigate the antiferromagnetic heavy fermion superconductor UPd2Al3, employing angle-resolved photoemission spectroscopy to unravel the complex electronic structure of its U 5? electrons. We observe unexpected characteristics that challenge the conventional temperature-dependent behavior of heavy fermion systems, revealing unexpected characteristics. At temperatures above the anticipated coherence temperature (?*), we observe itinerant U 5? electrons at temperatures higher than previously postulated. Additionally, a previously unidentified dispersionless band emerges around 600 meV below the Fermi energy, potentially linked to spin-orbit splitting within the U 5? states. Hybridization between the 5? electrons and conduction band was observed with an energy dispersion of 10 meV at low temperatures, suggesting that U 5? electrons near and at the Fermi surface have an itinerant nature. Temperature-dependent 5?−5? resonance spectra reveal that the 5? electron spectrum weight increases with lowering temperature and begins to decrease at temperatures significantly higher than the Néel temperature (??). We further show that the competition between the Kondo effect and Ruderman-Kittel-Kasuya-Yosida (RKKY) interactions may be responsible for the relocalization of 5? electrons, making relocalization a precursor to the establishment of magnetic order at lower temperatures. Our experiments also provide evidence that 5? electrons with the same orbital are involved in both the Kondo effect and RKKY interactions, suggesting that the two coexist at lower temperatures.
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| 43. |
- Song, Jiao-Jiao, et al.
(författare)
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The 4f-Hybridization Strength in CemMnIn3m+2n Heavy-Fermion Compounds Studied by Angle-Resolved Photoemission Spectroscopy
- 2021
-
Ingår i: Chinese Physics Letters. - : IOP Publishing. - 0256-307X .- 1741-3540. ; 38:10
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Tidskriftsartikel (refereegranskat)abstract
- We systemically investigate the nature of Ce 4f electrons in structurally layered heavy-fermion compounds CemMnIn3m+2n (with M = Co, Rh, Jr, and Pt, m = 1, 2, n = 0-2), at low temperature using on-resonance angle-resolved photoemission spectroscopy. Three heavy quasiparticle bands f(0), f(7/2)(1) and f(5/2)(1), are observed in all compounds, whereas their intensities and energy locations vary greatly with materials. The strong f(0) states imply that the localized electron behavior dominates the Ce 4f states. The Ce 4f electrons are partially hybridized with the conduction electrons, making them have the dual nature of localization and itinerancy. Our quantitative comparison reveals that the f(5/2)(1)-f (0) intensity ratio is more suitable to reflect the 4f-state hybridization strength.
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| 44. |
- Sung, Yun Ju, et al.
(författare)
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A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure
- 2019
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 28:15, s. 2615-2633
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
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| 45. |
- Takeuchi, Fumihiko, et al.
(författare)
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Interethnic analyses of blood pressure loci in populations of East Asian and European descent
- 2018
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, we perform a multi-stage genome-wide association study for BP (max N = 289,038) principally in East Asians and meta-analysis in East Asians and Europeans. We report 19 new genetic loci and ancestry-specific BP variants, conforming to a common ancestry-specific variant association model. At 10 unique loci, distinct non-rare ancestry-specific variants colocalize within the same linkage disequilibrium block despite the significantly discordant effects for the proxy shared variants between the ethnic groups. The genome-wide transethnic correlation of causal-variant effect-sizes is 0.898 and 0.851 for systolic and diastolic BP, respectively. Some of the ancestry-specific association signals are also influenced by a selective sweep. Our results provide new evidence for the role of common ancestry-specific variants and natural selection in ethnic differences in complex traits such as BP.
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| 46. |
- Wan, Cheng-Liang, et al.
(författare)
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Dynamics of slow electrons transmitting through straight glass capillary and tapered glass capillary
- 2016
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Ingår i: Wuli xuebao. - : Acta Physica Sinica, Chinese Physical Society and Institute of Physics, Chinese Academy of Sciences. - 1000-3290. ; 65:20
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Tidskriftsartikel (refereegranskat)abstract
- It has been found that the transmission rate of the electrons through insulating capillaries as a function of time/incident charge is not the same as that of the ions. The question arises that by using the electrons, if the negative charge patches can be formed to facilitate the transmission of the following electrons, thereby substantiating that the so-called guiding effect works also for electrons. This study aims to observe the time evolutions of the transmission of electrons through a straight glass tube and a tapered glass capillary. This will reveal the details of how and (or) if the negative charge patches can be formed when the electrons transport through them. In this work, a set of MCP/phosphor two-dimensional detection system based on Labview platform is developed to obtain the time evolution of the angular distribution of the transmitted electrons. The pulsed electron beams are obtained to test our detection system. The time evolution of the angular profile of 1.5 keV electrons transmitting through the glass tube/capillary is observed. The transmitted electrons are observed on the detector for a very short time and disappear for a time and then appear again for both the glass tube and tapered glass capillary, leading to an oscillation. The positive charge patches are formed in the insulating glass tube and tapered glass capillary since the secondary electron emission coefficient for the incident energy is larger than 1. It is due to the fact that fast discharge of the deposited charge leads to the increase of the transmission rate, while the fast blocking of the incident electrons due to the deposited positive charge leads to the decrease of the transmission rate. The geometrical configuration of the taper glass capillary tends to make the secondary electrons deposited at the exit part to form the negative patches that facilitate the transmission of electrons. This suggests that if the stable transmission needs to be reached for producing the electron micro-beam by using tapered glass capillaries, the steps must be taken to have the proper grounding and shielding of the glass capillaries and tubes. Our results show a difference in transmission through the insulating capillary between electrons and highly charged ions.
