| 1. |
- Ramdas, S., et al.
(author)
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A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
- 2022
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 109:8, s. 1366-1387
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Journal article (peer-reviewed)abstract
- A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
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| 2. |
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| 5. |
- He, J., et al.
(author)
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Development and Evaluation of an Ensemble-Based Data Assimilation System for Regional Reanalysis Over the Tibetan Plateau and Surrounding Regions
- 2019
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In: Journal of Advances in Modeling Earth Systems. - 1942-2466. ; 11:8, s. 2503-2522
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Journal article (peer-reviewed)abstract
- The Tibetan Plateau is regarded as the Earth's Third Pole, which is the source region of several major rivers that impact more 20% the world population. This high‐altitude region is reported to have been undergoing much greater rate of weather changes under global warming, but the existing reanalysis products are inadequate for depicting the state of the atmosphere, particularly with regard to the amount of precipitation and its diurnal cycle. An ensemble Kalman filter (EnKF) data assimilation system based on the limited‐area Weather Research and Forecasting (WRF) model was evaluated for use in developing a regional reanalysis over the Tibetan Plateau and the surrounding regions. A 3‐month prototype reanalysis over the summer months (June−August) of 2015 using WRF‐EnKF at a 30‐km grid spacing to assimilate nonradiance observations from the Global Telecommunications System was developed and evaluated against independent sounding and satellite observations in comparison to the ERA‐Interim and fifth European Centre for Medium‐Range Weather Forecasts Reanalysis (ERA5) global reanalysis. Results showed that both the posterior analysis and the subsequent 6‐ to 12‐hr WRF forecasts of the prototype regional reanalysis compared favorably with independent sounding observations, satellite‐based precipitation versus those from ERA‐Interim and ERA5 during the same period. In particular, the prototype regional reanalysis had clear advantages over the global reanalyses of ERA‐Interim and ERA5 in the analysis accuracy of atmospheric humidity, as well as in the subsequent downscale‐simulated precipitation intensity, spatial distribution, diurnal evolution, and extreme occurrence.
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| 6. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)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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| 7. |
- Zhou, Y., et al.
(author)
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Roles of miRNAs in microcystin-LR-induced Sertoli cell toxicity
- 2015
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In: Toxicology and Applied Pharmacology. - : Elsevier BV. - 0041-008X .- 1096-0333. ; 287:1, s. 1-8
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Journal article (peer-reviewed)abstract
- Microcystin (MC)-LR, a cyclic heptapeptide, is a potent reproductive system toxin. To understand the molecular mechanisms of MC-induced reproductive system cytotoxicity, we evaluated global changes of miRNA and mRNA expression in mouse Sertoli cells following MC-LR treatment. Our results revealed that the exposure to MC-LR resulted in an altered miRNA expression profile that might be responsible for the modulation of mRNA expression. Bio-functional analysis indicated that the altered genes were involved in specific cellular processes, including cell death and proliferation. Target gene analysis suggested that junction injury in Sertoli cells exposed to MC-LR might be mediated by miRNAs through the regulation of the Sertoli cell-Sertoli cell pathway. Collectively, these findings may enhance our understanding on the modes of action of MC-LR on mouse Sertoli cells as well as the molecular mechanisms underlying the toxicity of MC-LR on the male reproductive system. (C) 2015 Elsevier Inc. All rights reserved.
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| 8. |
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- 2019
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Journal article (peer-reviewed)
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| 9. |
- Aartsen, M. G., et al.
(author)
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Multiwavelength follow-up of a rare IceCube neutrino multiplet
- 2017
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In: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 607
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Journal article (peer-reviewed)abstract
- On February 17, 2016, the IceCube real-time neutrino search identified, for the first time, three muon neutrino candidates arriving within 100 s of one another, consistent with coming from the same point in the sky. Such a triplet is expected once every 13.7 years as a random coincidence of background events. However, considering the lifetime of the follow-up program the probability of detecting at least one triplet from atmospheric background is 32%. Follow-up observatories were notified in order to search for an electromagnetic counterpart. Observations were obtained by Swift's X-ray telescope, by ASAS-SN, LCO and MASTER at optical wavelengths, and by VERITAS in the very-high-energy gamma-ray regime. Moreover, the Swift BAT serendipitously observed the location 100 s after the first neutrino was detected, and data from the Fermi LAT and HAWC observatory were analyzed. We present details of the neutrino triplet and the follow-up observations. No likely electromagnetic counterpart was detected, and we discuss the implications of these constraints on candidate neutrino sources such as gamma-ray bursts, core-collapse supernovae and active galactic nucleus flares. This study illustrates the potential of and challenges for future follow-up campaigns.
