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- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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4. |
- 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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- 2019
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Tidskriftsartikel (refereegranskat)
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6. |
- Abelev, Betty, et al.
(författare)
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Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
- 2013
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
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Tidskriftsartikel (refereegranskat)abstract
- Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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7. |
- Abelev, Betty, et al.
(författare)
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Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :11
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Tidskriftsartikel (refereegranskat)abstract
- The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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8. |
- Abelev, Betty, et al.
(författare)
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Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :7
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Tidskriftsartikel (refereegranskat)abstract
- We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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9. |
- An, Junghwa, et al.
(författare)
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Permanent Genetic Resources added to Molecular Ecology Resources Database 1 October 2009-30 November 2009
- 2010
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Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:2, s. 404-408
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Tidskriftsartikel (refereegranskat)abstract
- This article documents the addition of 411 microsatellite marker loci and 15 pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Acanthopagrus schlegeli, Anopheles lesteri, Aspergillus clavatus, Aspergillus flavus, Aspergillus fumigatus, Aspergillus oryzae, Aspergillus terreus, Branchiostoma japonicum, Branchiostoma belcheri, Colias behrii, Coryphopterus personatus, Cynogolssus semilaevis, Cynoglossus semilaevis, Dendrobium officinale, Dendrobium officinale, Dysoxylum malabaricum, Metrioptera roeselii, Myrmeciza exsul, Ochotona thibetana, Neosartorya fischeri, Nothofagus pumilio, Onychodactylus fischeri, Phoenicopterus roseus, Salvia officinalis L., Scylla paramamosain, Silene latifo, Sula sula, and Vulpes vulpes. These loci were cross-tested on the following species: Aspergillus giganteus, Colias pelidne, Colias interior, Colias meadii, Colias eurytheme, Coryphopterus lipernes, Coryphopterus glaucofrenum, Coryphopterus eidolon, Gnatholepis thompsoni, Elacatinus evelynae, Dendrobium loddigesii Dendrobium devonianum, Dysoxylum binectariferum, Nothofagus antarctica, Nothofagus dombeyii, Nothofagus nervosa, Nothofagus obliqua, Sula nebouxii, and Sula variegata. This article also documents the addition of 39 sequencing primer pairs and 15 allele specific primers or probes for Paralithodes camtschaticus.
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10. |
- 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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11. |
- 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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12. |
- Kim, Joon Tae, et al.
(författare)
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Dual antiplatelet Use for extended period taRgeted to AcuTe ischemic stroke with presumed atherosclerotic OrigiN (DURATION) trial : Rationale and design
- 2023
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Ingår i: International Journal of Stroke. - : SAGE Publications. - 1747-4930 .- 1747-4949. ; 18:8, s. 1015-1020
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: The optimal duration of dual antiplatelet therapy (DAPT) with clopidogrel-aspirin for the large artery atherosclerotic (LAA) stroke subtype has been debated. Aims: To determine whether the 1-year risk of recurrent vascular events could be reduced by a longer duration of DAPT in patients with the LAA stroke subtype. Methods and study design: A total of 4806 participants will be recruited to detect a statistically significant relative risk reduction of 22% with 80% power and a two-sided alpha error of 0.05, including a 10% loss to follow-up. This is a registry-based, multicenter, prospective, randomized, open-label, blinded end point study designed to evaluate the efficacy and safety of a 12-month duration of DAPT compared with a 3-month duration of DAPT in the LAA stroke subtype. Patients will be randomized (1:1) to either DAPT for 12 months or DAPT for 3 months, followed by monotherapy (either aspirin or clopidogrel) for the remaining 9 months. Study outcomes: The primary efficacy outcome of the study is a composite of stroke (ischemic or hemorrhagic), myocardial infarction, and all-cause mortality for 1 year after the index stroke. The secondary efficacy outcomes are (1) stroke, (2) ischemic stroke or transient ischemic attack, (3) hemorrhagic stroke, and (4) all-cause mortality. The primary safety outcome is major bleeding. Discussion: This study will help stroke physicians determine the appropriate duration of dual therapy with clopidogrel-aspirin for patients with the LAA stroke subtype. Trial registration: URL: https://cris.nih.go.kr/cris. CRIS Registration Number: KCT0004407.
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13. |
- Qian, Yan, et al.
(författare)
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Quantification for total demethylation potential of environmental samples utilizing the EGFP reporter gene
- 2016
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Ingår i: Journal of Hazardous Materials. - : Elsevier. - 0304-3894 .- 1873-3336. ; 306, s. 278-285
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Tidskriftsartikel (refereegranskat)abstract
- Abstract The demethylation potential of pollutants is arguably an innate component of their toxicity in environmental samples. A method was developed for determining the total demethylation potential of food samples (TDQ). The demethylation epigenetic toxicity was determined using the Hep G2 cell line transfected with pEGFP-C3 plasmids containing a methylated promoter of the EGFP reporter gene. The total demethylation potential of the sample extracts (the 5-AZA-CdR demethylation toxic equivalency) can be quantified within one week by using a standard curve of the 5-AZA-CdR demethylation agent. To explore the applicability of TDQ for environmental samples, 17 groundwater samples were collected from heavy polluted Kuihe river and the total demethylation potentials of the sample extracts were measured successfully. Meaningful demethylation toxic equivalencies ranging from 0.00050 to 0.01747 μM were found in all groundwater sample extracts. Among 19 kinds of inorganic substance, As and Cd played important roles for individual contribution to the total demethylation epigenetic toxicity. The TDQ assay is reliable and fast for quantifying the DNA demethylation potential of environmental sample extracts, which may improve epigenetic toxicity evaluations for human risk assessment, and the consistent consuming of groundwater alongside the Kuihe river pose unexpected epigenetic health risk to the local residents.