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| 47. |
- Wan, Kang, et al.
(författare)
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A Multilayer-Stacked UWB Yagi Antenna
- 2017
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Ingår i: 2017 International Symposium on Antennas and Propagation, ISAP 2017. - 9781538604656 ; Volume 2017-January, s. 1-2
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Konferensbidrag (refereegranskat)abstract
- By taking advantage of a wideband bow-tie antenna in the Yagi configuration, a novel multilayer-stacked ultra-wideband (UWB) Yagi antenna is proposed. First, the fundamental 3-layered UWB Yagi model is studied with respect to a few critical dimensions. Then, several directors are added to form a multilayer-stacked Yagi antenna, where the width of the directors is optimized in a monotonic decreasing manner. A sixlayered UWB Yagi antenna is studied by simulations. It covers 3.4-10.6 GHz with its return loss better than 10 dB, and it achieves a high directivity up to 13 dBi and a relative cross-polar level better than -10 dB in the whole band.
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| 48. |
- Wang, Dandan, et al.
(författare)
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Ultrafast carrier dynamics of near-band-edge emission in single-crystal ZnO nanorods
- 2011
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Ingår i: Materials research bulletin. - : Elsevier Science B.V., Amsterdam.. - 0025-5408 .- 1873-4227. ; 46:6, s. 937-940
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Tidskriftsartikel (refereegranskat)abstract
- We report on rational synthesis and optical characteristics of highly crystallined ZnO nanorods which were grown by a facile chemical vapor transport method. Temperature-dependent photoluminescence spectra of as-fabricated ZnO nanorods are dominated by near-band-edge emission with a characteristic fine structure due to high crystallinity. Furthermore, the recombination emission involving carrier dynamics of near-band-edge emission in ZnO nanorods was systematically investigated by temperature-dependent time-resolved photoluminescence spectroscopy. Recombination peaks pertaining to the exciton emissions are monitored and resolved in both temporal and spatial regimes.
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| 49. |
- Wang, Jian-HUa, et al.
(författare)
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Influence of Features of Natural Soft Clay on Embankment Behavior
- 2013
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Ingår i: Pavement and Geotechnical Engineering for Transportation. - Reston, VA : American Society of Civil Engineers. ; , s. 111-116
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Konferensbidrag (refereegranskat)abstract
- This paper aims to investigate the influence of different features of natural soft clays, namely anisotropy, destructuration, on modeling the long-term behavior of embankments. The newly developed elasto-viscoplastic model is used for this purpose. The parameters determined from conventional triaxial and oedometer tests are employed for simulations, with additional parameters required representing different soil features. The finite element predictions by using the model coupled with Biot's consolidation theory compare the results for settlement, horizontal displacement and excess pore pressures. All simulations demonstrate that all three features influence significantly the predictions.
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| 50. |
- Wang, Liyun, et al.
(författare)
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Serious selenium deficiency in the serum of patients with Kashin-Beck disease and the effect of nano-selenium on their chondrocytes
- 2020
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Ingår i: Biological Trace Element Research. - : Springer. - 0163-4984 .- 1559-0720. ; 194:1, s. 96-104
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Tidskriftsartikel (refereegranskat)abstract
- To investigate selenium (Se) concentrations in serum of patients with rheumatoid arthritis (RA), osteoarthritis (OA), and Kashin-Beck disease (KBD), together with the effect of Se supplement (chondroitin sulfate [CS] nano-Se [SeCS]) on CS structure-modifying sulfotransferases in KBD chondrocyte. Fifty serum samples from each group with aged-matched (40-60 years), normal control (N), RA, OA, and KBD (25 males and females, respectively) were collected to determine Se concentrations. Furthermore, the KBD chondrocytes were divided into two groups following the intervention for 24 h: (a) non-treated KBD group and (b) SeCS-treated KBD group (100 ng/mL SeCS). The ultrastructural changes in chondrocytes were observed by transmission electron microscopy (TEM). Live/dead staining was used to observe cell viability. The expression of CS-modifying sulfotransferases including carbohydrate sulfotransferase 12, 13, and 15 (CHST-12, CHST-13, and CHST-15, respectively), and uronyl 2-O-sulfotransferase (UST) were examined by quantitative real-time polymerase chain reaction and western blotting analysis after SeCS intervention. The Se concentrations in serum of KBD, OA, and RA patients were lower than those in control. In OA, RA, and control, Se concentrations were higher in male than in female, while it is opposite in KBD. In the cell experiment, cell survival rate and mitochondrial density were increased in SeCS-treated KBD groups. Expressions of CHST-15, or CHST-12, and CHST-15 on the mRNA or protein level were significantly increased. Expression of UST slightly increased on the mRNA level, but no change was visible on the protein level. Se deficiency in serum of RA, OA, and KBD was observed. SeCS supplemented in KBD chondrocytes improved their survival rate, ameliorated their ultrastructure, and increased the expression of CS structure-modifying sulfotransferases.
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