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| 10. |
- An, Junghwa, et al.
(author)
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Permanent Genetic Resources added to Molecular Ecology Resources Database 1 October 2009-30 November 2009
- 2010
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In: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:2, s. 404-408
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Journal article (peer-reviewed)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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| 11. |
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| 17. |
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| 18. |
- Sun, XT, et al.
(author)
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Inflammatory cell-derived CXCL3 promotes pancreatic cancer metastasis through a novel myofibroblast-hijacked cancer escape mechanism
- 2022
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In: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 71:1, s. 129-147
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Journal article (peer-reviewed)abstract
- Pancreatic ductal adenocarcinoma (PDAC) is the most lethal malignancy and lacks effective treatment. We aimed to understand molecular mechanisms of the intertwined interactions between tumour stromal components in metastasis and to provide a new paradigm for PDAC therapy.DesignTwo unselected cohorts of 154 and 20 patients with PDAC were subjected to correlation between interleukin (IL)-33 and CXCL3 levels and survivals. Unbiased expression profiling, and genetic and pharmacological gain-of-function and loss-of-function approaches were employed to identify molecular signalling in tumour-associated macrophages (TAMs) and myofibroblastic cancer-associated fibroblasts (myoCAFs). The role of the IL-33–ST2–CXCL3–CXCR2 axis in PDAC metastasis was evaluated in three clinically relevant mouse PDAC models.ResultsIL-33 was specifically elevated in human PDACs and positively correlated with tumour inflammation in human patients with PDAC. CXCL3 was highly upregulated in IL-33-stimulated macrophages that were the primary source of CXCL3. CXCL3 was correlated with poor survival in human patients with PDAC. Mechanistically, activation of the IL-33–ST2–MYC pathway attributed to high CXCL3 production. The highest level of CXCL3 was found in PDAC relative to other cancer types and its receptor CXCR2 was almost exclusively expressed in CAFs. Activation of CXCR2 by CXCL3 induced a CAF-to-myoCAF transition and α-smooth muscle actin (α-SMA) was uniquely upregulated by the CXCL3–CXCR2 signalling. Type III collagen was identified as the CXCL3–CXCR2-targeted adhesive molecule responsible for myoCAF-driven PDAC metastasis.ConclusionsOur work provides novel mechanistic insights into understanding PDAC metastasis by the TAM-CAF interaction and targeting each of these signalling components would provide an attractive and new paradigm for treating pancreatic cancer.
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| 19. |
- Wang, Z., et al.
(author)
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Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention
- 2022
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 54:9, s. 1332-1344
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Journal article (peer-reviewed)abstract
- Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention. Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits.
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| 20. |
- Abdo, A. A., et al.
(author)
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Multi-wavelength observations of the flaring gamma-ray blazar 3C 66A in 2008 October
- 2011
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 726:1, s. 43-
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Journal article (peer-reviewed)abstract
- The BL Lacertae object 3C 66A was detected in a flaring state by the Fermi Large Area Telescope (LAT) and VERITAS in 2008 October. In addition to these gamma-ray observations, F-GAMMA, GASP-WEBT, PAIRITEL, MDM, ATOM, Swift, and Chandra provided radio to X-ray coverage. The available light curves show variability and, in particular, correlated flares are observed in the optical and Fermi-LAT gamma-ray band. The resulting spectral energy distribution can be well fitted using standard leptonic models with and without an external radiation field for inverse Compton scattering. It is found, however, that only the model with an external radiation field can accommodate the intra-night variability observed at optical wavelengths.
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| 21. |
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| 22. |
- Aliu, E., et al.