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17. |
- George, Julie, et al.
(författare)
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Comprehensive genomic profiles of small cell lung cancer
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 524:7563, s. 47-U73
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Tidskriftsartikel (refereegranskat)abstract
- We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Dex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.
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18. |
- 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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19. |
- Jin, Yukun, et al.
(författare)
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Mixed Insulating State for van der Waals CoPS3
- 2022
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Ingår i: Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 13:45, s. 10486-10493
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Tidskriftsartikel (refereegranskat)abstract
- Large-scale high-quality van der Waals CoPS3single crystals are synthesized using a chemical vapor transport (CVT) method. The crystallographic structure and electronic properties of this layered material are systematically studied using different spectroscopic methods (XPS, NEXAFS, and resonant photoelectron spectroscopy) accompanied by density functional theory (DFT) calculations. All experimental and theoretical data allow assignment of this material to the class of mixed Mott-Hubbard/charge-transfer insulator with Udd≅ Δ. All obtained results can enrich the information on the new class of van der Waals materials, transition metal phosphorus trichalcogenides, and help to further effectively exploit their electronic, optical, and transport properties, which are important for adopting this kind of materials into different application areas, such as spintronics and catalysis.
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20. |
- 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
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
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Tidskriftsartikel (refereegranskat)abstract
- We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
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21. |
- Lee, Hyun-Seob, et al.
(författare)
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Foxa2 and Nurr1 Synergistically Yield A9 Nigral Dopamine Neurons Exhibiting Improved Differentiation, Function, and Cell Survival
- 2010
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Ingår i: Stem Cells. - : Oxford University Press (OUP). - 1549-4918 .- 1066-5099. ; 28:3, s. 501-512
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Tidskriftsartikel (refereegranskat)abstract
- Effective dopamine (DA) neuron differentiation from neural precursor cells (NPCs) is prerequisite for precursor/stem cell-based therapy of Parkinson's disease (PD). Nurr1, an orphan nuclear receptor, has been reported as a transcription factor that can drive DA neuron differentiation from non-dopaminergic NPCs in vitro. However, Nurr1 alone neither induces full neuronal maturation nor expression of proteins found specifically in midbrain DA neurons. In addition, Nurr1 expression is inefficient in inducing DA phenotype expression in NPCs derived from certain species such as mouse and human. We show here that Foxa2, a forkhead transcription factor whose role in midbrain DA neuron development was recently revealed, synergistically cooperates with Nurr1 to induce DA phenotype acquisition, midbrain-specific gene expression, and neuronal maturation. Thus, the combinatorial expression of Nurr1 and Foxa2 in NPCs efficiently yielded fully differentiated nigral (A9)-type midbrain neurons with clearly detectable DA neuronal activities. The effects of Foxa2 in DA neuron generation were observed regardless of the brain regions or species from which NPCs were derived. Furthermore, DA neurons generated by ectopic Foxa2 expression were more resistant to toxins. Importantly, Foxa2 expression resulted in a rapid cell cycle exit and reduced cell proliferation. Consistently, transplantation of NPCs transduced with Nurr1 and Foxa2 generated grafts enriched with midbrain-type DA neurons but reduced number of proliferating cells, and significantly reversed motor deficits in a rat PD model. Our findings can be applied to ongoing attempts to develop an efficient and safe precursor/stem cell-based therapy for PD. STEM CELLS 2010; 28: 501-512
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22. |
- Naghavi, Mohsen, et al.
(författare)
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Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
- 2015
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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 385:9963, s. 117-171
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Tidskriftsartikel (refereegranskat)abstract
- Background Up-to-date evidence on levels and trends for age-sex-specifi c all-cause and cause-specifi c mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specifi c all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specifi c causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65.3 years (UI 65.0-65.6) in 1990, to 71.5 years (UI 71.0-71.9) in 2013, while the number of deaths increased from 47.5 million (UI 46.8-48.2) to 54.9 million (UI 53.6-56.3) over the same interval. Global progress masked variation by age and sex: for children, average absolute diff erences between countries decreased but relative diff erences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative diff erences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10.7%, from 4.3 million deaths in 1990 to 4.8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specifi c mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.
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23. |
- Nik-Zainal, Serena, et al.
(författare)
-
Landscape of somatic mutations in 560 breast cancer whole-genome sequences
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 534:7605, s. 47-54
-
Tidskriftsartikel (refereegranskat)abstract
- We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, another with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.
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24. |
- Pan, Di, et al.
(författare)
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Probabilistic Prediction of Collisions between Cyclists and Vehicles Based on Uncertainty of Cyclists’ Movements
- 2023
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Ingår i: Transportation Research Record. - : SAGE Publications. - 0361-1981 .- 2169-4052. ; 2677:3, s. 1151-1164
-
Tidskriftsartikel (refereegranskat)abstract
- The uncertainty of cyclists’ movements has a significant impact on predicting the risk of collisions between cyclists and vehicles. The purpose of this study was to provide a method for assessing collision risk using probability, taking into account the uncertainty of cyclists’ movements. A cyclist model was first developed using a first-order Markov model. Then, based on Monte Carlo sampling, the distribution characteristics of the minimum distance and the time-to-collision (TTC) between the vehicle and the cyclist were extracted. By fitting these features, the probability density functions of the collision distance and TTC were estimated to derive the collision probabilities. The effectiveness of the collision probability prediction model was benchmarked against a deterministic crash risk prediction model (autonomous emergency braking [AEB] system) applied to three real-world cases previously reconstructed in an in-depth crash database. The results show that the collision probability prediction model can effectively predict the risk of collisions between cyclists and vehicles with better accuracy than AEB systems using a fixed trigger threshold. This study is a valuable reference for the development of advanced vehicle collision avoidance systems to protect cyclists and other vulnerable road users.
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25. |
- Qian, Li-Bing, et al.
(författare)
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Transmission of electrons through the conical glass capillary with the grounded conducting outer surface
- 2017
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Ingår i: Wuli xuebao. - : Acta Physica Sinica, Chinese Physical Society and Institute of Physics, Chinese Academy of Sciences. - 1000-3290. ; 66:12
-
Tidskriftsartikel (refereegranskat)abstract
- The transmission of 1.5 keV-electrons through a conical glass capillary is reported. This study aims to understand the so-called guiding effect for the negatively charged particles (e.g. electrons). The guiding mechanism is understood quite well with positively charged particles in particular highly charged ions, but not clear with electrons, i. e., even the basic scheme mediated by the existence of negative charge patches to guide the electrons is still somewhat controversial.. The study of the charging-up dynamics causing the electrons transport inside the capillary will shed light on this issue. In order to perform this, a data acquisition system has been setup to follow the time evolution of the two-dimensional angular distribution of the transmitted electrons. The electrons are detected by the multi-channel plate (MCP) detector with a phosphor screen. The image from the phosphor screen is recorded by a charge-coupled device camera. The timing signals for the detected events are extracted from the back stack of the MCP detector and recorded by the data acquisition system, synchronized with the acquired images. The electron beam has a size of 0.5 mm x 0.5 mm and a divergence of less than 0.35.. The inner diameter of the straight part of the capillary is 1.2 mm and the exit diameter is 225 mu m. A small conducting aperture of 0.3 mm in diameter is placed at the entrance of the capillary. Two-dimensional angular distribution of the transmitted electrons through conical glass capillary and its time evolution are measured. The results show that the transmission rate decreases and reaches to a constant value for the completely discharged glass capillary with time going by. The centroid of the angular distribution moves to an asymptotic value while the width remains unchanged. These transmission characteristics are different from those indicated in our previous work (2016 Acta Phys: Si n: 65 204103). The difference originates from the different manipulations of the capillary outer surface. A conducting layer is coated on the outer surface of the capillary and grounded in this work. This isolates various discharge/charge channels and forms a new stable discharge channel. The transmission rate as a function of the tilt angle shows that the allowed transmission occurs at the tilt angle limited by the geometrical factors, i. e., the geometrical opening angle given by the aspect ratio as well as the beam divergence. The transmission characteristics suggest that most likely there are formed no negative patches to facilitate the electron transmission through the glass capillary at this selected beam energy. It is different from that of highly charged ions, where the formation of the charge patches prohibits the close collisions between the following ions and guides them out of the capillary.
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26. |
- 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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27. |
- Wen, Peter J., et al.
(författare)
-
Actin dynamics provides membrane tension to merge fusing vesicles into the plasma membrane
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Vesicle fusion is executed via formation of an Omega-shaped structure (Omega-profile), followed by closure (kiss-and-run) or merging of the Omega-profile into the plasma membrane (full fusion). Although Omega-profile closure limits release but recycles vesicles economically, Omega-profile merging facilitates release but couples to classical endocytosis for recycling. Despite its crucial role in determining exocytosis/endocytosis modes, how Omega-profile merging is mediated is poorly understood in endocrine cells and neurons containing small similar to 30-300 nm vesicles. Here, using confocal and super-resolution STED imaging, force measurements, pharmacology and gene knockout, we show that dynamic assembly of filamentous actin, involving ATP hydrolysis, N-WASP and formin, mediates Omega-profile merging by providing sufficient plasma membrane tension to shrink the Omega-profile in neuroendocrine chromaffin cells containing similar to 300 nm vesicles. Actin-directed compounds also induce Omega-profile accumulation at lamprey synaptic active zones, suggesting that actin may mediate Omega-profile merging at synapses. These results uncover molecular and biophysical mechanisms underlying Omega-profile merging.
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28. |
- Wen, Wanqing, et al.
(författare)
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Genome-wide association studies in East Asians identify new loci for waist-hip ratio and waist circumference
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Sixty genetic loci associated with abdominal obesity, measured by waist circumference (WC) and waist-hip ratio (WHR), have been previously identified, primarily from studies conducted in Europeanancestry populations. We conducted a meta-analysis of associations of abdominal obesity with approximately 2.5 million single nucleotide polymorphisms (SNPs) among 53,052 (for WC) and 48,312 (for WHR) individuals of Asian descent, and replicated 33 selected SNPs among 3,762 to 17,110 additional individuals. We identified four novel loci near the EFEMP1, ADAMTSL3, CNPY2, and GNAS genes that were associated with WC after adjustment for body mass index (BMI); two loci near the NID2 and HLA-DRB5 genes associated with WHR after adjustment for BMI, and three loci near the CEP120, TSC22D2, and SLC22A2 genes associated with WC without adjustment for BMI. Functional enrichment analyses revealed enrichment of corticotropin-releasing hormone signaling, GNRH signaling, and/or CDK5 signaling pathways for those newly-identified loci. Our study provides additional insight on genetic contribution to abdominal obesity.
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29. |
- Zhang, Guojie, et al.