(author)
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Multiwavelength Observations of the Previously Unidentified Blazar RX J0648.7+1516
- 2011
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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 742:2
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Journal article (peer-reviewed)abstract
- We report on the VERITAS discovery of very high energy (VHE) gamma-ray emission above 200 GeV from the high-frequency-peaked BL Lac (HBL) object RX J0648.7+1516 (GB J0648+1516), associated with 1FGL J0648.8+1516. The photon spectrum above 200 GeV is fitted by a power law dN/dE = F 0(E/E 0)–Γ with a photon index Γ of 4.4 ± 0.8stat ± 0.3syst and a flux normalization F 0 of (2.3 ± 0.5stat ± 1.2sys) × 10–11 TeV–1 cm–2 s–1 with E 0 = 300 GeV. No VHE variability is detected during VERITAS observations of RX J0648.7+1516 between 2010 March 4 and April 15. Following the VHE discovery, the optical identification and spectroscopic redshift were obtained using the Shane 3 m Telescope at the Lick Observatory, showing the unidentified object to be a BL Lac type with a redshift of z = 0.179. Broadband multiwavelength observations contemporaneous with the VERITAS exposure period can be used to subclassify the blazar as an HBL object, including data from the MDM observatory, Swift-UVOT, and X-Ray Telescope, and continuous monitoring at photon energies above 1 GeV from the FermiLarge Area Telescope (LAT). We find that in the absence of undetected, high-energy rapid variability, the one-zone synchrotron self-Compton (SSC) model overproduces the high-energy gamma-ray emission measured by the Fermi-LAT over 2.3 years. The spectral energy distribution can be parameterized satisfactorily with an external-Compton or lepto-hadronic model, which have two and six additional free parameters, respectively, compared to the one-zone SSC model.
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| 27. |
- Leong, D. P., et al.
(author)
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Reference ranges of handgrip strength from 125,462 healthy adults in 21 countries: a prospective urban rural epidemiologic (PURE) study
- 2016
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In: Journal of cachexia, sarcopenia and muscle. - : Wiley. - 2190-5991 .- 2190-5991. ; 7:5, s. 535-546
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Journal article (peer-reviewed)abstract
- BACKGROUND: The measurement of handgrip strength (HGS) has prognostic value with respect to all-cause mortality, cardiovascular mortality and cardiovascular disease, and is an important part of the evaluation of frailty. Published reference ranges for HGS are mostly derived from Caucasian populations in high-income countries. There is a paucity of information on normative HGS values in non-Caucasian populations from low- or middle-income countries. The objective of this study was to develop reference HGS ranges for healthy adults from a broad range of ethnicities and socioeconomically diverse geographic regions. METHODS: HGS was measured using a Jamar dynamometer in 125,462 healthy adults aged 35-70 years from 21 countries in the Prospective Urban Rural Epidemiology (PURE) study. RESULTS: HGS values differed among individuals from different geographic regions. HGS values were highest among those from Europe/North America, lowest among those from South Asia, South East Asia and Africa, and intermediate among those from China, South America, and the Middle East. Reference ranges stratified by geographic region, age, and sex are presented. These ranges varied from a median (25th-75th percentile) 50 kg (43-56 kg) in men <40 years from Europe/North America to 18 kg (14-20 kg) in women >60 years from South East Asia. Reference ranges by ethnicity and body-mass index are also reported. CONCLUSIONS: Individual HGS measurements should be interpreted using region/ethnic-specific reference ranges.
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| 28. |
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| 29. |
- Liu, X M, et al.
(author)
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A tool for evaluating the quality of laminated particleboard countertop
- 2016
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In: Wood and Fiber Science. - 0735-6161. ; 48:4, s. 297-301
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Journal article (peer-reviewed)abstract
- To evaluate the quality of laminated particleboard, a typical type of laminate was used in laminating particleboard with operational parameters similar to industry operation. Pull-off tests using Elcometer 510 were conducted. In addition, panel vertical density profiles (VDP) and the pH of particleboard at different layers were tested. The results showed that the laminated panel bonded by polyvinyl acetate (PVA) glue had higher pull-off strength than that of the phenol formaldehyde (PF) glue within corresponding sanding thickness. Sanding off 0.0762 mm resulted in higher pull-off strength than sanding off 0.0254 mm. The laminates had the highest pull-off strength when the PB were sanded off 0.0762 mm and glued by PVA. This has provided a solution to improve lamination pull-of strength for industry. The test results have also shown that the laminated panels produced in the manufactures have the potential to be improved. It also indicates that Elcometer 510 is a good tool to evaluate the particleboard lamination quality.