(författare)
-
Comparative genomics reveals insights into avian genome evolution and adaptation
- 2014
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6215, s. 1311-1320
-
Tidskriftsartikel (refereegranskat)abstract
- Birds are the most species-rich class of tetrapod vertebrates and have wide relevance across many research fields. We explored bird macroevolution using full genomes from 48 avian species representing all major extant clades. The avian genome is principally characterized by its constrained size, which predominantly arose because of lineage-specific erosion of repetitive elements, large segmental deletions, and gene loss. Avian genomes furthermore show a remarkably high degree of evolutionary stasis at the levels of nucleotide sequence, gene synteny, and chromosomal structure. Despite this pattern of conservation, we detected many non-neutral evolutionary changes in protein-coding genes and noncoding regions. These analyses reveal that pan-avian genomic diversity covaries with adaptations to different lifestyles and convergent evolution of traits.
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30. |
- Zhang, Huai, et al.
(författare)
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A global survey on the use of the international classification of diseases codes for metabolic dysfunction-associated fatty liver disease.
- 2024
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Ingår i: Hepatology international. - 1936-0541.
-
Tidskriftsartikel (refereegranskat)abstract
- With the implementation of the 11th edition of the International Classification of Diseases (ICD-11) and the publication of the metabolic dysfunction-associated fatty liver disease (MAFLD) nomenclature in 2020, it is important to establish consensus for the coding of MAFLD in ICD-11. This will inform subsequent revisions of ICD-11.Using the Qualtrics XM and WJX platforms, questionnaires were sent online to MAFLD-ICD-11 coding collaborators, authors of papers, and relevant association members.A total of 890 international experts in various fields from 61 countries responded to the survey. We also achieved full coverage of provincial-level administrative regions in China. 77.1% of respondents agreed that MAFLD should be represented in ICD-11 by updating NAFLD, with no significant regional differences (77.3% in Asia and 76.6% in non-Asia, p=0.819). Over 80% of respondents agreed or somewhat agreed with the need to assign specific codes for progressive stages of MAFLD (i.e. steatohepatitis) (92.2%), MAFLD combined with comorbidities (84.1%), or MAFLD subtypes (i.e., lean, overweight/obese, and diabetic) (86.1%).This global survey by a collaborative panel of clinical, coding, health management and policy experts, indicates agreement that MAFLD should be coded in ICD-11. The data serves as a foundation for corresponding adjustments in the ICD-11 revision.
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31. |
- Abbafati, Cristiana, et al.
(författare)
-
- 2020
-
Tidskriftsartikel (refereegranskat)
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32. |
- Ai, Jin Wei, et al.
(författare)
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Clinical Characteristics of COVID-19 Patients With Gastrointestinal Symptoms : An Analysis of Seven Patients in China
- 2020
-
Ingår i: Frontiers in Medicine. - : Frontiers Media SA. - 2296-858X. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: Patients with novel coronavirus disease 2019 (COVID-19) can present with gastrointestinal symptoms as their initial symptoms or as the main manifestations during disease progression, but the clinical characteristics of these patients are still unknown. Methods: We identified COVID-19 patients who admitted to Xiangyang No. 1 People's Hospital and presented with gastrointestinal symptoms as their initial or main symptoms. Their medical records were reviewed by two independent clinical scientists. The epidemiological and clinical characteristics as well as the clinical outcomes were analyzed. Results: Among 142 confirmed COVID-19 cases, 7 (4.9%) of them presented with gastrointestinal symptoms. Three patients had gastrointestinal symptoms as the initial symptoms and chief complaints, and 4 patients as the main symptoms during disease progression. Six patients had symptoms of diarrhea (3–16 days), 7 with anorexia (7–22 days), 6 with upper abdominal discomfort (1–7 days), and 4 with nausea (1–7 days), 1 with heartburn lasting 2 days, and 2 with vomiting symptoms (1 day). The chest CT scan showed typical COVID-19 imaging features, and associated with the progression of the disease. During treatment, 2 patients died due to organ failure. Discussion: COVID-19 patients with gastrointestinal symptoms are relatively rare and might be misdiagnosed. The clinical features include watery stools, anorexia, and upper abdominal discomfort. These patients may have severe disease and be associated with a poor prognosis. The underlying mechanisms of SARS-CoV-2 related gastrointestinal symptoms need to clarify in future studies.
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33. |
- Ariyawansa, Hiran A., et al.
(författare)
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Fungal diversity notes 111–252—taxonomic and phylogenetic contributions to fungal taxa
- 2015
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Ingår i: Fungal diversity. - : Springer Science and Business Media LLC. - 1560-2745 .- 1878-9129. ; 75, s. 27-274
-
Tidskriftsartikel (refereegranskat)abstract
- This paper is a compilation of notes on 142 fungal taxa, including five new families, 20 new genera, and 100 new species, representing a wide taxonomic and geographic range. The new families, Ascocylindricaceae, Caryosporaceae and Wicklowiaceae (Ascomycota) are introduced based on their distinct lineages and unique morphology. The new Dothideomycete genera Pseudomassariosphaeria (Amniculicolaceae), Heracleicola, Neodidymella and P s e u d o m i c ros p h a e r i o p s i s ( D id y m e l l a c e a e ) , P s e u d o p i t h o m y c e s ( D i d y m o s p h a e r i a c e a e ) , Brunneoclavispora, Neolophiostoma and Sulcosporium (Halotthiaceae), Lophiohelichrysum (Lophiostomataceae), G a l l i i c o l a , Popul o c re s c e n t i a a nd Va g i c o l a (Phaeosphaeriaceae), Ascocylindrica (Ascocylindricaceae), E l o n g a t o p e d i c e l l a t a ( R o u s s o e l l a c e a e ) , Pseudoasteromassaria (Latoruaceae) and Pseudomonodictys (Macrodiplodiopsidaceae) are introduced. The newly described species of Dothideomycetes (Ascomycota) are Pseudomassariosphaeria bromicola (Amniculicolaceae), Flammeascoma lignicola (Anteagloniaceae), Ascocylindrica marina (Ascocylindricaceae) , Lembosia xyliae (Asterinaceae), Diplodia crataegicola and Diplodia galiicola ( B o t r yosphae r i a cea e ) , Caryospor a aquat i c a (Caryosporaceae), Heracleicola premilcurensis and Neodi dymell a thai landi cum (Didymellaceae) , Pseudopithomyces palmicola (Didymosphaeriaceae), Floricola viticola (Floricolaceae), Brunneoclavispora bambusae, Neolophiostoma pigmentatum and Sulcosporium thailandica (Halotthiaceae), Pseudoasteromassaria fagi (Latoruaceae), Keissleriella dactylidicola (Lentitheciaceae), Lophiohelichrysum helichrysi (Lophiostomataceae), Aquasubmersa japonica (Lophiotremataceae) , Pseudomonodictys tectonae (Macrodiplodiopsidaceae), Microthyrium buxicola and Tumidispora shoreae (Microthyriaceae), Alloleptosphaeria clematidis, Allophaeosphaer i a c y t i s i , Allophaeosphae r i a subcylindrospora, Dematiopleospora luzulae, Entodesmium artemisiae, Galiicola pseudophaeosphaeria, Loratospora(Basidiomycota) are introduced together with a new genus Neoantrodiella (Neoantrodiellaceae), here based on both morphology coupled with molecular data. In the class Agaricomycetes, Agaricus pseudolangei, Agaricus haematinus, Agaricus atrodiscus and Agaricus exilissimus (Agaricaceae) , Amanita m e l l e i a l b a , Amanita pseudosychnopyramis and Amanita subparvipantherina (Amanitaceae), Entoloma calabrum, Cora barbulata, Dictyonema gomezianum and Inocybe granulosa (Inocybaceae), Xerocomellus sarnarii (Boletaceae), Cantharellus eucalyptorum, Cantharellus nigrescens, Cantharellus tricolor and Cantharellus variabilicolor (Cantharellaceae), Cortinarius alboamarescens, Cortinarius brunneoalbus, Cortinarius ochroamarus, Cortinarius putorius and Cortinarius seidlii (Cortinariaceae), Hymenochaete micropora and Hymenochaete subporioides (Hymenochaetaceae), Xylodon ramicida (Schizoporaceae), Colospora andalasii (Polyporaceae), Russula guangxiensis and Russula hakkae (Russulaceae), Tremella dirinariae, Tremella graphidis and Tremella pyrenulae (Tremellaceae) are introduced. Four new combinations Neoantrodiella gypsea, Neoantrodiella thujae (Neoantrodiellaceae), Punctulariopsis cremeoalbida, Punctulariopsis efibulata (Punctulariaceae) are also introduced here for the division Basidiomycota. Furthermore Absidia caatinguensis, Absidia koreana and Gongronella koreana (Cunninghamellaceae), Mortierella pisiformis and Mortierella formosana (Mortierellaceae) are newly introduced in the Zygomycota, while Neocallimastix cameroonii and Piromyces irregularis (Neocallimastigaceae) ar e i n t roduced i n the Neocallimastigomycota. Reference specimens or changes in classification and notes are provided for Alternaria ethzedia, Cucurbitaria ephedricola, Austropleospora, Austropleospora archidendri, Byssosphaeria rhodomphala, Lophiostoma caulium, Pseudopithomyces maydicus, Massariosphaeria, Neomassariosphaeria and Pestalotiopsis montellica.
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34. |
- Arvidsson, Emma, et al.
(författare)
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Acoustic design of ordinary rooms using absorbers and diffusers
- 2020
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Ingår i: Proceedings of 2020 International Congress on Noise Control Engineering, INTER-NOISE 2020. - 9788994021362
-
Konferensbidrag (refereegranskat)abstract
- With different activities in a room, room acoustic requirements differ and when the acoustic requirements are different, acoustic treatment must be adapted. This study focuses on room acoustics in ordinary public rooms such as classrooms and offices. By tradition the acoustic treatment in these rooms is an absorbent ceiling. Experiments have been carried out in a classroom where the baseline in the acoustic treatment was a highly absorptive acoustic ceiling. This treatment has then been combined with different configurations of diffusers and wall absorbers where the coverage and pattern of the different treatments has been tested to evaluate their effect on the room acoustic parameters. Furthermore, several configurations with different diffuser directionality have been evaluated. The room acoustic parameters reverberation time, speech clarity and sound strength were assessed. The results show a clear correspondence in the room acoustic parameters for the different treatments used, as well as a frequency dependence. Here we discuss the interpretation of these results and how this new information can be used to obtain the room acoustic requirements for a specific activity.
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35. |
- Ballantyne, Kaye N., et al.