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| 30. |
- Mascher, Martin, et al.
(author)
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A chromosome conformation capture ordered sequence of the barley genome
- 2017
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 544:7651, s. 427-433
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Journal article (peer-reviewed)abstract
- Cereal grasses of the Triticeae tribe have been the major food source in temperate regions since the dawn of agriculture. Their large genomes are characterized by a high content of repetitive elements and large pericentromeric regions that are virtually devoid of meiotic recombination. Here we present a high-quality reference genome assembly for barley (Hordeum vulgare L.). We use chromosome conformation capture mapping to derive the linear order of sequences across the pericentromeric space and to investigate the spatial organization of chromatin in the nucleus at megabase resolution. The composition of genes and repetitive elements differs between distal and proximal regions. Gene family analyses reveal lineage-specific duplications of genes involved in the transport of nutrients to developing seeds and the mobilization of carbohydrates in grains. We demonstrate the importance of the barley reference sequence for breeding by inspecting the genomic partitioning of sequence variation in modern elite germplasm, highlighting regions vulnerable to genetic erosion.
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| 31. |
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| 32. |
- Miller, V., et al.
(author)
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Availability, affordability, and consumption of fruits and vegetables in 18 countries across income levels: findings from the Prospective Urban Rural Epidemiology (PURE) study
- 2016
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In: Lancet Global Health. - : Elsevier BV. - 2214-109X. ; 4:10
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Journal article (peer-reviewed)abstract
- Background Several international guidelines recommend the consumption of two servings of fruits and three servings of vegetables per day, but their intake is thought to be low worldwide. We aimed to determine the extent to which such low intake is related to availability and affordability. Methods We assessed fruit and vegetable consumption using data from country-specific, validated semi-quantitative food frequency questionnaires in the Prospective Urban Rural Epidemiology (PURE) study, which enrolled participants from communities in 18 countries between Jan 1, 2003, and Dec 31, 2013. We documented household income data from participants in these communities; we also recorded the diversity and non-sale prices of fruits and vegetables from grocery stores and market places between Jan 1, 2009, and Dec 31, 2013. We determined the cost of fruits and vegetables relative to income per household member. Linear random effects models, adjusting for the clustering of households within communities, were used to assess mean fruit and vegetable intake by their relative cost. Findings Of 143 305 participants who reported plausible energy intake in the food frequency questionnaire, mean fruit and vegetable intake was 3.76 servings (95% CI 3.66-3.86) per day. Mean daily consumption was 2.14 servings (1.93-2.36) in low-income countries (LICs), 3.17 servings (2.99-3.35) in lower-middle-income countries (LMICs), 4.31 servings (4.09-4.53) in upper-middle-income countries (UMICs), and 5.42 servings (5.13-5.71) in high-income countries (HICs). In 130 402 participants who had household income data available, the cost of two servings of fruits and three servings of vegetables per day per individual accounted for 51.97% (95% CI 46.06-57.88) of household income in LICs, 18.10% (14.53-21.68) in LMICs, 15.87% (11.51-20.23) in UMICs, and 1.85% (-3.90 to 7.59) in HICs (p(trend) = 0.0001). In all regions, a higher percentage of income to meet the guidelines was required in rural areas than in urban areas (p<0.0001 for each pairwise comparison). Fruit and vegetable consumption among individuals decreased as the relative cost increased (p(trend) = 0.00040). Interpretation The consumption of fruit and vegetables is low worldwide, particularly in LICs, and this is associated with low aff ordability. Policies worldwide should enhance the availability and aff ordability of fruits and vegetables.
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| 33. |
- Qu, L. X., et al.