(författare)
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Toward Male Individualization with Rapidly Mutating Y-Chromosomal Short Tandem Repeats
- 2014
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Ingår i: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 35:8, s. 1021-1032
-
Tidskriftsartikel (refereegranskat)abstract
- Relevant for various areas of human genetics, Y-chromosomal short tandem repeats (Y-STRs) are commonly used for testing close paternal relationships among individuals and populations, and for male lineage identification. However, even the widely used 17-loci Yfiler set cannot resolve individuals and populations completely. Here, 52 centers generated quality-controlled data of 13 rapidly mutating (RM) Y-STRs in 14,644 related and unrelated males from 111 worldwide populations. Strikingly, greater than99% of the 12,272 unrelated males were completely individualized. Haplotype diversity was extremely high (global: 0.9999985, regional: 0.99836-0.9999988). Haplotype sharing between populations was almost absent except for six (0.05%) of the 12,156 haplotypes. Haplotype sharing within populations was generally rare (0.8% nonunique haplotypes), significantly lower in urban (0.9%) than rural (2.1%) and highest in endogamous groups (14.3%). Analysis of molecular variance revealed 99.98% of variation within populations, 0.018% among populations within groups, and 0.002% among groups. Of the 2,372 newly and 156 previously typed male relative pairs, 29% were differentiated including 27% of the 2,378 father-son pairs. Relative to Yfiler, haplotype diversity was increased in 86% of the populations tested and overall male relative differentiation was raised by 23.5%. Our study demonstrates the value of RMY-STRs in identifying and separating unrelated and related males and provides a reference database.
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36. |
- 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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37. |
- Björk, Petra, et al.
(författare)
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A novel conserved RNA-binding domain protein, RBD-1, is essential for ribosome biogenesis
- 2002
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Ingår i: Molecular Biology of the Cell. - 1059-1524 .- 1939-4586. ; 13:10, s. 3683-3695
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Tidskriftsartikel (refereegranskat)abstract
- Synthesis of the ribosomal subunits from pre-rRNA requires a large number of trans-acting proteins and small nucleolar ribonucleoprotein particles to execute base modifications, RNA cleavages, and structural rearrangements. We have characterized a novel protein, RNA-binding domain-1 (RBD-1), that is involved in ribosome biogenesis. This protein contains six consensus RNA-binding domains and is conserved as to sequence, domain organization, and cellular location from yeast to human. RBD-1 is essential in Caenorhabditis elegans. In the dipteran Chironomus tentans, RBD-1 (Ct-RBD-1) binds pre-rRNA in vitro and anti-Ct-RBD-1 antibodies repress pre-rRNA processing in vivo. Ct-RBD-1 is mainly located in the nucleolus in an RNA polymerase I transcription-dependent manner, but it is also present in discrete foci in the interchromatin and in the cytoplasm. In cytoplasmic extracts, 20-30% of Ct-RBD-1 is associated with ribosomes and, preferentially, with the 40S ribosomal subunit. Our data suggest that RBD-1 plays a role in structurally coordinating pre-rRNA during ribosome biogenesis and that this function is conserved in all eukaryotes.
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38. |
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39. |
- Chen, Geng, et al.
(författare)
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Experimental Test of the State Estimation-Reversal Tradeoff Relation in General Quantum Measurements
- 2014
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Ingår i: Physical Review X. - 2160-3308. ; 4:5, s. 021043-
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Tidskriftsartikel (refereegranskat)abstract
- When a measurement has limited strength, only partial information, regarding the initial state, is extracted, and, correspondingly, there is a probability to reverse its effect on the system and retrieve the original state. Recently, a clear and direct quantitative description of this complementary relationship, in terms of a tradeoff relation, was developed by Y. K. Cheong and S. W. Lee. [Phys. Rev. Lett. 109, 150402 (2012)]. Here, this tradeoff relation is experimentally verified using polarization-encoded single photons from a quantum dot. Measurement operators representing a complete range, from not affecting the system to a projection to a single polarization state, are realized. In addition, for each measurement operator, an optimal reversal operator is also implemented. The upper bound of the tradeoff relation is mapped to experimental parameters representing the measurement strength. Our results complement the theoretical work and provide a hands-on characterization of general quantum measurements.
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40. |
- Chen, Jiajia, et al.
(författare)
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Characterization of Longitudinal Thermal Conductivity of Graphene Film
- 2021
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Ingår i: 2021 22nd International Conference on Electronic Packaging Technology, ICEPT 2021.
-
Konferensbidrag (refereegranskat)abstract
- The chase of high performance by chip manufacturers has greatly increased the power consumption of integrated circuits, which brings great challenges to the heat dissipation of electronics systems. It has also slowed down following up of the Moore's Law, and it is expected to hit the wall soon [1]. Graphene film with high in-plane thermal conductivity is one of the key materials to make it possible for electronics industry to continue to follow the Moore's Law. However, there are few studies focusing on the longitudinal thermal conductivity of graphene films. The purpose of this study is to investigate the longitudinal thermal conductivity of graphene films according to ASTM D5470 [2]. The results show that the longitudinal thermal conductivity of the pressed graphene film is greater than that of the unpressurized graphene film. The longitudinal thermal conductivity is 10.6 W/m· K for the unpressurized graphene film and 20.6 W/m· K for the pressed graphene film.
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41. |
- Chen, Shi-Peng, et al.