(author)
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Quantitative numerical analysis of flow past a circular cylinder at Reynolds number between 50 and 200
- 2013
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In: Journal of Fluids and Structures. - : Elsevier BV. - 1095-8622 .- 0889-9746. ; 39, s. 347-370
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Journal article (peer-reviewed)abstract
- Results of numerical simulations are presented for flow past a stationary circular cylinder at low Reynolds numbers (Re=50-200). The simulations were carried out using a finite-volume code employing a fractional step method with second-order accuracy in both space and time. A sensitivity study on numerical parameters concerning the domain size, grid independence and time step resolution was carried out in detail for Re=100. Global time-averaged results on force coefficients, non-dimensional velocities and pressures, including their corresponding r.m.s. values, as well as various quantities related to the separation and vortex shedding characteristics are presented. A non-monotonous streamwise velocity recovery in the intermediate wake is observed for Re > 50, a phenomenon that has been grossly overlooked in the past. There are two plateaus along the wake centerline, in particular for Re=200. The first, which is the most distinct, ranges from about x=9 to x=16 at a wake deficit velocity of 0.38, x being counted in diameters behind the cylinder axis; the second one appears from x=25 to x=28 at a wake deficit velocity of 0.54. This phenomenon seems to be related to an associated change-over in the orientation of the von Karman vortices and the merging trends, especially for Re=200 beyond x=25, as observed from instantaneous vorticity fields. Three-dimensional simulations using spanwise lengths of 10 and 12 (diameters) were carried out at Re=200. After a long initial phase with regular three-dimensional mode A flow features increasing very slowly in amplitude, the flow went into a state with distinct pulsating forces acting on the cylinder, the pulsations being seemingly randomly localized across the cylinder span. In this second, much more chaotic, flow state, the time-averaged results were in agreement with previous experiments and with parts of previous numerical studies.
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| 34. |
- Shrine, N, et al.
(author)
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Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk
- 2023
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 55:3, s. 410-
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Journal article (peer-reviewed)abstract
- Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.
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| 35. |
- Slättberg, Nils, et al.
(author)
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Spatial and temporal patterns of planetary boundary layer height during 1979-2018 over the Tibetan Plateau using ERA5
- 2022
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In: International Journal of Climatology. - : Wiley. - 0899-8418 .- 1097-0088. ; 42:6, s. 3360-3377
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Journal article (peer-reviewed)abstract
- Planetary boundary layer height (PBLH) is a key meteorological parameter that is affected by and influences exchanges of energy, momentum, and mass between the surface and the atmosphere, but there are few comprehensive studies on the PBLH climatology over the Tibetan Plateau (TP). This study presents a multi-decadal climatology of PBLH over the TP by using high-resolution reanalysis data (ERA5) for the period 1979-2018. The ERA5 PBLH was first evaluated against radiosonde-derived PBLH from four sites. For most of the observation periods and sites, ERA5 captured the diurnal cycles reasonably well, although the highest peaks in the radiosonde-derived PBLH were often not captured. Next, long-term means and trends, seasonality and diurnal cycles of the PBLHs were examined. The results show that average PBLHs in the central and southwestern TP are higher than those in the west and east. On an interannual time scale, the PBLH is positively correlated with the North Atlantic Oscillation in western and southeastern TP in winter, eastern TP in summer, and central TP in autumn, while a negative correlation is seen for northeastern TP in winter. The summertime PBLH in the central and southwestern TP is negatively correlated to the Indian summer monsoon. As for the seasonal cycle, the PBLH in the western TP reaches its peak in August, while the PBLH in the eastern TP exhibits an earlier summer peak in June. In the central TP, the PBLH is the highest in April and displays a minimum during summer, corresponding to a precipitation peak and a dip in surface sensible heat flux. The climatological diurnal cycles of PBLH are generally affected by the insolation and reach their peaks in the afternoon when a large range in PBLH variation is also found.
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| 36. |
- Veres, P., et al.
(author)
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Observation of inverse Compton emission from a long gamma-ray burst
- 2019
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In: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 575:7783, s. 459-
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Journal article (peer-reviewed)abstract
- Long-duration gamma-ray bursts (GRBs) originate from ultra-relativistic jets launched from the collapsing cores of dying massive stars. They are characterized by an initial phase of bright and highly variable radiation in the kiloelectron volt-to-mega electronvoltband, which is probably produced within the jet and lasts from milliseconds to minutes, known as the prompt emission(1,2). Subsequently, the interaction of the jet with the surrounding medium generates shock waves that are responsible for the afterglow emission, which lasts from days to months and occurs over a broad energy range from the radio to the gigaelectronvolt bands(1-6). The afterglow emission is generally well explained as synchrotron radiation emitted by electrons accelerated by the external shock(7-9). Recently, intense long-lasting emission between 0.2 and 1 teraelectronvolts was observed from GRB 190114C(10,11). Here we report multifrequency observations of GRB 190114C, and study the evolution in time of the GRB emission across 17 orders of magnitude in energy, from 5 x 10(-6) to 10(12) electronvolts. We find that the broadband spectral energy distribution is double-peaked, with the teraelectronvolt emission constituting a distinct spectral component with power comparable to the synchrotron component. This component is associated with the afterglow and is satisfactorily explained by inverse Compton up-scattering of synchrotron photons by high-energy electrons. We find that the conditions required to account for the observed teraelectronvolt component are typical for GRBs, supporting the possibility that inverse Compton emission is commonly produced in GRBs.
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| 37. |
- Wang, Fang, et al.
(author)
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Emerging contaminants: A One Health perspective
- 2024
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In: Innovation. - 2666-6758. ; 5
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Research review (peer-reviewed)abstract
- Environmental pollution is escalating due to rapid global development that often prioritizes human needs over planetary health. Despite global efforts to mitigate legacy pollutants, the continuous introduction of new substances remains a major threat to both people and the planet. In response, global initiatives are focusing on risk assessment and regulation of emerging contaminants, as demonstrated by the ongoing efforts to establish the UN's Intergovernmental Science-Policy Panel on Chemicals, Waste, and Pollution Prevention. This review identifies the sources and impacts of emerging contaminants on planetary health, emphasizing the importance of adopting a One Health approach. Strategies for monitoring and addressing these pollutants are discussed, underscoring the need for robust and socially equitable environmental policies at both regional and international levels. Urgent actions are needed to transition toward sustainable pollution management practices to safeguard our planet for future generations.
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- Zhang, Hui, et al.
(author)
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The impact of a three-phase video-assisted debriefing on nursing students debriefing experiences, perceived stress and facilitators practices : A mixed methods study
- 2020
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In: Nurse Education Today. - : Elsevier. - 0260-6917 .- 1532-2793. ; 90
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Journal article (peer-reviewed)abstract
- Background: As an integral part of simulation, debriefing helps learners to construct knowledge through reflecting, internalizing, and relating. Video-assisted debriefing (VAD) adds audio-visual captures and reviews to support traditional verbal debriefing (VD), but evidence evaluating its educational effects has been mixed, with limited attention focusing on its structure development. Aims: This study aimed to 1) investigate the effects of a three-phase VAD in enhancing nursing students debriefing experiences and perceived stress compared to VD and 2) to explore its impact on facilitators debriefing practices. Methods: A mixed-methods design was adopted. The quantitative phase involved a prospective controlled trial on 145 nursing students from a university in Singapore who were randomized into the intervention cluster (n = 72) and the control cluster (n = 73). The debriefing experience scale (DES), the stress visual analogue scale (Stress VAS), and the debriefing assessment for simulation in healthcare (DASH (c) student version) were used as outcome measures. For the qualitative component, a purposive sample of eight facilitators evaluated their own debriefing practices using the DASH (c) instructor version and each completed an open-ended question survey. Qualitative data were analyzed using content analysis. Results: Students from the intervention cluster significantly improved their debriefing experiences (p = 0.01), experienced comparable stress, and had better impressions of VAD facilitators practices (p < 0.001) compared to those in the control cluster. Repeated VAD significantly reduced students stress (p < 0.001). Students viewed the VAD facilitators as more effective than the VD facilitators. Three categories were derived from the qualitative comments: the act of debriefing, the crux of VAD, and debriefing for success. Conclusion: The three-phase VAD significantly improved nursing students debriefing experiences without adding extra stress. It also helped to improve facilitators practices. Future research will benefit from exploring how experts facilitate the three-phase VAD "on the ground" and its effect on learning transfer and cost-effectiveness.
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| 39. |
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