(författare)
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Guanidine-based protic ionic liquids as highly efficient intermolecular scissors for dissolving natural cellulose
- 2023
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Ingår i: Green Chemistry. - : Royal Society of Chemistry. - 1463-9262 .- 1463-9270. ; 25:22, s. 9322-9334
-
Tidskriftsartikel (refereegranskat)abstract
- The development of highly efficient and environmentally friendly solvents for dissolving cellulose, which is the most abundant natural polymer on Earth, remains a challenge, hindering its full utilization. Herein, a green protic ionic liquid, 1,1,3,3-tetramethylguanidinium methoxyacetate ([TMGH][MAA]), was found to exhibit attractive capacity to dissolve natural cellulose with an appropriate TMG/MAA molar ratio of 7 : 3 at 80 degrees C. The solubility of cotton linter and ultra-high molecular weight cotton fibers reached 13% (w/w) and 3% (w/w), respectively, surpassing that of most solvent systems currently used for the dissolution of cellulose. The experimental and simulation results verified that the excellent dissolution ability of [TMGH][MAA] for cellulose is mainly attributed to the destruction of the intrinsic hydrogen-bond networks in cellulose by the synergistic interactions of the [TMGH] cations and [MAA] anions with the hydroxyl groups in the cellulose chains, acting as highly efficient "intermolecular scissors". The superiority of this novel dissolution system was further demonstrated by the remarkable comprehensive properties of the regenerated cellulose film including satisfactory thermostability, high transparency, and excellent mechanical properties. Furthermore, the satisfactory recovery performance of this solvent highlights its significant feasibility for large-scale industrial manufacturing. The proposed [TMGH][MAA] in this study exhibits great potential as a next-generation processing solvent for dissolving, and thus processing cellulose, promoting the sustainable development of high-value-added cellulose materials.
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42. |
- Chen, Zhuo, et al.
(författare)
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Large mechanical properties enhancement in ceramics through vacancy-mediated unit cell disturbance
- 2023
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Tailoring vacancies is a feasible way to improve the mechanical properties of ceramics. However, high concentrations of vacancies usually compromise the strength (or hardness). We show that a high elasticity and flexural strength could be achieved simultaneously using a nitride superlattice architecture with disordered anion vacancies up to 50%. Enhanced mechanical properties primarily result from a distinctive deformation mechanism in superlattice ceramics, i.e., unit-cell disturbances. Such a disturbance substantially relieves local high-stress concentration, thus enhancing deformability. No dislocation activity involved also rationalizes its high strength. The work renders a unique understanding of the deformation and strengthening/toughening mechanism in nitride ceramics.
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43. |
- Cho, Daeheum, et al.
(författare)
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Imaging of transition charge densities involving carbon core excitations by all X-ray sum-frequency generation
- 2019
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Ingår i: Philosophical Transactions. Series A. - : The Royal Society. - 1364-503X .- 1471-2962. ; 377:2145
-
Tidskriftsartikel (refereegranskat)abstract
- X-ray diffraction signals from the time-evolving molecular charge density induced by selective core excitation of chemically inequivalent carbon atoms are calculated. A narrowband X-ray pulse selectively excites the carbon K-edge of the –CH3 or –CH2F groups in fluoroethane (CH3–CH2F). Each excitation creates a distinct core coherence which depends on the character of the electronic transition. Direct propagation of the reduced single-electron density matrix, using real-time time-dependent density functional theory, provides the time-evolving charge density following interactions with external fields. The interplay between partially filled valence molecular orbitals upon core excitation induces characteristic femtosecond charge migration which depends on the core–valence coherence, and is monitored by the sum-frequency generation diffraction signal.
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44. |
- de Jong, R. S., et al.
(författare)
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4MOST : Project overview and information for the First Call for Proposals
- 2019
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Ingår i: The Messenger. - : European Southern Observatory. - 0722-6691. ; 175, s. 3-11
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- We introduce the 4-metre Multi-Object Spectroscopic Telescope (4MOST), a new high-multiplex, wide-field spectroscopic survey facility under development for the four-metre-class Visible and Infrared Survey Telescope for Astronomy (VISTA) at Paranal. Its key specifications are: a large field of view (FoV) of 4.2 square degrees and a high multiplex capability, with 1624 fibres feeding two low-resolution spectrographs (R = λ/Δλ ~ 6500), and 812 fibres transferring light to the high-resolution spectrograph (R ~ 20 000). After a description of the instrument and its expected performance, a short overview is given of its operational scheme and planned 4MOST Consortium science; these aspects are covered in more detail in other articles in this edition of The Messenger. Finally, the processes, schedules, and policies concerning the selection of ESO Community Surveys are presented, commencing with a singular opportunity to submit Letters of Intent for Public Surveys during the first five years of 4MOST operations.
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45. |
- Du, Lei, et al.
(författare)
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Giant Atoms in a Synthetic Frequency Dimension
- 2022
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Ingår i: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 128:22
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Tidskriftsartikel (refereegranskat)abstract
- Giant atoms that interact with real-space waveguides at multiple spatial points have attracted extensive attention due to their unique interference effects. Here we propose a feasible scheme for constructing giant atoms in a synthetic frequency dimension with, e.g., a dynamically modulated superconducting resonator and a tailored three-level artificial atom. Both analytical and numerical calculations show good agreement between our scheme and real-space two-level giant atoms. In particular, the symmetry of the model in momentum space can be broken by tuning the phase of the external field applied on the atom, enabling chiral interactions between the atom and the frequency lattice. We further demonstrate the possibility of simulating cascaded interaction and directional excitation transfer in the frequency dimension by directly extending our model to involve more such effective giant atoms.
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46. |
- Fan, Jin, et al.
(författare)
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Investigation of ultra-wideband Bowtie antennas for phased array feed application
- 2020
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Ingår i: International Journal of RF and Microwave Computer-Aided Engineering. - : Hindawi Limited. - 1096-4290 .- 1099-047X. ; 30:11
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Tidskriftsartikel (refereegranskat)abstract
- In this article, two new ultra-wideband (UWB) dual-polarized Bowtie antennas are investigated as the elements for a phased array feed for reflectors. In addition to its UWB impedance matching characteristic, the Bowtie antennas have stable large beam-width and a low cross-polar level over a wide frequency band with a compact size, which is an essence for phased array applications. The simulated and measured results state a low ohmic loss, good impedance matching (S11 below −15 dB) and good radiation performance, with a simple structure for easy manufacturing. The proposed antennas can be good candidates for phased array feed (PAF) in FAST and the SKA (square kilometer array) pathfinder PHAROS2 projects, and massive MIMO antennas in wireless communication systems.
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47. |
- Forssén, Jens, 1968, et al.
(författare)
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Toolbox from the EC FP7 HOSANNA project for the reduction of road and rail traffic noise in the outdoor environment
- 2014
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Ingår i: Transport Research Arena 2014, Paris, France. ; , s. 10-
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Konferensbidrag (refereegranskat)abstract
- This paper offers a brief overview of innovative methods for road and rail traffic noise reduction between sourceand receiver. These include using new barrier designs, planting of trees, treatments of ground and road surfacesand greening of building façades and roofs using natural materials, like vegetation, soil and other substrates incombination with recycled materials and artificial elements. The abatements are assessed in terms of numericallypredicted sound level reductions, perceptual effects and cost–benefit analysis. Useful reductions of noise fromurban roads and tramways are predicted for 1-m-high urban noise barriers and these are increased by addinginter-lane barriers. A 3 m wide 0.3 m high lattice ground treatment, a carefully planted 15-m-wide tree belt andreplacing 50 m of paved areas by grassland are predicted to give similar reductions. Tree belts are shown to bevery cost-effective and combining tall barriers with a row of trees reduces the negative impact of wind. Greenroofs may significantly reduce the noise at the quiet side of buildings.
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48. |
- Forssén, Jens, 1968, et al.
(författare)
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Åtgärder i utomhusmiljön för att minska buller från väg- och tågtrafik – resultat från EU-projektet HOSANNA
- 2013
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Ingår i: LjudBladet, Svenska akustiska sällskapet. - 1403-2317. ; 3, s. 16-28
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Denna artikel ger en kort översikt av bulleråtgärder, resulterande från EU-projektet HOSANNA, för minskning av buller från väg- och spårtrafik under ljudets utbredning. Dessa verktyg inkluderar användning av ny skärmdesign, plantering av träd, förbättringar av mark- och vägytor samt vegetation på byggnadsfasader och tak, med hjälp av naturmaterial, såsom vegetation, jord och andra substrat i kombination med återvunnet material och artificiella element. De akustiska insättningsdämpningarna bedöms genom numeriska beräkningar, perceptuella effekter och kostnadsnyttoanalys. En betydande minskning av buller från väg- och spårtrafik förutsägs för ett 1-m-högt urbant bullerskydd. Detta kan förbättras, upp till ca 10 dB insättningsdämpning, genom att placera ytterligare skydd mellan körfälten. Ett 3 m brett och 0,3 m högt rutnät, ett omsorgsfullt planterat 15 m brett trädbälte samt att ersätta 50 meter asfalterad mark med gräsmark förutspås ge bullerminskningar om 5–8 dB, medan användning av fasadvegetation och gröna tak kan minska nivån på innergårdar med upp till ca 4 respektive 7 dB. Trädbälten visar sig vara mycket kostnadseffektiva och kombinationer av höga skärmar med en rad av träd minskar de negativa effekterna av vind på bullerskärmars insättningsdämpning. Gröna tak kan minska bullret på den tysta sidan av byggnader.
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49. |
- Gong, Xinjian, et al.
(författare)
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Fabrication and Characterization of Graphene/polyimide Composite Film
- 2021
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Ingår i: 2021 23rd European Microelectronics and Packaging Conference and Exhibition, EMPC 2021.
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Konferensbidrag (refereegranskat)abstract
- A flexible graphene and polyimide composite film was designed and fabricated in this study. A polyimide solution was used as an adhesive layer to connect graphene film and polyimide film by hot-pressing. Laser flash thermal analysis method was carried out to evaluate the thermal diffusion coefficient of different thicknesses of the fabricated films at various temperatures. Bending test was carried out to evaluate the stability and reliability of the composite film. Scanning electron microscopy was applied to characterize the cross-section of the composite film before and after the peel test. IR imaging was employed to compare the heat diffusion of the composite film and traditional flexible copper clad laminate. The results show that the composite film has significantly better thermal diffusion capacity than traditional flexible copper clad laminate.
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50. |
- Gorski, Mathias, et al.
(författare)
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1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function.
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- HapMap imputed genome-wide association studies (GWAS) have revealed >50 loci at which common variants with minor allele frequency >5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-analysis of kidney function based on the estimated glomerular filtration rate (eGFR) in 110,517 European ancestry participants using 1000 Genomes imputed data. We identified 10 novel loci with p-value < 5 × 10(-8) previously missed by HapMap-based GWAS. Six of these loci (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SNPs unique to the 1000 Genomes reference panel. Using pathway analysis, we identified 39 significant (FDR < 0.05) genes and 127 significantly (FDR < 0.05) enriched gene sets, which were missed by our previous analyses. Among those, the 10 identified novel genes are part of pathways of kidney development, carbohydrate metabolism, cardiac septum development and glucose metabolism. These results highlight the utility of re-imputing from denser reference panels, until whole-genome sequencing becomes feasible in large samples.
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